J. of Cardiovasc. Trans. Res. (2014) 7:263–265 DOI 10.1007/s12265-014-9557-5
Novel Non-pharmacological Approaches to Heart Failure William T. Abraham & Gaetano M. De Ferrari
Received: 18 February 2014 / Accepted: 24 February 2014 / Published online: 27 March 2014 # Springer Science+Business Media New York 2014
Heart failure is a major public health problem and is associated with increased morbidity and mortality. As the life expectancy increases and the population ages, the overall prevalence of heart failure continues to rise. Indeed, while less than 2 % of the overall adult population in developed countries has heart failure, this percentage exceeds 10 % among subjects above 70 years of age [1]. Before 1990, 60 to 70 % of patients died within 5 years of the diagnosis leading to the suggestion that the disease could be more malignant than most types of cancer [2]. In the past 20–25 years, considerable improvements in the therapeutic approach to patients with heart failure have led to a reduction in hospitalization of 30–50 % and to a smaller but still significant reduction in mortality [3]. In the first part of this period, the improvement was due to the implementation of a pharmacological approach with beta-adrenergic blockers, angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin II receptor blockers (ARBs), and aldosterone receptor blockers [4]. These agents produced a relative risk reduction in mortality ranging from 20 % (for ACE-Is) to 30 % (for betablockers) [5]. In the second half of the period, no additional pharmacological agent significantly affecting the prognosis of heart failure was introduced. The further improvement was due to the increased use of implantable cardioverter-
Associate Editor Craig Stolen oversaw the review of this article W. T. Abraham Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH, USA G. M. De Ferrari (*) Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy e-mail: [email protected] G. M. De Ferrari Cardiovascular Clinical Research Center, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
defibrillators (ICDs) and of cardiac resynchronization therapy (CRT) devices [6]. Despite these improvements, morbidity and mortality related to heart failure remain unacceptably high. We believe that the improvement in the prognosis of this disease in the next two decades will be based to a great extent on novel nonpharmacological approaches. The use of ventricular assist devices has been approved many years ago, but it will start to significantly impact prognosis in the next years also with the introduction of simpler and less invasive devices. The present special issue of the Journal of Cardiovascular Translational Research deals with novel investigational nonpharmacological approaches to heart failure that are currently under evaluation and may become applicable in the next decade. The present issue is composed by two sections: the first on “mechanical” devices and the second on “autonomic modulation” approaches. The first section focuses on mechanical approaches to improve hemodynamics and/or cardiac structure and function. Recently, functional mitral regurgitation has emerged as a target for heart failure therapy, as observational studies have demonstrated the high prevalence of significant functional mitral regurgitation in chronic systolic heart failure and its association with poor clinical outcomes [7, 8]. Conceptually, a decrease in mitral regurgitant volume might favorably influence left ventricular loading conditions so as to improve symptoms, promote left ventricular reverse remodeling, and improve clinical outcomes. Observational studies of surgical mitral valve repair or replacement seem to support this hypothesis. However, there has been reluctance within the heart failure community to refer patients for such an invasive procedure without a strong evidence from randomized controlled trials. Alternative, minimally invasive approaches to reducing mitral regurgitation have been developed. One such approach, the MitraClip, has recently been approved by the US Food and Drug Administration to treat patients with significant symptomatic degenerative mitral regurgitation (≥3+) who have a
264
too high risk for surgery [9]. The potential role of this and other devices for treating functional mitral regurgitation in heart failure is discussed in the paper from Dr. Denti, Dr. Maisano, and Dr. Alfieri [10]. A variety of surgical and percutaneous devices have been developed to reshape or restore left ventricular geometry and volume toward normal. While the results with surgical ventricular restoration have been mixed [11, 12], newer minimally invasive and percutaneous implanted devices are under investigation for this purpose. Among these devices, the PARAC HUTE device, has produced encouraging preliminary clinical data [13] and is undergoing further evaluation in a pivotal randomized controlled outcomes trial [14]. Dr. Oliveira and Dr. Costa review historical and current left ventricular restoration devices [15]. The role of ventricular assistance is now well established in the management of end-stage heart failure. Left ventricular assist devices improve outcomes compared to medical therapy in inotrope-dependent end-stage patients [16]. Left ventricular assist devices have been proposed for heart failure patients who are less sick but remain substantially symptomatic. Their primary limitation in this population stems from the bloodcontacting nature of the devices, leading to the risk of thrombus formation, thromboembolism (including stroke), intravascular infection, and bleeding due to required anticoagulation. An alternative approach, leveraging well-understood concepts and decades of clinical experience with intra-aortic counterpulsation devices, is the use of implantable extraaortic counterpulsation devices. These devices have no blood-contacting surface and augment both systolic and diastolic pressure/flow. In this issue, Dr. Solanki discusses these devices in detail and their potential for advanced but not endstage heart failure [17]. The second section deals with the possibility of interventional autonomic modulation as a novel therapeutic approach. The first paper of this series starts from the consideration that most of the pharmacological approaches that have proven effectiveness in patients with heart failure enhance baroreceptor responsiveness [18]. Almost 50 years ago, Dr. Braunwald showed the potential of carotid sinus nerve stimulation to treat patients with angina [19], but this approach was subsequently abandoned due to technical difficulties. The rationale for electrical baroreceptor activation is strong and the experimental data are promising. The first clinical approach was based on a very extensive bilateral surgery, but the novel electrode design appears to produce similar effects on blood pressure reduction with a much less invasive unilateral approach. Since this technique appears to effectively reduce blood pressure and left ventricular hypertrophy, it may also be suitable for the treatment of heart failure with preserved left ventricular function, a condition with very limited effective treatment options. Parasympathetic augmentation can be produced also by direct stimulation of the vagus nerve as detailed in the second
J. of Cardiovasc. Trans. Res. (2014) 7:263–265
paper of the section [20]. This technique was first shown experimentally to be effective against malignant arrhythmias [21] and has been approved clinically for the treatment of drug refractory epilepsy [22]. Following a feasibility study evaluation and a small European pilot study, three larger trials are presently evaluating this approach in patients with depressed left ventricular function, including a large phase III pivotal trial. The subsequent contribution addresses spinal cord stimulation [23], a technique that has been used for decades for the treatment of pain conditions including angina pectoris, refractory to conventional therapies [24]. Spinal cord stimulation has been shown to improve left ventricular function and to reduce the occurrence of malignant ventricular arrhythmias in animal models of heart failure. The present paper evaluates optimal site and intensity of spinal cord stimulation and discusses the potential of this technique in the treatment of patients with advanced cardiac disease. At variance with the techniques described above that require the implantation of a stimulating electrode and a device, the approaches described in the last two papers of this section deal with denervation techniques that are performed “once and forever”. Renal denervation, usually performed by means of radiofrequency catheter ablation, has been extensively used in Europe, in the absence of an approval by the FDA, following the favorable clinical experience obtained in the treatment of several clinical conditions characterized by sympathetic hyperactivity, first of all resistant hypertension. The manuscript by Böhm et al. [25] presents the results of the studies in hypertension as well as the first pilot trials in patients with heart failure that all concur to suggest a potential role for this technique in the future. Finally, the issue is closed by a paper presenting the rationale behind the hypothesis of approaching patients with heart failure with cardiac sympathetic denervation [26], a surgical technique that is currently used for the prevention of malignant arrhythmias in arrhythmogenic disorders of genetic origin. Although this possibility has yet to be tested, its one in a lifetime nature may potentially offer advantages in a few unconventional conditions. Overall, we are confident that some of the techniques described in this issue will survive the present experimental phase of the development and will help to improve the prognosis of patients with heart failure.
Conflict of Interest Dr. Abraham has received consulting fees from About Vascular, Cardiokinetix, CVRx, St. Jude Medical, and Sunshine Heart. Dr. De Ferrari receives fees for his role as a member of the steering committee of the NECTAR-HF trial supported by Boston Scientific. He received compensation from BioControl for his role as a consultant and as a member of the steering committee of the CardioFit Multicentre Study until 2009.
J. of Cardiovasc. Trans. Res. (2014) 7:263–265
References 1. Mosterd, A., & Hoes, A. W. (2007). Clinical epidemiology of heart failure. Heart, 93, 1137–1146. 2. Stewart, S., MacIntyre, K., Hole, D. J., Capewell, S., & McMurray, J. J. (2001). More ‘malignant’ than cancer? Five-year survival following a first admission for heart failure. European Journal of Heart Failure, 3, 315–322. 3. Jhund, P. S., Macintyre, K., Simpson, C. R., Lewsey, J. D., Stewart, S., Redpath, A., Chalmers, J. W., Capewell, S., & McMurray, J. J. (2009). Long-term trends in first hospitalization for heart failure and subsequent survival between 1986 and 2003: a population study of 5.1 million people. Circulation, 119, 515–523. 4. Deedwania, P. C., & Carbajal, E. (2012). Evidence-based therapy for heart failure. Medical Clinics of North America, 96, 915–931. 5. Fonarow, G. C., Yancy, C. W., Hernandez, A. F., Peterson, E. D., Spertus, J. A., & Heidenreich, P. A. (2011). Potential impact of optimal implementation of evidence-based heart failure therapies on mortality. American Heart Journal, 161, 1024–1030. 6. Zipes, D. P., Camm, A. J., Borggrefe, M., Buxton, A. E., Chaitman, B., Fromer, M., Gregoratos, G., Klein, G., Moss, A. J., Myerburg, R. J., Priori, S. G., Quinones, M. A., Roden, D. M., Silka, M. J., & Tracy, C. (2006). ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death—executive summary: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (writing committee to develop guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death). European Heart Journal, 27, 2099–2140. 7. Robbins, J. D., Maniar, P. B., Cotts, W., Parker, M. A., Bonow, R. O., & Gheorghiade, M. (2003). Prevalence and severity of mitral regurgitation in chronic systolic heart failure. American Journal of Cardiology, 91, 360–362. 8. Trichon, B. H., Felker, G. M., Shaw, L. K., Cabell, C. H., & O’Connor, C. M. (2003). Relation of frequency and severity of mitral regurgitation to survival among patients with left ventricular systolic dysfunction and heart failure. American Journal of Cardiology, 91, 538–543. 9. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ DeviceApprovalsandClearances/Recently-ApprovedDevices/ ucm375149.htm. Accessed 10 Feb 2014. 10. Denti, P., Maisano, F., & Alfieri, O. (2014). Devices for mitral valve repair. Journal of Cardiovascular Translational Research. doi:10. 1007/s12265-014-9543-y. 11. Athanasuleas, C. L., Buckberg, G. D., Stanley, A. W. H., Siler, W., Dor, V., Di Donato, M., Menicanti, L., de Oliveira, S. A., Beyersdorf, F., Kron, I. L., Suma, H., Kouchoukos, N. T., Moore, W., McCarthy, P. M., Oz, M. C., Fontan, F., Scott, M. L., Accola, K. A., & RESTORE Group. (2004). Surgical ventricular restoration in the treatment of congestive heart failure due to post-infarction ventricular dilation. Journal of the American College of Cardiology, 44, 1439–1445. 12. Velazquez, E. J., Lee, K. L., Deja, M. A., Jain, A., Sopko, G., Marchenko, A., Ali, I. S., Pohost, G., Gradinac, S., Abraham, W. T., Yii, M., Prabhakaran, D., Szwed, H., Ferrazzi, P., Petrie, M. C., O’Connor, C. M., Panchavinnin, P., She, L., Bonow, R. O., Rankin, G. R., Jones, R. H., Rouleau, J. L., & Investigators, S. T. I. C. H. (2011). Coronary-artery bypass surgery in patients with left ventricular dysfunction. New England Journal of Medicine, 364, 1607–1616.
265 13. Mazzaferri, E. L., Jr., Gradinac, S., Sagic, D., Otasevic, P., Hasan, A. K., Goff, T. L., Sievert, H., Wunderlich, N., Nikolic, S. D., & Abraham, W. T. (2012). Percutaneous left ventricular partitioning in patients with chronic heart failure and a prior anterior myocardial infarction: results of the percutaneous ventricular restoration in chronic heart failure patients trial. American Heart Journal, 163, 812–820. 14. Costa, M. A., Pencina, M., Nikolic, S., Engels, T., Templin, B., & Abraham, W. T. (2013). The PARACHUTE IV trial design and rationale: percutaneous ventricular restoration using the parachute device in patients with ischemic heart failure and dilated left ventricles. American Heart Journal, 165, 531–536. 15. Oliveira, G. H., Al-Kindi, S. G., Bezerra, H., & Costa, M. A. (2014). Left ventricular restoration devices. Journal of Cardiovascular Translational Research. doi:10.1007/s12265-014-9552-x. 16. Rose, E. A., Gelijns, A. C., Moskowitz, A. J., Heitjan, D. F., Stevenson, L. W., Dembitsky, W., Long, J. W., Ascheim, D. D., Tierney, A. R., Levitan, R. G., Watson, J. T., Meier, P., Ronan, N. S., Shapiro, P. A., Lazar, R. M., Miller, L. W., Gupta, L., Frazier, O. H., Desvigne-Nickens, P., Oz, M. C., Poirier, V. L., & Randomized evaluation of mechanical assistance for the treatment of congestive heart failure (REMATCH) study group. (2001). Long-term use of a left ventricular assist device for end-stage heart failure. New England Journal of Medicine, 345, 1435–1443. 17. Solanki, P. (2014). Aortic counterpulsation: c-pulse and other devices for cardiac support. Journal of Cardiovascular Translational Research. doi:10.1007/s12265-014-9548-6. 18. Gronda, E., Lovett, E. G., Tarascio, M., Georgakopoulos, D., Grassi, G., & Vanoli, E. (2014). The baroreceptor as a therapeutic target for heart failure. Journal of Cardiovascular Translational Research. doi: 10.1007/s12265-014-9546-8. 19. Braunwald, E., Epstein, S. E., Glick, G., Wechsler, A. S., & Braunwald, N. S. (1967). Relief of angina pectoris by electrical stimulation of the carotid-sinus nerves. New England Journal of Medicine, 277, 1278–1283. 20. De Ferrari, G. M. (2014). Vagal stimulation in heart failure. Journal of Cardiovascular Translational Research. doi:10.1007/s12265-0149540-1. 21. De Ferrari, G. M., Vanoli, E., & Schwartz, P. J. (1994). Vagal activity and ventricular fibrillation. In M. N. Levy & P. J. Schwartz (Eds.), Vagal control of the heart: experimental basis and clinical implications (pp. 613–636). Armonk: Futura Publishing Co. 22. Morrow, J. I., Bingham, E., Craig, J. J., & Gray, W. J. (2000). Vagal nerve stimulation in patients with refractory epilepsy. Effect on seizure frequency, severity and quality of life. Seizure, 9, 442–445. 23. Lopshire, Z. (2014). Spinal cord stimulation for heart failure: preclinical studies to determine optimal stimulation parameters for clinical efficacy. Journal of Cardiovascular Translational Research. doi:10. 1007/s12265-014-9547-7. 24. Foreman, R. D. (2007). Neurological mechanisms of chest pain and cardiac disease. Cleveland Clinic Journal of Medicine, 74(Suppl 1), S30–S33. 25. Böhm, M., Ewen, S., Linz, D., Reil, J.-C., Schirmer, S., Ukena, C., et al. (2014). Renal denervation: a novel non-pharmacological approach in heart failure. Journal of Cardiovascular Translational Research. doi:10.1007/s12265-014-9549-5. 26. De Ferrari, G. M., Schwartz, P. J. (2014). Left cardiac sympathetic denervation in patients with heart failure: a new indication for an old intervention? Journal of Cardiovascular Translational Research. doi: 10.1007/s12265-014-9541-0.
Novel Non-pharmacological Approaches to Heart Failure William T. Abraham & Gaetano M. De Ferrari
Received: 18 February 2014 / Accepted: 24 February 2014 / Published online: 27 March 2014 # Springer Science+Business Media New York 2014
Heart failure is a major public health problem and is associated with increased morbidity and mortality. As the life expectancy increases and the population ages, the overall prevalence of heart failure continues to rise. Indeed, while less than 2 % of the overall adult population in developed countries has heart failure, this percentage exceeds 10 % among subjects above 70 years of age [1]. Before 1990, 60 to 70 % of patients died within 5 years of the diagnosis leading to the suggestion that the disease could be more malignant than most types of cancer [2]. In the past 20–25 years, considerable improvements in the therapeutic approach to patients with heart failure have led to a reduction in hospitalization of 30–50 % and to a smaller but still significant reduction in mortality [3]. In the first part of this period, the improvement was due to the implementation of a pharmacological approach with beta-adrenergic blockers, angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin II receptor blockers (ARBs), and aldosterone receptor blockers [4]. These agents produced a relative risk reduction in mortality ranging from 20 % (for ACE-Is) to 30 % (for betablockers) [5]. In the second half of the period, no additional pharmacological agent significantly affecting the prognosis of heart failure was introduced. The further improvement was due to the increased use of implantable cardioverter-
Associate Editor Craig Stolen oversaw the review of this article W. T. Abraham Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH, USA G. M. De Ferrari (*) Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy e-mail: [email protected] G. M. De Ferrari Cardiovascular Clinical Research Center, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
defibrillators (ICDs) and of cardiac resynchronization therapy (CRT) devices [6]. Despite these improvements, morbidity and mortality related to heart failure remain unacceptably high. We believe that the improvement in the prognosis of this disease in the next two decades will be based to a great extent on novel nonpharmacological approaches. The use of ventricular assist devices has been approved many years ago, but it will start to significantly impact prognosis in the next years also with the introduction of simpler and less invasive devices. The present special issue of the Journal of Cardiovascular Translational Research deals with novel investigational nonpharmacological approaches to heart failure that are currently under evaluation and may become applicable in the next decade. The present issue is composed by two sections: the first on “mechanical” devices and the second on “autonomic modulation” approaches. The first section focuses on mechanical approaches to improve hemodynamics and/or cardiac structure and function. Recently, functional mitral regurgitation has emerged as a target for heart failure therapy, as observational studies have demonstrated the high prevalence of significant functional mitral regurgitation in chronic systolic heart failure and its association with poor clinical outcomes [7, 8]. Conceptually, a decrease in mitral regurgitant volume might favorably influence left ventricular loading conditions so as to improve symptoms, promote left ventricular reverse remodeling, and improve clinical outcomes. Observational studies of surgical mitral valve repair or replacement seem to support this hypothesis. However, there has been reluctance within the heart failure community to refer patients for such an invasive procedure without a strong evidence from randomized controlled trials. Alternative, minimally invasive approaches to reducing mitral regurgitation have been developed. One such approach, the MitraClip, has recently been approved by the US Food and Drug Administration to treat patients with significant symptomatic degenerative mitral regurgitation (≥3+) who have a
264
too high risk for surgery [9]. The potential role of this and other devices for treating functional mitral regurgitation in heart failure is discussed in the paper from Dr. Denti, Dr. Maisano, and Dr. Alfieri [10]. A variety of surgical and percutaneous devices have been developed to reshape or restore left ventricular geometry and volume toward normal. While the results with surgical ventricular restoration have been mixed [11, 12], newer minimally invasive and percutaneous implanted devices are under investigation for this purpose. Among these devices, the PARAC HUTE device, has produced encouraging preliminary clinical data [13] and is undergoing further evaluation in a pivotal randomized controlled outcomes trial [14]. Dr. Oliveira and Dr. Costa review historical and current left ventricular restoration devices [15]. The role of ventricular assistance is now well established in the management of end-stage heart failure. Left ventricular assist devices improve outcomes compared to medical therapy in inotrope-dependent end-stage patients [16]. Left ventricular assist devices have been proposed for heart failure patients who are less sick but remain substantially symptomatic. Their primary limitation in this population stems from the bloodcontacting nature of the devices, leading to the risk of thrombus formation, thromboembolism (including stroke), intravascular infection, and bleeding due to required anticoagulation. An alternative approach, leveraging well-understood concepts and decades of clinical experience with intra-aortic counterpulsation devices, is the use of implantable extraaortic counterpulsation devices. These devices have no blood-contacting surface and augment both systolic and diastolic pressure/flow. In this issue, Dr. Solanki discusses these devices in detail and their potential for advanced but not endstage heart failure [17]. The second section deals with the possibility of interventional autonomic modulation as a novel therapeutic approach. The first paper of this series starts from the consideration that most of the pharmacological approaches that have proven effectiveness in patients with heart failure enhance baroreceptor responsiveness [18]. Almost 50 years ago, Dr. Braunwald showed the potential of carotid sinus nerve stimulation to treat patients with angina [19], but this approach was subsequently abandoned due to technical difficulties. The rationale for electrical baroreceptor activation is strong and the experimental data are promising. The first clinical approach was based on a very extensive bilateral surgery, but the novel electrode design appears to produce similar effects on blood pressure reduction with a much less invasive unilateral approach. Since this technique appears to effectively reduce blood pressure and left ventricular hypertrophy, it may also be suitable for the treatment of heart failure with preserved left ventricular function, a condition with very limited effective treatment options. Parasympathetic augmentation can be produced also by direct stimulation of the vagus nerve as detailed in the second
J. of Cardiovasc. Trans. Res. (2014) 7:263–265
paper of the section [20]. This technique was first shown experimentally to be effective against malignant arrhythmias [21] and has been approved clinically for the treatment of drug refractory epilepsy [22]. Following a feasibility study evaluation and a small European pilot study, three larger trials are presently evaluating this approach in patients with depressed left ventricular function, including a large phase III pivotal trial. The subsequent contribution addresses spinal cord stimulation [23], a technique that has been used for decades for the treatment of pain conditions including angina pectoris, refractory to conventional therapies [24]. Spinal cord stimulation has been shown to improve left ventricular function and to reduce the occurrence of malignant ventricular arrhythmias in animal models of heart failure. The present paper evaluates optimal site and intensity of spinal cord stimulation and discusses the potential of this technique in the treatment of patients with advanced cardiac disease. At variance with the techniques described above that require the implantation of a stimulating electrode and a device, the approaches described in the last two papers of this section deal with denervation techniques that are performed “once and forever”. Renal denervation, usually performed by means of radiofrequency catheter ablation, has been extensively used in Europe, in the absence of an approval by the FDA, following the favorable clinical experience obtained in the treatment of several clinical conditions characterized by sympathetic hyperactivity, first of all resistant hypertension. The manuscript by Böhm et al. [25] presents the results of the studies in hypertension as well as the first pilot trials in patients with heart failure that all concur to suggest a potential role for this technique in the future. Finally, the issue is closed by a paper presenting the rationale behind the hypothesis of approaching patients with heart failure with cardiac sympathetic denervation [26], a surgical technique that is currently used for the prevention of malignant arrhythmias in arrhythmogenic disorders of genetic origin. Although this possibility has yet to be tested, its one in a lifetime nature may potentially offer advantages in a few unconventional conditions. Overall, we are confident that some of the techniques described in this issue will survive the present experimental phase of the development and will help to improve the prognosis of patients with heart failure.
Conflict of Interest Dr. Abraham has received consulting fees from About Vascular, Cardiokinetix, CVRx, St. Jude Medical, and Sunshine Heart. Dr. De Ferrari receives fees for his role as a member of the steering committee of the NECTAR-HF trial supported by Boston Scientific. He received compensation from BioControl for his role as a consultant and as a member of the steering committee of the CardioFit Multicentre Study until 2009.
J. of Cardiovasc. Trans. Res. (2014) 7:263–265
References 1. Mosterd, A., & Hoes, A. W. (2007). Clinical epidemiology of heart failure. Heart, 93, 1137–1146. 2. Stewart, S., MacIntyre, K., Hole, D. J., Capewell, S., & McMurray, J. J. (2001). More ‘malignant’ than cancer? Five-year survival following a first admission for heart failure. European Journal of Heart Failure, 3, 315–322. 3. Jhund, P. S., Macintyre, K., Simpson, C. R., Lewsey, J. D., Stewart, S., Redpath, A., Chalmers, J. W., Capewell, S., & McMurray, J. J. (2009). Long-term trends in first hospitalization for heart failure and subsequent survival between 1986 and 2003: a population study of 5.1 million people. Circulation, 119, 515–523. 4. Deedwania, P. C., & Carbajal, E. (2012). Evidence-based therapy for heart failure. Medical Clinics of North America, 96, 915–931. 5. Fonarow, G. C., Yancy, C. W., Hernandez, A. F., Peterson, E. D., Spertus, J. A., & Heidenreich, P. A. (2011). Potential impact of optimal implementation of evidence-based heart failure therapies on mortality. American Heart Journal, 161, 1024–1030. 6. Zipes, D. P., Camm, A. J., Borggrefe, M., Buxton, A. E., Chaitman, B., Fromer, M., Gregoratos, G., Klein, G., Moss, A. J., Myerburg, R. J., Priori, S. G., Quinones, M. A., Roden, D. M., Silka, M. J., & Tracy, C. (2006). ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death—executive summary: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (writing committee to develop guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death). European Heart Journal, 27, 2099–2140. 7. Robbins, J. D., Maniar, P. B., Cotts, W., Parker, M. A., Bonow, R. O., & Gheorghiade, M. (2003). Prevalence and severity of mitral regurgitation in chronic systolic heart failure. American Journal of Cardiology, 91, 360–362. 8. Trichon, B. H., Felker, G. M., Shaw, L. K., Cabell, C. H., & O’Connor, C. M. (2003). Relation of frequency and severity of mitral regurgitation to survival among patients with left ventricular systolic dysfunction and heart failure. American Journal of Cardiology, 91, 538–543. 9. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ DeviceApprovalsandClearances/Recently-ApprovedDevices/ ucm375149.htm. Accessed 10 Feb 2014. 10. Denti, P., Maisano, F., & Alfieri, O. (2014). Devices for mitral valve repair. Journal of Cardiovascular Translational Research. doi:10. 1007/s12265-014-9543-y. 11. Athanasuleas, C. L., Buckberg, G. D., Stanley, A. W. H., Siler, W., Dor, V., Di Donato, M., Menicanti, L., de Oliveira, S. A., Beyersdorf, F., Kron, I. L., Suma, H., Kouchoukos, N. T., Moore, W., McCarthy, P. M., Oz, M. C., Fontan, F., Scott, M. L., Accola, K. A., & RESTORE Group. (2004). Surgical ventricular restoration in the treatment of congestive heart failure due to post-infarction ventricular dilation. Journal of the American College of Cardiology, 44, 1439–1445. 12. Velazquez, E. J., Lee, K. L., Deja, M. A., Jain, A., Sopko, G., Marchenko, A., Ali, I. S., Pohost, G., Gradinac, S., Abraham, W. T., Yii, M., Prabhakaran, D., Szwed, H., Ferrazzi, P., Petrie, M. C., O’Connor, C. M., Panchavinnin, P., She, L., Bonow, R. O., Rankin, G. R., Jones, R. H., Rouleau, J. L., & Investigators, S. T. I. C. H. (2011). Coronary-artery bypass surgery in patients with left ventricular dysfunction. New England Journal of Medicine, 364, 1607–1616.
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