Extending the Boundaries of Cardiac Resynchronization Therapy: Efficacy in Atrial Fibrillation, New York Heart Association Class II, and Narrow QRS Heart Failure Patients

doi:10.1016/j.cardfail.2009.12.018

Journal of Cardiac Failure

Volume 16, Issue 5, May 2010, Pages 432-438

https://doi.org/10.1016/j.cardfail.2009.12.018 Get rights and content

Abstract

Background

Large-scale clinical trials have demonstrated the benefits of cardiac resynchronization therapy (CRT) in patients with New York Heart Association (NYHA) Class III/IV heart failure, systolic left ventricular dysfunction, and a wide QRS. However, additional patient groups may also benefit from CRT.

Methodsand Results

We meta-analyzed clinical benefits of CRT in heart failure patients with narrow QRS, atrial fibrillation (AF) and NYHA Class II symptoms. Thirteen trials of 2882 patients contributed to this meta-analysis. In the narrow versus wide QRS group comparison, no difference in benefit was observed for change in left ventricular ejection fraction (standardized mean difference [SMD] 0.30, 95% confidence interval [CI] −0.37 to 0.97) or left ventricular end systolic volume (SMD 0.30, 95% CI −1.14 to 1.74). The benefit was greater in the wide QRS group for the 6-minute walk test (SMD 1.27, 95% CI 0.59 to 1.96) and NYHA class improvement (SMD 1.24, 95% CI 0.72 to 1.75). In the atrial fibrillation (AF) versus sinus rhythm (SR) group comparison, no difference in benefit was observed for change in left ventricular ejection fraction (SMD −0.38, 95% CI −1.28 to 0.53) or NYHA improvement (SMD 0.32, 95% CI −0.77 to 1.40). In the NYHA II versus NYHA III/IV group comparison, no difference in benefit was observed for change in left ventricular end diastolic diameter (SMD 0.05, 95% CI -0.94 to 1.05) or left ventricular end systolic diameter (SMD 0.74, 95% CI −1.98 to 3.46).

Conclusions

Large-scale clinical outcome trials of CRT are warranted in heart failure patients with narrow QRS, AF, and NYHA II, given the similar benefits observed to those with wide QRS, SR, and NYHA III/IV for many parameters.

Section snippets

Methods

Studies were eligible for inclusion in this meta-analysis if they compared the benefits of CRT between patients with (1) narrow QRS and wide QRS, (2) AF and SR, or (3) NYHA Class II and NYHA Class III/IV symptoms. Studies that described the benefits of CRT in patients with narrow QRS, SR, or NYHA II in comparison to similar patients who did not receive CRT were not able to be meta-analyzed because of the paucity of such studies. To compare and pool study results, “narrow QRS” was defined in

Results

Our search for studies, conducted in accordance with the Quality of Reporting of Meta-analyses (QUOROM) statement, is summarized in Figure 1. We identified 227 potentially suitable articles. Of these, 17 met our inclusion criteria. Four of these studies were not included in the analysis, as they did not report end points, which were also reported in at least 2 other studies6, 7, 8 or did not provide all the required data for meta-analysis.⁹ The remaining 13 studies were analyzed.10, 11, 12, 13,

Discussion

The results of this study demonstrate that CRT may potentially have applications beyond the current standard indications of SR, NYHA Class III/IV symptoms, widened QRS, and LVEF <35%.

A similar improvement in NYHA class and LVEF was observed in patients with atrial fibrillation and those in sinus rhythm. In addition, this study demonstrated a similar benefit from CRT in patients with NYHA Class II compared with NYHA Class III/IV symptoms for the end points of left ventricular end-diastolic

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Monitoring of physical activity and heart rate variability in patients with chronic heart failure using cardiac resynchronization devices
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Cardiac resynchronization therapy in patients with a narrow QRS complex

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Cited by (22)

Association of Eligibility for a Sodium-Glucose Cotransporter 2 Inhibitor and Cardiovascular Events in Patients With Atrial Fibrillation
2022, Canadian Journal of Cardiology
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce heart failure (HF) in a broad range of populations, but they have not been studied specifically in patients with atrial fibrillation (AF). We aimed to examine the association between SGLT2i eligibility and cardiovascular events in patients with AF to evaluate the potential utility of SGLT2is for AF management.
We pooled data from 2 randomized controlled trials (RCTs) of patients with AF (RE-LY and ACTIVE-W). Among patients assigned to anticoagulation arms, those meeting the enrollment criteria from at least 1 of the phase 3 SGLT2i RCTs were classified as “SGLT2i eligible” and the remainder as “SGLT2i ineligible.” The primary outcome was the composite of HF hospitalization or cardiovascular death.
A total of 21,484 patients with AF (mean age: 71.2 ± 8.8, 36.1% women, median CHA₂DS₂-VASc Score = 3) were included. The proportion of patients with AF eligible for SGLT2i was 41.2%. SGLT2i-eligible patients had higher rates of cardiovascular death or hospitalization for HF (5.8 vs 3.2 per 100 person-years, P_log-rank < 0.001), cardiovascular death (3.9 vs 1.5 per 100 person-years, P_log-rank < 0.001), and hospitalization for HF (2.5 vs 1.9 per 100 person-years, P_log-rank < 0.001). The age- and sex-adjusted model showed that SGLT2i-eligible patients were at a higher risk of cardiovascular death and hospitalization for HF (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.79-2.17; P < 0.001), cardiovascular death (HR, 2.75; 95% CI, 2.41-3.13; P < 0.001), and hospitalization for HF (HR, 1.41; 95% CI, 1.23-1.62; P < 0.001) than ineligible patients.
Most patients with AF do not currently have indications for SGLT2is but still have substantial risk of cardiovascular events. Future randomized trials should evaluate the efficacy of SGLT2is in patients with AF.
Les inhibiteurs du cotransporteur sodium-glucose de type 2 (iSGLT2) permettent de réduire les symptômes d’insuffisance cardiaque (IC) dans un large éventail de cas, mais leur utilisation n’a pas été étudiée chez les patients atteints de fibrillation auriculaire (FA). Nous avons voulu examiner l’association entre l’admissibilité au traitement par les iSGLT2 et les événements cardiovasculaires chez les patients atteints de FA afin d’évaluer l’utilité potentielle de ces agents dans la prise en charge de la FA.
Nous avons regroupé les données de deux essais contrôlés randomisés (RE-LY et ACTIVE-W) menés auprès de patients atteints de FA. Au sein des groupes sous anticoagulothérapie, les patients répondant aux critères d’inscription d’au moins un des essais contrôlés randomisés de phase III sur les iSGLT2 étaient réputés « admissibles au traitement par les iSGLT2 » et les autres « non admissibles au traitement par les iSGLT2 ». Le critère d’évaluation principal était un critère composite comprenant les hospitalisations pour cause d’IC ou les décès d’origine cardiovasculaire.
Au total, 21 484 patients atteints de FA (âge moyen : 71,2 ± 8,8 ans, 36,1 % de femmes, score CHA₂DS₂-VASc médian = 3) ont été inclus dans notre étude. La proportion de patients atteints de FA admissibles au traitement par les iSGLT2 était de 41,2 %. Les taux de mortalité cardiovasculaire ou d’hospitalisations pour cause d’IC étaient plus élevés chez les patients admissibles au traitement par les iSGLT2 (5,8 vs 3,2 pour 100 années-personnes, p_log-rank < 0,001); décès d’origine cardiovasculaire : 3,9 vs 1,5 pour 100 années-personnes, p_log-rank < 0,001; hospitalisations pour cause d’IC : 2,5 vs 1,9 pour 100 années-personnes, p_log-rank < 0,001. De plus, selon le modèle corrigé en fonction de l’âge et du sexe, les patients admissibles au traitement par les iSGLT2D ont été associés à un risque plus élevé de décès d’origine cardiovasculaire et d’hospitalisations pour cause d’IC (rapport des risques instantanés [RRI] : 1,97; intervalle de confiance [IC] à 95 % : 1,79-2,17; p < 0,001), de décès d’origine cardiovasculaire (RRI : 2,75; IC à 95 % : 2,41-3,13; p < 0,001) et d’hospitalisations pour cause d’IC (RRI : 1,41; IC à 95 % : 1,23-1,62; p < 0,001).
Il n’y a actuellement pas d’indication des iSGLT2 pour la plupart des cas de FA; pourtant, les patients atteints de FA demeurent exposés à un risque substantiel d’événements cardiovasculaires. Des essais randomisés s’imposent pour évaluer l’efficacité des iSGLT2 en présence de FA.
Does permanent atrial fibrillation modify response to cardiac resynchronization therapy in heart failure patients?
2017, Revista Portuguesa de Cardiologia
Citation Excerpt :
Similarly, some authors have shown that CRT in AF patients improves symptoms,14,30 while others suggest that CRT is only effective after AV junction ablation, which was certainly not the case in our patients. In contrast to our results, some previous studies in AF patients demonstrated that, despite similar changes in LVEF, there was less improvement in NYHA functional class.25,26,31 An important issue is the CRT response rate, bearing in mind that definitions of CRT response in the literature differ widely.32
The benefits of cardiac resynchronization therapy (CRT) documented in heart failure (HF) may be influenced by atrial fibrillation (AF). We aimed to compare CRT response in patients in AF and in sinus rhythm (SR).
We prospectively studied 101 HF patients treated by CRT. Rates of clinical, echocardiographic and functional response, baseline NYHA class and variation, left ventricular ejection fraction, volumes and mass, atrial volumes, cardiopulmonary exercise test (CPET) duration (CPET dur), peak oxygen consumption (VO₂max) and ventilatory efficiency (VE/VCO₂ slope) were compared between AF and SR patients, before and at three and six months after implantation of a CRT device.
All patients achieved ≥95% biventricular pacing, and 5.7% underwent atrioventricular junction ablation. Patients were divided into AF (n=35) and SR (n=66) groups; AF patients were older, with larger atrial volumes and lower CPET dur and VO₂max before CRT. The percentages of clinical and echocardiographic responders were similar in the two groups, but there were more functional responders in the AF group (71% vs. 39% in SR patients; p=0.012). In SR patients, left atrial volume and left ventricular mass were significantly reduced (p=0.015 and p=0.021, respectively), whereas in AF patients, CPET dur (p=0.003) and VO₂max (p=0.001; 0.083 age-adjusted) showed larger increases.
Clinical and echocardiographic response rates were similar in SR and AF patients, with a better functional response in AF. Improvement in left ventricular function and volumes occurred in both groups, but left ventricular mass reduction and left atrial reverse remodeling were seen exclusively in SR patients (ClinicalTrials.gov identifier: NCT02413151; FCT code: PTDC/DES/120249/2010).
Os benefícios da terapêutica de ressincronização cardíaca (TRC), documentados na insuficiência cardíaca (IC), poderão ser influenciados pela fibrilhação auricular (FA). Pretendemos avaliar comparativamente efeitos TRC em doentes em FA e em ritmo sinusal (RS).
Foram estudados prospetivamente 101 doentes submetidos a TRC. Percentagens de respondedores clínicos, ecocardiográficos e funcionais, valores basais e variação de classe NYHA, fração de ejeção, volumes e massa ventriculares esquerdos, volumes auriculares, duração da prova de esforço cardiorrespiratória (PECR dur), consumo pico de oxigénio (VO2p) e eficiência ventilatória de esforço (VE/VCO2) foram comparados entre grupos FA e RS, pré-implantação TRC e nos seis meses após implantação.
Os doentes tiveram percentagens de pacing biventricular ≥95%, com 5,7% de ablação auriculoventricular juncional. Definimos grupo FA (n=35) e grupo RS (n=66), tendo os doentes com FA idade superior, maiores volumes auriculares, menores PECR dur e VO2p pré-CRT. Percentagens de respondedores clínicos e ecocardiográficos foram idênticas nos dois grupos, mas de respondedores funcionais foram superiores nos doentes FA (71 versus 39% no grupo RS; p=0,012). Nos doentes RS verificou-se a redução significativa do volume auricular esquerdo e da massa ventricular esquerda (p=0,015 e p=0,021, respetivamente) e nos doentes com FA maior aumento da PECR dur (p=0,003) e VO2p (p=0,001; p=0,083 ajustado para idade).
As respostas clínica e ecocardiográfica à TRC foram semelhantes nos doentes FA e RS, com resposta funcional superior em FA. A melhoria de função e dimensões ventriculares esquerdas foi idêntica nos dois grupos, contudo redução de massa ventricular esquerda e remodelagem inversa auricular esquerda foram exclusivas de doentes RS (ClinicalTrials.gov Identifier: NCT02413151; FCT code: PTDC/DES/120249/2010).
2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy
2014, Revista Espanola de Cardiologia
Comparison of cardiac resynchronization therapy outcomes in patients with New York Heart Association functional class I/II versus III/IV heart failure
2012, Journal of Cardiac Failure
Citation Excerpt :
Finally, although this study was neither blinded nor randomized, the specific data on CV hospitalizations and core lab echos indicate that the results in real-world patients are similar to those reported in pivotal randomized clinical trials. Recent review papers11–13 and large meta-analyses8,14,15 have supported the use of CRT in NYHA functional class I/II HF patients. These data have been predominantly based on 3 large multicenter randomized trials (REVERSE, MADIT-CRT, and RAFT) of CRT-D versus defibrillator, demonstrating significant benefits of CRT in patients with NYHA functional class I/II HF (although RAFT excluded NYHA functional class I).
Several randomized trials have shown that cardiac resynchronization therapy (CRT) benefits New York Heart Association (NYHA) functional class I/II heart failure (HF) patients, but it is unknown if similar outcomes occur in the real-world.
All patients receiving CRT between 2003 and 2008 with ejection fraction (EF) ≤35% and QRS duration ≥120 ms were included. Outcomes assessed were subjective clinical response, echocardiographic response, and survival free of cardiovascular (CV) hospitalization. Baseline demographics in functional class I/II (n = 155) and functional class III/IV (n = 512) were similar, except for differences in age and several comorbidities. Clinical response was similar in both groups. The functional class I/II group had a greater decrease in left ventricular (LV) end-diastolic dimension (P = .031), and trended toward greater improvements in LV end-systolic dimension (P = .056) and EF (P = .059). The functional class I/II group had a better 5-year survival rate (79 vs 54%; P < .0001) and survival free of CV hospitalization (45% vs 26%; P < .0001).
In this real-world clinical scenario, NYHA functional class I/II CRT patients improved clinical status, and LV function and size as good as or better than those in NYHA functional class III/IV patients. These observations provide further support for the use of CRT in patients with mild symptoms of HF.
Heart failure patients selection for cardiac resynchronization therapy
2011, European Journal of Internal Medicine
Citation Excerpt :
Interventricular and intraventricular dyssynchrony are common in heart failure patients, regardless of QRS duration [65]. In a meta-analysis of 5 trials comparing patients with QRS < 120 ms with those with QRS ≥ 120 ms, there was no statistically significant difference in benefit from CRT between the 2 groups for LVEF or LVESV, though a significantly greater benefit with respect to 6 min walking distance and NYHA improvement was found in the wide QRS group [66]. Response to CRT in narrow QRS group was similar to those with wide QRS when asynchrony was defined by septo-lateral delay of ≥ 65 ms [49].
Cardiac resynchronization therapy (CRT) is an established treatment for refractory chronic heart failure (CHF) patients with ventricular dyssynchrony. The patient selection for this therapy remains the basis for response improvement. Various parameters, methods and technology for identification of appropriate patient are under research. The influences of age and gender, disease progress stage such as mild and late stage CHF including right ventricular dysfunction, dyssynchrony and scar identified by imaging techniques like echocardiography, magnetic resonance and nuclear imaging, and atrial fibrillation on CRT benefits were respectively discussed. This review summarizes the current advancement in these areas.
Pacemaker and Atrioventricular Junction Ablation in Patients With Atrial Fibrillation—A Systematic Review of Systematic Review and Meta-Analysis
2021, Frontiers in Cardiovascular Medicine

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: Prof Henry Krum is on the executive committee of the EchoCRT trial, which is sponsored by Biotronik, Inc.

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Review ArticleExtending the Boundaries of Cardiac Resynchronization Therapy: Efficacy in Atrial Fibrillation, New York Heart Association Class II, and Narrow QRS Heart Failure Patients

Abstract

Background

Methodsand Results

Conclusions

Section snippets

Methods

Results

Discussion

Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay

N Engl J Med

Cardiac resynchronization in chronic heart failure

N Engl J Med

Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure

N Engl J Med

The effect of cardiac resynchronization on morbidity and mortality in heart failure

N Engl J Med

Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses

Lancet

Cardiac-resynchronization therapy in heart failure with narrow QRS complexes

N Engl J Med

Cardiac efficiency and oxygen consumption measured with 11C-acetate PET after long-term cardiac resynchronization therapy

J Nucl Med

Monitoring of physical activity and heart rate variability in patients with chronic heart failure using cardiac resynchronization devices

Am J Cardiol

Doeschronic atrial fibrillation affect response rates to cardiac resynchronization therapy?

Heart Rhythm

Long-term effectiveness of cardiac resynchronization therapy in patients with refractory heart failure and “narrow” QRS

J Am Coll Cardiol

Cardiac resynchronization therapy in patients with a narrow QRS complex

J Am Coll Cardiol

Comparison of usefulness of cardiac resynchronization therapy in patients with atrial fibrillation and heart failure versus patients with sinus rhythm and heart failure

Am J Cardiol

Four-year efficacy of cardiac resynchronization therapy on exercise tolerance and disease progression: the importance of performing atrioventricular junction ablation in patients with atrial fibrillation

J Am Coll Cardiol

Three years of cardiac resynchronization therapy: could superior benefits be obtained in patients with heart failure and narrow QRS?

Pacing Clin Electrophysiol

Initial experience with an implantable cardioverter-defibrillator incorporating cardiac resynchronization therapy

J Am Coll Cardiol

Review Article
Extending the Boundaries of Cardiac Resynchronization Therapy: Efficacy in Atrial Fibrillation, New York Heart Association Class II, and Narrow QRS Heart Failure Patients