All-cause Mortality Research Articles

Clinical outcomes of patients with heart failure with improved ejection fraction after acute MI: a multicenter prospective study from the COREA-AMI Registry

Abstract Background The 2021 Universal Definition of Heart Failure introduce a new classification, heart failure with improved ejection fraction (HFimpEF). As yet, little is known about the long-term clinical outcomes of patients with HFimpEF after acute myocardial infarction (AMI). Methods From a multicenter, prospective cohort of AMI patients undergoing PCI, patients with an initial echocardiogram at the time of PCI and at least one follow-up echocardiogram one month to two years after the initial event were considered for analysis. HFimpEF was defined as initial left ventricular ejection fraction (LVEF)≤40% and at least one follow-up LVEF>40% with an increase of ≥10% from baseline. Persistent HFrEF was defined as LVEF ≤40% without interval improvement. Patients with LVEF>40% were defined as having preserved LVEF. The primary endpoint was all-cause mortality. Results In total, 3038 patients with repeated echocardiogram measurements were selected for initial analysis. 187 patients were identified as having HFimpEF, 190 patients had persistent HFrEF, 631 patients had HFmrEF, and 2030 patients had preserved EF. Kaplan-Meier analysis revealed that HFimpEF was associated with improved survival compared to chronic HFrEF, but inferior to preserved LVEF (log-rank p<0.001). Even after multivariate Cox regression analysis was done to account for confounding variables, HFimpEF was associated with reduced mortality compared to persistent HFrEF (HR 0.49, 95% CI 0.31-0.78). Compared to patients with preserved LVEF, HFimpEF patients had a tendency toward higher mortality, but did not reach statistical significance (HR 1.18, 95% CI 0.80-1.76). Conclusion HFimpEF is associated with decreased all-cause mortality compared to persistent HFrEF in patients with AMI.

C-Reactive Protein-to-Serum Chloride Ratio: A Novel Marker of All-Cause Mortality in Maintenance Haemodialysis Patients

Background and Objectives: hypochloremia is an emerging risk factor for mortality in patients with chronic kidney disease. The pathophysiological mechanisms of this finding are not very clear. Some studies suggest the influence of inflammation as a synergistic factor, so we set out to analyse the association of a novel C-reactive protein-to-serum chloride ratio (CRP/Cl−) with the prognosis of maintenance haemodialysis patients and to assess its relationship with fluid status and body composition measured by bioimpedance. Materials and Methods: the present work is a retrospective cohort study of maintenance haemodialysis patients from our chronic outpatient haemodialysis programme between 1 January 2022 and 31 December 2022. (n = 281). Survival time was collected for all patients and analysed using the Kaplan–Meier method. A Cox proportional hazards regression model was used to evaluate survival probabilities. Variables included in the model were selected using a stepwise selection procedure based on the corrected Akaike information criterion (AICc), which balances model fit and complexity. Results: during a median follow-up of 306 days, 34 patients died. Patients in the fourth quartile of the CRP/Cl− (>0.118 mg/mEq) had higher overall mortality (log-rank test, p = 0.0011). In the Cox multivariate analysis, the variables significantly associated with higher mortality were higher modified Charlson index (MCI), lower body surface area (BSA), lower interdialytic weight gain (IDWG), and higher CRP/Cl− ratio. The latter variable was independently associated with higher overall mortality (adjusted hazard ratio = 1.027; 95% confidence interval [CI], 1.000–1.055 p = 0.0469). Conclusions: Higher CRP/Cl− ratio values were associated with higher all-cause mortality in our maintenance haemodialysis patients.

Examining prognostic scores for short-term major adverse cardiovascular events prediction following primary PCI: a comparative analysis

Abstract Background Accurately predicting short-term MACE (major adverse cardiac events) following primary PCI remains a clinical challenge. This study aims to assess the effectiveness of four established risk scores in predicting short-term MACE after primary PCI (percutaneous coronary intervention). Methodology We enrolled a cohort of consecutive adult patients diagnosed with STEMI (ST elevation myocardial infarction) undergoing primary PCI in this prospective observational study. Patients were followed at the interval of 3 months up for up to 12 months, and MACE events were recorded. Additionally, we obtained TIMI, PAMI, CADILLAC, and GRACE scores. Results A total of 2839 patients (79.3% male, mean age 55.6 ± 11.2 years) were included. Over a median follow-up of 244 days, the composite MACE rate was 18.3% (519). All-cause mortality was 13.5% (384), re-infarction requiring revascularization was 4.3% (121), heart failure-related re-hospitalization was 2.6% (74), stent thrombosis occurred in 5.6% (160), and CVA (cerebrovascular accident) events were documented in 1% (28). The AUC (area under the curve) for TIMI, PAMI, CADILLAC, and GRACE scores were 0.658 [0.630-0.685], 0.658 [0.632-0.684], 0.669 [0.644-0.695], and 0.675 [0.649-0.701], respectively, for the prediction of MACE. On multivariable Cox regression, medium and high-risk categories based on GRACE score were independent predictors of MACE with adjusted HR (hazard ratio) of 1.52 [1.21-1.92]; p<0.001 and 1.92 [1.34-2.75]; p<0.001, respectively. Conclusion A significant proportion of patients experienced short-term MACE after primary PCI. While none of the assessed scores demonstrated significant predictive power, the GRACE score exhibited comparatively better predictive ability than TIMI, PAMI, and CADILLAC scores

Derivation and external validation of new ESC 0/1-h algorithm cut-offs for high-sensitivity troponin T and I in the cancer population

Abstract Background The diagnostic performance of high-sensitivity cardiac troponin T/I (hs-cTnT/I) and the efficacy of the European Society of Cardiology (ESC) 0/1h-hs-cTnT/I-algorithms for the early diagnosis of non-ST-elevation myocardial infarction (NSTEMI) is reduced in cancer patients presenting to the emergency department (ED) with chest pain.[1] Purpose This study aimed to derive and externally validate new cut-offs for the ESC 0/1h-hs-cTnT/I-algorithms in chest pain patients with active or past cancer. Methods Patients presenting with acute chest discomfort to the ED were prospectively enrolled in an international multicenter diagnostic study. Final diagnoses were centrally adjudicated by 2 independent cardiologists applying the fourth universal definition of myocardial infarction using all available medical records, cardiac imaging, and serial hs-cTnT/I. Hs-cTn concentrations were measured at presentation and after 1 hour. New assay-specific cutoffs for the ESC 0/1h-hs-cTnT/I-algorithm were derived and externally validated in two independent cohorts. Results Among 541 and 516 eligible patients with 0h and 1h hs-cTnT and hs-cTnI values, respectively, application of the current ESC 0/1h-hs-cTnT/I algorithm triaged 317 (58.6%) and 306 (59.3%) patients to either rule-out or rule-in, leaving 224 (41.4%) and 210 (40.7%) patients in the observe-zone of the ESC 0/1h-hs-cTnT/I algorithm, respectively. The novel ESC 0/1h-hs-cTnT cut-offs ruled out NSTEMI with a cut-off <8 ng/L at presentation (if chest pain onset >3 hours) or <14 ng/L together with a 0/1-hour delta <3 ng/L, ruling-out 241 patients (44.5%) with a sensitivity and negative predictive value (NPV) of 99.2% and 99.6%, respectively. The novel ESC 0/1h-hs-cTnI cutoffs ruled out NSTEMI with a cut-off <7 ng/L at presentation (if chest pain onset >3 hours) or <10 ng/L together with a 0/1-hour delta <3 ng/L, ruling-out 281 patients (54.5%) with a sensitivity and NPV of 99.1% and 99.6, respectively. Findings were confirmed in both internal and external validation (Figure 1). A total of 167 (32.8%) patients died at 5-years, of whom 61 died of cardiovascular causes, and 30 (5.9%) patients had an MI at 5 years. 5-year all-cause mortality for the rule-out group was similar for both the current and the novel ESC 0/1-h algorithm, although the novel one identified patients in the observe zone group as having the highest mortality (Figure 2). Incidence of 5-year cardiovascular mortality or AMI provided by the current ESC 0/1h-algorithm was similar for the rule-in and observe zone groups for both hs-cTnT and hs-cTnI. Conclusions In chest pain patients with a history of cancer, new derived assay-specific cutoffs for the ESC 0/1h-hs-cTnT/I-algorithm achieved a higher proportion of patients triaged to either rule-out or rule-in without decreasing safety. The low mortality rate of the rule-out group identified by the new algorithm further reassures on the safety of the new derived cut-offs.Sensitivity analysis in the APACE cohort5-year all-cause mortality

Effects of Sacubitril/Valsartan on all-cause hospitalizations in heart failure: participant-level pooled analysis of PARADIGM-HF and PARAGON-HF

Abstract Background Sacubitril/valsartan is indicated to reduce the risk of cardiovascular (CV) death and heart failure (HF) hospitalizations in patients with chronic HF. However, many of these patients are older and have multiple comorbidities that increase the risk of hospitalizations other than HF, yet the effects of sacubitril/valsartan on hospitalizations of any cause have not been well described. Methods PARADIGM-HF and PARAGON-HF were phase-3, global multicenter randomized clinical trials that evaluated sacubitril/valsartan versus enalapril (in PARADIGM-HF) or valsartan (in PARAGON-HF) across the spectrum of left ventricular ejection fraction (LVEF; ≤40% in PARADIGM-HF and ≥45% in PARAGON-HF). We pooled individual participant-level data from these 2 trials to examine the effects of sacubitril/valsartan on time-to-first investigator-reported all-cause and cause-specific hospitalization using Cox proportional hazards models, stratified by geographic region and trial. We additionally examined heterogeneity in treatment response by LVEF. Results Over 2.8 years median follow-up, among 13,194 participants in the pooled PARADIGM-HF/PARAGON-HF, sacubitril/valsartan significantly reduced the risk of all-cause hospitalizations compared with renin-angiotensin system inhibitor (HR 0.92; 95% CI 0.88-0.97; P=0.002); Figure 1 Panel A. The absolute risk reduction (ARR) was 2.1 per 100 patient-years corresponding to a number-needed-to-treat (NNT) of 48 patient-years of treatment exposure to prevent 1 all-cause hospitalization. Reductions in overall hospitalizations among patients with identifiable causes (N=5,783) seemed to be primarily driven by lower rates of cardiac and pulmonary hospitalizations associated with sacubitril/valsartan. Patients treated with sacubitril/valsartan did not have a higher rate of composite non-cardiac hospitalizations (Figure 1 Panel B). Similarly, sacubitril/valsartan reduced the risk of the composite of all-cause hospitalization or all-cause mortality (HR 0.92; 95% CI 0.87-0.96; P<0.001), with an ARR of 2.5 per 100 patients-years and an NNT of 40 patient-years. For all-cause hospitalization, we observed significant heterogeneity by LVEF as a continuous measure (Pinteraction=0.027); treatment effects were most apparent in those with an LVEF below 60% (HR 0.91 95% CI 0.86-0.96; Figure 2). Conclusions In a pooled analysis of >13,000 patients with chronic HF, sacubitril/valsartan reduced hospitalization for any reason with benefits most apparent among those with an LVEF below normal.

Lipoprotein (a), coronary artery disease risk, and MACE in individuals without standard modifiable risk factors in the UK Biobank

Abstract Background A significant proportion of patients with coronary artery disease (CAD) lack standard modifiable risk factors (SMuRFs; smoking, hypercholesterolaemia, diabetes and hypertension), for example with recent analyses demonstrating that around 25% of patients with ST-elevation myocardial infarction are SMuRF-less(1). With continued focus on primary prevention in cardiovascular disease, the SMuRF-less subset is likely to increase over time. A body of evidence has implicated lipoprotein (a) in CAD, but no such studies have investigated this association in a purely SMuRF-less population. Purpose To investigate the role of lipoprotein (a) in predicting CAD risk and major adverse cardiovascular events (MACE) in a large, SMuRF-less cohort. Methods The UK Biobank is a large prospective multicentre study which recruited over 500,000 participants in the UK aged 37-73 years at entry between 2006-2010. SMuRFs were defined as 1) smoking (current or historical), 2) hypercholesterolaemia – lipid lowering medication on enrolment or total cholesterol >5.5mmol/L or LDL-C >3.5mmol/L, 3) previous diagnosis of diabetes mellitus, or HbA1c >48mmol/mol, 4) previous diagnosis of hypertension. MACE was defined as a composite of coronary artery disease – previous myocardial infarction, percutaneous coronary intervention or coronary artery bypass graft surgery –, stroke, or all-cause mortality. Results Of the total UK Biobank cohort, 46,139 participants were identified as SMuRF-less together with a valid lipoprotein (a) level. Median follow-up duration was 12yrs. In univariate analyses (Table 1), there was no significant difference in lipoprotein (a) concentrations between individuals with and without MACE (16.9 vs. 17.1nmol/L respectively, p = 0.913). The overall event rate was low, with just 3% MACE (1381 events) overall. Older age, male gender, apolipoprotein A, apolipoprotein B, HbA1c level, HDL cholesterol level and body mass index were all associated with MACE. In regard to all-cause mortality alone, there was no association with lipoprotein (a) level, although the other aforementioned parameters were all significantly associated with this outcome. Similarly, lipoprotein (a) was not a significant predictor of stroke. However, there was a large difference in lipoprotein (a) levels between patients with and without CAD (27.2 vs. 17.1nmol/L respectively, p = 0.004). In Kaplan-Meier analysis, lipoprotein (a) level above the 77th percentile (60.3nmol/L) was significantly associated with CAD (p=0.032). In Cox regression models, despite the low event rate, lipoprotein (a) was a significant predictor of CAD (HR 1.00-1.01, p=0.01), and importantly the only potentially modifiable parameter (N = 39,433, 111 events, Table 2). Conclusion Lipoprotein (a) independently predicts CAD in those without SMuRFs, highlighting the importance of checking this parameter in such patients, particularly given the novel antisense technologies in development which may lower lipoprotein (a)(2).Univariate analysesCox regression for CAD

GLP1-RA versus DPP4 inhibitors on cardiovascular outcomes: A three-year real-world analysis

Abstract Background Cardiovascular outcome trials of GLP1-RAs have massively impacted the clinical practice in the management of patients with type 2 diabetes. The cardiovascular protective properties of GLP1-RA compared to DPP4 have been demonstrated in an observational setting before, however recent methodological developments have enabled clinically relevant effect estimation. Aim This study aimed to evaluate the real-world cardiovascular outcomes of GLP1-RA versus DPP4 inhibitors in patients with type 2 diabetes and high cardiovascular risk. Methods In this study, we utilized the Danish nationwide registers to identify new users of GLP1-RA or DPP4 therapies from 2012 to 2022. Participants were required to be either at least 50 years of age and have one or more of the following conditions: hypertension, chronic obstructive pulmonary disease, cardiovascular disease, or chronic renal disease or be at least 60 years of age and have hypertension. Additionally, their glycated hemoglobin (HbA1c) levels needed to be 53 mmol/mol or higher within the year preceding their first prescription date for these therapies. The index date was defined as the initial prescription date, and comorbidities and medicine use were evaluated up to 10 years prior to this date. Individuals who had filled prescriptions for SGLT2 inhibitors within six months prior to their index date were excluded from the study. The outcome of interest was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE). Patients were followed for up to three years until MACE, all-cause mortality, emigration, or until the end of follow-up on December 31, 2022. To assess the three-year risk of MACE, the Aalen Johansson estimator was used. A casual inference framework was employed estimating the three-year average treatment effect using g-formula based on Cox regression with competing risk. Results A total of 26,190 individuals were included, with 19,494 initiating DPP4 inhibitor therapy and 6,696 initiating GLP1-RA therapy. The three-year risk of MACE was 8.56% (95% confidence interval [CI]: 8.11 to 9.00) for the DPP4 initiator group, compared to 4.76% (95% CI: 4.08 to 5.43) for the GLP1-RA initiator group. Emulating what would have happened had all included individuals initiated GLP1-RA treatment versus had all initiated treatment with DPP4, accounting for age, sex, income, education, degree of urbanization, diabetes duration, baseline hba1c level, co-medicine, and co-morbidities, we estimated an three-year average treatment effect of -2.05% (95% CI:-2.92;-1.18) , p-value<0.001) for GLP1-RA initiation versus DPP4 initiation for MACE. Conclusion Our findings suggest that GLP1-RA use is associated with a significantly lower risk of MACE compared to DPP4 inhibitors in a real-world population of patients with type 2 diabetes and high cardiovascular risk. This supports the cardiovascular protective role of GLP1-RA in clinical practice.

Association of cardio-cerebrovascular death with isolated diastolic hypertension: a nationally representative survey of 85, 138 adults

Abstract Background Recently, the 2023 European Society of Hypertension (ESH) guideline for hypertension management include isolated diastolic hypertension (IDH) as a distinct classification. But, studies have yielded inconsistent associations between IDH and cardiovascular disease (CVD) events. Method We obtained data from 85138 participants without CVD and antihypertensive medication use who included in the China Chronic Disease and Risk Factors Surveillance (CCDRFS) project 2010. We extracted data on deaths from any cause, cardiovascular diseases, and stroke during follow up. The hazard ratios (HR) and 95% confidence intervals (CI) for all-cause mortality, cardiovascular mortality, and stroke mortality associated with each blood pressure (BP) group were calculated using Cox proportional hazards models, with the normotension group as the reference. Our analyses were performed with sequential adjustment. In the first step, we carried out unadjusted analyses (model 1). In model 2, we added age, sex, ethnic, location, educational attainment, smoking status, alcohol drinking status, exercise, BMI, high-density-lipoprotein cholesterol, low-density-lipoprotein cholesterol, fasting glucose level as adjustment covariates. Results Overall, 57144 (67.1%) participants had normotension, 3826 (4.5%) participants had IDH, 11013 (12.9%) participants had isolated systolic hypertension (ISH), 13155 (15.5%) participants had systolic and diastolic hypertension (SDH). Compared with normotension, IDH was not statistically associated with a significantly increased risk of all-cause mortality (HR, 1.09 [95% CI, 0.86–1.39], model 2), or cardiovascular mortality (HR, 1.21 [95% CI, 0.74–1.96], model 2). On the contrary, IDH was significantly associated with a modestly higher risk of stroke mortality (HR, 1.84 [95% CI, 1.13–3.00], model 2). IDH was significantly associated with a modestly higher risk of stroke mortality in middle aged and older adults, but not young adults (age <45years). Similar results were obtained for men, while for women the associations between the prevalence of IDH and a higher incidence of stroke mortality were not significant. Stage 1 to stage 3 ISH or SDH were associated with a higher risk for all-cause mortality, cardiovascular mortality, and stroke mortality. Conclusion IDH was associated with an increased risk of stroke mortality among the large nationally representative Chinese population. Intervention for IDH may be effective in reducing the burden of stroke in China.

The role of anticoagulation in atrial high-rate episodes: a meta-analysis

Abstract Background The role of anticoagulation in patients with atrial high-rate episodes (AHRE), who have no prior history of atrial fibrillation or atrial flutter, is being extensively studied. Purpose Given the increased thrombo-embolic risk in patients who have atrial high-rate episodes, our aim was to evaluate whether anticoagulation leads to enhanced clinical outcomes compared to no anticoagulation (1). Methods We searched PubMed, EMBASE, and the Cochrane Library, through February 2024, for studies evaluating outcomes in patients with atrial high-rate episodes managed with oral anticoagulation (OAC) compared to those not managed with oral anticoagulation. Outcomes assessed were ischemic stroke, thromboembolic events, major bleeding, and all-cause mortality. A fixed-effects model was used to calculate pooled risk risk ratios (RR) and their 95% confidence intervals (CI). Results A total of 4 studies comprising 6788 patients were included. Anticoagulation was associated with a significant reduction in the risks of ischemic stroke (RR 0.66; 95% CI 0.49 - 0.90; P = 0.0084) and thromboembolic events (RR 0.70; 95% CI 0.55 - 0.89; P = 0.0037). Compared to atrial high-rate episodes not managed with anticoagulation, there was a significantly increased risk of major bleeding with anticoagulation (RR 1.57; 95% CI 1.23 - 2.00; P = 0.0002), while the risk of all-cause mortality was similar (RR 1.07; 95% CI 0.95 - 1.21; P = 0.2437). Conclusion Our study suggests that anticoagulation in patients with atrial high-rate episodes decreases the risks of ischemic stroke and thromboembolic events, while increasing the risk of major bleeding, compared patients not managed with anticoagulation. Our study does not show a mortality benefit with the use of anticoagulation in patients with atrial high-rate episodes. Further studies are needed to confirm the safety and efficacy of anticoagulation in atrial high-rate episodes.Forest Plots of Outcomes Assessed

The development and long-term maintenance of heart failure with improved ejection fraction after a heart failure hospitalization: how are mortality rates affected?

Abstract Background According to the current ESC HF Guidelines (GLs), the implementation of the guideline-directed medical therapy (GDMT) is of strategic importance in heart failure (HF) with reduced ejection fraction (HFrEF). In the effect of the successful implementation of the modern GDMT, significant improvement in terms of the left ventricular ejection fraction (LVEF) might be expected in HFrEF. Hence, a new HF category, the improved ejection fraction (HFimpEF), was introduced in the current ESC HF GLs, which has come to the spotlight in the recent years. However, its course and long-term prognosis are still not clearly understood. Aim To assess the development and long-term maintenance of the HFimpEF category among a consecutive patient cohort requiring hospitalization due to HFrEF, evaluate its effect on prognosis, and examine the independent predictors of its development. Patients and methods A retrospective analysis was carried in a real-world cohort of 270 HFrEF patients (male: 77%, age: 61[49-68]years, coronary artery disease: 47%, diabetes: 30%, hypertension: 60%, atrial fibrillation: 35%, LVEF: 25[20-30]%, eGFR at admission: 59[45-73]mL/min/1.73m², NT-proBNP at admission: 4733[2368-9711]pg/mL, SBP: 120[107-135]mmHg) hospitalized for HF in 2019-2023 at two tertiary cardiac centers. At admission the complex modern GDMT of HFrEF had been already introduced (RASi[ACEi/ARB/ARNI]: 61%, βB: 63%, MRA: 47%, SGLT2i: 6%) in the minority of the cohort. The improvement to the HFimpEF category was examined after the therapy optimization (OMT). All-cause mortality (ACM) rates were evaluated with Kaplan-Meier method and the predictors of the development to HFimpEF category were assessed with logistic regression analysis. Results In the total cohort at discharge, a high proportion of patients received RASis (94%), βBs (90%), MRAs (97%), and SGLT2is (35%). 79 patients (29%) evolved to the HFimpEF category after OMT. During the median 810 [456-1161] days of follow-up (FU), HFimpEF patients had lower, but unquestionably still increased mortality rates (29% vs. 10%, p=0.001; non-HFimpEF vs. HFimpEF patients). At two years of the FU period, based on the available echocardiographies, 98 % of the patients remained in the HFimpEF category. After performing a multivariate logistic regression analysis, the severity of the LV systolic dysfunction (LVSD) and the „de novo" diagnosis of HFrEF proved to be independent predictors of the development of the HFimpEF category. Conclusions In the effect of the implementation of GDMT, a significant proportion (29%) of our multimorbid, hospitalized HFrEF patient cohort improved to the HFimpEF category. The predictors of its development were the severity of the LVSD and "de novo" HFrEF diagnosis. During the FU period, most of the HFimpEF patients remained in this category. However, their persistently elevated mortality rates raise the awareness of the importance of the conscious application and maintenance of GDMT.

Outcomes of implantable cardioverter-defibrillators in patients with a left ventricular assist device: a systematic review and meta-analysis

Abstract Introduction Implantable Cardioverter-Defibrillators (ICDs) improve survival in advanced heart failure with reduced ejection fraction (HFrEF) and prevent sudden cardiac death. However, the prognostic benefits of ICDs among patients with a Left Ventricular Assist Device (LVAD) remain uncertain and controversial. Therefore, we conducted a systematic review and meta-analysis to assess the effectiveness and safety of ICD implantation among LVAD recipients. Methods We performed a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed and EMBASE for the peer-reviewed articles published in English assessing the impact of ICD implantation among LVAD recipients, till 10/01/2024. ICD implantation was defined as implantation before LVAD, simultaneous implantation with LVAD, or within 30 days of LVAD insertion. Two independent review authors assessed the quality and risk of bias of the included studies. A random-effect model was used to combine data in forest plots. The primary outcome was all-cause mortality associated with ICD implantation compared to no ICD implantation, and the secondary outcomes included ventricular arrhythmia (VT), and hemorrhagic stroke. Heterogeneity was assessed using Q test and I2, with I2 > 50% indicating marked heterogeneity. Results A total of 13 observational studies comprising 54571 recipients of LVAD were included in the analysis of the primary outcome. All-cause mortality was similar among patients with ICD versus no ICD (Odds Ratio [OR]= 0.77; 95% CI, 0.57-1.04, I2= 89%, P=0.09), as shown in Figure 1. Likewise, ICD implantation was associated with similar rates of VT and hemorrhagic stroke (VT: OR= 1.81, 95% Cl, 0.82-4.01, I2= 90%, P=0.14; hemorrhagic stroke: OR= 1.01, 95% Cl, 0.81-1.25, I2= 0%, P= 0.95). Conclusion Among patients with HFrEF and LVAD as advanced heart failure therapy, ICD implantation didn’t provide additional prognostic survival benefit, suggesting possible use of LVAD without ICD implantation.Figure 1.Forest plot of mortality

Estimated number of COVID-19 deaths averted by vaccination in Belgium

Abstract Background Vaccination campaigns have been rolled out globally to limit the impact of COVID-19 on severe health outcomes, including mortality. We aimed to estimate the number of averted deaths by COVID-19 vaccination in the Belgian population aged ≥65 years, between January 2021 and January 2023. Methods Nationwide data on COVID-19 infections, vaccinations and all-cause mortality were individually linked. We estimated Vaccine Effectiveness against COVID-19 mortality (VE) in persons having received a vaccine dose in the last 6 months using a Cox proportional hazards model adjusted for age, sex, time since vaccination, previous infection, comorbidities, province and income. COVID-19 death was defined as a death within 1-7 weeks after a positive SARS-CoV-2 laboratory-test. Based on obtained VE estimates, vaccine coverage and national COVID-19 mortality data, we estimated the number of averted deaths (expected deaths without vaccinating minus the reported deaths). Results By January 31st 2023, 11,033 COVID-19 deaths have been reported in Belgium. The average vaccine coverage was 48% during alpha, 85% during delta and 63% during omicron dominance. VE was estimated at 0-59 days after vaccination, for 65-79 year and ≥80 year-olds respectively, at 65% (58%-60%) and 35% (28%-41%) during Alpha, at 84% (82%-87%) and 79% (77%-81%) during Delta and at 83% (80%-85%) and 71% (68%-73%) during Omicron dominance. We estimated 10,042 deaths averted (range: 8,917-11,188) among the Belgian population aged ≥65 years, representing a 48% reduction (range 45%-50%) in the expected deaths. Out of 10,042 averted deaths, the majority was averted during Delta (47%; 4,670) or Omicron dominance (43%; 4,366), compared to during Alpha dominance (10%; 1,006). Conclusions Vaccinating against COVID-19 led to an important reduction in COVID-19-related mortality among the Belgian population ≥65 years, in particular during Delta and Omicron dominance, underscoring the effectiveness of vaccines against mortality. Key messages • Vaccinating against COVID-19 led to an important reduction of 48% in COVID-19-related mortality among the Belgian population ≥65 years, in particular during Delta and Omicron dominance. • Vaccine effectiveness against COVID-19 mortality was estimated as high in the Belgian population ≥65 years (range: 71-84%) during Delta and Omicron dominance, also among elderly over 80 years.

Clinical characteristics and long-term outcomes of patients with heart failure with supra-normal ejection fraction: data from LECRA-HF registry

Abstract Background Heart failure with preserved ejection fraction (HFpEF) remains insufficiently characterized subgroup of HF with increasing prevalence and limited treatment options. Relationship between clinically assessed left ventricular ejection fraction (LVEF) and survival showed that LVEF ≥65% is associated with higher mortality. Therefore, a novel category of heart failure with supra-normal left ventricular ejection fraction (HFsnEF) was introduced in 2019. However, clinical characteristics and long-term outcomes of HFsnEF patients remain insufficiently elucidated. Purpose We sought to characterize Polish HFsnEF patients and to provide their long-term mortality in comparison to HFpEF. Methods Of 1186 patients enrolled in the single-center Lesser Poland Cracovian Heart Failure (LECRA-HF) Registry between 2009 and 2019 and hospitalized due to HF decompensation 261 (22%) of them were those with LVEF ≥50%. 40 (15.3%) of them were classified as HFsnEF (LVEF ≥65%) and the remaining 221 (84.7%) as HFpEF. The data including patients’ demography, anthropometric measurements, cardiovascular risk factors, prior cardiological treatment and other comorbidities were collected. The long-term follow-up of all-cause mortality was obtained from the Polish National Death Registry. Results HFsnEF patients were less frequently hypertensive (75 vs 88.2%, P=0.026) and had higher baseline LVEF (65 [65-70] vs 55 [50-60] %, P<0.001) than HFpEF subjects. Furthermore, HFsnEF patients presented lower INR (1.1 [1-1.6] vs 1.3 [1.1-1.9], P=0.027) and total protein level (57 [25-63] vs (65.2 [60.2-69.9] g/L, P=0.008) on admission. HFsnEF patients were less frequently treated on discharge with mineralocorticoid receptor antagonists (25 vs 46.2%, P=0.013) as well as loop diuretics (60 vs 76%, P=0.017). The Kaplan-Meier analysis showed that all-cause mortality is higher in HFsnEF than in HFpEF (65.0 vs 55.2%, P=0.044, Figure 1). The independent predictors of long-term mortality were age and diagnosis of HFsnEF (HR 1.037, 95% CI 1.018-1.056 and HR 1.665, 95% CI 1.063-2.608, respectively). Conclusions Our findings indicate that every seventh Polish patient admitted with HFpEF could be classified as HFsnEF. Baseline characteristics of HFsnEF patients are different than HFpEF. Simultaneously, the HFsnEF diagnosis is associated with lower long-term survival.

Ankle brachial index,a non invasive tool predicts cardiovascular events after acute myocardial infarction:a 3 year follow -up study

Abstract Background / Introduction The ankle-brachial index (ABI) is a non-invasive tool that was initially used for the diagnosis of lower-extremity peripheral artery disease (PAD). It has been proven that ABI is a marker of atherosclerosis in other vascular sites and can therefore be used to predict cardiovascular events regardless the presence or not of PAD symptoms. Purpose This study aims to examine the prognostic value of ABI in the setting of acute myocardial infarction (MI), as up till now there is not enough relevant evidence. Method We followed up 441 patients [79% male;mean age 62 years;67% hypertnesive; 30% with diabetes mellitus (DM); 52% current smokers] who were hospitalized because of MI for a period of three years. All patients underwent baseline estimation of clinical and laboratory parameters during theri hospitalization.The ABI was measured according to established methodology using a certified automated device and abnormal ABI defined as a value ≤ 0.9. The primary endpoint was a composite of all-cause and cardiovascular death, as well as major cardiovascular events including decompensated heart failure, new acute coronary syndrome, cerebrovascular event, malignant arrhythmia, PAD event and new onset renal dysfunction. All events were assessed both in-hospital and within 3 years of follow-up. Results Our study population had a mean ABI of 1.1 (IQR: 1.00 to 1.18). With the use of reduced multivariate regression models ABI was proven to be a prognostic indicator for the in-hospital composite endpoint. Patients with an abnormal ABI had a threefold risk of in-hospital events [HR 2.93, 95% CI: 1.48-5.81, p=0.002]. After conducting multivariate analysis ABI maintained its predictive power of all-cause mortality [HR 2.88, 95% CI: 1.53 – 5.42, p=0.001], regardless of hypertension DM, LDL levels and smoking status of the study population in 3 years follow-up. Conclusion An impaired ABI is associated with greater risk of in-hospital events in patients with acute MI. Moreover, ABI emerges as an independent predictor of long-term all-cause mortality in those patients.The findings of this study suggest that subclinical and clinical PAD are associated with poor outcomes among patients with acute MI; thus, routine ABI tests enhance risk stratification and might carry important prognostic significance in these patients regardless of PAD symptoms.

A propensity score matched analysis of transcatheter aortic valve replacement in failed bioprosthetic valves

Abstract Introduction While recently published data indicate similar long-term results of transcatheter aortic valve replacement (TAVR) compared to surgical procedures, surgical aortic valve replacement (SAVR) remains the standard of care in low-risk patients. However, since life expectancy increases, a non-negligible number of patients experience bioprosthetic valve dysfunction with the need for reintervention, but long-term data of TAVR in failed bioprosthetic valves is scarce. Purpose The aim of the study was to analyse long-term data of patients with TAVR in failed bioprosthetic valves compared to patients with native valve TAVR. The primary endpoint was 6-year all-cause mortality and the main secondary endpoint was echocardiographic valve function. Methods Patients undergoing TAVR for severe aortic valve disease between December 2012 and December 2020 were retrospectively analysed. Prior TAVR or aortic valve homografts led to exclusion from the study. A 2:1 propensity score matching by the optimal neighbor matching algorithm was performed to overcome differences in baseline characteristics. Results Between December 2012 and December 2020, 3,423 patients received TAVR for severe aortic valve disease and met inclusion criteria for the study. Of those, 3,287 patients underwent native valve TAVR, whereas 136 patients experienced bioprosthetic valve dysfunction and were treated with TAVR-in-SAV. After 2:1 propensity score matching, baseline characteristics without any relation to prior SAVR were similar between both groups. Concerning postprocedural echocardiographic function, a less pronounced gradient reduction (57.0 vs. 71.0 %, p < 0.01, Figure 1) and a higher number of patients with elevated mean pressure gradient > 20 mmHg could be found after prior SAVR (19.4 vs. 3.0 %, p < 0.01). However, there was no difference regarding 6-year all-cause mortality between both groups (log rank test p = 0.8, Figure 2). Conclusions Besides a less pronounced gradient reduction and higher mean aortic pressure gradients after TAVR-in-SAV compared to patients with native valve TAVR, no differences in 6-year all-cause mortality could be observed in a propensity score matched analysis.Reduction of mean pressure gradient6-year all-cause mortality

Prognostic outcome of ACS in HTX patients after PCI

Abstract Background Cardiovascular disease (CVD) is the leading cause of mortality and morbidity worldwide, particularly in countries with limited access to healthcare [1,2]. Acute coronary syndrome is a collective term for several clinical conditions resulting from narrowing or occlusion of the coronary arteries [3,4]. Another group of patients affected by cardiovascular disease are those who have undergone heart transplantation. Long-term survival after transplantation is limited by cardiac allograft vasculopathy, a condition that affects the coronary arteries of the donor heart and causes diffuse narrowing [5,6]. Our retrospective analysis aims to compare the prognostic outcomes of HTX patients with ACS who underwent PCI with patients without a history of HTX. Results A total of 3194 patients with ACS were enrolled, of whom 1.16% (37) had a previous heart transplant. Patients with prior transplantation were on average younger (52.54 ± 15.13 vs. 69.76 ± 12.16, p < 0.001), had less dyspnea (p < 0.001) and a different distribution of ACS types (p < 0.001), as shown in Figure 1. There were no differences in sex (p = 0.287), BMI (p = 0.123), hypertension (p = 0.557), diabetes mellitus (p = 0.188) and previous myocardial infarction (p = 0.681). The majority of HTX patients were diagnosed with ISHLT CAV III (58.54%) and the average time to PCI was 12 years after transplantation. Multi-vessel disease was more common in HTX patients (p < 0.001). In addition, calcification was less frequent in the HTX group than in the control group (p < 0.001), and the lesion morphology was more diffuse in the HTX group (p < 0.001). On the other hand, there was no difference in the distribution of target vessels (p = 0.424), with the left anterior descending being the most frequently treated coronary artery, followed by the left circumflex and right coronary arteries. HTX patients received more stents (p < 0.001). There was also a difference in post-procedural TIMI flow achieved (p = 0.047), with less TIMI 3 flow achieved after PCI in the HTX group (80% vs. 93.59%). Technical success was less likely to be achieved in the HTX group (62.50% vs. 96.29%, p < 0.001), as was procedural success (47.06% vs. 89.68%, p < 0.001). There was no difference in the incidence of complications, which include perforation and bleeding (p = 0.284). All-cause mortality at three years (39.02% vs. 17.50%, p < 0.001), stroke (7.32% vs. 1.59%, p = 0.035) and myocardial infarction (p = 0.026) were higher in the HTX group. Over a period of three years, MACCE was more likely to occur in the HTX sub-group, which is shown graphically in Figure 2. Conclusion Interventional treatment of ACS in HTX patients is an option with a complication rate comparable to non-HTX patients and with a lower technical and procedural success - partly due to the diffuse nature of CAV and the involvement of distal and microvascular vessels. Overall MACCE and survival are inferior to the control population.Figure 1Figure 2

Body mass index may alter cardiovascular outcomes in patients with newly-diagnosed atrial fibrillation and previous stroke: an interaction analysis using longitudinal data from the GLORIA-AF registry

Abstract Background Patients with new onset atrial fibrillation (AF) and previous stroke (PS) are at higher risk of cardiovascular (CV) outcomes. An obesity paradox, where overweight or obese patients have better outcomes, has been seen. Whether body mass index (BMI) modify the risks of cardiovascular (CV) events and mortality in AF patients with PS remains uncertain. Purpose To ascertain whether BMI of AF patients with PS events alters risks of CV outcomes. Methods A cohort from phase III of the prospective GLORIA-AF (Global Registry on Long-Term Oral Anti-thrombotic Treatment in Patients With Atrial Fibrillation) was included. Risks of Major Adverse Cardiovascular Events (MACE), CV death, and all-cause mortality were analysed using COX proportional hazard regression with interaction terms added between PS and the BMI characteristics. Results Data from 17482 patients [median age: 71.0 (IQR: 64.0–78.0) years; 45.3% female] with newly-diagnosed AF were analysed and included in risk models. At baseline, 1840 (10.5%) patients with AF had PS in which 1694 (9.7%) and 170 (0.97%) patients had one (1 PS) and ≥2 (2 PS) respectively. After a median follow-up of 3.0 (IQR: 2.9–3.1) years, 1111 MACE, 562 CV deaths, and 1266 all-cause deaths were recorded. In a multivariate COX regression model, interaction between BMI and PS was significant in predicting risk of CV death (Pint =0.019). BMI was also associated with increased risk of CV death among AF patients with ≥1 PS. The interaction between PS and BMI was borderline significant in predicting MACE (Pint=0.063) and all-cause death (Pint=0.057). Figure 1 showed the different risks associated with different BMI statuses. Conclusion The risks of adverse CV outcomes were higher in AF patients with higher BMI and previous stroke. An obesity paradox was not evident in AF patients with previous stroke.Figure 1

Effect of physical activity level on the association of LBBB, heart failure, and mortality

Abstract Background The beneficial effect of physical activity (PA) on adverse cardiovascular outcomes in patients with heart failure (HF) and left bundle branch block (LBBB) is well established. Yet, the impact of PA on individuals with LBBB without evident HF remains unexplored. Our objective is to investigate how PA modifies the outcomes of new-onset LBBB patients concerning HF-related hospitalizations and mortality. Methods Among the UK Biobank participants without a diagnosis of HF, we identified individuals with new-onset LBBB and available PA quantification. Patients were dichotomized into normal QRS and LBBB groups, following by stratification according to summed minutes of PA per week. The primary outcome was all-cause mortality, and HF-related hospitalizations. Cox proportional hazard model and Kaplan-Meier survival analysis were applied. Results The final cohort comprised 367,934 individuals, with a mean age of 56.6±8.2 years and 47% male. Among them, 3,427 (0.9%) developed new-onset LBBB, characterized by advanced age, male predominance, and higher rates of comorbidities. Median summed PA minutes per week were 100 (IQR: 125-180), with no significant difference between normal QRS and LBBB patients. Over a median follow-up of 13.8 years (IQR: 13-14.5), 26,304 patients (7.15%) died. Kaplan-Meier analysis revealed higher mortality risk with reduced PA level and/or LBBB (log-rank p<0.001 for both). Multivariate Cox analysis adjusted for age, sex, and comorbidities showed LBBB patients had over 3.5-fold increased risk of death (HR 3.67, 95% CI 3.39-3.97, p<0.001) compared to normal QRS. The association of LBBB with mortality was modified by weekly PA minutes; those with <150 minutes had nearly 40% higher risk compared to those with ≥150 minutes (HR 3.78, 95% CI 3.43–4.15, p<0.001; HR 3.4, 95% CI 2.93–3.95, p<0.001; p for interaction=0.035). The protective effect of PA was 6% among normal QRS patients, compared to 22% among individuals with LBBB (HR 0.94, 95% CI 0.91 – 0.96, p<0.001 vs. HR 0.78, 95% CI 0.66 – 0.93, p=0.004). Similar findings were observed for HF hospitalizations. Conclusions Although the correlation between LBBB and adverse cardiovascular outcomes remained consistent across both levels of physical activity (PA), it was more pronounced among patients with low PA levels. When assessing the risk in patients with newly diagnosed LBBB, particular attention should be directed towards their PA status.

Effect of body mass index on mortality for diabetic patients with aortic stenosis

Abstract Background Several studies suggest an "obesity paradox," associating obesity with better cardiovascular outcomes compared to normal or underweight individuals (1-3). Purpose This study explores the impact of body mass index (BMI) on mortality in patients with diabetic mellitus (DM) and aortic stenosis (AS). Methods This is a retrospective cohort study conducted at a tertiary centre. Between 2014 and 2019, patients with DM who underwent echocardiography were screened (4). Patients were enrolled if AS was diagnosed, according to established guidelines (5). Two echocardiography specialists independently reviewed the echocardiography in the cohort. The index date of the DM-AS cohort was the first AS diagnosis by echocardiography, and detailed data collection methods are described in previous studies (6,7). Patients were categorized as underweight, normal weight, or obese based on BMI (<18.5, 18.5 to 27, and >27 kg/m2, respectively). Outcomes included all-cause mortality, cardiovascular, and non-cardiovascular death, which were adjudicated by a central committee. The occurrence times of the outcomes of interest were determined using diagnosis codes from electronic health records, and medical records were reviewed until the last clinical visit or death. Results Among 74,835 DM patients, 734 had AS. Normal weight comprised 65.5% (n=481), underweight 4.1% (N=30), and 30.4% were obese. With a median follow-up time of 34 months, 285 patients (38.8%) experienced outcomes of death, comprising 93 patients (32.7%) with cardiovascular death and 192 patients (67.3%) with non- cardiovascular death. Underweight patients had significantly higher all-cause mortality (HR 1.96, 95% CI 1.22 – 3.14, p = 0.005), while obese patients had significantly lower mortality (HR 0.79, 95% CI 0.68 - 0.91, p=0.001) compared to the normal group. Regarding etiologies, underweight patients had a higher risk of non- cardiovascular death (HR 2.47, 95% CI 1.44-4.25, p = 0.001), while obese patients had a lower risk of cardiovascular death (HR 0.66, 95% CI 0.50-0.86, p=0.003). Subgroup analysis showed a consistent trend without significant interaction. To elucidate the interaction of BMI as a continuous variable with outcomes, restricted cubic spline analysis was applied. Cardiovascular death showed a negative association with BMI across available BMI levels, and non-cardiovascular death exhibited a U curve, with the lowest hazard ratio occurring when BMI was between 25 to 30. Conclusion Our study underscored the significance of both cardiovascular and non-cardiovascular deaths as crucial contributors to overall mortality in DM patients with AS. Being underweight is associated with increased non- cardiovascular death, while obesity is linked to less cardiovascular death. Proposed mechanisms include reduced frailty, enhanced tolerance to guideline-directed medical therapies (GDMTs), and heightened disease awareness in the obese group (8,9).Kaplan–Meier analysis for outcomesAssociation between BMI and outcomes

Prognostic impact of left ventricular myocardial work in patients undergoing surgery for primary mitral regurgitation

Abstract Background Although left ventricular ejection fraction (LVEF) is widely used as a parameter for the assessment of LV systolic function, LVEF can overestimate LV systolic function in patients with severe mitral regurgitation (MR) due to its high load-dependency. Echocardiography-based, left ventricular myocardial work (LVMW) can assess LV function by incorporating LV afterload. Purpose This study aims to evaluate the prognostic value of LVMW indices in patients with primary MR undergoing mitral valve surgery. Methods Individuals who underwent mitral valve surgery for severe primary MR were included. All patients underwent transthoracic echocardiography before surgery. LVMW was derived from a vendor-specific package which integrates LV global longitudinal strain with sphygmomanometric blood pressure to construct pressure-strain loops during the cardiac cycle. (Figure 1) For the LVMW indices, previously-established normal values were used as thresholds. The primary endpoint was all-cause mortality after mitral valve surgery. Results A total of 309 patients (mean age 63 ± 12 years, 68% male) with severe, primary MR who underwent surgery, were included. The mean LV global work index (LVGWI) was 1977 ± 537 mmHg% and 132 (43%) patients had impaired LVGWI (≤ 1900 mmHg%). During a median follow-up of 5.0 years (interquartile range, 2.5-8.9), 27 (8.7%) patients died after mitral valve surgery. Patients with impaired LVGWI or LV GLS (≤ 20%) had lower survival rates compared to the group with preserved LVGWI (p <0.01) or LVGLS (p = 0.02), whereas there was no significant difference in the survival rate between patients with LVEF ≤ 60% and > 60%. (Figure 2) Furthermore, LVGWI ≤ 1900 mmHg% demonstrated incremental prognostic value over LVGLS (p = 0.049) for all-cause mortality. Conclusions In patients with severe, primary MR who underwent surgery, impaired pre-operative LVGWI was associated with a higher mortality risk. In addition, impaired LVGWI had incremental prognostic value over LVGLS. Based on these findings, LVMW is a promising parameter for predicting postoperative outcome and determining the optimal timing of valve surgery in patients with severe, primary MR.Fig1.Echo-derived Myocardial workFig2.Kaplan-Meier curves