Mini-VADs could transform heart failure therapy

SNOWMASS, COLO. – Survival in patients with advanced heart failure who receive a left ventricular assist device as destination therapy or as a bridge to transplant has increased dramatically in recent years – and the best may be yet to come.

"There is a robust pipeline of mini-VADs [mini–ventricular assist devices] providing partial circulatory support that should allow wider applicability," Dr. Michael J. Mack said at the Annual Cardiovascular Conference at Snowmass.

This new generation of smaller, ever-more-high-tech VADs now entering clinical trials is made up of devices designed for implantation via a shorter, less invasive, off-pump hybrid surgical procedure, which should reduce operative morbidity and mortality. The rechargeable battery will also be implanted. Some of the devices are even earmarked for implantation nonsurgically in the cath lab, explained Dr. Mack, a cardiothoracic surgeon who is medical director of the Baylor Health Care System in Plano, Tex.

The ease of implantation of these next-gen mini-VADs makes them suitable for use at an earlier stage in the development of heart failure than the two left ventricular assist devices (LVADs) now approved for long-term use in the United States. The expectation is that this earlier mechanical intervention might further improve patient outcomes, he added.

Two-year survival following implantation of the HeartMate II, the current workhorse LVAD, is 65%, the same as with heart transplantation. To put that in perspective, in the REMATCH trial, which more than a decade ago led to Food and Drug Administration (FDA) approval of the first LVAD as long-term therapy, 2-year survival with device therapy was just 25%.

Today at many top institutions, Dr. Mack said, the number of LVADs implanted as destination therapy – that is, as an alternative to heart transplantation – now dwarfs the number of heart transplants done. This reflects a widespread recognition that the organ donor pool is unlikely to grow larger despite many efforts. Indeed, the number of heart transplants performed in North America has remained constant at roughly 2,300 per year for the past 20 years.

The other LVAD approved as destination therapy or bridge to transplant is the HeartWare VAD. The FDA granted approval based upon the results of the 30-center, prospective ADVANCE trial, which demonstrated that the HeartWare VAD’s performance was noninferior to that of the HeartMate II (Circulation 2012;125:3191-200).

Both LVADs are small continuous-flow devices with only a single moving part. They are quiet and energy efficient. Their simplicity of design makes them less susceptible to mechanical wear and much more reliable than earlier-generation LVADs. Three-year device replacement rates are now less than 10%, according to Dr. Mack.

But the current LVADs have significant shortcomings. In a worldwide series of close to 6,000 patients who have received a device as destination therapy or bridge to transplant, the 3-year combined rate of bleeding, stroke, infection, device malfunction, or death was 86%. The 3-year stroke incidence was 19% (J. Heart Lung Transpl. 2013;32:141-56).

Bleeding is a major problem with these devices for three reasons. Virtually all LVAD recipients develop acquired von Willebrand’s disease. Moreover, patients are on warfarin because of their high stroke risk. And gastrointestinal bleeding is a significant problem due to the angiodysplasia and arteriovenous malformations that result from the nonpulsatile continuous blood flow.

Among the mini-VADs well along in the developmental pipeline are the MicroMed HeartAssist 5, which is 71 x 30 mm in size and weighs only 92 g. Also in development are the HeartWare Miniaturized VAD (MVAD), which is about the size of a golf ball, and the HeartMate III.

The device drawing the most interest from cardiac surgeons, however, is the CircuLite Synergy mini-VAD, which is the size of an AA battery. It’s implanted off-pump with a small right thoracotomy for left atrial access. The device sits in a pocket in the right deltoid-pectoral groove for axillary artery access. The inflow is from the left atrium, with outflow into the right subclavian artery.

This device will undergo further modification to a totally endovascular concept that avoids the right thoracotomy. Inflow will be through the subclavian vein via a transseptal puncture approach, with outflow into the subclavian artery.

"The idea is that this will become a cath lab procedure. The device will sit in a pocket similar to a pacemaker," Dr. Mack explained.

Although the future looks bright for mini-VADs, plenty of key questions about them still await answers, the surgeon noted. Among them: Will partial circulatory support be sufficient for all patients with advanced heart failure? Will it be possible to predict which patients with New York Heart Association class III heart failure are destined to progress to advanced disease, and if so, will early implantation of a partial support device in these less-sick patients have a favorable effect on their quality of life? Might it slow progression of heart failure, and perhaps even induce remission?

The answers are expected to come from ongoing and planned clinical trials of these investigational devices.

Dr. Clyde W. Yancy, who chaired the writing committee for the 2013 ACC/AHA (American College of Cardiology/American Heart Association) Guideline for the Management of Heart Failure (J. Am. Coll. Cardiol. 2013;62:e147-239), noted that the guidelines endorse LVADs as destination therapy or bridge to transplant or recovery in carefully selected patients with advanced heart failure with reduced ejection fraction, with a class IIa/level of evidence B recommendation.

"Mechanical circulatory support is no longer a Hail Mary pass. This is no longer an experimental intervention. This really should be incorporated in our usual thought processes in advanced heart failure," said Dr. Yancy, professor of medicine and of medical social sciences and chief of cardiology at Northwestern University, Chicago.

He noted that the guidelines list a number of clinical events and other findings that are useful in identifying patients who have progressed to advanced heart failure, at which point he said it’s time to communicate with a center that can evaluate the patient for a possible LVAD or heart transplantation. These indicators include two or more hospitalizations or emergency department visits for heart failure in the past year, progressive deterioration in renal function, intolerance to beta-blocker therapy, unexplained weight loss, or inability to walk one block on level ground because of fatigue or shortness of breath.

Dr. Mack and Dr. Yancy reported having no financial conflicts.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Survival in patients with advanced heart failure who receive a left ventricular assist device as destination therapy or as a bridge to transplant has increased dramatically in recent years – and the best may be yet to come.

"There is a robust pipeline of mini-VADs [mini–ventricular assist devices] providing partial circulatory support that should allow wider applicability," Dr. Michael J. Mack said at the Annual Cardiovascular Conference at Snowmass.

This new generation of smaller, ever-more-high-tech VADs now entering clinical trials is made up of devices designed for implantation via a shorter, less invasive, off-pump hybrid surgical procedure, which should reduce operative morbidity and mortality. The rechargeable battery will also be implanted. Some of the devices are even earmarked for implantation nonsurgically in the cath lab, explained Dr. Mack, a cardiothoracic surgeon who is medical director of the Baylor Health Care System in Plano, Tex.

The ease of implantation of these next-gen mini-VADs makes them suitable for use at an earlier stage in the development of heart failure than the two left ventricular assist devices (LVADs) now approved for long-term use in the United States. The expectation is that this earlier mechanical intervention might further improve patient outcomes, he added.

Two-year survival following implantation of the HeartMate II, the current workhorse LVAD, is 65%, the same as with heart transplantation. To put that in perspective, in the REMATCH trial, which more than a decade ago led to Food and Drug Administration (FDA) approval of the first LVAD as long-term therapy, 2-year survival with device therapy was just 25%.

Today at many top institutions, Dr. Mack said, the number of LVADs implanted as destination therapy – that is, as an alternative to heart transplantation – now dwarfs the number of heart transplants done. This reflects a widespread recognition that the organ donor pool is unlikely to grow larger despite many efforts. Indeed, the number of heart transplants performed in North America has remained constant at roughly 2,300 per year for the past 20 years.

The other LVAD approved as destination therapy or bridge to transplant is the HeartWare VAD. The FDA granted approval based upon the results of the 30-center, prospective ADVANCE trial, which demonstrated that the HeartWare VAD’s performance was noninferior to that of the HeartMate II (Circulation 2012;125:3191-200).

Both LVADs are small continuous-flow devices with only a single moving part. They are quiet and energy efficient. Their simplicity of design makes them less susceptible to mechanical wear and much more reliable than earlier-generation LVADs. Three-year device replacement rates are now less than 10%, according to Dr. Mack.

But the current LVADs have significant shortcomings. In a worldwide series of close to 6,000 patients who have received a device as destination therapy or bridge to transplant, the 3-year combined rate of bleeding, stroke, infection, device malfunction, or death was 86%. The 3-year stroke incidence was 19% (J. Heart Lung Transpl. 2013;32:141-56).

Bleeding is a major problem with these devices for three reasons. Virtually all LVAD recipients develop acquired von Willebrand’s disease. Moreover, patients are on warfarin because of their high stroke risk. And gastrointestinal bleeding is a significant problem due to the angiodysplasia and arteriovenous malformations that result from the nonpulsatile continuous blood flow.

Among the mini-VADs well along in the developmental pipeline are the MicroMed HeartAssist 5, which is 71 x 30 mm in size and weighs only 92 g. Also in development are the HeartWare Miniaturized VAD (MVAD), which is about the size of a golf ball, and the HeartMate III.

The device drawing the most interest from cardiac surgeons, however, is the CircuLite Synergy mini-VAD, which is the size of an AA battery. It’s implanted off-pump with a small right thoracotomy for left atrial access. The device sits in a pocket in the right deltoid-pectoral groove for axillary artery access. The inflow is from the left atrium, with outflow into the right subclavian artery.

This device will undergo further modification to a totally endovascular concept that avoids the right thoracotomy. Inflow will be through the subclavian vein via a transseptal puncture approach, with outflow into the subclavian artery.

"The idea is that this will become a cath lab procedure. The device will sit in a pocket similar to a pacemaker," Dr. Mack explained.

Although the future looks bright for mini-VADs, plenty of key questions about them still await answers, the surgeon noted. Among them: Will partial circulatory support be sufficient for all patients with advanced heart failure? Will it be possible to predict which patients with New York Heart Association class III heart failure are destined to progress to advanced disease, and if so, will early implantation of a partial support device in these less-sick patients have a favorable effect on their quality of life? Might it slow progression of heart failure, and perhaps even induce remission?

The answers are expected to come from ongoing and planned clinical trials of these investigational devices.

Dr. Clyde W. Yancy, who chaired the writing committee for the 2013 ACC/AHA (American College of Cardiology/American Heart Association) Guideline for the Management of Heart Failure (J. Am. Coll. Cardiol. 2013;62:e147-239), noted that the guidelines endorse LVADs as destination therapy or bridge to transplant or recovery in carefully selected patients with advanced heart failure with reduced ejection fraction, with a class IIa/level of evidence B recommendation.

"Mechanical circulatory support is no longer a Hail Mary pass. This is no longer an experimental intervention. This really should be incorporated in our usual thought processes in advanced heart failure," said Dr. Yancy, professor of medicine and of medical social sciences and chief of cardiology at Northwestern University, Chicago.

He noted that the guidelines list a number of clinical events and other findings that are useful in identifying patients who have progressed to advanced heart failure, at which point he said it’s time to communicate with a center that can evaluate the patient for a possible LVAD or heart transplantation. These indicators include two or more hospitalizations or emergency department visits for heart failure in the past year, progressive deterioration in renal function, intolerance to beta-blocker therapy, unexplained weight loss, or inability to walk one block on level ground because of fatigue or shortness of breath.

Dr. Mack and Dr. Yancy reported having no financial conflicts.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Survival in patients with advanced heart failure who receive a left ventricular assist device as destination therapy or as a bridge to transplant has increased dramatically in recent years – and the best may be yet to come.

"There is a robust pipeline of mini-VADs [mini–ventricular assist devices] providing partial circulatory support that should allow wider applicability," Dr. Michael J. Mack said at the Annual Cardiovascular Conference at Snowmass.

This new generation of smaller, ever-more-high-tech VADs now entering clinical trials is made up of devices designed for implantation via a shorter, less invasive, off-pump hybrid surgical procedure, which should reduce operative morbidity and mortality. The rechargeable battery will also be implanted. Some of the devices are even earmarked for implantation nonsurgically in the cath lab, explained Dr. Mack, a cardiothoracic surgeon who is medical director of the Baylor Health Care System in Plano, Tex.

The ease of implantation of these next-gen mini-VADs makes them suitable for use at an earlier stage in the development of heart failure than the two left ventricular assist devices (LVADs) now approved for long-term use in the United States. The expectation is that this earlier mechanical intervention might further improve patient outcomes, he added.

Two-year survival following implantation of the HeartMate II, the current workhorse LVAD, is 65%, the same as with heart transplantation. To put that in perspective, in the REMATCH trial, which more than a decade ago led to Food and Drug Administration (FDA) approval of the first LVAD as long-term therapy, 2-year survival with device therapy was just 25%.

Today at many top institutions, Dr. Mack said, the number of LVADs implanted as destination therapy – that is, as an alternative to heart transplantation – now dwarfs the number of heart transplants done. This reflects a widespread recognition that the organ donor pool is unlikely to grow larger despite many efforts. Indeed, the number of heart transplants performed in North America has remained constant at roughly 2,300 per year for the past 20 years.

The other LVAD approved as destination therapy or bridge to transplant is the HeartWare VAD. The FDA granted approval based upon the results of the 30-center, prospective ADVANCE trial, which demonstrated that the HeartWare VAD’s performance was noninferior to that of the HeartMate II (Circulation 2012;125:3191-200).

Both LVADs are small continuous-flow devices with only a single moving part. They are quiet and energy efficient. Their simplicity of design makes them less susceptible to mechanical wear and much more reliable than earlier-generation LVADs. Three-year device replacement rates are now less than 10%, according to Dr. Mack.

But the current LVADs have significant shortcomings. In a worldwide series of close to 6,000 patients who have received a device as destination therapy or bridge to transplant, the 3-year combined rate of bleeding, stroke, infection, device malfunction, or death was 86%. The 3-year stroke incidence was 19% (J. Heart Lung Transpl. 2013;32:141-56).

Bleeding is a major problem with these devices for three reasons. Virtually all LVAD recipients develop acquired von Willebrand’s disease. Moreover, patients are on warfarin because of their high stroke risk. And gastrointestinal bleeding is a significant problem due to the angiodysplasia and arteriovenous malformations that result from the nonpulsatile continuous blood flow.

Among the mini-VADs well along in the developmental pipeline are the MicroMed HeartAssist 5, which is 71 x 30 mm in size and weighs only 92 g. Also in development are the HeartWare Miniaturized VAD (MVAD), which is about the size of a golf ball, and the HeartMate III.

The device drawing the most interest from cardiac surgeons, however, is the CircuLite Synergy mini-VAD, which is the size of an AA battery. It’s implanted off-pump with a small right thoracotomy for left atrial access. The device sits in a pocket in the right deltoid-pectoral groove for axillary artery access. The inflow is from the left atrium, with outflow into the right subclavian artery.

This device will undergo further modification to a totally endovascular concept that avoids the right thoracotomy. Inflow will be through the subclavian vein via a transseptal puncture approach, with outflow into the subclavian artery.

"The idea is that this will become a cath lab procedure. The device will sit in a pocket similar to a pacemaker," Dr. Mack explained.

Although the future looks bright for mini-VADs, plenty of key questions about them still await answers, the surgeon noted. Among them: Will partial circulatory support be sufficient for all patients with advanced heart failure? Will it be possible to predict which patients with New York Heart Association class III heart failure are destined to progress to advanced disease, and if so, will early implantation of a partial support device in these less-sick patients have a favorable effect on their quality of life? Might it slow progression of heart failure, and perhaps even induce remission?

The answers are expected to come from ongoing and planned clinical trials of these investigational devices.

Dr. Clyde W. Yancy, who chaired the writing committee for the 2013 ACC/AHA (American College of Cardiology/American Heart Association) Guideline for the Management of Heart Failure (J. Am. Coll. Cardiol. 2013;62:e147-239), noted that the guidelines endorse LVADs as destination therapy or bridge to transplant or recovery in carefully selected patients with advanced heart failure with reduced ejection fraction, with a class IIa/level of evidence B recommendation.

"Mechanical circulatory support is no longer a Hail Mary pass. This is no longer an experimental intervention. This really should be incorporated in our usual thought processes in advanced heart failure," said Dr. Yancy, professor of medicine and of medical social sciences and chief of cardiology at Northwestern University, Chicago.

He noted that the guidelines list a number of clinical events and other findings that are useful in identifying patients who have progressed to advanced heart failure, at which point he said it’s time to communicate with a center that can evaluate the patient for a possible LVAD or heart transplantation. These indicators include two or more hospitalizations or emergency department visits for heart failure in the past year, progressive deterioration in renal function, intolerance to beta-blocker therapy, unexplained weight loss, or inability to walk one block on level ground because of fatigue or shortness of breath.

Dr. Mack and Dr. Yancy reported having no financial conflicts.

bjancin@frontlinemedcom.com