Predictors Of Outcome Research Articles

Right atrio-ventricular strain as a predictor of death in left-sided heart failure

Abstract Background Right ventricular (RV) strain is an established outcome predictor in heart failure (HF). However, the role of right atrial (RA) strain in the setting of left-sided HF is incompletely understood. Purpose We sought to evaluate the RV, RA and combined right atrio-ventricular (RAV) strain using speckle-tracking echocardiography in a cohort of patients with left-sided HF and to assess their prognostic role. Methods 121 consecutive patients (mean age 59±14 years, 74% men) with HF with reduced ejection fraction (HFrEF) referred to our echocardiography department were prospectively enrolled. The main endpoint was all-cause death. RV strain was measured as the average longitudinal strain of the basal, mid, and apical segments of the RV free wall and was reported as a positive value, thus a lower RV strain reflecting a greater longitudinal dysfunction. RA strain was defined as the maximal longitudinal displacement of the atrial wall at end-systole, corresponding to atrial reservoir function. RAV strain was defined as the sum of RV strain and RA strain. Results During a median follow-up of 19±11 months, 26 patients (21%) died. Patients who reached the endpoint had lower left ventricular ejection fraction (LVEF) (21±7% vs. 26±7%, p=0.001), lower tricuspid annular plane systolic excursion (16±3 vs. 18±5, p=0.02) and lower RA strain (13± 10% vs. 18±11%, p=0.03). In univariable Cox regression, RV, RA and RAV strain were all predictors of death: HR=1.05 [95% CI, 1.00-1.11], p=0.045 for RV strain, HR=0.95 [95% CI, 0.91-0.99], p=0.02 for RA strain, HR=0.97 [95% CI, 0.94-0.99], p=0.01 for RAV strain. We constructed a multivariable model with well-established event predictors in HFrEF and one strain index at a time. After adjustment for LVEF, maximal left atrial volume, tricuspid regurgitation severity and pulmonary artery systolic pressure, only RAV strain remained an independent predictor of death (HR=0.97 [95% CI, 0.94-1.00], p=0.04), while RV strain and RA strain did not (p=0.07 for both). LVEF did not emerge as a predictor of death in multivariable regression (p=0.57). Conclusion In left-sided HF, RV and RA strain were predictors of death. Combining the longitudinal strain of both right heart chambers might improve risk stratification, since RAV strain remained the only independent predictor of adverse outcome after adjustment for confounders.

Is unsatisfactory outcome of alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy predictable?

Abstract Background Alcohol septal ablation (ASA) has been introduced for left ventricular outflow tract gradient (LVOTG) reduction in patients with hypertrophic obstructive cardiomyopathy (HOCM). However, some patients may not profit from ASA. Thus, we identified characteristics of patients with unsatisfactory outcome of ASA in a large single-center cohort. Methods Consecutive ASAs between 1997 and 2023, performed at our institution, were retrospectively enrolled. Those ASAs performed in patients with missing follow-up (FU), previous septal reduction therapy (SRT), and atypical HOCM were excluded. Patients with unsatisfactory outcome (PUO) were defined as continuing to meet the guideline criteria for SRT (NYHA ≥III or NYHA ≥II with exertional syncope and resting/exercise-induced LVOTG ≥50mmHg). PUO were compared to patients with good outcome (PGO). Results are expressed in % or median and interquartile range (IQR). Pre-procedural predictors of poor hemodynamic outcome were identified using logistic regression analysis. Results 65 of 1003 patients were PUO (6.5%). Those were younger (48.0 years [40.5-61.8] vs. 57.0 years [IQR 47.0-67.0] in PGO; p=0.0030), more often reported syncope at baseline (35.4% vs. 22.2% in PGO; p=0.0214), and had lower body-mass-index (26.4kg/m2 [23.8-29.2] vs. 27.7kg/m2 [25.2-23.1] in PGO; p=0.0160). In PUO, resting LVOTG was higher at baseline (53.0mmHg [24.5-82.0]) than in PGO (40.0mmHg [22.0-75.0]; p=0.0292; Table 1). Differences in sex, family history of sudden cardiac death, dyspnoea, medication, and interventricular septum diameter (IVSD) were not observed at baseline (all p>0.05; Table 1). Age (OR 1.023; CI: 1.005-1.042; p=0.0129), syncope at baseline (OR 1.890; CI: 1.049-3.324; p=0.0296), and BMI (OR 1.072; CI: 1.007-1.145; p=0.0355) were found to independently influence poor hemodynamic response to ASA using multiple logistic regression controlling for confounders. However, sex, baseline IVSD, and LVOTG were not found to influence poor hemodynamic outcome (p>0.05). There were no differences with regard to the number of embolized branches (1 in both groups), the size of the balloon used to cover the septal branch (1.5mm in both groups), the volume of ethanol (PUO: 1.4ml [1.0-2.0]; PGO: 1.5ml [1.2-2.0]), or creatine kinase release (PUO: 879.0U/l [375.0-1187.0]; PGO: 842.0U/l [501.5 - 1234]) (all p>0.05). At 6-months-FU, PUO had significantly higher IVSD (18.0mm [13.5-22.0] vs. 16.0mm [12.0-19.0] in PGO; p=0.008), higher resting LVOTG (31.0mmHg [20.0-55.5] vs. 14.0mmHg [10.0-22.0] in PGO; p<0.0001) and higher exercise-induced LVOTG (105.0mmHg [84.5-143.0] vs. 35.0mmHg [22.0-64.0] in PGO; p<0.0001). Conclusion ASA was overall effective with only few patients experiencing unsatisfactory outcome. Syncope, age, and BMI were found predicting poor hemodynamic outcome.Baseline characteristics

Chronotropic incompetence as a critical predictor for cardiovascular outcomes in heart failure with preserved ejection function

Abstract Background Chronotropic incompetence (CI), linked with exercise intolerance, is a prevalent feature of heart failure with preserved ejection fraction (HFpEF). Our study aimed to explore the impact of CI on cardiovascular outcomes in HFpEF patients. Methods From November 2019 to December 2022, we enrolled 359 subjects who underwent invasive cardiopulmonary exercise testing (iCPET) due to heart failure symptoms. After excluding individuals without HFpEF (those with resting pulmonary capillary wedge pressure [PCWP] < 15mmHg or exercise PCWP < 25mmHg), we identified 113 patients for long-term follow-up. Our assessment of cardiovascular outcomes encompassed hospitalization for heart failure (HHF) and cardiovascular death. We employed Cox regression analysis to evaluate the associations between exercise hemodynamic parameters and outcomes. Results Among the cohort, 85 (75.2%) subjects with CI were older (71 vs. 66 years) and more frequently women (61 vs. 28%) compared to those without CI. At peak exercise, patients with CI exhibited significantly reduced left atrial booster strain, impaired right ventricle-arterial coupling, decreased systemic vascular resistance, cardiac output (CO), stroke volume, VO2, respiratory exchange ratio, and minute ventilation/carbon dioxide production (VE/VCO2) slope. A significant increase in PCWP (36 ± 10 vs. 26 ± 11mmHg, p=0.012) was noted in patients with CI. Over a median follow-up of 22.6 months, 20 (17.7%) subjects experienced cardiovascular events. Multivariate Cox proportional analyses revealed that CI (Hazard ratio [HR] 1.725, 95% confidence intervals [CI] 1.212-2.413) and an elevated PCWP/CO slope (HR 1.829, 95% CI 1.331-2.382) were predictive of outcomes. Conclusions Patients with CI demonstrated heightened filling pressure, a steeper VE-VCO2 slope, and reduced VO2 compared to those without CI. These factors likely contribute to adverse cardiovascular outcomes in HFpEF patients with CI.

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

Estimated aortic pulse wave velocity predicts adverse events in females with thoracic aortic aneurysms

Abstract Introduction Despite being more common in males, thoracic aortic aneurysms (TAAs) have worse prognosis in females. Females with TAA are 3x more likely to experience acute aortic syndromes, and 40% more likely to die than their male counterparts, but mechanisms underlying this paradox are incompletely understood. The estimated aortic pulse wave velocity (e-PWV) is a marker of aortic stiffness that can be used widely due to its simplicity, as it does not require specialized equipment. We have previously shown that e-PWV was independently associated with faster TAA growth,(1) and that this association was twice as strong in females than males, but the role of e-PWV as a predictor of adverse outcomes in TAA remains unknown. Purpose We sought to evaluate the sex-specific association of e-PWV with adverse outcomes in patients with TAA. Methods We performed a prospective study of 102 males and 48 females with TAA. e-PWV was calculated according to validated equations utilizing age, mean arterial pressure, and presence/absence of cardiovascular risk factors.(2) The primary outcome was a composite of acute aortic syndromes, death, or elective aortic surgery. We used a Cox proportional hazard model to determine the independent association of e-PWV with the primary outcome, adjusted for age, BSA, aneurysm size and location, hypertension, and pulse pressure. Sex-specific models were performed if the interaction of sex*e-PWV was significant (P≤0.05). Univariate logistic regression models were performed to determine the c-statistic for e-PWV in predicting adverse outcomes, and the best e-PWV cutoff for this prediction was established based on sensitivity and specificity. Kaplan-Meier curves were performed using this cut-off. Results A summary of study design and results is presented in Picture 1. Mean age was 62±12 years, 70 (47%) had degenerative etiology, baseline aneurysm size was 46.3±4.3mm, and e-PWV was 9.5±1.9 m/s (not different between sexes, P>0.07 for each). Mean follow-up was 4.6±2.4 years in females and 5.5±2.3 years in males, P=0.031. The primary outcome occurred in 37 (25%) participants (3 dissections, 3 intramural hematomas, 1 aortic rupture, 22 elective surgical repairs and 11 deaths - 3 of which followed surgery). The interaction term sex*e-PWV was significant (P=0.0001), so sex-specific models were performed. e-PWV independently predicted the primary outcome in females (HR for 1m/s increase in e-PWV: 3.4; 95% confidence interval (CI): 1.1-14.7, P=0.033), but not in males (HR: 0.87; 95% CI: 0.50-1.51, P=0.622). In females, e-PWV had a c-statistic of 0.860 for the detection of the primary outcome, with a best e-PWV cutoff of 11.58 m/s (73% sensitivity, 92% specificity). Kaplan-Meier curves for the primary outcome in females using this cutoff are shown in Picture 2. Conclusion e-PWV independently predicts adverse outcomes in females with TAA, highlighting a novel marker for risk stratification and therapeutic targeting.Study summaryKaplan-Meier curves

The associations of triglyceride glucose and its derived indexes with 10-year cardiovascular disease risk in a Chinese community-based population

Abstract Background The triglyceride-glucose (TyG) index has been regarded as a reliable surrogate marker of insulin resistance and an independent predictor of cardiovascular outcomes. However, the associations of the derived TyG indexes with incident CVD risk are controversial, and that the relevant data are sparse for the Chinese population studies. Objectives We aimed to investigate the association of TyG index and its derived indexes with incident CVD risk and to compare their predictive capacity in the Chinese community-based population. Methods We conducted a prospective cohort study on subjects from a Beijing community in China who were free of prevalent stroke or myocardial infarction at baseline. The primary endpoint was a new-onset major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, first non-fatal stroke, and first non-fatal acute myocardial infarction. Cox proportional-hazards regression analyses and time-dependent receiver operator characteristic curve analyses were performed. Results A total of 8,806 participants were included. The mean age was 56.51 ± 8.93 years, and 5,679 (64.5%) were female. The median value of TyG index, TyG-BMI, TyG-WC, and TyG-WHtR were 8.71 (8.34-9.12), 226.37 (201.02-252.87), 720.80 (653.52-791.03), and 4.47 (4.07-4.90), respectively. During a mean 9.7-year follow-up, a total of 877 (10%) cases of MACE were recorded. The Kaplan–Meier curves showed significant differences in cumulative hazards of new-onset MACE among tertiles of abovementioned indexes (Log rank P < 0.0001) (Figure 1). Multivariable Cox regression analyses revealed that TyG index, TyG-BMI, TyG-WC, and TyG-WHtR were positively associated with the hazards of MACE. Compared with tertile 1, the multivariable adjusted HRs (95% CIs) of incident CVD for tertile 3 were 1.26 (1.01-1.56), 1.57 (1.15-2.14), 1.54 (1.19-2.00), and 1.81 (1.40-2.33) for TyG, TyG-BMI, TyG-WC, and TyG-WHtR, respectively (Figure 2). There are no significant differences in the Harrell's C indexes among the various indexes compared to the TyG index (TyG index: 0.758 [0.743-0.774], TyG-BMI: 0.758 [0.743-0.773], TyG-WC: 0.758 [0.743-0.774], and TyG-WHtR: 0.760 [0.745-0.775]). Conclusions Higher TyG and its derived indexes are significantly associated with an increased risk of 10-year MACE. Our results suggest that TyG and its derived indexes may serve as a useful marker for stratifying CVD risk in the general population.

Multiple comorbidities are associated with poor prognosis in patients with ADHF-HFpEF and non-frailty or mild frailty but not moderate-severe frailty -PURSUIT-HFpEF Registry-

Abstract Background A variety of comorbidities are frequently observed and represent a major problem in the management of patients with heart failure. Frailty is a strong predictor of poor clinical outcome in patients with heart failure, which may be partially attributable to the presence of multiple comorbidities. However, it remains to be clarified whether frailty is prognostically useful in relation to multiple comorbidities in patients with acute decompensated heart failure and preserved ejection fraction (ADHF-HFpEF). Purpose The purpose of this study is to investigate the relationship between frailty, multiple comorbidities and prognosis in patients with ADHF-HFpEF. Methods We prospectively studied 1028 patients with ADHF-HFpEF. Frailty was assessed using Clinical Frailty Scale (CFS). Multiple comorbidities were defined as the presence of 4 or more factors from the following 11 groups: diabetes, obesity, lung disease, anemia, renal dysfunction, electrolyte disorder, dyslipidemia, depression, hypertension, stroke and cancer. The primary outcome of this study was the composite endpoint of all-cause mortality and rehospitalization for worsening heart failure. Results During a mean follow-up period of 1.6±1.3 years, 454 patients underwent primary outcome. CFS (p<0.001) and the number of comorbidities (p=0.006) were significantly independently associated with primary outcome after multivariate adjustment. Kaplan-Meier analysis revealed that patients with multiple comorbidities had significantly higher risk for primary outcome than those without multiple comorbidities in the group with non-frailty (defined as CFS of 1 or 2, p=0.019) and mild frailty (CFS of 3 or 4, p=0.036). However, there was no significant difference in the group with moderate or greater frailty (CFS of 5 or more) in patients with ADHF-HFpEF. Conclusion(s) Multiple comorbidities would be associated with poor prognosis in patients with ADHF-HFpEF and non-frailty or mild frailty but not in patients with moderate or greater frailty.Multiple comorbidities and MACE risk

Prognosticating short-term outcomes in STE-ACS patients with intra-procedure slow flow/no-reflow: an analysis of predictive factors in primary percutaneous coronary revascularization

Abstract Background "ST-segment elevation myocardial infarction (STEMI)" is the most lethal form of "ischemic heart disease (IHD).primary "percutaneous coronary intervention (PCI)" as the first-line treatment for STEMI patients, as it offers better outcomes compared to other medical or surgical options [1,2]. One major concern in interventional cardiology is the occurrence of "slow flow/no-reflow (SF/NR)", which refers to the poor myocardial perfusion to the infarct-related artery as a result of microvascular obstruction. Objectives In this study, we compared the incidence of short-term outcomes between two groups of patients based on the occurrence of intra-procedure "slow flow/no-reflow (SF/NR)" and identified predictors of short-term outcomes. Method This study enrolled a series of consecutive patients who underwent primary "percutaneous coronary intervention (PCI)" for "ST-elevation myocardial infarction (STEMI)". The patients who developed SF/NR during the procedure were compared with their counterparts for the incidence of short-term "major adverse cardiovascular events (MACE)". Furthermore, the study aimed to identify predictors of short-term mortality in these patients. Result In this study, a total of 2,582 patients were included. Among them, 79.1% (2,042) were male. The average age of the patients was 55.7 ± 11.2 years. Intra-procedure SF/NR was observed in 21.7% (560) of the patients. During median short-term follow-up of 180 [144-205] days, patients with SF/NR exhibited higher incidence of all-cause mortality (23.6% vs. 12.3%; p<0.001), and MACE (30.4% vs. 16.9%; p<0.001) with hazard ratio of 1.82 [1.46-2.27; p<0.001] and 1.69 [1.39-2.05; p<0.001], respectively. Among patients with SF/NR, adjusted odds ratio for total ischemic time: 1.04 [1.00-1.07; p=0.041], random blood sugar levels: 1.01 [1.00-1.01; p<0.001], intubation status: 2.79 [1.26-6.18; p=0.011], post-procedure sub-optimal flow: 1.76 [1.04-2.98; p=0.034], and intra-procedural arrhythmias: 5.48 [2.03-14.79; p<0.001] were found to be independent predictors of short-term mortality. Conclusion In conclusion, the presence of intra-procedure SF/NR carries significant prognostic implications. Patients with intra-procedure SF/NR face a significantly higher risk of short-term adverse outcomes.

The CT-derived fat-free muscle fraction is associated with inflammation and predicts outcome in patients with aortic stenosis undergoing TAVR

Abstract Background The ESC guidelines underscore the importance of objective risk stratification in making patient-centered decision for valve interventions. However, they primarily rely on surgical risk scores, not considering essential factors such as frailty. Computed tomography (CT) is a routine part of the pre-interventional workup in patients undergoing TAVR and allows for body composition analysis, including the assessment of fat-free muscle fraction (FFMF) as an indicator of muscle quality. Purpose This study aimed to assess the correlation between FFMF and both inflammation and endocrine disorders, and to investigate the predictive value of FFMF in patients with aortic stenosis undergoing TAVR. Methods The study included 789 patients undergoing TAVR between 2017 and 2019. Evaluations involved CT scans to assess body composition. Using densitometric thresholds, the skeletal muscle area at L3/L4 level was separated into fatty and lean muscle to calculate the FFMF. The cohort was divided into tertiles of high, medium, and low FFMF, Figure 1. Results The study population was 45.5% female with a mean age of 81.2±6.0 years. Overall, 261 (33.1%) patients had a high FFMF, 293 (37.1%) had a medium FFMF, and 235 (29.8%) had a low FFMF. Patients with a low FFMF were older (82.3±5.9 vs 81.6±5.6 vs 79.8±6.2 years, p<0.01) and had higher rates of atrial fibrillation (52 vs 43 vs 37%, p<0.01), compared to those with a medium and high FFMF. Regarding body composition, low FFMF patients had a higher percentage of body fat (28.7±11.2 vs 26.8±9.1 vs 24.2±9.6%, p=0.01) and a lower percentage of body muscle (30.9±5.3 vs 31.3±4.2 vs 32.7±4.4%, p=0.03). Moreover, a low FFMF was associated with inflammation, as indicated by increased levels of C-reactive protein (6.3 vs 4.2 vs 3.1 mg/l, p<0.01) and procalcitonin (0.06 vs 0.05 vs 0.05 µg/l, p=0.01). Endocrinological assessment revealed lower levels of estradiol (6.8 vs 14.7 vs 15.0 pg/ml, p=0.02) and testosterone (0.18 vs 0.48 vs 2.35 ng/ml, p<0.01) as well as higher levels of cortisol (8.9 vs 7.7 vs 7.6μg/dl, p=0.05) in low FFMF patients. Regarding clinical outcomes, low FFMF was associated with increased one-year mortality (23.4%) compared to medium (11.6%) or low FFMF (3.8%, p<0.01), Figure 2A. This difference persisted over five years (p<0.01), Figure 2B. ROC curve analysis showed that FFMF had the strongest association with one-year mortality (AUC 0.75, p<0.01) and was superior to the STS-PROM (AUC 0.65) and EuroSCORE II (AUC 0.64). Multivariate analysis revealed that low FFMF was independently associated with mortality following TAVR (OR: 3.19 [CI: 1.64 – 6.22], p<0.01). Conclusion The CT-derived FFMF is associated with inflammation and endocrinological disorder in patients undergoing TAVR. Importantly, a low FFMF is a strong and independent predictor of dismal outcomes. FFMF assessment can seamlessly integrate into routine pre-interventional CTs, offering a promising objective parameter for outcome prediction.

Cardiovascular etiologies and risk factors of survival outcomes after resuscitation for out-of-hospital cardiac arrest: data from the KoCARC registry

Abstract Background The outcomes and characteristics of out-of-hospital cardiac arrest (OHCA) vary across geographic regions. The etiologies and prognoses of OHCA in Asian populations remain less established. This study aimed to investigate the etiologies and clinical characteristics of patients successfully resuscitated after OHCA and identify predictors of survival outcomes. Methods Data were extracted from a South Korean multicenter prospective registry of OHCA that included 64 tertiary hospitals from 2015 to 2018 (n=7577). The primary outcome was in-hospital mortality, and secondary outcome was the grade-1 cerebral performance category (CPC) score at discharge. Results Of the 7577 patients, 2066 achieved return of spontaneous circulation (ROSC) and were hospitalized and 915 (44·2%) presented with ventricular arrhythmia (VA) as their initial rhythm or on admission. The leading cause was obstructive coronary artery disease (n=413; 20·0%). Sudden unexplained death syndrome (SUDS) accounted for 67·5% of survivors, which were significantly lower with VA (82·7% vs. 48·3%, p<0.001). VA was an independent predictor of in-hospital mortality (adjusted hazard ratio [aHR] 0·72, 95% confidence interval 0·60–0·87) and the grade-1 CPC score at discharge (aHR 3·63, 95% CI 2·56–5·15). Other predictors of the primary outcome included age, ROSC on arrival, total arrest time, alertness on admission, extracorporeal membrane oxygenation use, targeted temperature management, implantable cardioverter defibrillator use, and coronary vasospasm. Conclusions SUDS was common in patients with ROSC after OHCA and thus needs to be evaluated comprehensively. VA was independently associated with favorable survival outcomes at discharge. Further management may improve clinical outcomes in patients with OHCA, particularly those with VA.

ChineseCVD: a web-based Chinese-specifi c cardiovascular risk calculator incorporating long COVID, COVID-19vaccination, SGLT2i and PCSK9i treatment effects

Abstract Background Web-based risk prediction tools for cardiovascular diseases are crucial for providing rapid risk estimates for busy clinicians, but there is none available specifically for Chinese subjects. This study developed ChineseCVD, a risk calculator for cardiovascular disease. Methods Adult patients attending government-funded family medicine clinics in Hong Kong between 1st January 2000 and 31st December 2003 were included. The primary outcome was major adverse cardiovascular events (MACE) defined as a composite of myocardial infarction, heart failure, transient ischaemic attacks/ischaemic strokes, and cardiovascular mortality. Results A total of 155,066 patients were used as the derivation cohort. Over a median follow-up of 16.1 (11.6-17.8) years, 31,061 (20.44%) had MACE. Cox regression identified male gender, age, comorbidities, cardiovascular medications, systolic and diastolic blood pressure, and laboratory test results (neutrophil-lymphocyte ratio, creatinine, ALP, AST, ALT, HbA1c, fasting glucose, triglyceride, LDL and HDL) as significant predictors of the above outcomes. ChineseCVD further incorporates the impact of smoking status, COVID-19 infection, number of COVID-19 vaccination doses, and modifier effects of newest medication classes of PCSK9i and SGLT2i. The calculator enables clinicians to demonstrate to patients how risks vary with different medications. Conclusions The ChineseCVD risk calculator enables rapid web-based risk assessment for adverse cardiovascular outcomes, thereby facilitating clinical decision-making at the bedside or in the clinic.

Predicting cardiovascular death 1-year after transcatheter aortic valve implantation: an artificial-intelligence based risk model

Abstract Background Prediction of cardiovascular death after transcatheter aortic valve implantation (TAVI) remains difficult. Currently, more lower risk patients are considered for TAVI and predicting not only immediate survival, but more longer-term outcomes seems important. Most developed risk tools use standard statistical approaches and focus mainly on short-term (30 days post-TAVI) outcomes. Purpose The aim of this project was to identify important predictors for worse outcomes after aortic valve replacement using machine learning features. Furthermore, we want to develop and artificial intelligence (AI) -model to predict cardiovascular death 1 year after TAVI. Methods For our analysis we used 725 patients with severe AS that underwent TAVI between 2008 and 2022 and were included in a prospective single centre observational study. Leveraging an automated machine learning framework, we systematically evaluated various machine learning algorithms including Random Forest, AdaBoost, Neural Networks, Randomized Decision Trees and and Gradient Boosting. Results We constructed prediction models utilizing three feature subsets: the top 10 most important features, the top 15 most important features (Figure 1), and all available features (n=66). Our analyses yielded area under curve (AUC) values of 0.71, 0.83, and 0.92, respectively (Figure 2). The best model was obtained by Randomized Decision Trees. NYHA classification, left ventricular ejection fraction, Charlson comorbidity index, posterior wall thickness and myocardial infarction 90-days before TAVI appeared as the most influential predictors for cardiovascular death within one year after TAVI. Conclusions Our model was able to identify the most important features indicating high risk for patients undergoing TAVI. Using the 15-feature model, we were able to accurately predict cardiovascular death 1 year after TAVI. AI-models to predict risk can be used to better inform/select patients undergoing TAVI.

Association between CMR derived hepatic T1 times, tricuspid regurgitation severity, and outcomes

Abstract Background Hepatic T1 times have been shown to predict adverse clinical outcomes. However, up to date, the various causes contributing to changes in hepatic T1 times are not fully understood. So far, strong correlations with liver congestion and hepatic fibrosis have been demonstrated. Valvular heart disease, especially tricuspid regurgitation (TR), can lead to congestive hepatopathy (CH) and might significantly increase liver T1 values. In contrast, hepatic steatosis – commonly present in patients with cardiovascular disease - would result in lower T1 values. Currently, no studies are investigating the relationship between hepatic T1 times and TR. Methods We retrospectively measured hepatic T1-times, displayed on standard cardiac T1-maps, in an all-comer CMR cohort. Only patients, who underwent a comprehensive transthoracic echocardiogram within three weeks of CMR were included. Results 1029 participants (67±17 y/o, 44% female) had mean hepatic T1-times of 605±79ms. Overall, 41% (417) presented with non/trace, 38% (391) mild, 13% (135) moderate, 8% (85) severe, massive, and torrential tricuspid regurgitation. Liver T1 times were significantly correlated with TR severity (no/trace: 586±72ms; mild: 601±74ms; moderate: 634±84ms; severe/massive/torrential: 665±83ms; r= 0.25, p<0.001). Additionally, when adjusted for higher NT-proBNP levels, and right ventricular function in a linear regression model, TR severity was associated with hepatic T1 times (p<0.001). During follow-up (mean 53±36months), a total of 326 (32%) events occurred. Patients with higher T1 times and more severe tricuspid regurgitation were more likely to suffer events (adj.HR 1.44 [95%CI:1.23-1.69] per 100ms increase, p<0.001). Conclusion Tricuspid regurgitation exerts a notable influence on hepatic T1 times which is likely attributable to hepatic congestion. Importantly, hepatic T1 times were associated with outcomes even after adjustment for NTproBNP, LVEF, and RVEF. This underscores the importance of hepatic T1 times as both a marker of tricuspid regurgitation and an independent predictor of clinical outcomes.

Association between left atrial dysfunction and adverse outcomes after tricuspid valve surgery for atrial functional tricuspid regurgitation

Abstract Objectives To identify factors associated with clinical outcomes in patients undergoing tricuspid valve (TV) surgery for atrial functional tricuspid regurgitation (AF- TR). Methods Among 1,670 patients who underwent TV surgery between January 2000 and December 2020, we included 83 AF-TR patients (69.1±9.2 years, 50 women) who had severe TR without any cause other than atrial fibrillation. A comprehensive analysis of right ventricular (RV) and left atrial (LA) function on preoperative and postoperative echocardiography was performed. LA function was evaluated by LA emptying fraction (LAEF), LA reservoir strain, and LA stiffness index. The primary outcome was a composite of all-cause death and heart failure hospitalization during follow up after surgery. Results For a median of 39.9 (interquartile range 19.9 to 55.8) months, the primary outcome occurred in 20 (24.1%) patients. Patients with a primary outcome showed significantly lower LAEF (9.7±7.3 vs. 21.8±6.7 %, p<0.001) and LA reservoir strain, and higher LA stiffness index than those without. However, there was no difference in RV chamber size and functional parameters according to the occurrence of a primary outcome. The restricted cubic spline plot exhibited a significant relationship between LAEF and primary outcome. The low baseline LAEF (<17%) group showed a poorer outcome than the high LAEF group (log rank p<0.001). In the Cox regression analysis, the low LAEF (<17%) was independent predictor for primary outcome (adjusted hazard ratio 13.5, 95% confidence interval 3.1–58.6). Conclusion In patients undergoing TV surgery with AF-TR, preoperative LA dysfunction was independently associated with adverse outcomes.Figure1

Mortality risk in patients with carotid artery disease undergoing carotid endarterectomy compared to the general population

Abstract Background Patients with carotid artery disease undergoing carotid endarterectomy (CEA) appear to be at high risk of all-cause mortality during their follow-up. However, the possible predictors of this adverse outcome are not elucidated yet. Purpose We aimed to test cardiovascular (CV) risk factors as possible predictors of all-cause mortality in patients undergoing CEA and to determine whether there is a difference between the mortality rate of our study cohort and the general population. We hypothesize that CEA-treated patients have a higher mortality rate during follow-up after surgery than the general population, which is not related to the presence of CV risk factors. Methods We prospectively enrolled and followed up patients undergoing CEA. Univariate and multivariable Cox regression were performed to test whether common CV risk factors (demographics, laboratory values, comorbidities, and events before CEA) were predictive of all-cause mortality. We then compared the standardized mortality ratio (SMR) of our population and the age-sex-matched Minnesota (MN) general population at 5,10, and 21 years of follow-up after CEA. Results A total of 710 patients were followed for a median of 7.1 [2.9-11.9] years after CEA. Mortality occurred in 198 (27.0%) patients during the follow-up. The median time to event was 11.0 [10.0-12.0] years. Age was the only predictor of all-cause mortality in CEA-treated patients in multivariable models adjusted for known CV risk factors (Model 1: HR 1.03 [95%CI 1.01-1.06]; p=0.004; Model 2: HR 1.02 [95%CI 1.00-1.04]; p=0.023) (Table 1). However, the CEA-treated group had a higher mortality rate than would have been expected in the MN population (log-rank p<0.001) (Fig.1A). Compared to the MN population, at 5 years of follow-up only patients <60 years old had a higher SMR (4.53 [1.95-8.92]; p=0.001), whereas, at 10 years and 21 years of follow-up, our study population had a higher mortality rate at any age (Fig.1B). Conclusions The elevated mortality risk post-CEA in our cohort cannot be solely attributed to chronological aging. The underlying process of atherosclerosis likely contributes to all-cause mortality, and plaque characteristics may offer additional insight into the risk stratification of this patient group.All cause mortality predictors after CEAStudy population vs. MN population SMR

Unveiling the prognostic journey: renal function trajectories in 'de novo' heart failure with reduced ejection fraction - insights from a cohort study and their impact on patient outcomes

Abstract Background HFrEF poses significant clinical challenges globally. Renal dysfunction frequently coexists with HF, exacerbating prognosis. However, the dynamic trajectory of renal function in 'de novo' HFrEF patients and its prognostic implications remain understudied. Methods We conducted a prospective cohort study involving 370 'de novo' HFrEF patients. Renal function was initially assessed upon admission and re-evaluated at the end of the titration period. The CKD-EPI formula was used for renal function assessment. Patients were followed up for a median of 15 months. Statistical analyses were performed to evaluate predictors of adverse outcomes. Results Baseline renal function significantly influenced outcomes, with eGFR < 45 ml/min associated with higher mortality and heart failure readmissions. Among patients with available renal function data at discharge (n=354), 87 (24.6%) had eGFR < 45 ml/min, while 267 (72.2%) ≥ 45 ml/min. Patients with eGFR < 45 ml/min exhibited older age, higher prevalence of comorbidities, lower haemoglobin levels, and higher creatinine and NT-proBNP levels, both at admission and discharge. Furthermore, they were less likely to receive certain heart failure medications at discharge. During follow-up, 46 deaths (13.0%) and 105 events of combined all-cause death and readmission due to heart failure (29.6%) occurred. Patients with eGFR ≥ 45 ml/min exhibited a lower overall mortality (HR: 0.29, p < 0.001) and all-cause death and heart failure readmissions (HR: 0.32, p < 0.001) both in univariate and multivariate analysis (HR: 0.63, p = 0.028 for mortality; HR: 0.53, p = 0.038 for combined endpoint). See Figure 1. Among patients with available renal function data at follow-up (n=304), 240 (78.9%) had eGFR ≥ 45 ml/min (stabilization or improvement), and 64 (21.1%) had eGFR < 45 ml/min (deterioration or previously < 45 ml/min). Patients with eGFR < 45 ml/min at follow-up exhibited older age, lower BMI, higher prevalence of comorbidities, lower haemoglobin levels, and higher NTproBNP levels at admission and discharge. They were also less likely to receive certain crucial heart failure medications at discharge and follow-up (Table 1). During follow-up, 31 deaths (10.1%) and 87 events of combined death and readmission due to heart failure (38.6%) occurred. In univariate analysis, patients with eGFR ≥ 45 ml/min exhibited a lower overall mortality (HR: 0.27, p < 0.001) and admissions (HR: 0.30, p < 0.001), which remained significant in multivariate analysis (HR: 0.43, p = 0.048 for mortality; HR: 46, p = 0.014 for admissions). See Figure 1. Conclusion Our findings underscore the importance of integrated heart-kidney care in 'de novo' HFrEF patients. Continuous monitoring of renal function and interventions to prevent deterioration are crucial for optimizing outcomes. Further research is needed to validate these findings and explore targeted therapeutic strategies for renal protection in HFrEF.

Impact of the lower extremity arterial calcification score on clinical outcomes after drug-coated balloon angioplasty for de novo femoropopliteal artery disease

Abstract Background Severe calcification, assessed using the peripheral artery calcification scoring system (PACCS), is associated with poor clinical outcomes after endovascular treatment (EVT) for de novo femoropopliteal lesions. However, the PACCS classification is a qualitative assessment performed in the angiographic room, and there are no established indicators for the quantitative assessment of calcification prior to treatment. Purpose We aimed to investigate the impact of the lower extremity arterial calcification score (LEACS) calculated using non-contrast lower limb computed tomography on clinical outcomes after drug-coated balloon angioplasty for de novo femoropopliteal artery disease. Methods We retrospectively analyzed the clinical outcomes of 141 consecutive patients treated at our center for de novo femoropopliteal artery disease using a drug-coated balloon between April 2018 and December 2022. Patients who did not undergo lower limb computed tomography before EVT were excluded from the analyses. LEACS was determined based on the method used to calculate the Agatston score for the coronary arteries. Each patient’s score consisted of a sum of calcification scores from ostium of superficial artery to the popliteal artery at the knee joint of treated limb. The primary and secondary outcomes measured were primary patency and clinically-driven target vessel revascularization (CD-TVR) at 1 year. Cox proportional hazards analysis was used to explore independent predictors of clinical outcomes. The study population was divided into higher and lower LEACS groups based on the cut-off value (1750), which best discriminated patency, and the outcomes were compared between the two groups. Results In the higher and lower LEACS groups, the mean age was 75.1 ± 9.1 years and 75.5 ± 11.0 years (p = 0.87) and the mean lesion length was 170.3±102.8 mm and 157.7±112.1 mm (p = 0.64), respectively. The higher LEACS group showed significantly lower 1-year patency than the lower LEACS group (53.5% vs. 84.3%, log-rank, p = 0.041). In addition, freedom from 1-year CD-TVR was significantly lower in the higher LEACS group than in the lower LEACS group (66.8% vs. 93.7%, p = 0.047). The Cox proportional hazard analysis showed that the higher LEACS group was an independent predictor of 1-year restenosis (odds ratio: 2.80, 95% confidence interval: 1.24–8.84, p=0.037), along with a small (< 5 mm) reference vessel diameter (odds ratio: 3.55, 95% confidence interval: 1.44–9.53, p=0.028). Conclusion Higher LEACS scores were independently associated with clinical outcomes after drug-coated balloon angioplasty for de novo femoropopliteal artery disease. Non-contrast lower limb computed tomography is an acceptable and feasible option for predicting the outcomes in patients with de novo femoropopliteal artery disease prior to treatment.

Association of Neutrophil extracellular traps burden with clinical and angiographic characteristics in patients with ST-elevation myocardial infarction

Abstract Background The precise triggers for arterial plaque rupture and the underlying pathophysiology of thrombogenesis remain elusive. Polymorphonuclear neutrophils (PMN), particularly their formation of Neutrophil Extracellular Traps (NETs), have garnered attention in the context of coronary atherothrombosis. This study sought to explore the association of NETs burden with clinical and angiographic characteristics in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (pPCI) and thrombus aspiration (TA). Methods This study included 336 consecutive STEMI patients undergoing pPCI and TA. Aspirated thrombi underwent histological analysis and NETs quantification via immunohistochemistry. Potential associations of clinical variables and angiographic outcomes with NETs burden were assessed. Results Manual TA was selectively performed in 72 cases with increased thrombotic burden and 60 thrombi were suitable for analysis. Most thrombi specimens displayed lytic features (63%) and almost three out of four specimens were identified as white thrombi. Increased NETs burden was significantly associated with prolonged pain-to-balloon time (>300 minutes) OR=10.29 (95% CI 2.11-42.22, p=0.001) and stress-induced hyperglycemia (SIH) OR=6.58 (95% CI 1.23-52.63, p=0.04) after multivariate regression analysis. Additionally, distal embolization (DE), a predictor of adverse outcomes, was more frequent among patients with an elevated NETs burden OR=16.9 (95% CI 4.23-44.52, p<0.001). Conversely, no significant association between NETs burden and final TIMI flow=3 was observed. Conclusion Elevated NETs burden in STEMI thrombi is linked to delayed reperfusion, SIH and increased risk of DE. Further research is needed to elucidate the role of NETs as a potential therapeutic target in acute atherothrombosis.

The effect of exercise on RV-PC coupling in asymptomatic patients with significant primary mitral regurgitation

Abstract Background Right ventricular–pulmonary circulation (RV-PC coupling) serves as an index to evaluate RV function in relation to underlying RV afterload. Although impaired RV-PC coupling has been proposed as a predictor of adverse outcomes in heart failure (HF) patients with secondary mitral regurgitation (MR), there is limited data available for patients with primary MR. Purpose The objective of this study was to assess and compare alterations in RV-PC coupling during exercise with bicycle stress echocardiography in individuals with asymptomatic moderate to severe primary MR (MR group) and normal subjects (Control group). Μethods All patients and controls underwent stress echocardiography with a supine bicycle. RV systolic function was evaluated with TAPSE and S’. The non-invasively measured RV-PC coupling was evaluated by indexing TAPSE and S’ to right ventricular systolic pressure (RVSP) during baseline echocardiogram and peak workload stages of bicycle SE. Results Among the 48 patients in the MR group (mean age 53.5±15.16 years, 58.3% female), 39 patients had moderate MR(81.3%), 5 patients had moderate-to-severe MR(10.4%), and 4 patients had severe MR(8.3%). The duration of stress echocardiogram was significantly shorter in the MR group compared to control group (8.11±2.39 min vs 10.5±1.05 min, respectively; p<.001). Left Ventricular Ejection Fraction (LVEF) was within normal limits in both groups {70.7±11.9 % vs 72.6±12.1 %(p=NS} and the dimensions of left ventricular cavity (end-diastolic and end-systolic diameters) were significantly larger in the MR group compared to control group (49.25±5.21 mm vs 45.6±4.08mm (p .016) and 31.81±4.27mm vs 29.07±4.21mm (p .033) respectively}. TAPSE and RVSP increased from baseline to peak dose [23.48 ±3.05mm vs 29.94±3.48mm (p < .001), 8.54±4.56mmHg vs 43.79±5.27mmHg (p < .001), respectively]. There were no significant differences in TAPSE/RVSP and S’/RVSP between the two groups at rest. However, a significantly steady decrease was observed from baseline to peak dose (0.84±0.16 mm/mmHg vs 0.72±0.19mm/mmHg (p <.001) and 0.52±0.11 cm/sec/mmHg vs 0.50±0.15 cm/sec/mmHg (p .004), respectively). Conversely, these parameters did not exhibit a significant decrease in the control group. Finally, there was no significant correlation observed between the changes in the index TAPSE/RVSP , ratio E/E’ and systolic blood pressure. Conclusions RV-PC coupling decreases during exercise in asymptomatic patients with moderate to severe MR, independently of left ventricular dynamic changes. In contrast , there is no significant change in RV-PC coupling observed in the control group. Therefore, future studies should aim to evaluate the incremental role of this novel index not only in the assessment and evaluation of patients with MR but also as a potential prognostic marker.TAPSE/RVSP GraphTable of echocardiographic measurements

Phenotype groups in atrial cardiomyopathy and their prognosis

Abstract Background Atrial cardiomyopathy (ACM) includes patients with heterogenous demographic characteristics and comorbidities. Defining phenotype groups with similar clinical characteristics is important for the effective treatment of these patients, and for their prognosis and prevention of ACM. Purpose To conduct a cluster analysis that could help us in phenotyping ACM and exploring the clinical complexity of this entity. Methods We performed a hierarchical cluster analysis based on Ward’s Method using 10 clinical binary variables (hypertension, diabetes mellitus, heart failure, obesity, chronic obstructive pulmonary disease, cancer, coronary artery disease, sinus node dysfunction or atrio-ventricular block, implanted pacemaker, and ischemic stroke), identifying the optimal number of clusters. We investigated differences in demographic, laboratory and echocardiographic parameters, and treatment between defined clusters, and assessed the impact of these factors on prognosis. Results Of 724 evaluated consecutive patients with dilated left atrium only 200 met the criteria for advanced atrial cardiomyopathy, defined as severely dilated left atrium with volume index (LAVI) ≥ 48 ml/m2, preserved left ventricular systolic function - ejection fraction ≥ 50%, without an overt valvular or ventricular disease, and were included in the analysis. Mean age of the studied population was 73.91 ± 9.74 years, 58 % of them were women. We identified 4 clusters: cluster 1 (n = 73, 36%) were younger overweight patients with paroxysmal atrial fibrillation (AF); cluster 2 (n = 56, 28%) - old patients with congestive heart failure (CHF) and low body mass index (BMI); cluster 3 (n = 34, 17%)- diabetic patients with obesity and CHF; and cluster 4 (n = 37, 19%) old patients with tachycardia-bradycardia syndrome, implanted pacemakers, and long -standing AF. Over a mean follow up of 20.6 months cluster 2 had the highest mortality rate (28.6%), followed by cluster 3 (20.6%), compared to the lower mortality rate of cluster 1 and 4 (11% and 10.8%, respectively, p=0.047). The presence of heart failure (HR 4.4, CI 1.5 ÷12.7, p=0.006), cancer (HR 3.3, CI 1.6 ÷ 6.9, p=0.002) and greater than moderate tricuspid regurgitation (HR 5.4, CI 2.6 ÷ 11.3, p<0.001) were predictors of poor outcome. Conclusion In patients with advanced atrial cardiomyopathy, four main clusters were identified, differentiated by distinct comorbidities. Both clinical and echocardiographic parameters were found to be associated with an increased risk of mortality.Phenotype clusters of ACMKaplan-Meier curves of clusters