Mechanical Circulatory Support for Select Patients Nears Transplant Survival Rates

SAN FRANCISCO – Data from the Interagency Registry for Mechanically Assisted Circulatory Support has identified significant risk factors for death following implantation of left ventricular assist devices as destination therapy. The findings will allow better targeting of patients who can expect 1- and 2-year survival rates on left ventricular assist devices (LVADs) that approach those seen with heart transplantation, according to Dr. James K. Kirklin.

"If we focus on the subset of stable patients without renal or severe right ventricular failure and without previous cardiac surgery, the 2-year survival with a continuous flow device is 80%," said Dr. Kirklin, professor of medicine and director of the division of cardiothoracic surgery at the University of Alabama at Birmingham.

LVAD destination therapy is not appropriate for patients with rapid hemodynamic deterioration, cardiogenic shock, or right ventricular failure, Dr. Kirklin said at the annual meeting of the American Association for Thoracic Surgery. But there is a significant subset of patients who do benefit, including many patients who have advanced heart failure and are not candidates for transplantation.

"Of particular importance is the INTERMACS [Interagency Registry for Mechanically Assisted Circulatory Support] level, which describes subsets of NYHA Class IV patients," Dr. Kirklin said. For example, level 1 describes patients in cardiogenic shock at the time of LVAD implant and was "the most important risk factor for early mortality." Of 112 patients with level 1 designation, 32 died during the study.

Also, right ventricular failure severe enough to require right ventricular assist device support in the same operation was the strongest predictor of mortality in the constant phase (hazard ratio, 3.2).

LVADs are increasingly being used as destination therapy, with LVADs accounting for nearly one-third of all mechanical circulatory support activity in the U.S.

Dr. Kirklin and his colleagues studied 5,407 patients who received a durable ventricular assist device or total artificial heart between June 2006 and December 2011 in the National Heart, Lung, and Blood Institute’s INTERMACS. The 1,287 patients who were not transplant-eligible and received a LVAD for destination therapy comprised the study group.

Significant risk factors for death included older age, larger body mass index, diabetes, a history of coronary artery bypass graft surgery, cardiogenic shock, low sodium, increased bilirubin, and use of a pulsatile flow LVAD, the results of a multivariate analysis indicated.

This is a "timely and important presentation," said invited study discussant Dr. Soon J. Park. "[The researchers] report that a significant percentage of destination therapy patients are achieving a survival rate that is comparable to those who undergo heart transplantation. Such a finding is especially astonishing in that these patients, by definition, were those deemed inappropriate [for] donor hearts. For a significant fraction of patients who were destined to die because heart transplant was not an option for them ... a vast majority will now be able to enjoy life on VAD support." Dr. Park is a cardiovascular surgeon at the Mayo Clinic Transplant Center in Rochester, Minn.

Representative survival after cardiac transplantation from the International Society for Heart and Lung Transplant Registry is approximately 80% at 2 years in a population with generally less comorbidities than the current destination therapy study group, Dr. Kirklin said. Of note, the INTERMACS destination therapy patients were older, a mean of 67 years, compared with 55 years in the transplant reference group. This survival rate of 80% was figured into the multivariate mortality risk factor analysis.

"Heart transplant had been the only option to prolong lives in patients with end-stage heart failure. With recent developments in VAD therapy, heart transplant seems to be the only viable option no longer," Dr. Park said. "VAD therapy can be rendered immediately and abundantly and it is going to change the natural history of end-stage heart failure dramatically, whether [the patient is] transplant eligible or not."

During a discussion that followed presentation of the study results, Dr. John Conte, director of mechanical circulatory support and a professor of surgery at Johns Hopkins Medicine, asked Dr. Kirklin if he is now ready to refer a subset of patients to mechanical support instead of heart transplantation.

"Yes," Dr. Kirklin replied. "I must say the actual identification of patients from the transplant list who could be triaged to mechanical support will depend on their comorbidity. "Remember that the low-risk, 40-year-old patient undergoing cardiac transplantation without other important comorbidities is not the patient one would want to triage to mechanical support. It will only be those patients on the transplant list with multiple, adverse comorbidities that we will initially select for triage."

Dr. Park asked Dr. Kirklin if it would ever make sense to consider VAD as primary therapy and reserve heart transplant as a secondary therapy.

"Of course the goal in the future will be to have an array of therapies which maximize long-term survival for patients, so whether that means initial VAD therapy followed by transplant or initial transplant followed by total artificial heart of course depends upon the rigorous analyses we will need to do in the future," Dr. Kirklin replied.

Although permanent treatment is the intention of destination therapy, the clinical situation may evolve over time and some patients may be considered for cardiac transplantation or device explant, Dr. Kirklin said. "These outcomes can be tracked. In the current era, less than 5% of DT [destination therapy] patients underwent transplant or explant within 2 years."

Dr. Kirklin is the principal investigator of the INTERMACS NHLBI contract.

SAN FRANCISCO – Data from the Interagency Registry for Mechanically Assisted Circulatory Support has identified significant risk factors for death following implantation of left ventricular assist devices as destination therapy. The findings will allow better targeting of patients who can expect 1- and 2-year survival rates on left ventricular assist devices (LVADs) that approach those seen with heart transplantation, according to Dr. James K. Kirklin.

"If we focus on the subset of stable patients without renal or severe right ventricular failure and without previous cardiac surgery, the 2-year survival with a continuous flow device is 80%," said Dr. Kirklin, professor of medicine and director of the division of cardiothoracic surgery at the University of Alabama at Birmingham.

LVAD destination therapy is not appropriate for patients with rapid hemodynamic deterioration, cardiogenic shock, or right ventricular failure, Dr. Kirklin said at the annual meeting of the American Association for Thoracic Surgery. But there is a significant subset of patients who do benefit, including many patients who have advanced heart failure and are not candidates for transplantation.

"Of particular importance is the INTERMACS [Interagency Registry for Mechanically Assisted Circulatory Support] level, which describes subsets of NYHA Class IV patients," Dr. Kirklin said. For example, level 1 describes patients in cardiogenic shock at the time of LVAD implant and was "the most important risk factor for early mortality." Of 112 patients with level 1 designation, 32 died during the study.

Also, right ventricular failure severe enough to require right ventricular assist device support in the same operation was the strongest predictor of mortality in the constant phase (hazard ratio, 3.2).

LVADs are increasingly being used as destination therapy, with LVADs accounting for nearly one-third of all mechanical circulatory support activity in the U.S.

Dr. Kirklin and his colleagues studied 5,407 patients who received a durable ventricular assist device or total artificial heart between June 2006 and December 2011 in the National Heart, Lung, and Blood Institute’s INTERMACS. The 1,287 patients who were not transplant-eligible and received a LVAD for destination therapy comprised the study group.

Significant risk factors for death included older age, larger body mass index, diabetes, a history of coronary artery bypass graft surgery, cardiogenic shock, low sodium, increased bilirubin, and use of a pulsatile flow LVAD, the results of a multivariate analysis indicated.

This is a "timely and important presentation," said invited study discussant Dr. Soon J. Park. "[The researchers] report that a significant percentage of destination therapy patients are achieving a survival rate that is comparable to those who undergo heart transplantation. Such a finding is especially astonishing in that these patients, by definition, were those deemed inappropriate [for] donor hearts. For a significant fraction of patients who were destined to die because heart transplant was not an option for them ... a vast majority will now be able to enjoy life on VAD support." Dr. Park is a cardiovascular surgeon at the Mayo Clinic Transplant Center in Rochester, Minn.

Representative survival after cardiac transplantation from the International Society for Heart and Lung Transplant Registry is approximately 80% at 2 years in a population with generally less comorbidities than the current destination therapy study group, Dr. Kirklin said. Of note, the INTERMACS destination therapy patients were older, a mean of 67 years, compared with 55 years in the transplant reference group. This survival rate of 80% was figured into the multivariate mortality risk factor analysis.

"Heart transplant had been the only option to prolong lives in patients with end-stage heart failure. With recent developments in VAD therapy, heart transplant seems to be the only viable option no longer," Dr. Park said. "VAD therapy can be rendered immediately and abundantly and it is going to change the natural history of end-stage heart failure dramatically, whether [the patient is] transplant eligible or not."

During a discussion that followed presentation of the study results, Dr. John Conte, director of mechanical circulatory support and a professor of surgery at Johns Hopkins Medicine, asked Dr. Kirklin if he is now ready to refer a subset of patients to mechanical support instead of heart transplantation.

"Yes," Dr. Kirklin replied. "I must say the actual identification of patients from the transplant list who could be triaged to mechanical support will depend on their comorbidity. "Remember that the low-risk, 40-year-old patient undergoing cardiac transplantation without other important comorbidities is not the patient one would want to triage to mechanical support. It will only be those patients on the transplant list with multiple, adverse comorbidities that we will initially select for triage."

Dr. Park asked Dr. Kirklin if it would ever make sense to consider VAD as primary therapy and reserve heart transplant as a secondary therapy.

"Of course the goal in the future will be to have an array of therapies which maximize long-term survival for patients, so whether that means initial VAD therapy followed by transplant or initial transplant followed by total artificial heart of course depends upon the rigorous analyses we will need to do in the future," Dr. Kirklin replied.

Although permanent treatment is the intention of destination therapy, the clinical situation may evolve over time and some patients may be considered for cardiac transplantation or device explant, Dr. Kirklin said. "These outcomes can be tracked. In the current era, less than 5% of DT [destination therapy] patients underwent transplant or explant within 2 years."

Dr. Kirklin is the principal investigator of the INTERMACS NHLBI contract.

SAN FRANCISCO – Data from the Interagency Registry for Mechanically Assisted Circulatory Support has identified significant risk factors for death following implantation of left ventricular assist devices as destination therapy. The findings will allow better targeting of patients who can expect 1- and 2-year survival rates on left ventricular assist devices (LVADs) that approach those seen with heart transplantation, according to Dr. James K. Kirklin.

"If we focus on the subset of stable patients without renal or severe right ventricular failure and without previous cardiac surgery, the 2-year survival with a continuous flow device is 80%," said Dr. Kirklin, professor of medicine and director of the division of cardiothoracic surgery at the University of Alabama at Birmingham.

LVAD destination therapy is not appropriate for patients with rapid hemodynamic deterioration, cardiogenic shock, or right ventricular failure, Dr. Kirklin said at the annual meeting of the American Association for Thoracic Surgery. But there is a significant subset of patients who do benefit, including many patients who have advanced heart failure and are not candidates for transplantation.

"Of particular importance is the INTERMACS [Interagency Registry for Mechanically Assisted Circulatory Support] level, which describes subsets of NYHA Class IV patients," Dr. Kirklin said. For example, level 1 describes patients in cardiogenic shock at the time of LVAD implant and was "the most important risk factor for early mortality." Of 112 patients with level 1 designation, 32 died during the study.

Also, right ventricular failure severe enough to require right ventricular assist device support in the same operation was the strongest predictor of mortality in the constant phase (hazard ratio, 3.2).

LVADs are increasingly being used as destination therapy, with LVADs accounting for nearly one-third of all mechanical circulatory support activity in the U.S.

Dr. Kirklin and his colleagues studied 5,407 patients who received a durable ventricular assist device or total artificial heart between June 2006 and December 2011 in the National Heart, Lung, and Blood Institute’s INTERMACS. The 1,287 patients who were not transplant-eligible and received a LVAD for destination therapy comprised the study group.

Significant risk factors for death included older age, larger body mass index, diabetes, a history of coronary artery bypass graft surgery, cardiogenic shock, low sodium, increased bilirubin, and use of a pulsatile flow LVAD, the results of a multivariate analysis indicated.

This is a "timely and important presentation," said invited study discussant Dr. Soon J. Park. "[The researchers] report that a significant percentage of destination therapy patients are achieving a survival rate that is comparable to those who undergo heart transplantation. Such a finding is especially astonishing in that these patients, by definition, were those deemed inappropriate [for] donor hearts. For a significant fraction of patients who were destined to die because heart transplant was not an option for them ... a vast majority will now be able to enjoy life on VAD support." Dr. Park is a cardiovascular surgeon at the Mayo Clinic Transplant Center in Rochester, Minn.

Representative survival after cardiac transplantation from the International Society for Heart and Lung Transplant Registry is approximately 80% at 2 years in a population with generally less comorbidities than the current destination therapy study group, Dr. Kirklin said. Of note, the INTERMACS destination therapy patients were older, a mean of 67 years, compared with 55 years in the transplant reference group. This survival rate of 80% was figured into the multivariate mortality risk factor analysis.

"Heart transplant had been the only option to prolong lives in patients with end-stage heart failure. With recent developments in VAD therapy, heart transplant seems to be the only viable option no longer," Dr. Park said. "VAD therapy can be rendered immediately and abundantly and it is going to change the natural history of end-stage heart failure dramatically, whether [the patient is] transplant eligible or not."

During a discussion that followed presentation of the study results, Dr. John Conte, director of mechanical circulatory support and a professor of surgery at Johns Hopkins Medicine, asked Dr. Kirklin if he is now ready to refer a subset of patients to mechanical support instead of heart transplantation.

"Yes," Dr. Kirklin replied. "I must say the actual identification of patients from the transplant list who could be triaged to mechanical support will depend on their comorbidity. "Remember that the low-risk, 40-year-old patient undergoing cardiac transplantation without other important comorbidities is not the patient one would want to triage to mechanical support. It will only be those patients on the transplant list with multiple, adverse comorbidities that we will initially select for triage."

Dr. Park asked Dr. Kirklin if it would ever make sense to consider VAD as primary therapy and reserve heart transplant as a secondary therapy.

"Of course the goal in the future will be to have an array of therapies which maximize long-term survival for patients, so whether that means initial VAD therapy followed by transplant or initial transplant followed by total artificial heart of course depends upon the rigorous analyses we will need to do in the future," Dr. Kirklin replied.

Although permanent treatment is the intention of destination therapy, the clinical situation may evolve over time and some patients may be considered for cardiac transplantation or device explant, Dr. Kirklin said. "These outcomes can be tracked. In the current era, less than 5% of DT [destination therapy] patients underwent transplant or explant within 2 years."

Dr. Kirklin is the principal investigator of the INTERMACS NHLBI contract.