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Dactylitis signals more severe psoriatic arthritis
SNOWMASS, COLO. – Dactylitis is a common and painful extra-articular manifestation of psoriatic arthritis that takes on added clinical significance because it’s also a marker of greater disease severity, Christopher T. Ritchlin, MD, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
Indeed, psoriatic arthritis (PsA) patients with dactylitis are more likely to have polyarticular disease and radiologic evidence of bony damage, noted Dr. Ritchlin, professor of medicine and chief of the allergy, immunology, and rheumatology division at the University of Rochester (N.Y.).
“We have no idea why this is,” confessed Dr. Ritchlin, who is also director of the Clinical Immunology Research Center at the university.
The differential diagnosis for dactylitis includes psoriatic arthritis, other spondyloarthropathies, sickle cell disease, tuberculosis, sarcoidosis, and pyogenic flexor tenosynovitis, a closed-space infection that is the major issue in the differential. Dr. Ritchlin sees many more cases of dactylitis due to PsA that get misdiagnosed as a flexor tendon sheath infection and inappropriately subjected to surgery and/or intravenous antibiotics than vice versa.
Pyogenic flexor tenosynovitis can be identified using the four Kanavel signs: diffuse swelling of a digit, often with discoloration; intense pain over the whole length of the tendon sheath, but limited to the sheath; the involved digit being held in a semiflexed posture; and exquisite pain upon passive extension of the digit, with the pain being worst at the proximal end.
University of Toronto investigators have demonstrated that, in their large longitudinal database of PsA patients, the prevalence of radiologic damage in participants with acute dactylitis of the hands is twice as great as in PsA patients without dactylitis.
“I’ve been struck over the years by how often I see psoriatic arthritis patients with dactylitic digits who not only have erosions but who actually have a complete fusion or ankylosis of the joint. The point is, when you have a joint with diffuse inflammation, in many patients it’s associated with activation of both osteoclasts and osteoblasts,” according to the rheumatologist.
Enthesitis
Enthesitis, another cardinal extra-articular manifestation of PsA, is defined by inflammation at the sites where tendons, ligaments, and joint capsules attach into bone. The most commonly involved sites are the Achilles tendon and plantar fascia.
“It can also involve a lot of other areas and can lead to misdiagnosis as a result. Many of these patients end up in rheumatologists’ offices with previous diagnoses ranging from fibromyalgia or other chronic pain syndromes to malingering,” Dr. Ritchlin said.
Sites to examine for enthesitis, in addition to the foot and Achilles tendon, include the patellar and quadriceps tendons, iliac crest, greater trochanter, lateral epicondyle, the small joints of the hands, and the supraspinatus tendon.
“We have a registry of several hundred psoriatic arthritis patients, and I’ve been struck by the amount of enthesopathy when we examine these points,” the rheumatologist observed.
Enthesitis is a prominent feature of both early and established PsA. Power Doppler ultrasound is more sensitive than radiographs at identifying it. Italian investigators have shown ultrasound to be useful in the differential diagnosis between early rheumatoid arthritis and early PsA in patients with hand involvement. They assessed 52 clinically involved joints in 26 patients with early PsA and 68 involved joints in 34 early-RA patients. Synovitis was detected in 91% of the joints of the RA patients, compared with only 60% of the PsA patients’ joints.
In contrast, soft tissue edema was present in 42% of the most clinically involved fingers of the early PsA patients, compared with just 3% in those with early RA. Central slip enthesitis was seen in 21% of the clinically involved proximal interphalangeal joints of the PsA patients but in none of those belonging to patients with early RA. Peritendon inflammation of the extensor digitorum tendon was noted in 54% of the joints of the PsA group, compared with less than 3% of the early RA group (Clin Exp Rheumatol. 2016 May-Jun;34[3]:459-65).
“Basically, if you do ultrasound, you see there is significantly more enthesitis in early psoriatic arthritis than early rheumatoid arthritis, which has certainly been our experience as well,” Dr. Ritchlin commented.
Enthesitis is not as simple a disease process as most physicians were taught in training. Dr. Ritchlin credits Dennis McGonagle, MD, of the University of Leeds (England) with introducing the now-accepted concept of a synovio-entheseal complex as being a key player in the expression of PsA (Arthritis Rheum. 2007 Aug;56[8]:2482-91).
“The old idea is that the enthesis inserts onto bone and that’s where the pathology is. But it’s more complicated than that,” Dr. Ritchlin explained.
Dr. McGonagle and his coworkers showed that fibrocartilagenous entheses attach to bone much more deeply than previously recognized, like a tree with deep roots. That makes for lots of intimate contact between bony cells and vascular channels. And key structures are located near the intersection of enthesis and bone, including bursae and synovial membrane. For example, the Achilles tendon synovio-entheseal complex includes sesamoid fibrocartilage, periosteal fibrocartilage, the retrocalcaneal bursa, subchondral bone, and enthesis fibrocartilage, as well as the tendon itself.
Dr. McGonagle and coworkers argued that the pathogenesis of tissue inflammation and damage in PsA involves biomechanical stress, with resultant synovial inflammation accompanied by the release of inflammatory cytokines, which in turn leads to diffuse inflammation in and around the area where the enthesis inserts.
“The purpose of the enthesis is to distribute force away from the area where the tendon inserts into bone. So when biomechanical stress pulls on that tendon, other adjacent areas are also affected. What’s come out from imaging studies is that there’s synovial inflammation, bursitis, and also inflammation in and around the fibrocartilage in areas of enthesitis,” Dr. Ritchlin said.
He reported serving as a consultant to half a dozen pharmaceutical companies.
bjancin@frontlinemedcom.com
SNOWMASS, COLO. – Dactylitis is a common and painful extra-articular manifestation of psoriatic arthritis that takes on added clinical significance because it’s also a marker of greater disease severity, Christopher T. Ritchlin, MD, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
Indeed, psoriatic arthritis (PsA) patients with dactylitis are more likely to have polyarticular disease and radiologic evidence of bony damage, noted Dr. Ritchlin, professor of medicine and chief of the allergy, immunology, and rheumatology division at the University of Rochester (N.Y.).
“We have no idea why this is,” confessed Dr. Ritchlin, who is also director of the Clinical Immunology Research Center at the university.
The differential diagnosis for dactylitis includes psoriatic arthritis, other spondyloarthropathies, sickle cell disease, tuberculosis, sarcoidosis, and pyogenic flexor tenosynovitis, a closed-space infection that is the major issue in the differential. Dr. Ritchlin sees many more cases of dactylitis due to PsA that get misdiagnosed as a flexor tendon sheath infection and inappropriately subjected to surgery and/or intravenous antibiotics than vice versa.
Pyogenic flexor tenosynovitis can be identified using the four Kanavel signs: diffuse swelling of a digit, often with discoloration; intense pain over the whole length of the tendon sheath, but limited to the sheath; the involved digit being held in a semiflexed posture; and exquisite pain upon passive extension of the digit, with the pain being worst at the proximal end.
University of Toronto investigators have demonstrated that, in their large longitudinal database of PsA patients, the prevalence of radiologic damage in participants with acute dactylitis of the hands is twice as great as in PsA patients without dactylitis.
“I’ve been struck over the years by how often I see psoriatic arthritis patients with dactylitic digits who not only have erosions but who actually have a complete fusion or ankylosis of the joint. The point is, when you have a joint with diffuse inflammation, in many patients it’s associated with activation of both osteoclasts and osteoblasts,” according to the rheumatologist.
Enthesitis
Enthesitis, another cardinal extra-articular manifestation of PsA, is defined by inflammation at the sites where tendons, ligaments, and joint capsules attach into bone. The most commonly involved sites are the Achilles tendon and plantar fascia.
“It can also involve a lot of other areas and can lead to misdiagnosis as a result. Many of these patients end up in rheumatologists’ offices with previous diagnoses ranging from fibromyalgia or other chronic pain syndromes to malingering,” Dr. Ritchlin said.
Sites to examine for enthesitis, in addition to the foot and Achilles tendon, include the patellar and quadriceps tendons, iliac crest, greater trochanter, lateral epicondyle, the small joints of the hands, and the supraspinatus tendon.
“We have a registry of several hundred psoriatic arthritis patients, and I’ve been struck by the amount of enthesopathy when we examine these points,” the rheumatologist observed.
Enthesitis is a prominent feature of both early and established PsA. Power Doppler ultrasound is more sensitive than radiographs at identifying it. Italian investigators have shown ultrasound to be useful in the differential diagnosis between early rheumatoid arthritis and early PsA in patients with hand involvement. They assessed 52 clinically involved joints in 26 patients with early PsA and 68 involved joints in 34 early-RA patients. Synovitis was detected in 91% of the joints of the RA patients, compared with only 60% of the PsA patients’ joints.
In contrast, soft tissue edema was present in 42% of the most clinically involved fingers of the early PsA patients, compared with just 3% in those with early RA. Central slip enthesitis was seen in 21% of the clinically involved proximal interphalangeal joints of the PsA patients but in none of those belonging to patients with early RA. Peritendon inflammation of the extensor digitorum tendon was noted in 54% of the joints of the PsA group, compared with less than 3% of the early RA group (Clin Exp Rheumatol. 2016 May-Jun;34[3]:459-65).
“Basically, if you do ultrasound, you see there is significantly more enthesitis in early psoriatic arthritis than early rheumatoid arthritis, which has certainly been our experience as well,” Dr. Ritchlin commented.
Enthesitis is not as simple a disease process as most physicians were taught in training. Dr. Ritchlin credits Dennis McGonagle, MD, of the University of Leeds (England) with introducing the now-accepted concept of a synovio-entheseal complex as being a key player in the expression of PsA (Arthritis Rheum. 2007 Aug;56[8]:2482-91).
“The old idea is that the enthesis inserts onto bone and that’s where the pathology is. But it’s more complicated than that,” Dr. Ritchlin explained.
Dr. McGonagle and his coworkers showed that fibrocartilagenous entheses attach to bone much more deeply than previously recognized, like a tree with deep roots. That makes for lots of intimate contact between bony cells and vascular channels. And key structures are located near the intersection of enthesis and bone, including bursae and synovial membrane. For example, the Achilles tendon synovio-entheseal complex includes sesamoid fibrocartilage, periosteal fibrocartilage, the retrocalcaneal bursa, subchondral bone, and enthesis fibrocartilage, as well as the tendon itself.
Dr. McGonagle and coworkers argued that the pathogenesis of tissue inflammation and damage in PsA involves biomechanical stress, with resultant synovial inflammation accompanied by the release of inflammatory cytokines, which in turn leads to diffuse inflammation in and around the area where the enthesis inserts.
“The purpose of the enthesis is to distribute force away from the area where the tendon inserts into bone. So when biomechanical stress pulls on that tendon, other adjacent areas are also affected. What’s come out from imaging studies is that there’s synovial inflammation, bursitis, and also inflammation in and around the fibrocartilage in areas of enthesitis,” Dr. Ritchlin said.
He reported serving as a consultant to half a dozen pharmaceutical companies.
bjancin@frontlinemedcom.com
SNOWMASS, COLO. – Dactylitis is a common and painful extra-articular manifestation of psoriatic arthritis that takes on added clinical significance because it’s also a marker of greater disease severity, Christopher T. Ritchlin, MD, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
Indeed, psoriatic arthritis (PsA) patients with dactylitis are more likely to have polyarticular disease and radiologic evidence of bony damage, noted Dr. Ritchlin, professor of medicine and chief of the allergy, immunology, and rheumatology division at the University of Rochester (N.Y.).
“We have no idea why this is,” confessed Dr. Ritchlin, who is also director of the Clinical Immunology Research Center at the university.
The differential diagnosis for dactylitis includes psoriatic arthritis, other spondyloarthropathies, sickle cell disease, tuberculosis, sarcoidosis, and pyogenic flexor tenosynovitis, a closed-space infection that is the major issue in the differential. Dr. Ritchlin sees many more cases of dactylitis due to PsA that get misdiagnosed as a flexor tendon sheath infection and inappropriately subjected to surgery and/or intravenous antibiotics than vice versa.
Pyogenic flexor tenosynovitis can be identified using the four Kanavel signs: diffuse swelling of a digit, often with discoloration; intense pain over the whole length of the tendon sheath, but limited to the sheath; the involved digit being held in a semiflexed posture; and exquisite pain upon passive extension of the digit, with the pain being worst at the proximal end.
University of Toronto investigators have demonstrated that, in their large longitudinal database of PsA patients, the prevalence of radiologic damage in participants with acute dactylitis of the hands is twice as great as in PsA patients without dactylitis.
“I’ve been struck over the years by how often I see psoriatic arthritis patients with dactylitic digits who not only have erosions but who actually have a complete fusion or ankylosis of the joint. The point is, when you have a joint with diffuse inflammation, in many patients it’s associated with activation of both osteoclasts and osteoblasts,” according to the rheumatologist.
Enthesitis
Enthesitis, another cardinal extra-articular manifestation of PsA, is defined by inflammation at the sites where tendons, ligaments, and joint capsules attach into bone. The most commonly involved sites are the Achilles tendon and plantar fascia.
“It can also involve a lot of other areas and can lead to misdiagnosis as a result. Many of these patients end up in rheumatologists’ offices with previous diagnoses ranging from fibromyalgia or other chronic pain syndromes to malingering,” Dr. Ritchlin said.
Sites to examine for enthesitis, in addition to the foot and Achilles tendon, include the patellar and quadriceps tendons, iliac crest, greater trochanter, lateral epicondyle, the small joints of the hands, and the supraspinatus tendon.
“We have a registry of several hundred psoriatic arthritis patients, and I’ve been struck by the amount of enthesopathy when we examine these points,” the rheumatologist observed.
Enthesitis is a prominent feature of both early and established PsA. Power Doppler ultrasound is more sensitive than radiographs at identifying it. Italian investigators have shown ultrasound to be useful in the differential diagnosis between early rheumatoid arthritis and early PsA in patients with hand involvement. They assessed 52 clinically involved joints in 26 patients with early PsA and 68 involved joints in 34 early-RA patients. Synovitis was detected in 91% of the joints of the RA patients, compared with only 60% of the PsA patients’ joints.
In contrast, soft tissue edema was present in 42% of the most clinically involved fingers of the early PsA patients, compared with just 3% in those with early RA. Central slip enthesitis was seen in 21% of the clinically involved proximal interphalangeal joints of the PsA patients but in none of those belonging to patients with early RA. Peritendon inflammation of the extensor digitorum tendon was noted in 54% of the joints of the PsA group, compared with less than 3% of the early RA group (Clin Exp Rheumatol. 2016 May-Jun;34[3]:459-65).
“Basically, if you do ultrasound, you see there is significantly more enthesitis in early psoriatic arthritis than early rheumatoid arthritis, which has certainly been our experience as well,” Dr. Ritchlin commented.
Enthesitis is not as simple a disease process as most physicians were taught in training. Dr. Ritchlin credits Dennis McGonagle, MD, of the University of Leeds (England) with introducing the now-accepted concept of a synovio-entheseal complex as being a key player in the expression of PsA (Arthritis Rheum. 2007 Aug;56[8]:2482-91).
“The old idea is that the enthesis inserts onto bone and that’s where the pathology is. But it’s more complicated than that,” Dr. Ritchlin explained.
Dr. McGonagle and his coworkers showed that fibrocartilagenous entheses attach to bone much more deeply than previously recognized, like a tree with deep roots. That makes for lots of intimate contact between bony cells and vascular channels. And key structures are located near the intersection of enthesis and bone, including bursae and synovial membrane. For example, the Achilles tendon synovio-entheseal complex includes sesamoid fibrocartilage, periosteal fibrocartilage, the retrocalcaneal bursa, subchondral bone, and enthesis fibrocartilage, as well as the tendon itself.
Dr. McGonagle and coworkers argued that the pathogenesis of tissue inflammation and damage in PsA involves biomechanical stress, with resultant synovial inflammation accompanied by the release of inflammatory cytokines, which in turn leads to diffuse inflammation in and around the area where the enthesis inserts.
“The purpose of the enthesis is to distribute force away from the area where the tendon inserts into bone. So when biomechanical stress pulls on that tendon, other adjacent areas are also affected. What’s come out from imaging studies is that there’s synovial inflammation, bursitis, and also inflammation in and around the fibrocartilage in areas of enthesitis,” Dr. Ritchlin said.
He reported serving as a consultant to half a dozen pharmaceutical companies.
bjancin@frontlinemedcom.com
The percutaneous mitral valve replacement pipe dream
SNOWMASS, COLO. – Percutaneous mitral valve replacement is unlikely to ever catch on in any way remotely approaching that of transcatheter aortic valve replacement for the treatment of aortic stenosis, Blase A. Carabello, MD, predicted at the Annual Cardiovascular Conference at Snowmass.
“We’ve spent $2 billion looking for methods of percutaneous mitral valve replacement, and yet, I have to wonder if that makes any sense,” said Dr. Carabello, professor of medicine and chief of cardiology at East Carolina University in Greenville, N.C.
“If repair is superior to replacement in primary MR [mitral regurgitation], which I think we all agree is true, and you don’t need to get rid of every last molecule of blood going backward across the mitral valve when you’ve got a good left ventricle, then a percutaneous replacement in primary MR would have only the niche of patients who are inoperable and whose leaflets can’t be grabbed by the MitraClip or some new percutaneous device down the road. And, in secondary MR, it doesn’t seem to matter whether you replace or repair the valve, so why not just repair it with a clip?” he argued.
Numerous nonrandomized studies have invariably demonstrated superior survival for surgical repair versus replacement in patients with primary MR.
“There’s never going to be a randomized controlled trial of repair versus replacement; there’s no equipoise there. We all believe that, in primary MR, repair is superior to replacement. There are no data anywhere to suggest the opposite. It’s essentially sacrosanct,” according to the cardiologist.
In contrast, a major randomized trial of surgical repair versus replacement has been conducted in patients with severe secondary MR. This NIH-funded study conducted by the Cardiothoracic Surgical Trials Network found no difference in survival between the two groups (N Engl J Med. 2016 Jan 28; 374[4]:344-53). That’s not a surprising result, Dr. Carabello said, since the underlying cause of this type of valve disease is a sick left ventricle. But, since surgical repair entails less morbidity than replacement – and a percutaneous repair with a leaflet-grasping device such as the MitraClip is simpler and safer than a surgical repair – it seems likely that the future treatment for secondary MR will be a percutaneous device, he said.
That future could depend upon the results of the ongoing COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy), in which the MitraClip is being studied as an alternative to surgical repair for significant secondary MR. The MitraClip, which doesn’t entail a concomitant annuloplasty, is currently approved by the Food and Drug Administration only for patients with primary, degenerative mitral regurgitation not amenable to surgical repair. But, if COAPT yields positive results, the role of the MitraClip will greatly expand.
An intriguing and poorly understood difference exists in the significance of residual mitral regurgitation following surgical repair as opposed to percutaneous MitraClip repair, Dr. Carabello observed.
“I go to the OR a lot, and I know of no surgeon [who] will leave 2+ MR behind. Most surgeons won’t leave 1+ MR behind. They’ll put the patient back on the pump to repair even mild residual MR, accepting only trace MR or zero before they leave the OR because they know that the best predictor of a failed mitral repair is the presence of residual MR in the OR,” he said.
In contrast, following successful deployment of the MitraClip most patients are left with 1-2+ MR. Yet, as was demonstrated in the 5-year results of the randomized EVEREST II trial (Endovascular Valve Edge-to-Edge Repair Study), this residual MR wasn’t a harbinger of poor outcomes long-term (J Am Coll Cardiol. 2015 Dec 29;66[25]:2844-54).
“You would have expected, with that much residual MR, there would be a perpetually increasing failure rate over time, but that didn’t happen. In Everest II, there was an early failure rate for percutaneous repair, where the MitraClip didn’t work and those patients required surgical mitral valve repair. But, after the first 6 months, the failure rate for the clip was exactly the same as the surgical failure rate, even though, with the clip, you start with more MR to begin with,” the cardiologist noted.
The MitraClip procedure is modeled after the surgical Alfieri double-orifice end-to-end stitch technique, which has been shown to have durable results when performed in conjunction with an annuloplasty ring for primary MR.
“The MitraClip essentially joins the valve in the middle the way the Alfieri stitch does, but it doesn’t appear to behave the same way. Why is that? Maybe the clip does something different than the Alfieri stitch on which it was modeled. Maybe that bar in the middle of the mitral valve does something in terms of scarring or stabilization that we don’t know about yet,” he speculated.
As for the prospects for percutaneous mitral valve replacement, Dr. Carabello said that this type of procedure “is a very difficult thing to do, and so far, has been met with a fair amount of failure. It’ll be very interesting to see what percentage of market share it gets 10 years down the road. My prediction is that, for mitral regurgitation, repair is always going to be it.”
Dr. Carabello reported serving on a data safety monitoring board for Edwards Lifesciences.
The author provides valuable insight into how the definition of “success” of a procedure can change depending on the approach to the problem. While the gold standard of open mitral valve repair is 1+ regurgitation or less, those promoting percutaneous valve replacement are willing to accept long term 1+ to 2+ regurgitation. New technology and innovation is critical in medicine, provided the results are at least equivalent or superior to the standard techniques.
The author provides valuable insight into how the definition of “success” of a procedure can change depending on the approach to the problem. While the gold standard of open mitral valve repair is 1+ regurgitation or less, those promoting percutaneous valve replacement are willing to accept long term 1+ to 2+ regurgitation. New technology and innovation is critical in medicine, provided the results are at least equivalent or superior to the standard techniques.
The author provides valuable insight into how the definition of “success” of a procedure can change depending on the approach to the problem. While the gold standard of open mitral valve repair is 1+ regurgitation or less, those promoting percutaneous valve replacement are willing to accept long term 1+ to 2+ regurgitation. New technology and innovation is critical in medicine, provided the results are at least equivalent or superior to the standard techniques.
SNOWMASS, COLO. – Percutaneous mitral valve replacement is unlikely to ever catch on in any way remotely approaching that of transcatheter aortic valve replacement for the treatment of aortic stenosis, Blase A. Carabello, MD, predicted at the Annual Cardiovascular Conference at Snowmass.
“We’ve spent $2 billion looking for methods of percutaneous mitral valve replacement, and yet, I have to wonder if that makes any sense,” said Dr. Carabello, professor of medicine and chief of cardiology at East Carolina University in Greenville, N.C.
“If repair is superior to replacement in primary MR [mitral regurgitation], which I think we all agree is true, and you don’t need to get rid of every last molecule of blood going backward across the mitral valve when you’ve got a good left ventricle, then a percutaneous replacement in primary MR would have only the niche of patients who are inoperable and whose leaflets can’t be grabbed by the MitraClip or some new percutaneous device down the road. And, in secondary MR, it doesn’t seem to matter whether you replace or repair the valve, so why not just repair it with a clip?” he argued.
Numerous nonrandomized studies have invariably demonstrated superior survival for surgical repair versus replacement in patients with primary MR.
“There’s never going to be a randomized controlled trial of repair versus replacement; there’s no equipoise there. We all believe that, in primary MR, repair is superior to replacement. There are no data anywhere to suggest the opposite. It’s essentially sacrosanct,” according to the cardiologist.
In contrast, a major randomized trial of surgical repair versus replacement has been conducted in patients with severe secondary MR. This NIH-funded study conducted by the Cardiothoracic Surgical Trials Network found no difference in survival between the two groups (N Engl J Med. 2016 Jan 28; 374[4]:344-53). That’s not a surprising result, Dr. Carabello said, since the underlying cause of this type of valve disease is a sick left ventricle. But, since surgical repair entails less morbidity than replacement – and a percutaneous repair with a leaflet-grasping device such as the MitraClip is simpler and safer than a surgical repair – it seems likely that the future treatment for secondary MR will be a percutaneous device, he said.
That future could depend upon the results of the ongoing COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy), in which the MitraClip is being studied as an alternative to surgical repair for significant secondary MR. The MitraClip, which doesn’t entail a concomitant annuloplasty, is currently approved by the Food and Drug Administration only for patients with primary, degenerative mitral regurgitation not amenable to surgical repair. But, if COAPT yields positive results, the role of the MitraClip will greatly expand.
An intriguing and poorly understood difference exists in the significance of residual mitral regurgitation following surgical repair as opposed to percutaneous MitraClip repair, Dr. Carabello observed.
“I go to the OR a lot, and I know of no surgeon [who] will leave 2+ MR behind. Most surgeons won’t leave 1+ MR behind. They’ll put the patient back on the pump to repair even mild residual MR, accepting only trace MR or zero before they leave the OR because they know that the best predictor of a failed mitral repair is the presence of residual MR in the OR,” he said.
In contrast, following successful deployment of the MitraClip most patients are left with 1-2+ MR. Yet, as was demonstrated in the 5-year results of the randomized EVEREST II trial (Endovascular Valve Edge-to-Edge Repair Study), this residual MR wasn’t a harbinger of poor outcomes long-term (J Am Coll Cardiol. 2015 Dec 29;66[25]:2844-54).
“You would have expected, with that much residual MR, there would be a perpetually increasing failure rate over time, but that didn’t happen. In Everest II, there was an early failure rate for percutaneous repair, where the MitraClip didn’t work and those patients required surgical mitral valve repair. But, after the first 6 months, the failure rate for the clip was exactly the same as the surgical failure rate, even though, with the clip, you start with more MR to begin with,” the cardiologist noted.
The MitraClip procedure is modeled after the surgical Alfieri double-orifice end-to-end stitch technique, which has been shown to have durable results when performed in conjunction with an annuloplasty ring for primary MR.
“The MitraClip essentially joins the valve in the middle the way the Alfieri stitch does, but it doesn’t appear to behave the same way. Why is that? Maybe the clip does something different than the Alfieri stitch on which it was modeled. Maybe that bar in the middle of the mitral valve does something in terms of scarring or stabilization that we don’t know about yet,” he speculated.
As for the prospects for percutaneous mitral valve replacement, Dr. Carabello said that this type of procedure “is a very difficult thing to do, and so far, has been met with a fair amount of failure. It’ll be very interesting to see what percentage of market share it gets 10 years down the road. My prediction is that, for mitral regurgitation, repair is always going to be it.”
Dr. Carabello reported serving on a data safety monitoring board for Edwards Lifesciences.
SNOWMASS, COLO. – Percutaneous mitral valve replacement is unlikely to ever catch on in any way remotely approaching that of transcatheter aortic valve replacement for the treatment of aortic stenosis, Blase A. Carabello, MD, predicted at the Annual Cardiovascular Conference at Snowmass.
“We’ve spent $2 billion looking for methods of percutaneous mitral valve replacement, and yet, I have to wonder if that makes any sense,” said Dr. Carabello, professor of medicine and chief of cardiology at East Carolina University in Greenville, N.C.
“If repair is superior to replacement in primary MR [mitral regurgitation], which I think we all agree is true, and you don’t need to get rid of every last molecule of blood going backward across the mitral valve when you’ve got a good left ventricle, then a percutaneous replacement in primary MR would have only the niche of patients who are inoperable and whose leaflets can’t be grabbed by the MitraClip or some new percutaneous device down the road. And, in secondary MR, it doesn’t seem to matter whether you replace or repair the valve, so why not just repair it with a clip?” he argued.
Numerous nonrandomized studies have invariably demonstrated superior survival for surgical repair versus replacement in patients with primary MR.
“There’s never going to be a randomized controlled trial of repair versus replacement; there’s no equipoise there. We all believe that, in primary MR, repair is superior to replacement. There are no data anywhere to suggest the opposite. It’s essentially sacrosanct,” according to the cardiologist.
In contrast, a major randomized trial of surgical repair versus replacement has been conducted in patients with severe secondary MR. This NIH-funded study conducted by the Cardiothoracic Surgical Trials Network found no difference in survival between the two groups (N Engl J Med. 2016 Jan 28; 374[4]:344-53). That’s not a surprising result, Dr. Carabello said, since the underlying cause of this type of valve disease is a sick left ventricle. But, since surgical repair entails less morbidity than replacement – and a percutaneous repair with a leaflet-grasping device such as the MitraClip is simpler and safer than a surgical repair – it seems likely that the future treatment for secondary MR will be a percutaneous device, he said.
That future could depend upon the results of the ongoing COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy), in which the MitraClip is being studied as an alternative to surgical repair for significant secondary MR. The MitraClip, which doesn’t entail a concomitant annuloplasty, is currently approved by the Food and Drug Administration only for patients with primary, degenerative mitral regurgitation not amenable to surgical repair. But, if COAPT yields positive results, the role of the MitraClip will greatly expand.
An intriguing and poorly understood difference exists in the significance of residual mitral regurgitation following surgical repair as opposed to percutaneous MitraClip repair, Dr. Carabello observed.
“I go to the OR a lot, and I know of no surgeon [who] will leave 2+ MR behind. Most surgeons won’t leave 1+ MR behind. They’ll put the patient back on the pump to repair even mild residual MR, accepting only trace MR or zero before they leave the OR because they know that the best predictor of a failed mitral repair is the presence of residual MR in the OR,” he said.
In contrast, following successful deployment of the MitraClip most patients are left with 1-2+ MR. Yet, as was demonstrated in the 5-year results of the randomized EVEREST II trial (Endovascular Valve Edge-to-Edge Repair Study), this residual MR wasn’t a harbinger of poor outcomes long-term (J Am Coll Cardiol. 2015 Dec 29;66[25]:2844-54).
“You would have expected, with that much residual MR, there would be a perpetually increasing failure rate over time, but that didn’t happen. In Everest II, there was an early failure rate for percutaneous repair, where the MitraClip didn’t work and those patients required surgical mitral valve repair. But, after the first 6 months, the failure rate for the clip was exactly the same as the surgical failure rate, even though, with the clip, you start with more MR to begin with,” the cardiologist noted.
The MitraClip procedure is modeled after the surgical Alfieri double-orifice end-to-end stitch technique, which has been shown to have durable results when performed in conjunction with an annuloplasty ring for primary MR.
“The MitraClip essentially joins the valve in the middle the way the Alfieri stitch does, but it doesn’t appear to behave the same way. Why is that? Maybe the clip does something different than the Alfieri stitch on which it was modeled. Maybe that bar in the middle of the mitral valve does something in terms of scarring or stabilization that we don’t know about yet,” he speculated.
As for the prospects for percutaneous mitral valve replacement, Dr. Carabello said that this type of procedure “is a very difficult thing to do, and so far, has been met with a fair amount of failure. It’ll be very interesting to see what percentage of market share it gets 10 years down the road. My prediction is that, for mitral regurgitation, repair is always going to be it.”
Dr. Carabello reported serving on a data safety monitoring board for Edwards Lifesciences.
Nutrition expert to heart patients: ‘Eat some cheese’
NEW ORLEANS – While many Americans have been dithering over the relative health benefits of high- versus low-carbohydrate diets, various pop-culture weight loss programs, vegetarianism, gluten-free living, and other nutritional matters, a quiet revolution in mainstream scientific thinking has occurred regarding the role of full-fat dairy products.
Saturated fatty acid–rich dairy products, formerly viewed as the enemy of cardiovascular health, have gone from foe to friend, according to Arne Astrup, MD, professor and head of the department of nutrition, exercise and sports at the University of Copenhagen.
“From all I have seen, I think it’s quite safe to recommend that our diabetics and heart patients eat some cheese without being afraid of it. I don’t think there’s any harmful effect, and it could actually be very beneficial,” Dr. Astrup continued.
For example, a recent comprehensive meta-analysis of 31 prospective cohort studies found that a high dairy intake was associated with a 9% reduction in the risk of stroke, compared with low or no dairy consumption. Of note, high cheese intake was associated with an 18% lower risk of coronary heart disease (CHD) and a 13% reduction in risk of stroke (Br J Nutr. 2016;115[4]:737-50).
Dutch investigators reported based upon their meta-analysis of 18 prospective cohort studies with 8-26 years of follow-up that stroke risk fell by 7% for each 200 mL of milk consumed per day. Consumption of 25 g/day or more of cheese was associated with a 13% reduction in stroke risk and an 8% lower risk of CHD (J Am Heart Assoc. 2016 May 20;5[5]. doi: 10.1161/JAHA.115.002787).
“The totality of evidence – meta-analyses of both observational studies and randomized controlled trials – cannot find any harmful effects of cheese on body fat, metabolic syndrome, type 2 diabetes, or cardiovascular disease,” he said. “And cheese has beneficial effects on LDL cholesterol, blood pressure, and postprandial triglycerides as compared with butter containing the same amount of saturated fatty acids.”
The classic lipid hypothesis of cardiovascular disease holds that dietary saturated fat raises blood cholesterol, in turn accelerating atherosclerosis and resultant coronary heart disease. But the published literature of the past few years indicates it’s not that simple. All saturated fats are not equally harmful. They have very different biologic effects, and the food matrix in which they occur seems to be important. The saturated fatty acids found in red meat are clearly damaging. Ditto trans fats.
In contrast, the saturated fats present in milk, hard cheeses, and fermented dairy products such as yogurt have been shown in a variety of study formats to be cardioprotective. They also appear to protect against other chronic diseases as well, according to the researcher.
“If we look at all the different meta-analyses addressing the various cardiovascular risk factors, it really looks like cheese, despite its high content of sodium and saturated fat, seems to exert some beneficial effects. So I think we need to address the food matrix much more. We’ve done controlled feeding trials in humans and found that if we give subjects the same amount of saturated fat from either butter or cheese, you see following the cheese [that] the subjects do not increase their total or LDL-cholesterol as you would expect based upon their intake of saturated fat. So there’s something going on with cheese,” Dr. Astrup said.
What’s going on, he continued, is the saturated fats in cheese benefit from the company they keep. Fermented dairy products contain an arm-long list of potentially beneficial nutrients, including protein, calcium, short-chain fatty acids, bioactive peptides, and phospholipids.
Take, for example, calcium: “We’ve found the calcium content of cheese completely modifies the metabolism of the saturated fat. The calcium seems to bind the bile acids and fatty acids, resulting in increased fecal fat secretion,” according to Dr. Astrup.
Although at the AHA meeting he focused mainly on the effects of cheese and other dairy products on cardiovascular health, in a recent review article he expanded upon the scientific evidence regarding the impact of these foods on the risks of obesity, type 2 diabetes, cancer, and osteoporosis (Food Nutr Res. 2016 Nov 22;60:32527).
There is solid evidence that a diet high in dairy products reduces the risk of childhood obesity and enhances body composition in adults. It aids in weight loss by promoting satiety during periods of energy restriction. A recent meta-analysis of observational studies found an inverse relationship between consumption of fermented dairy products – yogurt and cheese – and risk of type 2 diabetes (Am J Clin Nutr. 2016 Apr;103[4]:1111-24).
Regarding cancer, the World Cancer Research Fund has issued a series of evidence reviews concluding that dairy products probably protect against colorectal, breast, gastric, and bladder cancer. The jury is still out regarding prostate cancer risk.
A wealth of evidence indicates dairy consumption has a beneficial effect on bone health in children and adolescents. However, meta-analyses haven’t shown a protective effect against osteoporosis and fractures in adults. This is consistent with the adage that osteoporosis is a pediatric disease with geriatric consequences, Dr. Astrup noted.
He reported receiving research grants from the Danish Dairy Research Foundation, the Global Dairy Platform, the Danish Agriculture and Food Council, and the European Milk Forum. He serves on advisory boards for the Dutch Beer Knowledge Institute, Suntory, Weight Watchers, and several food companies.
This article is included so that vascular surgeons can adequately advise patients who request dietary information about ]dairy products. However, as a cheese lover myself, it will also permit cheese aficionados like myself to “cut the cheese” in an appropriate manner! My only concern is the long list of dairy groups that support Dr. Astrup’s research grants. I note that he also serves on the advisory board of the Dutch Beer Knowledge Institute. I look forward to his upcoming research project explaining the benefits of consuming large quantities of beer!
Russell H. Samson, MD, is the Medical Editor of Vascular Specialist.
This article is included so that vascular surgeons can adequately advise patients who request dietary information about ]dairy products. However, as a cheese lover myself, it will also permit cheese aficionados like myself to “cut the cheese” in an appropriate manner! My only concern is the long list of dairy groups that support Dr. Astrup’s research grants. I note that he also serves on the advisory board of the Dutch Beer Knowledge Institute. I look forward to his upcoming research project explaining the benefits of consuming large quantities of beer!
Russell H. Samson, MD, is the Medical Editor of Vascular Specialist.
This article is included so that vascular surgeons can adequately advise patients who request dietary information about ]dairy products. However, as a cheese lover myself, it will also permit cheese aficionados like myself to “cut the cheese” in an appropriate manner! My only concern is the long list of dairy groups that support Dr. Astrup’s research grants. I note that he also serves on the advisory board of the Dutch Beer Knowledge Institute. I look forward to his upcoming research project explaining the benefits of consuming large quantities of beer!
Russell H. Samson, MD, is the Medical Editor of Vascular Specialist.
NEW ORLEANS – While many Americans have been dithering over the relative health benefits of high- versus low-carbohydrate diets, various pop-culture weight loss programs, vegetarianism, gluten-free living, and other nutritional matters, a quiet revolution in mainstream scientific thinking has occurred regarding the role of full-fat dairy products.
Saturated fatty acid–rich dairy products, formerly viewed as the enemy of cardiovascular health, have gone from foe to friend, according to Arne Astrup, MD, professor and head of the department of nutrition, exercise and sports at the University of Copenhagen.
“From all I have seen, I think it’s quite safe to recommend that our diabetics and heart patients eat some cheese without being afraid of it. I don’t think there’s any harmful effect, and it could actually be very beneficial,” Dr. Astrup continued.
For example, a recent comprehensive meta-analysis of 31 prospective cohort studies found that a high dairy intake was associated with a 9% reduction in the risk of stroke, compared with low or no dairy consumption. Of note, high cheese intake was associated with an 18% lower risk of coronary heart disease (CHD) and a 13% reduction in risk of stroke (Br J Nutr. 2016;115[4]:737-50).
Dutch investigators reported based upon their meta-analysis of 18 prospective cohort studies with 8-26 years of follow-up that stroke risk fell by 7% for each 200 mL of milk consumed per day. Consumption of 25 g/day or more of cheese was associated with a 13% reduction in stroke risk and an 8% lower risk of CHD (J Am Heart Assoc. 2016 May 20;5[5]. doi: 10.1161/JAHA.115.002787).
“The totality of evidence – meta-analyses of both observational studies and randomized controlled trials – cannot find any harmful effects of cheese on body fat, metabolic syndrome, type 2 diabetes, or cardiovascular disease,” he said. “And cheese has beneficial effects on LDL cholesterol, blood pressure, and postprandial triglycerides as compared with butter containing the same amount of saturated fatty acids.”
The classic lipid hypothesis of cardiovascular disease holds that dietary saturated fat raises blood cholesterol, in turn accelerating atherosclerosis and resultant coronary heart disease. But the published literature of the past few years indicates it’s not that simple. All saturated fats are not equally harmful. They have very different biologic effects, and the food matrix in which they occur seems to be important. The saturated fatty acids found in red meat are clearly damaging. Ditto trans fats.
In contrast, the saturated fats present in milk, hard cheeses, and fermented dairy products such as yogurt have been shown in a variety of study formats to be cardioprotective. They also appear to protect against other chronic diseases as well, according to the researcher.
“If we look at all the different meta-analyses addressing the various cardiovascular risk factors, it really looks like cheese, despite its high content of sodium and saturated fat, seems to exert some beneficial effects. So I think we need to address the food matrix much more. We’ve done controlled feeding trials in humans and found that if we give subjects the same amount of saturated fat from either butter or cheese, you see following the cheese [that] the subjects do not increase their total or LDL-cholesterol as you would expect based upon their intake of saturated fat. So there’s something going on with cheese,” Dr. Astrup said.
What’s going on, he continued, is the saturated fats in cheese benefit from the company they keep. Fermented dairy products contain an arm-long list of potentially beneficial nutrients, including protein, calcium, short-chain fatty acids, bioactive peptides, and phospholipids.
Take, for example, calcium: “We’ve found the calcium content of cheese completely modifies the metabolism of the saturated fat. The calcium seems to bind the bile acids and fatty acids, resulting in increased fecal fat secretion,” according to Dr. Astrup.
Although at the AHA meeting he focused mainly on the effects of cheese and other dairy products on cardiovascular health, in a recent review article he expanded upon the scientific evidence regarding the impact of these foods on the risks of obesity, type 2 diabetes, cancer, and osteoporosis (Food Nutr Res. 2016 Nov 22;60:32527).
There is solid evidence that a diet high in dairy products reduces the risk of childhood obesity and enhances body composition in adults. It aids in weight loss by promoting satiety during periods of energy restriction. A recent meta-analysis of observational studies found an inverse relationship between consumption of fermented dairy products – yogurt and cheese – and risk of type 2 diabetes (Am J Clin Nutr. 2016 Apr;103[4]:1111-24).
Regarding cancer, the World Cancer Research Fund has issued a series of evidence reviews concluding that dairy products probably protect against colorectal, breast, gastric, and bladder cancer. The jury is still out regarding prostate cancer risk.
A wealth of evidence indicates dairy consumption has a beneficial effect on bone health in children and adolescents. However, meta-analyses haven’t shown a protective effect against osteoporosis and fractures in adults. This is consistent with the adage that osteoporosis is a pediatric disease with geriatric consequences, Dr. Astrup noted.
He reported receiving research grants from the Danish Dairy Research Foundation, the Global Dairy Platform, the Danish Agriculture and Food Council, and the European Milk Forum. He serves on advisory boards for the Dutch Beer Knowledge Institute, Suntory, Weight Watchers, and several food companies.
NEW ORLEANS – While many Americans have been dithering over the relative health benefits of high- versus low-carbohydrate diets, various pop-culture weight loss programs, vegetarianism, gluten-free living, and other nutritional matters, a quiet revolution in mainstream scientific thinking has occurred regarding the role of full-fat dairy products.
Saturated fatty acid–rich dairy products, formerly viewed as the enemy of cardiovascular health, have gone from foe to friend, according to Arne Astrup, MD, professor and head of the department of nutrition, exercise and sports at the University of Copenhagen.
“From all I have seen, I think it’s quite safe to recommend that our diabetics and heart patients eat some cheese without being afraid of it. I don’t think there’s any harmful effect, and it could actually be very beneficial,” Dr. Astrup continued.
For example, a recent comprehensive meta-analysis of 31 prospective cohort studies found that a high dairy intake was associated with a 9% reduction in the risk of stroke, compared with low or no dairy consumption. Of note, high cheese intake was associated with an 18% lower risk of coronary heart disease (CHD) and a 13% reduction in risk of stroke (Br J Nutr. 2016;115[4]:737-50).
Dutch investigators reported based upon their meta-analysis of 18 prospective cohort studies with 8-26 years of follow-up that stroke risk fell by 7% for each 200 mL of milk consumed per day. Consumption of 25 g/day or more of cheese was associated with a 13% reduction in stroke risk and an 8% lower risk of CHD (J Am Heart Assoc. 2016 May 20;5[5]. doi: 10.1161/JAHA.115.002787).
“The totality of evidence – meta-analyses of both observational studies and randomized controlled trials – cannot find any harmful effects of cheese on body fat, metabolic syndrome, type 2 diabetes, or cardiovascular disease,” he said. “And cheese has beneficial effects on LDL cholesterol, blood pressure, and postprandial triglycerides as compared with butter containing the same amount of saturated fatty acids.”
The classic lipid hypothesis of cardiovascular disease holds that dietary saturated fat raises blood cholesterol, in turn accelerating atherosclerosis and resultant coronary heart disease. But the published literature of the past few years indicates it’s not that simple. All saturated fats are not equally harmful. They have very different biologic effects, and the food matrix in which they occur seems to be important. The saturated fatty acids found in red meat are clearly damaging. Ditto trans fats.
In contrast, the saturated fats present in milk, hard cheeses, and fermented dairy products such as yogurt have been shown in a variety of study formats to be cardioprotective. They also appear to protect against other chronic diseases as well, according to the researcher.
“If we look at all the different meta-analyses addressing the various cardiovascular risk factors, it really looks like cheese, despite its high content of sodium and saturated fat, seems to exert some beneficial effects. So I think we need to address the food matrix much more. We’ve done controlled feeding trials in humans and found that if we give subjects the same amount of saturated fat from either butter or cheese, you see following the cheese [that] the subjects do not increase their total or LDL-cholesterol as you would expect based upon their intake of saturated fat. So there’s something going on with cheese,” Dr. Astrup said.
What’s going on, he continued, is the saturated fats in cheese benefit from the company they keep. Fermented dairy products contain an arm-long list of potentially beneficial nutrients, including protein, calcium, short-chain fatty acids, bioactive peptides, and phospholipids.
Take, for example, calcium: “We’ve found the calcium content of cheese completely modifies the metabolism of the saturated fat. The calcium seems to bind the bile acids and fatty acids, resulting in increased fecal fat secretion,” according to Dr. Astrup.
Although at the AHA meeting he focused mainly on the effects of cheese and other dairy products on cardiovascular health, in a recent review article he expanded upon the scientific evidence regarding the impact of these foods on the risks of obesity, type 2 diabetes, cancer, and osteoporosis (Food Nutr Res. 2016 Nov 22;60:32527).
There is solid evidence that a diet high in dairy products reduces the risk of childhood obesity and enhances body composition in adults. It aids in weight loss by promoting satiety during periods of energy restriction. A recent meta-analysis of observational studies found an inverse relationship between consumption of fermented dairy products – yogurt and cheese – and risk of type 2 diabetes (Am J Clin Nutr. 2016 Apr;103[4]:1111-24).
Regarding cancer, the World Cancer Research Fund has issued a series of evidence reviews concluding that dairy products probably protect against colorectal, breast, gastric, and bladder cancer. The jury is still out regarding prostate cancer risk.
A wealth of evidence indicates dairy consumption has a beneficial effect on bone health in children and adolescents. However, meta-analyses haven’t shown a protective effect against osteoporosis and fractures in adults. This is consistent with the adage that osteoporosis is a pediatric disease with geriatric consequences, Dr. Astrup noted.
He reported receiving research grants from the Danish Dairy Research Foundation, the Global Dairy Platform, the Danish Agriculture and Food Council, and the European Milk Forum. He serves on advisory boards for the Dutch Beer Knowledge Institute, Suntory, Weight Watchers, and several food companies.
Older recreational endurance athletes face sky-high AF risk
SNOWMASS, COLO. – , N. A. Mark Estes III, MD, said at the Annual Cardiovascular Conference at Snowmass.
“I see a very large number of former collegiate or professional athletes who come to me in their 40s, 50s, and 60s having recently developed A-fib. These are mainly men who’ve been doing high-intensity endurance exercise,” said Dr. Estes, professor of medicine and director of the New England Cardiac Arrhythmia Center at Tufts University in Boston.
This is an aspect of the athletic heart syndrome that has gone understudied and underappreciated, according to Dr. Estes, who asserted, “The best available evidence suggests that exercise, if excessive, is probably harmful. I know that’s heresy.”
He is coauthor of a forthcoming review on this topic to be published in the Journal of the American College of Cardiology – Electrophysiology. In it, he and his coauthors analyzed more than a half dozen published observational epidemiologic studies and concluded that the collective data show a classic J-shaped curve describes the relationship between physical activity level and risk of developing AF, but only in men. The risk is roughly 25% lower in men who regularly engage in moderate physical activity as defined in American Heart Association/American College of Cardiology guidelines, compared with that of sedentary men. But the AF risk shoots up dramatically in men who focus on intense exercise.
“As you get into the high-intensity/high-endurance end of the spectrum – typically more than 5 hours per week at greater than 80% of peak heart rate – the risk of A-fib increases up to 10-fold,” according to Dr. Estes.
“These are new data. They are important data. I think these data should impact the way we counsel people about exercise, particularly men who like to get into that high-intensity/high-endurance range,” the cardiologist continued.
This J-curve doesn’t apply to women, for reasons unclear. The analysis by Dr. Estes and his colleagues documented that women who engage in moderate physical activity have a lower risk of developing AF than do sedentary women, but unlike in men, the AF risk is lower still in women who favor high-intensity exercise.
“Maybe the explanation is in part endocrinologic differences, maybe in part due to women having smaller left atria and therefore less left atrial wall stress, less fibrosis. We really don’t know, but I think the observation, based on epidemiologic data, is valid,” he said.
Proposed multifactorial mechanisms for the increased incidence of AF in aging endurance athletes hinge in part upon basic science studies. These mechanisms include atrial inflammation and fibrosis, atrial enlargement, increased vagal tone, sympathetic nervous system stimulation, pulmonary vein triggers, genetic predisposition, and use of performance-enhancing substances.
Dr. Estes’ presentation struck a responsive chord with the audience. Numerous cardiologists rose to chime in that they, too, have encountered new-onset AF in middle-aged patients, friends, and medical colleagues who are serious cyclists, marathoners, and devotees of other forms of high-intensity endurance exercise to the tune of 10-20 hours per weekly.
“I know an electrophysiologist in his 60s who probably does 20 hours per week of spin and Cross-Fit classes and who is just now going into A-fib. How should I counsel him about this?” one audience member asked.
“You can’t tell these people to stop exercising,” Dr. Estes replied. “It’s so much a part of their identity. Their endorphin levels go down, and they feel depressed.”
For these patients he stresses what he called “the virtue of moderation.”
“If they have clinically important symptoms, many times we’ll decondition them. Often their symptoms will improve, and, in some instances, the A-fib will actually clear up and we don’t even need to go to any medical therapy,” Dr. Estes said.
His exercise prescription for deconditioning such patients is “basically nothing more than a moderate jog, a 10-minute mile. They should be able to carry on a conversation, with a peak heart rate no more than 60% of their maximum.”
If drug therapy is required, he favors rate control with beta blockers, as these patients generally don’t tolerate antiarrhythmic agents very well.
“Our threshold for AF ablation in these people is quite low because the response rate is high in paroxysmal AF in the absence of underlying structural heart disease,” he added.
Dr. Robert A. Vogel, who has been a consultant to the National Football League for a decade, commented, “I agree that you can exercise too much. These are the super-elite triathletes and so forth. A few of these folks not only get A-fib, but we’ve shown they can get accelerated atherosclerosis due to pervasive endothelial dysfunction caused by excessive athletics.”
“However, nothing here should be construed as saying exercise is bad for you. Athletes, even drug-taking cyclists and football players, actually live longer than similar nonathletes,” said Dr. Vogel, a cardiologist at the University of Colorado, Denver.
Dr. Estes was quick to agree.
“The cardiovascular benefits of exercise resoundingly overwhelm the adverse effects in that small group that experiences adverse effects,” he said.
Dr. Estes reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.
SNOWMASS, COLO. – , N. A. Mark Estes III, MD, said at the Annual Cardiovascular Conference at Snowmass.
“I see a very large number of former collegiate or professional athletes who come to me in their 40s, 50s, and 60s having recently developed A-fib. These are mainly men who’ve been doing high-intensity endurance exercise,” said Dr. Estes, professor of medicine and director of the New England Cardiac Arrhythmia Center at Tufts University in Boston.
This is an aspect of the athletic heart syndrome that has gone understudied and underappreciated, according to Dr. Estes, who asserted, “The best available evidence suggests that exercise, if excessive, is probably harmful. I know that’s heresy.”
He is coauthor of a forthcoming review on this topic to be published in the Journal of the American College of Cardiology – Electrophysiology. In it, he and his coauthors analyzed more than a half dozen published observational epidemiologic studies and concluded that the collective data show a classic J-shaped curve describes the relationship between physical activity level and risk of developing AF, but only in men. The risk is roughly 25% lower in men who regularly engage in moderate physical activity as defined in American Heart Association/American College of Cardiology guidelines, compared with that of sedentary men. But the AF risk shoots up dramatically in men who focus on intense exercise.
“As you get into the high-intensity/high-endurance end of the spectrum – typically more than 5 hours per week at greater than 80% of peak heart rate – the risk of A-fib increases up to 10-fold,” according to Dr. Estes.
“These are new data. They are important data. I think these data should impact the way we counsel people about exercise, particularly men who like to get into that high-intensity/high-endurance range,” the cardiologist continued.
This J-curve doesn’t apply to women, for reasons unclear. The analysis by Dr. Estes and his colleagues documented that women who engage in moderate physical activity have a lower risk of developing AF than do sedentary women, but unlike in men, the AF risk is lower still in women who favor high-intensity exercise.
“Maybe the explanation is in part endocrinologic differences, maybe in part due to women having smaller left atria and therefore less left atrial wall stress, less fibrosis. We really don’t know, but I think the observation, based on epidemiologic data, is valid,” he said.
Proposed multifactorial mechanisms for the increased incidence of AF in aging endurance athletes hinge in part upon basic science studies. These mechanisms include atrial inflammation and fibrosis, atrial enlargement, increased vagal tone, sympathetic nervous system stimulation, pulmonary vein triggers, genetic predisposition, and use of performance-enhancing substances.
Dr. Estes’ presentation struck a responsive chord with the audience. Numerous cardiologists rose to chime in that they, too, have encountered new-onset AF in middle-aged patients, friends, and medical colleagues who are serious cyclists, marathoners, and devotees of other forms of high-intensity endurance exercise to the tune of 10-20 hours per weekly.
“I know an electrophysiologist in his 60s who probably does 20 hours per week of spin and Cross-Fit classes and who is just now going into A-fib. How should I counsel him about this?” one audience member asked.
“You can’t tell these people to stop exercising,” Dr. Estes replied. “It’s so much a part of their identity. Their endorphin levels go down, and they feel depressed.”
For these patients he stresses what he called “the virtue of moderation.”
“If they have clinically important symptoms, many times we’ll decondition them. Often their symptoms will improve, and, in some instances, the A-fib will actually clear up and we don’t even need to go to any medical therapy,” Dr. Estes said.
His exercise prescription for deconditioning such patients is “basically nothing more than a moderate jog, a 10-minute mile. They should be able to carry on a conversation, with a peak heart rate no more than 60% of their maximum.”
If drug therapy is required, he favors rate control with beta blockers, as these patients generally don’t tolerate antiarrhythmic agents very well.
“Our threshold for AF ablation in these people is quite low because the response rate is high in paroxysmal AF in the absence of underlying structural heart disease,” he added.
Dr. Robert A. Vogel, who has been a consultant to the National Football League for a decade, commented, “I agree that you can exercise too much. These are the super-elite triathletes and so forth. A few of these folks not only get A-fib, but we’ve shown they can get accelerated atherosclerosis due to pervasive endothelial dysfunction caused by excessive athletics.”
“However, nothing here should be construed as saying exercise is bad for you. Athletes, even drug-taking cyclists and football players, actually live longer than similar nonathletes,” said Dr. Vogel, a cardiologist at the University of Colorado, Denver.
Dr. Estes was quick to agree.
“The cardiovascular benefits of exercise resoundingly overwhelm the adverse effects in that small group that experiences adverse effects,” he said.
Dr. Estes reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.
SNOWMASS, COLO. – , N. A. Mark Estes III, MD, said at the Annual Cardiovascular Conference at Snowmass.
“I see a very large number of former collegiate or professional athletes who come to me in their 40s, 50s, and 60s having recently developed A-fib. These are mainly men who’ve been doing high-intensity endurance exercise,” said Dr. Estes, professor of medicine and director of the New England Cardiac Arrhythmia Center at Tufts University in Boston.
This is an aspect of the athletic heart syndrome that has gone understudied and underappreciated, according to Dr. Estes, who asserted, “The best available evidence suggests that exercise, if excessive, is probably harmful. I know that’s heresy.”
He is coauthor of a forthcoming review on this topic to be published in the Journal of the American College of Cardiology – Electrophysiology. In it, he and his coauthors analyzed more than a half dozen published observational epidemiologic studies and concluded that the collective data show a classic J-shaped curve describes the relationship between physical activity level and risk of developing AF, but only in men. The risk is roughly 25% lower in men who regularly engage in moderate physical activity as defined in American Heart Association/American College of Cardiology guidelines, compared with that of sedentary men. But the AF risk shoots up dramatically in men who focus on intense exercise.
“As you get into the high-intensity/high-endurance end of the spectrum – typically more than 5 hours per week at greater than 80% of peak heart rate – the risk of A-fib increases up to 10-fold,” according to Dr. Estes.
“These are new data. They are important data. I think these data should impact the way we counsel people about exercise, particularly men who like to get into that high-intensity/high-endurance range,” the cardiologist continued.
This J-curve doesn’t apply to women, for reasons unclear. The analysis by Dr. Estes and his colleagues documented that women who engage in moderate physical activity have a lower risk of developing AF than do sedentary women, but unlike in men, the AF risk is lower still in women who favor high-intensity exercise.
“Maybe the explanation is in part endocrinologic differences, maybe in part due to women having smaller left atria and therefore less left atrial wall stress, less fibrosis. We really don’t know, but I think the observation, based on epidemiologic data, is valid,” he said.
Proposed multifactorial mechanisms for the increased incidence of AF in aging endurance athletes hinge in part upon basic science studies. These mechanisms include atrial inflammation and fibrosis, atrial enlargement, increased vagal tone, sympathetic nervous system stimulation, pulmonary vein triggers, genetic predisposition, and use of performance-enhancing substances.
Dr. Estes’ presentation struck a responsive chord with the audience. Numerous cardiologists rose to chime in that they, too, have encountered new-onset AF in middle-aged patients, friends, and medical colleagues who are serious cyclists, marathoners, and devotees of other forms of high-intensity endurance exercise to the tune of 10-20 hours per weekly.
“I know an electrophysiologist in his 60s who probably does 20 hours per week of spin and Cross-Fit classes and who is just now going into A-fib. How should I counsel him about this?” one audience member asked.
“You can’t tell these people to stop exercising,” Dr. Estes replied. “It’s so much a part of their identity. Their endorphin levels go down, and they feel depressed.”
For these patients he stresses what he called “the virtue of moderation.”
“If they have clinically important symptoms, many times we’ll decondition them. Often their symptoms will improve, and, in some instances, the A-fib will actually clear up and we don’t even need to go to any medical therapy,” Dr. Estes said.
His exercise prescription for deconditioning such patients is “basically nothing more than a moderate jog, a 10-minute mile. They should be able to carry on a conversation, with a peak heart rate no more than 60% of their maximum.”
If drug therapy is required, he favors rate control with beta blockers, as these patients generally don’t tolerate antiarrhythmic agents very well.
“Our threshold for AF ablation in these people is quite low because the response rate is high in paroxysmal AF in the absence of underlying structural heart disease,” he added.
Dr. Robert A. Vogel, who has been a consultant to the National Football League for a decade, commented, “I agree that you can exercise too much. These are the super-elite triathletes and so forth. A few of these folks not only get A-fib, but we’ve shown they can get accelerated atherosclerosis due to pervasive endothelial dysfunction caused by excessive athletics.”
“However, nothing here should be construed as saying exercise is bad for you. Athletes, even drug-taking cyclists and football players, actually live longer than similar nonathletes,” said Dr. Vogel, a cardiologist at the University of Colorado, Denver.
Dr. Estes was quick to agree.
“The cardiovascular benefits of exercise resoundingly overwhelm the adverse effects in that small group that experiences adverse effects,” he said.
Dr. Estes reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
Prediction: LVADs will rule end-stage heart failure
SNOWMASS, COLO. – Multifaceted progress in mechanical circulatory support as long-term therapy in end-stage heart failure is happening at a brisk pace, Y. Joseph C. Woo, MD, reported at the Annual Cardiovascular Conference at Snowmass.
declared Dr. Woo, professor and chair of the department of cardiothoracic surgery at Stanford (Calif.) University.
That’s quite a prediction, especially considering the source: Stanford is where the late Dr. Norman Shumway – widely considered “the father of heart transplantation” – performed the first adult heart transplant in the United States in 1968.
Dr. Woo was coauthor of an American Heart Association policy statement on the future of cardiovascular disease in the United States, which forecast a 25% increase in heart failure between 2010 and 2030 (Circulation. 2011 Mar 1;123[8]:933-44). There is simply no way that heart transplantation can begin to meet the projected growing need for effective therapy in patients with end-stage disease.
Here’s what Dr. Woo sees as the future of MCS:
Minimally invasive implantation
At Stanford, LVAD implantations are now routinely done off-pump on a beating heart.
“We clamp only when there is a sound reason, like the presence of left ventricular thrombus, where you run the risk of embolization without the cross clamp,” the surgeon said.
Concomitant valvular surgery
At Stanford and other centers of excellence, surgeons perform additional procedures as warranted while they implant an LVAD, including atrial fibrillation ablation, revascularization of the right heart coronaries, patent foramen ovale closure, and repair of the tricuspid, pulmonic, or aortic valves.
Enhanced right ventricular management
Survival is greatly impaired if a patient with an LVAD later requires the addition of a right ventricular assist device. This realization has led to the development of multiple preoperative risk scoring systems by the Stanford group (Ann Thorac Surg. 2013 Sep;96[3]:857-63) and others, including investigators at the Deutsche Herzzentrum Berlin, the world’s busiest heart transplant center. The purpose is to identify upfront those patients who are likely to later develop right heart failure so they can receive biventricular MCS from the start.
Adjunctive biologic therapies
Intramyocardial injection of 25 million allogeneic mesenchymal precursor cells during LVAD implantation appeared to be safe and showed a promising efficacy signal in a 30-patient, multicenter, double-blind, placebo-controlled, National Institutes of Health–sponsored proof of concept study in which Dr. Woo was a coinvestigator (Circulation. 2014 Jun 3;129[22]:2287-96).
The goal of this research effort is to provide a cell therapy assist to the LVAD as a bridge to recovery of left ventricular function such that the device might eventually no longer be needed, he explained.
These cells are immune privileged. They can be transplanted into recipients without need for immunosuppressive therapy or HLA matching, basically as an off the shelf product. Rather than transforming into cardiomyocytes, it appears that the mechanism by which the donor cells enhance cardiac performance in heart failure is via secretion of a shower of growth and angiogenic factors.
Based upon the encouraging results of the initial study, a 90-patient, phase II, double-blind clinical trial is underway. In order to better evaluate efficacy, this time the patients will receive 150 million mesenchymal precursor cells rather than 25 million.
New technologies
The developmental pipeline is chock full of MCS devices. The trend is to go smaller and simpler. HeartWare is developing a miniaturized version of its approved continuous flow centrifugal force LVAD. The ReliantHeart aVAD, an intraventricular device less than 2.5 cm in diameter, is approved in Europe and under study in the U.S. The Thoratec HeartMate III is a smaller version of the HeartMate II, which is FDA-approved as destination therapy. And the Circulite Synergy micropump, designed to provide partial circulatory support to patients who don’t require a full-force LVAD, is the size of a AA battery.
Dr. Woo reported having no financial conflicts.
bjancin@frontlinemedcom.com
SNOWMASS, COLO. – Multifaceted progress in mechanical circulatory support as long-term therapy in end-stage heart failure is happening at a brisk pace, Y. Joseph C. Woo, MD, reported at the Annual Cardiovascular Conference at Snowmass.
declared Dr. Woo, professor and chair of the department of cardiothoracic surgery at Stanford (Calif.) University.
That’s quite a prediction, especially considering the source: Stanford is where the late Dr. Norman Shumway – widely considered “the father of heart transplantation” – performed the first adult heart transplant in the United States in 1968.
Dr. Woo was coauthor of an American Heart Association policy statement on the future of cardiovascular disease in the United States, which forecast a 25% increase in heart failure between 2010 and 2030 (Circulation. 2011 Mar 1;123[8]:933-44). There is simply no way that heart transplantation can begin to meet the projected growing need for effective therapy in patients with end-stage disease.
Here’s what Dr. Woo sees as the future of MCS:
Minimally invasive implantation
At Stanford, LVAD implantations are now routinely done off-pump on a beating heart.
“We clamp only when there is a sound reason, like the presence of left ventricular thrombus, where you run the risk of embolization without the cross clamp,” the surgeon said.
Concomitant valvular surgery
At Stanford and other centers of excellence, surgeons perform additional procedures as warranted while they implant an LVAD, including atrial fibrillation ablation, revascularization of the right heart coronaries, patent foramen ovale closure, and repair of the tricuspid, pulmonic, or aortic valves.
Enhanced right ventricular management
Survival is greatly impaired if a patient with an LVAD later requires the addition of a right ventricular assist device. This realization has led to the development of multiple preoperative risk scoring systems by the Stanford group (Ann Thorac Surg. 2013 Sep;96[3]:857-63) and others, including investigators at the Deutsche Herzzentrum Berlin, the world’s busiest heart transplant center. The purpose is to identify upfront those patients who are likely to later develop right heart failure so they can receive biventricular MCS from the start.
Adjunctive biologic therapies
Intramyocardial injection of 25 million allogeneic mesenchymal precursor cells during LVAD implantation appeared to be safe and showed a promising efficacy signal in a 30-patient, multicenter, double-blind, placebo-controlled, National Institutes of Health–sponsored proof of concept study in which Dr. Woo was a coinvestigator (Circulation. 2014 Jun 3;129[22]:2287-96).
The goal of this research effort is to provide a cell therapy assist to the LVAD as a bridge to recovery of left ventricular function such that the device might eventually no longer be needed, he explained.
These cells are immune privileged. They can be transplanted into recipients without need for immunosuppressive therapy or HLA matching, basically as an off the shelf product. Rather than transforming into cardiomyocytes, it appears that the mechanism by which the donor cells enhance cardiac performance in heart failure is via secretion of a shower of growth and angiogenic factors.
Based upon the encouraging results of the initial study, a 90-patient, phase II, double-blind clinical trial is underway. In order to better evaluate efficacy, this time the patients will receive 150 million mesenchymal precursor cells rather than 25 million.
New technologies
The developmental pipeline is chock full of MCS devices. The trend is to go smaller and simpler. HeartWare is developing a miniaturized version of its approved continuous flow centrifugal force LVAD. The ReliantHeart aVAD, an intraventricular device less than 2.5 cm in diameter, is approved in Europe and under study in the U.S. The Thoratec HeartMate III is a smaller version of the HeartMate II, which is FDA-approved as destination therapy. And the Circulite Synergy micropump, designed to provide partial circulatory support to patients who don’t require a full-force LVAD, is the size of a AA battery.
Dr. Woo reported having no financial conflicts.
bjancin@frontlinemedcom.com
SNOWMASS, COLO. – Multifaceted progress in mechanical circulatory support as long-term therapy in end-stage heart failure is happening at a brisk pace, Y. Joseph C. Woo, MD, reported at the Annual Cardiovascular Conference at Snowmass.
declared Dr. Woo, professor and chair of the department of cardiothoracic surgery at Stanford (Calif.) University.
That’s quite a prediction, especially considering the source: Stanford is where the late Dr. Norman Shumway – widely considered “the father of heart transplantation” – performed the first adult heart transplant in the United States in 1968.
Dr. Woo was coauthor of an American Heart Association policy statement on the future of cardiovascular disease in the United States, which forecast a 25% increase in heart failure between 2010 and 2030 (Circulation. 2011 Mar 1;123[8]:933-44). There is simply no way that heart transplantation can begin to meet the projected growing need for effective therapy in patients with end-stage disease.
Here’s what Dr. Woo sees as the future of MCS:
Minimally invasive implantation
At Stanford, LVAD implantations are now routinely done off-pump on a beating heart.
“We clamp only when there is a sound reason, like the presence of left ventricular thrombus, where you run the risk of embolization without the cross clamp,” the surgeon said.
Concomitant valvular surgery
At Stanford and other centers of excellence, surgeons perform additional procedures as warranted while they implant an LVAD, including atrial fibrillation ablation, revascularization of the right heart coronaries, patent foramen ovale closure, and repair of the tricuspid, pulmonic, or aortic valves.
Enhanced right ventricular management
Survival is greatly impaired if a patient with an LVAD later requires the addition of a right ventricular assist device. This realization has led to the development of multiple preoperative risk scoring systems by the Stanford group (Ann Thorac Surg. 2013 Sep;96[3]:857-63) and others, including investigators at the Deutsche Herzzentrum Berlin, the world’s busiest heart transplant center. The purpose is to identify upfront those patients who are likely to later develop right heart failure so they can receive biventricular MCS from the start.
Adjunctive biologic therapies
Intramyocardial injection of 25 million allogeneic mesenchymal precursor cells during LVAD implantation appeared to be safe and showed a promising efficacy signal in a 30-patient, multicenter, double-blind, placebo-controlled, National Institutes of Health–sponsored proof of concept study in which Dr. Woo was a coinvestigator (Circulation. 2014 Jun 3;129[22]:2287-96).
The goal of this research effort is to provide a cell therapy assist to the LVAD as a bridge to recovery of left ventricular function such that the device might eventually no longer be needed, he explained.
These cells are immune privileged. They can be transplanted into recipients without need for immunosuppressive therapy or HLA matching, basically as an off the shelf product. Rather than transforming into cardiomyocytes, it appears that the mechanism by which the donor cells enhance cardiac performance in heart failure is via secretion of a shower of growth and angiogenic factors.
Based upon the encouraging results of the initial study, a 90-patient, phase II, double-blind clinical trial is underway. In order to better evaluate efficacy, this time the patients will receive 150 million mesenchymal precursor cells rather than 25 million.
New technologies
The developmental pipeline is chock full of MCS devices. The trend is to go smaller and simpler. HeartWare is developing a miniaturized version of its approved continuous flow centrifugal force LVAD. The ReliantHeart aVAD, an intraventricular device less than 2.5 cm in diameter, is approved in Europe and under study in the U.S. The Thoratec HeartMate III is a smaller version of the HeartMate II, which is FDA-approved as destination therapy. And the Circulite Synergy micropump, designed to provide partial circulatory support to patients who don’t require a full-force LVAD, is the size of a AA battery.
Dr. Woo reported having no financial conflicts.
bjancin@frontlinemedcom.com
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
Big changes ahead in heart failure management
SNOWMASS, COLO. – Advances in remote telemedical management show enormous promise as a means of preventing costly heart failure hospitalizations, William T. Abraham, MD, said at the Annual Cardiovascular Conference at Snowmass.
He characterized the decades-old conventional approach to heart failure management as a reactive strategy focused on making medication adjustments based upon weight changes and worsening signs and symptoms. But these physiologic markers of acute decompensation aren’t actionable; that is, they don’t occur until it’s too late to successfully intervene to prevent hospitalization.
It’s now clear that objective, measurable changes in intracardiac and pulmonary artery pressures as well as increases in lung fluid volume precede symptomatic decompensation episodes by several weeks. These early harbingers are reliably detectable by telemedical monitoring via small implantable pressure sensors or, noninvasively, using wearable sensors embedded in a vest.
“By moving upstream, we hope to develop a more proactive preventive approach to managing heart failure patients so that we can implement a medical intervention during this presymptomatic phase of worsening heart failure and avert a heart failure hospitalization,” the cardiologist explained.
That has already been demonstrated in several studies in which remote physicians checked the home monitoring data daily and promptly increased the dose of diuretics when pressure readings or lung fluid volume climbed above normal: The elevated readings quickly retreated and heart failure hospitalizations occurred much less frequently than with conventional management.
“Well-structured outpatient care could reduce the need for hospital admission, facilitate early intervention, prevent crisis management, and avoid complications or disease management in these patients,” Dr. Abraham observed.
Finding best telemedicine options
But this high-tech patient management strategy is not quite ready for prime time use in daily clinical practice.
“We’re still sorting through this field and trying to figure out the best telemedicine options,” according to Dr. Abraham.
He cited several recent large, well-conducted randomized trials that have persuasively shown that there’s no point in applying home telemedicine in order to quickly respond to changes in a heart failure patient’s blood pressure, weight, and symptom status.
“The horse is already out of the barn at that point in time,” according to the cardiologist.
For example, the BEAT-HF (Better Effectiveness After Transition–Heart Failure) trial included 1,437 patients hospitalized for heart failure at eight California academic medical centers who were randomized to usual care or an intervention that combined health-coaching telephone calls and protocols for physician or nurse response to daily telemetric data on patient blood pressure, symptoms, heart rate, weight, and symptoms. The intervention turned out to have absolutely no effect on the 180-day rate of readmissions, which was roughly 50% in both groups (JAMA Intern Med. 2016 Mar;176[3]:310-8).
The PCDM (Patient-Centered Disease Management) trial was a multicenter Veterans Affairs study that randomized heart failure patients to usual care or a comprehensive intervention involving collaborative care by a cardiologist, psychiatrist, primary care physician, and nurse coordinator; screening and treatment for depression; and home telemonitoring of heart failure decompensation symptoms. The multifaceted intervention had no effect on the 1-year readmission rate (JAMA Intern Med. 2015 May;175[5]:725-32).
“To date, I would challenge you to find any adequately powered randomized, controlled trial in heart failure disease management that demonstrates that the way we’ve been doing things really keeps heart failure patients out of the hospital. So, it is time for a paradigm shift and some new technologies in our armamentarium,” Dr. Abraham said.
CardioMEMS system
Several remote telemedical management systems for heart failure, which measure early preclinical harbingers of acute decompensation, have received Food and Drug Administration approval. Many more are in development. Dr. Abraham highlighted two approved systems for which he was a coinvestigator in clinical trials.
The CardioMEMS system uses a pressure sensor the size of a small paper clip that is placed in a branch of the pulmonary artery, where it readily becomes endothelialized. Device implantation can be carried out by any cardiologist who can perform a right heart catheterization, be it an electrophysiologist, interventionalist, heart failure specialist, or general cardiologist. It takes only about an additional 7 minutes to deploy the sensor following a standard diagnostic right heart catheterization. The system doesn’t use a battery and has no moving parts.
“Now, with more than 10 years experience, we have yet to see a sensor failure. It’s a highly reliable system,” according to the cardiologist.
Once a day the patient lies down, pushes a button, and the sensor is simultaneously powered up while the data on pulmonary artery pressure waveforms and systolic and diastolic pressures is extracted using radiofrequency energy.
In the randomized, multicenter, controlled, single-blind CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) trial, Dr. Abraham and coinvestigators demonstrated that pulmonary artery pressure-guided heart failure management reduced the rate of heart failure hospitalizations in the CardioMEMS group by 33% during the first 18 months of the trial and by 48% in the subsequent 13 months (Lancet. 2016 Jan 30;387[10017]:453-61).
“It’s important to note that the results were positive in diastolic as well as systolic heart failure. Patients with a baseline left ventricular ejection fraction of 40% or more saw a 50% reduction in the risk of heart failure hospitalizations, and those with an LVEF of 50% or more saw a 70% reduction,” Dr. Abraham said.
Other implantable hemodynamic monitors
Numerous other implantable pressure sensors are in development for management of heart failure, including other pulmonary artery pressure sensors as well as left atrial pressure monitors.
“You’re going to hear a lot more about this field of implantable hemodynamic monitors in the future,” the cardiologist predicted.
Dr. Abraham was also a coinvestigator in an observational study of a wearable sensor based upon radar technology developed for the military and subsequently applied to rescue searches through rubble for earthquake survivors. This remote dielectric sensing (ReDS) technology has been miniaturized, with the sensors embedded in an FDA-approved vest. The heart failure patient dons the SensiVest for 90 seconds once per day for measurement of the absolute amount of fluid in the lungs. The data is automatically transmitted to a secured site in the cloud, where the physician can review the results and adjust medications in response to early evidence of fluid buildup.
“The normal lung is composed of 20%-35% fluid. So when that fluid content is elevated, patients with heart failure have wet lungs and they’re decompensating. You increase their diuretics to bring it back down into normal range,” he explained.
In the observational study, conducted in Israel, hospital readmission rates were reduced by 87% through the use of ReDS-guided patient management using the system marketed by Sensible Medical Innovations. Dr. Abraham and his coinvestigators are now seeking to confirm those results in the prospective, multicenter, randomized, controlled U.S. SMILE study.
Dr. Abraham reported serving as a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude Medical.
SNOWMASS, COLO. – Advances in remote telemedical management show enormous promise as a means of preventing costly heart failure hospitalizations, William T. Abraham, MD, said at the Annual Cardiovascular Conference at Snowmass.
He characterized the decades-old conventional approach to heart failure management as a reactive strategy focused on making medication adjustments based upon weight changes and worsening signs and symptoms. But these physiologic markers of acute decompensation aren’t actionable; that is, they don’t occur until it’s too late to successfully intervene to prevent hospitalization.
It’s now clear that objective, measurable changes in intracardiac and pulmonary artery pressures as well as increases in lung fluid volume precede symptomatic decompensation episodes by several weeks. These early harbingers are reliably detectable by telemedical monitoring via small implantable pressure sensors or, noninvasively, using wearable sensors embedded in a vest.
“By moving upstream, we hope to develop a more proactive preventive approach to managing heart failure patients so that we can implement a medical intervention during this presymptomatic phase of worsening heart failure and avert a heart failure hospitalization,” the cardiologist explained.
That has already been demonstrated in several studies in which remote physicians checked the home monitoring data daily and promptly increased the dose of diuretics when pressure readings or lung fluid volume climbed above normal: The elevated readings quickly retreated and heart failure hospitalizations occurred much less frequently than with conventional management.
“Well-structured outpatient care could reduce the need for hospital admission, facilitate early intervention, prevent crisis management, and avoid complications or disease management in these patients,” Dr. Abraham observed.
Finding best telemedicine options
But this high-tech patient management strategy is not quite ready for prime time use in daily clinical practice.
“We’re still sorting through this field and trying to figure out the best telemedicine options,” according to Dr. Abraham.
He cited several recent large, well-conducted randomized trials that have persuasively shown that there’s no point in applying home telemedicine in order to quickly respond to changes in a heart failure patient’s blood pressure, weight, and symptom status.
“The horse is already out of the barn at that point in time,” according to the cardiologist.
For example, the BEAT-HF (Better Effectiveness After Transition–Heart Failure) trial included 1,437 patients hospitalized for heart failure at eight California academic medical centers who were randomized to usual care or an intervention that combined health-coaching telephone calls and protocols for physician or nurse response to daily telemetric data on patient blood pressure, symptoms, heart rate, weight, and symptoms. The intervention turned out to have absolutely no effect on the 180-day rate of readmissions, which was roughly 50% in both groups (JAMA Intern Med. 2016 Mar;176[3]:310-8).
The PCDM (Patient-Centered Disease Management) trial was a multicenter Veterans Affairs study that randomized heart failure patients to usual care or a comprehensive intervention involving collaborative care by a cardiologist, psychiatrist, primary care physician, and nurse coordinator; screening and treatment for depression; and home telemonitoring of heart failure decompensation symptoms. The multifaceted intervention had no effect on the 1-year readmission rate (JAMA Intern Med. 2015 May;175[5]:725-32).
“To date, I would challenge you to find any adequately powered randomized, controlled trial in heart failure disease management that demonstrates that the way we’ve been doing things really keeps heart failure patients out of the hospital. So, it is time for a paradigm shift and some new technologies in our armamentarium,” Dr. Abraham said.
CardioMEMS system
Several remote telemedical management systems for heart failure, which measure early preclinical harbingers of acute decompensation, have received Food and Drug Administration approval. Many more are in development. Dr. Abraham highlighted two approved systems for which he was a coinvestigator in clinical trials.
The CardioMEMS system uses a pressure sensor the size of a small paper clip that is placed in a branch of the pulmonary artery, where it readily becomes endothelialized. Device implantation can be carried out by any cardiologist who can perform a right heart catheterization, be it an electrophysiologist, interventionalist, heart failure specialist, or general cardiologist. It takes only about an additional 7 minutes to deploy the sensor following a standard diagnostic right heart catheterization. The system doesn’t use a battery and has no moving parts.
“Now, with more than 10 years experience, we have yet to see a sensor failure. It’s a highly reliable system,” according to the cardiologist.
Once a day the patient lies down, pushes a button, and the sensor is simultaneously powered up while the data on pulmonary artery pressure waveforms and systolic and diastolic pressures is extracted using radiofrequency energy.
In the randomized, multicenter, controlled, single-blind CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) trial, Dr. Abraham and coinvestigators demonstrated that pulmonary artery pressure-guided heart failure management reduced the rate of heart failure hospitalizations in the CardioMEMS group by 33% during the first 18 months of the trial and by 48% in the subsequent 13 months (Lancet. 2016 Jan 30;387[10017]:453-61).
“It’s important to note that the results were positive in diastolic as well as systolic heart failure. Patients with a baseline left ventricular ejection fraction of 40% or more saw a 50% reduction in the risk of heart failure hospitalizations, and those with an LVEF of 50% or more saw a 70% reduction,” Dr. Abraham said.
Other implantable hemodynamic monitors
Numerous other implantable pressure sensors are in development for management of heart failure, including other pulmonary artery pressure sensors as well as left atrial pressure monitors.
“You’re going to hear a lot more about this field of implantable hemodynamic monitors in the future,” the cardiologist predicted.
Dr. Abraham was also a coinvestigator in an observational study of a wearable sensor based upon radar technology developed for the military and subsequently applied to rescue searches through rubble for earthquake survivors. This remote dielectric sensing (ReDS) technology has been miniaturized, with the sensors embedded in an FDA-approved vest. The heart failure patient dons the SensiVest for 90 seconds once per day for measurement of the absolute amount of fluid in the lungs. The data is automatically transmitted to a secured site in the cloud, where the physician can review the results and adjust medications in response to early evidence of fluid buildup.
“The normal lung is composed of 20%-35% fluid. So when that fluid content is elevated, patients with heart failure have wet lungs and they’re decompensating. You increase their diuretics to bring it back down into normal range,” he explained.
In the observational study, conducted in Israel, hospital readmission rates were reduced by 87% through the use of ReDS-guided patient management using the system marketed by Sensible Medical Innovations. Dr. Abraham and his coinvestigators are now seeking to confirm those results in the prospective, multicenter, randomized, controlled U.S. SMILE study.
Dr. Abraham reported serving as a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude Medical.
SNOWMASS, COLO. – Advances in remote telemedical management show enormous promise as a means of preventing costly heart failure hospitalizations, William T. Abraham, MD, said at the Annual Cardiovascular Conference at Snowmass.
He characterized the decades-old conventional approach to heart failure management as a reactive strategy focused on making medication adjustments based upon weight changes and worsening signs and symptoms. But these physiologic markers of acute decompensation aren’t actionable; that is, they don’t occur until it’s too late to successfully intervene to prevent hospitalization.
It’s now clear that objective, measurable changes in intracardiac and pulmonary artery pressures as well as increases in lung fluid volume precede symptomatic decompensation episodes by several weeks. These early harbingers are reliably detectable by telemedical monitoring via small implantable pressure sensors or, noninvasively, using wearable sensors embedded in a vest.
“By moving upstream, we hope to develop a more proactive preventive approach to managing heart failure patients so that we can implement a medical intervention during this presymptomatic phase of worsening heart failure and avert a heart failure hospitalization,” the cardiologist explained.
That has already been demonstrated in several studies in which remote physicians checked the home monitoring data daily and promptly increased the dose of diuretics when pressure readings or lung fluid volume climbed above normal: The elevated readings quickly retreated and heart failure hospitalizations occurred much less frequently than with conventional management.
“Well-structured outpatient care could reduce the need for hospital admission, facilitate early intervention, prevent crisis management, and avoid complications or disease management in these patients,” Dr. Abraham observed.
Finding best telemedicine options
But this high-tech patient management strategy is not quite ready for prime time use in daily clinical practice.
“We’re still sorting through this field and trying to figure out the best telemedicine options,” according to Dr. Abraham.
He cited several recent large, well-conducted randomized trials that have persuasively shown that there’s no point in applying home telemedicine in order to quickly respond to changes in a heart failure patient’s blood pressure, weight, and symptom status.
“The horse is already out of the barn at that point in time,” according to the cardiologist.
For example, the BEAT-HF (Better Effectiveness After Transition–Heart Failure) trial included 1,437 patients hospitalized for heart failure at eight California academic medical centers who were randomized to usual care or an intervention that combined health-coaching telephone calls and protocols for physician or nurse response to daily telemetric data on patient blood pressure, symptoms, heart rate, weight, and symptoms. The intervention turned out to have absolutely no effect on the 180-day rate of readmissions, which was roughly 50% in both groups (JAMA Intern Med. 2016 Mar;176[3]:310-8).
The PCDM (Patient-Centered Disease Management) trial was a multicenter Veterans Affairs study that randomized heart failure patients to usual care or a comprehensive intervention involving collaborative care by a cardiologist, psychiatrist, primary care physician, and nurse coordinator; screening and treatment for depression; and home telemonitoring of heart failure decompensation symptoms. The multifaceted intervention had no effect on the 1-year readmission rate (JAMA Intern Med. 2015 May;175[5]:725-32).
“To date, I would challenge you to find any adequately powered randomized, controlled trial in heart failure disease management that demonstrates that the way we’ve been doing things really keeps heart failure patients out of the hospital. So, it is time for a paradigm shift and some new technologies in our armamentarium,” Dr. Abraham said.
CardioMEMS system
Several remote telemedical management systems for heart failure, which measure early preclinical harbingers of acute decompensation, have received Food and Drug Administration approval. Many more are in development. Dr. Abraham highlighted two approved systems for which he was a coinvestigator in clinical trials.
The CardioMEMS system uses a pressure sensor the size of a small paper clip that is placed in a branch of the pulmonary artery, where it readily becomes endothelialized. Device implantation can be carried out by any cardiologist who can perform a right heart catheterization, be it an electrophysiologist, interventionalist, heart failure specialist, or general cardiologist. It takes only about an additional 7 minutes to deploy the sensor following a standard diagnostic right heart catheterization. The system doesn’t use a battery and has no moving parts.
“Now, with more than 10 years experience, we have yet to see a sensor failure. It’s a highly reliable system,” according to the cardiologist.
Once a day the patient lies down, pushes a button, and the sensor is simultaneously powered up while the data on pulmonary artery pressure waveforms and systolic and diastolic pressures is extracted using radiofrequency energy.
In the randomized, multicenter, controlled, single-blind CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) trial, Dr. Abraham and coinvestigators demonstrated that pulmonary artery pressure-guided heart failure management reduced the rate of heart failure hospitalizations in the CardioMEMS group by 33% during the first 18 months of the trial and by 48% in the subsequent 13 months (Lancet. 2016 Jan 30;387[10017]:453-61).
“It’s important to note that the results were positive in diastolic as well as systolic heart failure. Patients with a baseline left ventricular ejection fraction of 40% or more saw a 50% reduction in the risk of heart failure hospitalizations, and those with an LVEF of 50% or more saw a 70% reduction,” Dr. Abraham said.
Other implantable hemodynamic monitors
Numerous other implantable pressure sensors are in development for management of heart failure, including other pulmonary artery pressure sensors as well as left atrial pressure monitors.
“You’re going to hear a lot more about this field of implantable hemodynamic monitors in the future,” the cardiologist predicted.
Dr. Abraham was also a coinvestigator in an observational study of a wearable sensor based upon radar technology developed for the military and subsequently applied to rescue searches through rubble for earthquake survivors. This remote dielectric sensing (ReDS) technology has been miniaturized, with the sensors embedded in an FDA-approved vest. The heart failure patient dons the SensiVest for 90 seconds once per day for measurement of the absolute amount of fluid in the lungs. The data is automatically transmitted to a secured site in the cloud, where the physician can review the results and adjust medications in response to early evidence of fluid buildup.
“The normal lung is composed of 20%-35% fluid. So when that fluid content is elevated, patients with heart failure have wet lungs and they’re decompensating. You increase their diuretics to bring it back down into normal range,” he explained.
In the observational study, conducted in Israel, hospital readmission rates were reduced by 87% through the use of ReDS-guided patient management using the system marketed by Sensible Medical Innovations. Dr. Abraham and his coinvestigators are now seeking to confirm those results in the prospective, multicenter, randomized, controlled U.S. SMILE study.
Dr. Abraham reported serving as a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude Medical.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
Familial hypercholesterolemia: Look for it!
SNOWMASS, COLO. – Familial hypercholesterolemia (FH), the most common genetic cause of premature atherosclerotic cardiovascular disease, affects an estimated 1 in 250 Americans. It doesn’t help that physicians are doing a terrible job of finding and treating them, Robert A. Vogel, MD, said at the Annual Cardiovascular Conference at Snowmass.
Indeed, it’s estimated that U.S. physicians diagnose fewer than 1% of affected individuals, as compared with a world’s-best 71% rate in the Netherlands, 43% in Norway, 13% in Sweden, and 12% in the United Kingdom (Eur Heart J. 2013 Dec 1;34[45]:3478-90a).
“You all have patients with FH in your practices. You have the parents, who already have atherosclerotic cardiovascular disease, but the kids need to be identified as well. Nothing is as gratifying as preventing disease in someone who would suffer a stroke or MI in the future,” the cardiologist continued.
FH is present in 7.5% of men and fully 11.1% of women with coronary heart disease (CHD), according to an analysis of more than 7,000 CHD patients in the EUROASPIRE IV study (Atherosclerosis. 2015 Jul;241[1]:169-75). Swiss investigators have shown, in a prospective study of 4,534 patients with acute coronary syndrome, that those who have FH are at significantly greater 1-year risk of recurrent fatal and nonfatal coronary events (Circulation. 2016 Sep 6;134[10]:698-709).
“You’re going to do worse after an MI if you have FH. These are very-high-risk folks. We need to find them because treatment is effective,” Dr. Vogel emphasized.
Three different sets of diagnostic criteria are available for FH: the Dutch Lipid Clinic Network diagnostic criteria, the Simon Broome criteria, and most recently, the American Heart Association criteria (Circulation. 2015 Dec 1;132[22]:2167-92).
There are common themes among the three sets of diagnostic criteria: Think FH when you encounter an LDL cholesterol level greater than 190 mg/dL in a patient not on statin therapy or more than 130 mg/dL on statin therapy, a personal or family history of premature atherosclerotic cardiovascular disease, or a patient with the characteristic findings of FH on physical examination.
These characteristic physical findings are xanthelasmas, corneal arcus, tuberous xanthomas, and Achilles tendon xanthomas, which Dr. Vogel called “the sine qua non of FH.”
The importance of tendon xanthomas as a manifestation of FH is vividly illustrated in the Dutch diagnostic criteria. Under the Dutch points-based scheme, various numbers of points are given for LDL level; a personal or family history of premature CAD, peripheral vascular disease, or stroke; positive physical findings; and a genetic test positive for a functional mutation in the LDL receptor gene. “Definite FH” requires a total of more than eight points, and a finding of tendon xanthomas alone provides six of them.
Tendon xanthomas are not only a key diagnostic feature, they are also important prognostically. They indicate that a patient is going to do relatively worse, independent of LDL level or LDL receptor gene mutation status (Arterioscler Thromb Vasc Biol. 2005 Sep;25[9]:1960-5).
A genetic test isn’t needed most of the time to diagnose FH, but it’s nevertheless helpful because it provides specific information about the patient’s LDL receptor status. A patient with a receptor-negative mutation in the LDL receptor gene is going to be much less responsive to maximum-intensity statin therapy than if defective LDL receptors are present.
Another test well worth ordering in a patient with FH is a lipoprotein(a) measurement. As shown in the prospective SAFEHEART trial (Spanish Familial Hypercholesterolemia Cohort Study), lipoprotein(a) is an independent predictor of cardiovascular disease in both men and women with FH. The risk is highest in those with lipoprotein(a) above 50 mg/dL – a normal level is below 30 mg/dL – who carry a null mutation in the LDL receptor gene (J Am Coll Cardiol. 2014 May 20;63[19]:1982-9).
Dr. Vogel reported serving as U.S. national coordinator for the ongoing ODYSSEY trial of the PCSK9 inhibitor alirocumab for cardiovascular risk reduction.
SNOWMASS, COLO. – Familial hypercholesterolemia (FH), the most common genetic cause of premature atherosclerotic cardiovascular disease, affects an estimated 1 in 250 Americans. It doesn’t help that physicians are doing a terrible job of finding and treating them, Robert A. Vogel, MD, said at the Annual Cardiovascular Conference at Snowmass.
Indeed, it’s estimated that U.S. physicians diagnose fewer than 1% of affected individuals, as compared with a world’s-best 71% rate in the Netherlands, 43% in Norway, 13% in Sweden, and 12% in the United Kingdom (Eur Heart J. 2013 Dec 1;34[45]:3478-90a).
“You all have patients with FH in your practices. You have the parents, who already have atherosclerotic cardiovascular disease, but the kids need to be identified as well. Nothing is as gratifying as preventing disease in someone who would suffer a stroke or MI in the future,” the cardiologist continued.
FH is present in 7.5% of men and fully 11.1% of women with coronary heart disease (CHD), according to an analysis of more than 7,000 CHD patients in the EUROASPIRE IV study (Atherosclerosis. 2015 Jul;241[1]:169-75). Swiss investigators have shown, in a prospective study of 4,534 patients with acute coronary syndrome, that those who have FH are at significantly greater 1-year risk of recurrent fatal and nonfatal coronary events (Circulation. 2016 Sep 6;134[10]:698-709).
“You’re going to do worse after an MI if you have FH. These are very-high-risk folks. We need to find them because treatment is effective,” Dr. Vogel emphasized.
Three different sets of diagnostic criteria are available for FH: the Dutch Lipid Clinic Network diagnostic criteria, the Simon Broome criteria, and most recently, the American Heart Association criteria (Circulation. 2015 Dec 1;132[22]:2167-92).
There are common themes among the three sets of diagnostic criteria: Think FH when you encounter an LDL cholesterol level greater than 190 mg/dL in a patient not on statin therapy or more than 130 mg/dL on statin therapy, a personal or family history of premature atherosclerotic cardiovascular disease, or a patient with the characteristic findings of FH on physical examination.
These characteristic physical findings are xanthelasmas, corneal arcus, tuberous xanthomas, and Achilles tendon xanthomas, which Dr. Vogel called “the sine qua non of FH.”
The importance of tendon xanthomas as a manifestation of FH is vividly illustrated in the Dutch diagnostic criteria. Under the Dutch points-based scheme, various numbers of points are given for LDL level; a personal or family history of premature CAD, peripheral vascular disease, or stroke; positive physical findings; and a genetic test positive for a functional mutation in the LDL receptor gene. “Definite FH” requires a total of more than eight points, and a finding of tendon xanthomas alone provides six of them.
Tendon xanthomas are not only a key diagnostic feature, they are also important prognostically. They indicate that a patient is going to do relatively worse, independent of LDL level or LDL receptor gene mutation status (Arterioscler Thromb Vasc Biol. 2005 Sep;25[9]:1960-5).
A genetic test isn’t needed most of the time to diagnose FH, but it’s nevertheless helpful because it provides specific information about the patient’s LDL receptor status. A patient with a receptor-negative mutation in the LDL receptor gene is going to be much less responsive to maximum-intensity statin therapy than if defective LDL receptors are present.
Another test well worth ordering in a patient with FH is a lipoprotein(a) measurement. As shown in the prospective SAFEHEART trial (Spanish Familial Hypercholesterolemia Cohort Study), lipoprotein(a) is an independent predictor of cardiovascular disease in both men and women with FH. The risk is highest in those with lipoprotein(a) above 50 mg/dL – a normal level is below 30 mg/dL – who carry a null mutation in the LDL receptor gene (J Am Coll Cardiol. 2014 May 20;63[19]:1982-9).
Dr. Vogel reported serving as U.S. national coordinator for the ongoing ODYSSEY trial of the PCSK9 inhibitor alirocumab for cardiovascular risk reduction.
SNOWMASS, COLO. – Familial hypercholesterolemia (FH), the most common genetic cause of premature atherosclerotic cardiovascular disease, affects an estimated 1 in 250 Americans. It doesn’t help that physicians are doing a terrible job of finding and treating them, Robert A. Vogel, MD, said at the Annual Cardiovascular Conference at Snowmass.
Indeed, it’s estimated that U.S. physicians diagnose fewer than 1% of affected individuals, as compared with a world’s-best 71% rate in the Netherlands, 43% in Norway, 13% in Sweden, and 12% in the United Kingdom (Eur Heart J. 2013 Dec 1;34[45]:3478-90a).
“You all have patients with FH in your practices. You have the parents, who already have atherosclerotic cardiovascular disease, but the kids need to be identified as well. Nothing is as gratifying as preventing disease in someone who would suffer a stroke or MI in the future,” the cardiologist continued.
FH is present in 7.5% of men and fully 11.1% of women with coronary heart disease (CHD), according to an analysis of more than 7,000 CHD patients in the EUROASPIRE IV study (Atherosclerosis. 2015 Jul;241[1]:169-75). Swiss investigators have shown, in a prospective study of 4,534 patients with acute coronary syndrome, that those who have FH are at significantly greater 1-year risk of recurrent fatal and nonfatal coronary events (Circulation. 2016 Sep 6;134[10]:698-709).
“You’re going to do worse after an MI if you have FH. These are very-high-risk folks. We need to find them because treatment is effective,” Dr. Vogel emphasized.
Three different sets of diagnostic criteria are available for FH: the Dutch Lipid Clinic Network diagnostic criteria, the Simon Broome criteria, and most recently, the American Heart Association criteria (Circulation. 2015 Dec 1;132[22]:2167-92).
There are common themes among the three sets of diagnostic criteria: Think FH when you encounter an LDL cholesterol level greater than 190 mg/dL in a patient not on statin therapy or more than 130 mg/dL on statin therapy, a personal or family history of premature atherosclerotic cardiovascular disease, or a patient with the characteristic findings of FH on physical examination.
These characteristic physical findings are xanthelasmas, corneal arcus, tuberous xanthomas, and Achilles tendon xanthomas, which Dr. Vogel called “the sine qua non of FH.”
The importance of tendon xanthomas as a manifestation of FH is vividly illustrated in the Dutch diagnostic criteria. Under the Dutch points-based scheme, various numbers of points are given for LDL level; a personal or family history of premature CAD, peripheral vascular disease, or stroke; positive physical findings; and a genetic test positive for a functional mutation in the LDL receptor gene. “Definite FH” requires a total of more than eight points, and a finding of tendon xanthomas alone provides six of them.
Tendon xanthomas are not only a key diagnostic feature, they are also important prognostically. They indicate that a patient is going to do relatively worse, independent of LDL level or LDL receptor gene mutation status (Arterioscler Thromb Vasc Biol. 2005 Sep;25[9]:1960-5).
A genetic test isn’t needed most of the time to diagnose FH, but it’s nevertheless helpful because it provides specific information about the patient’s LDL receptor status. A patient with a receptor-negative mutation in the LDL receptor gene is going to be much less responsive to maximum-intensity statin therapy than if defective LDL receptors are present.
Another test well worth ordering in a patient with FH is a lipoprotein(a) measurement. As shown in the prospective SAFEHEART trial (Spanish Familial Hypercholesterolemia Cohort Study), lipoprotein(a) is an independent predictor of cardiovascular disease in both men and women with FH. The risk is highest in those with lipoprotein(a) above 50 mg/dL – a normal level is below 30 mg/dL – who carry a null mutation in the LDL receptor gene (J Am Coll Cardiol. 2014 May 20;63[19]:1982-9).
Dr. Vogel reported serving as U.S. national coordinator for the ongoing ODYSSEY trial of the PCSK9 inhibitor alirocumab for cardiovascular risk reduction.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
Consider ultraslow thrombolysis for mechanical valve thrombosis
SNOWMASS, COLO. – Ultraslow infusion of a very-low-dose thrombolytic agent for treatment of mechanical prosthetic valve thrombosis appears to be as effective as surgery – the former first-line therapy – and sports a far lower stroke risk, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass.
“I’m not saying you have to use this, but I think it’s reasonable to consider it, especially if the patient is at high risk for surgery and low risk for thrombolysis,” according to Dr. Nishimura, professor of cardiovascular diseases and hypertension at the Mayo Clinic in Rochester, Minn.
He added that he and his Mayo colleagues have begun using the novel therapy and are favorably impressed with the resultant complete normalization of valve gradients and low complication rate.
Dr. Nishimura was cochair of the writing committee for the current American College of Cardiology/American Heart Association guidelines for management of valvular heart disease (Circulation. 2014 Jun 10;129[23]:e521-643). Those guidelines state that emergency surgery is the treatment of choice for thrombosis of a left-sided mechanical heart valve. That strong recommendation was based on a dozen nonrandomized studies reported prior to 2013 which showed a 95% success rate with surgery compared with 75% with conventional large-bolus thrombolytic therapy, a high 10%-12% mortality with either form of therapy, and a stroke risk of 12%-14% with thrombolytic therapy, substantially higher than for surgery.
Since release of the ACC/AHA guidelines, however, there’s been an important new development: Three groups outside of the United States have pioneered ultraslow thrombolytic therapy for mechanical prosthetic valve thrombosis. The supporting evidence comes from cohort studies, with no randomized trials done to date. But the collective reported experience from these three research teams shows a 90%-95% success rate – comparable to surgery – along with stroke and mortality rates in the low single digits.
The Turkish group waits until the patient’s international normalized ratio (INR) is below 2.5, then administers 25 mg of tissue plasminogen activator guided by transesophageal echocardiography (TEE) over 25 hours.
“We traditionally give 90 mg over 1 hour, so this is very, very slow therapy,” Dr. Nishimura observed.
After the 24-hour infusion, TEE is repeated. If imaging shows the clot is not resolved, another 25 mg of tissue plasminogen activator is given over 24 hours. This process is repeated for up to 8 days as needed (Am Heart J. 2015 Aug;170[2]:409-18).
Dr. Nishimura advised reserving ultraslow thrombolytic therapy for patients who are hemodynamically stable; this treatment takes a while to work, so patients in severe heart failure should be sent straight away to surgery. The novel therapy is best suited for patients with recent-onset mechanical valve thrombosis, a low INR, TEE evidence that the clot isn’t huge, and/or when surgical expertise isn’t readily available.
Before you can treat a prosthetic mechanical valve thrombosis, however, you have to make the diagnosis. Here’s what Dr. Nishimura recommends: First, suspect the condition on the basis of clinical symptoms of heart failure and dull, muffled S1 and S2 sounds on auscultation, especially in a patient who presents with a low INR.
Next, prove that obstruction is present via Doppler echocardiographic evidence of an abnormal gradient across the mechanical valve.
Finally, determine if the mechanical valve shows abnormal disc motion with sticking leaflets. TEE is excellent for visualizing a mechanical mitral valve but isn’t helpful if it’s a mechanical aortic valve.
“Old-fashioned fluoroscopy is the best approach for looking at leaflet motion in the atrial valve and mitral valve. We’ve got 3-D cine now that provides beautiful images, but if you can get the same information with a quick fluoroscopy, go with the fluoroscopy,” the cardiologist suggested.
He reported having no financial conflicts of interest.
SNOWMASS, COLO. – Ultraslow infusion of a very-low-dose thrombolytic agent for treatment of mechanical prosthetic valve thrombosis appears to be as effective as surgery – the former first-line therapy – and sports a far lower stroke risk, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass.
“I’m not saying you have to use this, but I think it’s reasonable to consider it, especially if the patient is at high risk for surgery and low risk for thrombolysis,” according to Dr. Nishimura, professor of cardiovascular diseases and hypertension at the Mayo Clinic in Rochester, Minn.
He added that he and his Mayo colleagues have begun using the novel therapy and are favorably impressed with the resultant complete normalization of valve gradients and low complication rate.
Dr. Nishimura was cochair of the writing committee for the current American College of Cardiology/American Heart Association guidelines for management of valvular heart disease (Circulation. 2014 Jun 10;129[23]:e521-643). Those guidelines state that emergency surgery is the treatment of choice for thrombosis of a left-sided mechanical heart valve. That strong recommendation was based on a dozen nonrandomized studies reported prior to 2013 which showed a 95% success rate with surgery compared with 75% with conventional large-bolus thrombolytic therapy, a high 10%-12% mortality with either form of therapy, and a stroke risk of 12%-14% with thrombolytic therapy, substantially higher than for surgery.
Since release of the ACC/AHA guidelines, however, there’s been an important new development: Three groups outside of the United States have pioneered ultraslow thrombolytic therapy for mechanical prosthetic valve thrombosis. The supporting evidence comes from cohort studies, with no randomized trials done to date. But the collective reported experience from these three research teams shows a 90%-95% success rate – comparable to surgery – along with stroke and mortality rates in the low single digits.
The Turkish group waits until the patient’s international normalized ratio (INR) is below 2.5, then administers 25 mg of tissue plasminogen activator guided by transesophageal echocardiography (TEE) over 25 hours.
“We traditionally give 90 mg over 1 hour, so this is very, very slow therapy,” Dr. Nishimura observed.
After the 24-hour infusion, TEE is repeated. If imaging shows the clot is not resolved, another 25 mg of tissue plasminogen activator is given over 24 hours. This process is repeated for up to 8 days as needed (Am Heart J. 2015 Aug;170[2]:409-18).
Dr. Nishimura advised reserving ultraslow thrombolytic therapy for patients who are hemodynamically stable; this treatment takes a while to work, so patients in severe heart failure should be sent straight away to surgery. The novel therapy is best suited for patients with recent-onset mechanical valve thrombosis, a low INR, TEE evidence that the clot isn’t huge, and/or when surgical expertise isn’t readily available.
Before you can treat a prosthetic mechanical valve thrombosis, however, you have to make the diagnosis. Here’s what Dr. Nishimura recommends: First, suspect the condition on the basis of clinical symptoms of heart failure and dull, muffled S1 and S2 sounds on auscultation, especially in a patient who presents with a low INR.
Next, prove that obstruction is present via Doppler echocardiographic evidence of an abnormal gradient across the mechanical valve.
Finally, determine if the mechanical valve shows abnormal disc motion with sticking leaflets. TEE is excellent for visualizing a mechanical mitral valve but isn’t helpful if it’s a mechanical aortic valve.
“Old-fashioned fluoroscopy is the best approach for looking at leaflet motion in the atrial valve and mitral valve. We’ve got 3-D cine now that provides beautiful images, but if you can get the same information with a quick fluoroscopy, go with the fluoroscopy,” the cardiologist suggested.
He reported having no financial conflicts of interest.
SNOWMASS, COLO. – Ultraslow infusion of a very-low-dose thrombolytic agent for treatment of mechanical prosthetic valve thrombosis appears to be as effective as surgery – the former first-line therapy – and sports a far lower stroke risk, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass.
“I’m not saying you have to use this, but I think it’s reasonable to consider it, especially if the patient is at high risk for surgery and low risk for thrombolysis,” according to Dr. Nishimura, professor of cardiovascular diseases and hypertension at the Mayo Clinic in Rochester, Minn.
He added that he and his Mayo colleagues have begun using the novel therapy and are favorably impressed with the resultant complete normalization of valve gradients and low complication rate.
Dr. Nishimura was cochair of the writing committee for the current American College of Cardiology/American Heart Association guidelines for management of valvular heart disease (Circulation. 2014 Jun 10;129[23]:e521-643). Those guidelines state that emergency surgery is the treatment of choice for thrombosis of a left-sided mechanical heart valve. That strong recommendation was based on a dozen nonrandomized studies reported prior to 2013 which showed a 95% success rate with surgery compared with 75% with conventional large-bolus thrombolytic therapy, a high 10%-12% mortality with either form of therapy, and a stroke risk of 12%-14% with thrombolytic therapy, substantially higher than for surgery.
Since release of the ACC/AHA guidelines, however, there’s been an important new development: Three groups outside of the United States have pioneered ultraslow thrombolytic therapy for mechanical prosthetic valve thrombosis. The supporting evidence comes from cohort studies, with no randomized trials done to date. But the collective reported experience from these three research teams shows a 90%-95% success rate – comparable to surgery – along with stroke and mortality rates in the low single digits.
The Turkish group waits until the patient’s international normalized ratio (INR) is below 2.5, then administers 25 mg of tissue plasminogen activator guided by transesophageal echocardiography (TEE) over 25 hours.
“We traditionally give 90 mg over 1 hour, so this is very, very slow therapy,” Dr. Nishimura observed.
After the 24-hour infusion, TEE is repeated. If imaging shows the clot is not resolved, another 25 mg of tissue plasminogen activator is given over 24 hours. This process is repeated for up to 8 days as needed (Am Heart J. 2015 Aug;170[2]:409-18).
Dr. Nishimura advised reserving ultraslow thrombolytic therapy for patients who are hemodynamically stable; this treatment takes a while to work, so patients in severe heart failure should be sent straight away to surgery. The novel therapy is best suited for patients with recent-onset mechanical valve thrombosis, a low INR, TEE evidence that the clot isn’t huge, and/or when surgical expertise isn’t readily available.
Before you can treat a prosthetic mechanical valve thrombosis, however, you have to make the diagnosis. Here’s what Dr. Nishimura recommends: First, suspect the condition on the basis of clinical symptoms of heart failure and dull, muffled S1 and S2 sounds on auscultation, especially in a patient who presents with a low INR.
Next, prove that obstruction is present via Doppler echocardiographic evidence of an abnormal gradient across the mechanical valve.
Finally, determine if the mechanical valve shows abnormal disc motion with sticking leaflets. TEE is excellent for visualizing a mechanical mitral valve but isn’t helpful if it’s a mechanical aortic valve.
“Old-fashioned fluoroscopy is the best approach for looking at leaflet motion in the atrial valve and mitral valve. We’ve got 3-D cine now that provides beautiful images, but if you can get the same information with a quick fluoroscopy, go with the fluoroscopy,” the cardiologist suggested.
He reported having no financial conflicts of interest.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
The two faces of mitral regurgitation
SNOWMASS, COLO. – Primary mitral regurgitation and secondary mitral regurgitation may sound a lot alike, but they are in fact starkly different diseases, Blase A. Carabello, MD, said at the Annual Cardiovascular Conference at Snowmass.
“They are almost entirely different in their etiologies, in their pathophysiologies, and in their therapies,” according to Dr. Carabello, professor of medicine and chief of cardiology at East Carolina University in Greenville, N.C.
“On the other hand, if you fix the valve, you fix the disease,” he said.
In contrast, in secondary MR, the dysfunctional valve is a result of the ventricular problem, not its cause.
“In secondary MR, it’s the ventricle that made the valve sick. It’s the regional wall motion abnormalities, the displacement of the papillary muscles, and the dilation of the mitral annulus that pulls the mitral valve apart and prevents it from coapting,” he explained.
Dr. Carabello, who was on the writing committee for the current American College of Cardiology/American Heart Association guidelines on management of valvular heart disease (Circulation. 2014 Jun 10;129[23]:e521-643), highlighted other key distinctions between the two diseases.
Primary MR
“Primary MR, unlike aortic regurgitation, is not well tolerated. Early repair is key,” the cardiologist stressed.
The ACC/AHA guidelines emphasize the importance of early referral for surgery for primary MR because of surgery’s proven survival benefit. The triggers for surgery, as described in the guidelines, are easy to remember, namely, “symptoms/60/50/40.” That is, it’s time to move on to surgery when any of the following occurs: The patient becomes even mildly symptomatic, the left ventricular ejection fraction (LVEF) drops to 60%, the pulmonary artery pressure climbs to 50 mm Hg, or the LV end-systolic dimension reaches 40 mm.
Dr. Carabello said he believes those surgical thresholds are conservative, and it’s best to make the surgical referral when a patient approaches one or more of those triggers, but before actually reaching them.
“That’s the way I practice: Don’t wait for any of those things. Just get it done. One advantage to early repair is the patient can’t get lost to follow-up. They’re repaired, and they can’t take it out,” he said.
It’s possible that the next iteration of the guidelines will utilize stricter thresholds for surgery. French investigators have shown that surgery for primary MR achieves a significantly higher rate of normal LV function if the operation occurs when patients have an LVEF of 64% or more and an LV end-systolic dimension of less than 37 mm (Eur J Echocardiogr. 2011 Sep;12[9]:702-10). So far, though, there hasn’t been a confirmatory study.
“I think the normal EF in primary MR is about 70%. By the time the EF in a patient with primary MR gets down into the 50s, you’re looking at an extraordinarily sick ventricle,” according to Dr. Carabello.
The impetus for including the “symptoms/60/50/40” surgical triggers in the guidelines is to encourage physicians to make the surgical referral earlier than has often been the case. Too frequently, the surgical referral is delayed until damage to the ventricle is irreversible, with a resultant worsened prognosis.
“The natural history is such that, from the time a patient with severe primary MR enters your office to the annual mortality risk reaching 50% is only about 5 years. So if you’re going to do watchful waiting, fine, but remember: You don’t have all that long to watch and wait before something bad happens to these folks,” the cardiologist cautioned.
He added that it’s possible that, in the future, cardiac biomarkers will be utilized to help predict the long-term mortality risk of patients under medical management of their primary MR. In a recent study of 1,331 patients with primary MR, the investigators showed that the ratio of B-type natriuretic peptide (BNP) to the upper limit of normal BNP, adjusted for age and sex, was a powerful independent predictor of this risk (J Am Coll Cardiol. 2016 Sep 20;68[12]:1297-307).
The guidelines state that mitral valve repair is preferable to replacement as long as the heart team determines there’s at least a 95% chance of a durable repair. That’s because the operative mortality associated with replacement is significantly higher than with repair.
Secondary MR
Unlike in primary MR, it’s unclear whether surgery prolongs life for patients with secondary MR, or if mitral repair is superior to replacement. Thus, the current guidelines recommend surgery only for patients who are still severely symptomatic despite maximal guideline-directed medical therapy for heart failure as well as cardiac resynchronization therapy, provided they have a conduction system abnormality and qualify for the device therapy.
“If you’ve done all that and they’re still sick, I think that surgery or the MitraClip may benefit them very much,” Dr. Carabello said.
In the United States, the MitraClip transcatheter device is approved only for the treatment of primary MR in inoperable patients. But in the rest of the world, roughly three-quarters of these devices are used for treatment of secondary MR. That potential indication is currently under study in the United States in the phase III COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation).
“In the acute setting, the changes in hemodynamic variables and left ventricular performance that occur with the MitraClip are quite dramatic, with a marked decrease in wedge pressure and a markedly increased stroke volume, which is what it’s supposed to do. So I’m encouraged. We’ll wait for the results of the COAPT trial, which I believe is likely to demonstrate a reduction in hospitalizations and certainly an improvement in patient symptoms. But I doubt very much that we’ll ever see a change in lifespan because the ventricle is still sick, and we in 2017 have not found a way yet to revive a sick ventricle. It’s unlikely that fixing the MR will do so,” according to Dr. Carabello.
He reported serving on a data safety monitoring board for Edwards Lifesciences.
SNOWMASS, COLO. – Primary mitral regurgitation and secondary mitral regurgitation may sound a lot alike, but they are in fact starkly different diseases, Blase A. Carabello, MD, said at the Annual Cardiovascular Conference at Snowmass.
“They are almost entirely different in their etiologies, in their pathophysiologies, and in their therapies,” according to Dr. Carabello, professor of medicine and chief of cardiology at East Carolina University in Greenville, N.C.
“On the other hand, if you fix the valve, you fix the disease,” he said.
In contrast, in secondary MR, the dysfunctional valve is a result of the ventricular problem, not its cause.
“In secondary MR, it’s the ventricle that made the valve sick. It’s the regional wall motion abnormalities, the displacement of the papillary muscles, and the dilation of the mitral annulus that pulls the mitral valve apart and prevents it from coapting,” he explained.
Dr. Carabello, who was on the writing committee for the current American College of Cardiology/American Heart Association guidelines on management of valvular heart disease (Circulation. 2014 Jun 10;129[23]:e521-643), highlighted other key distinctions between the two diseases.
Primary MR
“Primary MR, unlike aortic regurgitation, is not well tolerated. Early repair is key,” the cardiologist stressed.
The ACC/AHA guidelines emphasize the importance of early referral for surgery for primary MR because of surgery’s proven survival benefit. The triggers for surgery, as described in the guidelines, are easy to remember, namely, “symptoms/60/50/40.” That is, it’s time to move on to surgery when any of the following occurs: The patient becomes even mildly symptomatic, the left ventricular ejection fraction (LVEF) drops to 60%, the pulmonary artery pressure climbs to 50 mm Hg, or the LV end-systolic dimension reaches 40 mm.
Dr. Carabello said he believes those surgical thresholds are conservative, and it’s best to make the surgical referral when a patient approaches one or more of those triggers, but before actually reaching them.
“That’s the way I practice: Don’t wait for any of those things. Just get it done. One advantage to early repair is the patient can’t get lost to follow-up. They’re repaired, and they can’t take it out,” he said.
It’s possible that the next iteration of the guidelines will utilize stricter thresholds for surgery. French investigators have shown that surgery for primary MR achieves a significantly higher rate of normal LV function if the operation occurs when patients have an LVEF of 64% or more and an LV end-systolic dimension of less than 37 mm (Eur J Echocardiogr. 2011 Sep;12[9]:702-10). So far, though, there hasn’t been a confirmatory study.
“I think the normal EF in primary MR is about 70%. By the time the EF in a patient with primary MR gets down into the 50s, you’re looking at an extraordinarily sick ventricle,” according to Dr. Carabello.
The impetus for including the “symptoms/60/50/40” surgical triggers in the guidelines is to encourage physicians to make the surgical referral earlier than has often been the case. Too frequently, the surgical referral is delayed until damage to the ventricle is irreversible, with a resultant worsened prognosis.
“The natural history is such that, from the time a patient with severe primary MR enters your office to the annual mortality risk reaching 50% is only about 5 years. So if you’re going to do watchful waiting, fine, but remember: You don’t have all that long to watch and wait before something bad happens to these folks,” the cardiologist cautioned.
He added that it’s possible that, in the future, cardiac biomarkers will be utilized to help predict the long-term mortality risk of patients under medical management of their primary MR. In a recent study of 1,331 patients with primary MR, the investigators showed that the ratio of B-type natriuretic peptide (BNP) to the upper limit of normal BNP, adjusted for age and sex, was a powerful independent predictor of this risk (J Am Coll Cardiol. 2016 Sep 20;68[12]:1297-307).
The guidelines state that mitral valve repair is preferable to replacement as long as the heart team determines there’s at least a 95% chance of a durable repair. That’s because the operative mortality associated with replacement is significantly higher than with repair.
Secondary MR
Unlike in primary MR, it’s unclear whether surgery prolongs life for patients with secondary MR, or if mitral repair is superior to replacement. Thus, the current guidelines recommend surgery only for patients who are still severely symptomatic despite maximal guideline-directed medical therapy for heart failure as well as cardiac resynchronization therapy, provided they have a conduction system abnormality and qualify for the device therapy.
“If you’ve done all that and they’re still sick, I think that surgery or the MitraClip may benefit them very much,” Dr. Carabello said.
In the United States, the MitraClip transcatheter device is approved only for the treatment of primary MR in inoperable patients. But in the rest of the world, roughly three-quarters of these devices are used for treatment of secondary MR. That potential indication is currently under study in the United States in the phase III COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation).
“In the acute setting, the changes in hemodynamic variables and left ventricular performance that occur with the MitraClip are quite dramatic, with a marked decrease in wedge pressure and a markedly increased stroke volume, which is what it’s supposed to do. So I’m encouraged. We’ll wait for the results of the COAPT trial, which I believe is likely to demonstrate a reduction in hospitalizations and certainly an improvement in patient symptoms. But I doubt very much that we’ll ever see a change in lifespan because the ventricle is still sick, and we in 2017 have not found a way yet to revive a sick ventricle. It’s unlikely that fixing the MR will do so,” according to Dr. Carabello.
He reported serving on a data safety monitoring board for Edwards Lifesciences.
SNOWMASS, COLO. – Primary mitral regurgitation and secondary mitral regurgitation may sound a lot alike, but they are in fact starkly different diseases, Blase A. Carabello, MD, said at the Annual Cardiovascular Conference at Snowmass.
“They are almost entirely different in their etiologies, in their pathophysiologies, and in their therapies,” according to Dr. Carabello, professor of medicine and chief of cardiology at East Carolina University in Greenville, N.C.
“On the other hand, if you fix the valve, you fix the disease,” he said.
In contrast, in secondary MR, the dysfunctional valve is a result of the ventricular problem, not its cause.
“In secondary MR, it’s the ventricle that made the valve sick. It’s the regional wall motion abnormalities, the displacement of the papillary muscles, and the dilation of the mitral annulus that pulls the mitral valve apart and prevents it from coapting,” he explained.
Dr. Carabello, who was on the writing committee for the current American College of Cardiology/American Heart Association guidelines on management of valvular heart disease (Circulation. 2014 Jun 10;129[23]:e521-643), highlighted other key distinctions between the two diseases.
Primary MR
“Primary MR, unlike aortic regurgitation, is not well tolerated. Early repair is key,” the cardiologist stressed.
The ACC/AHA guidelines emphasize the importance of early referral for surgery for primary MR because of surgery’s proven survival benefit. The triggers for surgery, as described in the guidelines, are easy to remember, namely, “symptoms/60/50/40.” That is, it’s time to move on to surgery when any of the following occurs: The patient becomes even mildly symptomatic, the left ventricular ejection fraction (LVEF) drops to 60%, the pulmonary artery pressure climbs to 50 mm Hg, or the LV end-systolic dimension reaches 40 mm.
Dr. Carabello said he believes those surgical thresholds are conservative, and it’s best to make the surgical referral when a patient approaches one or more of those triggers, but before actually reaching them.
“That’s the way I practice: Don’t wait for any of those things. Just get it done. One advantage to early repair is the patient can’t get lost to follow-up. They’re repaired, and they can’t take it out,” he said.
It’s possible that the next iteration of the guidelines will utilize stricter thresholds for surgery. French investigators have shown that surgery for primary MR achieves a significantly higher rate of normal LV function if the operation occurs when patients have an LVEF of 64% or more and an LV end-systolic dimension of less than 37 mm (Eur J Echocardiogr. 2011 Sep;12[9]:702-10). So far, though, there hasn’t been a confirmatory study.
“I think the normal EF in primary MR is about 70%. By the time the EF in a patient with primary MR gets down into the 50s, you’re looking at an extraordinarily sick ventricle,” according to Dr. Carabello.
The impetus for including the “symptoms/60/50/40” surgical triggers in the guidelines is to encourage physicians to make the surgical referral earlier than has often been the case. Too frequently, the surgical referral is delayed until damage to the ventricle is irreversible, with a resultant worsened prognosis.
“The natural history is such that, from the time a patient with severe primary MR enters your office to the annual mortality risk reaching 50% is only about 5 years. So if you’re going to do watchful waiting, fine, but remember: You don’t have all that long to watch and wait before something bad happens to these folks,” the cardiologist cautioned.
He added that it’s possible that, in the future, cardiac biomarkers will be utilized to help predict the long-term mortality risk of patients under medical management of their primary MR. In a recent study of 1,331 patients with primary MR, the investigators showed that the ratio of B-type natriuretic peptide (BNP) to the upper limit of normal BNP, adjusted for age and sex, was a powerful independent predictor of this risk (J Am Coll Cardiol. 2016 Sep 20;68[12]:1297-307).
The guidelines state that mitral valve repair is preferable to replacement as long as the heart team determines there’s at least a 95% chance of a durable repair. That’s because the operative mortality associated with replacement is significantly higher than with repair.
Secondary MR
Unlike in primary MR, it’s unclear whether surgery prolongs life for patients with secondary MR, or if mitral repair is superior to replacement. Thus, the current guidelines recommend surgery only for patients who are still severely symptomatic despite maximal guideline-directed medical therapy for heart failure as well as cardiac resynchronization therapy, provided they have a conduction system abnormality and qualify for the device therapy.
“If you’ve done all that and they’re still sick, I think that surgery or the MitraClip may benefit them very much,” Dr. Carabello said.
In the United States, the MitraClip transcatheter device is approved only for the treatment of primary MR in inoperable patients. But in the rest of the world, roughly three-quarters of these devices are used for treatment of secondary MR. That potential indication is currently under study in the United States in the phase III COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation).
“In the acute setting, the changes in hemodynamic variables and left ventricular performance that occur with the MitraClip are quite dramatic, with a marked decrease in wedge pressure and a markedly increased stroke volume, which is what it’s supposed to do. So I’m encouraged. We’ll wait for the results of the COAPT trial, which I believe is likely to demonstrate a reduction in hospitalizations and certainly an improvement in patient symptoms. But I doubt very much that we’ll ever see a change in lifespan because the ventricle is still sick, and we in 2017 have not found a way yet to revive a sick ventricle. It’s unlikely that fixing the MR will do so,” according to Dr. Carabello.
He reported serving on a data safety monitoring board for Edwards Lifesciences.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
IgG4-related disease can strike any organ system
SNOWMASS, COLO. – Progress in the understanding and treatment of immunoglobulin G4–related disease is occurring “at lightning speed,” John H. Stone, MD, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
Eight or nine years ago no one had heard of immunoglobulin G4–related disease (IgG4-RD). Today, because of the broad swath the disease cuts, it’s a hot research topic in every subspecialty of medicine as well as surgery, pathology, and radiology.
This new understanding of IgG4-RD, he added, is opening the door to novel treatments.
“This is not a new disease. It was there when we were all in medical school, and for hundreds of years before that. But it’s really only in the last decade that we have come to understand that the disease can affect literally every organ system in the body with syndromes that we once thought were isolated organ-specific syndromes but we now recognize are part of a multiorgan disease currently called IgG4-related disease,” the rheumatologist said.
IgG4-RD is an immune-mediated fibroinflammatory condition characterized histopathologically by three hallmark features in involved tissue: obliterative phlebitis, storiform fibrosis, and a dense lymphoplasmacytic infiltrate.
Clinically, IgG4-RD often presents as a mass lesion that can affect any organ.
“I have many patients who’ve undergone modified Whipple procedures because they were thought to have adenocarcinoma of the pancreas,” according to Dr. Stone.
Other common presentations include Riedel’s thyroiditis, autoimmune pancreatitis, sclerosing cholangitis, sialadenitis, dacryoadenitis, periaortitis, an eosinophilic rash, and pseudotumor of the lung, lymph nodes, or orbits.
“Retroperitoneal fibrosis is a common and underappreciated manifestation. It may be the most common subsyndrome associated with IgG4-related disease,” he observed.
Another common presentation involves atopic disease – asthma, allergic rhinitis, eczema, eosinophilia, nasal polyps – developing out of the blue in middle age or later life. This observation led some other investigators to posit that IgG4-RD is a T-helper type 2–driven disease, an assertion debunked by Dr. Stone and coworkers (Allergy. 2014 Feb;69[2]:269-72).
Dr. Stone and his coinvestigators have published the largest series of patients with biopsy-proven IgG4-RD reported to date (Arthritis Rheumatol. 2015 Sep; 67[9]:2466-75). The average age at disease onset was 50 years. Of note, multiorgan involvement was the norm: 24% of patients had two organs involved, and 38% had three or more.
Analysis of this large patient series has led Dr. Stone to a surprising conclusion about the nature of IgG4-RD: “We have greatly overemphasized the importance of IgG4 in this condition,” he asserted.
Indeed, a mere 51% of the patients with clinically active untreated IgG4-RD in his series had an elevated serum IgG level. Dr. Stone characterized IgG4 as “kind of a wimpy antibody” incapable of driving the disease process because it is a noninflammatory immunoglobulin. This has led to speculation that IgG4 functions as what he termed an “antigen sink,” attempting to bind antigen at sites of inflammation.
But while an elevated serum IgG4 is of limited utility for diagnostic purposes, Dr. Stone and coworkers have demonstrated that it is of value as a predictor of relapse. Among patients with a treatment-induced remission, those in the top quartile in terms of baseline pretreatment serum IgG4 were 6.2-fold more likely to relapse (Rheumatology [Oxford]. 2016 Jun;55[6]:1000-8).
“This is a very useful marker for patients who are going to need chronic ongoing therapy. The notion of putting such patients on steroids for months and years is not appealing,” he said.
Levels of circulating plasmablasts as measured by peripheral blood flow cytometry, especially IgG4-positive plasmablasts, have proven much more helpful than serum IgG4 levels as a diagnostic tool, a reliable biomarker of disease activity, and a therapeutic target. Levels of these short-lived CD19+CD38+CD27+ plasmablasts are enormously elevated independent of serum IgG4 in patients with active IgG4-RD.
“One of the questions I’m most often asked is whether IgG4-related disease is a premalignant condition. My answer is no. The plasmablast expansion is oligoclonal, not polyclonal,” Dr. Stone continued.
He described IgG4-RD as “a continuous dance between T cells and B cells.” The latest thinking regarding pathogenesis is that type 2 T follicular helper cells activate B cells, which become memory B cells or plasmablasts. These activated B cells and plasmablasts present antigen to CD4+ cytotoxic T cells at sites of disease. Dr. Stone and his coinvestigators recently identified these CD4+ cytotoxic T cells as a novel population of clonally expanded T cells with SLAMF7 as a surface marker. The cells secrete interferon-gamma, interleukin-1, and transforming growth factor-beta, all of which are capable of driving the intense fibrosis characteristic of IgG4-RD. In addition, these CD4+ cytotoxic T cells secrete granzyme B and perforin, previously thought to be released mainly by natural killer T cells.
Joint American College of Rheumatology/European League Against Rheumatism classification criteria for the disease are expected to be finalized this winter at the Third International Symposium on IgG4-Related Diseases.
Treatment with rituxumab
Glucocorticoids remain the first-line therapy in IgG4-related disease, but it’s essential to bear in mind that their long-term efficacy in this immune-mediated fibroinflammatory disease is the exception rather than the rule, Dr. Stone said at the symposium.
Dr. Stone was a coauthor of an international expert consensus statement on the treatment of IgG4-related disease (IgG4-RD), which emphasized that point (Arthritis Rheumatol. 2015 Jul;67[7]:1688-99).
“I typically start with prednisone at 40 mg/day, and there’s a dramatic response in these patients. Then I taper them off after 2-3 months. If 2-3 months doesn’t put them into a long-term sustained remission, it’s time to go to something else,” said Dr. Stone.
So what’s the next move, then, after steroids fail? Dr. Stone was a pioneer in the strikingly successful use of B cell depletion via rituximab (Rituxan) in patients with IgG4-RD. First he and his coinvestigators demonstrated that this off-label use of rituximab led to rapid clinical and histologic improvement (Ann Rheum Dis. 2015 Jun; 74[6]:1171-7), then they showed it also causes levels of circulating plasmablasts, serum IgG4, and biomarkers of fibrosis to plunge, suggesting B cell depletion may halt the destructive process of collagen deposition that characterizes this immune-related disease (Ann Rheum Dis. 2015 Dec;74[12]:2236-43). They have also reported that patients with very elevated baseline serum IgG4 levels are at more than sixfold increased risk of relapse at a median of 244 days from their first rituximab infusion (Rheumatology [Oxford]. 2016 Jun;55[6]:1000-8).
The success with rituximab is just one example of how improved understanding of the pathophysiology of IgG4-RD has opened the door to novel treatments. Dr. Stone is the lead investigator in an ongoing phase II, open-label study in which 15 patients with active IgG4-RD will receive intravenous XmAb5871 every 2 weeks for 6 months to evaluate the effect on the IgG4-RD Responder Index. XmAb5871 is a monoclonal antibody that binds to CD19 and FCgammaRIIb in order to downregulate activated B cells and plasmablasts. It is also being developed for treatment of systemic lupus erythematosus.
Dr. Stone and his coinvestigators are working on a therapeutic approach to IgG4-RD that targets antigen presentation by activated B cells to CD4+ cytotoxic T cells at sites of disease. These CD4+ cytotoxic T cells contain signaling lymphocyte activation molecule F7 (SLAMF7) as a surface marker. Elotuzumab (Empliciti), an immunostimulatory humanized monoclonal antibody targeting SLAMF7, is already on the market for treatment of multiple myeloma, he noted.
Dr. Stone reported receiving IgG4-RD-related research funding from and serving as a consultant to Genentech and Xencor, which is developing XmAb5871.
SNOWMASS, COLO. – Progress in the understanding and treatment of immunoglobulin G4–related disease is occurring “at lightning speed,” John H. Stone, MD, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
Eight or nine years ago no one had heard of immunoglobulin G4–related disease (IgG4-RD). Today, because of the broad swath the disease cuts, it’s a hot research topic in every subspecialty of medicine as well as surgery, pathology, and radiology.
This new understanding of IgG4-RD, he added, is opening the door to novel treatments.
“This is not a new disease. It was there when we were all in medical school, and for hundreds of years before that. But it’s really only in the last decade that we have come to understand that the disease can affect literally every organ system in the body with syndromes that we once thought were isolated organ-specific syndromes but we now recognize are part of a multiorgan disease currently called IgG4-related disease,” the rheumatologist said.
IgG4-RD is an immune-mediated fibroinflammatory condition characterized histopathologically by three hallmark features in involved tissue: obliterative phlebitis, storiform fibrosis, and a dense lymphoplasmacytic infiltrate.
Clinically, IgG4-RD often presents as a mass lesion that can affect any organ.
“I have many patients who’ve undergone modified Whipple procedures because they were thought to have adenocarcinoma of the pancreas,” according to Dr. Stone.
Other common presentations include Riedel’s thyroiditis, autoimmune pancreatitis, sclerosing cholangitis, sialadenitis, dacryoadenitis, periaortitis, an eosinophilic rash, and pseudotumor of the lung, lymph nodes, or orbits.
“Retroperitoneal fibrosis is a common and underappreciated manifestation. It may be the most common subsyndrome associated with IgG4-related disease,” he observed.
Another common presentation involves atopic disease – asthma, allergic rhinitis, eczema, eosinophilia, nasal polyps – developing out of the blue in middle age or later life. This observation led some other investigators to posit that IgG4-RD is a T-helper type 2–driven disease, an assertion debunked by Dr. Stone and coworkers (Allergy. 2014 Feb;69[2]:269-72).
Dr. Stone and his coinvestigators have published the largest series of patients with biopsy-proven IgG4-RD reported to date (Arthritis Rheumatol. 2015 Sep; 67[9]:2466-75). The average age at disease onset was 50 years. Of note, multiorgan involvement was the norm: 24% of patients had two organs involved, and 38% had three or more.
Analysis of this large patient series has led Dr. Stone to a surprising conclusion about the nature of IgG4-RD: “We have greatly overemphasized the importance of IgG4 in this condition,” he asserted.
Indeed, a mere 51% of the patients with clinically active untreated IgG4-RD in his series had an elevated serum IgG level. Dr. Stone characterized IgG4 as “kind of a wimpy antibody” incapable of driving the disease process because it is a noninflammatory immunoglobulin. This has led to speculation that IgG4 functions as what he termed an “antigen sink,” attempting to bind antigen at sites of inflammation.
But while an elevated serum IgG4 is of limited utility for diagnostic purposes, Dr. Stone and coworkers have demonstrated that it is of value as a predictor of relapse. Among patients with a treatment-induced remission, those in the top quartile in terms of baseline pretreatment serum IgG4 were 6.2-fold more likely to relapse (Rheumatology [Oxford]. 2016 Jun;55[6]:1000-8).
“This is a very useful marker for patients who are going to need chronic ongoing therapy. The notion of putting such patients on steroids for months and years is not appealing,” he said.
Levels of circulating plasmablasts as measured by peripheral blood flow cytometry, especially IgG4-positive plasmablasts, have proven much more helpful than serum IgG4 levels as a diagnostic tool, a reliable biomarker of disease activity, and a therapeutic target. Levels of these short-lived CD19+CD38+CD27+ plasmablasts are enormously elevated independent of serum IgG4 in patients with active IgG4-RD.
“One of the questions I’m most often asked is whether IgG4-related disease is a premalignant condition. My answer is no. The plasmablast expansion is oligoclonal, not polyclonal,” Dr. Stone continued.
He described IgG4-RD as “a continuous dance between T cells and B cells.” The latest thinking regarding pathogenesis is that type 2 T follicular helper cells activate B cells, which become memory B cells or plasmablasts. These activated B cells and plasmablasts present antigen to CD4+ cytotoxic T cells at sites of disease. Dr. Stone and his coinvestigators recently identified these CD4+ cytotoxic T cells as a novel population of clonally expanded T cells with SLAMF7 as a surface marker. The cells secrete interferon-gamma, interleukin-1, and transforming growth factor-beta, all of which are capable of driving the intense fibrosis characteristic of IgG4-RD. In addition, these CD4+ cytotoxic T cells secrete granzyme B and perforin, previously thought to be released mainly by natural killer T cells.
Joint American College of Rheumatology/European League Against Rheumatism classification criteria for the disease are expected to be finalized this winter at the Third International Symposium on IgG4-Related Diseases.
Treatment with rituxumab
Glucocorticoids remain the first-line therapy in IgG4-related disease, but it’s essential to bear in mind that their long-term efficacy in this immune-mediated fibroinflammatory disease is the exception rather than the rule, Dr. Stone said at the symposium.
Dr. Stone was a coauthor of an international expert consensus statement on the treatment of IgG4-related disease (IgG4-RD), which emphasized that point (Arthritis Rheumatol. 2015 Jul;67[7]:1688-99).
“I typically start with prednisone at 40 mg/day, and there’s a dramatic response in these patients. Then I taper them off after 2-3 months. If 2-3 months doesn’t put them into a long-term sustained remission, it’s time to go to something else,” said Dr. Stone.
So what’s the next move, then, after steroids fail? Dr. Stone was a pioneer in the strikingly successful use of B cell depletion via rituximab (Rituxan) in patients with IgG4-RD. First he and his coinvestigators demonstrated that this off-label use of rituximab led to rapid clinical and histologic improvement (Ann Rheum Dis. 2015 Jun; 74[6]:1171-7), then they showed it also causes levels of circulating plasmablasts, serum IgG4, and biomarkers of fibrosis to plunge, suggesting B cell depletion may halt the destructive process of collagen deposition that characterizes this immune-related disease (Ann Rheum Dis. 2015 Dec;74[12]:2236-43). They have also reported that patients with very elevated baseline serum IgG4 levels are at more than sixfold increased risk of relapse at a median of 244 days from their first rituximab infusion (Rheumatology [Oxford]. 2016 Jun;55[6]:1000-8).
The success with rituximab is just one example of how improved understanding of the pathophysiology of IgG4-RD has opened the door to novel treatments. Dr. Stone is the lead investigator in an ongoing phase II, open-label study in which 15 patients with active IgG4-RD will receive intravenous XmAb5871 every 2 weeks for 6 months to evaluate the effect on the IgG4-RD Responder Index. XmAb5871 is a monoclonal antibody that binds to CD19 and FCgammaRIIb in order to downregulate activated B cells and plasmablasts. It is also being developed for treatment of systemic lupus erythematosus.
Dr. Stone and his coinvestigators are working on a therapeutic approach to IgG4-RD that targets antigen presentation by activated B cells to CD4+ cytotoxic T cells at sites of disease. These CD4+ cytotoxic T cells contain signaling lymphocyte activation molecule F7 (SLAMF7) as a surface marker. Elotuzumab (Empliciti), an immunostimulatory humanized monoclonal antibody targeting SLAMF7, is already on the market for treatment of multiple myeloma, he noted.
Dr. Stone reported receiving IgG4-RD-related research funding from and serving as a consultant to Genentech and Xencor, which is developing XmAb5871.
SNOWMASS, COLO. – Progress in the understanding and treatment of immunoglobulin G4–related disease is occurring “at lightning speed,” John H. Stone, MD, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
Eight or nine years ago no one had heard of immunoglobulin G4–related disease (IgG4-RD). Today, because of the broad swath the disease cuts, it’s a hot research topic in every subspecialty of medicine as well as surgery, pathology, and radiology.
This new understanding of IgG4-RD, he added, is opening the door to novel treatments.
“This is not a new disease. It was there when we were all in medical school, and for hundreds of years before that. But it’s really only in the last decade that we have come to understand that the disease can affect literally every organ system in the body with syndromes that we once thought were isolated organ-specific syndromes but we now recognize are part of a multiorgan disease currently called IgG4-related disease,” the rheumatologist said.
IgG4-RD is an immune-mediated fibroinflammatory condition characterized histopathologically by three hallmark features in involved tissue: obliterative phlebitis, storiform fibrosis, and a dense lymphoplasmacytic infiltrate.
Clinically, IgG4-RD often presents as a mass lesion that can affect any organ.
“I have many patients who’ve undergone modified Whipple procedures because they were thought to have adenocarcinoma of the pancreas,” according to Dr. Stone.
Other common presentations include Riedel’s thyroiditis, autoimmune pancreatitis, sclerosing cholangitis, sialadenitis, dacryoadenitis, periaortitis, an eosinophilic rash, and pseudotumor of the lung, lymph nodes, or orbits.
“Retroperitoneal fibrosis is a common and underappreciated manifestation. It may be the most common subsyndrome associated with IgG4-related disease,” he observed.
Another common presentation involves atopic disease – asthma, allergic rhinitis, eczema, eosinophilia, nasal polyps – developing out of the blue in middle age or later life. This observation led some other investigators to posit that IgG4-RD is a T-helper type 2–driven disease, an assertion debunked by Dr. Stone and coworkers (Allergy. 2014 Feb;69[2]:269-72).
Dr. Stone and his coinvestigators have published the largest series of patients with biopsy-proven IgG4-RD reported to date (Arthritis Rheumatol. 2015 Sep; 67[9]:2466-75). The average age at disease onset was 50 years. Of note, multiorgan involvement was the norm: 24% of patients had two organs involved, and 38% had three or more.
Analysis of this large patient series has led Dr. Stone to a surprising conclusion about the nature of IgG4-RD: “We have greatly overemphasized the importance of IgG4 in this condition,” he asserted.
Indeed, a mere 51% of the patients with clinically active untreated IgG4-RD in his series had an elevated serum IgG level. Dr. Stone characterized IgG4 as “kind of a wimpy antibody” incapable of driving the disease process because it is a noninflammatory immunoglobulin. This has led to speculation that IgG4 functions as what he termed an “antigen sink,” attempting to bind antigen at sites of inflammation.
But while an elevated serum IgG4 is of limited utility for diagnostic purposes, Dr. Stone and coworkers have demonstrated that it is of value as a predictor of relapse. Among patients with a treatment-induced remission, those in the top quartile in terms of baseline pretreatment serum IgG4 were 6.2-fold more likely to relapse (Rheumatology [Oxford]. 2016 Jun;55[6]:1000-8).
“This is a very useful marker for patients who are going to need chronic ongoing therapy. The notion of putting such patients on steroids for months and years is not appealing,” he said.
Levels of circulating plasmablasts as measured by peripheral blood flow cytometry, especially IgG4-positive plasmablasts, have proven much more helpful than serum IgG4 levels as a diagnostic tool, a reliable biomarker of disease activity, and a therapeutic target. Levels of these short-lived CD19+CD38+CD27+ plasmablasts are enormously elevated independent of serum IgG4 in patients with active IgG4-RD.
“One of the questions I’m most often asked is whether IgG4-related disease is a premalignant condition. My answer is no. The plasmablast expansion is oligoclonal, not polyclonal,” Dr. Stone continued.
He described IgG4-RD as “a continuous dance between T cells and B cells.” The latest thinking regarding pathogenesis is that type 2 T follicular helper cells activate B cells, which become memory B cells or plasmablasts. These activated B cells and plasmablasts present antigen to CD4+ cytotoxic T cells at sites of disease. Dr. Stone and his coinvestigators recently identified these CD4+ cytotoxic T cells as a novel population of clonally expanded T cells with SLAMF7 as a surface marker. The cells secrete interferon-gamma, interleukin-1, and transforming growth factor-beta, all of which are capable of driving the intense fibrosis characteristic of IgG4-RD. In addition, these CD4+ cytotoxic T cells secrete granzyme B and perforin, previously thought to be released mainly by natural killer T cells.
Joint American College of Rheumatology/European League Against Rheumatism classification criteria for the disease are expected to be finalized this winter at the Third International Symposium on IgG4-Related Diseases.
Treatment with rituxumab
Glucocorticoids remain the first-line therapy in IgG4-related disease, but it’s essential to bear in mind that their long-term efficacy in this immune-mediated fibroinflammatory disease is the exception rather than the rule, Dr. Stone said at the symposium.
Dr. Stone was a coauthor of an international expert consensus statement on the treatment of IgG4-related disease (IgG4-RD), which emphasized that point (Arthritis Rheumatol. 2015 Jul;67[7]:1688-99).
“I typically start with prednisone at 40 mg/day, and there’s a dramatic response in these patients. Then I taper them off after 2-3 months. If 2-3 months doesn’t put them into a long-term sustained remission, it’s time to go to something else,” said Dr. Stone.
So what’s the next move, then, after steroids fail? Dr. Stone was a pioneer in the strikingly successful use of B cell depletion via rituximab (Rituxan) in patients with IgG4-RD. First he and his coinvestigators demonstrated that this off-label use of rituximab led to rapid clinical and histologic improvement (Ann Rheum Dis. 2015 Jun; 74[6]:1171-7), then they showed it also causes levels of circulating plasmablasts, serum IgG4, and biomarkers of fibrosis to plunge, suggesting B cell depletion may halt the destructive process of collagen deposition that characterizes this immune-related disease (Ann Rheum Dis. 2015 Dec;74[12]:2236-43). They have also reported that patients with very elevated baseline serum IgG4 levels are at more than sixfold increased risk of relapse at a median of 244 days from their first rituximab infusion (Rheumatology [Oxford]. 2016 Jun;55[6]:1000-8).
The success with rituximab is just one example of how improved understanding of the pathophysiology of IgG4-RD has opened the door to novel treatments. Dr. Stone is the lead investigator in an ongoing phase II, open-label study in which 15 patients with active IgG4-RD will receive intravenous XmAb5871 every 2 weeks for 6 months to evaluate the effect on the IgG4-RD Responder Index. XmAb5871 is a monoclonal antibody that binds to CD19 and FCgammaRIIb in order to downregulate activated B cells and plasmablasts. It is also being developed for treatment of systemic lupus erythematosus.
Dr. Stone and his coinvestigators are working on a therapeutic approach to IgG4-RD that targets antigen presentation by activated B cells to CD4+ cytotoxic T cells at sites of disease. These CD4+ cytotoxic T cells contain signaling lymphocyte activation molecule F7 (SLAMF7) as a surface marker. Elotuzumab (Empliciti), an immunostimulatory humanized monoclonal antibody targeting SLAMF7, is already on the market for treatment of multiple myeloma, he noted.
Dr. Stone reported receiving IgG4-RD-related research funding from and serving as a consultant to Genentech and Xencor, which is developing XmAb5871.
EXPERT ANALYSIS FROM THE WINTER RHEUMATOLOGY SYMPOSIUM