Reduction In All-cause Mortality Research Articles

The Impact of Coronary Ischemia Assessment on Outcomes in Those With Scar-Dependent Ventricular Tachycardia.

Guidance and outcomes of coronary ischemia assessment (IA) in those with structural heart disease (SHD), presenting with monomorphic ventricular tachycardia (MMVT) is unclear. To assess the impact of IA on arrhythmic and non-arrhythmic outcomes in those with SHD. Patients presenting with MMVT over a 6-year period to a tertiary center were retrospectively analyzed. Propensity score-matched analysis was performed comparing those undergoing IA to those who did not. The primary endpoint was a composite of VT recurrence, appropriate ICD therapy, heart failure hospitalization, and death. Secondary analysis of the individual components of the composite was performed. Kaplan-Meier, univariate and multivariate analysis was performed to compare the two groups and derive predictors of poor outcomes. Two hundred and seventeen patients (57.6% ICM) were analyzed. 55.8% underwent IA. Following propensity score-matching, 120 patients remained. At 12 months, freedom from the primary endpoint was 68.3% of those undergoing IA versus 43.3% who did not, p < 0.001, multivariate HR 0.56 (0.34-0.92). This was driven by a reduction in all-cause mortality, with a 12-month survival of 98.3% in those undergoing IA versus 86.5% in those not undergoing IA (p < 0.01). Coronary intervention was associated with a significantly higher event-free 12-month survival compared to those who did not undergo intervention (82.4% vs 51.5%, respectively, p = 0.01). Patients with SHD presenting MMVT who undergo an IA have significantly improved freedom from VT recurrence, appropriate ICD therapies, HF hospitalization, and death compared to those who do not, driven by a reduction in mortality.

Effectiveness of treat-to-target cholesterol-lowering interventions on cardiovascular disease and all-cause mortality risk in the community-dwelling population: a target trial emulation.

Little is known about the long-term effectiveness of risk-based treat-to-target cholesterol-lowering interventions on cardiovascular risk. Here, we show the emulated effectiveness of guideline-recommended low-density and non-high-density lipoprotein cholesterol-lowering interventions using the absolute risk reduction (ARR) and the restricted mean event-free time-based number needed to treat (NNT). With 5,375 participants, the 29-year risks for cardiovascular disease (CVD), all-cause mortality, and atherosclerotic CVD were 18.6%, 25.6%, and 17.7%, respectively. Long-term treat-to-target interventions showed significant reductions in CVD (ARR -2.3%, 95%CI -3.4% to -0.8%; NNT 115), all-cause mortality (-3.0%, -4.3% to -1.8%; 95), and atherosclerotic CVD (-2.6%, -3.5% to -1.2%; 104). Such effects appear more pronounced in women, smokers, and those with body mass index < 24 kg/m² or higher adherence rates.

Abstract 4113486: Cardiovascular Benefits of Sotagliflozin in Diabetic Populations: A Meta-Analysis

Background: Sotagliflozin, an inhibitor of both SGLT1 and SGLT2, is under investigation for potential cardioprotective effects in diabetic patients. Aims: This study assesses the efficacy and cardiovascular benefits of sotagliflozin in patients with type 1 or type 2 diabetes at high cardiovascular risk or with diagnosed heart failure. Methods: We systematically searched digital databases including ClinicalTrials.gov, PubMed, Google Scholar, Cochrane, Medline, and Embase, using a PICOS-based strategy and the PRISMA framework for data reporting. Randomized controlled trials comparing sotagliflozin against placebo over a minimum duration of eight weeks were analyzed using Review Manager (RevMan) 5.4.1. Results: Our meta-analysis included 7 studies with 16,315 participants with all studies comparing either 200 or 400 mg sotagliflozin to placebo. The meta analaysis revealed significant improvements in reduction the total number of cardiovascular deaths [OR= 0.70 (95% CI (0.51- 0.95)), p = 0.02]; reduction in Non-fatal MI [OR=0.76 (95% CI (0.70- 0.84)), p &lt; 0.00001]; reduction in the incidence of hospitalizations due to HF [OR=0.54 (95% CI (0.44, 0.66)), p &lt; 0.00001]; reduction In urgent hospitalizations [OR=0.66 (95% CI (0.53, 0.83)), p=0.0004]; improvement in LVEF&gt;50% [ OR= 0.41 (95%CI (0.34, 0.51)), p&lt;0.0001] and reduction in systolic blood pressure mean reduction of -0.81 (95% CI (1.36, -0.25)), p=0.005]. However there was no statistically significant reduction in all cause mortality [0.73 (95% CI (0.42, 1.26)), p=0.26] . Conclusion: Sotagliflozin significantly reduces the incidence of cardiovascular deaths, adverse events, and hospitalizations in diabetic patients at high risk of cardiovascular complications.

Abstract 4137009: Treating Elderly Cardiogenic Shock Patients with a Microaxial Flow Pump; Is It DANGERous?

Background: The Danish German Cardiogenic Shock trial (DanGer Shock) recently showed a reduction in all-cause mortality when treating selected patients with ST-segment elevation myocardial infarction (STEMI) and cardiogenic shock with a microaxial flow pump (mAFP). Whether there is an age-related differential survival benefit is unknown. Objective: To assess the influence of age on 180-day all-cause mortality in patients with STEMI and cardiogenic shock randomized in DanGer Shock. Methods: In DanGer Shock (an open-label, international, multicenter trial), 355 adult patients (aged ≥18 years with no upper age limit) with STEMI and cardiogenic shock were included and randomized to a mAFP (Impella CP) plus standard care or standard care alone. Patients were stratified in quartiles according to age, and logistic regression analyses were used to assess mortality according to age quartiles, and to evaluate whether age modified the treatment effect of the mAFP. Results: From lowest to highest quartile, patients’ ages ranged from 31-59, 60-69, 70-76, and 77-92, respectively. There were no differences in blood pressure, lactate level, left ventricular ejection fraction and shock severity across age groups. However, the proportion of females (41%) and the prevalence of hypertension (64%) was higher in patients aged ≥77 years (highest quartile), while more patients aged &lt;60 years (lowest quartile) had been resuscitated before randomization. Mortality increased incrementally from the lowest quartile to the highest (31% vs. 47% vs. 61% vs. 73%, p log-rank &lt;0.001), with an adjusted odds ratio for death at 180 days of 5.50 (95%CI 2.65-11.8, p&lt;0.001) in the highest quartile compared to the lowest. Patients in the three lower quartiles had a lower absolute mortality at 180 days if randomized to the mAFP group, whereas patients in the highest quartile had a higher mortality if randomized to the mAFP group, p=0.028 for interaction, Figure. Conclusion: In patients with STEMI-related cardiogenic shock, the overall mortality increased with advancing age, and treatment benefit of the mAFP appeared to diminish in the eldest patients. (DanGer Shock, NCT01633502)

Abstract 4148089: Comparative Efficacy of Carvedilol versus Metoprolol in Patients with Implantable Cardioverter Defibrillators and Ventricular Arrhythmias: A Systematic Review and Meta-Analysis

Background: Ventricular arrhythmias are major causes of morbidity and mortality in patients with cardiovascular disease. Implantable cardioverter-defibrillators (ICDs) are commonly used to prevent sudden cardiac death in these patients. However, patients with ICDs frequently experience recurrent arrhythmias and inappropriate shocks, which can impact their quality of life. Beta-blockers, specifically carvedilol and metoprolol, are commonly prescribed to manage these arrhythmias. This meta-analysis aims to compare the impact of both medications in this patient population. Methods: A comprehensive literature search was conducted to identify relevant studies comparing carvedilol to metoprolol in patients with ventricular arrhythmias or ICDs. Study outcomes included all-cause mortality, recurrent ventricular arrhythmia, and inappropriate ICD shocks. Effect estimates are presented as hazard ratios (HR) with 95% confidence intervals (CI). Results: 1,453 studies were identified through database search. After full-text screening, a total of 5 studies involving 9,292 patients were included. We found no significant difference in the incidence of recurrent ventricular arrhythmias between carvedilol and metoprolol (HR = 0.99, 95% CI [0.75, 1.32], P = 0.97). Additionally, Carvedilol showed a trend toward reduction of all-cause mortality (HR = 0.83, 95% CI [0.68, 1.03], P = 0.09). On the other hand, Carvedilol was associated with a statistically significant reduction of inappropriate ICD shocks (HR = 0.61, 95% CI [0.48, 0.78], P &lt; 0.001). Conclusion: Carvedilol may offer additional benefits over metoprolol in managing patients with ventricular arrhythmias or ICDs, particularly in minimizing the incidence of inappropriate ICD shocks. However, no significant difference was found in terms of all-cause mortality and recurrent ventricular arrhythmia incidence. Further research is needed to confirm these findings and guide clinical decision-making.

Abstract 4116340: The Effect of Periprocedural Statin Therapy on Mortality and Cardiovascular Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis

Background: Transcatheter aortic valve replacement (TAVR) stands as a notable alternative to surgery for severe aortic stenosis (AS). Despite the established benefits of statins in cardiovascular pathologies, their specific impact in patients with severe AS undergoing TAVR remains uncertain. Our study aims to assess whether perioperative statin use improves survival and outcomes post-TAVR. Methods: A search was conducted across various databases to retrieve studies comparing perioperative statin use versus no statin use in patients undergoing TAVR. The primary outcome of interest was all-cause mortality (ACM). Secondary outcomes included stroke, acute kidney injury (AKI), 30-day mortality, myocardial infarction (MI), cardiovascular complications, and in-hospital mortality. Comprehensive Meta-Analysis Software (v. 3) was used to pool odds ratio (OR) under a random-effects model, with statistical significance set at p &lt; 0.05. Results: Our analysis encompassing 20663 patients from 15 observational studies found that perioperative statin use was associated with a significant reduction in ACM (OR= 0.71, 95% CI: 0.61-0.83, I 2 = 50.3%, p&lt;0.001). Although not statistically significant, perioperative statin use demonstrated a trend towards a decreased risk of stroke (OR= 0.90, 95% CI: 0.68-1.19, I 2 = 0%, p= 0.455), AKI (OR= 0.99, 95% CI: 0.75-1.31, I 2 = 49%, p= 0.968), and 30-day mortality (OR= 0.71, 95% CI: 0.46-1.10, I 2 = 0%, p= 0.126), and no difference was seen in the risk of MI (OR= 1.72, 95% CI: 0.73-4.04, I 2 = 0%, p= 0.214), cardiovascular complications (OR= 1.12, 95% CI: 0.91-1.37, I 2 = 0%, p= 0.297), and in-hospital mortality (OR= 0.42, 95% CI: 0.13-1.38, I 2 = 65.8%, p= 0.151) (Figure 1 and 2). Conclusion: Perioperative statin therapy reduces all-cause mortality in TAVR patients but shows limited impact on other outcomes. Further large-scale prospective studies and trials are necessary to corroborate our findings.

Abstract 4121516: Efficacy of Sentinel Cerebral Embolic Protection Device in Transcatheter Aortic Valve Replacement: A Meta-Analysis of Randomized Controlled Trials and Propensity Score Matched Studies

Background: Transcatheter aortic valve replacement (TAVR) is frequently associated with stroke due to debris embolization. Although the risk of stroke with the newer-generation devices is lower, stroke still represents a significant cause of mortality and morbidity after TAVR. The Sentinel cerebral embolic protection (CEP) device (Boston Scientific) is a dual embolic filter device designed to capture debris dislodged during TAVR. The current literature concerning the efficacy of Sentinel CEP in the reduction of stroke in patients undergoing TAVR is limited and inconsistent. Aim: This meta-analysis aimed to compare clinical outcomes with Sentinel CEP device in patients undergoing TAVR. Methods: A comprehensive systematic literature search was performed on PubMed, Embase, Cochrane Library and Clinicaltrial.gov from inception until 1st May 2024 to retrieve randomized controlled trials (RCTs) and propensity-matched studies comparing TAVR with and without the Sentinel CEP device. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using the DerSimonian-Laird random-effects model, with a p-value of &lt;0.05 considered statistically significant. Results: 6 studies with a total of 25,130 patients undergoing TAVR (12608: Sentinel CEP device; 12522: Without Sentinel CEP device) were included in this meta-analysis. The use of the Sentinel CEP device in TAVR was associated with a statistically significant lower risk of acute kidney injury [OR: 0.89; 95% CI: 0.81, 0.97; p=0.01]. The use of Sentinel CEP device in TAVR was associated with a statistically insignificant trend towards reduction in stroke [OR: 0.80; 95% CI: 0.58, 1.10; p=0.18], all-cause mortality [OR: 0.74; 95% CI: 0.51, 1.07; p=0.11], and major vascular complications [OR: 0.74; 95% CI: 0.46, 1.19; p=0.21]. Conclusion: The use of the Sentinel CEP device in patients undergoing TAVR does not lead to a statistically significant reduction in stroke, all-cause mortality, and major vascular complications; however, the risk of acute kidney injury is lower. Large, multicentric RCTs are warranted to corroborate the findings of this meta-analysis.

Effect of statin on long-term outcomes in persistent tobacco users receiving percutaneous coronary intervention: A longitudinal, retrospective cohort study.

The role of statins in improving cardiovascular outcomes is well established, but little is known about their impacts on long-term outcomes in persistent tobacco users with stable coronary artery disease (CAD) who receive percutaneous coronary intervention (PCI). A population of persistent smokers with CAD treated by PCI was analyzed. From 2012 through 2019, a cohort of 907 persistent tobacco users with stable CAD undergoing PCI were enrolled from the inpatient department of Taichung Tzu Chi Hospital, Taiwan. We surveyed statin users and non-statin users after index PCI, and general characteristics, major risk factors, angiographic findings, and long-term clinical outcome were compared. Kaplan-Meier curve was used to compare the survival difference and Cox proportional hazard model was used to analyze the predictors for all-cause mortality and major adverse cardiovascular events, including cardiovascular (CV) mortality, myocardial infarction, and repeated PCI procedures. The statin group had a higher average total cholesterol (P < .01) and low-density lipoprotein cholesterol (LDL-C) level (P < .01) and was younger (P < .01) than the non-statin group. Ninety-six point one percent patients in the statin group had a LDL-C level below 100 mg/dL after treatment. They also had a more frequent history of acute coronary syndrome and lower prevalence of chronic kidney disease than the non-statin group (both P < .01). Freedom from all-cause and CV mortality were lower in the non-statin group than the statin group (both P < .01). After adjustment for age and chronic kidney disease, statin treatment no longer reduced the risk of CV mortality (hazard ratio: 0.32, 95% confidence interval = 0.07-1.49), but was still associated with a reduction in all-cause mortality (hazard ratio: 0.27, 95% confidence interval = 0.10-0.75). In persistent tobacco users undergoing PCI, patients treated with statin for LDL-C values above 100 mg/dL had a similar level of cardiovascular protection as those with LDL-C below 100 mg/dL and without statin treatment. Therefore, smoking attenuates pleiotropic effect of statin. Nevertheless, statin therapy was still associated with a reduction of all-cause mortality.

All-cause and cause-specific mortality risks in individuals with diabetes living alone: A large-scale population-based cohort study

AimsThe rise in one-person households is a global trend. We aimed to investigate mortality risk in individuals with diabetes living alone (IDLA) using a large-scale population-based database. MethodsA total of 2,447,557 adults with type 2 diabetes were identified from the Korean National Health Information Database. One-person households were defined based on the number of registered family members. The risks of all-cause and cause-specific mortalities were estimated using a multivariable Cox proportional hazards regression model. ResultsDuring a median follow-up period of 6.0 years, 191,084 deaths (7.8 %) occurred. IDLA had a higher risk of mortality compared to those not living alone after adjusting for potential confounders (HR 1.20, 95 % CI: 1.18–1.22). This association was more prominent in younger individuals, men, and those with low income, and it was dependent on the duration of living alone. The risks of cause-specific mortality were all significantly higher in the IDLA group compared with the non-IDLA group. Adherence to favorable lifestyle behaviors was associated with a significant reduction in all-cause mortality, particularly in IDLA. ConclusionsThe elevated risk of mortality in IDLA highlights the need for tailored medical interventions and social assistance, particularly for those with unhealthy lifestyles or low income.

Neuroprotective effects of GLP-1 receptor agonists in neurodegenerative Disorders: A Large-Scale Propensity-Matched cohort study

BackgroundGLP-1 receptor agonists, traditionally used for treating type 2 diabetes mellitus and obesity, have demonstrated anti-inflammatory properties. However, their potential neuroprotective effects in neurodegenerative disorders remain unclear. ObjectiveTo evaluate the impact of GLP-1 receptor agonists on the risk of developing various neurodegenerative conditions in obese patients. MethodsThis comprehensive retrospective cohort study analyzed data from 5,307,845 obese adult patients across 73 healthcare organizations in 17 countries. Propensity score matching was performed, resulting in 102,935 patients in each cohort. We compared the risk of developing neurodegenerative disorders between obese patients receiving GLP-1 receptor agonist therapy and those who were not. ResultsObese patients treated with GLP-1 receptor agonists showed significantly lower risks of developing Alzheimer’s disease (RR = 0.627, 95 %CI = 0.481–0.817), Lewy body dementia (RR = 0.590, 95 %CI = 0.462–0.753), and vascular dementia (RR = 0.438, 95 %CI = 0.327–0.588). The risk reduction for Parkinson’s disease was not statistically significant overall (RR = 0.784, 95 %CI = 0.580–1.058) but was significant for semaglutide users (RR = 0.574, 95 %CI = 0.369–0.893). Semaglutide consistently showed the most pronounced protective effects across all disorders. Additionally, a significant reduction in all-cause mortality was observed (HR = 0.525, 95 %CI = 0.493–0.558). ConclusionThis study provides evidence that the effects of GLP-1 receptor agonists may extend beyond their known metabolic and cardioprotective benefits to include neuroprotection, associated with a decreased risk of developing various neurodegenerative disorders. These findings suggest the potential for expanding the therapeutic applications of GLP-1 receptor agonists to improve neurocognitive outcomes. Further research is warranted to elucidate the mechanisms underlying these neuroprotective effects and to explore their clinical applications in neurodegenerative disease prevention and treatment.

TAKE AN OLD DRUG AND STAY YOUNG? METFORMIN AS AN ANTI-AGING MEDICATION – A LITERATURE REVIEW.

AIMS: Metformin is the main drug used in the treatment of type 2 diabetes mellitus, and the most widely prescribed oral antihyperglycemic medication. Its mechanism of action is still not completely understood and research into new uses for the compound is still ongoing, with one possible novel application of the medication being to combat aging on both the cellular and the macroscopic level. The aim of the study is to evaluate the current state of knowledge on metformin’s potential as a lifespan-extending and anti-senescence drug, present evidence on the matter and assess possible lanes of further study into such effects. METHODS: The literature review was performed using Internet research paper databases (PubMed, Google Scholar, Medline), using articles available in English. RESULTS: Multiple papers suggest tentative support for the notion that metformin may contribute to slowing cellular senescence, as well as to extending the human lifespan. Theoretical knowledge exists that shows possible routes of action of metformin in this regard. CONCLUSIONS: There is ample evidence in the literature for metformin’s possible effects as an anti-aging drug. Numerous cellular pathways by which it could exert lifespan-extending effects have been elucidated, and in vivo studies on some non-human animals have shown a measurable decrease in their production of aging markers, as well as an increase in the lifespan. Studies on diabetic patients have also demonstrated a significant reduction in all-cause mortality in that particular group. However, there is a lack of data and a need for more research that would investigate metformin’s potential as a universal anti-senescence agent more directly. Two large-scale studies (MILES and TAME) in the area are currently underway.

Modern heart failure treatment is superior to conventional treatment across the left ventricular ejection spectrum: Real-life data from the Swedish Heart Failure Registry 2013-2020

Abstract Background Heart failure (HF) is a clinical syndrome characterized by high mortality and morbidity. In 2016, Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), was recommended as a new treatment option for HF in patients with HFrEF. In the 2021 European Society of Cardiology guidelines for treatment of HFrEF patients Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were introduced because they demonstrated significantly reduced HF events or cardiovascular (CV) mortality. Since ARNI and SGLT2i were introduced to treat HF, its therapeutic regimen has modernized from previous treatment with beta-blocker (BB) and angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARB) with mineralocorticoid receptor antagonist (MRA) as added-on in HF with reduced ejection fraction (HFrEF). Purpose This study is aimed to compare effectiveness of modern therapy including ARNI and SGLT2i with conventional heart failure treatment. Conventional HF treatment includes (BB, ACEi/ARB, with or without MRA) and modern heart failure treatment (BB, ACEi/ARB, MRA, SGLT2i or BB, ARNI, MRA with/without SGLT2i) in real-world. Methods This observational study (2013-2020), using the Swedish HF Registry, involved 20,849 HF patients. Patients received either conventional (BB, ACEi/ARB, with/without MRA, n=20,140) or modern (BB, ACEi/ARB, MRA, SGLT2i or BB, ARNI, MRA with/without SGLT2i, n=709) treatment at the index visit. The endpoints were all-cause and cardiovascular (CV) mortality. Results Modern HF therapy was associated with a significant 28% reduction in all-cause mortality compared to conventional HF treatment (adjusted HR [aHR]: 0.72 (95% CI 0.54 - 0.96), p=0.024), and had 33% reduced all-cause mortality (aHR: 0.67 (95% CI 0.48 - 0.94), p=0.019) within 2 years of index registration. Similarly, modern HF therapy was associated with a significant 62% reduction in CV mortality compared to conventional HF treatment (aHR: 0.38 (95% CI 0.21 - 0.68), p=0.0013). In addition, we found a 58% reduced CV mortality (aHR 0.42 (95% CI 0.22 - 0.79), p=0.0067) within 2 years of index registration. In the propensity score 1:1 matched cohort in which ARNI was included in the matching procedure, i.e., no ARNI was used in any of the two treatment groups and the effect of SGLT2i was the target assessment. The results were associated with a statistically significant risk reduction of 42% in all-cause mortality in the modern HF treatment group compared to the conventional treatment group (aHR: 0.58 (95% CI 0.36 - 0.94), p=0.028), and a 49% (aHR: 0.51 (95% CI 0.29 - 0.89), p=0.018) risk reduction within 2 years of index registration. Conclusion This study demonstrates that modern HF therapy in a real-world Swedish HF population is associated with a statistically significant risk reduction in all-cause and CV mortality, regardless of EF, sex, age, eGFR, and etiology of HF compared to conventional HF therapy.Central Illustration

Effect of catheter ablation in atrial fibrillation patients irrespective of their baseline heart failure: An updated meta-analysis

Abstract Introduction Patients with atrial fibrillation (AF) are associated with higher morbidity and mortality. Catheter ablation (CA) is supposed to improve outcomes in these patients. We aimed to update the evidence regarding CA in AF patients irrespective of their baseline heart failure. Methods We searched PubMed, Scopus, WOS, and Cochrane until February 2024 for relevant studies assessing the impact of CA compared to medical regimens in AF patients with and without heart failure. Outcomes of interest were all-cause mortality, cardiovascular mortality, hospitalization for HF, hospitalization for other cardiovascular causes, and stroke. Results 13 studies were included with a total of 18370 patients. In HF patients, irrespective to their ejection fraction, CA was associated with a significant reduction in all-cause mortality (RR 0.40, 95%CI [0.37 to 0.44], cardiovascular mortality (RR 0.36, 95%CI [0.32 to 0.42]), hospitalization from HF (RR 0.65, 95%CI [0.51 to 0.82]), hospitalization from other cardiovascular causes (RR 0.71, 95%CI [0.57 to 0.89]), and the incidence of stroke (RR 0.55, 95%CI [0.50 to 0.62]). Also, six studies with a total of 2015 patients compared CA to medical treatment in AF patients with HFrEF and HFpEF. CA showed a significant reduction in all-cause mortality in HFpEF patients compared to HFrEF (RR 0.46, 95%CI [0.25 to 0.85]) with no significant differences in terms of other studied outcomes. Moreover, six studies compared CA to medical treatment in HF vs no HF with a total of 2931 patients. Patients with AF and no HF had a significant reduction in all-cause mortality (RR .041, 95%CI [0.20 to 0.80]), with no significant differences in stroke or AF recurrence. Conclusion Current evidence supports the use of catheter ablation in atrial fibrillation patients, irrespective of their baseline heart failure, to achieve lower mortality and hospitalization rates.all-cause mortalitycardiovascular mortality

The effects of angiotensin receptor-neprilysin inhibitors on clinical outcomes in heart failure with mildly reduced or preserved ejection fraction: real-world evidence from the CCA Database-HF Center

Abstract Background Recent clinical trials have demonstrated the potential efficacy and safety of angiotensin receptor-neprilysin inhibitors (ARNI) in patients with heart failure (HF) with mildly reduced or preserved ejection fraction. Nevertheless, the generalizability of these findings in real-world clinical settings remains to be determined. We aimed to compare the real-world effectiveness of ARNI versus angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB)on clinical outcomes in HF patients with mildly reduced or preserved ejection fraction. Methods Patient-level data was derived from the China Cardiovascular Association Database-HF Center Registry. We included exclusively a subpopulation of HF patients with left ventricular ejection fraction (LVEF) &amp;gt;40% and comorbid with hypertension. Patients prescripted with ARNI at discharge and sustaining to ARNI therapy during follow-up were categorized as the ARNI group, while those maintaining the usage of ACEI/ARB after discharge were designated as the ACEI/ARB group. In complete cases, the primary endpoint of all-cause mortality at one year was assessed by the 1:1 propensity score matching (PSM) method. Results In all HF patients with LVEF &amp;gt;40% comorbid with hypertension, the usage of ARNI has increased from 0.9% in 2017 to 37.2% in 2021. A total of 3348 patients in the ARNI group and 7688 patients in the ACEI/ARB group were identified for comparative effectiveness. After 1:1 PSM, 5482 patients were included in the primary analysis, with 2741 patients in each treatment arm. The proportion of patients receiving higher dosages of ARNI (200mg/d and 400mg/d) was 20.9%, 26.6%, 29.2%, and 30.3% at discharge, 1-month, 3-month, and 1-year, respectively. Over the 1-year follow-up, ARNI was associated with a 20% relative reduction in all-cause death compared to the ACEI/ARB therapy (10.5% vs. 12.9%, adjusted hazard ratio [HR], 0.80 [95% CI, 0.69-0.94], P=0.005). The absolute risk difference in all-cause death between ARNI and ACEI/ARB arms was 2.88 per 100 patient-years (incidence rate difference, -2.88 [95% CI, -4.86 to -0.9]). Cardiovascular death also tended to decrease in the ARNI group but with missed statistical significance (4.5% vs. 4.9%, adjusted HR, 0.89 [95% CI, 0.70-1.14], P=0.373). Treatment benefits were more significant in those with LVEF between 40-50% (adjusted HR, 0.62 [95% CI, 0.48-0.79]), 50-60% (adjusted HR, 0.85 [95% CI, 0.68-1.06]), but not observed in HF patients with LVEF&amp;gt;60% (adjusted HR, 1.80 [95% CI, 1.08-2.98]; Pinteraction&amp;lt;0.001). Conclusion In real-world clinical settings, treatment with ARNI was associated with a significant relative risk reduction in all-cause mortality compared with ACEI/ARB in HF patients with mildly reduced or preserved LVEF. The cardiovascular benefit was concentrated in patients with LVEF ≤60%.

The impact of daily step count with mobile health apps on clinical outcomes among general population

Abstract Background/Introduction Numerous studies have investigated the correlation between daily step count and the reduction of all-cause mortality and cardiovascular events. However, the optimal daily step count for the general population remains controversial. Purpose This study aims to assess cardiovascular risk based on individual step counts using a large cohort that includes step count data from mHealth Apps (Kencom), health checkups databases, and Japanese insurance claims databases. Methods We analyzed data from 85,204 users registered with Kencom between January 2016 and September 2021. The mean step count during one year before and after baseline data collection was used to define each individual's step count. We divided participants into low (N=45,539) and high (N=39,665) step count groups based on their mean step counts. Additionally, we categorized users into five groups based on their step counts (&amp;lt;4000; 4000-5999; 6000-7999; 8000-9999; and ≥10000) to evaluate cardiovascular events. The primary outcome was the occurrence of cardiovascular events, including myocardial infarction, stroke, angina pectoris, heart failure, and atrial fibrillation, as classified by the International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10). The cumulative incidence was estimated over 5 years. Results The high step count group was generally younger and predominantly male. No significant differences in cardiovascular risk factors such as hypertension, dyslipidemia, diabetes mellitus, and current smoking status were found between the two groups. Stratifying baseline characteristics by step count revealed significant differences among the five groups, with the exception of sex. The cumulative incidence of cardiovascular events was significantly lower in the high step count group compared to the low step count group (6.5% vs. 7.5%, log-rank P=0.005, Figure 1). After adjusting for confounding factors, the risk reduction of the high step count group remained significant (HR: 0.92, 95% CI: 0.87-0.98, P=0.005). Among the five step count groups, the incidence of primary outcome significantly differed, with only Group 5 (≥10000 steps) showing a significant reduction in the risk of cardiovascular events compared to Group 1 (&amp;lt;4000 steps) after adjustment (HR: 0.87, 95% CI: 0.77-0.99, P=0.03). Subgroup analyses based on sex indicated that the risk reduction was significant in males in Group 5 but not in females. Conclusion The risk of cardiovascular events was higher in the low step count group compared to the high step count group. After adjusting for confounders, only the highest step count group (≥10,000 steps/day) showed a significant reduction in cardiovascular event risk compared to the lowest step count group.

Incidence of systolic heart failure and need for implantable cardiac defibrillators in patients with atrial fibrillation who had catheter ablation versus antiarrhythmic medical therapy

Abstract Background The CASTLE-AF trial demonstrated that patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) who underwent catheter ablation (CA) showed improved patient outcomes. These outcomes included a reduction in all-cause mortality and heart failure hospitalizations along with an improvement in left ventricular ejection fraction, when compared to those receiving medical therapy alone. However, there is no data regarding development of novel HFrEF and the need for implantable cardiac defibrillator (ICD) in patients with AF who underwent CA vs. those on antiarrhythmic therapy (AAD). Purpose This study aims to assess if there is a difference in the development of HFrEF and the need for ICD intervention amongst AF patients who underwent CA vs. those on AAD. We hypothesize that patients with AF who underwent CA will have a decrease in the development of HFrEF and mitigation in the need for ICD intervention compared to AAD alone. Methods A large retrospective, multicentre database was utilized to identify patients aged 18-80 with AF from 2017-2023. Two cohorts were subsequently established based on treatment received: 1) CA vs. 2) AAD (amiodarone, flecainide, dronedarone, dofetilide, propafenone, sotalol). Patients with crossover between the groups were excluded. Student’s t-test was performed to compare baseline characteristics between cohorts. Relevant comorbidities, atrial fibrillation types, and cardiovascular medications were used for propensity matching. Kaplan Meier curves were calculated to compare outcomes at 5 years such as HFrEF development, ICD implantation, mortality, and hospitalizations. Results Patients that underwent CA (n=32,774) and AAD (n=345,882) were propensity matched yielding 32,670 patients per cohort. CA demonstrated a significantly decreased need for ICD intervention compared to AAD (1.69% vs. 3.28%; HR=0.559; 95% CI [0.503, 0.621], log rank p&amp;lt;0.0001). Secondary outcomes showed significant reduction in development of systolic heart failure (4.83% vs. 10.60%; HR=0.499; 95% CI [0.467, 0.533], log rank p&amp;lt;0.0001), overall hospitalizations (12.03% vs. 27.32%; HR=0.440; 95% CI [0.420, 0.461], log rank p&amp;lt;0.0001), and all-cause mortality (2.38% vs. 14.19%; HR=0.188; 95% CI [0.174, 0.203], log rank p&amp;lt;0.0001) with catheter ablation. Conclusions Patients that underwent CA had a significant reduction in development of systolic heart failure and mitigation in the need for ICD implantation when compared to those on AAD alone. Randomized clinical trials are needed to better understand this relationship and to further define which subpopulation of atrial fibrillation patients would derive the most benefit from CA.

The efficacy of catheter ablation compared to medical therapy in heart failure patients with concomitant atrial fibrillation: A meta-analysis of randomized controlled trials

Abstract Introduction The management of atrial fibrillation in patients with heart failure continues to be a topic of ongoing debate. We conducted a meticulous comparison between two primary treatment modalities: catheter ablation versus medical therapy. Our aim is to assess the efficacy of these interventions in patients presenting with both atrial fibrillation and heart failure, drawing from the randomized controlled trials. Methods A comprehensive literature search was conducted up to February 2024, utilizing databases including PubMed, EMBASE, and Clinicaltrials.gov. A total of 10 randomized studies were identified and their data were extracted and analyzed. The primary outcomes assessed included the impact of catheter ablation on all-cause mortality, cardiovascular death, left ventricular ejection fraction (LVEF %), and 6-minute walk test (6MWT) in meters. Data were analyzed utilizing a random-effects model to calculate weighted mean differences for LVEF and 6MWT, and risk ratios for all-cause mortality and cardiovascular death on Review Manager 5.3 (RevMan 5.3) software. Results In totality, data from 1944 heart failure patients (N = 966 on catheter ablation; N = 978 on medical therapy) with concomitant atrial fibrillation were included. Patients in the catheter ablation group exhibited a significant reduction in all-cause mortality (RR 0.63 [95% CI 0.48, 0.83]; P=0.001; I2 = 17%). Moreover, there was a notable decrease in cardiovascular death among patients undergoing catheter ablation (RR 0.53 [95% CI 0.34, 0.81]; P=0.004; I2 = 20%). Patients who underwent catheter ablation demonstrated a marked improvement in LVEF (MD 5.79 [95% CI 3.13, 8.44]; P &amp;lt;0.0001; I2 = 82%). The 6MWT revealed superior outcomes in the catheter ablation group (MD 22.69 [95% CI 9.87, 35.50]; P=0.0005; I2 = 38%). Conclusion Heart failure patients with concomitant atrial fibrillation undergoing catheter ablation therapy exhibited notable improvements in LVEF and 6MWT, alongside a significantly reduced risk of all-cause mortality and cardiovascular death compared to those receiving solely medical therapy. These findings shed light on the potential advantages and superior outcomes associated with catheter ablation therapy in preserving cardiac chamber function and mitigating mortality in such a patient cohort. However, further investigations are warranted to understand the long-term benefits and optimal management strategies for such individuals.

Remote monitoring of implantable cardioverter defibrillators: a systematic review and meta-analysis of randomised controlled trials

Abstract Background Remote monitoring (RM) of implantable cardioverter defibrillators (ICD) has been widely adopted as the standard follow-up strategy [1]. Observational data [2,3] has suggested morbidity and mortality reduction associated with RM compared to traditional in-person ICD follow-up, however, randomised controlled trials (RCTs) demonstrate heterogeneous results. Purpose To assess the impact of RM of ICDs on morbidity and mortality through a systematic review and meta-analysis of RCTs comparing RM versus in-person follow-up. Methods PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and reference lists were searched for RCTs evaluating RM compared to in-person follow-up of patients with ICDs or cardiac resynchronisation therapy with defibrillator (CRT-D) devices. Meta-analyses of all-cause mortality, cardiovascular (CVD) hospitalisation and inappropriate ICD shock rates were performed. Results Literature search identified 1011 relevant publications, out of which 15 RCTs [4-18] involving a total of 7579 patients (13 RCTs reporting mortality rate, 7 RCTs reporting CVD hospitalisation rate, 6 RCTs reporting inappropriate ICD shock rate) met the inclusion criteria. Pooled analyses demonstrated that RM is not associated with a significant reduction in all-cause mortality (OR 0.95; 95% CI 0.78-1.16; p=0.60)(Figure 1, panel a) or odds of CVD hospitalisation (OR 0.95; 95% CI 0.72-1.25; p=0.70) (Figure 1, panel b). RM was, however, shown to be associated with significantly lower odds of receiving an inappropriate ICD shock compared to the control group (OR 0.63; 95% CI 0.46-0.88; p=0.006) (Figure 1, panel c). The IN-TIME study (the only RCT that independently reached statistical significance in terms of RM effect on mortality) enrolled patients exclusively with a Biotronik ICD or CRT-D; this raised the question as to whether the choice of vendor had an impact on mortality. Our subgroup analysis of the Biotronik device studies demonstrated that there was no significant all-cause mortality benefit (OR 0.87, 95% CI 0.59-1.27; p=0.46). Conclusions This meta-analysis of 15 RCTs including 7579 patients suggests that RM of ICDs is associated with a reduction in inappropriate ICD shocks, without a significant reduction in mortality or CVD hospitalisation when compared to in-person follow-up. Further studies comparing different RM processing and alert response models are warranted.

Catheter ablation vs medical management for atrial fibrillation in patients with heart failure: a systematic review and metanalysis

Abstract Background Current guidelines recommend a class IIa recommendation for catheter ablation in Atrial Fibrillation [AFIB]. Traditionally, catheter ablation has been known to be more effective in maintaining sinus rhythm than pharmacological management. However, there is sparse evidence to suggest that this translates to improved clinical outcomes in patients with heart failure. We did a systematic review and meta-analysis of randomized trials to compare the efficacy of ablation vs medical management for AFIB in heart failure. Methods A systematic search was conducted for randomized trials from inception to Jan 2024 for studies comparing the outcomes of catheter ablation vs medical management for AFIB in heart failure. The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular (CV) mortality, heart failure hospitalizations, change in LV ejection fraction (LVEF), AF recurrence rate, 6-minute walk test (6MWT), change in MLHFQ scores and cerebrovascular events. Random-effects models were used to calculate the pooled incidence, mean difference (MD), and risk ratios (RRs) with 95% confidence intervals (CIs). Results A total of 10 RCTs with 2,348 patients were included in this study. Pulmonary vein isolation was the mainstay ablation strategy used. Compared with medical management, Ablation was associated with a significant reduction in all-cause mortality (RR- 0.61; 95% CI, 0.48-0.78; P&amp;lt;0.0001). Ablation was also associated with lower cardiovascular (CV) mortality (RR- 0.52; 95% CI, 0.36-0.75; P&amp;lt;0.0004), heart failure hospitalizations (RR- 0.67; 95% CI, 0.54-0.82; P&amp;lt;0.0001) and AF recurrence rate (RR- 0.43; 95% CI, 0.25-0.75; P&amp;lt;0.003). The study showed an improvement in LVEF (RR - 6.05; 95% CI, 3.35-8.75; P&amp;lt;0.0001), 6MWT (RR- 13.99; 95% CI, 4.18-23.81; P&amp;lt;0.005) and in MLHFQ score (RR -6.98; 95% CI, -12.03 to -1.93; P&amp;lt;0.007. There was a statistically significant difference between the 2 cohorts in the rates of cerebrovascular events (RR- 0.68; 95% CI, 0.35-1.30; P&amp;lt;0.24). Conclusion Randomized trials have shown clear benefits with catheter ablation compared to medical management for AFIB in heart failure. Ablation has demonstrated significantly lower all-cause mortality, reduced CV mortality, HF hospitalizations, AFIB recurrence rate, and improvement in LVEF. Patients who underwent catheter ablation showed improvement in functional outcomes like 6MWT and MLHFQ scores. There was no difference in the incidence of cerebrovascular events compared to medical management. This study adds to the growing evidence in the literature for ablation therapy; however, more trials are needed to identify patients for optimal benefits across the spectrum of heart failure patients.Forest PlotsForest Plots

All-cause mortality and incidence of appropriate therapy from a primary preventive implantable cardioverter defibrillator in patients with non-ischemic dilated cardiomyopathy

Abstract Background The DANISH study published in 2016 indicated limited benefit of primary prevention implantable cardioverter-defibrillator (ICD) in patients with non-ischemic dilated cardiomyopathy (niDCM). We aimed to investigate the long-term outcome and incidence of ICD therapy in patients with niDCM implanted on primary prevention indication during 2014-2022. Methods A total of 116 patients with niDCM were prospectively included for primary prevention ICD implantation between 2014 and 2022 in the multicenter IMPROVE study (clinical trials NCT02286908). All patients were examined with electrocardiogram, echocardiography and blood sampling at inclusion. The primary outcome was all-cause mortality, and the secondary outcome was appropriate ICD therapy. Outcomes were compared in patients included from 2014 to end of 2016 (DCM2014-16, n=49) and from 2017-2022 (DCM2017-22, n=67). Results At inclusion, patients in DCM2017-22 were younger (54 years [interquartile range (IQR) 44-68] vs. 64 years [IQR 55-70], p=0.001), had higher left ventricular ejection fraction (LVEF) (33% [IQR 25-38] vs. 24% [IQR 21-31], p&amp;lt;0.001) and less frequently received cardiac-resynchronization therapy defibrillator (6% vs. 29%, p=0.001) compared to DCM2014-16. Over a median 4.4-year follow-up, the all-cause mortality was 14%, of which 10% occurred in the DCM2017-22 patients (2.6 events/100 person-years), and 18% in the DCM2014-16 patients (4.0 events/100 person-years), p=0.38. There was no difference in appropriate ICD therapy between the two groups (p=0.90). Conclusion Patients receiving primary prevention ICD for niDCM after publication of the DANISH study were younger with higher LVEF, indicating a change in clinical practice after the publication. Despite this, there was no significant reduction in all-cause mortality or difference in appropriate ICD therapies. Unchanged mortality and event-rates may indicate the correct identification of high-risk patients.