Individualized cardiac resynchronization therapy: current status

Research Reports in Clinical Cardiology Dovepress open access to scientific and medical research Review Research Reports in Clinical Cardiology downloaded from https://www.dovepress.com/ by 37.59.46.207 on 12-Jul-2018 For personal use only. Open Access Full Text Article Individualized cardiac resynchronization therapy: current status This article was published in the following Dove Press journal: Research Reports in Clinical Cardiology 7 November 2014 Number of times this article has been viewed Martin H Ruwald 1,2 Niels E Bruun 1,3 Department of Cardiology, Gentofte Hospital, Hellerup, Denmark; 2Heart Research Follow-up Program, Division of Cardiology, University of Rochester Medical Center, Rochester, NY, USA; 3 Clinical Institute, Aalborg University, Aalborg, Denmark 1 Introduction – clinical trials and development Correspondence: Martin H Ruwald Heart Research Follow-up Program, Division of Cardiology, University of Rochester Medical Center, 265 Crittenden Boulevard, Rochester, 14642 NY, USA Email Approximately 2% of the adult population in developed countries has clinical heart failure (HF), increasing prevalence with age, to more than 10% in patients .70 years old.1,2 At least half of these patients have systolic HF with reduced left ventricular ejection fraction (LVEF) (ie, heart failure with reduced ejection fraction [HfrEF]). The mainstay of pharmacological treatment for HFrEF during the last 2–3 decades has been a combined treatment, with inhibitors of the renin–angiotensin system and blockers of the beta-adrenergic and aldosterone receptors, which has reduced morbidity and mortality significantly.1 Although medical management has been successful in approximately 10%–15% of all HF patients, further patients have electrical conduction abnormalities and continuously depressed systolic function.3,4 Cardiac resynchronization therapy (CRT) has developed as a device-based treatment option available for patients with drug-refractory, mild, moderate, or severe heart failure. This device treatment modality has been shown to improve morbidity and mortality significantly, and has been confirmed in recent meta-analyses, but the therapy has so far been limited only to patients with depressed LVEF and specific electrical activation disturbances.5–14 The recent European CRT survey15 showed, however, that the CRT indications used in 305 submit your manuscript | www.dovepress.com Research Reports in Clinical Cardiology 2014:5 305–317 Dovepress © 2014 Ruwald and Bruun. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php http://dx.doi.org/10.2147/RRCC.S50541 Powered by TCPDF (www.tcpdf.org) Abstract: Cardiac resynchronization therapy (CRT) has shown a substantial reduction in heart failure patient morbidity and mortality, with improvement in quality of life as well as symptoms. The therapy is, however, limited to approximately 10%–15% of heart failure patients and, typically, 30% do not derive benefit from the device. For optimal outcomes with CRT, the correct selection of patients is of paramount importance. The first parameter is depressed left ventricular systolic function, and the second is a wide QRS complex. Different nuances among clinical trials have rendered guidelines pragmatic and compromising, but also conflicting and confusing. A large proportion of real-life CRTs are implanted in patients where the evidence for benefit is scarce or not present. Further, for optimal benefit, patients require evidence-directed medical therapy at maximal doses, effective placement of ventricular leads, and high biventricular pacing percentages, along with optimized atrioventricular (AV) and interventricular interval device programming. These items, as well as specific clinical characteristics, such as AV block and atrial fibrillation, in the context of CRT indications, are discussed. This review focuses on these issues to guide the clinician through guidelines, with an evidence-based update on the current status of CRT. Keywords: Cardiac resynchronization therapy, prognosis, review, biventricular pacing, guideline, indications Dovepress Research Reports in Clinical Cardiology downloaded from https://www.dovepress.com/ by 37.59.46.207 on 12-Jul-2018 For personal use only. Ruwald and Bruun daily clinical practice went beyond what was recommended based on the landmark clinical trials, including implantation of the device in patients without conduction disturbances and in patients with permanent atrial fibrillation. Landmark studies were initiated in the late 1990s and first evaluated the use of a CRT pacemaker (CRT-P) in moderate to severe HF patients (New York Heart Association [NYHA] classes III and Ambulatory IV). The MUSTIC,16 MIRACLE,8 and PATH-CHF17 trials demonstrated, in 2001 and 2002, short-term effects, with improvements in walking distance, quality of life, and NYHA class with the use of CRT-P, compared to optimal medical therapy. In 2003 and 2004, the CONTAK-CD18 and MIRACLE ICD I19 and II20 trials compared change to CRT with a defibrillator (CRT-D) to implantable cardioverter defibrillator (ICD) and found improved oxygen uptake, improved quality of life, walking distance, and NYHA class; and also during short-term follow-up for patients in NYHA classes ranging from II–IV. The COMPANION5 and CARE-HF6 trials from 2004 and 2005 provided the substance of long-term evidence determining the efficacy of CRT-P for NYHA III and Ambulatory IV, with significant reductions in mortality and all-cause or cardiovascular hospitalizations. Further, COMPANION had a third arm, randomized to use CRT-D, that was also associated with improved outcome, but there was insufficient statistical significance to show any additional benefit, as compared to CRT-P, and the trial was not designed for this. In 2008, the REVERSE21 trial indicated improvement in HF clinical composite score for mildly symptomatic NYHA class I and II patients in CRT-D versus ICD, and in 2009, the MADIT-CRT7 trial showed significant reductions in a combined end point of HF hospitalizations and all-cause mortality in patients with NYHA I or II symptoms. These were followed in 2010 by the RAFT9 trial that compared CRT-D to ICD in NYHA class IIIII, and confirmed benefit by reductions in HF hospitalization or all-cause death in CRT-D. Long-term follow-up (7 years) of MADIT-CRT22 was recently published, showing significant reduction in all-cause mortality for CRT-D, compared to ICD, while l (...truncated)