In-hospital Death Research Articles

Echocardiographic predictors of mortality in cardiac intensive care unit patients with pulmonary hypertension

Abstract Background Pulmonary Hypertension (PH) is a diverse condition associated with elevated mortality. We sought to determine the association of Transthoracic Echocardiography (TTE) parameters with in-hospital mortality in patients with PH admitted to Cardiac Intensive Care Unit (CICU). Methods We included 1 Clinic CICU admissions from 2007 to 2018, with available TTE parameters within the first day of CICU admission who had PH defined as an estimated right ventricular systolic pressure (RVSP) ≥36 mmHg. The primary outcome was in-hospital mortality, evaluated using logistic regression. Results We included 3085 unique CICU patients with PH, predominantly WHO group 2 and 3. Median age was 73.7 (63.8, 82.4) years, and 1343 (43.5%) were females. Heart failure (65.6%) and respiratory failure (34.0%) were the most common admission diagnoses. The median RVSP was 47 (41, 56) mmHg, and 1314 (42.6%) had RVSP ≥50 mmHg. A total of 337 (10.9%) patients died during hospitalization. In-hospital deaths had higher RVSP (51 versus 47 mmHg, p <0.001), reflecting higher right atrial (RA) pressure (14 versus 10 mmHg, p <0.001) (Figure). In-hospital mortality increased with worse TTE parameters reflecting Right Ventricle-Pulmonary Artery (RV-PA) coupling, such as Tricuspid Annular Plane Systolic Excursion/ Right Ventricular Systolic Pressure (RVSP), Tricuspid Annular Systolic Velocity (TASV)/RVSP and TASV/ Tricuspid Regurgitation velocity ratios. Conclusion In CICU patients with PH, we have identified the specific Doppler TTE parameters with strong associations with outcomes. Specifically, RA pressure and parameters of RV-PA coupling had the highest discrimination for in-hospital mortality. Comprehensive Doppler TTE is valuable for identification of high-risk PH patients to facilitate further investigation plans, management, and prognostication. Figure: In-hospital mortality in association with right ventricular (RV) function and right atrial pressure (RAP).In-hospital mortality in association wit

Investigation of age-related in-hospital outcomes of left atrial appendage occlusion in germany

Abstract Background The aim of this study was to assess demographics, in-hospital mortality and baseline characteristics of hospital cases with a left atrial appendage occlusion (LAAO) procedure in relation to patient age. Methods This is a retrospective observational analysis of all German in-hospital cases from 2016 to 2022 with a coded LAAO procedure using the Diagnose Related Groups (DRG) statistics database of the Research Data Center of the Federal Statistical Office. Results In total 40435 cases were observed in the investigated time period. Over the 5 years studied we found a significant shift towards an older patient collective. Compared to 28,3% in 2016, in 2022 40,1% of all patients were over 80 years of age (a rise of 152 %). Cases of patients with over 85 years of age increased from 7.7 % to 11.4 % during the same time period. We observed an in-hospital death rate for patients <70, 70-75, 80-85 and >85 years of age in 0.8, 1.0, 1.4 and 2.2 % respectively. Further we saw significant higher rates of intensified care treatment, pericardial effusion, acute kidney injury and red blood cell transfusion for patients >80 years of age. In unadjusted and adjusted logistic regression models age was significantly associated with a higher rate of in-hospital death. Conclusions In this study we present real world data from a health-care-system level. Our main findings were an increasing age in patients undergoing LAAO procedures and an independent association of age with in-house mortality and complications. This data provides a further basis to balance risks and benefits of LAAO procedure as a preventive treatment.

Long-term outcomes of percutaneous coronary intervention versus coronary artery bypass grafting in women with severe coronary artery disease

Abstract Background The optimal revascularization strategy for severe coronary artery disease (CAD) in women remains controversial. Despite differences between women and men in the development of CAD, there remains a paucity of comparative real-world observational evidence comparing percutaneous coronary intervention (PCI) to coronary artery bypass grafting (CABG) in women. Purpose We evaluated short and long-term outcomes of PCI and CABG in women with severe CAD. Methods We conducted a propensity score-matched retrospective cohort study using linked clinical and administrative databases in Ontario, Canada to obtain records of women with left main, 3-vessel disease, or 2-vessel disease with proximal left anterior descending artery involvement undergoing PCI or CABG from April 1st, 2012 to December 31st, 2021. Patients who were >80 years of age and patients who underwent urgent or emergent procedures were excluded for the primary analysis. The primary outcome was a composite of myocardial infarction, stroke, repeat revascularization, and death (MACCE). Secondary outcomes included the individual components of MACCE and a composite of readmission for MI, heart failure, and stroke. Following multiple imputation and propensity score-matching, the Cox proportional hazards model and Fine-Gray sub-distribution hazard model with robust variance estimators accounting for death as a competing risk were used to evaluate long-term outcomes. Results In the primary cohort, 2469 patients underwent PCI and 3,721 patients underwent CABG. After propensity score matching, including by coronary disease territory, 2,033 well-balanced pairs were identified, with standardized mean differences <0.10 for all covariates. In-hospital death and stroke were significantly lower with PCI than with CABG (0.7% vs 1.5%, p=0.036) and (<0.2% vs 1.4%, p<0.001), respectively, and there was no difference in perioperative MI between PCI and CABG (1.1% vs 0.6%, p=0.121). At a median (IQR) of 5.1 (2.9-7.5) years, major adverse cardiac and cerebrovascular events (MACCE) was higher with PCI compared with CABG (37.7% vs 23.3%, HR 1.79, [95% CI: 1.66-1.91], p<0.001) (Figure 1). All-cause mortality was higher with PCI compared with CABG (17.8% vs 13.4%, HR 1.33, [95% CI: 1.21-1.45], p<0.001) (Figure 2). The composite readmission outcome (MI, heart failure, stroke) was higher with PCI compared with CABG (16.2% vs 11.2%, HR 1.42, [95% CI: 1.37-1.48], p<0.001). Conclusion In women with severe CAD, CABG appears to be associated with a long-term reduction in MACCE and mortality compared with PCI. Our findings provide evidence to suggest women with severe CAD may derive greater long-term benefit from CABG compared to PCI and suggest that the treatment recommendation should shift towards CABG in appropriately selected women.Figure 1.MACCE free survivalFigure 2.Overall survival

Vaccination status and long COVID symptoms among patients hospitalized with COVID-19: the WHF COVID-19 Long-term Study

Abstract Background COVID-19 vaccinations have been found to be effective in reducing the severity of COVID-19 infection and in-hospital deaths; however, insufficient evidence exists about the effect of vaccination on long term morbidity and mortality after hospitalization in patients from low- and middle-income countries. Methods The global WHF COVID-19 Long-Term Follow-up Study recruited 2,504 COVID-19 hospitalized patients from 26 collaborating sites in 16 countries between January 2022 - June 2023. Patients were followed up , at 1, 3, 6, and 9-12 months post-discharge to examine short- and long-term physical and psycho-social outcomes. A standardised questionnaire was used to collect data on demographics, pre-existing comorbidities, COVID-19 symptoms on admission, vaccination status, and outcomes at discharge, including persisting symptoms, new onset hypertension or diabetes, major adverse cardiovascular events (MACE), and mortality. We compared persistent long COVID symptoms, MACE, and mortality outcomes up to one year by COVID-19 vaccination status. Results The majority of study participants were Asians (78%), males (56%) with a mean (SD) age of 59.2 (19.9) years and from low- and middle-income (65%), upper middle-income (20%) and high-income (15%) countries. The most commonly reported comorbidities were hypertension: 54% and diabetes: 38%. Approximately two-thirds of the patients had received at least one dose of COVID-19 vaccination prior to hospitalization. Unvaccinated patients were more likely to present with dyspnea (60% vs 53%, p-value<0.001) and acute respiratory infection (15% vs 9%, p-value<0.001) during hospitalization. Unvaccinated patients also had twice the in-hospital mortality rate, compared with vaccinated patients (6% vs 3%, p-value<0.001). Unvaccinated patients had a greater incidence of MACE (23% vs 18%, p-value=0.016) during hospitalization and across all follow-up visits. Unvaccinated patients also had a higher mortality rate across all follow-up visits (mortality at one year post-discharge 14% vs 10%, p<0.001). At the 9-12 month follow-up, about a quarter of the patients had at least one long COVID symptom, but unvaccinated patients had a higher rate of long COVID symptoms, including fatigue (23% vs 14%, p<0.001), palpitations (17% to 7%, p-value<0.001), and anxiety (13% to 7%, p=0.002). Conclusions Our data highlight the long-term protective effect of COVID-19 vaccination on reducing morbidity and mortality among COVID-19 patients after hospital discharge. However, a substantial proportion of COVID-19 vaccinated patients still showed persistent long COVID symptoms (22%) and mortality (10%). Future research is needed to investigate individual- and health system-level factors contributing to poor health outcomes post-COVID-19 infection.

Subclinical left ventricular dysfunction detected by speckle tracking echocardiography predicts mortality in COVID-19 patients

Abstract In COVID-19 patients, both preexisting cardiovascular disease and cardiac injury resulting from SARS-CoV-2 infection are associated with increased mortality. In this patient population the value of speckle tracking echocardiography (STE) for detecting high-risk patients has not been evaluated thoroughly. Aim The aim of study was to determine the prevalence of subclinical myocardial dysfunction revealed by STE and its association with in-hospital and two-year mortality in patients with COVID-19 and preserved left ventricular ejection fraction (LVEF). Methods The study group comprised 163 consecutive patients with preserved LVEF(>/=50%) and maintained right ventricular function evaluated by assessment of tricuspid annular plane systolic excursion (TAPSE >14 mm) hospitalized in the cardiology department due to COVID-19 in 2020 and 2021. All patients underwent transthoracic echocardiographic examination with off-line analysis using STE. Left ventricular global longitudinal strain(GLS), right ventricular global longitudinal strain (RV-GLS), right ventricular free wall strain(RV-FWS) and myocardial work parameters: global work index(GWI), global wasted work(GWW), global constructive work(GCW) and global work efficiency(GWE) were measured. The primary outcome was in-hospital and two-year mortality. Results 96 patients (mean age 66 years, 59 [61%] male) had adequate image quality to evaluate deformation-derived parameters.19 patients (19.8%) died during hospitalization and 9 (9,4%) patients died within two years after discharge. In-hospital non-survivors were older, had lower baseline oxygen saturation(SpO2) and had higher NTproBNP. In non-survivors STE revealed significant impairment of LV and RV function compared to the group of survivors(Table 1). The independent predictors of in-hospital death were: age (OR 1.1 [95% CI 1.01 – 1.19]), SpO2 on admission (OR 0.83 [95% CI 0.75 – 0.93]), NTproBNP (OR 1.0003 [95% CI 1.0001 – 1.0006]) and LV-GLS (OR 1.45 (1.06 – 1.99)]. Based on the analysis of the ROC curves, the cut-off points optimal for predicting in-hospital death were identified: age >71 years (sensitivity [sens.] 74%, specificity [spec.] 68%) , baseline SpO2 value ≤ 89% (sens. 89%, spec. 74%,) NTproBNP >951 pg/ml (sens. 79%, spec. 58%) and GLS >-16% (sens. 63%, spec. 89%). The independent predictors of two-year mortality were: age (OR 1.10 [95% CI 1.02 – 1.19]), Sp02 on admission (OR 0.82 [95% CI 0.73 – 0.91]) and NTproBNP (OR 1.0006 [95% CI 1.0001 – 1.0011]).Based on the ROC curve analysis, the cut-off points optimal for predicting death within 24 months after COVID-19 were also identified: age>71 years (sens. 71%; spec. 72%), Sp02 <89% (sens. 69%, spec. 73%), NTproBNP >520 pg/ml (sens. 89%, spec. 48%). Conclusions STE allows for the detection of subclinical myocardial dysfunction in COVID-19 patients with preserved LVEF. However, LV GLS is the only independent STE-based predictor of in-hospital mortality in this patient population.

Revascularization strategies in elderly patients with acute coronary syndromes and multivessel disease: comparative analysis of culprit-only vs complete revascularization

Abstract Background Acute coronary syndromes (ACS) are more challenging in elderly patients, particularly when related to multivessel disease (MVD). Concerns about outcomes, and the lack of evidence, lead to more conservative treatment. While benefits of complete revascularization are well established among the youngest, doubts persist in older patients. Despite FIRE trial having showed superiority of complete revascularization with coronary physiology, in older patients with ACS and MVD, more evidence is needed. Methods Multicenter retrospective cohort of 629 patients, older than 75 years, with ACS and MVD, was divided into complete or culprit-only revascularization groups. In-hospital outcome of death and major adverse cardiovascular events (MACE) and follow-up outcome of death and cardiovascular hospital admission were assessed. Results From the 629 patients, 383 (61%) were submitted to PCI, of which 66% (n=254) were submitted to culprit-only revascularization and 34% (n=129) to complete revascularization. Culprit-only group's mean age was 83±5 years and median age in complete revascularization group was 81 (IQ 78-84) years. There was similar number of female patients in both groups (42% and 37%, p=0,26), and the culprit only group was significantly older (p=0,006). There were more ST-segment elevation myocardial infarctions in culprit- only group (p<0,001). Regarding diabetes, previous ACS, Killip classification, heart failure, stroke, peripheral artery disease, and chronic kidney disease, there were no statistically significant differences between groups (p>0,05). Complete revascularization was associated with lower in-hospital events, with 36% against 48% in culprit-only (p=0,025 OR 0,62 [0,4-0,9]), mainly due to lower in-hospital deaths, with 3% against 13% (p<0,01 OR 0,3 [0,15-0,67]) but also due to lower in-hospital MACE with 29% against 27% (p=0,02 OR 0,6 [0,4-0,9]). The mean follow-up was 13±7 months, during which, in complete revascularization group, there was non-statistically significant decrease of deaths, with 13% against 15% (p=0,4), hospital readmissions, with 21,8%, in comparison with 24,9% (p=0,2), and composite outcome, with 35% and 40% (p=0,16) of composite events in the culprit-only group There was a non-statistically significant decrease of the mean for survival time for culprit only group which was 10±8 months comparing with complete group of 13±8 months (p=0,16). Conclusion In older patients with ACS and MVD the ideal strategy is yet to be determined. Still complete revascularization strategy showed a statistically significant decrease of in-hospital death and MACE, and non-statistically significant decrease in follow-up mortality and readmissions. This study suggests, like FIRE trial, that when clinically and anatomically feasible, it seems legit to attempt complete revascularization in elderly patients with ACS and MVD.

Efficacy and safety of reduced-dose and slow-infusion intravenous alteplase regimen in patients with acute pulmonary embolism at intermediate-high-risk

Abstract Background In patients with intermediate-high-risk (IHR) pulmonary embolism (PE), full-dose systemic thrombolytic treatment (STT) has been documented to lower the risk of hemodynamic decompensation and mortality, at the expense of an elevated risk of life-threatening bleeding. In this study, we aimed to evaluate the safety of reduced-dose STT regimen while maintaining effective reperfusion. Methods This single-center study comprised 124 retrospectively evaluated patients (female 58.9 % and mean age 55.4+15.8 years) diagnosed with acute PE at IHR status in accordance with European Society of Cardiology (ESC) 2019 acute PE guidelines in whom intravenous (i.v.) alteplase treatments were utilized. Patients fulfilling at least one of the following criteria have been included in the study: systolic blood pressure ≤ 110 mm Hg, heart rate > 100 bpm, SaO2 < 90 % on room air, respiratory rate > 20 breaths per minute, or serum lactate > 2 mmol/L. Exclusion criteria were any contraindication for STT and symptom onset > 14 days. Standard protocol for initial STT was i.v. infusion of alteplase of 25 mg over 4-6 hours. After completion of the infusion, a second STT in the same manner if one of the following criteria were present; heart rate > 100 bpm, SaO2 < 90 % or signs of organ hypoperfusion. Results Syncope and concomitant deep vein thrombosis were documented in 27.4 % and 49.2 % of patients, respectively. Baseline vital measures were as follows; heart rate: 112 +16.6 bpm, systolic blood pressure: 123+14.9 mm Hg, SaO2: 89 % (85-93), serum lactate 2.35 (1.6-2.9) mmol/L. Median alteplase dose and infusion duration were 50 (25-50) mg and 6 (4-10) hours, respectively. There were significant improvements in clinical parameters, pulmonary thrombus burden, pressure strain and right ventricular size and function as assessed by computed tomography and echocardiography (p< 0.001 for all). Minor and major bleeding events occurred in 3.2 % and 4.8 % of patients, respectively. One major bleed was due to cerebellar hemorrhage, but did not require surgery and patient was discharged without sequela. There were 6 (4.8 %) in-hospital deaths in which 2 were attributed to major hemorrhages and 4 due to hemodynamic decompensation. Conclusion In patients with acute IHR PE, reduced-dose and slow-infusion i.v. alteplase regimen seems to be a clinically relevant and safe reperfusion alternative to full-dose STT protocols associated with well-known major bleeding risks.

Comparison of endovascular therapy and open surgical revascularization in patients with acute superior mesenteric artery occlusion

Abstract Background Acute mesenteric ischemia (AMI) is rare, and few large-scale trials have evaluated endovascular therapy (EVT) and open surgical revascularisation (OS). This study aimed to assess clinical outcomes after EVT or OS for acute superior mesenteric artery occlusion (SMAO) and identify predictors of mortality and bowel resection. Methods Data from the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination database from April 2012 to March 2020 were retrospectively analyzed. Overall, 746 patients with acute SMAO who underwent revascularisation were classified into two groups: EVT (n=475) or OS (n=271). The primary clinical outcome was in-hospital mortality. The secondary outcomes were bowel resection, bleeding complications (transfusion or endoscopic hemostasis), major adverse cardiovascular events (MACEs), hospitalisation duration, and cost. Results The in-hospital death or bowel resection rate was approximately 30%. In-hospital mortality (22.5% vs. 21.4%, p=0.72), bowel resection (8.2% vs. 8.5%, p=0.90), and MACEs (11.6% vs. 9.2%, p=0.32) were comparable between the EVT and OS groups, respectively (Table.1). EVT was advantageous in terms of hospitalisation duration and cost (both p<0.0001). Interaction analyses revealed that EVT and OS had no significant difference in terms of in-hospital death in patients with thromboembolic and atherothrombotic characteristics (Figure.1). Multivariate logistic regression analysis revealed that advanced age, decreased activities of daily living, chronic kidney disease, and old myocardial infarction were significant predictive factors for in-hospital mortality. Diabetes Mellitus was a predictor of bowel resection after revascularisation. Conclusions EVT was comparable to OS in terms of clinical outcomes in patients with acute SMAO. Some predictive factors for mortality or bowel resection were obtained. Clinical implications EVT may be a feasible alternative to OS, potentially impacting clinical practice as a less invasive option for managing patients with acute SMAO.In-hospital clinical outcomesInteraction effect test for mortality

Prognostic impact of the tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure ratio in acute pulmonary embolism

Abstract Background Currently available risk stratification models for acute pulmonary embolism (PE) include hemodynamic status, cardiac biomarkers, right ventricle (RV) dysfunction on imaging, and clinical scores. Focusing on length-tension relationship of the ventricle might have a superior predictive capability over RV dysfunction in terms of mortality and classification of patients with acute PE. In this study, our hypothesis suggests that tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary artery pressure (sPAP) ratio has superior predictive capability for in-hospital mortality in patients with acute PE compared to TAPSE or sPAP as distinct measures. Methods This single-center study comprised retrospectively evaluated 703 patients referred to our tertiary cardiovascular center with acute PE. We divided patients into quartiles by TAPSE/sPAP ratio. Different models were developed to quantify the predictive relationship between in-hospital death and echocardiographic measurements. A base model was created with variables including risk status and RV/LV ratio >1. Then, to evaluate the predictive contribution of each measurement; TAPSE/sPAP, TAPSE, and sPAP were sequentially added to the base model. After that, the performance of each model was evaluated. Results Predictive and discriminative power was the highest in model containing TAPSE/sPAP. There was still a significant inverse association between TAPSE/sPAP and risk of in-hospital death even after adjusting by risk status and RV/LV ratio >1. ROC curve analysis for TAPSE/sPAP revealed the best cut-off value as 0.34. Conclusion The outcomes of our study reveals that the ratio of TAPSE/sPAP serves as a more potent predictor of mortality than either of the two measurements taken separately. The interpretation and utilization of the TAPSE/sPAP cut-off value in acute PE can assist in identifying patients at risk of deterioration and guide the consideration of more intensive treatment options across all risk groups.

A regional multicentre prospective survey addressing sport-related myocardial infarction: clinical characteristics of 155 patients and one year follow-up

Abstract Background Exercise is a keystone of cardiovascular prevention; however, it is also a powerful trigger of acute cardiovascular events including sudden cardiac arrest and acute myocardial infarction. Contemporary studies addressing these sport-related myocardial infarction (SR-MI) are scarce. Aim To describe clinical characteristics and follow-up of SR-MI. Methods We conducted a regional multicentric prospective survey addressing patients admitted for a SR-MI in 2 intensive coronary units. SR-MI was defined as MI onset occurring during sport or within the 1st hour of recovery. A one-year follow-up was performed by phone call. Results From April 1st 2018 to February 23th 2023, 155 SRMI were included, of whom 13 (8.4%) were female, median age was 61-y. (IQR 54-66). Cycling was the most frequent sport (32.5%) followed by fitness and hiking (12.6% each) then jogging (11.3%) (Figure). Most were ST elevation MI (68.8%). The main risk factors were dyslipidaemia (33.8%), hypertension (27.3%) and tobacco smoking (24.5%). No cardiovascular risk factor other than age was identified in 38 patients (25.7%). Prodromal symptoms were reported by 66 subjects (42.6%). SR-MI occurred mostly during exercise (60.6%). Out of hospital cardiac arrest (OHCA) occurred in 20 (12.6%) patients, more commonly among patients with prior coronary artery disease (CAD) (p = 0.02) and tobacco smoking (p=0.047). A significant single vessel disease was observed in 67 patients (43.2%); revascularization was performed by stenting in 134 patients (86.5%) and surgery in 11 (7.1%). In-hospital death occurred in 4 patients and was associated to OHCA (p=0.007). Among the survivors at time of discharge (151 patients), 141 were eligible to follow-up, none one lost: one patient died suddenly at home, one suffered from a recurrent MI, one experienced a cardioversion from his implantable cardioverter defibrillator (ICD) and an ICD was implanted in 4 others. A cardiovascular rehabilitation was performed in 101 patients (65.2%); from the 30 smokers at the time of SRMI, 26 declared smoking cessation. Conclusions Among patients admitted for a SR-MI, most were male. Prodromal symptoms were common but neglected. OHCA occurred in 1 patient out of 8 and was associated with history of CAD, tobacco smoking and in-hospital death. Such findings highlight the need for mass education to prevention including recognition of prodromal symptoms and management of cardiac arrest. In this exercising population, rehabilitation rate was high and quitting tobacco was commonly achieved.Table

Increased risk of cardiovascular events in the weeks following hospitalised COPD exacerbations: the EXACOS-CV French nationwide case-crossover study

Abstract Introduction Previous studies indicate that in people living with chronic obstructive pulmonary disease (COPD), the risk of myocardial infarction (MI), heart failure (HF) decompensation, arrhythmias and ischemic stroke increases following a COPD exacerbation. This association has not been explored for detailed types of cardiovascular events (CVE), namely for different types of myocardial infarction. Objective To quantify the risk of CVE following a COPD exacerbation overall, and by detailed type of CVE. Methods A case-crossover study was conducted using the French national hospital discharge database (Programme de Médicalisation des Systèmes d'Information, PMSI). Case-patients: (i) were aged≥40 years with a COPD diagnosis; (ii) hospitalised in 2018-2019 for CVE; (iii) experienced the CVE within 24 weeks of a hospitalised exacerbation of COPD. Hospitalisation date for CVE was index date. Conditional logistic regression models estimated the association between a hospitalised exacerbation and CVE (overall and by type of CVE) – expressed as odds ratios (OR) – comparing the odds of a hospitalised COPD exacerbation during the risk period (4 weeks prior to index date) versus control periods (9-24 weeks prior to index date). Results Among 122,172 patients with COPD hospitalised for a severe CVE in 2018-2019, 9,840 (8%) had a hospitalised exacerbation of COPD in the prior 24 weeks and qualified as case-patients. Mean age was 76.8 years (SD 10.7); 6,496 (66%) were male. The most frequent CVE were decompensated heart failure (n=5,888, 60%) and acute coronary syndrome (n=1,070, 11%); in-hospital death in the 24 weeks following an exacerbation of COPD occurred in 950 (10%) patients. Median time elapsed between hospitalised exacerbation and CVE (any type) was 43 days (Figure 1); the shortest delays were observed for non-STEMI (24 days) and resuscitated cardiac arrest (28 days). Risk of CVE in the 4 weeks following a hospitalised COPD exacerbation was 3-times the risk in the 9-24 weeks post-exacerbation (OR 3.0; 95%CI 2.9-3.2 – Figure 2). This increase in risk was observed for each individual type of CVE. The highest effect size was observed for non-STEMI (OR 5.3; 95%CI 4.5-6.3). Conclusion The risk of CVE substantially increases following a hospitalised exacerbation of COPD overall and for all types of CVE (acute ischemic events, arrhythmias, and heart failure decompensation). The first month following a hospitalised exacerbation is a period of vulnerability for people living with COPD, with some variability in the magnitude and temporality of risk increase according to the type of CVE. These results stress the need for immediate and sustained monitoring of exacerbating COPD patients to prevent a subsequent severe cardiac event. In addition, exacerbations prevention is an essential target of COPD treatment.

Comparing the ability of GRACE 2.0 and GRACE 3 scores for predicting in-hospital mortality in patients with and without diabetes

Abstract Background Sex-specific refinement of GRACE 2.0 was published as GRACE 3.0 (G3). The relative ability of G3 in predicting in-hospital mortality in diabetic patients has not been explored. Purpose Explore the ability of G3 in determining in-hospital mortality in patients with and without diabetes. Methods Retrospective cohort analysis of data on NSTEMI and UA patients admitted in two hospitals between 2010 and 2019 entered into the Myocardial Infarction National Audit Project database. All baseline characteristics and G2, G3 scores were recorded. In hospital death was recorded from hospital records. The discriminative power of the G2 score was determined by comparing the area under the receiver operating characteristic curve (c-statistics). Accuracy of calibration was evaluated by plotting the mean predicted vs observed mortality in each decile of predicted risk, Hosmer-Lemeshow (HL) goodness-off it test and the Nagelkerke R2 (NR2). Results G3 was calculated in 2768 patients (age 69±14yrs, 62.3% male, 877(31.7%) with diabetes. Median risk for the cohort was 1.3%, (95% CI 1.2 to 1.4). G3 risk was higher in patients with diabetes (median 2.0 IQR 0.6 to 5.5 vs 1.0 IQR 0.3 to 3.7, p<0.0001). In-hospital mortality occurred in 68 (2.5%) patients with no difference between the diabetes groups (3.1% and 2.2% died in the DM and non-DM groups respectively). In the whole cohort, G3 reclassified 139(7.5%) patients in low-intermediate to high risk-category and 159(17.4%) patients in high to low-intermediate category. 10.1% and 6.5% were upgraded and 16.1% and 18.1% were downgraded in DM and non-DM groups. Overall discriminatory power of G3 (AUC 0.87, 95% CI 0.86 to 0.88, p<0.0001) was excellent but no different from G2 (AUC 0.86 95% CI 0.85 to 0.88, p<0.0001) (δAUC 0.009, p=0.461). In patients with diabetes, G3 yielded higher AUC (AUC 0.85, 95% CI 0.83 to 0.87, p<0.0001) than G2 (AUC 0.82, 95% CI 0.79 to 0.84, p<0.00101) but this was not statistically significant (δAUC 0.031, p=0.142). In patients without DM, the difference was smaller (δAUC 0.002, p=0.906). Neither G2 (δAUC 0.061, p=0.185) nor G3 (δAUC 0.028, p=0.473) was better in discrimination in DM compared to non-DM groups (Fig1A,B). In the diabetic group, calibration plot for the G3 score showed suboptimal calibration with consistent overestimation of the risk across all risk deciles (Figure1C), with the HL test showing significant differences between the observed and predicted values (p <0.0001) and the NR2 was low 0.09. The GRACE 2 score showed better calibration (Fig1D) (HL: p=0.09, NR2 0.11). In patients without diabetes, calibration plot for the G3 (HL: p= 0.17; NR2 0.33) (Fig1E) and G2 (HL: p=0.15, NR2 0.25) (Fig1F) shows similar pattern of overestimation of the risk less so for latter. Conclusion G3 and G2 shows excellent discrimination for in-hospital mortality in both diabetic and non-diabetic patients. G2 seems to show better calibration than G3 for diabetic patients.

Statin use before acute coronary syndrome and coronary risk factors, clinical presentation, interventions, and outcomes: ACC-NCDR-CathPCI Registry in India

Abstract Background Statins are used for coronary artery disease (CAD) primary and secondary prevention. Limited studies on the association of statin use before acute coronary syndrome (ACS) with clinical presentation and outcomes are available. Purpose We compared statin-user and statin-naïve ACS patients for clinical and angiographic findings and in-hospital and 3-year outcomes following percutaneous coronary intervention (PCI). Methods Successive patients with ACS who underwent PCI from Sep’17 to Dec’23 were enrolled in the ACC-NCDR-CathPCI registry in India. Details of risk factors, clinical presentation, coronary angiography, interventions and in-hospital were recorded. Follow-up data in a sub-cohort recruited from Apr’19 to Mar’22 were obtained for incident major cardiovascular events (MCE) (cardiovascular deaths, recurrent ACS, PCI and bypass surgery). Results 8296 ACS patients were enrolled; prior statin use was in 3149 (38%) and statin naïve were 5147 (62%). Statin-user vs statin-naïve patients were older (61.6+10 vs 59.7+11y), with more hypertension (60.1 vs 48.6%), diabetes (35.8 vs 31.8%), pre-existing CAD (PCI 20.9 vs 9.1%; CABG 5.0 vs 2.3%) and lower mean total, LDL, and NHDL cholesterol (p<0.001). Statin users had less ST-elevation myocardial infarction (STEMI) (28.4% vs 45.2%), more non-STEMI (65.2 vs 50.8%), better LVEF (46.3+10 vs 44.5+10%), >2 coronary stents (35.5 vs 29.5%), lower mechanical circulatory support (2.2 vs 3.9%) and lower median hospitalization (66.1 vs 68.5h) (p<0.001). In statin-users incidence of in-hospital CAD deaths was 29 (0.92%) vs 78 (1.52%) (odds ratio, OR 0.61, 95% confidence intervals 0.39-0.93) and all-cause deaths 33 (1.05) vs 91(1.77%) (OR 0.59, 95%CI 0.39-0.88) (p<0.01). ORs attenuated following multivariate adjustments for risk factors, clinical presentation and interventions. In the follow up cohort (n=3813, high-intensity statins 99.6%), among baseline statin-users incident MCE was 98 (6.9%) vs 214 (8.9%) (hazard ratio, HR 0.76, 95%CI 0.59-0.97) and CVD deaths were in 46 (3.2%) vs 113 (4.7%) (HR 0.68, 95%CI 0.48-0.96) with attenuation following adjustment for baseline clinical variables and interventions. Conclusions Acute coronary syndrome patients taking pre-admission statins have significantly lower in-hospital and long-term cardiovascular and all-cause mortality following PCI.

Proenkephalin improves risk prediction in acute coronary syndromes: derivation and external validation of the KID-ACS risk score

Abstract Background Early assessment of renal and mortality risk in patients with acute coronary syndromes (ACS) is essential to guide treatment decisions according to international guidelines. Circulating proenkephalin (PENK) is a stable opioid metabolite with fast response to changes in kidney function. Purpose This study examined the predictive value of PENK for acute kidney injury (AKI) and mortality in patients presenting with acute coronary syndromes (ACS). Methods Plasma PENK levels were measured using a validated sandwich immunoassay in a prospective multicentre ACS cohort from Switzerland (n = 4 787) and in validation cohorts from the UK (n = 1 141) and Czechia (n = 920). A biomarker-enhanced risk score for simultaneous prediction of both in-hospital acute kidney injury (AKI) and 30-day death (KID-ACS score) with model coefficients adjusted to the outcome was derived and externally validated. In the development of the in-hospital AKI model, patients from one participating study centre were reserved for external validation (Swiss validation cohort). Results Circulating PENK ranked among the top predictors of renal outcomes and mortality in patients with ACS. Accounting for established risk factors and risk models, circulating PENK levels at presentation were independently associated with in-hospital AKI (per log2 increase: adjusted odds ratio [OR] 1.56, 95% CI 1.14 – 2.12, P = 0.005) and with 30-day mortality (per log2 increase: adjusted OR 2.69, 95% CI 1.89 – 3.84, P < 0.001). Dynamic changes in PENK levels within the first 12-24 hours after presentation were strongly and independently associated with in-hospital AKI (increase vs. decrease: adjusted OR 2.83, 95% CI 1.98 – 4.05, P < 0.001). The simple 6-item KID-ACS risk score for in-hospital AKI and 30-day mortality integrates PENK levels at presentation and showed an AUC of 0.72 (95% CI 0.68 – 0.76) for in-hospital AKI, and of 0.91 (95% CI 0.87 – 0.95) for 30-day mortality in the derivation cohort. Upon external validation, KID-ACS had similarly high performance for in-hospital AKI (Swiss validation cohort: AUC 0.73, 95% CI 0.70 – 0.77; Czech validation cohort: 0.74, 95% CI 0.68 – 0.80) and 30-day mortality (UK validation cohort: AUC of 0.87, 95% CI 0.82 – 0.91; Czech validation cohort: 0.91, 95% CI 0.87 – 0.94). The simple 6-item KID-ACS score was non-inferior to established risk models and significantly outperformed the CA-AKI risk score in predicting in-hospital AKI (Zurich cohort: delta AUC 0.11, 95% CI 0.07 – 0.15, P = 0.001) and the GRACE 2.0 in predicting 30-day mortality (UK cohort: delta AUC 0.05, 95% CI 0.01 – 0.09, P = 0.027). Conclusions Circulating PENK was identified as independent predictor of in-hospital AKI and 30-day mortality in patients with ACS. The simple 6-item KID-ACS risk score integrates circulating PENK levels and provides a novel tool for simultaneous assessment of renal and mortality risk in patients presenting with ACS.Independent Predictive Value PENKPerformance and validation of KID-ACS

The hemodynamic classification system for hemodynamic-related adverse events in left ventricular assist device patients

Abstract Background Durable left ventricular assist device (LVAD) physiology predisposes to right heart failure (RHF) and aortic insufficiency (AI), recently labelled hemodynamic-related adverse events (HDREs). However, the pathophysiology, incidence, and associated morbidity of HDREs remains largely unsettled due to heterogeneity in data reporting. Purpose We sought to validate the recently proposed LVAD Hemodynamic Classification System (HCS) for HDREs. Methods RHF and AI HDREs were retrospectively adjudicated, staged (mild to severe) and phenotyped (isolated or combined RHF/AI-HDREs) based on the HCS assessed at 6-month post-LVAD implant among 183 consecutive patients undergoing LVAD implant at a quaternary heart failure center, and either alive at 6-month on support (n=175) or deceased due to late HDREs 1 to 6 months post-LVAD implant (n=8). The primary outcome was a composite of first HF hospitalization or cardiovascular death between 6 and 24 months after LVAD-implant. Results At 6-month assessment, RHF-HDRE was adjudicated in all patients, while AI-HDRE could not be adjudicated in 22 (12.0%) patients. Overall, 53 (29.0%) patients developed an RHF-HDRE, and 26 (16.0%) an AI-HDRE (phenotypes: 39 isolated RHF, 15 isolated AI, 11 combined RHF-AI, 3 not-adjudicated). During pre-LVAD assessment, age and pulmonary artery pulsatility index were independently associated with RHF-HDRE; and pre-LVAD AI and systolic pulmonary artery pressure with AI-HDRE. Patients developing the combined RHF-AI phenotype required the most intensive bundle of critical care pre-LVAD implantation, had more frequent pre-LVAD RV dysfunction, the highest rate of early post-LVAD RHF, and the most prominent features of suboptimal left ventricular unloading, RV dysfunction, peripheral congestion, renal damage and impaired functional capacity at 6-month assessment. RHF-HDRE (adj-HR 2.69, 95%CI 1.14-6.34, p=0.024), AI-HDRE (adj-HR 4.21, 95%CI 1.70-10.40, p=0.002) and HDRE phenotype (isolated RHF or AI HDRE vs. no HDRE: adj-HR 2.80, 95%CI 1.03-7.62, p=0.044; combined RHF and AI HDRE vs. no HDRE: adj-HR 4.53, 95%CI 1.33-15.35, p=0.015) were associated with the primary outcome. A graded increase in primary outcome was observed with rising RHF and AI stages. Conclusions The LVAD Hemodynamic Classification System for HDREs identifies pathophysiological and clinical clusters of patients with significant prognostic implications. It may help the development of targeted strategies to mitigate HDREs and improve the success of long-term LVAD support.

Cardiovascular mortality with oral potassium-binders in patients with CKD and heart failure

Abstract Introduction Hyperkalemia is an inherent consequence of advancing chronic kidney disease (CKD) as a result of the kidney’s decreased ability to excrete potassium. Heart failure patients with concomitant CKD may not tolerate maximum doses of guideline-directed medical therapies (GDMT) like ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), angiotensin receptor/neprilysin inhibitors (ARNI) and mineralocorticoid receptor antagonists (MRA) due to dose-limiting hyperkalemia. Many randomized controlled trials in heart failure exclude patients with advanced CKD. Two oral therapies exist to manage hyperkalemia - patiromer sorbitex calcium and sodium zirconium cyclosilicate. This study aims to identify the potassium-binder with better outcomes as defined by less readmissions, hyperkalemia episodes, and death. Purpose This project was undertaken to better understand the impact of using potassium-binders in CKD patients with heart failure. Improved management of hyperkalemia will be an avenue for optimization of GDMT in this population. Methods and materials The TriNetX research network was used for this study. Two cohorts of patients were created by using International Classification of Disease 10 (ICD-10) codes and CPT codes. Both cohorts consisted of patients with no prior history of hyperkalemia within 30 days of hospital discharge at which time one cohort was prescribed patiromer and the other received sodium zirconium cyclosilicate. Each cohort was prohibited from exposure to the other medication. The cohorts were balanced by propensity score matching and the greedy nearest neighbor algorithm for age, race, gender, ethnicity. They were also balanced for systolic and diastolic heart failure diagnoses, and for each individual stage of CKD (1 through 5 and end stage). They were also balanced for use of ACEi, ARBs, and MRAs. This resulted in 8,921 patients in each arm. They were then evaluated for the outcomes of hospital readmission, hyperkalemia episodes (>6.1 mmol/L), and death within 12 months. Results Patients treated with patiromer were more likely to be hospitalized over the following twelve months (44% vs 40%, RR 1.11, 95% CI (1.07,1.15), p value <0.0001). They were also more likely to experience hyperkalemia (11.7% vs 9.2%, RR 1.27, 95% CI (1.16,1.38), p value <0.0001). Patiromer was also associated with slightly greater all cause mortality (27% vs 25%, RR 1.08, 95% CI (1.03,1.13), p value 0.0021). Discussion This study demonstrates patiromer has more readmissions and hyperkalemia episodes along with greater mortality. In conclusion, sodium zirconium cyclosilicate was found to have better outcomes compared to that of patiromer. Further studies are necessary to better understand the utility of using sodium zirconium cyclosilicate as maintenance therapy for hyperkalemia in order to maximize GDMT in CKD patients with heart failure.

Effectiveness of empagliflozin in patients with heart failure and COPD: Results from EMPEROR-Preserved and EMPEROR-Reduced

Abstract Background Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are chronic, progressive syndromes that share numerous risk factors and clinical symptoms. We sought to analyse the relationship between COPD status and outcomes in patients receiving empagliflozin or placebo in the EMPEROR-Preserved and EMPEROR-Reduced trials. Methods and results We analyzed data of 9,718 patients, including 1,238 (12.7%) with COPD. Compared to patients without COPD, patients with COPD were more likely to be in NYHA class III (19.4 vs. 28.4%), to be male (62.4 vs. 69.0%), to have higher body mass index (29.0±5.7 vs. 29.5±6.1 kg/m2), to be white, to be smoker or ex-smoker (47.1 vs. 71.9%), to be older (69.6±10.5 vs. 72.1±8.7y, all p<0.0001), to have a longer duration of HF (5.0 vs. 5.4y, p=0.04), to have higher haemoglobin and high-sensitivity troponin T values (both p<0.01), and a trend towards more advanced kidney dysfunction. Patients with COPD exhibited a higher adjusted risk of reaching the primary endpoint of first HF hospitalization or CV death compared to those without COPD (adjusted hazard ratio [HR] 1.52, 95% confidence interval [95% CI] 1.28-1.80, p<0.0001). The favorable impact of empagliflozin on the primary outcome remained consistent regardless of COPD status at baseline (no COPD: HR 0.76, 95% CI 0.68-0.84, COPD: HR 0.82, 95% CI 0.66-1.03, p for interaction 0.50, Figure). The effects on HF hospitalizations, cardiovascular and all-cause mortality were not affected by COPD status. The Kansas City Cardiomyopathy Questionnaire showed similar improvement in patients with or without COPD treated with empagliflozin. The distribution of adverse events was comparable between patients receiving empagliflozin and those on placebo, irrespective of COPD status at baseline. Conclusions COPD is frequently encountered in patients with HF and associated with worse outcomes. Among patients with COPD, treatment with empagliflozin is associated with consistent efficacy on outcomes and improvement in quality of life as in patients without COPD.

Different right ventricular mechanics in atrial and ventricular secondary tricuspid regurgitation and their prognostic role. A multicentric three-dimensional echocardiography study

Abstract Background/Introduction Secondary tricuspid regurgitation (STR) can develop from markedly different etiologies. Both progressive dilation and dysfunction of the right atrium (atrial phenotype, ASTR), and adverse right ventricular (RV) remodeling (ventricular phenotype, VSTR) may result in STR. RV function is a major determinant of outcome in patients with STR. However, data about how RV function adapts to ASTR and VSTR are scarce, and the prognostic implications of RV mechanics in ASTR and VSTR remain to be clarified. Purpose Accordingly, we aimed to investigate the RV mechanical patterns in ASTR and VSTR and to examine their prognostic role using three-dimensional (3D) echocardiography. Methods We enrolled 192 patients with STR (60% women) who underwent clinically indicated transthoracic echocardiography in a multicentric prospective observational study. The primary outcome was defined as a composite of heart failure hospitalization or cardiac death. STR etiology was assessed based on the TVARC criteria (ventricular STR n=134, atrial STR n=58). STR severity was categorized using STR effective regurgitant orifice area according to current guidelines. We assessed RV function by measuring the tricuspid annular plane systolic excursion (TAPSE) by M-mode echocardiography and RV ejection fraction (EF) by 3D echocardiography. In addition, we imported the 3D RV meshes into the ReVISION software package (Argus Cognitive, Inc, Lebanon, USA) to quantify the relative contribution of the longitudinal (LEFi), radial (REFi), and anteroposterior motion components (AEFi) to total RV EF. Results ASTR and VSTR patients had comparable TAPSE (17±5 mm vs. 18±5 mm, p=0.10), while RV EF was significantly higher in ASTR (54±7% vs. 47±10% p<0.001). Although LEFi (0.37±0.08 vs. 0.38±0.10, p=0.95) and AEFi (0.45±0.08 vs. 0.44±0.11, p=0.53) were comparable between ASTR and VSTR, REFi was significantly lower in VSTR (0.52±0.09 vs. 0.47±0.12, p<0.01). RF EF was comparable among STR severity grades (mild vs. moderate vs. severe: 50±11 vs. 49±9 vs. 50±10%, respectively, p=0.85). Conversely, LEFi was significantly higher in mild and moderate STR vs severe STR (0.39±0.08 vs. 0.39±0.09 vs. 0.35±0.10, respectively, p=0.04). Using multivariable Cox regression based on variables significant in the univariate analysis, REFi was a significant independent predictor of outcome in the entire cohort (hazard ratio: 0.978 [CI, 0.959-0.999], p= 0.037). Conclusions Using 3D echocardiographic assessment, ASTR and VSTR patients demonstrated significant differences in the RV mechanical pattern, with a lower contribution of the radial contraction in the case of ventricular STR etiology. While RV EF was comparable between STR severity grades, the relative importance of the longitudinal motion significantly differed. Notably, the relative contribution of radial motion to RV function demonstrated independent prognostic value in patients with STR.RV mechanics in STR severity stages

Effects of body mass index on worsening of heart failure and all-cause death in patients with heart failure and reduced left ventricular ejection fraction: a 10-year follow-up study

Abstract Background/Introduction Obesity in patients with heart failure (HF) with reduced ejection fraction (HFrEF) is common, and with the emergence of effective anti-obesity drugs, a better understanding of the relation between BMI and clinical outcome in HFrEF is needed. Purpose This study aimed to analyse whether a body mass index (BMI) above 27 kg/m2 (cut-off used in trials) is associated with a greater rate of all-cause death and HF hospitalization in patients with HFrEF. Methods We included 1,017 medically optimized according to existing HF guidelines at the time and clinically stable HF patients with a left ventricular ejection fraction of <45% from the NorthStar study. Patients were included between 2005 and 2009 and followed for 10 years using Danish nationwide registries. The outcomes of interest were all-cause death and hospital discharge for HF (overnight stay). Descriptive statistics were grouped according to tertiles of BMI. The association between BMI as a continuous variable and the outcomes of interest was analysed using restricted cubic splines in Cox proportional-hazards models. Reported were hazard ratios (HR) with 95% confidence intervals (CI) adjusted for relevant prognostic covariates (reference: BMI = 27 kg/m2). Results At enrolment, the median age was 69 years, 75% were men, and the median BMI was 26.3 kg/m2 (Table 1). Patients in the upper 3rd BMI tertile were younger (median age 67), had a lower level of NT-proBNP level (median 737.5 pg/ml) and a higher proportion of diabetes (29.9%). During 10 years of follow-up, HF hospitalization occurred in 683 patients (61.7%), and 623 patients died (56.3%). A BMI above 27 kg/m2 was associated with a higher rate of HF hospitalization (significantly from BMI 35.2 kg/m2: HR 1.30 [CI 1.00-1.68]; Figure 1). Similar findings were observed for all-cause mortality (significantly from BMI 35.7 kg/m2: HR 1.27 [CI 1.00-1.62]) Conclusion In patients with HFrEF, a BMI above 27 kg/m2 was associated with a higher rate of HF hospitalization and all-cause death. Efforts to find effective and safe approaches to reducing weight in obese patients with HFrEF are warranted.Figure 1

Direct Oral Anticoagulants versus Vitamin K Antagonists for the management of left ventricular thrombus after myocardial infarction: A meta-analysis

Abstract Background/Introduction Left ventricular (LV) thrombus formation is not an uncommon complication after acute myocardial infarction (AMI) in the modern era of early reperfusion. The optimal anticoagulation regimen in this clinical scenario remains poorly-defined. Purpose The present meta-analysis sought to investigate the efficacy and safety profile of direct oral anticoagulants (DOACs) compared with Vitamin K antagonists (VKAs) for the management of LV thrombus following AMI. Methods A systematic literature review was conducted in electronic databases to identify studies reporting efficacy and safety outcome data regarding the use of DOACs versus VKAs for patients with LV thrombus after MI. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and random-effects meta-analyses were conducted to synthesize pooled ORs. Results Eight studies comprising a total of 605 patients were included (Table). DOACs were associated with an almost 2-fold higher likelihood for achieving thrombus resolution compared to VKAs (pooled OR 1.95 [1.25-3.04]; p =0.003, I2 =0 %), while they achieved a 70% lower risk for systemic embolism (pooled OR 0.30 [0.12-0.75]; p =0.01, I2 =0%). The use of DOACs was associated with a 54% lower risk for bleeding compared to VKAs (pooled OR 0.46 [0.26-0.84]; p =0.01, I2 =0 %). Overall, patients receiving DOACs had a 63% lower risk to reach the composite outcome of any bleeding, systemic embolism, cardiovascular hospitalization, or all-cause death, compared with patients using VKAs (pooled OR 0.37 [0.23-0.60]; p <0.0001, I2 =0%) (Figure). Conclusion DOACs appear to have a more favorable efficacy and safety profile compared to VKAs for the management of LV thrombus following AMI.Graphical abstractTable