Estimated glomerular filtration rate slope and risk of primary and secondary major adverse cardiovascular events and heart failure hospitalization in people with type 2 diabetes: An analysis of the EXSCEL trial.

AIM: The decline in estimated glomerular filtration rate (eGFR), a significant predictor of cardiovascular disease (CVD), occurs heterogeneously in people with diabetes because of various risk factors. We investigated the role of eGFR decline in predicting CVD events in people with type 2 diabetes in both primary and secondary CVD prevention settings. MATERIALS AND METHODS: Bayesian joint modelling of repeated measures of eGFR and time to CVD event was applied to the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial to examine the association between the eGFR slope and the incidence of major adverse CV event/hospitalization for heart failure (MACE/hHF) (non-fatal myocardial infarction, non-fatal stroke, CV death, or hospitalization for heart failure). The analysis was adjusted for age, sex, smoking, systolic blood pressure, baseline eGFR, antihypertensive and lipid-lowering medication, diabetes duration, atrial fibrillation, high-density cholesterol, total cholesterol, HbA1c and treatment allocation (once-weekly exenatide or placebo). RESULTS: Data from 11 101 trial participants with (n = 7942) and without (n = 3159) previous history of CVD were analysed. The mean ± SD eGFR slope per year in participants without and with previous CVD was -0.68 ± 1.67 and -1.03 ± 2.13 mL/min/1.73 m2, respectively. The 5-year MACE/hHF incidences were 7.5% (95% CI 6.2, 8.8) and 20% (95% CI 19, 22), respectively. The 1-SD decrease in the eGFR slope was associated with increased MACE/hHF risks of 48% (HR 1.48, 95% CI 1.12, 1.98, p = 0.007) and 33% (HR 1.33, 95% CI 1.18,1.51, p < 0.001) in participants without and with previous CVD, respectively. CONCLUSIONS: eGFR trajectories over time significantly predict incident MACE/hHF events in people with type 2 diabetes with and without existing CVD, with a higher hazard ratio for MACE/hHF in the latter group.

Predicting worsening heart failure hospitalizations in patients with implantable cardioverter defibrillators: is it all about alerts? A pooled analysis of nine trials.

AIMS: To predict worsening heart failure hospitalizations (WHFHs) in patients with implantable defibrillators and remote monitoring, the HeartInsight algorithm (Biotronik, Berlin, Germany) calculates a heart failure (HF) score combining seven physiologic parameters: 24 h heart rate (HR), nocturnal HR, HR variability, atrial tachyarrhythmia, ventricular extrasystoles, patient activity, and thoracic impedance. We compared temporal trends of the HF score and its components 12 weeks before a WHFH with 12-week trends in patients without WHFH, to assess whether trends indicate deteriorating HF regardless of alert status. METHODS AND RESULTS: Data from nine clinical trials were pooled, including 2050 patients with a defibrillator capable of atrial sensing, ejection fraction ≤ 35%, NYHA class II/III, no long-standing atrial fibrillation, and 369 WHFH from 259 patients. The mean HF score was higher in the WHFH group than in the no WHFH group (42.3 ± 26.1 vs. 30.7 ± 20.6, P < 0.001) already at the beginning of 12 weeks. The mean HF score further increased to 51.6 ± 26.8 until WHFH (+22% vs. no WHFH group, P = 0.003). As compared to the no WHFH group, the algorithm components either were already higher 12 weeks before WHFH (24 h HR, HR variability, thoracic impedance) or significantly increased until WHFH (nocturnal HR, atrial tachyarrhythmia, ventricular extrasystoles, patient activity). CONCLUSION: The HF score was significantly higher at, and further increased during 12 weeks before WHFH, as compared to the no WHFH group, with seven components showing different behaviour and contribution. Temporal trends of HF score may serve as a quantitative estimate of HF condition and evolution prior to WHFH.

Association between BMI and Efficacy of SGLT2 Inhibitors in Patients with Heart Failure or at Risk of Heart Failure: A Meta-Analysis Based on Randomized Controlled Trials.

INTRODUCTION: This meta-analysis aimed to investigate the effect of SGLT2 inhibitors on the prognosis of patients with heart failure (HF) or at risk of HF across different body mass index (BMI). METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Library for all randomized controlled trials comparing SGLT2 inhibitors with placebo in patients with HF or at risk of HF and extracted relevant data up to April 2023 for meta-analysis. RESULTS: A total of 29,500 patients were enrolled in the selected five studies. The results showed that patients treated with SGLT2 inhibitors had lower HF hospitalization (HHF) or cardiovascular (CV) mortality compared to those taking placebo (hazard ratio [HR] = 0.73, p < 0.001). Patients taking SGLT2 inhibitors also had a lower all-cause mortality rate than those taking placebo (HR = 0.85, p = 0.017). In BMI subgroup analysis, the HHF rate in the experimental group was lower than that in the control group at BMI ≤24.9 kg/m2, 25.0-29.9 kg/m2, and ≥30.0 kg/m2. There was no significant difference in CV mortality between the two groups at BMI ≤24.9 kg/m2 (HR = 0.91, p = 0.331) and 25.0-29.9 kg/m2 (HR = 0.92, p = 0.307). However, when the BMI was ≥30.0 kg/m2, CV mortality with SGLT2 inhibitors was lower than in the control group (HR = 0.79, p = 0.002). When patients had a BMI ≤24.9 kg/m2 (HR = 0.85, p = 0.033) and 25.0-29.9 kg/m2 (HR = 0.83, p = 0.046), the all-cause mortality was lower in the experimental group than in the control group. However, there was no significant difference between the 2 groups in patients with a BMI ≥30.0 kg/m2 (HR = 0.87, p = 0.094). CONCLUSION: SGLT2 inhibitors improve the prognosis in patients with HF or at risk of HF. This effect is affected by BMI.

Mortality and Heart Failure Hospitalization Among Young Adults With and Without Cardiogenic Shock After Acute Myocardial Infarction.

OBJECTIVES: To investigate risk factors and outcomes of cardiogenic shock complicating acute myocardial infarction (AMI-CS) in young patients with AMI. BACKGROUND: AMI-CS is associated with high morbidity and mortality rates. Data regarding AMI-CS in younger individuals are limited. METHODS AND RESULTS: Consecutive patients with type 1 AMI aged 18-50 years admitted to 2 large tertiary-care academic centers were included, and they were adjudicated as having cardiogenic shock (CS) by physician review of electronic medical records using the Society for Cardiovascular Angiography and Interventions CS classification system. Outcomes included all-cause mortality (ACM), cardiovascular mortality (CVM) and 1-year hospitalization for heart failure (HHF). In addition to using the full population, matching was also used to define a comparator group in the non-CS cohort. Among 2097 patients (mean age 44 ± 5.1 years, 74% white, 19% female), AMI-CS was present in 148 (7%). Independent risk factors of AMI-CS included ST-segment elevation myocardial infarction, left main disease, out-of-hospital cardiac arrest, female sex, peripheral vascular disease, and diabetes. Over median follow-up of 11.2 years, young patients with AMI-CS had a significantly higher risk of ACM (adjusted HR 2.84, 95% CI 1.68-4.81; P < 0.001), CVM (adjusted HR 4.01, 95% CI 2.17-7.71; P < 0.001), and 1-year HHF (adjusted HR 5.99, 95% CI 2.04-17.61; P = 0.001) compared with matched non-AMI-CS patients. Over the course of the study, there was an increase in the incidence of AMI-CS among young patients with MI as well as rising mortality rates for patients with both AMI-CS and non-AMI-CS. CONCLUSIONS: Of young patients with AMI, 7% developed AMI-CS, which was associated with a significantly elevated risk of mortality and HHF.

Fewer Worsening Heart Failure Events With HeartLogic on top of Standard Care: a Propensity-Matched Cohort Analysis.

BACKGROUND: The implantable cardiac defibrillator-based HeartLogic algorithm aims to detect impending fluid retention in patients with heart failure (HF). Studies show that HeartLogic is safe to integrate into clinical practice. The current study investigates whether HeartLogic provides clinical benefit on top of standard care and device telemonitoring in patients with HF. METHODS: A multicenter, retrospective, propensity-matched cohort analysis was performed in patients with HF and implantable cardiac defibrillators, and it compared HeartLogic to conventional telemonitoring. The primary endpoint was the number of worsening HF events. Hospitalizations and ambulatory visits due to HF were also evaluated. RESULTS: Propensity score matching yielded 127 pairs (median age 68 years, 80% male). Worsening HF events occurred more frequently in the control group (2; IQR 0-4) compared to the HeartLogic group (1; IQR 0-3; P = 0.004). The number of HF hospitalization days was higher in controls than in the HeartLogic group (8; IQR 5-12 vs 5; IQR 2-7; P = 0.023), and ambulatory visits for diuretic escalation were more frequent in the control group than in the HeartLogic group (2; IQR 0-3 vs 1; IQR 0-2; P = 0.0001). CONCLUSION: Integrating the HeartLogic algorithm in a well-equipped HF care path on top of standard care is associated with fewer worsening HF events and shorter duration of fluid retention-related hospitalizations.

Classification of Heart Failure Events by Severity: Insights From the VICTORIA Trial.

BACKGROUND: Hospitalization due to heart failure (HFH) is a major source of morbidity, consumes significant economic resources and is a key endpoint in HF clinical trials. HFH events vary in severity and implications, but they are typically considered equivalent when analyzing clinical trial outcomes. OBJECTIVES: We aimed to evaluate the frequency and severity of HF events, assess treatment effects and describe differences in outcomes by type of HF event in VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction). METHODS: VICTORIA compared vericiguat with placebo in patients with HF with reduced ejection fraction (< 45%) and a recent worsening HF event. All HFHs were prospectively adjudicated by an independent clinical events committee (CEC) whose members were blinded to treatment assignment. We evaluated the frequency and clinical impact of HF events by severity, categorized by highest intensity of HF treatment (urgent outpatient visit or hospitalization treated with oral diuretics, intravenous diuretics, intravenous vasodilators, intravenous inotropes, or mechanical support) and treatment effect by event categories. RESULTS: In VICTORIA, 2948 HF events occurred in 5050 enrolled patients. Overall total CEC HF events for vericiguat vs placebo were 43.9 vs 49.1 events/100 patient-years (P = 0.01). Hospitalization for intravenous diuretics was the most common type of HFH event (54%). HF event types differed markedly in their clinical implications for both in-hospital and post-discharge events. We observed no difference in the distribution of HF events between randomized treatment groups (P = 0.78). CONCLUSION: HF events in large global trials vary significantly in severity and clinical implications, which may have implications for more nuanced trial design and interpretation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT02861534).

Extremes of both weight gain and weight loss are associated with increased incidence of heart failure and cardiovascular death: evidence from the CANVAS Program and CREDENCE.

BACKGROUND: Obesity is an independent risk factor for cardiovascular disease (CVD) in patients with type 2 diabetes (T2D). However, it is not known to what extent weight fluctuations might be associated with adverse outcomes. We aimed at assessing the associations between extreme weight changes and cardiovascular outcomes in two large randomised controlled trials of canagliflozin in patients with T2D and high cardiovascular (CV) risk. METHODS: In the study populations of the CANVAS Program and CREDENCE trials, weight change was evaluated between randomization and week 52-78, defining subjects in the top 10% of the entire distribution of weight changes as gainers, subjects in the bottom 10% as losers and the remainder as stable. Univariate and multivariate Cox proportional hazards models were used to test the associations between weight changes categories, randomised treatment and covariates with heart failure hospitalisation (hHF) and the composite of hHF and CV death. RESULTS: Median weight gain was 4.5 kg in gainers and median weight loss was 8.5 kg in losers. The clinical phenotype of gainers as well as that of losers were similar to that of stable subjects. Weight change within each category was only slightly larger with canagliflozin than placebo. In both trials, gainers and losers had a higher risk of hHF and of hHF/CV death compared with stable at univariate analysis. In CANVAS, this association was still significant by multivariate analysis for hHF/CV death in both gainers and losers vs. stable (hazard ratio - HR 1.61 [95% confidence interval - CI: 1.20-2.16] and 1.53 [95% CI 1.14-2.03] respectively). Results were similar in CREDENCE for gainers vs. stable (adjusted HR for hHF/CV death 1.62 [95% CI 1.19-2.16]) CONCLUSIONS: Extremes of weight gain or loss were independently associated with a higher risk of the composite of hHF and CV death. In patients with T2D and high CV risk, large changes in body weight should be carefully assessed in view of individualised management. TRIALS REGISTRATION: CANVAS ClinicalTrials.gov number: NCT01032629. CREDENCE ClinicalTrials.gov number: NCT02065791.

Improved prognosis after cardiac resynchronization therapy over a decade.

AIMS: The past decade has seen an increased delivery of cardiac resynchronization therapy (CRT) for patients with heart failure (HF). We explored whether clinical outcomes after CRT have changed from the perspective of an entire public healthcare system. METHODS AND RESULTS: A national database covering the population of England (56.3 million in 2019) was used to explore clinical outcomes after CRT from 2010 to 2019. A total of 64 698 consecutive patients (age 71.4 ± 11.7 years; 74.8% male) underwent CRT-defibrillation [n = 32 313 (49.7%)] or CRT-pacing [n = 32 655 (50.3%)] implantation. From 2010-2011 to 2018-2019, there was a 76% increase in CRT implantations. During the same period, the proportion of patients with hypertension (59.6-73.4%), diabetes (26.5-30.8%), and chronic kidney disease (8.62-22.5%) increased, as did the Charlson comorbidity index (CCI ≥ 3 from 20.0% to 25.1%) (all P < 0.001). Total mortality decreased at 30 days (1.43-1.09%) and 1 year (9.51-8.13%) after implantation (both P < 0.001). At 2 years, total mortality [hazard ratio (HR): 0.72; 95% confidence interval (CI) 0.69-0.76] and total mortality or HF hospitalization (HR: 0.59; 95% CI 0.57-0.62) decreased from 2010-2011 to 2018-2019, after correction for age, race, sex, device type (CRT-defibrillation or pacing), comorbidities (hypertension, diabetes, chronic kidney disease, and myocardial infarction), or the CCI (HR: 0.81; 95% CI 0.77-0.85). CONCLUSIONS: From the perspective of an entire public health system, survival has improved and HF hospitalizations have decreased after CRT implantation over the past decade. This prognostic improvement has occurred despite an increasing comorbidity burden.

Catheter ablation for patients with atrial fibrillation and heart failure with reduced and preserved ejection fraction: insights from the KiCS-AF multicentre cohort study.

AIMS: The usefulness of catheter ablation (CA) for atrial fibrillation (AF) across a broad spectrum of heart failure (HF) patients remains to be established. We assessed the association of CA with both health-related quality of life (QoL) and cardiovascular events among HF patients with reduced and preserved left ventricular ejection fraction (LVEF) in an 'all-comer' outpatient-based AF registry. METHODS AND RESULTS: Of 3303 patients with AF consecutively enrolled in a retrospective multicentre registry that mandated the Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) questionnaire at registration and 1-year follow-up, we extracted data from 530 patients complicating clinical HF. The association between CA and both 1-year change in AFEQT Overall Summary (AFEQT-OS) scores and 2-year composite clinical outcomes (including all-cause death, stroke, and HF hospitalization) was assessed by multivariable analyses. The median duration of AF was 108 days (52-218 days), and 83.4% had LVEF >35%. Overall, 75 patients (14.2%) underwent CA for AF within 1-year after registration. At 1-year follow-up, 67.2% in the ablation group showed clinically meaningful improvements of ≥ 5 points in AFEQT-OS score than 47.8% in the non-ablation group {adjusted odds ratio, 2.03 [95% confidence interval (CI): 1.13-3.64], P = 0.017}. Furthermore, the composite endpoint of all-cause death, stroke, and HF hospitalization occurred less frequently in the ablation group than the non-ablation group [adjusted hazard ratio, 0.27 (95% CI: 0.09-0.86), P = 0.027]. CONCLUSION: Among AF-HF patients, CA was associated with improved QoL and lower risk of cardiovascular events against drug therapy alone, even for patients with mildly reduced and preserved LVEF.

Timing of cardiac resynchronization therapy implantation.

AIMS: The optimum timing of cardiac resynchronization therapy (CRT) implantation is unknown. We explored long-term outcomes after CRT in relation to the time interval from a first heart failure hospitalization (HFH) to device implantation. METHODS AND RESULTS: A database covering the population of England (56.3 million in 2019) was used to quantify clinical outcomes after CRT implantation in relation to first HFHs. From 2010 to 2019, 64 968 patients [age: 71.4 ± 11.7 years; 48 606 (74.8%) male] underwent CRT implantation, 57% in the absence of a previous HFH, 12.9% during the first HFH, and 30.1% after ≥1 HFH. Over 4.54 (2.80-6.71) years [median (interquartile range); 272 989 person-years], the time in years from the first HFH to CRT implantation was associated with a higher risk of total mortality [hazard ratio (HR); 95% confidence intervals (95% CI)] (1.15; 95% CI 1.14-1.16, HFH (HR: 1.26; 95% CI 1.24-1.28), and the combined endpoint of total mortality or HFH (HR: 1.19; 95% CI 1.27-1.20) than CRT in patients with no previous HFHs, after co-variate adjustment. Total mortality (HR: 1.67), HFH (HR: 2.63), and total mortality or HFH (HR: 1.92) (all P < 0.001) were highest in patients undergoing CRT ≥2 years after the first HFH. CONCLUSION: In this study of a healthcare system covering an entire nation, delays from a first HFH to CRT implantation were associated with progressively worse long-term clinical outcomes. The best clinical outcomes were observed in patients with no previous HFH and in those undergoing CRT implantation during the first HFH. CONDENSED ABSTRACT: The optimum timing of CRT implantation is unknown. In this study of 64 968 consecutive patients, delays from a first heart failure hospitalization (HFH) to CRT implantation were associated with progressively worse long-term clinical outcomes. Each year from a first HFH to CRT implantation was associated with a 21% higher risk of total mortality and a 34% higher risk of HFH. The best outcomes after CRT were observed in patients with no previous HFHs and in those undergoing implantation during their first HFH.

Long-Term Clinical Outcome After Alcohol Septal Ablation and Its Periprocedural Predictive Factors in Japan　- A Retrospective Observational Study.

BACKGROUND: Evidence is limited regarding long-term clinical outcomes after alcohol septal ablation (ASA) for patients with hypertrophic obstructive cardiomyopathy and its periprocedural predictive factors in Japan.Methods and Results: This retrospective observational study included 44 patients who underwent ASA between 1998 and 2022 in a single center. We evaluated the periprocedural change in variables and long-term clinical outcomes after the procedure. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure. The secondary outcome was all-cause death. Using multivariable Poisson regression with robust error variance, we predicted underlying periprocedural factors related to primary outcome development. ASA decreased the median pressure gradient at the left ventricular outflow tract from 88 to 33 mmHg and reduced moderate or severe mitral regurgitation (MR), present in 53% of patients before ASA, to 16%. Over a median 6-year follow-up, the cumulative incidence of the primary outcome at 5 and 10 years was 16.5% and 25.6%, respectively. After multivariable analysis, moderate or severe MR after ASA was significantly associated with the primary outcome (relative risk 8.78; 95% confidence interval 1.34-57.3; P=0.024). All-cause mortality after ASA was 15.1% and 28.9% at 5 and 10 years, respectively. CONCLUSIONS: This study presents long-term clinical outcomes after ASA in Japan. Moderate or severe MR after ASA was significantly associated with the composite of cardiovascular death or hospitalization for heart failure.

Prevention of Cardiovascular Events in Patients With Chronic Kidney Disease.

OBJECTIVE: To examine the evidence base for lifestyle and pharmacologic interventions to reduce the risk of cardiovascular events in patients with chronic kidney disease, with an emphasis on reporting available data in distinct subtypes. DATA SOURCES: A PubMed search (origin to February 2023) was conducted and references for selected studies were reviewed to identify additional articles. Search terms included chronic kidney disease, major adverse cardiovascular events, and heart failure hospitalization. STUDY SELECTION AND DATA ANALYSIS: English language studies reporting cardiovascular outcomes data in patients with chronic kidney disease were included. DATA SYNTHESIS: Much of the data on interventions to prevent cardiovascular events in patients with chronic kidney disease are derived from observational studies or subgroup analyses of trials of broader populations. Some common recommendations, such as weight loss, may be harmful in certain patients. Others may only offer benefits in subgroups, such as those with albuminuria. Newer agents, such as SGLT2 inhibitors and finerenone, have clearer evidence of cardiovascular benefit, but these may also apply only to specific subgroups. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Given the prevalence of chronic kidney disease and its attendant cardiovascular risk, it is important to understand which interventions offer the greatest benefit. CONCLUSIONS: Patients diagnosed with chronic kidney disease have markedly increased risk of cardiovascular events, including myocardial infarction, stroke, heart failure, and cardiovascular death. However, until recently, there were few cardiovascular outcome studies that targeted enrollment specifically to those patients. Certain drugs now have shown benefits to cardiovascular end points in this population.

Left bundle branch pacing versus biventricular pacing for cardiac resynchronization therapy: A systematic review and meta-analysis.

INTRODUCTION: Cardiac resynchronization therapy (CRT) reduces heart failure (HF) hospitalization and all-cause mortality in HF patients with left bundle branch block (LBBB). Biventricular pacing (BVP) is the gold standard for achieving CRT, but about 30%-40% of patients do not respond to BVP-CRT. Recent studies showed that left bundle branch pacing (LBBP) provided remarkable results in CRT. Therefore, we conducted a meta-analysis aiming to compare LBBP-CRT versus BVP-CRT in HF patients. METHODS: We systematically searched the electronic databases for studies published from inception to December 29, 2022 and focusing on LBBP-CRT versus BVP-CRT in HF patients. The primary endpoint was HF hospitalization. The effect size was estimated using a random-effect model as Risk Ratio (RR) and mean difference (MD). RESULTS: Ten studies enrolling 1063 patients met the inclusion criteria. Compared to BVP-CRT, LBBP-CRT led to significant reduction in HF hospitalization [7.9% vs.14.5%; RR: 0.60 (95%CI: 0.39-0.93); p = .02], QRSd [MD: 30.26 ms (95%CI: 26.68-33.84); p < .00001] and pacing threshold [MD: -0.60 (95%CI: -0.71 to -0.48); p < .00001] at follow up. Furthermore, LBBP-CRT improved LVEF [MD: 5.78% (95%CI: 4.78-6.77); p < .00001], the rate of responder [88.5% vs.72.5%; RR: 1.19 (95%CI: 1.07-1.32); p = .002] and super-responder [60.8% vs. 36.5%; RR: 1.56 (95%CI: 1.27-1.91); p < .0001] patients and the NYHA class [MD: -0.42 (95%CI: -0.71 to -0.14); p < .00001] compared to BVP-CRT. CONCLUSION: In HF patients, LBBP-CRT was superior to BVP-CRT in reducing HF hospitalization. Further significant benefits occurred within the LBBP-CRT group in terms of QRSd, LVEF, pacing thresholds, NYHA class and the rate of responder and super-responder patients.

The efficacy and safety of adaptive servo-ventilation therapy for heart failure with preserved ejection fraction.

It is unclear whether adaptive servo-ventilation (ASV) therapy for heart failure with preserved ejection fraction (HFpEF) is effective. The aim of this study was to investigate the details of ASV use, and to evaluate the effectiveness and safety of ASV in real-world HFpEF patients. We retrospectively enrolled 36 HFpEF patients at nine cardiovascular centers who initiated ASV therapy during hospitalization or on outpatient basis and were able to continue using it at home from 2012 to 2017 and survived for at least one year thereafter. The number of hospitalizations for heart failure (HF) during the 12 months before and 12 months after introduction of ASV at home was compared. The median number of HF hospitalizations for each patient was significantly reduced from 1 [interquartile range: 1-2] in the 12 months before introduction of ASV to 0 [0-0] in the 12 months after introduction of ASV (p < 0.001). In subgroup analysis, reduction in heart failure hospitalization was significantly greater in female patients, patients with a body mass index < 25, and those with moderate or severe tricuspid valve regurgitation. In patients with HFpEF, the number of HF hospitalizations was significantly decreased after the introduction of ASV. HFpEF patients with female sex, BMI < 25, or moderate to severe tricuspid valve regurgitation are potential candidates who might benefit from ASV therapy.

Clinical outcomes of left bundle branch area pacing compared to His bundle pacing.

INTRODUCTION: His bundle pacing (HBP) is the most physiologic form of pacing and has been associated with reduced risk for heart failure hospitalization (HFH) and mortality compared to right ventricular pacing. Left bundle branch area pacing (LBBAP) is a safe and effective alternative option for patients needing ventricular pacing. The aim of this study was to compare the clinical outcomes between LBBAP and HBP among a large cohort of patients undergoing permanent pacemaker implantation. METHODS: This observational registry included consecutive patients with AV block/AV node ablation who underwent de novo permanent pacemaker implantations with successful LBBAP or HBP between April 2018 and October 2020. The primary outcome was the composite endpoint of time to death from any cause or HFH. Secondary outcomes included the composite endpoint among patients with prespecified ventricular pacing burden and individual outcomes. RESULTS: The study population included 359 patients who met the inclusion criteria (163 in the HBP and 196 in the LBBAP group). Paced QRSd during LBBAP was similar to HBP (125 ± 20.2 vs. 126 ± 23.5 ms, p = .643). There were no statistically significant differences in the primary composite outcome in LBBAP (17.3%) compared to HBP (24.5%) (hazard ratio [HR]: 1.15, 95% CI: 0.72-1.82, p = .552). Secondary outcomes of death (10% vs. 17%; HR: 1.3, 95% CI: 0.73-2.33, p = .38) and HFH (10% vs. 12%; HR: 1.02, 95% CI: 0.54-1.94, p = .94) were not different among both groups. CONCLUSIONS: There were no statistically significant differences in the clinical outcomes of death or HFH in LBBAP when compared to HBP.

Patient-reported and Clinical Outcomes Among Patients Hospitalized for Heart Failure With Reduced Versus Preserved Ejection Fraction.

BACKGROUND: Differences between patients hospitalized for heart failure with reduced ejection fraction (HFrEF) vs HF with preserved EF (HFpEF) are not well-characterized, particularly as pertains to in-hospital decongestion and longitudinal patient-reported outcomes. The objective of this analysis was to compare patient-reported and clinical outcomes between patients hospitalized with HFrEF vs HFpEF. METHODS AND RESULTS: The Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial enrolled 7141 patients hospitalized for HF with reduced or preserved EF. We assessed the association between an EF ≤ 40% vs an EF >40% with in-hospital decongestion, risk of rehospitalization and mortality, and quality of life as measured by the EuroQOL 5 Dimensions (EQ-5D). Among 5800 patients (81%) with complete EF data, 4782 (82%) had an EF ≤40% and 1018 (18%) had an EF >40%. Both groups demonstrated similar rates of decongestion by weight change and urine volume through 24 hours, a similar risk of 30-day mortality and HF rehospitalization, and a similar 180-day mortality. Patients with HFpEF had worse EQ-5D scores at hour 24 (median 0.76, [interquartile range (IQR) 0.51-0.84] vs 0.78 [IQR 0.57-0.84]; P = .01) that persisted through discharge (0.81 [IQR 0.69-0.86] vs 0.83 [IQR 0.71-1.00]; P < .001) and the 30-day follow-up (0.78 [IQR 0.60-0.85] vs 0.83 [IQR 0.71-1.00]; P < .001). After adjustment, these differences were attenuated and not statistically significant. CONCLUSIONS: In this large, multinational cohort of patients hospitalized for HF, patients with an EF ≤ 40% vs an EF >40% experienced similar in-hospital decongestion and postdischarge clinical outcomes. Patients with an EF >40% reported worse in-hospital and postdischarge patient-reported health status, but these measures were similar to HFrEF after accounting for other clinical factors.

Left Bundle Branch Area Pacing versus Biventricular Pacing for Cardiac Resynchronization Therapy on Morbidity and Mortality.

BACKGROUND: Left bundle branch area pacing (LBBAP) has emerged as an alternative to biventricular pacing (BVP) for cardiac resynchronization therapy (CRT). We aimed to compare the morbidity and mortality associated with LBBAP versus BVP in patients undergoing CRT implantation. METHODS: Consecutive patients who received CRT from two high-volume implantation centers were retrospectively recruited. The primary endpoint was a composite of all-cause death and heart failure hospitalization, and the secondary endpoint was all-cause death. RESULTS: A total of 491 patients receiving CRT (154 via LBBAP and 337 via BVP) were included, with a median follow-up of 31 months. The primary endpoint was reached by 21 (13.6%) patients in the LBBAP group, as compared with 74 (22.0%) patients in the BVP group [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.43-1.14, P = 0.15]. There were 10 (6.5%) deaths in the LBBAP group, as compared with 31 (9.2%) in the BVP group (HR 0.91, 95% CI 0.44-1.86, P = 0.79). No significant difference was observed in the risk of either the primary or secondary endpoint between LBBAP and BVP after multivariate Cox regression (HR 0.74, 95% CI 0.45-1.23, P = 0.24, and HR 0.77, 95% CI 0.36-1.67, P = 0.51, respectively) or propensity score matching (HR 0.72, 95% CI 0.41-1.29, P = 0.28, and HR 0.69, 95% CI 0.29-1.65, P = 0.40, respectively). CONCLUSION: LBBAP was associated with a comparable effect on morbidity and mortality relative to BVP in patients with indications for CRT.

Mortality and readmission risk in relation to QRS duration among patients hospitalized for heart failure with preserved ejection fraction.

BACKGROUND: In ambulatory patients with heart failure (HF) with preserved ejection fraction (HFpEF), QRS prolongation (QRS > 120 msec) and left bundle branch block (LBBB) each carry an increased risk of cardiovascular mortality and/or HF hospitalization. Less is known about implications of conduction abnormalities following an acute HF hospitalization for HFpEF. METHODS AND RESULTS: A retrospective cohort of 1454 patients discharged from after a HF hospitalization between 2015 and 2019 with ejection fraction (EF) ≥ 45% were identified (age 75.1 ± 10.8 years, EF 58.5% ± 10.2%). All patients' electrocardiograms were classified by QRS duration (prolonged - 545 [37.5%] vs. normal [QRS ≤ 120 msec] 909 [62.5%]). QRS prolongation was comprised of: LBBB (4.2%), right bundle branch block (RBBB, 18.3%), intraventricular conduction delay (9.7%), and ventricularly paced (9.7%). Over 4.09 ± 1.00 years, 769 (52.9%) patients died. Survival was similar between normal and prolonged QRS cohorts with an age and sex adjusted hazard ratio of 1.01 (95%CI: 0.87-1.17, p = 0.16). Recurrent HF hospitalization occurred in 91 (16.7%) with QRS prolongation vs. 90 (9.9%) without (odds ratio: 1.82 [95%CI: 1.33-2.50, p < 0.001]). RBBB carried 2.26 higher odds of recurrent HF hospitalization (95%CI: 1.56-3.28). CONCLUSIONS: Following a HF hospitalization, QRS prolongation increased the odds of re-admission for HF in patients with HFpEF without differences in overall mortality.

Association of sodium-glucose cotransporter-2 inhibitors with outcomes in type 2 diabetes with reduced and preserved left ventricular ejection fraction: Analysis from the CVD-REAL 2 study.

This study of real-world data from the Maccabi database in Israel compared the risk of heart failure hospitalization (HHF) or death in patients with type 2 diabetes (T2D) initiating sodium-glucose cotransporter-2 (SGLT2) inhibitors versus other glucose-lowering drugs (OGLDs) according to baseline left ventricular (LV) ejection fraction (EF). After propensity-matching patients by baseline EF there were 10 614 episodes of treatment initiation; 57% had diabetes for >10 years, the mean glycated haemoglobin level was 66 mmol/mol (8.2%), ∼43% had cardiovascular disease, ∼7% had heart failure and ∼ 20% had chronic kidney disease. A total of 2876 patients (∼9%) had reduced EF (<50%). Over a mean follow-up of 1.5 years there were 371 HHFs or deaths, 88 (23.7%) in patients with reduced EF. Initiation of SGLT2 inhibitors versus OGLDs was associated with lower risk of HHF or death overall (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.46-0.70]; P < 0.001) and in patients with both reduced EF (HR 0.61, 95% CI 0.40-0.93) and preserved EF (HR 0.55, 95% CI 0.43-0.70), with no significant heterogeneity (Pinteraction = 0.72). Our findings from real-world clinical practice show that the lower risk of HHF and death associated with use of SGLT2 inhibitors versus OGLDs is consistent in T2D patients with both reduced and preserved EF.

Comparison of clinical outcomes and left ventricular remodeling after ST-elevation myocardial infarction between patients with and without diabetes mellitus.

Left ventricular remodeling (LVR) after ST-elevation myocardial infarction (STEMI) is generally thought to be an adaptive but compromising phenomenon particularly in patients with diabetes mellitus (DM). However, whether the extent of LVR is associated with poor prognostic outcome with or without DM after STEMI in the modern era of reperfusion therapy has not been elucidated. This was a single-center retrospective observational study. Altogether, 243 patients who were diagnosed as having STEMI between January 2016 and March 2019, and examined with echocardiography at baseline (at the time of index admission) and mid-term (from 6 to 11 months after index admission) follow-up were included and divided into the DM (n = 98) and non-DM groups (n = 145). The primary outcome was major adverse cardiovascular events (MACEs) defined as the composite of all-cause death, heart failure (HF) hospitalization, and non-fatal myocardial infarction. The median follow-up duration was 621 days (interquartile range: 304-963 days). The DM group was significantly increased the rate of MACEs (P = 0.020) and HF hospitalization (P = 0.037) compared with the non-DM group, despite of less LVR. Multivariate Cox regression analyses revealed that the patients with DM after STEMI were significantly associated with MACEs (Hazard ratio [HR] 2.79, 95% confidence interval [CI] 1.20-6.47, P = 0.017) and HF hospitalization (HR 3.62, 95% CI 1.19-11.02, P = 0.023) after controlling known clinical risk factors. LVR were also significantly associated with MACEs (HR 2.44, 95% CI 1.03-5.78, P = 0.044) and HF hospitalization (HR 3.76, 95% CI 1.15-12.32, P = 0.029). The patients with both DM and LVR had worse clinical outcomes including MACEs and HF hospitalization, suggesting that it is particularly critical to minimize LVR after STEMI in patients with DM.