Prognostic Evaluation of Chagasic and Non-Chagasic Patients Undergoing Pacemaker Implantation and Cardiac Resynchronization in a Tertiary Center. / Prognóstico de Pacientes Chagásicos e não Chagásicos Submetidos a Implante de Marca-passo e Ressincronizador Cardíaco em Centro Terciário.

BACKGROUND: Chagas cardiomyopathy (ChCC) is one of the causes of the implantation of pacemakers (PM) in many patients and has been associated with an adverse prognosis. OBJECTIVES: To compare the prognosis of the chagasic and non-chagasic populations undergoing PM and cardiac resynchronizer implantation. METHODS: Observational, retrospective study, which analyzed a cohort of patients who underwent implantation of these devices, in a tertiary center, from October 2007 to December 2017, comparing the chagasic group with non-chagasic patients. The non-parametric Kaplan-Meier method was used to calculate patient survival. The significance level adopted in the statistical analysis was 5%. The primary outcome was mortality from any cause, while the secondary outcomes were the occurrence of hospitalization and the combination of hospitalization and death. RESULTS: A total of 911 patients were included, of which 23.4% had ChCC. In a Cox analysis adjusted for sex and age, Chagas disease (ChD) was not associated with an increased risk of death (HR: 1.14, CI:95%, 0.86-1.51, p=0.365), hospitalization (HR: 0.79, CI:95%, 0.61-1.04, p=0.09) or combined outcome of death and hospitalization (HR: 0.90, CI:95%, 0.72-1 .12, p=0.49). CONCLUSIONS: ChD was not associated with an increased risk of death, hospitalization, or combined outcome of death and hospitalization, even after adjustment for sex and age. These results contrast with those of previous studies and suggest changes in the quality of care of patients with cardiomyopathy.

FUNDAMENTO: A cardiomiopatia chagásica (CCh) é responsável pelo implante de marca-passo (MP) em muitos pacientes, tendo sido associada a prognóstico adverso. OBJETIVOS: Comparar o prognóstico da população chagásica e não chagásica submetida ao implante de MP e ressincronizador cardíaco. MÉTODOS: Estudo observacional, retrospectivo, que analisou coorte de pacientes submetidos a implante desses dispositivos, em centro terciário, de outubro 2007 a dezembro de 2017, comparando o grupo de pacientes chagásicos com os não-chagásicos. O método não paramétrico de Kaplan-Meier foi utilizado para calcular a sobrevida dos pacientes. O nível de significância adotado na análise estatística foi de 5%. O desfecho primário foi a mortalidade por qualquer causa, enquanto os desfechos secundários foram a ocorrência de internação e o desfecho combinado internação e morte. RESULTADOS: Um total de 911 pacientes foram incluídos, sendo que 23,4% apresentavam CCh. Em análise de Cox ajustada por sexo e idade, a doença de Chagas (dCh) não esteve associada ao risco aumentado de morte (HR: 1,14, IC:95%, 0,86-1,51, p=0,365), internação (HR: 0,79, IC:95%, 0,61-1,04, p=0,09) ou desfecho combinado morte e internação (HR: 0,90, IC:95%, 0,72-1,12, p=0,49). CONCLUSÕES: A dCh não se associou ao aumento do risco de morte, internação, ou desfecho combinado morte e internação, mesmo após ajuste para sexo e idade. Tais resultados se contrapõem aos de estudos prévios e sugerem modificação da qualidade do cuidado ao paciente cardiopata.

Outcomes of Cardiac Resynchronization Therapy by New York Heart Association Class: A Patient-Level Meta-Analysis.

BACKGROUND: Data on the benefits of cardiac resynchronization therapy (CRT) in patients with severe heart failure symptoms are limited. We investigated the relative effects of CRT in patients with ambulatory New York Heart Association (NYHA) IV versus III functional class at the time of device implantation. METHODS AND RESULTS: In this meta-analysis, we pooled patient-level data from the MIRACLE (Multicenter InSync Randomized Clinical Evaluation), MIRACLE-ICD (Multicenter InSync Implantable Cardioversion Defibrillation Randomized Clinical Evaluation), and COMPANION (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure) trials. Outcomes evaluated were time to the composite end point of the first heart failure hospitalization or all-cause mortality, and time to all-cause mortality alone. The association between CRT and outcomes was evaluated using a Bayesian hierarchical Weibull survival regression model. We assessed if this association differed between NYHA III and IV groups by adding an interaction term between CRT and NYHA class as a random effect. A sensitivity analysis was performed by including data from RAFT (Resynchronization-Defibrillation for Ambulatory Heart Failure). Our pooled analysis included 2309 patients. Overall, CRT was associated with a longer time to heart failure hospitalization or all-cause mortality (adjusted hazard ratio [aHR], 0.79 [95% credible interval [CI], 0.64-0.99]; posterior probability or P=0.044), with a similar association with time to all-cause mortality (aHR, 0.78 [95% CI, 0.59-1.03]; P=0.083). Associations of CRT with outcomes were not significantly different for those in NYHA III and IV classes (ratio of aHR, 0.72 [95% CI, 0.30-1.27]; P=0.23 for heart failure hospitalization/mortality; ratio of aHR, 0.70 [95% CI, 0.35-1.34]; P=0.27 for all-cause mortality alone). The sensitivity analysis, including RAFT data, did not show a significant relative CRT benefit between NYHA III and IV classes. CONCLUSIONS: Overall, there was no significant difference in the association of CRT with either outcome for patients in NYHA functional class III compared with functional class IV.

Left bundle branch area pacing in heart failure: A systematic review and meta-analysis with meta-regression.

INTRODUCTION: Left bundle branch area pacing is an alternative to biventricular pacing. In this study, we aim to summarize the available evidence on the feasibility, efficacy, and safety of left bundle branch block area pacing (LBBAP). OBJECTIVES: The study summarizes the available evidence on the feasibility, efficacy, and safety of left bundle branch block area pacing (LBBAP). BACKGROUND: Cardiac resynchronization therapy (CRT) reduced mortality and hospitalizations in heart failure (HF) patients with a left ventricular ejection fraction (LVEF) ≤ 35% and concomitant LBBB. Recently LBBAP has been studied as a more physiological alternative to achieve CRT. METHOD: A search of PubMed, EMBASE, and Cochrane databases were performed to identify studies examining the role of LBBAP for CRT in heart failure. Comprehensive meta-analysis version 4 was used for meta-regression to examine variables that contribute to data heterogeneity. RESULT: Eighteen studies, 17 observational and one randomized controlled trial (RCT) were examined. A total of 3906 HF patients who underwent CRT (2036 LBBAP vs. 1870 biventricular pacing [BVP]) were included. LBBAP was performed successfully in 90.4% of patients. Compared to baseline, LBBAP was associated with a reduction in QRS duration (MD: -47.23 ms 95% confidence interval [CI]: -53.45, -41.01), an increase in LVEF (MD: 15.22%, 95% CI: 13.5, 16.94), and a reduction in NYHA class (MD: -1.23, 95% CI: -1.41, -1.05). Compared to BVP, LBBAP was associated with a significant reduction in QRS duration (MD: -20.69 ms, 95% CI: -25.49, -15.88) and improvement in LVEF (MD: 4.78%, 95% CI: 3.30, 6.10). Furthermore, LBBAP was associated with a significant reduction in HF hospitalization (odds ratio [OR]: 0.44, 95% CI: 0.34, 0.56) and all-cause mortality (OR: 0.67, 95% CI: 0.52, 0.86) compared to BVP. CONCLUSION: LBBAP was associated with improved ventricular electrical synchrony compared to BVP, as well as better echocardiographic and clinical outcomes.

Myocardial Fibrosis Predicts Ventricular Arrhythmias and Sudden Death After Cardiac Electronic Device Implantation.

BACKGROUND: Increasing evidence supports a link between myocardial fibrosis (MF) and ventricular arrhythmias. OBJECTIVES: The purpose of this study was to determine whether presence of myocardial fibrosis on visual assessment (MFVA) and gray zone fibrosis (GZF) mass predicts sudden cardiac death (SCD) and ventricular fibrillation/sustained ventricular tachycardia after cardiac implantable electronic device (CIED) implantation. METHODS: In this prospective study, total fibrosis and GZF mass, quantified using cardiovascular magnetic resonance, was assessed in relation to the primary endpoint of SCD and the secondary, arrhythmic endpoint of SCD or ventricular arrhythmias after CIED implantation. RESULTS: Among 700 patients (age 68.0 ± 12.0 years), 27 (3.85%) experienced a SCD and 121 (17.3%) met the arrhythmic endpoint over median 6.93 years (IQR: 5.82-9.32 years). MFVA predicted SCD (HR: 26.3; 95% CI: 3.7-3,337; negative predictive value: 100%). In competing risk analyses, MFVA also predicted the arrhythmic endpoint (subdistribution HR: 19.9; 95% CI: 6.4-61.9; negative predictive value: 98.6%). Compared with no MFVA, a GZF mass measured with the 5SD method (GZF5SD) >17 g was associated with highest risk of SCD (HR: 44.6; 95% CI: 6.12-5,685) and the arrhythmic endpoint (subdistribution HR: 30.3; 95% CI: 9.6-95.8). Adding GZF5SD mass to MFVA led to reclassification of 39% for SCD and 50.2% for the arrhythmic endpoint. In contrast, LVEF did not predict either endpoint. CONCLUSIONS: In CIED recipients, MFVA excluded patients at risk of SCD and virtually excluded ventricular arrhythmias. Quantified GZF5SD mass added predictive value in relation to SCD and the arrhythmic endpoint.

In permanent AF with narrow QRS, AV junction ablation + CRT vs. rate-control drug therapy reduced mortality.

SOURCE CITATION: Brignole M, Pentimalli F, Palmisano P, et al. AV junction ablation and cardiac resynchronization for patients with permanent atrial fibrillation and narrow QRS: the APAF-CRT mortality trial. Eur Heart J. 2021;42:4731-9. 34453840.

Temporal trends in outcome and patient characteristics in dilated cardiomyopathy, data from the Swedish Heart Failure Registry 2003-2015.

BACKGROUND: Temporal trends in clinical composition and outcome in dilated cardiomyopathy (DCM) are largely unknown, despite considerable advances in heart failure management. We set out to study clinical characteristics and prognosis over time in DCM in Sweden during 2003-2015. METHODS: DCM patients (n = 7873) from the Swedish Heart Failure Registry were divided into three calendar periods of inclusion, 2003-2007 (Period 1, n = 2029), 2008-2011 (Period 2, n = 3363), 2012-2015 (Period 3, n = 2481). The primary outcome was the composite of all-cause death, transplantation and hospitalization during 1 year after inclusion into the registry. RESULTS: Over the three calendar periods patients were older (p = 0.022), the proportion of females increased (mean 22.5%, 26.4%, 27.6%, p = 0.0001), left ventricular ejection fraction was higher (p = 0.0014), and symptoms by New York Heart Association less severe (p < 0.0001). Device (implantable cardioverter defibrillator and/or cardiac resynchronization) therapy increased by 30% over time (mean 11.6%, 12.3%, 15.1%, p < 0.0001). The event rates for mortality, and hospitalization were consistently decreasing over calendar periods (p < 0.0001 for all), whereas transplantation rate was stable. More advanced physical symptoms correlated with an increased risk of a composite outcome over time (p = 0.0043). CONCLUSIONS: From 2003 until 2015, we observed declining mortality and hospitalizations in DCM, paralleled by a continuous change in both demographic profile and therapy in the DCM population in Sweden, towards a less affected phenotype.

Comparative efficacy of image-guided techniques in cardiac resynchronization therapy: a meta-analysis.

BACKGROUND: Several studies have illustrated the use of echocardiography, magnetic resonance imaging, and nuclear imaging to optimize left ventricular (LV) lead placement to enhance the response of cardiac resynchronization therapy (CRT) in heart failure patients. We aimed to conduct a meta-analysis to determine the incremental efficacy of image-guided CRT over standard CRT. METHODS: We searched PubMed, Cochrane library, and EMBASE to identify relevant studies. The outcome measures of cardiac function and clinical outcomes were CRT response, concordance of the LV lead to the latest sites of contraction (concordance of LV), heart failure (HF) hospitalization, mortality rates, changes of left ventricular ejection fraction (LVEF), and left ventricular end-systolic volume (LVESV). RESULTS: The study population comprised 1075 patients from eight studies. 544 patients underwent image-guided CRT implantation and 531 underwent routine implantation without imaging guidance. The image-guided group had a significantly higher CRT response and more on-target LV lead placement than the control group (RR, 1.33 [95% CI, 1.21 to 1.47]; p < 0.01 and RR, 1.39 [95% CI, 1.01 to 1.92]; p < 0.05, respectively). The reduction of LVESV in the image-guided group was significantly greater than that in the control group (weighted mean difference, - 12.46 [95% CI, - 18.89 to - 6.03]; p < 0.01). The improvement in LVEF was significantly higher in the image-guided group (weighted mean difference, 3.25 [95% CI, 1.80 to 4.70]; p < 0.01). Pooled data demonstrated no significant difference in HF hospitalization and mortality rates between two groups (RR, 0.89 [95% CI, 0.16 to 5.08]; p = 0.90, RR, 0.69 [95% CI, 0.37 to 1.29]; p = 0.24, respectively). CONCLUSIONS: This meta-analysis indicates that image-guided CRT is correlated with improved CRT volumetric response and cardiac function in heart failure patients but not with lower hospitalization or mortality rate.

Right ventricular lead location and outcomes among patients with cardiac resynchronization therapy: A meta-analysis.

BACKGROUND: Cardiac resynchronization therapy (CRT) has been demonstrated to improve heart failure (HF) symptoms, reverse LV remodeling, and reduce mortality and HF hospitalization (HFH) in patients with a reduced left ventricular (LV) ejection fraction (LVEF). Prior studies examining outcomes based on right ventricular (RV) lead position among CRT patients have provided mixed results. We performed a systematic review and meta-analysis of randomized controlled trials and prospective observational studies comparing RV apical (RVA) and non-apical (RVNA) lead position in CRT. METHODS: Our meta-analysis was constructed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews and meta-analyses. We searched EMBASE and MEDLINE. Eligible studies reported on at least one of the following outcomes of interest: all-cause mortality, the composite endpoint of death and first HFH hospitalization, change in LVEF, New York Heart Association (NYHA) class improvement, and change in LV end systolic volume (LVESV). We performed meta-analysis summaries using a DerSimonian-Laird random-effects model and conservatively used the Knapp-Hartung approach to adjust the standard errors of the estimated model coefficients. RESULTS: We included nine studies representing a total of 1832 patients. Of those, 1318 (72%) patients had RVA lead placement and 514 (28%) had RVNA lead placement. The mean age of patients was 65.5 ± 4.4 years, and they were predominantly men (69%-97%). There was no statistically significant difference in all-cause mortality by RVA vs. RVNA (OR = 0.77, 95% CI 0.32-1.89; I2 = 16.7%, p = 0.31), or in the combined endpoint of all-cause mortality and first HFH (OR 0.88, 95% CI 0.62-1.25; I2 = 0%, p = 0.84). Also, there was no difference between RVA and RVNA for NYHA class improvement (OR = 1.03, 95% CI 0.9-1.17; I2 = 0%, p = 0.99), change in LVEF (mean difference (MD) = 1.33, 95% CI -1.45 to 4.10; I2 = 47%; p = 0.093), and change in LVESV (MD = -1.11, 95% CI -3.34 to 1.12; I2 = 0%; p = 0.92). CONCLUSION: This meta-analysis shows that in CRT pacing, RV lead position does not appear to be associated with clinical outcomes or LV reverse remodeling. Further studies should focus on the relationship of RV lead vis-à-vis LV lead location, and its clinical importance.

Clinical and prognostic implications of phenomapping in patients with heart failure receiving cardiac resynchronization therapy.

BACKGROUND: Despite having an indication for cardiac resynchronization therapy according to current guidelines, patients with heart failure with reduced ejection fraction who receive cardiac resynchronization therapy do not consistently derive benefit from it. AIM: To determine whether unsupervised clustering analysis (phenomapping) can identify distinct phenogroups of patients with differential outcomes among cardiac resynchronization therapy recipients from routine clinical practice. METHODS: We used unsupervised hierarchical cluster analysis of phenotypic data after data reduction (55 clinical, biological and echocardiographic variables) to define new phenogroups among 328 patients with heart failure with reduced ejection fraction from routine clinical practice enrolled before cardiac resynchronization therapy. Clinical outcomes and cardiac resynchronization therapy response rate were studied according to phenogroups. RESULTS: Although all patients met the recommended criteria for cardiac resynchronization therapy implantation, phenomapping analysis classified study participants into four phenogroups that differed distinctively in clinical, biological, electrocardiographic and echocardiographic characteristics and outcomes. Patients from phenogroups 1 and 2 had the most improved outcome in terms of mortality, associated with cardiac resynchronization therapy response rates of 81% and 78%, respectively. In contrast, patients from phenogroups 3 and 4 had cardiac resynchronization therapy response rates of 39% and 59%, respectively, and the worst outcome, with a considerably increased risk of mortality compared with patients from phenogroup 1 (hazard ratio 3.23, 95% confidence interval 1.9-5.5 and hazard ratio 2.49, 95% confidence interval 1.38-4.50, respectively). CONCLUSIONS: Among patients with heart failure with reduced ejection fraction with an indication for cardiac resynchronization therapy from routine clinical practice, phenomapping identifies subgroups of patients with differential clinical, biological and echocardiographic features strongly linked to divergent outcomes and responses to cardiac resynchronization therapy. This approach may help to identify patients who will derive most benefit from cardiac resynchronization therapy in "individualized" clinical practice.

Validation of Three European Risk Scores to Predict Long-Term Outcomes for Patients Receiving Cardiac Resynchronization Therapy in an Asian Population.

To validate externally and recalibrate three European risk scores for all-cause mortality and transplantation in patients receiving cardiac resynchronization therapy (CRT) in an Asian population. Data were collected at our institution between January 2010 and December 2017. The primary endpoints were all-cause mortality and heart transplantation. Of the 506 patients who were followed for 2 years, 104 reached the primary endpoint. The Kaplan-Meier event-free survival analysis, stratified according to the three scores, yielded significant results (log-rank test, all P < 0.05), with a good fit between the predicted and observed event rates (Hosmer-Lemeshow goodness-of-fit test, all P > 0.05). The ScREEN score yielded the best discriminatory power for the primary endpoints compared with the VALID-CRT and EAARN scores. ScREEN was the best predictor of all-cause mortality and heart transplantation. Risk scores based on different populations should be selected cautiously. Graphical Abstract.

Transcatheter Mitral Valve Repair in Patients With and Without Cardiac Resynchronization Therapy: The COAPT Trial.

BACKGROUND: In the COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation), treatment of heart failure (HF) patients with moderate-severe or severe secondary mitral regurgitation with transcatheter mitral valve repair (TMVr) using the MitraClip plus guideline-directed medical therapy (GDMT) reduced 2-year rates of HF hospitalization and all-cause mortality compared with GDMT alone. Whether the benefits of the MitraClip extend to patients with previously implanted cardiac resynchronization therapy (CRT) is unknown. We sought to examine the effect of prior CRT in patients enrolled in COAPT. METHODS: Patients (N=614) with moderate-severe or severe secondary mitral regurgitation who remained symptomatic despite maximally tolerated doses of GDMT were randomized 1:1 to the MitraClip (TMVr arm) versus GDMT only (control arm). Outcomes were assessed according to prior CRT use. RESULTS: Among 614 patients, 224 (36.5%) had prior CRT (115 and 109 randomized to TMVr and control, respectively) and 390 (63.5%) had no CRT (187 and 203 randomized to TMVr and control, respectively). Patients with CRT had similar 2-year rates of the composite of death or HF hospitalization compared with those without CRT (57.6% versus 55%, P=0.32). Death or HF hospitalization at 2 years was lower with TMVr versus control treatment in patients with prior CRT (48.6% versus 67.2%, hazard ratio, 0.60 [95% CI, 0.42-0.86]) and without CRT (42.5% versus 66.9%, hazard ratio, 0.52 [95% CI, 0.39-0.69]; adjusted Pinteraction=0.23). The effects of TMVr with the MitraClip on reducing the 2-year rates of all-cause death (adjusted Pinteraction=0.14) and HF hospitalization (adjusted Pinteraction=0.82) were also consistent in patients with and without CRT as were improvements in quality-of-life and exercise capacity. CONCLUSIONS: In the COAPT trial, TMVr with the MitraClip improved the 2-year prognosis of patients with HF and moderate-severe or severe secondary mitral regurgitation who remained symptomatic despite maximally tolerated GDMT, regardless of prior CRT implantation. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01626079.

Cardiac resynchronization therapy and its effects in patients with type 2 DIAbetes mellitus OPTimized in automatic vs. echo guided approach. Data from the DIA-OPTA investigators.

OBJECTIVES: To evaluate the effects of cardiac resynchronization therapy (CRTd) in patients with type 2 diabetes mellitus (T2DM) optimized via automatic vs. echocardiography-guided approach. BACKGROUND: The suboptimal atrio-ventricular (AV) and inter-ventricular (VV) delays optimization reduces CRTd response. Therefore, we hypothesized that automatic CRTd optimization might improve clinical outcomes in T2DM patients. METHODS: We designed a prospective, multicenter study to recruit, from October 2016 to June 2019, 191 consecutive failing heart patients with T2DM, and candidate to receive a CRTd. Study outcomes were CRTd responders rate, hospitalizations for heart failure (HF) worsening, cardiac deaths and all cause of deaths in T2DM patients treated with CRTd and randomly optimized via automatic (n 93) vs. echocardiography-guided (n 98) approach at 12 months of follow-up. RESULTS: We had a significant difference in the rate of CRTd responders (68 (73.1%) vs. 58 (59.2%), p 0.038), and hospitalizations for HF worsening (12 (16.1%) vs. 22 (22.4%), p 0.030) in automatic vs. echocardiography-guided group of patients. At multivariate Cox regression analysis, the automatic guided approach (3.636 [1.271-10.399], CI 95%, p 0.016) and baseline highest values of atrium pressure (automatic SonR values, 2.863 [1.537-6.231], CI 95%, p 0.006) predicted rate of CRTd responders. In automatic group, we had significant difference in SonR values comparing the rate of CRTd responders vs. non responders (1.24 ± 0.72 g vs. 0.58 ± 0.46 g (follow-up), p 0.001), the rate of hospitalizations for HF worsening events (0.48 ± 0.29 g vs. 1.18 ± 0.43 g, p 0.001), and the rate of cardiac deaths ( 1.13 ± 0.72 g vs. 0.65 ± 0.69 g, p 0.047). CONCLUSIONS: Automatic optimization increased CRTd responders rate, and reduced hospitalizations for HF worsening. Intriguingly, automatic CRTd and highest baseline values of SonR could be predictive of CRTd responders. Notably, there was a significant difference in SonR values for CRTd responders vs. non responders, and about hospitalizations for HF worsening and cardiac deaths. Clinical trial ClinicalTrials.gov Identifier NCT04547244.

Left Ventricular Enlargement, Cardiac Resynchronization Therapy Efficacy, and Impact of MultiPoint Pacing.

BACKGROUND: Left ventricular (LV) epicardial pacing results in slowly propagating paced wavefronts. We postulated that this effect might limit cardiac resynchronization therapy efficacy in patients with LV enlargement using conventional biventricular pacing with single-site LV pacing, but be mitigated by LV stimulation from 2 widely spaced sites using MultiPoint pacing with wide anatomic separation (MPP-AS: ≥30 mm). We tested this hypothesis in the multicenter randomized MPP investigational device exemption trial. METHODS: Following implant, quadripolar biventricular single-site pacing was activated in all patients (n=506). From 3 to 9 months postimplant, among patients with available baseline LV end-diastolic volume (LVEDV) measures, 188 received biventricular single-site pacing and 43 received MPP-AS. Patients were dichotomized by median baseline LVEDV indexed to height (LVEDVIMedian). Outcomes were measured by the clinical composite score (primary efficacy end point), quality of life, LV structural remodeling (↑EF >5% and ↓ESV 10%) and heart failure event/cardiovascular death. RESULTS: LVEDVIMedian was 1.1 mL/cm. Baseline characteristics differed in patients with LVEDVI>Median versus LVEDVI≤Median. Among patients with LVEDVI>Median, biventricular single-site pacing was less efficacious compared to patients with LVEDVI≤Median (clinical composite score, 65% versus 79%). In contrast, MPP-AS programming generated greater clinical composite score response (92% versus 65%, P=0.023) and improved quality of life (-31.0±29.7 versus -15.7±22.1, P=0.038) versus biventricular single-site pacing in patients with LVEDVI>Median. Reverse remodeling trended better with MPP-AS programming. In patients with LVEDVI>Median, heart failure event rate increased following the 3-month randomization point with biventricular single-site pacing (0.0150±0.1725 in LVEDVI>Median versus -0.0190±0.0808 in LVEDVI ≤Median, P=0.012), but no heart failure event occurred in patients with MPP-AS programming between 3 and 9 months in LVEDVI>Median. All measured outcomes did not differ in patients receiving MPP-AS and biventricular single-site pacing with LVEDVI≤Median. CONCLUSIONS: Conventional biventricular single-site pacing, even with a quadripolar lead, has reduced efficacy in patients with LV enlargement. However, the greatest response rate in patients with larger hearts was observed when programmed to MPP-AS pacing.

Outcomes of Cardiac Resynchronization Therapy in Patients with Hypothyroidism and Heart Failure.

BACKGROUND: Hypothyroidism is known to be associated with adverse clinical outcomes in heart failure. The association between hypothyroidism and cardiac resynchronization therapy outcomes in patients with severe heart failure is not clear. METHODS: The study included 1316 patients who received cardiac resynchronization therapy between 2002 and 2015. Baseline demographics and cardiac resynchronization therapy outcomes, including left ventricular ejection fraction, New York Heart Association class, appropriate implantable cardioverter-defibrillator therapy, and all-cause mortality, were collected from the electronic health record. RESULTS: Of the study cohort, 350 patients (26.6%) were classified as the hypothyroidism group. The median duration of follow-up was 3.6 years (interquartile range, 1.7-6.2 years). Hypothyroidism was not associated with a higher risk of all-cause mortality in patients receiving CRT for heart failure. The risk of appropriate implantable cardioverter-defibrillator therapy significantly increased in association with increased baseline thyroid-stimulating hormone level in the entire cohort (hazard ratio, 1.23 per 5mIU/L increase; 95% CI, 1.01-1.5; P = 0.04) as well as in the hypothyroid group (hazard ratio, 1.44 per 5mIU/L increase; 95% CI, 1.13-1.84; P = 0.004). CONCLUSIONS: CRT improves cardiac function in hypothyroid patients. The ventricular arrhythmic events requiring ICD therapies are associated with baseline TSH level, which might be considered as an important biomarker to stratify the risk of sudden death for patients with heart failure and hypothyroidism.

Machine Learning of 12-Lead QRS Waveforms to Identify Cardiac Resynchronization Therapy Patients With Differential Outcomes.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves heart failure outcomes but has significant nonresponse rates, highlighting limitations in ECG selection criteria: QRS duration (QRSd) ≥150 ms and subjective labeling of left bundle branch block (LBBB). We explored unsupervised machine learning of ECG waveforms to identify CRT subgroups that may differentiate outcomes beyond QRSd and LBBB. METHODS: We retrospectively analyzed 946 CRT patients with conduction delay. Principal component analysis (PCA) dimensionality reduction obtained a 2-dimensional representation of preCRT 12-lead QRS waveforms. k-means clustering of the 2-dimensional PCA representation of 12-lead QRS waveforms identified 2 patient subgroups (QRS PCA groups). Vectorcardiographic QRS area was also calculated. We examined following 2 primary outcomes: (1) composite end point of death, left ventricular assist device, or heart transplant, and (2) degree of echocardiographic left ventricular ejection fraction (LVEF) change after CRT. RESULTS: Compared with QRS PCA Group 2 (n=425), Group 1 (n=521) had lower risk for reaching the composite end point (HR, 0.44 [95% CI, 0.38-0.53]; P<0.001) and experienced greater mean LVEF improvement (11.1±11.7% versus 4.8±9.7%; P<0.001), even among patients with LBBB with QRSd ≥150 ms (HR, 0.42 [95% CI, 0.30-0.57]; P<0.001; mean LVEF change 12.5±11.8% versus 7.3±8.1%; P=0.001). QRS area also stratified outcomes but had significant differences from QRS PCA groups. A stratification scheme combining QRS area and QRS PCA group identified patients with LBBB with similar outcomes to non-LBBB patients (HR, 1.32 [95% CI, 0.93-1.62]; difference in mean LVEF change: 0.8% [95% CI, -2.1% to 3.7%]). The stratification scheme also identified patients with LBBB with QRSd <150 ms with comparable outcomes to patients with LBBB with QRSd ≥150 ms (HR, 0.93 [95% CI, 0.67-1.29]; difference in mean LVEF change: -0.2% [95% CI, -2.7% to 3.0%]). CONCLUSIONS: Unsupervised machine learning of ECG waveforms identified CRT subgroups with relevance beyond LBBB and QRSd. This method may assist in objective classification of bundle branch block morphology in CRT.

Reappraisal on pharmacological and mechanical treatments of heart failure.

Heart failure (HF) is a highly frequent disorder with considerable morbidity, hospitalization, and mortality; thus, it invariably places pressure on clinical and public health systems in the modern world. There have been notable advances in the definition, diagnosis, and treatment of HF, and newly developed agents and devices have been widely adopted in clinical practice. Here, this review first summarizes the current emerging therapeutic agents, including pharmacotherapy, device-based therapy, and the treatment of some common comorbidities, to improve the prognosis of HF patients. Then, we discuss and point out the commonalities and areas for improvement in current clinical studies of HF. Finally, we highlight the gaps in HF research. We are looking forward to a bright future with reduced morbidity and mortality from HF.

The association of mechanical dyssynchrony and resynchronization therapy with survival in heart failure with a wide QRS complex: a two-world study.

Setting up a randomized trial to assess the association of mechanical dyssynchrony (MD) and the success of cardiac resynchronization therapy (CRT) in heart failure with a wide QRS complex is ethically challenging. We therefore investigated this association in a retrospective cohort study observing different treatment strategies which were chosen based on the availability of health care resources. The survival of 500 patients from six Western European centers treated with CRT was compared to their 137 Eastern European counterparts not treated with CRT, with regard to the presence of MD. MD was visually assessed and was defined as the presence of apical rocking and/or septal flash. Patients were followed for a mean of 26 ± 8 months for the occurrence of death of any cause. As compared with medical therapy alone, CRT was associated with a more favorable survival (hazard ratio (HR), 0.53; 95% confidence interval (CI) 0.35-0.79; P = 0.002). Patients with MD treated by CRT had better survival than patients belonging to all other groups-they showed 72%, 66% and 56% reduction in all-cause mortality, respectively, compared to patients with MD not treated by CRT (HR 0.28; 95% CI 0.17-0.44), patients without MD treated by CRT (HR 0.34; 95% CI 0.22-0.52) and patients without MD not treated by CRT (HR 0.44; 95% CI 0.25-0.76). Patients with wide QRS complex who are treated with CRT have a significantly better survival when MD is present.