Shoei K. Stephen Huang, M.D.
November 10, 2005

Heart failure (HF) is a worldwide pandemic. It afflicts approximately 22 million individuals worldwide with 2 million new cases annually. The five-year mortality rate is as high as 50% as a result of progressive pump failure or sudden death. Sixty percent of the HF population has NYHA Class II and III symptoms. Pharmacologic therapies have made a major impact in this group. However, despite the benefits of pharmacologic therapy, approximately 20% of HF patients will have moderate to severe symptoms with an annual mortality rate as high as 50%.

A rapidly evolving adjunctive therapeutic modality involves using implanted electrical devices: cardiac resynchronization with or without implantable cardioverter defibrillators (ICD). Approximately 15% of all HF patients and more than 30% of patients with moderate to severe symptoms have inter- and intraventricular conduction delays with QRS duration greater than 120 ms that may lead to mechanical dyssynchrony of right and left ventricular contraction. Furthermore, prolonged conduction has been associated with adverse outcomes. QRS prolongation has adverse consequences on cardiac performance due to intraventricular dyssynchrony, atrioventricular (AV) dyssynchrony, and interventricular dyssynchrony. Intraventricular dyssynchrony appears to be the most important, and it reduces max
dP/dT, increases mitral regurgitation duration, delays in LV systolic and diastolic events, and reduces diastolic filling times. The net result is a disturbance in transseptal pressures and volumes, causing abnormal septal deflections and a reduced septal wall contribution to LV erformance. CRT should partially or wholly correct intraventricular, AV, and interventricular dyssynchrony and result in improved cardiac performance. Data from clinical trials performed in the U.S., Canada, and Europe indicate that the CRT can be implanted with safety and success in more than 87% of patients.

Many major controlled trials of CRT and CRT-D (CRT combined with ICD) in HF have similar inclusion criteria: symptomatic NYHA Class II to IV HF, LVEF less than 35%, prolonged QRS durations (>120, >130, or >150 ms) and stability of medical therapy for HF prior to enrollment. The majority of
the completed trials designated functional status, exercise capacity, and quality of life as primary efficacy end points. Based on the studies ublished and reported to date, CRT improves quality of life, functional status, exercise capacity, and morbidity, and may exert favorable effects on cardiac structure and function.
COMPANION provided data that CRT resulted in a 20% reduction in the risk of all-cause mortality and all-cause hospitalization compared to optimal medical therapy. HF mortality and hospitalization were also reduced. In addition, all-cause mortality was reduced by 40% in the CRT-D arm of the trial.

Although the consensus has left us with a reasonable algorithm to guide HF management with a CRT, it also raises a multitude of issues and challenges that include long-term benefit, growing complexity of these device therapies, optimization of implantation and programmability, redefining patient populations most likely to benefit, economic impact, and ethical considerations.
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