==== Front ESC Heart FailESC Heart Fail10.1002/(ISSN)2055-5822EHF2ESC Heart Failure2055-5822John Wiley and Sons Inc. Hoboken 10.1002/ehf2.12297EHF212297ESCHF-18-00001Original Research ArticleOriginal Research ArticlesEligibility for cardiac resynchronization therapy in patients hospitalized with heart failure CRT in patients hospitalized with HFJ. Osmanska et al.Osmanska Joanna http://orcid.org/0000-0002-8419-0838 1 Hawkins Nathaniel M. nat.hawkins@ubc.ca 2 3 4 Toma Mustafa 2 3 4 Ignaszewski Andrew 2 3 4 Virani Sean A. 2 3 4 1 Institute of Cardiovascular and Medical Sciences University of Glasgow Glasgow UK 2 Division of Cardiology University of British Columbia Vancouver BC Canada 3 Vancouver General Hospital Vancouver BC Canada 4 BC Centre for Improved Cardiovascular Health St. Paul's Hospital 1081 Burrard Street Vancouver BC V6Z 1Y6 Canada * Correspondence to: Nathaniel M. Hawkins, BC Centre for Improved Cardiovascular Health, St. Paul's Hospital, 1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada. Tel: +1 (604) 682 2344 ext 65676. Email: nat.hawkins@ubc.ca 25 6 2018 8 2018 5 4 10.1002/ehf2.v5.4668 674 04 1 2018 28 3 2018 03 4 2018 © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.Abstract Aims Recent guidelines recommend cardiac resynchronization therapy (CRT) in mildly symptomatic heart failure (HF) but favour left bundle branch block (LBBB) morphology in patients with moderate QRS prolongation (120–150 ms). We defined how many patients hospitalized with HF fulfil these criteria. Methods and results A single‐centre retrospective cohort study of 363 consecutive patients hospitalized with HF (438 admissions) was performed. Electronic imaging, electrocardiograms, and records were reviewed. Overall, 153 patients (42%) had left ventricular ejection fraction (LVEF) ≤ 35%, and 34% of patients had QRS prolongation. Eighty patients (22%) were potentially eligible with LVEF ≤ 35% and QRS ≥ 120 ms or existing CRT. The majority (68 of 80) had a Class I or IIa recommendation according to international guidelines (LBBB or non‐LBBB QRS ≥ 150 ms or right ventricular pacing). Only a minority (12 of 80) had moderate QRS prolongation of non‐LBBB morphology. One‐quarter (n = 22) of patients fulfilling criteria were ineligible for reasons including dementia, co‐morbidities, or palliative care. A further eight patients required optimization of medical therapy. CRT was therefore immediately indicated in 50 patients. Of these, 29 were implanted or had existing CRT systems. Twenty‐one of the 80 patients eligible for CRT were not identified or treated (6% of the total hospitalized cohort). Conclusions Twenty‐two per cent of elderly real‐life patients hospitalized with HF fulfil LVEF and QRS criteria for CRT, most having a Class I or IIa indication. However, a large proportion is ineligible owing to co‐morbidities or requires medical optimization. Although uptake of CRT was reasonable, there remain opportunities for improvement. Cardiac resynchronization therapyHeart failureBundle branch blockEligibilityMedtronic source-schema-version-number2.0component-idehf212297cover-dateAugust 2018details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_NLMPMC version:version=5.4.4 mode:remove_FC converted:03.08.2018 Osmanska , J. , Hawkins , N. M. , Toma , M. , Ignaszewski , A. , and Virani , S. A. (2018 ) Eligibility for cardiac resynchronization therapy in patients hospitalized with heart failure . ESC Heart Failure , 5 : 668 –674 . 10.1002/ehf2.12297 . ==== Body Introduction Cardiac resynchronization therapy (CRT) improves symptoms and survival in patients with heart failure (HF). The American College of Cardiology/American Heart Association (ACC/AHA) 2008 and European Society of Cardiology (ESC) 2007 guidelines recommended CRT in patients with sinus rhythm, left ventricular ejection fraction (LVEF) ≤ 35%, QRS ≥ 120 ms, and New York Heart Association (NYHA) Functional Class III or ambulatory IV symptoms.1, 2 Among unselected patients hospitalized with HF, the proportion meeting these historic criteria was relatively consistent, ranging from 6% to 10%.3, 4, 5, 6, 7 Subsequent landmark clinical trials demonstrated similar benefits from CRT in patients with milder symptoms (NYHA Class I/II).8, 9 Evidence is also accruing of efficacy in patients with atrial fibrillation (AF) and milder left ventricular systolic dysfunction (LVSD) meeting criteria for pacing due to bradycardia.10 In parallel, analyses from trials and registries have consistently demonstrated limited efficacy of CRT in recipients with non‐left bundle branch block (non‐LBBB) conduction.11, 12 Updated international guidelines therefore expanded the indications for CRT to include mildly symptomatic patients, alongside clearer support for patients with AF and chronic right ventricular pacing.13, 14 A minor concomitant contraction in eligibility has occurred, with guidelines now favouring LBBB morphology in patients with moderate QRS prolongation. As outlined in a recent systematic review, no study to date has examined the proportion of patients fulfilling these new criteria.7 Methods Study cohort A quality assurance programme utilizing retrospective chart review was expanded to assess device candidacy. The study was approved by the institutional ethics board. Inclusion criteria were adults ≥ 18 years discharged with a primary diagnosis of HF from two acute care facilities in the Vancouver Coastal Health region, between 1 November 2011 and 31 March 2013. Both new diagnoses and readmissions were included. Deaths during the index hospitalization were excluded. Eligibility criteria for cardiac resynchronization therapy CRT is recommended in patients with LVEF ≤ 35%, NYHA Class II to IV symptoms, LBBB, or QRS ≥ 150 ms of any morphology (Table 1).13, 14 For non‐LBBB, QRS 120 to 150 ms, NYHA Class II to IV, receives an ESC Class IIb recommendation, while the ACC/AHA limits a similar recommendation to more advanced NYHA Class III/IV symptoms. CRT is supported in patients with AF who otherwise fulfil guideline criteria, and in those with NYHA Class III/IV symptoms likely to experience a significant proportion of right ventricular pacing for bradycardia. Table 1 Recommendation and level of evidence for cardiac resynchronization therapy in international guidelines, according to eligibility criteria Rhythm, QRS, morphology NYHA class LVEF ≤ 35% ESC 201313 ACC/AHA 201214 SR LBBB ≥150 ms II–IV I A I A or B ≥150 ms I (LVEF ≤ 30%) — IIb C ischaemic 120 to 150 ms II–IV I B IIa B SR non‐LBBB ≥150 ms II–IV IIa B IIa A NYHA III/IV IIb B NYHA II 120 to 150 ms II–IV IIb B — 120 to 150 ms III or IV — IIb B AF or pacing ≥120 ms II–IV — IIa B ≥120 ms III or IV IIa B — RV pacing III or IV I B upgrade IIa C upgrade IIa B de novo AF, atrial fibrillation; BBB, bundle branch block; LBBB, left bundle branch block; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; RV, right ventricular; SR, sinus rhythm. CRT eligibility required quantitative LVEF ≤ 35% or qualitatively moderate to severe LVSD on the most recent echocardiogram, nuclear multiple‐gated acquisition scan, contrast ventriculogram, or magnetic resonance imaging. The most recent LVEF was used in multiple assessments. In keeping with prior studies,15 EF measurements dating back further than 1 year were accepted if results remained applicable and further update was inappropriate, e.g. documented dysfunction with no change in therapy planned. All patients were hospitalized with a primary diagnosis of HF and, therefore, considered as NYHA Class II to IV. Electrocardiograms were recorded using the MUSE (GE Healthcare) system. Intraventricular conduction disturbance (IVCD) was defined according to ESC CRT guidelines.13 Complete LBBB: QRS ≥ 120 ms; QS or rS lead V1; broad notched or slurred R waves in lead I, aVL, V5, or V6; absent Q waves in leads V5 and V6. Complete right bundle branch block (RBBB): QRS ≥ 120 ms; rsr′, rsR′, and rSR′ in lead V1 or V2; wide S waves in leads I, V5, and V6. Non‐specific IVCD was defined as QRS ≥ 120 ms without typical features of LBBB or RBBB. Ineligibility criteria included left ventricular assist device, heart transplant, home inotropes, palliative care treatment, and anticipated short life expectancy. Previous studies have excluded patients with either missing LVEF or electrocardiogram (ECG). This approach discounts subjects unnecessarily, as those with narrow QRS or LVEF > 35% are ineligible for CRT irrespective of the alternate investigation. Although LVEF was unavailable for 12 patients, only two had concurrent QRS prolongation. Moreover, both these patients were receiving palliative or nursing home care. Therefore, overall eligibility could be satisfactorily determined for every patient. Data abstraction and statistical analysis Two trained clinical care analysts reviewed medical charts to assess guideline‐directed medical therapy rates and adherence to ACC Foundation/AHA clinical performance measures.16 The primary author reviewed all data fields related to CRT eligibility. A second cardiologist reviewed all ECGs with QRS > 100 ms. Both the admission and most recent chest radiography of all patients were reviewed to determine device and lead configuration. Baseline characteristics of patients eligible and ineligible for CRT were summarized by means with standard deviations for continuous variables and by frequencies and percentages for categorical variables. Means were compared using the Student t‐test and proportions compared using the χ2 test. Results Cardiac resynchronization therapy eligibility overall and uptake Of the 363 patients, 80 (22%) were broadly eligible with LVEF ≤ 35% and prolonged QRS ≥ 120 ms (n = 64), or existing CRT (n = 16) (Figure 1 ). However, one‐quarter (n = 22) of these patients were ineligible owing to dementia, co‐morbidities, palliative intent, or severe symptoms requiring inotropes or mechanical support. A further eight patients required optimization of medical therapy. Overall, therefore, CRT was indicated in 50 patients (14%). Sixteen patients (4%) already had CRT, with another 13 patients (4%) implanted during admission or soon after discharge. However, 21 eligible patients (6%) were not identified, split across general medicine (n = 16) and cardiology (n = 5). Figure 1 Proportion eligible for CRT and reasons for exclusion. Eighty patients (22%) had LVEF ≤ 35% and prolonged QRS ≥ 120 ms. Twenty were ineligible owing to co‐morbidities, and further eight patients required optimization of medical management. Out of remaining 50 eligible patients, 16 had existing CRT and further 13 were implanted during or soon after index admission. Twenty‐one patients were not identified. Baseline characteristics Baseline characteristics are presented in Table 2. Three hundred sixty‐three patients were identified in 438 consecutive hospitalizations including 75 readmissions. Mean age was 74 ± 14 years. The mean length of stay was 11.1 days, with more than half of patients (61%) admitted to internal medicine and one‐third (33%) to cardiology. Co‐morbidities were common. Approximately one‐third of patients had diabetes (36%), chronic kidney disease (CKD) (32%), and angina (35%). Approximately two‐thirds of patients (64%) were receiving either angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker, most of the remainder receiving hydralazine and nitrate in combination. Beta‐blockers were prescribed in 81%, with a similar proportion receiving loop diuretic. More than one‐third (35%) of patients received warfarin. Patients had a mean heart rate of 89 b.p.m. Sinus rhythm and AF were present in 56% and 41%, respectively. Table 2 Baseline characteristics Mean (±SD) or n (%) n = 363 Age (years) 73.5 ± 13.6 Men (%) 201 (55.4%) Length of stay 11.1 ± 12.6 Medical history Myocardial infarction 75 (20.7%) CABG 45 (12.4%) Cerebrovascular disease 49 (13.5%) Diabetes 129 (35.5%) Angina 127 (35.0%) COPD 66 (18.2%) Chronic kidney disease 116 (32.0%) Service Cardiology 120 (33.1%) Internal medicine 197 (54.3%) Clinical status Systolic blood pressure (mmHg) 141.7 ± 28.5% Diastolic blood pressure (mmHg) 77.4 ± 16.0% Medication at discharge ACEI or ARB 232 (63.9%) Beta‐blocker 296 (81.5%) MRA 85 (23.4%) Hydralazine 68 (18.7%) Nitrate patch 88 (24.2%) Loop diuretic 294 (81%) Warfarin 127 (35.0%) Ejection fraction During admission 227 (62.5%) Prior to admission 86 (23.7%) By transthoracic echocardiogram 345 (95%) By other modalities 18 (5%) Mean ejection fraction (%) 41.9 ± 17.7 Moderate–severe mitral regurgitation 120 (33.1%) ECG Heart rate (b.p.m.) 88.6 ± 26.3 Sinus rhythm 202 (55.6%) Atrial fibrillation 150 (41.3%) Pacing rhythm 11 (3.0%) Laboratory Haemoglobin (g/L) 120.7 ± 22.2 Creatinine (μmol/L) 126.8 ± 76.4 Brain natriuretic peptide 1127.1 ± 1059.2 ACEI, angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; CABG, coronary artery bypass graft; COPD, chronic obstructive pulmonary disease; MRA, mineralocorticoid receptor antagonist. Imaging and left ventricular ejection fraction Mean EF was 42 ± 18%. Overall, 153 patients (42%) had LVEF ≤ 35%. One‐third of patients (33%) had moderate or severe mitral regurgitation at baseline. Most patients had LVEF documented (97%), the majority using echocardiography (345 out of 363, 95%). Ejection fraction was measured during, before, and after admission in 63%, 24%, and 14% of patients, respectively. Of particular relevance, almost all patients with QRS prolongation (n = 125) had recent LVEF (n = 120, 96%), except those in which assessment was clearly inappropriate, e.g. advanced dementia. Electrocardiogram Overall, 34% of patients had QRS prolongation, increasing to 50% of those with LVEF ≤ 35% (Table 3). Intermediate QRS prolongation (120–150 ms) and severe QRS prolongation (≥150 ms) were both more common in patients with reduced LVEF ≤ 35% than in the overall population, respectively, 20% vs. 15% and 30% vs. 19%. LBBB was the dominant morphology, accounting for 40% and 51% of QRS prolongation, respectively, in the overall and LVEF ≤ 35% groups. RBBB was less common in those with depressed ejection fraction than in the overall population. Finally, right ventricular pacing was often associated with severe QRS prolongation. Table 3 Prevalence of electrocardiogram abnormalities in the overall population and subgroup with reduced left ventricular ejection fraction All patients LVEF ≤ 35% n = 363 QRS 120–149 ms n = 55 (15%) QRS ≥ 150 ms n = 70 (19%) n = 153 QRS 120–149 ms n = 31 (20%) QRS ≥ 150 ms n = 46 (30%) LBBB 50 (14%) 23 (42%) 27 (39%) 39 (25%) 16 (52%) 23 (50%) RBBB 19 (5%) 10 (18%) 9 (13%) 5 (3%) 2 (6%) 3 (7%) IVCD 17 (5%) 16 (29%) 1 (1%) 11 (7%) 10 (32%) 1 (2%) RV pacing 23 (6%) 5 (9%) 18 (26%) 9 (6%) 2 (6%) 7 (15%) CRT pacing 16 (4%) 1 (2%) 15 (21%) 13 (8%) 1 (3%) 12 (4%) CRT, cardiac resynchronization therapy; IVCD, intraventricular conduction disturbance; LBBB, left bundle branch block; LVEF, left ventricular ejection fraction; RBBB, right bundle branch block; RV, right ventricular. Strength of recommendation for cardiac resynchronization therapy‐eligible patients The majority of eligible patients (85%, n = 68 of 80) had a Class I or IIa recommendation according to ACC or ESC criteria (LBBB or non‐LBBB QRS prolongation ≥ 150 ms or right ventricular pacing). Only 15% of eligible patients had non‐LBBB with moderate QRS prolongation (Table 4). Table 4 Disposition and strength of recommendation for cardiac resynchronization therapy‐eligible patients n = 363 I or IIa recommendation LBBB or non‐LBBB QRS ≥ 150 ms or RV pacing IIb recommendation Non‐LBBB QRS 120–150 ms Total 68 (18.7%) 12 (3.3%) Eligible fulfilling criteria 48 (13.2%) 2 (0.6%) Existing CRT 16 (4.4%) Not applicable Implanted or planned 13 (3.6%) 0 Eligibility not recognized 19 (5.2%) 2 (0.6%) Ineligible otherwise meeting criteria 20 (5.5%) 10 (2.8%) Optimization with LVEF recovery—medical, revascularization, valve 6 (1.7%) 2 (0.6%) Contraindication 14 (3.9%) 8 (2.2%) DNAR, dementia, advanced age 5 (1.4%) 3 (0.8%) Co‐morbidities, frailty, palliative 4 (1.1%) 3 (0.8%) Patient declined, non‐compliance 2 (0.6%) 1 (0.2%) Transplant/LVAD 3 (0.8%) 1 (0.2%) CRT, cardiac resynchronization therapy; DNAR, do not attempt resuscitation; LBBB, left bundle branch block; LVAD, left ventricular assist device; LVEF, left ventricular ejection fraction; RV, right ventricular. Discussion A number of studies have examined CRT candidacy in patients hospitalized with HF.3, 4, 5, 6, 17, 18, 19 However, this is the first study to apply recent guideline criteria using both QRS duration and morphology, and to examine reasons for ineligibility in detail. A high proportion of patients fulfilled criteria, the majority being those most likely to benefit, i.e. LBBB or broad QRS prolongation ≥ 150 ms. Although CRT uptake was reasonable, 6% of the overall hospitalized population were eligible yet not identified. Cardiac resynchronization therapy eligibility Our findings are similar to a Belgian study of 322 consecutive hospitalized patients, in terms of overall eligibility (22% vs. 25%) and prevalence of LVEF ≤ 35% (42% vs. 40%).17 Other studies reported a lower prevalence but relied on administrative or registry data with LVEF only available in one‐thirds to two‐thirds of cases.3, 5, 6 This emphasizes the need for chart‐level data to identify device eligibility. Ejection fraction was measured during admission in 65% and available in 97% of patients overall. To our knowledge, the one other study reporting timing of LVEF measurement yielded similar results (63% and 100% among 674 patients hospitalized with HF).4 Updated international guidelines recommend QRS prolongation ≥ 150 ms for non‐LBBB morphology, with narrower non‐LBBB receiving a lower‐grade recommendation (IIb). The impact of this eligibility contraction, in terms of candidacy, appears relatively minor in our cohort. The dominant morphology of conduction disturbance was LBBB, particularly in those with significantly impaired ventricular function. Only 12 of the 80 eligible patients (15%) exhibited non‐LBBB QRS of 120 to 150 ms. Cardiac resynchronization therapy ineligibility In the few studies reporting ineligibility for CRT, the prevalence ranges from 1% to 21%.3, 5, 15, 20, 21 The highest estimates were obtained using detailed chart abstraction, emphasizing once more the granularity needed to identify contraindications. In our elderly unselected population, 30 of 80 (38%) patients fulfilling EF‐QRS criteria were ineligible: 22 (28%) owing to medical contraindication or patient preference and eight (10%) requiring further medical optimization. This high prevalence of ineligibility reflects the frail, multi‐morbid, hospitalized cohort. Of note, true guideline adherence rates will be significantly underestimated by failure to account for these patients and modify the eligible denominator. Co‐morbidities and generalizability The prevalence of co‐morbidities was similar to the Canadian Enhanced Feedback for Effective Cardiac Treatment (EFFECT) study, the largest report of CRT eligibility in hospitalized patients.5 Approximately one‐third of patients had AF, angina, diabetes, and CKD, with somewhat fewer having cerebrovascular and chronic obstructive pulmonary disease. In our study, patients were elderly (mean age 73 years), again comparable with those in EFFECT (73 years) and contemporary HF registries.22, 23 Our patients are therefore comparable with real‐world populations, but nearly a decade older than those enrolled in landmark clinical trials.8 While age and co‐morbidity should not be barriers to device therapy, the survival benefit and cost‐effectiveness of CRT vs. defibrillators in such populations certainly merit consideration. Cardiac resynchronization therapy uptake The prevalence of existing CRT in our patients (4.4%) lies between estimates from the ESC‐HF Pilot Survey (3.3%) and Italian IN‐HF national registry (5.4%).23, 24 Moreover, the total rate of existing or newly implanted CRT in eligible patients (58%, 29/50) compares favourably with that of other series, including the Get With the Guidelines Heart Failure programme.25 The IMPROVE‐HF (Registry to Improve the Use of Evidence‐Based Heart Failure Therapies in the Outpatient Setting) quality improvement programme increased CRT utilization dramatically from 37% to 66% over 2 years in the outpatient setting.26 No similar initiative has been undertaken for those hospitalized with HF. Our results suggest that 10–15% of all patients hospitalized with HF are candidates for CRT. The opportunity of hospitalization Our findings highlight the opportunity presented by hospitalization to identify device‐eligible patients. First, patients are relatively unselected. Specialized clinics inherently have barriers to care, including primary care detection, referral practices, and socio‐geographical factors.27 By contrast, hospitalization defines a group of patients with severe HF, arguably selecting more deprived patients with less primary care contact.28 Second, almost all patients had sufficient electronic information to assess device eligibility. Third, hospital‐based heart function and electrophysiology services often share either physical location or at least common referral pathways. Finally, some patients may already be medically optimized and appropriate for immediate device implantation or upgrade during the index hospitalization. Limitations A number of limitations merit consideration. The sample size prohibits detailed subgroup analysis and multivariable modelling to examine barriers to CRT. NYHA functional class was infrequently reported, although almost all hospitalized patients are symptomatic (98% in one cohort) and NYHA class is subjective and dynamic.4 The results only represent the experience of two centres and associated systems of care. Conclusions Our results are encouraging, with rates of CRT uptake among eligible patients approaching that observed following intervention in IMPROVE‐HF. Nevertheless, systems of care must improve. Failure to deliver guideline indicated life‐prolonging therapy should be a ‘never event’. Hospitalization may provide an opportunity to identify eligible patients but requires closer integration of data systems and services. Conflict of interest None declared. Funding This work was supported by Medtronic investigator initiated grant. ==== Refs References 1 Vardas PE , Auricchio A , Blanc JJ , Daubert JC , Drexler H , Ector H , Gasparini M , Linde C , Morgado FB , Oto A , Sutton R , Trusz‐Gluza M , European Society of Cardiology , European Heart Rhythm Association . Guidelines for cardiac pacing and cardiac resynchronization therapy: The Task Force for Cardiac Pacing and Cardiac Resynchronization Therapy of the European Society of Cardiology. Developed in collaboration with the European Heart Rhythm Association . Eur Heart J 2007 ; 28 : 2256 –2295 .17726042 2 Epstein AE , DiMarco JP , Ellenbogen KA , Estes NA 3rd , Freedman RA , Gettes LS , Gillinov AM , Gregoratos G , Hammill SC , Hayes DL , Hlatky MA , Newby LK , Page RL , Schoenfeld MH , Silka MJ , Stevenson LW , Sweeney MO , Smith SC Jr , Jacobs AK , Adams CD , Anderson JL , Buller CE , Creager MA , Ettinger SM , Faxon DP , Halperin JL , Hiratzka LF , Hunt SA , Krumholz HM , Kushner FG , Lytle BW , Nishimura RA , Ornato JP , Page RL , Riegel B , Tarkington LG , Yancy CW , American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices) , American Association for Thoracic Surgery; Society of Thoracic Surgeons . ACC/AHA/HRS 2008 Guidelines for Device‐Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons . Circulation 2008 ; 117 : e350 –e408 .18483207 3 Nayar V , Hiari N , Prasad R , Belham MR , Dutka DP , Pugh PJ . Eligibility for cardiac resynchronisation therapy among patients with heart failure, according to UK NICE guideline criteria . Int J Cardiol 2013 ; 168 : 4401 –4402 .23706281 4 Garcia‐Pinilla JM , Jimenez‐Navarro MF , Anguita‐Sanchez M , Martinez‐Martinez A , Torres‐Calvo F , investigators of the R . How many patients admitted for heart failure are eligible for cardiac resynchronization therapy? Analysis of the Andalusian Heart Failure Registry (RAIC) Study . Rev Esp Cardiol 2007 ; 60 : 38 –44 .17288954 5 McAlister FA , Tu JV , Newman A , Lee DS , Kimber S , Cujec B , Armstrong PW . How many patients with heart failure are eligible for cardiac resynchronization? Insights from two prospective cohorts . Eur Heart J 2006 ; 27 : 323 –329 .16105850 6 Farwell D , Patel NR , Hall A , Ralph S , Sulke AN . How many people with heart failure are appropriate for biventricular resynchronization? Eur Heart J 2000 ; 21 : 1246 –1250 .10924314 7 Hawkins NM , Bennett MT , Andrade JG , Virani SA , Krahn AD , Ignaszewski A , Toma M . Review of eligibility for cardiac resynchronization therapy . Am J Cardiol 2015 ; 116 : 318 –324 .25975724 8 Moss AJ , Hall WJ , Cannom DS , Klein H , Brown MW , Daubert JP , Estes NA 3rd , Foster E , Greenberg H , Higgins SL , Pfeffer MA , Solomon SD , Wilber D , Zareba W , MADIT‐CRT Trial Investigators . Cardiac‐resynchronization therapy for the prevention of heart‐failure events . N Engl J Med 2009 ; 361 : 1329 –1338 .19723701 9 Tang AS , Wells GA , Talajic M , Arnold MO , Sheldon R , Connolly S , Hohnloser SH , Nichol G , Birnie DH , Sapp JL , Yee R , Healey JS , Rouleau JL , Resynchronization‐Defibrillation for Ambulatory Heart Failure Trial Investigators . Cardiac‐resynchronization therapy for mild‐to‐moderate heart failure . N Engl J Med 2010 ; 363 : 2385 –2395 .21073365 10 Curtis AB , Worley SJ , Adamson PB , Chung ES , Niazi I , Sherfesee L , Shinn T , Sutton MS , Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) Trial Investigators . Biventricular pacing for atrioventricular block and systolic dysfunction . N Engl J Med 2013 ; 368 : 1585 –1593 .23614585 11 Bilchick KC , Kamath S , DiMarco JP , Stukenborg GJ . Bundle‐branch block morphology and other predictors of outcome after cardiac resynchronization therapy in Medicare patients . Circulation 2010 ; 122 : 2022 –2030 .21041691 12 Birnie DH , Ha A , Higginson L , Sidhu K , Green M , Philippon F , Thibault B , Wells G , Tang A . Impact of QRS morphology and duration on outcomes after cardiac resynchronization therapy: results from the Resynchronization‐Defibrillation for Ambulatory Heart Failure Trial (RAFT) . Circ Heart Fail 2013 ; 6 : 1190 –1198 .23995437 13 Brignole M , Auricchio A , Baron‐Esquivias G , Bordachar P , Boriani G , Breithardt OA , Cleland J , Deharo JC , Delgado V , Elliott PM , Gorenek B , Israel CW , Leclercq C , Linde C , Mont L , Padeletti L , Sutton R , Vardas PE , ESC Committee for Practice Guidelines (CPG) , Zamorano JL , Achenbach S , Baumgartner H , Bax JJ , Bueno H , Dean V , Deaton C , Erol C , Fagard R , Ferrari R , Hasdai D , Hoes AW , Kirchhof P , Knuuti J , Kolh P , Lancellotti P , Linhart A , Nihoyannopoulos P , Piepoli MF , Ponikowski P , Sirnes PA , Tamargo JL , Tendera M , Torbicki A , Wijns W , Windecker S , Document Reviewers , Kirchhof P , Blomstrom‐Lundqvist C , Badano LP , Aliyev F , Bänsch D , Baumgartner H , Bsata W , Buser P , Charron P , Daubert JC , Dobreanu D , Faerestrand S , Hasdai D , Hoes AW , le Heuzey JY , Mavrakis H , McDonagh T , Merino JL , Nawar MM , Nielsen JC , Pieske B , Poposka L , Ruschitzka F , Tendera M , van Gelder I , Wilson CM . 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA) . Eur Heart J 2013 ; 34 : 2281 –2329 .23801822 14 Epstein AE , DiMarco JP , Ellenbogen KA , Estes NA 3rd , Freedman RA , Gettes LS , Gillinov AM , Gregoratos G , Hammill SC , Hayes DL , Hlatky MA , Newby LK , Page RL , Schoenfeld MH , Silka MJ , Stevenson LW , Sweeney MO , Tracy CM , Epstein AE , Darbar D , DiMarco JP , Dunbar SB , Estes NA 3rd , Ferguson TB Jr , Hammill SC , Karasik PE , Link MS , Marine JE , Schoenfeld MH , Shanker AJ , Silka MJ , Stevenson LW , Stevenson WG , Varosy PD , American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines , Heart Rhythm Society . 2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device‐based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society . J Am Coll Cardiol 2013 ; 61 : e6 –e75 .23265327 15 Atwater BD , Dai D , Allen‐Lapointe NM , Al‐Khatib SM , Zimmer LO , Sanders GD , Peterson ED . Is heart failure guideline adherence being underestimated? The impact of therapeutic contraindications . Am Heart J 2012 ; 164 : 750 , e751–755 .23137506 16 Bonow RO , Ganiats TG , Beam CT , Blake K , Casey DE Jr , Goodlin SJ , Grady KL , Hundley RF , Jessup M , Lynn TE , Masoudi FA , Nilasena D , Piña IL , Rockswold PD , Sadwin LB , Sikkema JD , Sincak CA , Spertus J , Torcson PJ , Torres E , Williams MV , Wong JB , American College of Cardiology Foundation , American Heart Association Task Force on Performance Measures , American Medical Association‐Physician Consortium for Performance Improvement . ACCF/AHA/AMA‐PCPI 2011 performance measures for adults with heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Performance Measures and the American Medical Association‐Physician Consortium for Performance Improvement . Circulation 2012 ; 125 : 2382 –2401 .22528524 17 De Sutter J , Weytjens C , Van de Veire N , Provenier F , Vande Kerckhove B , Willems AM , De Laet N , Van Camp G . Prevalence of potential cardiac resynchronization therapy candidates and actual use of cardiac resynchronization therapy in patients hospitalized for heart failure . Eur J Heart Fail 2011 ; 13 : 412 –415 .21138909 18 Guyomar Y , Houchaymi Z , Graux P , Heuls S , Rihani R , Cornaert P , Moulin C , Grimaud JP , Dutoit A . Indications for multisite pacing in patients with heart failure . Am J Cardiol 2001 ; 88 : 688 –690 .11564400 19 Lucas CMHB , Cleuren GVJ , Kirchhof CJHJ . Selection of patients for cardiac resynchronisation therapy (CRT) in an unselected heart failure population . Neth Hear J 2006 ; 14 : 14 –18 . 20 Curtis AB , Yancy CW , Albert NM , Stough WG , Gheorghiade M , Heywood JT , McBride ML , Mehra MR , Oconnor CM , Reynolds D , Walsh MN , Fonarow GC . Cardiac resynchronization therapy utilization for heart failure: findings from IMPROVE HF . Am Heart J 2009 ; 158 : 956 –964 .19958862 21 Lyons KJ , Podder M , Ezekowitz JA . Rates and reasons for device‐based guideline eligibility in patients with heart failure . Heart Rhythm 2014 ; 11 : 1983 –1990 .25101484 22 Ezekowitz JA , Hu J , Delgado D , Hernandez AF , Kaul P , Leader R , Proulx G , Virani S , White M , Zieroth S , O'Connor C , Westerhout CM , Armstrong PW . Acute heart failure: perspectives from a randomized trial and a simultaneous registry . Circ Heart Fail 2012 ; 5 : 735 –741 .23032196 23 Maggioni AP , Dahlström U , Filippatos G , Chioncel O , Leiro MC , Drozdz J , Fruhwald F , Gullestad L , Logeart D , Metra M , Parissis J , Persson H , Ponikowski P , Rauchhaus M , Voors A , Nielsen OW , Zannad F , Tavazzi L , Heart Failure Association of ESC (HFA) . EURObservational Research Programme: the Heart Failure Pilot Survey (ESC‐HF Pilot) . Eur J Heart Fail 2010 ; 12 : 1076 –1084 .20805094 24 Oliva F , Mortara A , Cacciatore G , Chinaglia A , Di Lenarda A , Gorini M , Metra M , Senni M , Maggioni AP , Tavazzi L , IN‐HF Outcome Investigators . Acute heart failure patient profiles, management and in‐hospital outcome: results of the Italian Registry on Heart Failure Outcome . Eur J Heart Fail 2012 ; 14 : 1208 –1217 .22833614 25 Piccini JP , Hernandez AF , Dai D , Thomas KL , Lewis WR , Yancy CW , Peterson ED , Fonarow GC , for the Get With the Guidelines Steering Committee and Hospitals . Use of cardiac resynchronization therapy in patients hospitalized with heart failure . Circulation 2008 ; 118 : 926 –933 .18697821 26 Fonarow GC , Albert NM , Curtis AB , Stough WG , Gheorghiade M , Heywood JT , McBride ML , Inge PJ , Mehra MR , O'Connor CM , Reynolds D , Walsh MN , Yancy CW . Improving evidence‐based care for heart failure in outpatient cardiology practices: primary results of the Registry to Improve the Use of Evidence‐Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF) . Circulation 2010 ; 122 : 585 –596 .20660805 27 Curtis JP , Luebbert JJ , Wang Y , Rathore SS , Chen J , Heidenreich PA , Hammill SC , Lampert RI , Krumholz HM . Association of physician certification and outcomes among patients receiving an implantable cardioverter‐defibrillator . JAMA 2009 ; 301 : 1661 –1670 .19383957 28 Hawkins NM , Jhund PS , McMurray JJ , Capewell S . Heart failure and socioeconomic status: accumulating evidence of inequality . Eur J Heart Fail 2012 ; 14 : 138 –146 .22253454