Microneedling therapy, also known as collagen induction therapy or percutaneous collagen induction, is an increasingly popular treatment modality for skin rejuvenation. The approach employs small needles to puncture the skin and stimulate local collagen production in a minimally invasive manner. Recently, clinicians have incorporated the use of platelet-rich plasma (PRP) with the aim of augmenting cosmetic outcomes. In this article, we examine the utility of this approach by reviewing comparison studies of microneedling therapy with and without the application of PRP.

Dr. Gary Goldenberg demonstrates microneedling with platelet-rich plasma in a procedural video available here.

Microneedling Therapy

The use of microneedling first gained attention in the 1990s. Initially, Camirand and Doucet¹ described tattooing without pigment for the treatment of achromatic and hypertrophic scars. Fernandes² evolved this concept and developed a drum-shaped device with fine protruding needles to puncture the skin. Microneedling devices have expanded in recent years and now include both cord- and battery-powered pens and rollers, with needles ranging in length from 0.25 to 3.0 mm.

Treatment with microneedling promotes skin rejuvenation by creating small puncture wounds in the epidermis and dermis. This injury triggers the wound healing cascade and alters the modulation of growth factors to promote regenerative effects.^3,4 Following microneedling therapy, increases occur in elastic fiber formation, collagen deposition, and dermal thickness (Figure).⁵ Of interesting histologic note, collagen is deposited in the normal lattice pattern following this treatment rather than in the parallel bundles typical of scars.⁶ Microneedling preserves the overall integrity of the epidermal layers and basement membrane, allowing the epidermis to heal without abnormality, verified on histology by a normal stratum corneum, enhanced stratum granulosum, and normal rete ridges.⁷

Photographs courtesy of Joel L. Cohen, MD (Colorado, USA).

Microneedling has demonstrated several uses beyond general skin rejuvenation. In patients with atrophic acne scars, therapy can lead to improved scar appearance, skin texture, and patient satisfaction.^8,9 Hypertrophic and dyspigmented burn scars on the body, face, arms, and legs have shown to be receptive to repeated treatments.¹⁰ Microneedling also has shown promise in treating androgenic alopecia, increasing hair regrowth in patients who previously showed poor response to conventional therapy with minoxidil and finasteride.^11,12

Platelet-Rich Plasma

Platelet-rich plasma is developed by enriching blood with an autologous concentration of platelets. The preparation of PRP begins with whole blood, commonly obtained peripherally by venipuncture. Samples undergo centrifugation to allow separation of the blood into 3 layers: platelet-poor plasma, PRP, and erythrocytes.¹³ The typical platelet count of whole blood is approximately 200,000/µL; PRP aims to prepare a platelet count of at least 1,000,000/µL in a 5-mL volume.¹⁴

An attractive component of PRP is its high concentration of growth factors, including platelet-derived growth factor, transforming growth factor, vascular endothelial growth factor, and epithelial growth factor.¹⁵ Because of the regenerative effects of these proteins, PRP has been investigated as a modality to augment wound healing in a variety of clinical areas, such as maxillofacial surgery, orthopedics, cardiovascular surgery, and treatment of soft tissue ulcers.¹⁶

Combination Use of Microneedling and PRP

Several studies have compared the effects of microneedling with and without the application of PRP (Table).^17-20 In an animal model, Akcal et al¹⁷ examined the effects of microneedling and PRP on skin flap survival. Eight rats were randomly divided into 5 groups: sham, control, microneedling alone, microneedling plus PRP, and microneedling plus platelet-poor plasma. Treatments were applied to skin flaps after 4 hours of induced ischemia. The surviving flap area was measured, with results demonstrating significantly higher viable areas in the microneedling plus PRP group relative to all other groups (P<.01). On histologic examination, the microneedling plus PRP group showed well-organized epidermal layers and a dermal integrity that matched the dermis of the sham group.¹⁷

Asif et al¹⁸ performed a split-face comparison study of 50 patients with atrophic acne scars. On the right side, microneedling was performed followed by intradermal injections and topical application of PRP. On the left side, microneedling was performed followed by intradermal injections of distilled water. The study included 3 treatment sessions with 1 month between each session. Scars were assessed using the Goodman and Baron scale,²¹ which is designed to grade the morphology of postacne scarring. Scars on the right side improved by 62.2% and scars on the left side improved by 45.8%; prior to treatment, both sides demonstrated similar severity scores, but final severity scores were significantly reduced in the microneedling plus PRP group relative to the microneedling plus distilled water group (P<.00001). No residual side effects from treatment were reported.¹⁸

Examining the degree of improvement more carefully, microneedling plus PRP yielded excellent improvement in 40% (20/50) of patients and good improvement in 60% (30/50).¹⁸ Microneedling plus distilled water led to excellent improvement in 10% (5/50) and good improvement in 84% (42/50). Given that microneedling plus distilled water still provided good to excellent results in 94% of patients, the addition of PRP was helpful though not necessary in achieving meaningful benefit.¹⁸

In another split-face study, Fabbrocini et al¹⁹ evaluated 12 adult patients with acne scars. The right side of the face received microneedling plus PRP, while the left side received microneedling alone. Two treatments were performed 8 weeks apart. Severity scores (0=no lesions; 10=maximum severity) were used to assess patient outcomes throughout the study. Acne scars improved on both sides of the face following the treatment period, but the reduction in scar severity with microneedling plus PRP (3.5 points) was significantly greater than with microneedling alone (2.6 points)(P<.05). Patients tended to experience2 to 3 days of mild swelling and erythema after treatment regardless of PRP addition. With only 12 patients, the study was limited by a small sample size. The 10-point grading system differed from the Goodman and Baron scale in that it lacked corresponding qualitative markers, likely decreasing reproducibility.¹⁹

Chawla²⁰ compared the effectiveness of combination therapy with microneedling plus PRP versus microneedling and vitamin C application. In a split-face study of 30 patients with atrophic acne scars, the right side of the face was treated with microneedling plus PRP and the left side was treated with microneedling plus vitamin C. Four sessions were performed with an interval of 1 month in between treatments. The Goodman and Baron Scale was used to assess treatment efficacy. Overall, both treatments led to improved outcomes, but in categorizing patients who demonstrated poor responses, a significantly larger percentage existed in the microneedling plus vitamin C group (37% [10/27]) versus the microneedling plus PRP group (22% [6/27])(P=.021). Additionally, aggregate patient satisfaction scores were higher with microneedling plus PRP relative to microneedling plus vitamin C (P=.01). Of note, assessments of improvement were performed by the treating physician and patient satisfaction reports were completed with knowledge of the therapies and cost factor, which may have influenced results.²⁰

Conclusion

Microneedling therapy continues to evolve with a range of applications now emerging in dermatology. As PRP has gained popularity, there has been increased interest in its utilization to amplify the regenerative effects of microneedling. Although the number of direct comparisons examining microneedling with and without PRP is limited, the available evidence indicates that the addition of PRP may improve cosmetic outcomes. These results have been demonstrated primarily in the management of acne scars, but favorable effects may extend to other indications. Continued study is warranted to further quantify the degree of these benefits and to elucidate optimal treatment schedules.

In addition, it is important to consider a cost-benefit analysis of PRP. The price of PRP varies depending on the clinical site but in certain cases may double the cost of a microneedling treatment session. Although studies have demonstrated a statistically significant benefit to PRP, the clinical significance of this supplementary treatment must be weighed against the increased expense. A discussion should take place with the consideration that microneedling alone can provide a satisfactory result for some patients.

Microneedling therapy, also known as collagen induction therapy or percutaneous collagen induction, is an increasingly popular treatment modality for skin rejuvenation. The approach employs small needles to puncture the skin and stimulate local collagen production in a minimally invasive manner. Recently, clinicians have incorporated the use of platelet-rich plasma (PRP) with the aim of augmenting cosmetic outcomes. In this article, we examine the utility of this approach by reviewing comparison studies of microneedling therapy with and without the application of PRP.

Dr. Gary Goldenberg demonstrates microneedling with platelet-rich plasma in a procedural video available here.

Microneedling Therapy

The use of microneedling first gained attention in the 1990s. Initially, Camirand and Doucet¹ described tattooing without pigment for the treatment of achromatic and hypertrophic scars. Fernandes² evolved this concept and developed a drum-shaped device with fine protruding needles to puncture the skin. Microneedling devices have expanded in recent years and now include both cord- and battery-powered pens and rollers, with needles ranging in length from 0.25 to 3.0 mm.

Treatment with microneedling promotes skin rejuvenation by creating small puncture wounds in the epidermis and dermis. This injury triggers the wound healing cascade and alters the modulation of growth factors to promote regenerative effects.^3,4 Following microneedling therapy, increases occur in elastic fiber formation, collagen deposition, and dermal thickness (Figure).⁵ Of interesting histologic note, collagen is deposited in the normal lattice pattern following this treatment rather than in the parallel bundles typical of scars.⁶ Microneedling preserves the overall integrity of the epidermal layers and basement membrane, allowing the epidermis to heal without abnormality, verified on histology by a normal stratum corneum, enhanced stratum granulosum, and normal rete ridges.⁷

Photographs courtesy of Joel L. Cohen, MD (Colorado, USA).

Microneedling has demonstrated several uses beyond general skin rejuvenation. In patients with atrophic acne scars, therapy can lead to improved scar appearance, skin texture, and patient satisfaction.^8,9 Hypertrophic and dyspigmented burn scars on the body, face, arms, and legs have shown to be receptive to repeated treatments.¹⁰ Microneedling also has shown promise in treating androgenic alopecia, increasing hair regrowth in patients who previously showed poor response to conventional therapy with minoxidil and finasteride.^11,12

Platelet-Rich Plasma

Platelet-rich plasma is developed by enriching blood with an autologous concentration of platelets. The preparation of PRP begins with whole blood, commonly obtained peripherally by venipuncture. Samples undergo centrifugation to allow separation of the blood into 3 layers: platelet-poor plasma, PRP, and erythrocytes.¹³ The typical platelet count of whole blood is approximately 200,000/µL; PRP aims to prepare a platelet count of at least 1,000,000/µL in a 5-mL volume.¹⁴

An attractive component of PRP is its high concentration of growth factors, including platelet-derived growth factor, transforming growth factor, vascular endothelial growth factor, and epithelial growth factor.¹⁵ Because of the regenerative effects of these proteins, PRP has been investigated as a modality to augment wound healing in a variety of clinical areas, such as maxillofacial surgery, orthopedics, cardiovascular surgery, and treatment of soft tissue ulcers.¹⁶

Combination Use of Microneedling and PRP

Several studies have compared the effects of microneedling with and without the application of PRP (Table).^17-20 In an animal model, Akcal et al¹⁷ examined the effects of microneedling and PRP on skin flap survival. Eight rats were randomly divided into 5 groups: sham, control, microneedling alone, microneedling plus PRP, and microneedling plus platelet-poor plasma. Treatments were applied to skin flaps after 4 hours of induced ischemia. The surviving flap area was measured, with results demonstrating significantly higher viable areas in the microneedling plus PRP group relative to all other groups (P<.01). On histologic examination, the microneedling plus PRP group showed well-organized epidermal layers and a dermal integrity that matched the dermis of the sham group.¹⁷

Asif et al¹⁸ performed a split-face comparison study of 50 patients with atrophic acne scars. On the right side, microneedling was performed followed by intradermal injections and topical application of PRP. On the left side, microneedling was performed followed by intradermal injections of distilled water. The study included 3 treatment sessions with 1 month between each session. Scars were assessed using the Goodman and Baron scale,²¹ which is designed to grade the morphology of postacne scarring. Scars on the right side improved by 62.2% and scars on the left side improved by 45.8%; prior to treatment, both sides demonstrated similar severity scores, but final severity scores were significantly reduced in the microneedling plus PRP group relative to the microneedling plus distilled water group (P<.00001). No residual side effects from treatment were reported.¹⁸

Examining the degree of improvement more carefully, microneedling plus PRP yielded excellent improvement in 40% (20/50) of patients and good improvement in 60% (30/50).¹⁸ Microneedling plus distilled water led to excellent improvement in 10% (5/50) and good improvement in 84% (42/50). Given that microneedling plus distilled water still provided good to excellent results in 94% of patients, the addition of PRP was helpful though not necessary in achieving meaningful benefit.¹⁸

In another split-face study, Fabbrocini et al¹⁹ evaluated 12 adult patients with acne scars. The right side of the face received microneedling plus PRP, while the left side received microneedling alone. Two treatments were performed 8 weeks apart. Severity scores (0=no lesions; 10=maximum severity) were used to assess patient outcomes throughout the study. Acne scars improved on both sides of the face following the treatment period, but the reduction in scar severity with microneedling plus PRP (3.5 points) was significantly greater than with microneedling alone (2.6 points)(P<.05). Patients tended to experience2 to 3 days of mild swelling and erythema after treatment regardless of PRP addition. With only 12 patients, the study was limited by a small sample size. The 10-point grading system differed from the Goodman and Baron scale in that it lacked corresponding qualitative markers, likely decreasing reproducibility.¹⁹

Chawla²⁰ compared the effectiveness of combination therapy with microneedling plus PRP versus microneedling and vitamin C application. In a split-face study of 30 patients with atrophic acne scars, the right side of the face was treated with microneedling plus PRP and the left side was treated with microneedling plus vitamin C. Four sessions were performed with an interval of 1 month in between treatments. The Goodman and Baron Scale was used to assess treatment efficacy. Overall, both treatments led to improved outcomes, but in categorizing patients who demonstrated poor responses, a significantly larger percentage existed in the microneedling plus vitamin C group (37% [10/27]) versus the microneedling plus PRP group (22% [6/27])(P=.021). Additionally, aggregate patient satisfaction scores were higher with microneedling plus PRP relative to microneedling plus vitamin C (P=.01). Of note, assessments of improvement were performed by the treating physician and patient satisfaction reports were completed with knowledge of the therapies and cost factor, which may have influenced results.²⁰

Conclusion

Microneedling therapy continues to evolve with a range of applications now emerging in dermatology. As PRP has gained popularity, there has been increased interest in its utilization to amplify the regenerative effects of microneedling. Although the number of direct comparisons examining microneedling with and without PRP is limited, the available evidence indicates that the addition of PRP may improve cosmetic outcomes. These results have been demonstrated primarily in the management of acne scars, but favorable effects may extend to other indications. Continued study is warranted to further quantify the degree of these benefits and to elucidate optimal treatment schedules.

In addition, it is important to consider a cost-benefit analysis of PRP. The price of PRP varies depending on the clinical site but in certain cases may double the cost of a microneedling treatment session. Although studies have demonstrated a statistically significant benefit to PRP, the clinical significance of this supplementary treatment must be weighed against the increased expense. A discussion should take place with the consideration that microneedling alone can provide a satisfactory result for some patients.

Microneedling therapy, also known as collagen induction therapy or percutaneous collagen induction, is an increasingly popular treatment modality for skin rejuvenation. The approach employs small needles to puncture the skin and stimulate local collagen production in a minimally invasive manner. Recently, clinicians have incorporated the use of platelet-rich plasma (PRP) with the aim of augmenting cosmetic outcomes. In this article, we examine the utility of this approach by reviewing comparison studies of microneedling therapy with and without the application of PRP.

Dr. Gary Goldenberg demonstrates microneedling with platelet-rich plasma in a procedural video available here.

Microneedling Therapy

The use of microneedling first gained attention in the 1990s. Initially, Camirand and Doucet¹ described tattooing without pigment for the treatment of achromatic and hypertrophic scars. Fernandes² evolved this concept and developed a drum-shaped device with fine protruding needles to puncture the skin. Microneedling devices have expanded in recent years and now include both cord- and battery-powered pens and rollers, with needles ranging in length from 0.25 to 3.0 mm.

Treatment with microneedling promotes skin rejuvenation by creating small puncture wounds in the epidermis and dermis. This injury triggers the wound healing cascade and alters the modulation of growth factors to promote regenerative effects.^3,4 Following microneedling therapy, increases occur in elastic fiber formation, collagen deposition, and dermal thickness (Figure).⁵ Of interesting histologic note, collagen is deposited in the normal lattice pattern following this treatment rather than in the parallel bundles typical of scars.⁶ Microneedling preserves the overall integrity of the epidermal layers and basement membrane, allowing the epidermis to heal without abnormality, verified on histology by a normal stratum corneum, enhanced stratum granulosum, and normal rete ridges.⁷

Photographs courtesy of Joel L. Cohen, MD (Colorado, USA).

Microneedling has demonstrated several uses beyond general skin rejuvenation. In patients with atrophic acne scars, therapy can lead to improved scar appearance, skin texture, and patient satisfaction.^8,9 Hypertrophic and dyspigmented burn scars on the body, face, arms, and legs have shown to be receptive to repeated treatments.¹⁰ Microneedling also has shown promise in treating androgenic alopecia, increasing hair regrowth in patients who previously showed poor response to conventional therapy with minoxidil and finasteride.^11,12

Platelet-Rich Plasma

Platelet-rich plasma is developed by enriching blood with an autologous concentration of platelets. The preparation of PRP begins with whole blood, commonly obtained peripherally by venipuncture. Samples undergo centrifugation to allow separation of the blood into 3 layers: platelet-poor plasma, PRP, and erythrocytes.¹³ The typical platelet count of whole blood is approximately 200,000/µL; PRP aims to prepare a platelet count of at least 1,000,000/µL in a 5-mL volume.¹⁴

An attractive component of PRP is its high concentration of growth factors, including platelet-derived growth factor, transforming growth factor, vascular endothelial growth factor, and epithelial growth factor.¹⁵ Because of the regenerative effects of these proteins, PRP has been investigated as a modality to augment wound healing in a variety of clinical areas, such as maxillofacial surgery, orthopedics, cardiovascular surgery, and treatment of soft tissue ulcers.¹⁶

Combination Use of Microneedling and PRP

Several studies have compared the effects of microneedling with and without the application of PRP (Table).^17-20 In an animal model, Akcal et al¹⁷ examined the effects of microneedling and PRP on skin flap survival. Eight rats were randomly divided into 5 groups: sham, control, microneedling alone, microneedling plus PRP, and microneedling plus platelet-poor plasma. Treatments were applied to skin flaps after 4 hours of induced ischemia. The surviving flap area was measured, with results demonstrating significantly higher viable areas in the microneedling plus PRP group relative to all other groups (P<.01). On histologic examination, the microneedling plus PRP group showed well-organized epidermal layers and a dermal integrity that matched the dermis of the sham group.¹⁷

Asif et al¹⁸ performed a split-face comparison study of 50 patients with atrophic acne scars. On the right side, microneedling was performed followed by intradermal injections and topical application of PRP. On the left side, microneedling was performed followed by intradermal injections of distilled water. The study included 3 treatment sessions with 1 month between each session. Scars were assessed using the Goodman and Baron scale,²¹ which is designed to grade the morphology of postacne scarring. Scars on the right side improved by 62.2% and scars on the left side improved by 45.8%; prior to treatment, both sides demonstrated similar severity scores, but final severity scores were significantly reduced in the microneedling plus PRP group relative to the microneedling plus distilled water group (P<.00001). No residual side effects from treatment were reported.¹⁸

Examining the degree of improvement more carefully, microneedling plus PRP yielded excellent improvement in 40% (20/50) of patients and good improvement in 60% (30/50).¹⁸ Microneedling plus distilled water led to excellent improvement in 10% (5/50) and good improvement in 84% (42/50). Given that microneedling plus distilled water still provided good to excellent results in 94% of patients, the addition of PRP was helpful though not necessary in achieving meaningful benefit.¹⁸

In another split-face study, Fabbrocini et al¹⁹ evaluated 12 adult patients with acne scars. The right side of the face received microneedling plus PRP, while the left side received microneedling alone. Two treatments were performed 8 weeks apart. Severity scores (0=no lesions; 10=maximum severity) were used to assess patient outcomes throughout the study. Acne scars improved on both sides of the face following the treatment period, but the reduction in scar severity with microneedling plus PRP (3.5 points) was significantly greater than with microneedling alone (2.6 points)(P<.05). Patients tended to experience2 to 3 days of mild swelling and erythema after treatment regardless of PRP addition. With only 12 patients, the study was limited by a small sample size. The 10-point grading system differed from the Goodman and Baron scale in that it lacked corresponding qualitative markers, likely decreasing reproducibility.¹⁹

Chawla²⁰ compared the effectiveness of combination therapy with microneedling plus PRP versus microneedling and vitamin C application. In a split-face study of 30 patients with atrophic acne scars, the right side of the face was treated with microneedling plus PRP and the left side was treated with microneedling plus vitamin C. Four sessions were performed with an interval of 1 month in between treatments. The Goodman and Baron Scale was used to assess treatment efficacy. Overall, both treatments led to improved outcomes, but in categorizing patients who demonstrated poor responses, a significantly larger percentage existed in the microneedling plus vitamin C group (37% [10/27]) versus the microneedling plus PRP group (22% [6/27])(P=.021). Additionally, aggregate patient satisfaction scores were higher with microneedling plus PRP relative to microneedling plus vitamin C (P=.01). Of note, assessments of improvement were performed by the treating physician and patient satisfaction reports were completed with knowledge of the therapies and cost factor, which may have influenced results.²⁰

Conclusion

Microneedling therapy continues to evolve with a range of applications now emerging in dermatology. As PRP has gained popularity, there has been increased interest in its utilization to amplify the regenerative effects of microneedling. Although the number of direct comparisons examining microneedling with and without PRP is limited, the available evidence indicates that the addition of PRP may improve cosmetic outcomes. These results have been demonstrated primarily in the management of acne scars, but favorable effects may extend to other indications. Continued study is warranted to further quantify the degree of these benefits and to elucidate optimal treatment schedules.

In addition, it is important to consider a cost-benefit analysis of PRP. The price of PRP varies depending on the clinical site but in certain cases may double the cost of a microneedling treatment session. Although studies have demonstrated a statistically significant benefit to PRP, the clinical significance of this supplementary treatment must be weighed against the increased expense. A discussion should take place with the consideration that microneedling alone can provide a satisfactory result for some patients.

Twelve weeks of combination therapy with elbasvir and grazoprevir (EBR/GZR) achieved sustained virologic response in 98% of treatment-naive patients with compensated cirrhosis and chronic hepatitis C (HCV) genotype 1, 4, or 6 infections, and in 89% of treatment-experienced patients, according to a pooled analysis of six industry-sponsored trials.

Concomitant ribavirin offered “no incremental benefit” for treatment-naive patients, while 16 or 18 weeks of EBR and GZR with ribavirin achieved SVR12 in 100% of treatment-experienced patients, wrote Ira M. Jacobson, MD, of Mount Sinai Beth Israel and Icahn School of Medicine at Mount Sinai, New York, and his associates. The report was published in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.01.050).

Regardless of treatment history, genotype 1a patients with resistance-associated variants (RAV) in HCV nonstructural protein 5A (NS5A) needed ribavirin to achieve sustained virologic response (SVR) rates above 90%, the researchers emphasized. “Both patients with HCV genotype 1a infection with baseline RAVs who received 16 or 18 weeks of EBR/GZR and ribavirin achieved SVR12,” the researchers noted. Elbasvir is an HCV NS5A inhibitor, and GZR is an HCV NS3/4A protease inhibitor. In 2016, the Food and Drug Administration approved them in combination (Zepatier) for chronic genotype 1 and genotype 4 HCV. Studies have confirmed the benefits of treating HCV even when patients have cirrhosis, but they can be challenging to treat, especially if they have already failed a regimen that included a direct-acting antiviral agent, the investigators noted.

To explore the efficacy of EBR/GZR in compensated, Child-Pugh A cirrhosis, they studied 402 such patients with HCV genotype 1, 4, or 6 infections whose baseline HCV RNA level exceeded 10,000 IU. Patients had participated in one of six phase II/III clinical trials and had received EBR/GZR 50 mg/100 mg once daily for 12-18 weeks, with or without ribavirin (800-1400 mg/day based on body weight). Treatment-naive patients received 12 weeks of treatment, while treatment-experienced patients received 12, 16, or 18 weeks of treatment.

Twelve weeks of ribavirin did not boost SVR for either treatment-naive (90%) or treatment-experienced patients (91%), the researchers said. However, all 49 treatment-experienced patients who received EBR/GZR plus ribavirin for 16 or 18 weeks achieved SVR12, compared to 94% of patients who received EBR/GZR without ribavirin for 16 or 18 weeks.

Virologic failure was more common with HCV genotype 1a infections than with genotype 1b or 4 infection, especially if patients previously had not responded to interferon, the researchers noted. Eight of 11 (73%) patients with HCV genotype 1a infection and baseline NS5A RAVs achieved SVR12, compared with 98% of GT1a-infected patients without RAVs at baseline. But EBR/GZR was effective in various other subgroups, including patients with less than 100,000 platelets per microL, serum albumin below 3.5 g/dL, and FibroScan scores below 25 kPa. These findings suggest that EBR/GZR remains effective in patients with advanced compensated cirrhosis, the investigators said.

Most patients tolerated therapy, but six stopped treatment because of adverse events, including one episode of severe, possibly treatment-related abdominal pain. Also, four patients had late, asymptomatic rises in alanine aminotransferase (ALT) after first normalizing on treatment, and one patient stopped treatment because of grade 4 ALT elevation with eosinophilia. “There were no decompensation events in this generally healthy cirrhotic population, and no other evidence of declining liver function while on treatment,” the researchers added.

The integrated analysis was not prespecified, nor was it powered to compare outcomes between treatment arms. Only three patients had genotype 6 infection, and all were treatment-experienced. Only 23 patients had genotype 4 infection. Also, most patients had well-compensated cirrhosis. Finally, the trials varied in terms of how they defined cirrhosis, the investigators noted.

Merck, which funded the study, makes elbasvir and grazoprevir. The investigators acknowledged medical writing and editorial assistance from ApotheCom, which Merck funded. Dr. Jacobson disclosed consulting relationships and grant funding from Merck, AbbVie, Bristol-Myers Squibb, Gilead, Intercept, Janssen, and Trek.

Twelve weeks of combination therapy with elbasvir and grazoprevir (EBR/GZR) achieved sustained virologic response in 98% of treatment-naive patients with compensated cirrhosis and chronic hepatitis C (HCV) genotype 1, 4, or 6 infections, and in 89% of treatment-experienced patients, according to a pooled analysis of six industry-sponsored trials.

Concomitant ribavirin offered “no incremental benefit” for treatment-naive patients, while 16 or 18 weeks of EBR and GZR with ribavirin achieved SVR12 in 100% of treatment-experienced patients, wrote Ira M. Jacobson, MD, of Mount Sinai Beth Israel and Icahn School of Medicine at Mount Sinai, New York, and his associates. The report was published in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.01.050).

Regardless of treatment history, genotype 1a patients with resistance-associated variants (RAV) in HCV nonstructural protein 5A (NS5A) needed ribavirin to achieve sustained virologic response (SVR) rates above 90%, the researchers emphasized. “Both patients with HCV genotype 1a infection with baseline RAVs who received 16 or 18 weeks of EBR/GZR and ribavirin achieved SVR12,” the researchers noted. Elbasvir is an HCV NS5A inhibitor, and GZR is an HCV NS3/4A protease inhibitor. In 2016, the Food and Drug Administration approved them in combination (Zepatier) for chronic genotype 1 and genotype 4 HCV. Studies have confirmed the benefits of treating HCV even when patients have cirrhosis, but they can be challenging to treat, especially if they have already failed a regimen that included a direct-acting antiviral agent, the investigators noted.

To explore the efficacy of EBR/GZR in compensated, Child-Pugh A cirrhosis, they studied 402 such patients with HCV genotype 1, 4, or 6 infections whose baseline HCV RNA level exceeded 10,000 IU. Patients had participated in one of six phase II/III clinical trials and had received EBR/GZR 50 mg/100 mg once daily for 12-18 weeks, with or without ribavirin (800-1400 mg/day based on body weight). Treatment-naive patients received 12 weeks of treatment, while treatment-experienced patients received 12, 16, or 18 weeks of treatment.

Twelve weeks of ribavirin did not boost SVR for either treatment-naive (90%) or treatment-experienced patients (91%), the researchers said. However, all 49 treatment-experienced patients who received EBR/GZR plus ribavirin for 16 or 18 weeks achieved SVR12, compared to 94% of patients who received EBR/GZR without ribavirin for 16 or 18 weeks.

Virologic failure was more common with HCV genotype 1a infections than with genotype 1b or 4 infection, especially if patients previously had not responded to interferon, the researchers noted. Eight of 11 (73%) patients with HCV genotype 1a infection and baseline NS5A RAVs achieved SVR12, compared with 98% of GT1a-infected patients without RAVs at baseline. But EBR/GZR was effective in various other subgroups, including patients with less than 100,000 platelets per microL, serum albumin below 3.5 g/dL, and FibroScan scores below 25 kPa. These findings suggest that EBR/GZR remains effective in patients with advanced compensated cirrhosis, the investigators said.

Most patients tolerated therapy, but six stopped treatment because of adverse events, including one episode of severe, possibly treatment-related abdominal pain. Also, four patients had late, asymptomatic rises in alanine aminotransferase (ALT) after first normalizing on treatment, and one patient stopped treatment because of grade 4 ALT elevation with eosinophilia. “There were no decompensation events in this generally healthy cirrhotic population, and no other evidence of declining liver function while on treatment,” the researchers added.

The integrated analysis was not prespecified, nor was it powered to compare outcomes between treatment arms. Only three patients had genotype 6 infection, and all were treatment-experienced. Only 23 patients had genotype 4 infection. Also, most patients had well-compensated cirrhosis. Finally, the trials varied in terms of how they defined cirrhosis, the investigators noted.

Merck, which funded the study, makes elbasvir and grazoprevir. The investigators acknowledged medical writing and editorial assistance from ApotheCom, which Merck funded. Dr. Jacobson disclosed consulting relationships and grant funding from Merck, AbbVie, Bristol-Myers Squibb, Gilead, Intercept, Janssen, and Trek.

Twelve weeks of combination therapy with elbasvir and grazoprevir (EBR/GZR) achieved sustained virologic response in 98% of treatment-naive patients with compensated cirrhosis and chronic hepatitis C (HCV) genotype 1, 4, or 6 infections, and in 89% of treatment-experienced patients, according to a pooled analysis of six industry-sponsored trials.

Concomitant ribavirin offered “no incremental benefit” for treatment-naive patients, while 16 or 18 weeks of EBR and GZR with ribavirin achieved SVR12 in 100% of treatment-experienced patients, wrote Ira M. Jacobson, MD, of Mount Sinai Beth Israel and Icahn School of Medicine at Mount Sinai, New York, and his associates. The report was published in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.01.050).

Regardless of treatment history, genotype 1a patients with resistance-associated variants (RAV) in HCV nonstructural protein 5A (NS5A) needed ribavirin to achieve sustained virologic response (SVR) rates above 90%, the researchers emphasized. “Both patients with HCV genotype 1a infection with baseline RAVs who received 16 or 18 weeks of EBR/GZR and ribavirin achieved SVR12,” the researchers noted. Elbasvir is an HCV NS5A inhibitor, and GZR is an HCV NS3/4A protease inhibitor. In 2016, the Food and Drug Administration approved them in combination (Zepatier) for chronic genotype 1 and genotype 4 HCV. Studies have confirmed the benefits of treating HCV even when patients have cirrhosis, but they can be challenging to treat, especially if they have already failed a regimen that included a direct-acting antiviral agent, the investigators noted.

To explore the efficacy of EBR/GZR in compensated, Child-Pugh A cirrhosis, they studied 402 such patients with HCV genotype 1, 4, or 6 infections whose baseline HCV RNA level exceeded 10,000 IU. Patients had participated in one of six phase II/III clinical trials and had received EBR/GZR 50 mg/100 mg once daily for 12-18 weeks, with or without ribavirin (800-1400 mg/day based on body weight). Treatment-naive patients received 12 weeks of treatment, while treatment-experienced patients received 12, 16, or 18 weeks of treatment.

Twelve weeks of ribavirin did not boost SVR for either treatment-naive (90%) or treatment-experienced patients (91%), the researchers said. However, all 49 treatment-experienced patients who received EBR/GZR plus ribavirin for 16 or 18 weeks achieved SVR12, compared to 94% of patients who received EBR/GZR without ribavirin for 16 or 18 weeks.

Virologic failure was more common with HCV genotype 1a infections than with genotype 1b or 4 infection, especially if patients previously had not responded to interferon, the researchers noted. Eight of 11 (73%) patients with HCV genotype 1a infection and baseline NS5A RAVs achieved SVR12, compared with 98% of GT1a-infected patients without RAVs at baseline. But EBR/GZR was effective in various other subgroups, including patients with less than 100,000 platelets per microL, serum albumin below 3.5 g/dL, and FibroScan scores below 25 kPa. These findings suggest that EBR/GZR remains effective in patients with advanced compensated cirrhosis, the investigators said.

Most patients tolerated therapy, but six stopped treatment because of adverse events, including one episode of severe, possibly treatment-related abdominal pain. Also, four patients had late, asymptomatic rises in alanine aminotransferase (ALT) after first normalizing on treatment, and one patient stopped treatment because of grade 4 ALT elevation with eosinophilia. “There were no decompensation events in this generally healthy cirrhotic population, and no other evidence of declining liver function while on treatment,” the researchers added.

The integrated analysis was not prespecified, nor was it powered to compare outcomes between treatment arms. Only three patients had genotype 6 infection, and all were treatment-experienced. Only 23 patients had genotype 4 infection. Also, most patients had well-compensated cirrhosis. Finally, the trials varied in terms of how they defined cirrhosis, the investigators noted.

Merck, which funded the study, makes elbasvir and grazoprevir. The investigators acknowledged medical writing and editorial assistance from ApotheCom, which Merck funded. Dr. Jacobson disclosed consulting relationships and grant funding from Merck, AbbVie, Bristol-Myers Squibb, Gilead, Intercept, Janssen, and Trek.

The last decade has been a period of advancement for the lesbian, gay, bisexual, and transgender (LGBT) community for legal protections and visibility. Although the journey to acceptance and equality is far from over, this progress has appropriately extended to medical academia as physicians search for ways to become more inclusive and effective care providers for their LGBT patients.¹ In a recent cross-sectional study, Ginsberg et al² examined the role for dermatologists in the care of transgender patients. The investigators concluded that dermatologists should play a larger role in a transgender patient’s physical transformation.² It is our opinion that dermatologists need to be comfortable building rapport with LGBT patients and to become attuned to their specific needs to provide effective care.

When forging a relationship with an LGBT patient, assumptions can damage rapport. Two assumptions that should be avoided include presuming heterosexuality or, on the other hand, assuming risk for disease based on known LGBT status. A dermatologist who takes a cursory sexual history, or none at all, assuming his/her patient is heterosexual creates an environment in which a nonheterosexual patient feels uncomfortable being honest and open. Although there is enough literature to support the claim that some sexual minority groups have increased risk for sexually transmitted infections (STIs),³ it is dangerous to assume a patient’s risk based solely on sexual orientation. An abstinent patient or a patient in a long-term, monogamous, same-sex relationship, for instance, may feel stereotyped by a dermatologist who wants to screen him/her for an STI. The best step in building a therapeutic relationship is to cast out these assumptions and allow LGBT patients to be open about themselves and their sexual practices. Sexual histories should be asked in nonjudgmental ways that are related to the health of the patient, leading to relevant and useful information for their care. For example, ask patients, “Do you have sex with men, women, or both?” This question should be delivered in a matter-of-fact tone, which conveys to the patient that the provider merely wants an answer to guide patient care.

Dermatologists can tailor their encounters to the specific needs of sexual minority patients. The medical literature is rich with examples of conditions that occur at greater frequency in specific sexual minority groups. Sexually transmitted infections, particularly human immunodeficiency virus, are important causes of morbidity and mortality among sexual minorities, especially men who have sex with men (MSM).^3,4 Anal and penile human papillomavirus (HPV) infection and HPV-associated anal carcinoma risk are increased in MSM.^5,6 The literature has remained inconclusive on the use of anal Papanicolaou tests for diagnosis; however, dermatologists have a duty to at least examine the perianal and genital area of any patient at risk for HPV-related disease or STIs.^7,8 For younger patients, the HPV vaccine can help prevent certain types of HPV infection and likely reduce a patient’s risk for condyloma acuminatum and other sequelae of the virus. Guidelines have been expanded to include men aged 13 to 21 years and up to 26 years.⁹ More research is needed to determine if detection and prevention of these types of HPV infection using the vaccine in MSM actually leads to a decreased incidence of anal carcinoma.

Certain LGBT groups may benefit from a dermatologist’s care outside the realm of infectious diseases. One study found that increased indoor tanning use in MSM correlated with increased risk for nonmelanoma skin cancer.¹⁰ Lesbians have been found to be less likely to pursue preventative health examinations in general, including skin checks.¹¹ Finally, transgender patients can utilize dermatologists for help with transformative procedures and side effects of hormonal treatment such as androgenic acne.^1,4

Cutaneous and beyond, the future of LGBT health care in the United States is affected by the institutions that train future physicians. There is a trend toward incorporating formal LGBT curricula into medical schools and academic centers.¹² The Penn Medicine Program for LGBT Health (Philadelphia, Pennsylvania) is a pilot program geared toward both educating future clinicians and providing equal and unbiased care to LGBT patients.¹² Programs such as this one give rise to a new generation of physicians who feel comfortable and aware of the needs of their LGBT patients.

In a time when LGBT patients are becoming more comfortable claiming their sexual and gender identities openly, there is a need for dermatologists to provide individualized unbiased care, which can best be achieved by building rapport through assumption-free history taking, performing thorough physical examinations that include the genital and perianal area, and passing these good practices on to trainees.

The last decade has been a period of advancement for the lesbian, gay, bisexual, and transgender (LGBT) community for legal protections and visibility. Although the journey to acceptance and equality is far from over, this progress has appropriately extended to medical academia as physicians search for ways to become more inclusive and effective care providers for their LGBT patients.¹ In a recent cross-sectional study, Ginsberg et al² examined the role for dermatologists in the care of transgender patients. The investigators concluded that dermatologists should play a larger role in a transgender patient’s physical transformation.² It is our opinion that dermatologists need to be comfortable building rapport with LGBT patients and to become attuned to their specific needs to provide effective care.

When forging a relationship with an LGBT patient, assumptions can damage rapport. Two assumptions that should be avoided include presuming heterosexuality or, on the other hand, assuming risk for disease based on known LGBT status. A dermatologist who takes a cursory sexual history, or none at all, assuming his/her patient is heterosexual creates an environment in which a nonheterosexual patient feels uncomfortable being honest and open. Although there is enough literature to support the claim that some sexual minority groups have increased risk for sexually transmitted infections (STIs),³ it is dangerous to assume a patient’s risk based solely on sexual orientation. An abstinent patient or a patient in a long-term, monogamous, same-sex relationship, for instance, may feel stereotyped by a dermatologist who wants to screen him/her for an STI. The best step in building a therapeutic relationship is to cast out these assumptions and allow LGBT patients to be open about themselves and their sexual practices. Sexual histories should be asked in nonjudgmental ways that are related to the health of the patient, leading to relevant and useful information for their care. For example, ask patients, “Do you have sex with men, women, or both?” This question should be delivered in a matter-of-fact tone, which conveys to the patient that the provider merely wants an answer to guide patient care.

Dermatologists can tailor their encounters to the specific needs of sexual minority patients. The medical literature is rich with examples of conditions that occur at greater frequency in specific sexual minority groups. Sexually transmitted infections, particularly human immunodeficiency virus, are important causes of morbidity and mortality among sexual minorities, especially men who have sex with men (MSM).^3,4 Anal and penile human papillomavirus (HPV) infection and HPV-associated anal carcinoma risk are increased in MSM.^5,6 The literature has remained inconclusive on the use of anal Papanicolaou tests for diagnosis; however, dermatologists have a duty to at least examine the perianal and genital area of any patient at risk for HPV-related disease or STIs.^7,8 For younger patients, the HPV vaccine can help prevent certain types of HPV infection and likely reduce a patient’s risk for condyloma acuminatum and other sequelae of the virus. Guidelines have been expanded to include men aged 13 to 21 years and up to 26 years.⁹ More research is needed to determine if detection and prevention of these types of HPV infection using the vaccine in MSM actually leads to a decreased incidence of anal carcinoma.

Certain LGBT groups may benefit from a dermatologist’s care outside the realm of infectious diseases. One study found that increased indoor tanning use in MSM correlated with increased risk for nonmelanoma skin cancer.¹⁰ Lesbians have been found to be less likely to pursue preventative health examinations in general, including skin checks.¹¹ Finally, transgender patients can utilize dermatologists for help with transformative procedures and side effects of hormonal treatment such as androgenic acne.^1,4

Cutaneous and beyond, the future of LGBT health care in the United States is affected by the institutions that train future physicians. There is a trend toward incorporating formal LGBT curricula into medical schools and academic centers.¹² The Penn Medicine Program for LGBT Health (Philadelphia, Pennsylvania) is a pilot program geared toward both educating future clinicians and providing equal and unbiased care to LGBT patients.¹² Programs such as this one give rise to a new generation of physicians who feel comfortable and aware of the needs of their LGBT patients.

In a time when LGBT patients are becoming more comfortable claiming their sexual and gender identities openly, there is a need for dermatologists to provide individualized unbiased care, which can best be achieved by building rapport through assumption-free history taking, performing thorough physical examinations that include the genital and perianal area, and passing these good practices on to trainees.

The last decade has been a period of advancement for the lesbian, gay, bisexual, and transgender (LGBT) community for legal protections and visibility. Although the journey to acceptance and equality is far from over, this progress has appropriately extended to medical academia as physicians search for ways to become more inclusive and effective care providers for their LGBT patients.¹ In a recent cross-sectional study, Ginsberg et al² examined the role for dermatologists in the care of transgender patients. The investigators concluded that dermatologists should play a larger role in a transgender patient’s physical transformation.² It is our opinion that dermatologists need to be comfortable building rapport with LGBT patients and to become attuned to their specific needs to provide effective care.

When forging a relationship with an LGBT patient, assumptions can damage rapport. Two assumptions that should be avoided include presuming heterosexuality or, on the other hand, assuming risk for disease based on known LGBT status. A dermatologist who takes a cursory sexual history, or none at all, assuming his/her patient is heterosexual creates an environment in which a nonheterosexual patient feels uncomfortable being honest and open. Although there is enough literature to support the claim that some sexual minority groups have increased risk for sexually transmitted infections (STIs),³ it is dangerous to assume a patient’s risk based solely on sexual orientation. An abstinent patient or a patient in a long-term, monogamous, same-sex relationship, for instance, may feel stereotyped by a dermatologist who wants to screen him/her for an STI. The best step in building a therapeutic relationship is to cast out these assumptions and allow LGBT patients to be open about themselves and their sexual practices. Sexual histories should be asked in nonjudgmental ways that are related to the health of the patient, leading to relevant and useful information for their care. For example, ask patients, “Do you have sex with men, women, or both?” This question should be delivered in a matter-of-fact tone, which conveys to the patient that the provider merely wants an answer to guide patient care.

Dermatologists can tailor their encounters to the specific needs of sexual minority patients. The medical literature is rich with examples of conditions that occur at greater frequency in specific sexual minority groups. Sexually transmitted infections, particularly human immunodeficiency virus, are important causes of morbidity and mortality among sexual minorities, especially men who have sex with men (MSM).^3,4 Anal and penile human papillomavirus (HPV) infection and HPV-associated anal carcinoma risk are increased in MSM.^5,6 The literature has remained inconclusive on the use of anal Papanicolaou tests for diagnosis; however, dermatologists have a duty to at least examine the perianal and genital area of any patient at risk for HPV-related disease or STIs.^7,8 For younger patients, the HPV vaccine can help prevent certain types of HPV infection and likely reduce a patient’s risk for condyloma acuminatum and other sequelae of the virus. Guidelines have been expanded to include men aged 13 to 21 years and up to 26 years.⁹ More research is needed to determine if detection and prevention of these types of HPV infection using the vaccine in MSM actually leads to a decreased incidence of anal carcinoma.

Certain LGBT groups may benefit from a dermatologist’s care outside the realm of infectious diseases. One study found that increased indoor tanning use in MSM correlated with increased risk for nonmelanoma skin cancer.¹⁰ Lesbians have been found to be less likely to pursue preventative health examinations in general, including skin checks.¹¹ Finally, transgender patients can utilize dermatologists for help with transformative procedures and side effects of hormonal treatment such as androgenic acne.^1,4

Cutaneous and beyond, the future of LGBT health care in the United States is affected by the institutions that train future physicians. There is a trend toward incorporating formal LGBT curricula into medical schools and academic centers.¹² The Penn Medicine Program for LGBT Health (Philadelphia, Pennsylvania) is a pilot program geared toward both educating future clinicians and providing equal and unbiased care to LGBT patients.¹² Programs such as this one give rise to a new generation of physicians who feel comfortable and aware of the needs of their LGBT patients.

In a time when LGBT patients are becoming more comfortable claiming their sexual and gender identities openly, there is a need for dermatologists to provide individualized unbiased care, which can best be achieved by building rapport through assumption-free history taking, performing thorough physical examinations that include the genital and perianal area, and passing these good practices on to trainees.

Hospitalist specialty code becomes official designation

On April 3, 2017, “hospitalist” becomes an official specialty designation under Medicare – the code itself is C6. Starting on that date, hospitalists can change their specialty designation on the Medicare enrollment application. Specialty codes are self-designated and describe the kind of medicine that health care providers practice. Appropriate use of specialty codes helps distinguish differences among providers and improves the quality of utilization data. SHM applied for a specialty code for hospitalists nearly 3 years ago, and the Centers for Medicare & Medicaid Services approved the application in February 2016.

Stand with your fellow hospitalists and make sure to declare “I’m a C6.”

Assess your knowledge in hospital medicine with SPARK ONE

SHM recently launched SPARK ONE, a comprehensive online self-assessment tool created specifically for hospital medicine professionals. The activity contains 450-plus vignette-style multiple-choice questions covering 100% of the American Board of Internal Medicine’s Focused Practice in Hospital Medicine (FPHM) exam blueprint. This online tool is your complete resource for successfully preparing for the FPHM exam, or assessing your general knowledge in hospital medicine.

White paper now available: Hospitalist Attitudes Toward Electronic Medical Records

SHM’s Health Information Technology Committee diligently analyzed survey results that captured hospitalists’ attitudes towards electronic medical records, resulting in a white paper now available. The purpose of this paper is to effect change on EHR systems by informing conversations with decision makers and to provide hospital medicine a definitive voice in the landscape of the tumultuous world of electronic medical record systems.

SHM believes hospitalists are especially qualified to evaluate these systems, and the survey results paint a grim picture of the effectiveness and usability of the systems that hospitalists spend the majority of their time interacting with. These results should serve as a call to action to accelerate the pace of advancement and innovation in health care technology.

By sharing these results, SHM hopes to raise awareness of the unacceptable performance of existing systems that contributes to slower-than-desired improvement in quality and safety as well as increasing provider frustration. SHM strongly believes that health care needs a renewed focus on initial goals of technology adoption. View the white paper at hospitalmedicine.org/EHR.

Join the Early-Career Academic Hospitalist Speed Mentoring Session at Hospital Medicine 2017

The SHM “speed mentoring” session, held on Tuesday, May 2 from noon to 1:00 p.m. at Hospital Medicine 2017, is designed to assist early-career hospitalists in specific areas of career development by providing a fresh perspective and rapid advice.

Early-career hospitalists will be matched with three senior advisors by area of interest. The “mentee” will spend 10-15 minutes with each advisor and will then rotate to the next advisor. After the session, there will be time for additional informal discussion and networking among advisors and peers.

Pre-registration by March 31, 2017 is required; it will not be possible to register for this activity on-site at HM17. There is no additional fee to register. Registration will be limited to the first 20 participants. Visit hospitalmedicine2017.org/academic today.

Now available: 4 new antimicrobial stewardship modules

SHM has developed four new antimicrobial stewardship modules to help you demonstrate an understanding of best practices to optimize and improve antimicrobial prescribing within your hospital:

1. Optimizing Antibiotic Use for Hospitalized Patients

2. Best Practices in Treatment of UTIs: “Low-Hanging Fruit”

3. Best Practices in Acute Bacterial Skin Infection

4. Antibiotic Use for Inpatient Respiratory Infections

View these resources at hospitalmedicine.org/abx.

Network with the largest gathering of pediatric hospital medicine professionals

Pediatric Hospital Medicine 2017 (PHM 2017) will be held July 20-23 at the Omni Nashville located in Nashville, Tenn. PHM 2017 offers an all-inclusive arrangement of educational and networking opportunities planned specifically for the pediatric hospital medicine professional. More than 100 concurrent sessions to choose from over the 4 days of the conference allow participants to get the best out of their PHM 2017 experience.

Earn free CME in the enhanced SHM Learning Portal

You asked, and we listened: Introducing the enhanced SHM Learning Portal! The SHM Learning Portal, the online learning home for hospitalists with all eLearning initiatives in one place, just launched a brand-new responsive design in March 2016.

Launching this summer, SHM’s new Learning Portal will offer a better way to access and track online CME, with member discounts to a growing library of content. For more information, visit www.shmlearningportal.org.

Bringing SHM to you with local chapter meetings

Attend a chapter meeting and experience SHM locally. Chapters provide focused educational topics through key speakers and presentations and the opportunity to network with other hospitalists in your area. Find a chapter meeting close to you at hospitalmedicine.org/chapters.

A new look for SHM’s Center for Hospital Innovation & Improvement

Just as hospital medicine is evolving, so is SHM’s group dedicated to developing quality improvement safety tools and programs to meet health care’s changing needs. SHM is proud to unveil a new look for its Center for Hospital Innovation & Improvement this month. Stay tuned for more, and visit hospitalmedicine.org/QI for the latest offerings in a variety of quality improvement topics and clinical areas.

Stand out as a leader with the Fellow in Hospital Medicine designation

Applications for SHM’s Fellow in Hospital Medicine designation open on April 17, 2017. You may be eligible if you have been a member of SHM for at least 3 years and have been involved in key quality improvement programs and leadership roles in hospital medicine. Learn more and apply at hospitalmedicine.org/fellows.

Mr. Radler is Communications Specialist at the Society of Hospital Medicine.

Hospitalist specialty code becomes official designation

On April 3, 2017, “hospitalist” becomes an official specialty designation under Medicare – the code itself is C6. Starting on that date, hospitalists can change their specialty designation on the Medicare enrollment application. Specialty codes are self-designated and describe the kind of medicine that health care providers practice. Appropriate use of specialty codes helps distinguish differences among providers and improves the quality of utilization data. SHM applied for a specialty code for hospitalists nearly 3 years ago, and the Centers for Medicare & Medicaid Services approved the application in February 2016.

Stand with your fellow hospitalists and make sure to declare “I’m a C6.”

Assess your knowledge in hospital medicine with SPARK ONE

SHM recently launched SPARK ONE, a comprehensive online self-assessment tool created specifically for hospital medicine professionals. The activity contains 450-plus vignette-style multiple-choice questions covering 100% of the American Board of Internal Medicine’s Focused Practice in Hospital Medicine (FPHM) exam blueprint. This online tool is your complete resource for successfully preparing for the FPHM exam, or assessing your general knowledge in hospital medicine.

White paper now available: Hospitalist Attitudes Toward Electronic Medical Records

SHM’s Health Information Technology Committee diligently analyzed survey results that captured hospitalists’ attitudes towards electronic medical records, resulting in a white paper now available. The purpose of this paper is to effect change on EHR systems by informing conversations with decision makers and to provide hospital medicine a definitive voice in the landscape of the tumultuous world of electronic medical record systems.

SHM believes hospitalists are especially qualified to evaluate these systems, and the survey results paint a grim picture of the effectiveness and usability of the systems that hospitalists spend the majority of their time interacting with. These results should serve as a call to action to accelerate the pace of advancement and innovation in health care technology.

By sharing these results, SHM hopes to raise awareness of the unacceptable performance of existing systems that contributes to slower-than-desired improvement in quality and safety as well as increasing provider frustration. SHM strongly believes that health care needs a renewed focus on initial goals of technology adoption. View the white paper at hospitalmedicine.org/EHR.

Join the Early-Career Academic Hospitalist Speed Mentoring Session at Hospital Medicine 2017

The SHM “speed mentoring” session, held on Tuesday, May 2 from noon to 1:00 p.m. at Hospital Medicine 2017, is designed to assist early-career hospitalists in specific areas of career development by providing a fresh perspective and rapid advice.

Early-career hospitalists will be matched with three senior advisors by area of interest. The “mentee” will spend 10-15 minutes with each advisor and will then rotate to the next advisor. After the session, there will be time for additional informal discussion and networking among advisors and peers.

Pre-registration by March 31, 2017 is required; it will not be possible to register for this activity on-site at HM17. There is no additional fee to register. Registration will be limited to the first 20 participants. Visit hospitalmedicine2017.org/academic today.

Now available: 4 new antimicrobial stewardship modules

SHM has developed four new antimicrobial stewardship modules to help you demonstrate an understanding of best practices to optimize and improve antimicrobial prescribing within your hospital:

1. Optimizing Antibiotic Use for Hospitalized Patients

2. Best Practices in Treatment of UTIs: “Low-Hanging Fruit”

3. Best Practices in Acute Bacterial Skin Infection

4. Antibiotic Use for Inpatient Respiratory Infections

View these resources at hospitalmedicine.org/abx.

Network with the largest gathering of pediatric hospital medicine professionals

Pediatric Hospital Medicine 2017 (PHM 2017) will be held July 20-23 at the Omni Nashville located in Nashville, Tenn. PHM 2017 offers an all-inclusive arrangement of educational and networking opportunities planned specifically for the pediatric hospital medicine professional. More than 100 concurrent sessions to choose from over the 4 days of the conference allow participants to get the best out of their PHM 2017 experience.

Earn free CME in the enhanced SHM Learning Portal

You asked, and we listened: Introducing the enhanced SHM Learning Portal! The SHM Learning Portal, the online learning home for hospitalists with all eLearning initiatives in one place, just launched a brand-new responsive design in March 2016.

Launching this summer, SHM’s new Learning Portal will offer a better way to access and track online CME, with member discounts to a growing library of content. For more information, visit www.shmlearningportal.org.

Bringing SHM to you with local chapter meetings

Attend a chapter meeting and experience SHM locally. Chapters provide focused educational topics through key speakers and presentations and the opportunity to network with other hospitalists in your area. Find a chapter meeting close to you at hospitalmedicine.org/chapters.

A new look for SHM’s Center for Hospital Innovation & Improvement

Just as hospital medicine is evolving, so is SHM’s group dedicated to developing quality improvement safety tools and programs to meet health care’s changing needs. SHM is proud to unveil a new look for its Center for Hospital Innovation & Improvement this month. Stay tuned for more, and visit hospitalmedicine.org/QI for the latest offerings in a variety of quality improvement topics and clinical areas.

Stand out as a leader with the Fellow in Hospital Medicine designation

Applications for SHM’s Fellow in Hospital Medicine designation open on April 17, 2017. You may be eligible if you have been a member of SHM for at least 3 years and have been involved in key quality improvement programs and leadership roles in hospital medicine. Learn more and apply at hospitalmedicine.org/fellows.

Mr. Radler is Communications Specialist at the Society of Hospital Medicine.

Hospitalist specialty code becomes official designation

On April 3, 2017, “hospitalist” becomes an official specialty designation under Medicare – the code itself is C6. Starting on that date, hospitalists can change their specialty designation on the Medicare enrollment application. Specialty codes are self-designated and describe the kind of medicine that health care providers practice. Appropriate use of specialty codes helps distinguish differences among providers and improves the quality of utilization data. SHM applied for a specialty code for hospitalists nearly 3 years ago, and the Centers for Medicare & Medicaid Services approved the application in February 2016.

Stand with your fellow hospitalists and make sure to declare “I’m a C6.”

Assess your knowledge in hospital medicine with SPARK ONE

SHM recently launched SPARK ONE, a comprehensive online self-assessment tool created specifically for hospital medicine professionals. The activity contains 450-plus vignette-style multiple-choice questions covering 100% of the American Board of Internal Medicine’s Focused Practice in Hospital Medicine (FPHM) exam blueprint. This online tool is your complete resource for successfully preparing for the FPHM exam, or assessing your general knowledge in hospital medicine.

White paper now available: Hospitalist Attitudes Toward Electronic Medical Records

SHM’s Health Information Technology Committee diligently analyzed survey results that captured hospitalists’ attitudes towards electronic medical records, resulting in a white paper now available. The purpose of this paper is to effect change on EHR systems by informing conversations with decision makers and to provide hospital medicine a definitive voice in the landscape of the tumultuous world of electronic medical record systems.

SHM believes hospitalists are especially qualified to evaluate these systems, and the survey results paint a grim picture of the effectiveness and usability of the systems that hospitalists spend the majority of their time interacting with. These results should serve as a call to action to accelerate the pace of advancement and innovation in health care technology.

By sharing these results, SHM hopes to raise awareness of the unacceptable performance of existing systems that contributes to slower-than-desired improvement in quality and safety as well as increasing provider frustration. SHM strongly believes that health care needs a renewed focus on initial goals of technology adoption. View the white paper at hospitalmedicine.org/EHR.

Join the Early-Career Academic Hospitalist Speed Mentoring Session at Hospital Medicine 2017

The SHM “speed mentoring” session, held on Tuesday, May 2 from noon to 1:00 p.m. at Hospital Medicine 2017, is designed to assist early-career hospitalists in specific areas of career development by providing a fresh perspective and rapid advice.

Early-career hospitalists will be matched with three senior advisors by area of interest. The “mentee” will spend 10-15 minutes with each advisor and will then rotate to the next advisor. After the session, there will be time for additional informal discussion and networking among advisors and peers.

Pre-registration by March 31, 2017 is required; it will not be possible to register for this activity on-site at HM17. There is no additional fee to register. Registration will be limited to the first 20 participants. Visit hospitalmedicine2017.org/academic today.

Now available: 4 new antimicrobial stewardship modules

SHM has developed four new antimicrobial stewardship modules to help you demonstrate an understanding of best practices to optimize and improve antimicrobial prescribing within your hospital:

1. Optimizing Antibiotic Use for Hospitalized Patients

2. Best Practices in Treatment of UTIs: “Low-Hanging Fruit”

3. Best Practices in Acute Bacterial Skin Infection

4. Antibiotic Use for Inpatient Respiratory Infections

View these resources at hospitalmedicine.org/abx.

Network with the largest gathering of pediatric hospital medicine professionals

Pediatric Hospital Medicine 2017 (PHM 2017) will be held July 20-23 at the Omni Nashville located in Nashville, Tenn. PHM 2017 offers an all-inclusive arrangement of educational and networking opportunities planned specifically for the pediatric hospital medicine professional. More than 100 concurrent sessions to choose from over the 4 days of the conference allow participants to get the best out of their PHM 2017 experience.

Earn free CME in the enhanced SHM Learning Portal

You asked, and we listened: Introducing the enhanced SHM Learning Portal! The SHM Learning Portal, the online learning home for hospitalists with all eLearning initiatives in one place, just launched a brand-new responsive design in March 2016.

Launching this summer, SHM’s new Learning Portal will offer a better way to access and track online CME, with member discounts to a growing library of content. For more information, visit www.shmlearningportal.org.

Bringing SHM to you with local chapter meetings

Attend a chapter meeting and experience SHM locally. Chapters provide focused educational topics through key speakers and presentations and the opportunity to network with other hospitalists in your area. Find a chapter meeting close to you at hospitalmedicine.org/chapters.

A new look for SHM’s Center for Hospital Innovation & Improvement

Just as hospital medicine is evolving, so is SHM’s group dedicated to developing quality improvement safety tools and programs to meet health care’s changing needs. SHM is proud to unveil a new look for its Center for Hospital Innovation & Improvement this month. Stay tuned for more, and visit hospitalmedicine.org/QI for the latest offerings in a variety of quality improvement topics and clinical areas.

Stand out as a leader with the Fellow in Hospital Medicine designation

Applications for SHM’s Fellow in Hospital Medicine designation open on April 17, 2017. You may be eligible if you have been a member of SHM for at least 3 years and have been involved in key quality improvement programs and leadership roles in hospital medicine. Learn more and apply at hospitalmedicine.org/fellows.

Mr. Radler is Communications Specialist at the Society of Hospital Medicine.

Clinical question: Can alarm fatigue in pediatric inpatient settings be safely mitigated by modifying alarm limits with data-driven vital sign reference ranges?

Background: The management of patient alarms in the hospital is a significant safety issue, with the large majority of alarms (85%-99%) either false or not clinically significant. This leads to provider desensitization or alarm fatigue, which has been shown to contribute to adverse events.

In 2014, the Joint Commission made the issue of alarm system safety and alarm fatigue a priority for hospitals.¹ Multiple studies have been published addressing alarm fatigue in hospitalized adult patients, but this issue is less well studied in pediatrics, including little guidance on optimizing alarm parameters. Widely used reference ranges and guides are based on limited evidence, primarily based on observational data in healthy outpatients or consensus data.

Study Design: Retrospective, cross-sectional study.

Setting: Single-site, 311-bed quaternary-care academic hospital, both general medical and surgical units.

Synopsis: Vital signs were extracted from the institution’s electronic health record (EHR) for all general medical and surgical patients discharged between Jan. 1, 3013, and May 3, 2014, excluding critically ill children and physiologically implausible vital signs. Two different sets were used, a training set (patients discharged between Jan. 1, 2013, and Dec. 31, 2013) and a validation set (Jan. 1, 2014-May 3, 2014). One HR and RR pair was randomly selected for each 4-hour interval during hospitalization, with a maximum of 10 HR and RR pairs per patient. Age-stratified percentiles were calculated using this data. The 5th and 95th percentile limits using the study data were compared with the 5th and 95th percentile values in the 2013 study, and the reference ranges currently in use at the institution (2004 National Institutes of Health ranges).²

The training set used 62,508 vital sign measurements for 7,202 patients to calculate percentiles for HR and RR among 14 different age groups. The validation set consisted of 82,993 vital sign measurements for 2,287 patients. Using the 5th and 95th percentiles for HR and RR resulted in 24,045 (55.6%) fewer out-of-range measurements in the validation set compared to NIH reference ranges (45% fewer HR values, 61% fewer RR values). This finding, as well as the vital sign percentile ranges, was consistent with the data published in the 2013 study.²

Data for all 148 out-of-ICU RRT and CRA events during the same time period were reviewed using manual chart review. Evaluating vital signs within the 12 hours preceding the events, 144 patients had out-of-range HR or RR measurements using NIH ranges. One hundred thirty-six (94.4%) of these 144 patients also had out-of-range measurements using the study-derived 5th and 95th percentile values.

Manual chart review of the remaining eight patients who had normal HR or RR demonstrated that the RRT or CRA interventions occurred for clinical indications that did no rely on HR or RR measurement (for example, desaturations, difficulty breathing, hematemesis), so the data-driven parameters did not miss any of these events.

Bottom line: In this retrospective study, using data-driven HR and RR parameters was at least as safe as the NIH-published reference ranges currently in use in this hospital. In addition to maintaining safety related to RRT and CRA events, use of the data-driven parameters resulted in 55.6% fewer out-of-range vital sign measurements in the studied population. This may reduce the frequency of false alarms and improve alarm fatigue, and should be studied prospectively in the future.

Citation: Goel VV, Poole SF, Longhurst CA, et al. Safety analysis of proposed data-driven physiologic alarm parameters for hospitalized children. J Hosp Med. 2016;11(12):817-823.
 

Dr. Galloway is a pediatric hospitalist at Sanford Children’s Hospital in Sioux Falls, S.D., assistant professor of pediatrics at the University of South Dakota Sanford School of Medicine, and vice chief of the division of hospital pediatrics at USD SSOM and Sanford Children’s Hospital.

References

1. The Joint Commission. Alarm system safety. Available at: https://www.jointcommission.org/assets/1/18/R3_Report_Issue_5_12_2_13_Final.pdf. Published December 11, 2013.

2. Bonafide CP, Brady PW, Keren R, Conway PH, Marsolo K, Daymont C. Development of heart and respiratory rate percentile curves for hospitalized children. Pediatrics. 2013;131(4):e1150-1157.

Clinical question: Can alarm fatigue in pediatric inpatient settings be safely mitigated by modifying alarm limits with data-driven vital sign reference ranges?

Background: The management of patient alarms in the hospital is a significant safety issue, with the large majority of alarms (85%-99%) either false or not clinically significant. This leads to provider desensitization or alarm fatigue, which has been shown to contribute to adverse events.

In 2014, the Joint Commission made the issue of alarm system safety and alarm fatigue a priority for hospitals.¹ Multiple studies have been published addressing alarm fatigue in hospitalized adult patients, but this issue is less well studied in pediatrics, including little guidance on optimizing alarm parameters. Widely used reference ranges and guides are based on limited evidence, primarily based on observational data in healthy outpatients or consensus data.

Study Design: Retrospective, cross-sectional study.

Setting: Single-site, 311-bed quaternary-care academic hospital, both general medical and surgical units.

Synopsis: Vital signs were extracted from the institution’s electronic health record (EHR) for all general medical and surgical patients discharged between Jan. 1, 3013, and May 3, 2014, excluding critically ill children and physiologically implausible vital signs. Two different sets were used, a training set (patients discharged between Jan. 1, 2013, and Dec. 31, 2013) and a validation set (Jan. 1, 2014-May 3, 2014). One HR and RR pair was randomly selected for each 4-hour interval during hospitalization, with a maximum of 10 HR and RR pairs per patient. Age-stratified percentiles were calculated using this data. The 5th and 95th percentile limits using the study data were compared with the 5th and 95th percentile values in the 2013 study, and the reference ranges currently in use at the institution (2004 National Institutes of Health ranges).²

The training set used 62,508 vital sign measurements for 7,202 patients to calculate percentiles for HR and RR among 14 different age groups. The validation set consisted of 82,993 vital sign measurements for 2,287 patients. Using the 5th and 95th percentiles for HR and RR resulted in 24,045 (55.6%) fewer out-of-range measurements in the validation set compared to NIH reference ranges (45% fewer HR values, 61% fewer RR values). This finding, as well as the vital sign percentile ranges, was consistent with the data published in the 2013 study.²

Data for all 148 out-of-ICU RRT and CRA events during the same time period were reviewed using manual chart review. Evaluating vital signs within the 12 hours preceding the events, 144 patients had out-of-range HR or RR measurements using NIH ranges. One hundred thirty-six (94.4%) of these 144 patients also had out-of-range measurements using the study-derived 5th and 95th percentile values.

Manual chart review of the remaining eight patients who had normal HR or RR demonstrated that the RRT or CRA interventions occurred for clinical indications that did no rely on HR or RR measurement (for example, desaturations, difficulty breathing, hematemesis), so the data-driven parameters did not miss any of these events.

Bottom line: In this retrospective study, using data-driven HR and RR parameters was at least as safe as the NIH-published reference ranges currently in use in this hospital. In addition to maintaining safety related to RRT and CRA events, use of the data-driven parameters resulted in 55.6% fewer out-of-range vital sign measurements in the studied population. This may reduce the frequency of false alarms and improve alarm fatigue, and should be studied prospectively in the future.

Citation: Goel VV, Poole SF, Longhurst CA, et al. Safety analysis of proposed data-driven physiologic alarm parameters for hospitalized children. J Hosp Med. 2016;11(12):817-823.
 

Dr. Galloway is a pediatric hospitalist at Sanford Children’s Hospital in Sioux Falls, S.D., assistant professor of pediatrics at the University of South Dakota Sanford School of Medicine, and vice chief of the division of hospital pediatrics at USD SSOM and Sanford Children’s Hospital.

References

1. The Joint Commission. Alarm system safety. Available at: https://www.jointcommission.org/assets/1/18/R3_Report_Issue_5_12_2_13_Final.pdf. Published December 11, 2013.

2. Bonafide CP, Brady PW, Keren R, Conway PH, Marsolo K, Daymont C. Development of heart and respiratory rate percentile curves for hospitalized children. Pediatrics. 2013;131(4):e1150-1157.

Clinical question: Can alarm fatigue in pediatric inpatient settings be safely mitigated by modifying alarm limits with data-driven vital sign reference ranges?

Background: The management of patient alarms in the hospital is a significant safety issue, with the large majority of alarms (85%-99%) either false or not clinically significant. This leads to provider desensitization or alarm fatigue, which has been shown to contribute to adverse events.

In 2014, the Joint Commission made the issue of alarm system safety and alarm fatigue a priority for hospitals.¹ Multiple studies have been published addressing alarm fatigue in hospitalized adult patients, but this issue is less well studied in pediatrics, including little guidance on optimizing alarm parameters. Widely used reference ranges and guides are based on limited evidence, primarily based on observational data in healthy outpatients or consensus data.

Study Design: Retrospective, cross-sectional study.

Setting: Single-site, 311-bed quaternary-care academic hospital, both general medical and surgical units.

Synopsis: Vital signs were extracted from the institution’s electronic health record (EHR) for all general medical and surgical patients discharged between Jan. 1, 3013, and May 3, 2014, excluding critically ill children and physiologically implausible vital signs. Two different sets were used, a training set (patients discharged between Jan. 1, 2013, and Dec. 31, 2013) and a validation set (Jan. 1, 2014-May 3, 2014). One HR and RR pair was randomly selected for each 4-hour interval during hospitalization, with a maximum of 10 HR and RR pairs per patient. Age-stratified percentiles were calculated using this data. The 5th and 95th percentile limits using the study data were compared with the 5th and 95th percentile values in the 2013 study, and the reference ranges currently in use at the institution (2004 National Institutes of Health ranges).²

The training set used 62,508 vital sign measurements for 7,202 patients to calculate percentiles for HR and RR among 14 different age groups. The validation set consisted of 82,993 vital sign measurements for 2,287 patients. Using the 5th and 95th percentiles for HR and RR resulted in 24,045 (55.6%) fewer out-of-range measurements in the validation set compared to NIH reference ranges (45% fewer HR values, 61% fewer RR values). This finding, as well as the vital sign percentile ranges, was consistent with the data published in the 2013 study.²

Data for all 148 out-of-ICU RRT and CRA events during the same time period were reviewed using manual chart review. Evaluating vital signs within the 12 hours preceding the events, 144 patients had out-of-range HR or RR measurements using NIH ranges. One hundred thirty-six (94.4%) of these 144 patients also had out-of-range measurements using the study-derived 5th and 95th percentile values.

Manual chart review of the remaining eight patients who had normal HR or RR demonstrated that the RRT or CRA interventions occurred for clinical indications that did no rely on HR or RR measurement (for example, desaturations, difficulty breathing, hematemesis), so the data-driven parameters did not miss any of these events.

Bottom line: In this retrospective study, using data-driven HR and RR parameters was at least as safe as the NIH-published reference ranges currently in use in this hospital. In addition to maintaining safety related to RRT and CRA events, use of the data-driven parameters resulted in 55.6% fewer out-of-range vital sign measurements in the studied population. This may reduce the frequency of false alarms and improve alarm fatigue, and should be studied prospectively in the future.

Citation: Goel VV, Poole SF, Longhurst CA, et al. Safety analysis of proposed data-driven physiologic alarm parameters for hospitalized children. J Hosp Med. 2016;11(12):817-823.
 

Dr. Galloway is a pediatric hospitalist at Sanford Children’s Hospital in Sioux Falls, S.D., assistant professor of pediatrics at the University of South Dakota Sanford School of Medicine, and vice chief of the division of hospital pediatrics at USD SSOM and Sanford Children’s Hospital.

References

1. The Joint Commission. Alarm system safety. Available at: https://www.jointcommission.org/assets/1/18/R3_Report_Issue_5_12_2_13_Final.pdf. Published December 11, 2013.

2. Bonafide CP, Brady PW, Keren R, Conway PH, Marsolo K, Daymont C. Development of heart and respiratory rate percentile curves for hospitalized children. Pediatrics. 2013;131(4):e1150-1157.

FEATURED POST: “A Renewed Call to Overhaul Hospital Observation Care”

In response to concerns about Medicare beneficiary out-of-pocket financial risk, Congress unanimously passed the NOTICE Act, which President Obama signed into law August 5, 2015. This law states that all Medicare beneficiaries hospitalized for 24 hours or more as outpatients under observation must to be notified in writing that they are outpatients “not later than 36 hours after the time such individual begins receiving such services” as well as the associated “implications for cost-sharing.” Last month, the Centers for Medicare & Medicaid Services (CMS) released the final Medicare Outpatient Observation Notice (MOON) that hospitals will start delivering to patients no later than March 8, 2017 to comply with the law. Patients or their representatives must sign the form to acknowledge receipt.

Dr. Sheehy is a physician and associate professor at the University of Wisconsin School of Medicine and Public Health.

Read the full text of this blog post at http://blogs.hospitalmedicine.org/Blog/a-renewed-call-to-overhaul-hospital-observation-care/

Also on The Hospital Leader…

• New ABIM MOC Two-Year Plan for Internal Medicine Threatens the Focused Practice in Hospital Medicine By Burke Kealey, MD, SFHM

• The Nursing Home Get Out of Jail Card (“We Don’t Want Our Patient Back”). It’s Now Adios. By Brad Flansbaum, DO, MPH, MHM

• The Inmates Are Running the Asylum By Tracy Cardin, ACNP-BC, SFHM

• Do Clinicians Understand Quality Metric Data? By Danielle Scheurer, MD, MSCR, SFHM

• Fake News! Get Your Fake News Here! By Jordan Messler, MD, SFHM
 

FEATURED POST: “A Renewed Call to Overhaul Hospital Observation Care”

In response to concerns about Medicare beneficiary out-of-pocket financial risk, Congress unanimously passed the NOTICE Act, which President Obama signed into law August 5, 2015. This law states that all Medicare beneficiaries hospitalized for 24 hours or more as outpatients under observation must to be notified in writing that they are outpatients “not later than 36 hours after the time such individual begins receiving such services” as well as the associated “implications for cost-sharing.” Last month, the Centers for Medicare & Medicaid Services (CMS) released the final Medicare Outpatient Observation Notice (MOON) that hospitals will start delivering to patients no later than March 8, 2017 to comply with the law. Patients or their representatives must sign the form to acknowledge receipt.

Dr. Sheehy is a physician and associate professor at the University of Wisconsin School of Medicine and Public Health.

Read the full text of this blog post at http://blogs.hospitalmedicine.org/Blog/a-renewed-call-to-overhaul-hospital-observation-care/

Also on The Hospital Leader…

• New ABIM MOC Two-Year Plan for Internal Medicine Threatens the Focused Practice in Hospital Medicine By Burke Kealey, MD, SFHM

• The Nursing Home Get Out of Jail Card (“We Don’t Want Our Patient Back”). It’s Now Adios. By Brad Flansbaum, DO, MPH, MHM

• The Inmates Are Running the Asylum By Tracy Cardin, ACNP-BC, SFHM

• Do Clinicians Understand Quality Metric Data? By Danielle Scheurer, MD, MSCR, SFHM

• Fake News! Get Your Fake News Here! By Jordan Messler, MD, SFHM
 

FEATURED POST: “A Renewed Call to Overhaul Hospital Observation Care”

In response to concerns about Medicare beneficiary out-of-pocket financial risk, Congress unanimously passed the NOTICE Act, which President Obama signed into law August 5, 2015. This law states that all Medicare beneficiaries hospitalized for 24 hours or more as outpatients under observation must to be notified in writing that they are outpatients “not later than 36 hours after the time such individual begins receiving such services” as well as the associated “implications for cost-sharing.” Last month, the Centers for Medicare & Medicaid Services (CMS) released the final Medicare Outpatient Observation Notice (MOON) that hospitals will start delivering to patients no later than March 8, 2017 to comply with the law. Patients or their representatives must sign the form to acknowledge receipt.

Dr. Sheehy is a physician and associate professor at the University of Wisconsin School of Medicine and Public Health.

Read the full text of this blog post at http://blogs.hospitalmedicine.org/Blog/a-renewed-call-to-overhaul-hospital-observation-care/

Also on The Hospital Leader…

• New ABIM MOC Two-Year Plan for Internal Medicine Threatens the Focused Practice in Hospital Medicine By Burke Kealey, MD, SFHM

• The Nursing Home Get Out of Jail Card (“We Don’t Want Our Patient Back”). It’s Now Adios. By Brad Flansbaum, DO, MPH, MHM

• The Inmates Are Running the Asylum By Tracy Cardin, ACNP-BC, SFHM

• Do Clinicians Understand Quality Metric Data? By Danielle Scheurer, MD, MSCR, SFHM

• Fake News! Get Your Fake News Here! By Jordan Messler, MD, SFHM
 

By age 15 years, 3.1% of adolescents in Denver developed celiac disease, and another 2% developed a lesser degree of celiac disease autoimmunity, according to a 20-year prospective longitudinal study.

“Although more than 5% of children may experience a period of celiac disease autoimmunity [CDA], not all develop celiac disease [CD] or require gluten-free diets,” Edwin Liu, MD, of University of Colorado School of Medicine and Children’s Hospital Colorado (Aurora, Colo.), wrote with his associates in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.02.002). Most celiac autoimmunity probably develops before age 10, “which informs future efforts for universal screening,” they added.

Source: American Gastroenterological Association

About 40% of the general population has the HLA-DQ2 or DQ8 risk genotypes for celiac disease [CD], but little is known about rates of celiac disease among children in the United States, the researchers said. To help fill this gap, they analyzed celiac-risk HLA genotypes for 31,766 infants born between 1993 and 2004 from the Diabetes Autoimmunity Study in the Young. The 1,339 children with HLA risk genotypes were followed for up to 20 years.

By age 15 years, 66 of these children (4.9%) had developed tissue transglutaminase autoantibodies (tTGA) consistent with CDA, and also met criteria for CD, the researchers said. Another 46 (3.4%) children developed only CDA, of whom 46% experienced spontaneous resolution of tTGA seropositivity without treatment. By using genotype-specific risk weighting for population frequencies of HLA, the researchers estimated that 2.4% of the general population of Denver had CDA by age 5 years, 4.3% had CDA by age 10 years, and 5.1% had CDA by age 15 years. Estimated rates of CD were 1.6%, 2.8%, and 3.1%, respectively.

These findings suggest a significant rise in the incidence of CD compared with historical estimates in the United States, and reflect recent studies “using different approaches in North America,” the researchers said. Reasons for the “dramatic increase” are unknown, but environmental causes seem likely, especially given the absence of identified genetic differences and marked changes in the prevalence of CD during the past 2 decades, they added.

Several other reports have documented fluctuating and transient tTGA antibodies in children, the researchers noted. Awareness of transient CD autoantibodies might limit public acceptance of universal screening programs for CD, they said. “Continued long-term follow-up will identify whether the autoimmunity in these subjects truly abates and tolerance develops, or if CDA will recur in time, possibly in response to additional stimulating events,” they added. “At present, low positive tTGA results should be interpreted with caution, and do not necessarily indicate need for biopsy or for treatment.”

The study did not include the DR5/DR7 risk genotype, which accounts for less than 5% of CD cases. The study also did not account for the estimated 2.5% of the general population that has DR3/DR7, which can be considered high risk, the researchers said. Thus, the study is conservative and might underestimate the real incidence of CD or CDA, they added.

The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.

By age 15 years, 3.1% of adolescents in Denver developed celiac disease, and another 2% developed a lesser degree of celiac disease autoimmunity, according to a 20-year prospective longitudinal study.

“Although more than 5% of children may experience a period of celiac disease autoimmunity [CDA], not all develop celiac disease [CD] or require gluten-free diets,” Edwin Liu, MD, of University of Colorado School of Medicine and Children’s Hospital Colorado (Aurora, Colo.), wrote with his associates in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.02.002). Most celiac autoimmunity probably develops before age 10, “which informs future efforts for universal screening,” they added.

Source: American Gastroenterological Association

About 40% of the general population has the HLA-DQ2 or DQ8 risk genotypes for celiac disease [CD], but little is known about rates of celiac disease among children in the United States, the researchers said. To help fill this gap, they analyzed celiac-risk HLA genotypes for 31,766 infants born between 1993 and 2004 from the Diabetes Autoimmunity Study in the Young. The 1,339 children with HLA risk genotypes were followed for up to 20 years.

By age 15 years, 66 of these children (4.9%) had developed tissue transglutaminase autoantibodies (tTGA) consistent with CDA, and also met criteria for CD, the researchers said. Another 46 (3.4%) children developed only CDA, of whom 46% experienced spontaneous resolution of tTGA seropositivity without treatment. By using genotype-specific risk weighting for population frequencies of HLA, the researchers estimated that 2.4% of the general population of Denver had CDA by age 5 years, 4.3% had CDA by age 10 years, and 5.1% had CDA by age 15 years. Estimated rates of CD were 1.6%, 2.8%, and 3.1%, respectively.

These findings suggest a significant rise in the incidence of CD compared with historical estimates in the United States, and reflect recent studies “using different approaches in North America,” the researchers said. Reasons for the “dramatic increase” are unknown, but environmental causes seem likely, especially given the absence of identified genetic differences and marked changes in the prevalence of CD during the past 2 decades, they added.

Several other reports have documented fluctuating and transient tTGA antibodies in children, the researchers noted. Awareness of transient CD autoantibodies might limit public acceptance of universal screening programs for CD, they said. “Continued long-term follow-up will identify whether the autoimmunity in these subjects truly abates and tolerance develops, or if CDA will recur in time, possibly in response to additional stimulating events,” they added. “At present, low positive tTGA results should be interpreted with caution, and do not necessarily indicate need for biopsy or for treatment.”

The study did not include the DR5/DR7 risk genotype, which accounts for less than 5% of CD cases. The study also did not account for the estimated 2.5% of the general population that has DR3/DR7, which can be considered high risk, the researchers said. Thus, the study is conservative and might underestimate the real incidence of CD or CDA, they added.

The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.

By age 15 years, 3.1% of adolescents in Denver developed celiac disease, and another 2% developed a lesser degree of celiac disease autoimmunity, according to a 20-year prospective longitudinal study.

“Although more than 5% of children may experience a period of celiac disease autoimmunity [CDA], not all develop celiac disease [CD] or require gluten-free diets,” Edwin Liu, MD, of University of Colorado School of Medicine and Children’s Hospital Colorado (Aurora, Colo.), wrote with his associates in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.02.002). Most celiac autoimmunity probably develops before age 10, “which informs future efforts for universal screening,” they added.

Source: American Gastroenterological Association

About 40% of the general population has the HLA-DQ2 or DQ8 risk genotypes for celiac disease [CD], but little is known about rates of celiac disease among children in the United States, the researchers said. To help fill this gap, they analyzed celiac-risk HLA genotypes for 31,766 infants born between 1993 and 2004 from the Diabetes Autoimmunity Study in the Young. The 1,339 children with HLA risk genotypes were followed for up to 20 years.

By age 15 years, 66 of these children (4.9%) had developed tissue transglutaminase autoantibodies (tTGA) consistent with CDA, and also met criteria for CD, the researchers said. Another 46 (3.4%) children developed only CDA, of whom 46% experienced spontaneous resolution of tTGA seropositivity without treatment. By using genotype-specific risk weighting for population frequencies of HLA, the researchers estimated that 2.4% of the general population of Denver had CDA by age 5 years, 4.3% had CDA by age 10 years, and 5.1% had CDA by age 15 years. Estimated rates of CD were 1.6%, 2.8%, and 3.1%, respectively.

These findings suggest a significant rise in the incidence of CD compared with historical estimates in the United States, and reflect recent studies “using different approaches in North America,” the researchers said. Reasons for the “dramatic increase” are unknown, but environmental causes seem likely, especially given the absence of identified genetic differences and marked changes in the prevalence of CD during the past 2 decades, they added.

Several other reports have documented fluctuating and transient tTGA antibodies in children, the researchers noted. Awareness of transient CD autoantibodies might limit public acceptance of universal screening programs for CD, they said. “Continued long-term follow-up will identify whether the autoimmunity in these subjects truly abates and tolerance develops, or if CDA will recur in time, possibly in response to additional stimulating events,” they added. “At present, low positive tTGA results should be interpreted with caution, and do not necessarily indicate need for biopsy or for treatment.”

The study did not include the DR5/DR7 risk genotype, which accounts for less than 5% of CD cases. The study also did not account for the estimated 2.5% of the general population that has DR3/DR7, which can be considered high risk, the researchers said. Thus, the study is conservative and might underestimate the real incidence of CD or CDA, they added.

The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.

SNOWMASS, COLO. – Physicians can expect to encounter more and more patients with inflammatory arthritis and other rheumatic adverse events induced by immune checkpoint inhibitors as a result of anticipated exponential growth in the use of these drugs to treat an expanding list of cancers, Clifton O. Bingham III, MD, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

These cancer immunotherapy–induced rheumatic diseases may superficially look like the classic forms of familiar autoimmune diseases, but they have highly atypical features that will affect treatment decisions.

Rheumatologic IRAE presentations

Inflammatory arthritis is the most common form of rheumatologic IRAE, followed by sicca syndrome. At the Johns Hopkins Arthritis Center, Dr. Bingham and his coworkers have 25 well-characterized patients with inflammatory arthritis resulting from an ICI, only 1 of whom is HLA-B27-positive.

“Also, just one is autoantibody-positive, even though they all look for all the world as though they have rheumatoid arthritis,” the rheumatologist observed.

This ICI-induced inflammatory arthritis initially presents most commonly in the midsize and large joints – knees, ankles, elbows – then expands to include small joints such as the wrists, proximal interphalangeal joints, and the metacarpophalangeal joints.

Notably, the Hopkins group also has three patients with classic reactive arthritis marked by conjunctivitis, urethritis, arthritis, and dactylitis.

“I don’t know about you, but, in our general rheumatology practice, we see maybe one case of reactive arthritis in several years, so this is something that has struck us as really quite interesting,” said Dr. Bingham, who is also director of research in the division of rheumatology at Johns Hopkins.

The arthritis center is also managing a group of patients with ICI-induced sicca syndrome, which is uniformly extremely severe and treatment resistant, as well as a couple of patients with myositis IRAE, one with polymyalgia rheumatica, and two with crystal disease that is highly inflammatory in nature, difficult to treat, and includes an inflammatory polyarthritis component not typical in patients with crystal arthritis.
 

Why physicians will see more rheumatologic IRAEs

ICIs have dramatically transformed the treatment of selected advanced-stage cancers. For example, whereas patients with metastatic melanoma historically had a 2-year survival rate of 5%, combination therapy with the ICIs ipilimumab (Yervoy) and nivolumab (Opdivo) resulted in a 60% rate of partial or complete remission in a landmark clinical trial.

The basis of cancer immunotherapy is the discovery that, in order for cancer cells to thrive, they emit blocking signals that downregulate the native ability of T cells to recognize and kill them. This is true for both solid tumors and hematologic malignancies. The ICIs inhibit these blocking signals, which include cytotoxic T-lymphocyte–associated protein 4 (CTLA4), programmed death-1 (PD-1), and programmed death ligand-1 (PDL-1), thereby freeing up the T cells for tumor fighting.

Because of the nonspecific mechanism of this T-cell activation, however, ICIs have, as their main toxicities, T-cell–mediated autoimmune inflammatory tissue damage, which gets lumped under the umbrella term IRAEs. It can affect almost every organ system. Skin rashes are the most common, colitis second. Other commonly encountered IRAEs include thyroiditis, hypophysitis, hepatitis, peripheral neuropathy, and pneumonitis.

In addition to the four currently approved ICIs – ipilimumab, nivolumab, pembrolizumab (Keytruda), and atezolizumab (Tecentriq) – investigational ICIs targeting CTLA4, PD-1, and/or PDL-1 are in development. Plus, new ICIs targeting other blocking signals, including lymphocyte activation gene-3, CD137, and T-cell immunoglobulin and mucin domain-3, are now in clinical trials.

Clinical trials aimed at expanding the indications of existing ICIs and using ICIs in earlier-stage cancers in an effort to improve rates of lasting remission are also underway.

All told, probably at least 400 clinical trials of ICIs are ongoing worldwide, the rheumatologist estimated.

“More people will be exposed to these drugs, and we’ll see more and more of these rheumatologic IRAEs,” Dr. Bingham predicted.
 

Rheumatologic IRAEs are seriously underdiagnosed

Back in the pre-ICI days, Dr. Bingham was coauthor of a major study which concluded that clinical trialists in oncology consistently downgrade the severity of rheumatologic adverse events, often by 1 or 2 grades (J Rheumatol. 2007 Jun;34[6]:1401-14).

Unpublished details of ICI clinical trials in melanoma that he obtained from Bristol-Myers Squibb suggest that the true rate of rheumatologic IRAEs is about 20%, or roughly double that reported in the studies. That’s because the adverse events–grading system used in oncology undercalls the severity of arthritis and autoimmune disorders.

Indeed, the National Cancer Institute’s Common Terminology Criteria for Adverse Events, used in oncology clinical trials, is confusing on the topic of musculoskeletal and connective tissue disorders as treatment-emergent adverse events, according to Dr. Bingham. He noted that an oncologist can code a swollen joint in three different ways – joint effusion, arthritis, or arthralgia – and it takes disabling interference with self-care in activities of daily living for that swollen joint to rise to the level of a Grade 3 adverse event. From a rheumatology trialist’s perspective, that would be a Grade 4 disability.

Plus, neither the product labeling nor the patient information guides for the approved immunotherapy drugs mention the importance of monitoring for rheumatologic IRAEs or their management.

“There is poor awareness of musculoskeletal and rheumatic IRAEs in the general oncology community,” Dr. Bingham asserted. “But, if you talk with any oncology nurses who work in a clinical trial, they will tell you they’re seeing these events with significant frequency and severity.”
 

Treatment and response

It’s critical to gain control of rheumatologic IRAEs quickly so that patients can get on with their cancer immunotherapy. Dr. Bingham uses intra-articular steroid injections for patients with oligoarthritis and high-dose oral prednisone for polyarticular disease. He starts methotrexate and/or leflunomide early because the conventional disease-modifying antirheumatic drugs have roughly a 2-month delay in onset of action. He has had several patients who are unable to taper steroids despite background methotrexate.

In the most severely affected patients, he has turned to biologic agents in consultation with their oncologists. Tumor necrosis factor (TNF) inhibitors are the ones he and other rheumatologists have used most often.

“Notably, we have not been able to taper down very well. We have patients who are out more than 2 years now who still require their TNF inhibitor to treat their inflammatory arthritis, and these are patients on conventional disease–modifying antirheumatic drugs as well. As soon as it’s tapered, the arthritis begins to come back,” according to Dr. Bingham.

In marked contrast, colitis as an IRAE typically clears in response to just one or two doses of a TNF inhibitor.

One audience member related that she’d encountered a roadblock in trying to get authorization for a TNF inhibitor for a patient with a rheumatologic IRAE secondary to ICI treatment for metastatic melanoma because the labeling states these agents are relatively contraindicated in melanoma patients. Dr. Bingham offered a tip: Collaborate with the patient’s oncologist.

“In most cases, oncologists can get infliximab for these patients and administer it in their infusion centers. They are able to get things authorized with very little trouble,” he said.

Besides, most of these patients with severe inflammatory arthritis meet conventional criteria for TNF inhibitor therapy, based on their number of infected joints and elevated acute phase reactants for longer than 6 weeks, Dr. Bingham noted.

“We’ve had some very interesting conversations with patients. It’s impressive to see the impact arthritis can have on people. A lot of patients have said, ‘I don’t care if I die. Get me functional right now.’ That’s pretty profound. Quality of life is still very important for people, even when dealing with life-threatening diseases,” he observed.

Oncologists are actually eager for their patients to get on steroid-sparing therapy because of concern that high doses of steroids may reduce the efficacy of cancer immunotherapy. That’s not an issue with the TNF inhibitors, the rheumatologist continued.

Turning to the utility of other classes of biologic agents, Dr. Bingham advised avoiding abatacept (Orencia) because its mechanism of action is likely to cause interference with the cancer immunotherapy. Rituximab (Rituxan) takes too long to act. Anakinra (Kineret), tofacitinib (Xeljanz), and tocilizumab (Actemra), on the other hand, are agents he is interested in using as alternatives to TNF inhibitors, although he hasn’t done so yet.
 

Use of ICIs in patients with preexisting autoimmune disease

The experience here is entirely anecdotal, since such patients have been excluded from ICI clinical trials, but the available evidence suggests physicians should be prepared for higher rheumatologic IRAE rates in this setting. Investigators at Vanderbilt University reported that 8 of 30 cancer patients with known preexisting autoimmune disease experienced flares of that disease when treated with ipilimumab, and 10 developed a new IRAE (Therap Adv Gastroenterol. 2016 Jul;9[4]:457-62).

The Hopkins group has three patients with preexisting rheumatoid arthritis and two with preexisting scleroderma who have received ICIs. All three rheumatoid arthritis patients flared. Rheumatologists are trying to manage these flares so the patients can continue on their ICI. One of the scleroderma patients experienced no change in that disease while on an ICI, while the other showed a definite improvement in scleroderma symptoms.

“I think the jury’s still out in terms of what you do about ICI therapy in patients with preexisting autoimmunity. The data would say that there’s maybe a 50-50 chance of the autoimmune disease becoming worse, but, if patients have an otherwise fatal cancer, I think it’s probably worth the chance,” Dr. Bingham said.

Anecdotal reports suggest that more severe IRAEs may be a favorable prognostic sign in terms of cancer eradication, but a lot more patient experience will be needed in order to be sure, the rheumatologist said.

Dr. Bingham reported serving as a consultant to Bristol-Myers Squibb.

bjancin@frontlinemedcom.com
 

SNOWMASS, COLO. – Physicians can expect to encounter more and more patients with inflammatory arthritis and other rheumatic adverse events induced by immune checkpoint inhibitors as a result of anticipated exponential growth in the use of these drugs to treat an expanding list of cancers, Clifton O. Bingham III, MD, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

These cancer immunotherapy–induced rheumatic diseases may superficially look like the classic forms of familiar autoimmune diseases, but they have highly atypical features that will affect treatment decisions.

Rheumatologic IRAE presentations

Inflammatory arthritis is the most common form of rheumatologic IRAE, followed by sicca syndrome. At the Johns Hopkins Arthritis Center, Dr. Bingham and his coworkers have 25 well-characterized patients with inflammatory arthritis resulting from an ICI, only 1 of whom is HLA-B27-positive.

“Also, just one is autoantibody-positive, even though they all look for all the world as though they have rheumatoid arthritis,” the rheumatologist observed.

This ICI-induced inflammatory arthritis initially presents most commonly in the midsize and large joints – knees, ankles, elbows – then expands to include small joints such as the wrists, proximal interphalangeal joints, and the metacarpophalangeal joints.

Notably, the Hopkins group also has three patients with classic reactive arthritis marked by conjunctivitis, urethritis, arthritis, and dactylitis.

“I don’t know about you, but, in our general rheumatology practice, we see maybe one case of reactive arthritis in several years, so this is something that has struck us as really quite interesting,” said Dr. Bingham, who is also director of research in the division of rheumatology at Johns Hopkins.

The arthritis center is also managing a group of patients with ICI-induced sicca syndrome, which is uniformly extremely severe and treatment resistant, as well as a couple of patients with myositis IRAE, one with polymyalgia rheumatica, and two with crystal disease that is highly inflammatory in nature, difficult to treat, and includes an inflammatory polyarthritis component not typical in patients with crystal arthritis.
 

Why physicians will see more rheumatologic IRAEs

ICIs have dramatically transformed the treatment of selected advanced-stage cancers. For example, whereas patients with metastatic melanoma historically had a 2-year survival rate of 5%, combination therapy with the ICIs ipilimumab (Yervoy) and nivolumab (Opdivo) resulted in a 60% rate of partial or complete remission in a landmark clinical trial.

The basis of cancer immunotherapy is the discovery that, in order for cancer cells to thrive, they emit blocking signals that downregulate the native ability of T cells to recognize and kill them. This is true for both solid tumors and hematologic malignancies. The ICIs inhibit these blocking signals, which include cytotoxic T-lymphocyte–associated protein 4 (CTLA4), programmed death-1 (PD-1), and programmed death ligand-1 (PDL-1), thereby freeing up the T cells for tumor fighting.

Because of the nonspecific mechanism of this T-cell activation, however, ICIs have, as their main toxicities, T-cell–mediated autoimmune inflammatory tissue damage, which gets lumped under the umbrella term IRAEs. It can affect almost every organ system. Skin rashes are the most common, colitis second. Other commonly encountered IRAEs include thyroiditis, hypophysitis, hepatitis, peripheral neuropathy, and pneumonitis.

In addition to the four currently approved ICIs – ipilimumab, nivolumab, pembrolizumab (Keytruda), and atezolizumab (Tecentriq) – investigational ICIs targeting CTLA4, PD-1, and/or PDL-1 are in development. Plus, new ICIs targeting other blocking signals, including lymphocyte activation gene-3, CD137, and T-cell immunoglobulin and mucin domain-3, are now in clinical trials.

Clinical trials aimed at expanding the indications of existing ICIs and using ICIs in earlier-stage cancers in an effort to improve rates of lasting remission are also underway.

All told, probably at least 400 clinical trials of ICIs are ongoing worldwide, the rheumatologist estimated.

“More people will be exposed to these drugs, and we’ll see more and more of these rheumatologic IRAEs,” Dr. Bingham predicted.
 

Rheumatologic IRAEs are seriously underdiagnosed

Back in the pre-ICI days, Dr. Bingham was coauthor of a major study which concluded that clinical trialists in oncology consistently downgrade the severity of rheumatologic adverse events, often by 1 or 2 grades (J Rheumatol. 2007 Jun;34[6]:1401-14).

Unpublished details of ICI clinical trials in melanoma that he obtained from Bristol-Myers Squibb suggest that the true rate of rheumatologic IRAEs is about 20%, or roughly double that reported in the studies. That’s because the adverse events–grading system used in oncology undercalls the severity of arthritis and autoimmune disorders.

Indeed, the National Cancer Institute’s Common Terminology Criteria for Adverse Events, used in oncology clinical trials, is confusing on the topic of musculoskeletal and connective tissue disorders as treatment-emergent adverse events, according to Dr. Bingham. He noted that an oncologist can code a swollen joint in three different ways – joint effusion, arthritis, or arthralgia – and it takes disabling interference with self-care in activities of daily living for that swollen joint to rise to the level of a Grade 3 adverse event. From a rheumatology trialist’s perspective, that would be a Grade 4 disability.

Plus, neither the product labeling nor the patient information guides for the approved immunotherapy drugs mention the importance of monitoring for rheumatologic IRAEs or their management.

“There is poor awareness of musculoskeletal and rheumatic IRAEs in the general oncology community,” Dr. Bingham asserted. “But, if you talk with any oncology nurses who work in a clinical trial, they will tell you they’re seeing these events with significant frequency and severity.”
 

Treatment and response

It’s critical to gain control of rheumatologic IRAEs quickly so that patients can get on with their cancer immunotherapy. Dr. Bingham uses intra-articular steroid injections for patients with oligoarthritis and high-dose oral prednisone for polyarticular disease. He starts methotrexate and/or leflunomide early because the conventional disease-modifying antirheumatic drugs have roughly a 2-month delay in onset of action. He has had several patients who are unable to taper steroids despite background methotrexate.

In the most severely affected patients, he has turned to biologic agents in consultation with their oncologists. Tumor necrosis factor (TNF) inhibitors are the ones he and other rheumatologists have used most often.

“Notably, we have not been able to taper down very well. We have patients who are out more than 2 years now who still require their TNF inhibitor to treat their inflammatory arthritis, and these are patients on conventional disease–modifying antirheumatic drugs as well. As soon as it’s tapered, the arthritis begins to come back,” according to Dr. Bingham.

In marked contrast, colitis as an IRAE typically clears in response to just one or two doses of a TNF inhibitor.

One audience member related that she’d encountered a roadblock in trying to get authorization for a TNF inhibitor for a patient with a rheumatologic IRAE secondary to ICI treatment for metastatic melanoma because the labeling states these agents are relatively contraindicated in melanoma patients. Dr. Bingham offered a tip: Collaborate with the patient’s oncologist.

“In most cases, oncologists can get infliximab for these patients and administer it in their infusion centers. They are able to get things authorized with very little trouble,” he said.

Besides, most of these patients with severe inflammatory arthritis meet conventional criteria for TNF inhibitor therapy, based on their number of infected joints and elevated acute phase reactants for longer than 6 weeks, Dr. Bingham noted.

“We’ve had some very interesting conversations with patients. It’s impressive to see the impact arthritis can have on people. A lot of patients have said, ‘I don’t care if I die. Get me functional right now.’ That’s pretty profound. Quality of life is still very important for people, even when dealing with life-threatening diseases,” he observed.

Oncologists are actually eager for their patients to get on steroid-sparing therapy because of concern that high doses of steroids may reduce the efficacy of cancer immunotherapy. That’s not an issue with the TNF inhibitors, the rheumatologist continued.

Turning to the utility of other classes of biologic agents, Dr. Bingham advised avoiding abatacept (Orencia) because its mechanism of action is likely to cause interference with the cancer immunotherapy. Rituximab (Rituxan) takes too long to act. Anakinra (Kineret), tofacitinib (Xeljanz), and tocilizumab (Actemra), on the other hand, are agents he is interested in using as alternatives to TNF inhibitors, although he hasn’t done so yet.
 

Use of ICIs in patients with preexisting autoimmune disease

The experience here is entirely anecdotal, since such patients have been excluded from ICI clinical trials, but the available evidence suggests physicians should be prepared for higher rheumatologic IRAE rates in this setting. Investigators at Vanderbilt University reported that 8 of 30 cancer patients with known preexisting autoimmune disease experienced flares of that disease when treated with ipilimumab, and 10 developed a new IRAE (Therap Adv Gastroenterol. 2016 Jul;9[4]:457-62).

The Hopkins group has three patients with preexisting rheumatoid arthritis and two with preexisting scleroderma who have received ICIs. All three rheumatoid arthritis patients flared. Rheumatologists are trying to manage these flares so the patients can continue on their ICI. One of the scleroderma patients experienced no change in that disease while on an ICI, while the other showed a definite improvement in scleroderma symptoms.

“I think the jury’s still out in terms of what you do about ICI therapy in patients with preexisting autoimmunity. The data would say that there’s maybe a 50-50 chance of the autoimmune disease becoming worse, but, if patients have an otherwise fatal cancer, I think it’s probably worth the chance,” Dr. Bingham said.

Anecdotal reports suggest that more severe IRAEs may be a favorable prognostic sign in terms of cancer eradication, but a lot more patient experience will be needed in order to be sure, the rheumatologist said.

Dr. Bingham reported serving as a consultant to Bristol-Myers Squibb.

bjancin@frontlinemedcom.com
 

SNOWMASS, COLO. – Physicians can expect to encounter more and more patients with inflammatory arthritis and other rheumatic adverse events induced by immune checkpoint inhibitors as a result of anticipated exponential growth in the use of these drugs to treat an expanding list of cancers, Clifton O. Bingham III, MD, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

These cancer immunotherapy–induced rheumatic diseases may superficially look like the classic forms of familiar autoimmune diseases, but they have highly atypical features that will affect treatment decisions.

Rheumatologic IRAE presentations

Inflammatory arthritis is the most common form of rheumatologic IRAE, followed by sicca syndrome. At the Johns Hopkins Arthritis Center, Dr. Bingham and his coworkers have 25 well-characterized patients with inflammatory arthritis resulting from an ICI, only 1 of whom is HLA-B27-positive.

“Also, just one is autoantibody-positive, even though they all look for all the world as though they have rheumatoid arthritis,” the rheumatologist observed.

This ICI-induced inflammatory arthritis initially presents most commonly in the midsize and large joints – knees, ankles, elbows – then expands to include small joints such as the wrists, proximal interphalangeal joints, and the metacarpophalangeal joints.

Notably, the Hopkins group also has three patients with classic reactive arthritis marked by conjunctivitis, urethritis, arthritis, and dactylitis.

“I don’t know about you, but, in our general rheumatology practice, we see maybe one case of reactive arthritis in several years, so this is something that has struck us as really quite interesting,” said Dr. Bingham, who is also director of research in the division of rheumatology at Johns Hopkins.

The arthritis center is also managing a group of patients with ICI-induced sicca syndrome, which is uniformly extremely severe and treatment resistant, as well as a couple of patients with myositis IRAE, one with polymyalgia rheumatica, and two with crystal disease that is highly inflammatory in nature, difficult to treat, and includes an inflammatory polyarthritis component not typical in patients with crystal arthritis.
 

Why physicians will see more rheumatologic IRAEs

ICIs have dramatically transformed the treatment of selected advanced-stage cancers. For example, whereas patients with metastatic melanoma historically had a 2-year survival rate of 5%, combination therapy with the ICIs ipilimumab (Yervoy) and nivolumab (Opdivo) resulted in a 60% rate of partial or complete remission in a landmark clinical trial.

The basis of cancer immunotherapy is the discovery that, in order for cancer cells to thrive, they emit blocking signals that downregulate the native ability of T cells to recognize and kill them. This is true for both solid tumors and hematologic malignancies. The ICIs inhibit these blocking signals, which include cytotoxic T-lymphocyte–associated protein 4 (CTLA4), programmed death-1 (PD-1), and programmed death ligand-1 (PDL-1), thereby freeing up the T cells for tumor fighting.

Because of the nonspecific mechanism of this T-cell activation, however, ICIs have, as their main toxicities, T-cell–mediated autoimmune inflammatory tissue damage, which gets lumped under the umbrella term IRAEs. It can affect almost every organ system. Skin rashes are the most common, colitis second. Other commonly encountered IRAEs include thyroiditis, hypophysitis, hepatitis, peripheral neuropathy, and pneumonitis.

In addition to the four currently approved ICIs – ipilimumab, nivolumab, pembrolizumab (Keytruda), and atezolizumab (Tecentriq) – investigational ICIs targeting CTLA4, PD-1, and/or PDL-1 are in development. Plus, new ICIs targeting other blocking signals, including lymphocyte activation gene-3, CD137, and T-cell immunoglobulin and mucin domain-3, are now in clinical trials.

Clinical trials aimed at expanding the indications of existing ICIs and using ICIs in earlier-stage cancers in an effort to improve rates of lasting remission are also underway.

All told, probably at least 400 clinical trials of ICIs are ongoing worldwide, the rheumatologist estimated.

“More people will be exposed to these drugs, and we’ll see more and more of these rheumatologic IRAEs,” Dr. Bingham predicted.
 

Rheumatologic IRAEs are seriously underdiagnosed

Back in the pre-ICI days, Dr. Bingham was coauthor of a major study which concluded that clinical trialists in oncology consistently downgrade the severity of rheumatologic adverse events, often by 1 or 2 grades (J Rheumatol. 2007 Jun;34[6]:1401-14).

Unpublished details of ICI clinical trials in melanoma that he obtained from Bristol-Myers Squibb suggest that the true rate of rheumatologic IRAEs is about 20%, or roughly double that reported in the studies. That’s because the adverse events–grading system used in oncology undercalls the severity of arthritis and autoimmune disorders.

Indeed, the National Cancer Institute’s Common Terminology Criteria for Adverse Events, used in oncology clinical trials, is confusing on the topic of musculoskeletal and connective tissue disorders as treatment-emergent adverse events, according to Dr. Bingham. He noted that an oncologist can code a swollen joint in three different ways – joint effusion, arthritis, or arthralgia – and it takes disabling interference with self-care in activities of daily living for that swollen joint to rise to the level of a Grade 3 adverse event. From a rheumatology trialist’s perspective, that would be a Grade 4 disability.

Plus, neither the product labeling nor the patient information guides for the approved immunotherapy drugs mention the importance of monitoring for rheumatologic IRAEs or their management.

“There is poor awareness of musculoskeletal and rheumatic IRAEs in the general oncology community,” Dr. Bingham asserted. “But, if you talk with any oncology nurses who work in a clinical trial, they will tell you they’re seeing these events with significant frequency and severity.”
 

Treatment and response

It’s critical to gain control of rheumatologic IRAEs quickly so that patients can get on with their cancer immunotherapy. Dr. Bingham uses intra-articular steroid injections for patients with oligoarthritis and high-dose oral prednisone for polyarticular disease. He starts methotrexate and/or leflunomide early because the conventional disease-modifying antirheumatic drugs have roughly a 2-month delay in onset of action. He has had several patients who are unable to taper steroids despite background methotrexate.

In the most severely affected patients, he has turned to biologic agents in consultation with their oncologists. Tumor necrosis factor (TNF) inhibitors are the ones he and other rheumatologists have used most often.

“Notably, we have not been able to taper down very well. We have patients who are out more than 2 years now who still require their TNF inhibitor to treat their inflammatory arthritis, and these are patients on conventional disease–modifying antirheumatic drugs as well. As soon as it’s tapered, the arthritis begins to come back,” according to Dr. Bingham.

In marked contrast, colitis as an IRAE typically clears in response to just one or two doses of a TNF inhibitor.

One audience member related that she’d encountered a roadblock in trying to get authorization for a TNF inhibitor for a patient with a rheumatologic IRAE secondary to ICI treatment for metastatic melanoma because the labeling states these agents are relatively contraindicated in melanoma patients. Dr. Bingham offered a tip: Collaborate with the patient’s oncologist.

“In most cases, oncologists can get infliximab for these patients and administer it in their infusion centers. They are able to get things authorized with very little trouble,” he said.

Besides, most of these patients with severe inflammatory arthritis meet conventional criteria for TNF inhibitor therapy, based on their number of infected joints and elevated acute phase reactants for longer than 6 weeks, Dr. Bingham noted.

“We’ve had some very interesting conversations with patients. It’s impressive to see the impact arthritis can have on people. A lot of patients have said, ‘I don’t care if I die. Get me functional right now.’ That’s pretty profound. Quality of life is still very important for people, even when dealing with life-threatening diseases,” he observed.

Oncologists are actually eager for their patients to get on steroid-sparing therapy because of concern that high doses of steroids may reduce the efficacy of cancer immunotherapy. That’s not an issue with the TNF inhibitors, the rheumatologist continued.

Turning to the utility of other classes of biologic agents, Dr. Bingham advised avoiding abatacept (Orencia) because its mechanism of action is likely to cause interference with the cancer immunotherapy. Rituximab (Rituxan) takes too long to act. Anakinra (Kineret), tofacitinib (Xeljanz), and tocilizumab (Actemra), on the other hand, are agents he is interested in using as alternatives to TNF inhibitors, although he hasn’t done so yet.
 

Use of ICIs in patients with preexisting autoimmune disease

The experience here is entirely anecdotal, since such patients have been excluded from ICI clinical trials, but the available evidence suggests physicians should be prepared for higher rheumatologic IRAE rates in this setting. Investigators at Vanderbilt University reported that 8 of 30 cancer patients with known preexisting autoimmune disease experienced flares of that disease when treated with ipilimumab, and 10 developed a new IRAE (Therap Adv Gastroenterol. 2016 Jul;9[4]:457-62).

The Hopkins group has three patients with preexisting rheumatoid arthritis and two with preexisting scleroderma who have received ICIs. All three rheumatoid arthritis patients flared. Rheumatologists are trying to manage these flares so the patients can continue on their ICI. One of the scleroderma patients experienced no change in that disease while on an ICI, while the other showed a definite improvement in scleroderma symptoms.

“I think the jury’s still out in terms of what you do about ICI therapy in patients with preexisting autoimmunity. The data would say that there’s maybe a 50-50 chance of the autoimmune disease becoming worse, but, if patients have an otherwise fatal cancer, I think it’s probably worth the chance,” Dr. Bingham said.

Anecdotal reports suggest that more severe IRAEs may be a favorable prognostic sign in terms of cancer eradication, but a lot more patient experience will be needed in order to be sure, the rheumatologist said.

Dr. Bingham reported serving as a consultant to Bristol-Myers Squibb.

bjancin@frontlinemedcom.com
 

Washington – Patients with heart failure with reduced ejection fraction and comorbid diabetes whose heart failure was treated with sacubitril/valsartan experienced significantly enhanced glycemic control in addition to reduced morbidity and mortality due to heart failure in the landmark PARADIGM-HF trial, Jelena P. Seferovic, MD, reported at the annual meeting of the American College of Cardiology.

PARADIGM-HF was a randomized, double-blind clinical trial of oral sacubitril/valsartan, an angiotensin receptor–neprilysin inhibitor, or ARNI, at 97 mg/103 mg twice daily versus enalapril at 10 mg twice daily in 8,442 patients with heart failure with reduced ejection fraction (HFrEF). The primary results, which demonstrated significant reductions in heart failure morbidity and mortality in the sacubitril/valsartan group, have been published (N Engl J Med. 2014 Sep 11;371[11]:993-1004). The findings led to Food and Drug Administration approval of the drug, marketed as Entresto, for HFrEF, as well as a top level Class I recommendation for the drug’s use in the 2016 ACC/AHA heart failure management guidelines.

Bruce Jancin/Frontline Medical News

bjancin@frontlinemedcom.com

Washington – Patients with heart failure with reduced ejection fraction and comorbid diabetes whose heart failure was treated with sacubitril/valsartan experienced significantly enhanced glycemic control in addition to reduced morbidity and mortality due to heart failure in the landmark PARADIGM-HF trial, Jelena P. Seferovic, MD, reported at the annual meeting of the American College of Cardiology.

PARADIGM-HF was a randomized, double-blind clinical trial of oral sacubitril/valsartan, an angiotensin receptor–neprilysin inhibitor, or ARNI, at 97 mg/103 mg twice daily versus enalapril at 10 mg twice daily in 8,442 patients with heart failure with reduced ejection fraction (HFrEF). The primary results, which demonstrated significant reductions in heart failure morbidity and mortality in the sacubitril/valsartan group, have been published (N Engl J Med. 2014 Sep 11;371[11]:993-1004). The findings led to Food and Drug Administration approval of the drug, marketed as Entresto, for HFrEF, as well as a top level Class I recommendation for the drug’s use in the 2016 ACC/AHA heart failure management guidelines.

Bruce Jancin/Frontline Medical News

bjancin@frontlinemedcom.com

Washington – Patients with heart failure with reduced ejection fraction and comorbid diabetes whose heart failure was treated with sacubitril/valsartan experienced significantly enhanced glycemic control in addition to reduced morbidity and mortality due to heart failure in the landmark PARADIGM-HF trial, Jelena P. Seferovic, MD, reported at the annual meeting of the American College of Cardiology.

PARADIGM-HF was a randomized, double-blind clinical trial of oral sacubitril/valsartan, an angiotensin receptor–neprilysin inhibitor, or ARNI, at 97 mg/103 mg twice daily versus enalapril at 10 mg twice daily in 8,442 patients with heart failure with reduced ejection fraction (HFrEF). The primary results, which demonstrated significant reductions in heart failure morbidity and mortality in the sacubitril/valsartan group, have been published (N Engl J Med. 2014 Sep 11;371[11]:993-1004). The findings led to Food and Drug Administration approval of the drug, marketed as Entresto, for HFrEF, as well as a top level Class I recommendation for the drug’s use in the 2016 ACC/AHA heart failure management guidelines.

Bruce Jancin/Frontline Medical News

bjancin@frontlinemedcom.com

A 43-year-old man presented to a community hospital with acute chest pain and shortness of breath and was diagnosed with anterior ST-elevation myocardial infarction. He was a smoker with a history of alcohol abuse, hypertension, and hyperlipidemia, and in the past he had undergone percutaneous coronary interventions to the right coronary artery and the first obtuse marginal artery.

Angiography showed total occlusion in the left anterior descending artery, 90% stenosis in the right coronary artery, and mild disease in the left circumflex artery. A drug-eluting stent was placed in the left anterior descending artery, resulting in good blood flow. 

However, his left ventricle continued to have severe dysfunction. An intra-aortic balloon pump was inserted. Afterward, computed tomography showed subsegmental pulmonary embolism with congestion. His mean arterial pressure was 60 mm Hg (normal 70–110), central venous pressure 12 mm Hg (3–8), pulmonary artery pressure 38/26 mm Hg (15–30/4–12), pulmonary capillary wedge pressure 24 mm Hg (2–15), and cardiac index 1.4 L/min (2.5–4).

The patient was started on dobutamine and norepinephrine and transferred to Cleveland Clinic on day 2. Over the next day, he had runs of ventricular tachycardia, for which he was given amiodarone and lidocaine. His urine output was low, and his serum creatinine was elevated at 1.65 mg/dL (baseline 1.2, normal 0.5–1.5). Liver function tests were also elevated, with aspartate aminotransferase at 115 U/L(14–40) and alanine aminotransferase at 187 U/L (10–54).

Poor oxygenation was evident: his arterial partial pressure of oxygen was 64 mm Hg (normal 75–100). He was intubated and given 100% oxygen with positive end-expiratory pressure of 12 cm H₂O.

Echocardiography showed a left ventricular ejection fraction of 15% (normal 55%–70%) and mild right ventricular dysfunction.

ECMO and then Impella placement

On his third hospital day, a venoarterial extracorporeal membrane oxygenation (ECMO) device was placed peripherally (Figure 1).

His hemodynamic variables stabilized, and he was weaned off dobutamine and norepinephrine. Results of liver function tests normalized, his urinary output increased, and his serum creatinine dropped to a normal 1.0 mg/dL. However, a chest radiograph showed pulmonary congestion, and echocardiography now showed severe left ventricular dysfunction.

On hospital day 5, the patient underwent surgical placement of an Impella 5.0 device (Abiomed, Danvers, MA) through the right axillary artery in an effort to improve his pulmonary edema. The ECMO device was removed. Placement of a venovenous ECMO device was deemed unnecessary when oxygenation improved with the Impella.

Three days after Impella placement, radiography showed improved edema with some remaining pleural effusion.

ACUTE CARDIOGENIC SHOCK

Cardiogenic shock remains a challenging clinical problem: patients with it are among the sickest in the hospital, and many of them die. ECMO was once the only therapy available and is still widely used. However, it is a 2-edged sword; complications such as bleeding, infection, and thrombosis are almost inevitable if it is used for long. Importantly, patients are usually kept intubated and bedridden.

In recent years, new devices have become available that are easier to place (some in the catheterization laboratory or even at the bedside) and allow safer bridging to recovery, transplant, or other therapies.

This case illustrates the natural history of cardiogenic shock and the preferred clinical approach: ie, ongoing evaluation that permits rapid response to evolving challenges.

In general, acute cardiogenic shock occurs within 24 to 48 hours after the initial insult, so even if a procedure succeeds, the patient may develop progressive hypotension and organ dysfunction. Reduced cardiac output causes a downward spiral with multiple systemic and inflammatory processes as well as increased nitric oxide synthesis, leading to progressive decline and eventual end-organ dysfunction.

Continuously evaluate

The cardiac team should continuously assess the acuity and severity of a patient’s condition, with the goals of maintaining end-organ perfusion and identifying the source of problems. Refractory cardiogenic shock, with tissue hypoperfusion despite vasoactive medications and treatment of the underlying cause, is associated with in-hospital mortality rates ranging from 30% to 50%.^1,2 The rates have actually increased over the past decade, as sicker patients are being treated.

When a patient presents with cardiogenic shock, we first try a series of vasoactive drugs and usually an intra-aortic balloon pump (Figure 2). We then tailor treatment depending on etiology. For example, a patient may have viral myocarditis and may even require a biopsy.

If cardiogenic shock is refractory, mechanical circulatory support devices can be a short-term bridge to either recovery or a new decision. A multidisciplinary team should be consulted to consider transplant, a long-term device, or palliative care. Sometimes a case requires “bridging to a bridge,” with several devices used short-term in turn.

Prognostic factors in cardiogenic shock

Several tools help predict outcome in a severely ill patient. End-organ function, indicated by blood lactate levels and estimated glomerular filtration rate, is perhaps the most informative and should be monitored serially.

CardShock³ is a simple scoring system based on age, mental status at presentation, laboratory values, and medical history. Patients receive 1 point for each of the following factors:

• Age > 75
• Confusion at presentation
• Previous myocardial infarction or coronary artery bypass grafting
• Acute coronary syndrome etiology
• Left ventricular ejection fraction < 40%
• Blood lactate level between 2 and 4 mmol/L, inclusively (2 points for lactate levels > 4 mmol/L)
• Estimated glomerular filtration rate between 30 and 60 mL/min/1.73 m², inclusively (2 points if < 30 mL/min/1.73 m²). 

Thus, scores range from 0 (best) to 9 (worst). A score of 0 to 3 points was associated with a 9% risk of death in the hospital, a score of 4 or 5 with a risk of 36%, and a score of 6 through 9 with a risk of 77%.³

The Survival After Veno-arterial ECMO (SAVE) score (www.save-score.com) is a prediction tool derived from a large international ECMO registry.⁴ It is based on patient age, diagnosis, and indicators of end-organ dysfunction. Scores range from –35 (worst) to +7 (best).

The mortality rate associated with postcardiotomy cardiogenic shock increases with the amount of inotropic support provided. In a 1996–1999 case series of patients who underwent open-heart surgery,⁵ the hospital mortality rate was 40% in those who received 2 inotropes in high doses and 80% in those who received 3. A strategy of early implementation of mechanical support is critical.

Selection criteria for destination therapy

Deciding whether a patient should receive a long-term device is frequently a challenge. The decision often must be based on limited information about not only the medical indications but also psychosocial factors that influence long-term success.

The Centers for Medicare and Medicaid Services have established criteria for candidates for left ventricular assist devices (LVADs) as destination therapy.⁶ Contraindications established for heart transplant should also be considered (Table 1).

CASE REVISITED

Several factors argued against LVAD placement in our patient. He had no health insurance and had been off medications. He smoked and said he consumed 3 hard liquor drinks per week. His Stanford Integrated Psychosocial Assessment for Transplantation score was 30 (minimally acceptable). He had hypoxia with subsegmental pulmonary edema, a strong contraindication to immediate transplant.

On the other hand, he had only mild right ventricular dysfunction. His CardShock score was 4 (intermediate risk, based on lactate 1.5 mmol/L and estimated glomerular filtration rate 52 mL/min/1.73 m²). His SAVE score was –9 (class IV), which overall is associated with a 30% risk of death (low enough to consider treatment).

During the patient’s time on temporary support, the team had the opportunity to better understand him and assess his family support and his ability to handle a permanent device. His surviving the acute course bolstered the team’s confidence that he could enjoy long-term survival with destination therapy.

CATHETERIZATION LABORATORY DEVICE CAPABILITIES

Although most implantation procedures are done in the operating room, they are often done in the catheterization laboratory because patients undergoing catheterization may not be stable enough for transfer, or an emergency intervention may be required during the night. Catheterization interventionists are also an important part of the team to help determine the best approach for long-term therapy.

The catheterization laboratory has multiple acute intervention options. Usually, decisions must be made quickly. In general, patients needing mechanical support are managed as follows:

• Those who need circulation support and oxygenation receive ECMO
• Those who need circulation support alone because of mechanical issues (eg, myocardial infarction) are considered for an intra-aortic balloon pump, Impella, or TandemHeart pump (Cardiac Assist, Pittsburgh, PA).

Factors that guide the selection of a temporary pump include:

• Left ventricular function
• Right ventricular function
• Aortic valve stenosis (some devices cannot be inserted through critical aortic stenosis)
• Aortic regurgitation (can affect some devices)
• Peripheral artery disease (some devices are large and must be placed percutaneously).

CHOOSING AMONG PERCUTANEOUS DEVICES

Circulatory support in cardiogenic shock improves outcomes, and devices play an important role in supporting high-risk procedures. The goal is not necessarily to use the device throughout the hospital stay. Acute stabilization is most important initially; a more considered decision about long-term therapy can be made when more is known about the patient.

Patient selection is the most important component of success. However, randomized data to support outcomes with the various devices are sparse and complicated by the critically ill state of the patient population.

SHORT-TERM CIRCULATORY SUPPORT: ECMO, IMPELLA, TANDEMHEART

A menu of options is available for temporary mechanical support. Options differ by their degree of circulatory support and ease of insertion (Table 2).

ECMO: A fast option with many advantages

ECMO has evolved and now can be placed quickly. A remote diagnostic platform such as CardioHub permits management at the bedside, in the medical unit, or in the cardiac intensive care unit.⁷

ECMO has several advantages. It can be used during cardiopulmonary bypass, it provides oxygenation, it is the only option in the setting of lung injury, it can be placed peripherally (without thoracotomy), and it is the only percutaneous option for biventricular support.

ECMO also has significant disadvantages

ECMO is a good device for acute resuscitation of a patient in shock, as it offers quick placement and resuscitation. But it is falling out of favor because of significant disadvantages.

Its major drawback is that it provides no left ventricular unloading. Although in a very unstable patient ECMO can stabilize end organs and restore their function, the lack of left ventricular unloading and reduced ventricular work threaten the myocardium. It creates extremely high afterload; therefore, in a left ventricle with poor function, wall tension and myocardial oxygen demand increase. Multiple studies have shown that coronary perfusion worsens, especially if the patient is cannulated peripherally. Because relative cerebral hypoxia occurs in many situations, it is imperative to check blood saturations at multiple sites to determine if perfusion is adequate everywhere.    

Ineffective left ventricular unloading with venoarterial ECMO is managed in several ways. Sometimes left ventricular distention is slight and the effects are subtle. Left ventricular distention causing pulmonary edema can be addressed with:

• Inotropes (in moderate doses)
• Anticoagulation to prevent left ventricular thrombus formation
• An intra-aortic balloon pump. Most patients on ECMO already have an intra-aortic balloon pump in place, and it should be left in to provide additional support. For those who do not have one, it should be placed via the contralateral femoral artery.

If problems persist despite these measures, apical cannulation or left ventricular septostomy can be performed.

Outcomes with ECMO have been disappointing. Studies show that whether ECMO was indicated for cardiac failure or for respiratory failure, survival is only about 25% at 5 years. Analyzing data only for arteriovenous ECMO, survival was 48% in bridged patients and 41% in patients who were weaned.

The Extracorporeal Life Support Organization Registry, in their international summary from 2010, found that 34% of cardiac patients on ECMO survived to discharge or transfer. Most of these patients had cardiogenic shock from acute myocardial infarction. Outcomes are so poor because of complications endemic to ECMO, eg, dialysis-dependent renal failure (about 40%) and neurologic complications (about 30%), often involving ischemic or hemorrhagic stroke.

Limb and pump complications were also significant in the past. These have been reduced with the new reperfusion cannula and the Quadrox oxygenator.  

Complications unique to ECMO should be understood and anticipated so that they can be avoided. Better tools are available, ie, Impella and TandemHeart.

Left-sided Impella: A longer-term temporary support

ECMO is a temporary fix that is usually used only for a few days. If longer support is needed, axillary placement of an Impella should be used as a bridge to recovery, transplant, or a durable LVAD.

The Impella device (Figure 3) is a miniature rotary blood pump increasingly used to treat cardiogenic shock. It is inserted retrograde across the aortic valve to provide short-term ventricular support. Most devices are approved by the US Food and Drug Administration (FDA) for less than 7 days of use, but we have experience using them up to 30 days. They are very hemocompatible, involving minimal hemolysis. Axillary placement allows early extubation and ambulation and is more stable than groin placement.

Several models are available: the 2.5 and 3.5 L/min devices can be placed percutaneously, while the 5 L/min model must be surgically placed in the axillary or groin region. Heparin is required with their use. They can replace ECMO. A right ventricular assist device (RVAD), Impella RP, is also available.

Physiologic impact of the Impella

The Impella fully unloads the left ventricle, reducing myocardial oxygen demand and increasing myocardial blood flow. It reduces end-diastolic volume and pressure, the mechanical work of the heart, and wall tension. Microvascular resistance is reduced, allowing increased coronary flow. Cardiac output and power are increased by multiple means.^8–11

The RECOVER 1 trial evaluated the 5L Impella placed after cardiac surgery. The cardiac index increased in all the patients, and the systemic vascular resistance and wedge pressure decreased.¹²

Unloading the ventricle is critical. Meyns  and colleagues¹³ found a fivefold reduction in infarct size from baseline in a left anterior descending occlusion model in pigs after off-loading the ventricle.

Impella has the advantage of simple percutaneous insertion (the 2.5 and CP models). It also tests right ventricular tolerance: if the right ventricle is doing well, one can predict with high certainty that it will tolerate an LVAD (eg, HeartWare, HeartMate 2 (Pleasanton, CA), or HeartMate 3 when available).

Disadvantages include that it provides only left ventricular support, although a right ventricular device can be inserted for dual support. Placement requires fluoroscopic or echocardiographic guidance.

TandemHeart requires septal puncture

The TandemHeart is approved for short-term and biventricular use. It consists of an extracorporeal centrifugal pump that withdraws blood from the left atrium via a trans-septal cannula placed through the femoral vein (Figure 4) and returns it to one or both femoral arteries. The blood is pumped at up to 5 L/min.

It is designed to reduce the pulmonary capillary wedge pressure, ventricular work, and myocardial oxygen demand and increase cardiac output and mean arterial pressure. It has the advantages of percutaneous placement and the ability to provide biventricular support with 2 devices. It can be used for up to 3 weeks. It can easily be converted to ECMO by either splicing in an oxygenator or adding another cannula.

Although the TandemHeart provides significant support, it is no longer often used. A 21F venous cannula must be passed to the left atrium by trans-septal puncture, which requires advanced skill and must be done in the catheterization laboratory. Insertion can take too much time and cause bleeding in patients taking an anticoagulant. Insertion usually destroys the septum, and removal requires a complete patch of the entire septum. Systemic anticoagulation is required. Other disadvantages are risks of hemolysis, limb ischemia, and infection with longer support times.

The CentriMag (Levitronix LLC; Framingham, MA) is an improved device that requires only 1 cannula instead of 2 to cover both areas.

DEVICES FOR RIGHT-SIDED SUPPORT

Most early devices were designed for left-sided support. The right heart, especially in failure, has been more difficult to manage. Previously the only option for a patient with right ventricular failure was venoarterial ECMO. This is more support than needed for a patient with isolated right ventricular failure and involves the risk of multiple complications from the device.

With more options available for the right heart (Table 3), we can choose the most appropriate device according to the underlying cause of right heart failure (eg, right ventricular infarct, pulmonary hypertension), the likelihood of recovery, and the expected time to recovery.

The ideal RVAD would be easy to implant, maintain, and remove. It would allow for chest closure and patient ambulation. It would be durable and biocompatible, so that it could remain implanted for months if necessary. It would cause little blood trauma, have the capability for adding an oxygenator for pulmonary support, and be cost-effective.

Although no single system has all these qualities, each available device fulfills certain combinations of these criteria, so the best one can be selected for each patient’s needs.

ECMO Rotaflow centrifugal pump: Fast, simple, inexpensive

A recent improvement to ECMO is the Rotaflow centrifugal pump (Maquet, Wayne, NJ), which is connected by sewing an 8-mm graft onto the pulmonary artery and placing a venous cannula in the femoral vein. If the patient is not bleeding, the chest can then be closed. This creates a fast, simple, and inexpensive temporary RVAD system. When the patient is ready to be weaned, the outflow graft can be disconnected at the bedside without reopening the chest.

The disadvantage is that the Rotaflow system contains a sapphire bearing. Although it is magnetically coupled, it generates heat and is a nidus for thrombus formation, which can lead to pump failure and embolization. This system can be used for patients who are expected to need support for less than 5 to 7 days. Beyond this duration, the incidence of complications increases. 

CentriMag Ventricular Assist System offers right, left, or bilateral support

The CentriMag Ventricular Assist System is a fully magnetically levitated pump containing no bearings or seals, and with the same technology as is found in many of the durable devices such as HeartMate 3. It is coupled with a reusable motor and is easy to use.

CentriMag offers versatility, allowing for right, left, or bilateral ventricular support. An oxygenator can be added for pulmonary edema and additional support. It is the most biocompatible device and is FDA-approved for use for 4 weeks, although it has been used successfully for much longer. It allows for chest closure and ambulation. It is especially important as a bridge to transplant. The main disadvantage is that insertion and removal require sternotomy.

Impella RP: One size does not fit all

The Impella RP (Figure 5) has an 11F catheter diameter, 23F pump, and a maximum flow rate of more than 4 L/minute. It has a unique 3-dimensional cannula design based on computed tomography 3-dimensional reconstructions from hundreds of patients.

The device is biocompatible and can be used for support for more than 7 days, although most patients require only 3 or 4 days. There is almost no priming volume, so there is no hemodilution.

The disadvantages are that it is more challenging to place than other devices, and some patients cannot use it because the cannula does not fit. It also does not provide pulmonary support. Finally, it is the most expensive of the 3 right-sided devices.

CASE REVISITED

The patient described at the beginning of this article was extubated on day 12 but was then reintubated. On day 20, a tracheotomy tube was placed. By day 24, he had improved so little that his family signed a “do-not-resuscitate–comfort-care-arrest” order (ie, if the patient’s heart or breathing stops, only comfort care is to be provided).

But slowly he got better, and the Impella was removed on day 30. Afterward, serum creatinine and liver function tests began rising again, requiring dobutamine for heart support.

On day 34, his family reversed the do-not-resuscitate order, and he was reevaluated for an LVAD as destination therapy. At this point, echocardiography showed a left ventricular ejection fraction of 10%, normal right ventricular function, with a normal heartbeat and valves. On day 47, a HeartMate II LVAD was placed.

On postoperative day 18, he was transferred out of the intensive care unit, then discharged to an acute rehabilitation facility 8 days later (hospital day 73). He was subsequently discharged.

At a recent follow-up appointment, the patient said that he was feeling “pretty good” and walked with no shortness of breath.

A 43-year-old man presented to a community hospital with acute chest pain and shortness of breath and was diagnosed with anterior ST-elevation myocardial infarction. He was a smoker with a history of alcohol abuse, hypertension, and hyperlipidemia, and in the past he had undergone percutaneous coronary interventions to the right coronary artery and the first obtuse marginal artery.

Angiography showed total occlusion in the left anterior descending artery, 90% stenosis in the right coronary artery, and mild disease in the left circumflex artery. A drug-eluting stent was placed in the left anterior descending artery, resulting in good blood flow. 

However, his left ventricle continued to have severe dysfunction. An intra-aortic balloon pump was inserted. Afterward, computed tomography showed subsegmental pulmonary embolism with congestion. His mean arterial pressure was 60 mm Hg (normal 70–110), central venous pressure 12 mm Hg (3–8), pulmonary artery pressure 38/26 mm Hg (15–30/4–12), pulmonary capillary wedge pressure 24 mm Hg (2–15), and cardiac index 1.4 L/min (2.5–4).

The patient was started on dobutamine and norepinephrine and transferred to Cleveland Clinic on day 2. Over the next day, he had runs of ventricular tachycardia, for which he was given amiodarone and lidocaine. His urine output was low, and his serum creatinine was elevated at 1.65 mg/dL (baseline 1.2, normal 0.5–1.5). Liver function tests were also elevated, with aspartate aminotransferase at 115 U/L(14–40) and alanine aminotransferase at 187 U/L (10–54).

Poor oxygenation was evident: his arterial partial pressure of oxygen was 64 mm Hg (normal 75–100). He was intubated and given 100% oxygen with positive end-expiratory pressure of 12 cm H₂O.

Echocardiography showed a left ventricular ejection fraction of 15% (normal 55%–70%) and mild right ventricular dysfunction.

ECMO and then Impella placement

On his third hospital day, a venoarterial extracorporeal membrane oxygenation (ECMO) device was placed peripherally (Figure 1).

His hemodynamic variables stabilized, and he was weaned off dobutamine and norepinephrine. Results of liver function tests normalized, his urinary output increased, and his serum creatinine dropped to a normal 1.0 mg/dL. However, a chest radiograph showed pulmonary congestion, and echocardiography now showed severe left ventricular dysfunction.

On hospital day 5, the patient underwent surgical placement of an Impella 5.0 device (Abiomed, Danvers, MA) through the right axillary artery in an effort to improve his pulmonary edema. The ECMO device was removed. Placement of a venovenous ECMO device was deemed unnecessary when oxygenation improved with the Impella.

Three days after Impella placement, radiography showed improved edema with some remaining pleural effusion.

ACUTE CARDIOGENIC SHOCK

Cardiogenic shock remains a challenging clinical problem: patients with it are among the sickest in the hospital, and many of them die. ECMO was once the only therapy available and is still widely used. However, it is a 2-edged sword; complications such as bleeding, infection, and thrombosis are almost inevitable if it is used for long. Importantly, patients are usually kept intubated and bedridden.

In recent years, new devices have become available that are easier to place (some in the catheterization laboratory or even at the bedside) and allow safer bridging to recovery, transplant, or other therapies.

This case illustrates the natural history of cardiogenic shock and the preferred clinical approach: ie, ongoing evaluation that permits rapid response to evolving challenges.

In general, acute cardiogenic shock occurs within 24 to 48 hours after the initial insult, so even if a procedure succeeds, the patient may develop progressive hypotension and organ dysfunction. Reduced cardiac output causes a downward spiral with multiple systemic and inflammatory processes as well as increased nitric oxide synthesis, leading to progressive decline and eventual end-organ dysfunction.

Continuously evaluate

The cardiac team should continuously assess the acuity and severity of a patient’s condition, with the goals of maintaining end-organ perfusion and identifying the source of problems. Refractory cardiogenic shock, with tissue hypoperfusion despite vasoactive medications and treatment of the underlying cause, is associated with in-hospital mortality rates ranging from 30% to 50%.^1,2 The rates have actually increased over the past decade, as sicker patients are being treated.

When a patient presents with cardiogenic shock, we first try a series of vasoactive drugs and usually an intra-aortic balloon pump (Figure 2). We then tailor treatment depending on etiology. For example, a patient may have viral myocarditis and may even require a biopsy.

If cardiogenic shock is refractory, mechanical circulatory support devices can be a short-term bridge to either recovery or a new decision. A multidisciplinary team should be consulted to consider transplant, a long-term device, or palliative care. Sometimes a case requires “bridging to a bridge,” with several devices used short-term in turn.

Prognostic factors in cardiogenic shock

Several tools help predict outcome in a severely ill patient. End-organ function, indicated by blood lactate levels and estimated glomerular filtration rate, is perhaps the most informative and should be monitored serially.

CardShock³ is a simple scoring system based on age, mental status at presentation, laboratory values, and medical history. Patients receive 1 point for each of the following factors:

• Age > 75
• Confusion at presentation
• Previous myocardial infarction or coronary artery bypass grafting
• Acute coronary syndrome etiology
• Left ventricular ejection fraction < 40%
• Blood lactate level between 2 and 4 mmol/L, inclusively (2 points for lactate levels > 4 mmol/L)
• Estimated glomerular filtration rate between 30 and 60 mL/min/1.73 m², inclusively (2 points if < 30 mL/min/1.73 m²). 

Thus, scores range from 0 (best) to 9 (worst). A score of 0 to 3 points was associated with a 9% risk of death in the hospital, a score of 4 or 5 with a risk of 36%, and a score of 6 through 9 with a risk of 77%.³

The Survival After Veno-arterial ECMO (SAVE) score (www.save-score.com) is a prediction tool derived from a large international ECMO registry.⁴ It is based on patient age, diagnosis, and indicators of end-organ dysfunction. Scores range from –35 (worst) to +7 (best).

The mortality rate associated with postcardiotomy cardiogenic shock increases with the amount of inotropic support provided. In a 1996–1999 case series of patients who underwent open-heart surgery,⁵ the hospital mortality rate was 40% in those who received 2 inotropes in high doses and 80% in those who received 3. A strategy of early implementation of mechanical support is critical.

Selection criteria for destination therapy

Deciding whether a patient should receive a long-term device is frequently a challenge. The decision often must be based on limited information about not only the medical indications but also psychosocial factors that influence long-term success.

The Centers for Medicare and Medicaid Services have established criteria for candidates for left ventricular assist devices (LVADs) as destination therapy.⁶ Contraindications established for heart transplant should also be considered (Table 1).

CASE REVISITED

Several factors argued against LVAD placement in our patient. He had no health insurance and had been off medications. He smoked and said he consumed 3 hard liquor drinks per week. His Stanford Integrated Psychosocial Assessment for Transplantation score was 30 (minimally acceptable). He had hypoxia with subsegmental pulmonary edema, a strong contraindication to immediate transplant.

On the other hand, he had only mild right ventricular dysfunction. His CardShock score was 4 (intermediate risk, based on lactate 1.5 mmol/L and estimated glomerular filtration rate 52 mL/min/1.73 m²). His SAVE score was –9 (class IV), which overall is associated with a 30% risk of death (low enough to consider treatment).

During the patient’s time on temporary support, the team had the opportunity to better understand him and assess his family support and his ability to handle a permanent device. His surviving the acute course bolstered the team’s confidence that he could enjoy long-term survival with destination therapy.

CATHETERIZATION LABORATORY DEVICE CAPABILITIES

Although most implantation procedures are done in the operating room, they are often done in the catheterization laboratory because patients undergoing catheterization may not be stable enough for transfer, or an emergency intervention may be required during the night. Catheterization interventionists are also an important part of the team to help determine the best approach for long-term therapy.

The catheterization laboratory has multiple acute intervention options. Usually, decisions must be made quickly. In general, patients needing mechanical support are managed as follows:

• Those who need circulation support and oxygenation receive ECMO
• Those who need circulation support alone because of mechanical issues (eg, myocardial infarction) are considered for an intra-aortic balloon pump, Impella, or TandemHeart pump (Cardiac Assist, Pittsburgh, PA).

Factors that guide the selection of a temporary pump include:

• Left ventricular function
• Right ventricular function
• Aortic valve stenosis (some devices cannot be inserted through critical aortic stenosis)
• Aortic regurgitation (can affect some devices)
• Peripheral artery disease (some devices are large and must be placed percutaneously).

CHOOSING AMONG PERCUTANEOUS DEVICES

Circulatory support in cardiogenic shock improves outcomes, and devices play an important role in supporting high-risk procedures. The goal is not necessarily to use the device throughout the hospital stay. Acute stabilization is most important initially; a more considered decision about long-term therapy can be made when more is known about the patient.

Patient selection is the most important component of success. However, randomized data to support outcomes with the various devices are sparse and complicated by the critically ill state of the patient population.

SHORT-TERM CIRCULATORY SUPPORT: ECMO, IMPELLA, TANDEMHEART

A menu of options is available for temporary mechanical support. Options differ by their degree of circulatory support and ease of insertion (Table 2).

ECMO: A fast option with many advantages

ECMO has evolved and now can be placed quickly. A remote diagnostic platform such as CardioHub permits management at the bedside, in the medical unit, or in the cardiac intensive care unit.⁷

ECMO has several advantages. It can be used during cardiopulmonary bypass, it provides oxygenation, it is the only option in the setting of lung injury, it can be placed peripherally (without thoracotomy), and it is the only percutaneous option for biventricular support.

ECMO also has significant disadvantages

ECMO is a good device for acute resuscitation of a patient in shock, as it offers quick placement and resuscitation. But it is falling out of favor because of significant disadvantages.

Its major drawback is that it provides no left ventricular unloading. Although in a very unstable patient ECMO can stabilize end organs and restore their function, the lack of left ventricular unloading and reduced ventricular work threaten the myocardium. It creates extremely high afterload; therefore, in a left ventricle with poor function, wall tension and myocardial oxygen demand increase. Multiple studies have shown that coronary perfusion worsens, especially if the patient is cannulated peripherally. Because relative cerebral hypoxia occurs in many situations, it is imperative to check blood saturations at multiple sites to determine if perfusion is adequate everywhere.    

Ineffective left ventricular unloading with venoarterial ECMO is managed in several ways. Sometimes left ventricular distention is slight and the effects are subtle. Left ventricular distention causing pulmonary edema can be addressed with:

• Inotropes (in moderate doses)
• Anticoagulation to prevent left ventricular thrombus formation
• An intra-aortic balloon pump. Most patients on ECMO already have an intra-aortic balloon pump in place, and it should be left in to provide additional support. For those who do not have one, it should be placed via the contralateral femoral artery.

If problems persist despite these measures, apical cannulation or left ventricular septostomy can be performed.

Outcomes with ECMO have been disappointing. Studies show that whether ECMO was indicated for cardiac failure or for respiratory failure, survival is only about 25% at 5 years. Analyzing data only for arteriovenous ECMO, survival was 48% in bridged patients and 41% in patients who were weaned.

The Extracorporeal Life Support Organization Registry, in their international summary from 2010, found that 34% of cardiac patients on ECMO survived to discharge or transfer. Most of these patients had cardiogenic shock from acute myocardial infarction. Outcomes are so poor because of complications endemic to ECMO, eg, dialysis-dependent renal failure (about 40%) and neurologic complications (about 30%), often involving ischemic or hemorrhagic stroke.

Limb and pump complications were also significant in the past. These have been reduced with the new reperfusion cannula and the Quadrox oxygenator.  

Complications unique to ECMO should be understood and anticipated so that they can be avoided. Better tools are available, ie, Impella and TandemHeart.

Left-sided Impella: A longer-term temporary support

ECMO is a temporary fix that is usually used only for a few days. If longer support is needed, axillary placement of an Impella should be used as a bridge to recovery, transplant, or a durable LVAD.

The Impella device (Figure 3) is a miniature rotary blood pump increasingly used to treat cardiogenic shock. It is inserted retrograde across the aortic valve to provide short-term ventricular support. Most devices are approved by the US Food and Drug Administration (FDA) for less than 7 days of use, but we have experience using them up to 30 days. They are very hemocompatible, involving minimal hemolysis. Axillary placement allows early extubation and ambulation and is more stable than groin placement.

Several models are available: the 2.5 and 3.5 L/min devices can be placed percutaneously, while the 5 L/min model must be surgically placed in the axillary or groin region. Heparin is required with their use. They can replace ECMO. A right ventricular assist device (RVAD), Impella RP, is also available.

Physiologic impact of the Impella

The Impella fully unloads the left ventricle, reducing myocardial oxygen demand and increasing myocardial blood flow. It reduces end-diastolic volume and pressure, the mechanical work of the heart, and wall tension. Microvascular resistance is reduced, allowing increased coronary flow. Cardiac output and power are increased by multiple means.^8–11

The RECOVER 1 trial evaluated the 5L Impella placed after cardiac surgery. The cardiac index increased in all the patients, and the systemic vascular resistance and wedge pressure decreased.¹²

Unloading the ventricle is critical. Meyns  and colleagues¹³ found a fivefold reduction in infarct size from baseline in a left anterior descending occlusion model in pigs after off-loading the ventricle.

Impella has the advantage of simple percutaneous insertion (the 2.5 and CP models). It also tests right ventricular tolerance: if the right ventricle is doing well, one can predict with high certainty that it will tolerate an LVAD (eg, HeartWare, HeartMate 2 (Pleasanton, CA), or HeartMate 3 when available).

Disadvantages include that it provides only left ventricular support, although a right ventricular device can be inserted for dual support. Placement requires fluoroscopic or echocardiographic guidance.

TandemHeart requires septal puncture

The TandemHeart is approved for short-term and biventricular use. It consists of an extracorporeal centrifugal pump that withdraws blood from the left atrium via a trans-septal cannula placed through the femoral vein (Figure 4) and returns it to one or both femoral arteries. The blood is pumped at up to 5 L/min.

It is designed to reduce the pulmonary capillary wedge pressure, ventricular work, and myocardial oxygen demand and increase cardiac output and mean arterial pressure. It has the advantages of percutaneous placement and the ability to provide biventricular support with 2 devices. It can be used for up to 3 weeks. It can easily be converted to ECMO by either splicing in an oxygenator or adding another cannula.

Although the TandemHeart provides significant support, it is no longer often used. A 21F venous cannula must be passed to the left atrium by trans-septal puncture, which requires advanced skill and must be done in the catheterization laboratory. Insertion can take too much time and cause bleeding in patients taking an anticoagulant. Insertion usually destroys the septum, and removal requires a complete patch of the entire septum. Systemic anticoagulation is required. Other disadvantages are risks of hemolysis, limb ischemia, and infection with longer support times.

The CentriMag (Levitronix LLC; Framingham, MA) is an improved device that requires only 1 cannula instead of 2 to cover both areas.

DEVICES FOR RIGHT-SIDED SUPPORT

Most early devices were designed for left-sided support. The right heart, especially in failure, has been more difficult to manage. Previously the only option for a patient with right ventricular failure was venoarterial ECMO. This is more support than needed for a patient with isolated right ventricular failure and involves the risk of multiple complications from the device.

With more options available for the right heart (Table 3), we can choose the most appropriate device according to the underlying cause of right heart failure (eg, right ventricular infarct, pulmonary hypertension), the likelihood of recovery, and the expected time to recovery.

The ideal RVAD would be easy to implant, maintain, and remove. It would allow for chest closure and patient ambulation. It would be durable and biocompatible, so that it could remain implanted for months if necessary. It would cause little blood trauma, have the capability for adding an oxygenator for pulmonary support, and be cost-effective.

Although no single system has all these qualities, each available device fulfills certain combinations of these criteria, so the best one can be selected for each patient’s needs.

ECMO Rotaflow centrifugal pump: Fast, simple, inexpensive

A recent improvement to ECMO is the Rotaflow centrifugal pump (Maquet, Wayne, NJ), which is connected by sewing an 8-mm graft onto the pulmonary artery and placing a venous cannula in the femoral vein. If the patient is not bleeding, the chest can then be closed. This creates a fast, simple, and inexpensive temporary RVAD system. When the patient is ready to be weaned, the outflow graft can be disconnected at the bedside without reopening the chest.

The disadvantage is that the Rotaflow system contains a sapphire bearing. Although it is magnetically coupled, it generates heat and is a nidus for thrombus formation, which can lead to pump failure and embolization. This system can be used for patients who are expected to need support for less than 5 to 7 days. Beyond this duration, the incidence of complications increases. 

CentriMag Ventricular Assist System offers right, left, or bilateral support

The CentriMag Ventricular Assist System is a fully magnetically levitated pump containing no bearings or seals, and with the same technology as is found in many of the durable devices such as HeartMate 3. It is coupled with a reusable motor and is easy to use.

CentriMag offers versatility, allowing for right, left, or bilateral ventricular support. An oxygenator can be added for pulmonary edema and additional support. It is the most biocompatible device and is FDA-approved for use for 4 weeks, although it has been used successfully for much longer. It allows for chest closure and ambulation. It is especially important as a bridge to transplant. The main disadvantage is that insertion and removal require sternotomy.

Impella RP: One size does not fit all

The Impella RP (Figure 5) has an 11F catheter diameter, 23F pump, and a maximum flow rate of more than 4 L/minute. It has a unique 3-dimensional cannula design based on computed tomography 3-dimensional reconstructions from hundreds of patients.

The device is biocompatible and can be used for support for more than 7 days, although most patients require only 3 or 4 days. There is almost no priming volume, so there is no hemodilution.

The disadvantages are that it is more challenging to place than other devices, and some patients cannot use it because the cannula does not fit. It also does not provide pulmonary support. Finally, it is the most expensive of the 3 right-sided devices.

CASE REVISITED

The patient described at the beginning of this article was extubated on day 12 but was then reintubated. On day 20, a tracheotomy tube was placed. By day 24, he had improved so little that his family signed a “do-not-resuscitate–comfort-care-arrest” order (ie, if the patient’s heart or breathing stops, only comfort care is to be provided).

But slowly he got better, and the Impella was removed on day 30. Afterward, serum creatinine and liver function tests began rising again, requiring dobutamine for heart support.

On day 34, his family reversed the do-not-resuscitate order, and he was reevaluated for an LVAD as destination therapy. At this point, echocardiography showed a left ventricular ejection fraction of 10%, normal right ventricular function, with a normal heartbeat and valves. On day 47, a HeartMate II LVAD was placed.

On postoperative day 18, he was transferred out of the intensive care unit, then discharged to an acute rehabilitation facility 8 days later (hospital day 73). He was subsequently discharged.

At a recent follow-up appointment, the patient said that he was feeling “pretty good” and walked with no shortness of breath.

A 43-year-old man presented to a community hospital with acute chest pain and shortness of breath and was diagnosed with anterior ST-elevation myocardial infarction. He was a smoker with a history of alcohol abuse, hypertension, and hyperlipidemia, and in the past he had undergone percutaneous coronary interventions to the right coronary artery and the first obtuse marginal artery.

Angiography showed total occlusion in the left anterior descending artery, 90% stenosis in the right coronary artery, and mild disease in the left circumflex artery. A drug-eluting stent was placed in the left anterior descending artery, resulting in good blood flow. 

However, his left ventricle continued to have severe dysfunction. An intra-aortic balloon pump was inserted. Afterward, computed tomography showed subsegmental pulmonary embolism with congestion. His mean arterial pressure was 60 mm Hg (normal 70–110), central venous pressure 12 mm Hg (3–8), pulmonary artery pressure 38/26 mm Hg (15–30/4–12), pulmonary capillary wedge pressure 24 mm Hg (2–15), and cardiac index 1.4 L/min (2.5–4).

The patient was started on dobutamine and norepinephrine and transferred to Cleveland Clinic on day 2. Over the next day, he had runs of ventricular tachycardia, for which he was given amiodarone and lidocaine. His urine output was low, and his serum creatinine was elevated at 1.65 mg/dL (baseline 1.2, normal 0.5–1.5). Liver function tests were also elevated, with aspartate aminotransferase at 115 U/L(14–40) and alanine aminotransferase at 187 U/L (10–54).

Poor oxygenation was evident: his arterial partial pressure of oxygen was 64 mm Hg (normal 75–100). He was intubated and given 100% oxygen with positive end-expiratory pressure of 12 cm H₂O.

Echocardiography showed a left ventricular ejection fraction of 15% (normal 55%–70%) and mild right ventricular dysfunction.

ECMO and then Impella placement

On his third hospital day, a venoarterial extracorporeal membrane oxygenation (ECMO) device was placed peripherally (Figure 1).

His hemodynamic variables stabilized, and he was weaned off dobutamine and norepinephrine. Results of liver function tests normalized, his urinary output increased, and his serum creatinine dropped to a normal 1.0 mg/dL. However, a chest radiograph showed pulmonary congestion, and echocardiography now showed severe left ventricular dysfunction.

On hospital day 5, the patient underwent surgical placement of an Impella 5.0 device (Abiomed, Danvers, MA) through the right axillary artery in an effort to improve his pulmonary edema. The ECMO device was removed. Placement of a venovenous ECMO device was deemed unnecessary when oxygenation improved with the Impella.

Three days after Impella placement, radiography showed improved edema with some remaining pleural effusion.

ACUTE CARDIOGENIC SHOCK

Cardiogenic shock remains a challenging clinical problem: patients with it are among the sickest in the hospital, and many of them die. ECMO was once the only therapy available and is still widely used. However, it is a 2-edged sword; complications such as bleeding, infection, and thrombosis are almost inevitable if it is used for long. Importantly, patients are usually kept intubated and bedridden.

In recent years, new devices have become available that are easier to place (some in the catheterization laboratory or even at the bedside) and allow safer bridging to recovery, transplant, or other therapies.

This case illustrates the natural history of cardiogenic shock and the preferred clinical approach: ie, ongoing evaluation that permits rapid response to evolving challenges.

In general, acute cardiogenic shock occurs within 24 to 48 hours after the initial insult, so even if a procedure succeeds, the patient may develop progressive hypotension and organ dysfunction. Reduced cardiac output causes a downward spiral with multiple systemic and inflammatory processes as well as increased nitric oxide synthesis, leading to progressive decline and eventual end-organ dysfunction.

Continuously evaluate

The cardiac team should continuously assess the acuity and severity of a patient’s condition, with the goals of maintaining end-organ perfusion and identifying the source of problems. Refractory cardiogenic shock, with tissue hypoperfusion despite vasoactive medications and treatment of the underlying cause, is associated with in-hospital mortality rates ranging from 30% to 50%.^1,2 The rates have actually increased over the past decade, as sicker patients are being treated.

When a patient presents with cardiogenic shock, we first try a series of vasoactive drugs and usually an intra-aortic balloon pump (Figure 2). We then tailor treatment depending on etiology. For example, a patient may have viral myocarditis and may even require a biopsy.

If cardiogenic shock is refractory, mechanical circulatory support devices can be a short-term bridge to either recovery or a new decision. A multidisciplinary team should be consulted to consider transplant, a long-term device, or palliative care. Sometimes a case requires “bridging to a bridge,” with several devices used short-term in turn.

Prognostic factors in cardiogenic shock

Several tools help predict outcome in a severely ill patient. End-organ function, indicated by blood lactate levels and estimated glomerular filtration rate, is perhaps the most informative and should be monitored serially.

CardShock³ is a simple scoring system based on age, mental status at presentation, laboratory values, and medical history. Patients receive 1 point for each of the following factors:

• Age > 75
• Confusion at presentation
• Previous myocardial infarction or coronary artery bypass grafting
• Acute coronary syndrome etiology
• Left ventricular ejection fraction < 40%
• Blood lactate level between 2 and 4 mmol/L, inclusively (2 points for lactate levels > 4 mmol/L)
• Estimated glomerular filtration rate between 30 and 60 mL/min/1.73 m², inclusively (2 points if < 30 mL/min/1.73 m²). 

Thus, scores range from 0 (best) to 9 (worst). A score of 0 to 3 points was associated with a 9% risk of death in the hospital, a score of 4 or 5 with a risk of 36%, and a score of 6 through 9 with a risk of 77%.³

The Survival After Veno-arterial ECMO (SAVE) score (www.save-score.com) is a prediction tool derived from a large international ECMO registry.⁴ It is based on patient age, diagnosis, and indicators of end-organ dysfunction. Scores range from –35 (worst) to +7 (best).

The mortality rate associated with postcardiotomy cardiogenic shock increases with the amount of inotropic support provided. In a 1996–1999 case series of patients who underwent open-heart surgery,⁵ the hospital mortality rate was 40% in those who received 2 inotropes in high doses and 80% in those who received 3. A strategy of early implementation of mechanical support is critical.

Selection criteria for destination therapy

Deciding whether a patient should receive a long-term device is frequently a challenge. The decision often must be based on limited information about not only the medical indications but also psychosocial factors that influence long-term success.

The Centers for Medicare and Medicaid Services have established criteria for candidates for left ventricular assist devices (LVADs) as destination therapy.⁶ Contraindications established for heart transplant should also be considered (Table 1).

CASE REVISITED

Several factors argued against LVAD placement in our patient. He had no health insurance and had been off medications. He smoked and said he consumed 3 hard liquor drinks per week. His Stanford Integrated Psychosocial Assessment for Transplantation score was 30 (minimally acceptable). He had hypoxia with subsegmental pulmonary edema, a strong contraindication to immediate transplant.

On the other hand, he had only mild right ventricular dysfunction. His CardShock score was 4 (intermediate risk, based on lactate 1.5 mmol/L and estimated glomerular filtration rate 52 mL/min/1.73 m²). His SAVE score was –9 (class IV), which overall is associated with a 30% risk of death (low enough to consider treatment).

During the patient’s time on temporary support, the team had the opportunity to better understand him and assess his family support and his ability to handle a permanent device. His surviving the acute course bolstered the team’s confidence that he could enjoy long-term survival with destination therapy.

CATHETERIZATION LABORATORY DEVICE CAPABILITIES

Although most implantation procedures are done in the operating room, they are often done in the catheterization laboratory because patients undergoing catheterization may not be stable enough for transfer, or an emergency intervention may be required during the night. Catheterization interventionists are also an important part of the team to help determine the best approach for long-term therapy.

The catheterization laboratory has multiple acute intervention options. Usually, decisions must be made quickly. In general, patients needing mechanical support are managed as follows:

• Those who need circulation support and oxygenation receive ECMO
• Those who need circulation support alone because of mechanical issues (eg, myocardial infarction) are considered for an intra-aortic balloon pump, Impella, or TandemHeart pump (Cardiac Assist, Pittsburgh, PA).

Factors that guide the selection of a temporary pump include:

• Left ventricular function
• Right ventricular function
• Aortic valve stenosis (some devices cannot be inserted through critical aortic stenosis)
• Aortic regurgitation (can affect some devices)
• Peripheral artery disease (some devices are large and must be placed percutaneously).

CHOOSING AMONG PERCUTANEOUS DEVICES

Circulatory support in cardiogenic shock improves outcomes, and devices play an important role in supporting high-risk procedures. The goal is not necessarily to use the device throughout the hospital stay. Acute stabilization is most important initially; a more considered decision about long-term therapy can be made when more is known about the patient.

Patient selection is the most important component of success. However, randomized data to support outcomes with the various devices are sparse and complicated by the critically ill state of the patient population.

SHORT-TERM CIRCULATORY SUPPORT: ECMO, IMPELLA, TANDEMHEART

A menu of options is available for temporary mechanical support. Options differ by their degree of circulatory support and ease of insertion (Table 2).

ECMO: A fast option with many advantages

ECMO has evolved and now can be placed quickly. A remote diagnostic platform such as CardioHub permits management at the bedside, in the medical unit, or in the cardiac intensive care unit.⁷

ECMO has several advantages. It can be used during cardiopulmonary bypass, it provides oxygenation, it is the only option in the setting of lung injury, it can be placed peripherally (without thoracotomy), and it is the only percutaneous option for biventricular support.

ECMO also has significant disadvantages

ECMO is a good device for acute resuscitation of a patient in shock, as it offers quick placement and resuscitation. But it is falling out of favor because of significant disadvantages.

Its major drawback is that it provides no left ventricular unloading. Although in a very unstable patient ECMO can stabilize end organs and restore their function, the lack of left ventricular unloading and reduced ventricular work threaten the myocardium. It creates extremely high afterload; therefore, in a left ventricle with poor function, wall tension and myocardial oxygen demand increase. Multiple studies have shown that coronary perfusion worsens, especially if the patient is cannulated peripherally. Because relative cerebral hypoxia occurs in many situations, it is imperative to check blood saturations at multiple sites to determine if perfusion is adequate everywhere.    

Ineffective left ventricular unloading with venoarterial ECMO is managed in several ways. Sometimes left ventricular distention is slight and the effects are subtle. Left ventricular distention causing pulmonary edema can be addressed with:

• Inotropes (in moderate doses)
• Anticoagulation to prevent left ventricular thrombus formation
• An intra-aortic balloon pump. Most patients on ECMO already have an intra-aortic balloon pump in place, and it should be left in to provide additional support. For those who do not have one, it should be placed via the contralateral femoral artery.

If problems persist despite these measures, apical cannulation or left ventricular septostomy can be performed.

Outcomes with ECMO have been disappointing. Studies show that whether ECMO was indicated for cardiac failure or for respiratory failure, survival is only about 25% at 5 years. Analyzing data only for arteriovenous ECMO, survival was 48% in bridged patients and 41% in patients who were weaned.

The Extracorporeal Life Support Organization Registry, in their international summary from 2010, found that 34% of cardiac patients on ECMO survived to discharge or transfer. Most of these patients had cardiogenic shock from acute myocardial infarction. Outcomes are so poor because of complications endemic to ECMO, eg, dialysis-dependent renal failure (about 40%) and neurologic complications (about 30%), often involving ischemic or hemorrhagic stroke.

Limb and pump complications were also significant in the past. These have been reduced with the new reperfusion cannula and the Quadrox oxygenator.  

Complications unique to ECMO should be understood and anticipated so that they can be avoided. Better tools are available, ie, Impella and TandemHeart.

Left-sided Impella: A longer-term temporary support

ECMO is a temporary fix that is usually used only for a few days. If longer support is needed, axillary placement of an Impella should be used as a bridge to recovery, transplant, or a durable LVAD.

The Impella device (Figure 3) is a miniature rotary blood pump increasingly used to treat cardiogenic shock. It is inserted retrograde across the aortic valve to provide short-term ventricular support. Most devices are approved by the US Food and Drug Administration (FDA) for less than 7 days of use, but we have experience using them up to 30 days. They are very hemocompatible, involving minimal hemolysis. Axillary placement allows early extubation and ambulation and is more stable than groin placement.

Several models are available: the 2.5 and 3.5 L/min devices can be placed percutaneously, while the 5 L/min model must be surgically placed in the axillary or groin region. Heparin is required with their use. They can replace ECMO. A right ventricular assist device (RVAD), Impella RP, is also available.

Physiologic impact of the Impella

The Impella fully unloads the left ventricle, reducing myocardial oxygen demand and increasing myocardial blood flow. It reduces end-diastolic volume and pressure, the mechanical work of the heart, and wall tension. Microvascular resistance is reduced, allowing increased coronary flow. Cardiac output and power are increased by multiple means.^8–11

The RECOVER 1 trial evaluated the 5L Impella placed after cardiac surgery. The cardiac index increased in all the patients, and the systemic vascular resistance and wedge pressure decreased.¹²

Unloading the ventricle is critical. Meyns  and colleagues¹³ found a fivefold reduction in infarct size from baseline in a left anterior descending occlusion model in pigs after off-loading the ventricle.

Impella has the advantage of simple percutaneous insertion (the 2.5 and CP models). It also tests right ventricular tolerance: if the right ventricle is doing well, one can predict with high certainty that it will tolerate an LVAD (eg, HeartWare, HeartMate 2 (Pleasanton, CA), or HeartMate 3 when available).

Disadvantages include that it provides only left ventricular support, although a right ventricular device can be inserted for dual support. Placement requires fluoroscopic or echocardiographic guidance.

TandemHeart requires septal puncture

The TandemHeart is approved for short-term and biventricular use. It consists of an extracorporeal centrifugal pump that withdraws blood from the left atrium via a trans-septal cannula placed through the femoral vein (Figure 4) and returns it to one or both femoral arteries. The blood is pumped at up to 5 L/min.

It is designed to reduce the pulmonary capillary wedge pressure, ventricular work, and myocardial oxygen demand and increase cardiac output and mean arterial pressure. It has the advantages of percutaneous placement and the ability to provide biventricular support with 2 devices. It can be used for up to 3 weeks. It can easily be converted to ECMO by either splicing in an oxygenator or adding another cannula.

Although the TandemHeart provides significant support, it is no longer often used. A 21F venous cannula must be passed to the left atrium by trans-septal puncture, which requires advanced skill and must be done in the catheterization laboratory. Insertion can take too much time and cause bleeding in patients taking an anticoagulant. Insertion usually destroys the septum, and removal requires a complete patch of the entire septum. Systemic anticoagulation is required. Other disadvantages are risks of hemolysis, limb ischemia, and infection with longer support times.

The CentriMag (Levitronix LLC; Framingham, MA) is an improved device that requires only 1 cannula instead of 2 to cover both areas.

DEVICES FOR RIGHT-SIDED SUPPORT

Most early devices were designed for left-sided support. The right heart, especially in failure, has been more difficult to manage. Previously the only option for a patient with right ventricular failure was venoarterial ECMO. This is more support than needed for a patient with isolated right ventricular failure and involves the risk of multiple complications from the device.

With more options available for the right heart (Table 3), we can choose the most appropriate device according to the underlying cause of right heart failure (eg, right ventricular infarct, pulmonary hypertension), the likelihood of recovery, and the expected time to recovery.

The ideal RVAD would be easy to implant, maintain, and remove. It would allow for chest closure and patient ambulation. It would be durable and biocompatible, so that it could remain implanted for months if necessary. It would cause little blood trauma, have the capability for adding an oxygenator for pulmonary support, and be cost-effective.

Although no single system has all these qualities, each available device fulfills certain combinations of these criteria, so the best one can be selected for each patient’s needs.

ECMO Rotaflow centrifugal pump: Fast, simple, inexpensive

A recent improvement to ECMO is the Rotaflow centrifugal pump (Maquet, Wayne, NJ), which is connected by sewing an 8-mm graft onto the pulmonary artery and placing a venous cannula in the femoral vein. If the patient is not bleeding, the chest can then be closed. This creates a fast, simple, and inexpensive temporary RVAD system. When the patient is ready to be weaned, the outflow graft can be disconnected at the bedside without reopening the chest.

The disadvantage is that the Rotaflow system contains a sapphire bearing. Although it is magnetically coupled, it generates heat and is a nidus for thrombus formation, which can lead to pump failure and embolization. This system can be used for patients who are expected to need support for less than 5 to 7 days. Beyond this duration, the incidence of complications increases. 

CentriMag Ventricular Assist System offers right, left, or bilateral support

The CentriMag Ventricular Assist System is a fully magnetically levitated pump containing no bearings or seals, and with the same technology as is found in many of the durable devices such as HeartMate 3. It is coupled with a reusable motor and is easy to use.

CentriMag offers versatility, allowing for right, left, or bilateral ventricular support. An oxygenator can be added for pulmonary edema and additional support. It is the most biocompatible device and is FDA-approved for use for 4 weeks, although it has been used successfully for much longer. It allows for chest closure and ambulation. It is especially important as a bridge to transplant. The main disadvantage is that insertion and removal require sternotomy.

Impella RP: One size does not fit all

The Impella RP (Figure 5) has an 11F catheter diameter, 23F pump, and a maximum flow rate of more than 4 L/minute. It has a unique 3-dimensional cannula design based on computed tomography 3-dimensional reconstructions from hundreds of patients.

The device is biocompatible and can be used for support for more than 7 days, although most patients require only 3 or 4 days. There is almost no priming volume, so there is no hemodilution.

The disadvantages are that it is more challenging to place than other devices, and some patients cannot use it because the cannula does not fit. It also does not provide pulmonary support. Finally, it is the most expensive of the 3 right-sided devices.

CASE REVISITED

The patient described at the beginning of this article was extubated on day 12 but was then reintubated. On day 20, a tracheotomy tube was placed. By day 24, he had improved so little that his family signed a “do-not-resuscitate–comfort-care-arrest” order (ie, if the patient’s heart or breathing stops, only comfort care is to be provided).

But slowly he got better, and the Impella was removed on day 30. Afterward, serum creatinine and liver function tests began rising again, requiring dobutamine for heart support.

On day 34, his family reversed the do-not-resuscitate order, and he was reevaluated for an LVAD as destination therapy. At this point, echocardiography showed a left ventricular ejection fraction of 10%, normal right ventricular function, with a normal heartbeat and valves. On day 47, a HeartMate II LVAD was placed.

On postoperative day 18, he was transferred out of the intensive care unit, then discharged to an acute rehabilitation facility 8 days later (hospital day 73). He was subsequently discharged.

At a recent follow-up appointment, the patient said that he was feeling “pretty good” and walked with no shortness of breath.