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      Changes in QRS Area and QRS Duration After Cardiac Resynchronization Therapy Predict Cardiac Mortality, Heart Failure Hospitalizations, and Ventricular Arrhythmias

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          Abstract

          Background

          Predicting clinical outcomes after cardiac resynchronization therapy ( CRT) and its optimization remain a challenge. We sought to determine whether pre‐ and postimplantation QRS area ( QRS area) predict clinical outcomes after CRT.

          Methods and Results

          In this retrospective study, QRS area, derived from pre‐ and postimplantation vectorcardiography, were assessed in relation to the primary end point of cardiac mortality after CRT with or without defibrillation. Other end points included total mortality, total mortality or heart failure ( HF) hospitalization, total mortality or major adverse cardiac events, and the arrhythmic end point of sudden cardiac death or ventricular arrhythmias with or without a shock. In patients (n=380, age 72.0±12.4 years, 68.7% male) undergoing CRT over 7.7 years (median follow‐up: 3.8 years [interquartile range 2.3–5.3]), preimplantation QRS area ≥102 μVs predicted cardiac mortality ( HR: 0.36; P<0.001), independent of QRS duration ( QRSd) and morphology ( P<0.001). A QRS area reduction ≥45 μVs after CRT predicted cardiac mortality ( HR: 0.19), total mortality ( HR: 0.50), total mortality or heart failure hospitalization ( HR: 0.44), total mortality or major adverse cardiac events ( HR: 0.43) (all P<0.001) and the arrhythmic end point ( HR: 0.26; P<0.001). A concomitant reduction in QRS area and QRSd was associated with the lowest risk of cardiac mortality and the arrhythmic end point (both HR: 0.12, P<0.001).

          Conclusions

          Pre‐implantation QRS area, derived from vectorcardiography, was superior to QRSd and QRS morphology in predicting cardiac mortality after CRT. A postimplant reduction in both QRS area and QRSd was associated with the best outcomes, including the arrhythmic end point.

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          Most cited references28

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          Cardiac-resynchronization therapy for the prevention of heart-failure events.

          This trial was designed to determine whether cardiac-resynchronization therapy (CRT) with biventricular pacing would reduce the risk of death or heart-failure events in patients with mild cardiac symptoms, a reduced ejection fraction, and a wide QRS complex. During a 4.5-year period, we enrolled and followed 1820 patients with ischemic or nonischemic cardiomyopathy, an ejection fraction of 30% or less, a QRS duration of 130 msec or more, and New York Heart Association class I or II symptoms. Patients were randomly assigned in a 3:2 ratio to receive CRT plus an implantable cardioverter-defibrillator (ICD) (1089 patients) or an ICD alone (731 patients). The primary end point was death from any cause or a nonfatal heart-failure event (whichever came first). Heart-failure events were diagnosed by physicians who were aware of the treatment assignments, but they were adjudicated by a committee that was unaware of assignments. During an average follow-up of 2.4 years, the primary end point occurred in 187 of 1089 patients in the CRT-ICD group (17.2%) and 185 of 731 patients in the ICD-only group (25.3%) (hazard ratio in the CRT-ICD group, 0.66; 95% confidence interval [CI], 0.52 to 0.84; P=0.001). The benefit did not differ significantly between patients with ischemic cardiomyopathy and those with nonischemic cardiomyopathy. The superiority of CRT was driven by a 41% reduction in the risk of heart-failure events, a finding that was evident primarily in a prespecified subgroup of patients with a QRS duration of 150 msec or more. CRT was associated with a significant reduction in left ventricular volumes and improvement in the ejection fraction. There was no significant difference between the two groups in the overall risk of death, with a 3% annual mortality rate in each treatment group. Serious adverse events were infrequent in the two groups. CRT combined with ICD decreased the risk of heart-failure events in relatively asymptomatic patients with a low ejection fraction and wide QRS complex. (ClinicalTrials.gov number, NCT00180271.) 2009 Massachusetts Medical Society
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            Cardiac-resynchronization therapy for mild-to-moderate heart failure.

            Cardiac-resynchronization therapy (CRT) benefits patients with left ventricular systolic dysfunction and a wide QRS complex. Most of these patients are candidates for an implantable cardioverter-defibrillator (ICD). We evaluated whether adding CRT to an ICD and optimal medical therapy might reduce mortality and morbidity among such patients. We randomly assigned patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of 120 msec or more or a paced QRS duration of 200 msec or more to receive either an ICD alone or an ICD plus CRT. The primary outcome was death from any cause or hospitalization for heart failure. We followed 1798 patients for a mean of 40 months. The primary outcome occurred in 297 of 894 patients (33.2%) in the ICD-CRT group and 364 of 904 patients (40.3%) in the ICD group (hazard ratio in the ICD-CRT group, 0.75; 95% confidence interval [CI], 0.64 to 0.87; P<0.001). In the ICD-CRT group, 186 patients died, as compared with 236 in the ICD group (hazard ratio, 0.75; 95% CI, 0.62 to 0.91; P = 0.003), and 174 patients were hospitalized for heart failure, as compared with 236 in the ICD group (hazard ratio, 0.68; 95% CI, 0.56 to 0.83; P<0.001). However, at 30 days after device implantation, adverse events had occurred in 124 patients in the ICD-CRT group, as compared with 58 in the ICD group (P<0.001). Among patients with NYHA class II or III heart failure, a wide QRS complex, and left ventricular systolic dysfunction, the addition of CRT to an ICD reduced rates of death and hospitalization for heart failure. This improvement was accompanied by more adverse events. (Funded by the Canadian Institutes of Health Research and Medtronic of Canada; ClinicalTrials.gov number, NCT00251251.).
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              Significance of QRS complex duration in patients with heart failure.

              Prolongation of QRS (> or =120 ms) occurs in 14% to 47% of heart failure (HF) patients. Left bundle branch block is far more common than right bundle branch block. Left-sided intraventricular conduction delay is associated with more advanced myocardial disease, worse left ventricular (LV) function, poorer prognosis, and a higher all-cause mortality rate compared with narrow QRS complex. It also predisposes heart failure patients to an increased risk of ventricular tachyarrhythmias, but the incidence of cardiac or sudden death remains unclear because of limited observations. A progressive increase in QRS duration worsens the prognosis. No electrocardiographic measure is specific enough to provide subgroup risk categorization for excluding or selecting HF patients for prophylactic implantable cardioverter-defibrillator (ICD) therapy. In ICD patients with HF, a wide underlying QRS complex more than doubles the cardiac mortality compared with a narrow QRS complex. There is a high incidence of an elevated defibrillation threshold at the time of ICD implantation in patients with QRS > or =200 ms. Mechanical LV dyssynchrony potentially treatable by ventricular resynchronization occurs in about 70% of HF patients with left-sided intraventricular conduction delay, a fact that would explain the lack of therapeutic response in about 30% of patients subjected to ventricular resynchronization according to standard criteria relying on QRS duration. The duration of the basal QRS complex does not reliably predict the clinical response to ventricular resynchronization, and QRS narrowing after cardiac resynchronization therapy does not correlate with hemodynamic and clinical improvement. Mechanical LV dyssynchrony is best shown by evolving echocardiographic techniques (predominantly tissue Doppler imaging) currently in the process of standardization.
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                Author and article information

                Contributors
                cardiologists@hotmail.com
                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                28 October 2019
                05 November 2019
                : 8
                : 21 ( doiID: 10.1002/jah3.v8.21 )
                : e013539
                Affiliations
                [ 1 ] Aston Medical Research Institute Aston Medical School Aston University Birmingham United Kingdom
                [ 2 ] PEACS Arnhem The Netherlands
                [ 3 ] Queen Elizabeth Hospital Birmingham United Kingdom
                Author notes
                [*] [* ] Correspondence to: Francisco Leyva, MD, Aston Medical Research Institute, Aston University Medical School, Aston University, Birmingham B4 7ET, United Kingdom. E‐mail: cardiologists@ 123456hotmail.com
                Article
                JAH34490
                10.1161/JAHA.119.013539
                6898809
                31657269
                a3724886-6899-483d-bdee-09f458126909
                © 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 07 June 2019
                : 05 September 2019
                Page count
                Figures: 8, Tables: 5, Pages: 16, Words: 8669
                Funding
                Funded by: Medtronic Plc
                Categories
                Original Research
                Original Research
                Arrhythmia and Electrophysiology
                Custom metadata
                2.0
                jah34490
                5 November 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.7.1 mode:remove_FC converted:12.11.2019

                Cardiovascular Medicine
                cardiac resynchronization therapy,left bundle branch block,qrs area,qrs duration,vectorcardiography,arrhythmias,catheter ablation and implantable cardioverter-defibrillator,heart failure

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