 |
|
| AATS/NHLBI: Cardiothoracic Surgery Exploring Collaborative Clinical Research Opportunities |
|
Title and Author Therapies for Advanced Heart Failure: Therapies on the HorizonDaniel Burkhoff, MD, PhD Abstract Despite advances in medical therapies, morbidity and mortality in advanced heart failure (particularly patients with NYHA IV symptoms and those in cardiogenic shock) remain very high. With few prospects for new pharmacologic thereapies, high hopes rest with surgical and newer device-based therapies. Indeed, one of the most impactful classes of therapies for advanced heart failure in the last decade is mechanical ventricular assist devices (VADs). This is despite the negative findings of the NIH-sponsored STICH study of surgical ventricular reconstruction (SVR) surgery, which have been criticized by some investigators. Currently or soon to be avaialbe therapeutic options on the horizon that highlight potentially fruitful areas of research in this domain include the following:Acute cardiogenic shock (CGS): Short-term mortality for CGS remains >40%. Small scale studies with acute percutaneous VADs (that pump ~3.5 L/min) failed to show survival benefits despite showing hemodynamic benefits. Similarly, drugs designed to address aspects of the acute inflammatory state (e.g., iNOS inhibitors) of CGS also failed to show a benefit. Use of hypothermia for this purpose is also being investigated. Two testable hypotheses emerge: 1) Can emergent intervention with percutaneous devices that provide full hemodynamic support (=5 L/min) improve survival and 2) Can the combination of effective hemodynamic support plus an anti-inflammatory strategy improve survival? VAD-induced Myocardial Infarct Size reduction: Limiting myocardial infarct size to prevent the development of heart failure by mechanically unloading the LV with short term use of a percutaneous VAD has been demonstrated in animals. Whether such benefit can be achieved in humans and the degree and duration of unloading required to achieve a therapeutic benefits are unknown. Full support versus partial support for chronic HF: With recent advances in VAD technology and reductions in adverse events, efforts are underway to investigate their use in patients who are "less sick" than those typically receiving VADs (i.e., in INTERMACS=4 compared to the typical INTERMACS=3 patient; e.g., REVIVE-IT study). Adverse events have the potential to be further reduced if smaller pumps placed with less invasive approaches (including devices deployable by percutaneous techniques) can be used. However, smaller devices pump less blood (partial hemodynamic support). This raises the fundamental question of how much blood flow is necessary from a VAD to interrupt the progression of heart failure and provide functional and morality benefits. Facilitated Myocardial Recovery for Chronic HF: VAD use is associated with a marked degree of reverse ventricular remodeling and, in some cases, recovery of LV function. Reports from one group suggests that aggressive medical management during VAD support markedly enhances the rate of recovery and the ability to explant VADs and achieve sustained improvements in LV function. This finding could not be repeated in a recent small scale multicenter study. Efforts to replicate and generalize these findings would represent a major advance in the field. Right Heart Failure during LVAD support: RV failure occurs in ~20% of patients receiving LV support. Accordingly, there is increasing need for long term RV support, though this is now more frequently being accomplished by adapting devices designed for the LV. The pathophysiology of RV failure and factors predisposing to right heart failure during LVAD support are not well understood. Systematic study of RV failure during LVAD support and development of new devices designed to optimially support the RV are warrented. Other Areas of Need: While some progress has been made in each of the areas noted above, other areas of significant unmet need include LVADs for Infants and Children and RVADs for patients with idiopathic pulmonary hypertension. Key Research Gap Requiring NHLBI Leadership The holy grail: Development of a widely applicable, safe, effective and affordable approach(s) to treating severe heart failure due to reduced left ventricular function. Because of cost and invasiveness, current LVADs do not address this problem on a large scale. Short of filling this gap, continue efforts to reduce adverse events associated with current technology LVADs and expand their use to less sick patients. Key Citations 1: Birks EJ, Tansley PD, Hardy J, George RS, Bowles CT, Burke M, Banner NR, Khaghani A, Yacoub MH. Left ventricular assist device and drug therapy for the reversal of heart failure. N Engl J Med 2006;355:1873-18842: Maybaum S, Mancini D, Xydas S, Starling RC, Aaronson K, Pagani FD, Miller LW, Margulies K, McRee S, Frazier OH, Torre-Amione G. Cardiac improvement during mechanical circulatory support: a prospective multicenter study of the LVAD Working Group. Circulation 2007;115:2497-2505 3: Meyns B, Rega F, Ector J, Droogne W, Vanhaecke J, Van HJ, Griffith B, Dowling R, Zucker M, Burkhoff D. Partial left ventricular support implanted through minimal access surgery as a bridge to cardiac transplant. J Thorac Cardiovasc Surg 2009;137:243-245 |
We Model Excellence |
|
Copyright © 2012 American Association for Thoracic Surgery
All rights reserved. IMPORTANT REMINDER: The preceding information is intended only to provide
general guidance and not as a definitive basis for diagnosis or treatment in any particular case.
It is very important that you consult a doctor about any specific medical problem or question.
All rights reserved. IMPORTANT REMINDER: The preceding information is intended only to provide
general guidance and not as a definitive basis for diagnosis or treatment in any particular case.
It is very important that you consult a doctor about any specific medical problem or question.