title: Cardiac contractility modulation: a novel approach for the treatment of heart failure.
abstract: Heart failure is a major health problem worldwide and, despite effective therapies, is expected to grow by almost 50 % over the next 15 years. Five-year mortality remains high at 50 % over 5 years. Because of the economic burden and large impact on quality of life, substantial effort has focused on treatments with multiple medical (beta-blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ARB), aldosterone antagonists, and combination of ARB/neprilysin blockers, ivabradine) and device therapies (ICD, CRT) which have been implemented to reduce disease burden and mortality. However, in the past decade only two new medical therapies and no devices have been approved by the US FDA for the treatment of heart failure. This review highlights the preclinical and clinical literature, and the implantation procedure, related to a relatively new therapeutic device for heart failure; cardiac contractility modulation (CCM). CCM delivers a biphasic high-voltage bipolar signal to the RV septum during the absolute refractory period, eliciting an acute increase in global contractility, and chronically producing a sustained improvement in quality of life, exercise tolerance, and heart failure symptoms. The technology is used commercially in Europe with nearly 3000 patients implanted worldwide. Indications include patients with reduced EF and normal or slightly prolonged QRS duration, thus filling an important therapeutic gap among the 2/3 of patients with heart failure who do not meet criteria for CRT. The mechanism by which CCM provides benefit can be seen at the cellular level where improved calcium handling (phosphorylation of phospholamban, upregulation of SERCA-2A), reversal of the fetal myocyte gene program associated with heart failure, and reverse remodeling are observed. Recent retrospective studies indicate a long-term mortality benefit. A pivotal randomized controlled study is currently being completed in the USA. CCM appears to be an effective, safe technology for the treatment of heart failure with reduced ejection fraction.
authors.affiliation: , 1516 Jefferson Hwy, New Orleans, LA, 70121, USA.
authors.forename: Freddy
authors.initials: F
authors.lastname: Abi-Samra
authors.affiliation: MD Medical College of Wisconsin, Milwaukee, WI, 53226, USA. dgutt@mcw.edu.
authors.forename: David
authors.identifier: 0000-0003-2814-7867
authors.initials: D
authors.lastname: Gutterman
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D058409:Cardiac Resynchronization Therapy Devices; D004599:Electric Stimulation Therapy / Q000295:instrumentation*; D004867:Equipment Design; D017079:Exercise Tolerance; D006333:Heart Failure / Q000453:epidemiology / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D013318:Stroke Volume; D018487:Ventricular Dysfunction, Left / Q000628:therapy*
chemical_list: D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors
keywords: Calcium handling; Cardiac contractility modulation; Device; Electrical therapy; HFrEF; SERCA2A