Emerging Therapies for Congestive Heart Failure

Abstract

The treatment of atherosclerotic heart disease has improved remarkably over the last several decades; however, the outlook for patients with symptomatic congestive heart failure with reduced ejection fraction remains bleak. Current drug therapies target the neurohormonal activation that accompanies congestive heart failure, but do not address the fundamental pathology inherent in this condition-the loss of contractile capacity. Stem cell therapies offer the possibility of rectifying this deficiency and normalizing left ventricular dimensions and cardiac performance by regenerating novel contractile tissue, thereby reversing the negative remodeling that portends progressive left ventricular dysfunction, worsening symptoms, and ultimately cardiogenic shock. Here we review the promise of stem cell therapies in the treatment of heart failure with reduced ejection fraction, the current state of clinical developments, and briefly comment on the future of the field.Over the last several decades, the development of a variety of novel cardiovascular therapeutics coupled with lifestyle modifications, such as smoking cessation, has resulted in a remarkable 30-35% decline in cardiovascular mortality and up to a 65% reduction in cardiovascular events. 1 Such statistics have led to the perception that cardiovascular disease has been "cured" however, cardiovascular disease accounts for more than one of every three deaths in the US 2 and ischemic heart disease remains the leading cause of death both worldwide and in the US. This is especially true in the elderly, where cardiovascular disease accounts for over 50% of all deaths in patients over age 75 and over 3-fold more deaths than cancer in patients over age 85. 2 As the treatment of acute myocardial infarction (MI) and chronic ischemic heart disease continues to improve, the burden of heart failure (HF) is accumulating both in terms of incidence and cost, with an estimated 38 million patients with this condition worldwide. 3 Current projections estimate that the prevalence of HF will increase by up to 46% over the next 18 years. By 2023, it is estimated that over 8 million patients in the US alone will have a diagnosis of congestive HF (CHF). 2 CHF remains the most common and expensive diagnosis in the Medicare system, with over 1 million annual hospitalizations for CHF in both the US and Europe. With the aging patient population, this number is expected to grow by over 50% in the next 15 years. 4 In addition, within 60 days of hospitalization for CHF, 30-50% of patients either die or are rehospitalized, with 20-30% mortality at 1 year and 40-50% mortality by 5 years. 5 The majority of medications that have been successful in treating CHF (angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers, aldosterone antagonists) target chronic neurohormonal aberrations that occur in response to this condition. While this approach was initially extremely effective, further attempts at continued targeting of the neurohormonal axis have bee...

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