Cox Regression Analysis Research Articles

Circulating secretoneurin concentrations predict cardiovascular death in ambulatory patients with heart failure

Abstract Background Secretoneurin (SN) is a novel biomarker, which predicts cardiovascular (CV)-related mortality in patients with acute dyspnea and sepsis. Higher SN concentrations have also been found associated with all-cause death in outpatients with heart failure (HF), but whether SN primarily reflects cardiovascular (CV)-related mortality in HF outpatients is not known. Objectives To evaluate the relation between SN concentrations and CV- & non-CV death in ambulatory patients with HF. Methods We studied 184 consecutive patients who attended our HF clinic for routine follow up and had stored blood samples available for SN analysis. SN concentrations were measured with a CE-marked SN ELISA assay. We assessed the associations between SN concentrations and CV & non-CV death. Mortality was ascertained using medical records, autopsy reports and death certificates, and CV deaths included sudden cardiac deaths or mortality due to myocardial infarction, HF or stroke. We assessed association with CV & non-CV death by Kaplan-Meier curves and by Cox proportional hazard regression analysis. Results Median age was 76 years (range: 38-94 years) and two thirds were male. Sixty-three percent had HF with reduced ejection fraction, 22% had NYHA III/IV symptoms and median NT-proBNP was 1079 (interquartile range: 462-2347) ng/L. Median SN level was 60 (range: 21-134) pmol/L. In multivariable linear regression analysis, impaired renal function and lower body-mass index were significantly associated with increasing (log)SN concentration. During median follow up of 540 days, there were 18 CV deaths, including 15 HF deaths, and 7 non-CV deaths. A higher SN concentration was associated with higher risk of CV death, while we did not find statistically significant association between SN concentrations and non-CV deaths (Figure). Patients with SN concentration in the top tertile had 15-fold increased risk of CV death compared to patients with SN concentration in the lowest tertile. In multivariable Cox regression analysis that adjusted for age, NYHA functional class, frailty status, increasing SN concentrations were independently associated with CV death: hazard ratio per logSN (95% CI): 3.01 (1.02-8.90), p=0.04. Conclusion In ambulatory patients with HF, circulating SN concentrations were predictive of CV death. Higher SN concentrations in ambulatory HF patients seemed to be linked to impaired renal function and lower body-mass index. Figure: Kaplan Meier curves illustrating the relation between SN tertiles and (A) CV mortality (B) Non-CV mortality.

Health-related quality of life and prognosis in cardiac sarcoidosis

Abstract Background Cardiac sarcoidosis (CS) is characterized by inflammatory myocardial disease, often leading to conduction disturbances, ventricular tachycardias, and heart failure. While factors like initial symptoms, LVEF, and troponin levels are known prognostic indicators, the impact of CS on health-related quality of life (HRQoL) is not well-understood. Additionally, limited data exists on the predictive value of FDG-PET in CS. Purpose This study aimed to assess HRQoL in CS patients and investigate its prognostic relevance concerning cardiac events. Methods Patients diagnosed with CS completed the RAND-36 general health-related questionnaire, covering eight dimensions. Clinical data were obtained from the Finnish myocardial inflammatory diseases registry. Follow-up data on cardiac events, including life-threatening ventricular tachyarrhythmias (VT/VF), heart transplant, left ventricular assist device (LVAD) implantation, pericardial tamponade, or death, were collected over 36 months. Results Of the 240 CS patients surveyed, 179 (75%) were female, with a median age of 56 [IQR 48 – 64]. CS patients reported significantly lower RAND-36 scores across all dimensions compared to the general Finnish population. Over the 3-year follow-up, 38 (16%) patients experienced cardiac-related adverse events, including VT/VF (26 cases), deaths (8 cases), heart transplants (2 cases), LVAD implantation (1 case), and pericardial tamponade (1 case). We divided CS patients into those without adverse event (N=202) and with adverse events (N=38). Interestingly, in four dimensions of PF 70.0 [50.0-90.0] vs 60.0 [33.8-80.0], p=0.019, RP 50.0 [0.0-100.0] vs 0.00 [0-56.3], p=0.002, MH 76.0 [59.0-88.0] vs 66.0 [51.0-84.0], p=0.036, and SF 75.0 [50-100] vs 62.5 [37.5-78.1], p=0.037 were significantly lower scores in the event group. Univariate Cox regression analysis (Table 1) revealed that physical functioning (PF) and role-physical (RP) dimensions, along with certain clinical factors, such as younger age, higher NYHA classification, elevated proBNP levels, lower hemoglobin levels, and the main manifestation of the disease as ventricular tachyarrhythmia, independently predicted adverse cardiac events. In the multivariate analysis, lower role-physical scores and younger age remained independent prognostic factors for adverse cardiac events. Conclusions Patients with CS demonstrated lower HRQoL compared to the general Finnish population. This study enhances our understanding of prognosis in CS and underscores the predictive value of HRQoL in identifying future adverse cardiac events, highlighting its relevance in the clinical management of these patients.

Coronary stent edge segments as determinant of clinical outcomes: An OCTOBER Trial Substudy

Abstract Background Small lumen dimensions and high plaque burden in stent edge segments are known risk factors for subsequent clinical events after percutaneous coronary intervention (PCI). The evidence using intravascular optical coherence tomography is scarce. Purpose This study aimed to characterize edge segments after PCI and the relation to clinical outcomes in the randomized OCTOBER trial on bifurcation PCI optimized using optical coherence tomography. Methods This is a predefined substudy of the OCTOBER Trial. Edge segments were analysed in detail for degree of stenosis and plaque composition using a dedicated software. Data was planned to be analysed using multi-level cox regression analysis, but descriptive statistics was applied due to very low event rates after OCT-guided PCI. Main endpoints were OCT-detected edge residual stenosis, lipid plaque, calcification, and dissections. Post PCI coronary angiography was analysed for diameter stenosis, edge segment length and minimal lumen diameter. Patients with cardiac events were diagnosed with angiography duringt the two-year follow-up period. Results A total of 597 patients were treated with OCT-guided PCI. Analysable final OCT scans with no additional treatment was available for 505 patients in the main vessel and for the side branch in 289 cases. At deadline for abstract submission 242 scans with 474 edges were analysed and included in preliminary results.Lesions with ≥30% diameter stenosis was found in 20% of proximal edges, 24% of distal edges and 37% of side branch (SB) edges. A plaque burdenOCT ≥180° was found in 74% of proximal edges, 48% of distal edges, and 52% of SB edges. A lipid plaque wafound in 35%, 11% and 14%, dissections in 15%, 6% and 12%, and ≥180° calcium was found in 7%, 4% and 4% of edges respectively. Six patients (1%) of the total OCT-guided population had an edge-related event during the median two-year follow-up. Only two of these 6 patients had post-procedural OCT-scans of the event-related edge, thus 4 of the cases were effectively angiographic guided. Conclusion Only a small fraction of edge segments in the OCTOBER Trial were left with residual edge disease exceeding protocol thresholds. This resulted in historically very low rate of edge related events. No evaluation of a stent edge by OCT in otherwise OCT guided patients appeared to be the main predictor of edge related events. Final results are presented at ESC 2024.

The condition of myocardium reserves score from a cloud-based analytics platform of Holter ECG data indicates better cardiometabolic function in heart failure

Abstract Introduction Cardiometabolic dysregulation, particularly type 2 diabetes mellitus (T2DM), is associated with subtle myocardial pathologies, even in individuals without known cardiovascular disease. These subclinical changes, often undetectable by standard electrocardiogram (ECG) analytics, can offer valuable insights into the relationship between metabolic health and cardiac function. Novel ECG markers, developed through machine learning and artificial intelligence (AI), may provide the sensitivity needed to detect such changes. Aim This study aims to evaluate novel composite cardiac parameters from an analytics platform in the context of heart failure (HF), seeking to understand their relationship to cardiometabolic dysregulation. Methods Data from the MyoVasc study, a prospective cohort on HF, were analysed. Participants underwent extensive clinical phenotyping, including a Holter ECG assessment. Holter ECG data was processed based on machine learning and AI models on a cloud-based analytics platform (Cardiolyse, Helsinki, Finland), generating both traditional and proprietary ECG, and heart rate variability cardiac health markers. LASSO-penalized logistic regression adjusted for sex and age was performed to select the marker most strongly associated with T2DM. The identified marker was then evaluated in relation to cardiac function and structure as well as HF-related outcome. Results A total of 953 subjects (mean±SD age 64.6±10.5 years; 35.7% women) were included in the analyses. Symptomatic HF stage C/D was present in 54.8% (n=522) of subjects and diabetes mellitus in 22.4% (n=213). The Condition of Myocardium Reserves Score (CMRS) was the novel composite cardiac parameter selected based on its relationship with T2DM. In a Poisson regression model with robust variance adjusted for sex and age, a lower score was associated with T2DM (Prevalence ratio per SD 1.24, 95% confidence interval [1.14;1.36], P=0.0002). In multivariable linear regressions adjusted for traditional cardiovascular risk factors, comorbidities, and medication, a higher CMRS was associated with better global longitudinal strain (β per SD –0.82 [–1.11;–0.53], P<0.0001), diastolic function (left ventricular E/e’; β per SD –0.04 [–0.06;–0.01], P=0.0059) and systolic function (LV ejection fraction; β per SD 2.06 [1.46;2.67], P<0.0001). A lower CMRS independently predicted all-cause death (Hazard ratio per SD 1.25 [1.09;1.45], P=0.0020) and worsening of HF (HR per SD 1.44 [1.21;1.72], P<0.0001) in Cox regression analysis adjusted for the same confounders. Conclusion The Condition of Myocardium Reserves Score exhibited a strong association with cardiometabolic dysregulation. A higher CMRS indicated preserved cardiac function, while a lower score independently predicted increased risk of all-cause death and worsening HF. This novel score offers potential as a non-invasive tool for assessing cardiometabolic health and stratifying risk in patients with HF.

Efficacy of meropenem against ceftazidime-avibactam-resistant Klebsiella pneumoniae producing KPC-31, KPC-33, KPC-90, KPC-106 and KPC-114.

Klebsiella pneumoniae producing KPC variants conferring resistance to ceftazidime-avibactam often remain susceptible to meropenem, suggesting a potential therapeutic use of this antibiotic. In this study, the efficacy of clinically relevant concentrations of meropenem was evaluated against high-risk clones of ceftazidime-avibactam-resistant K. pneumoniae strains producing KPC variants, in a tandem in vitro time-kill/in vivo Galleria mellonella survival model. In vitro/in vivo efficacy of meropenem against ceftazidime-avibactam-resistant K. pneumoniae of CG16, CG25 and CG258, producing KPC-31, KPC-33, KPC-90, KPC-106 and KPC-114 variants, was evaluated using EUCAST dosing recommendation adjusted to the G. mellonella model. For in vivo assays, untreated, meropenem (40 mg/kg × 1)-treated and ceftazidime-avibactam (40 mg/kg ceftazidime-10 mg/kg avibactam × 1)-treated groups were established, with 60 larvae per group. Kaplan-Meier curves, log-rank tests, univariate Cox regression and hazard ratios (HR) were used to assess treatment effects (P < 0.05). For all KPC-variant producers, time-kill assays showed >3 log-kills reduction (-6.91 ± 1.28 SD) after 6 h interaction when exposed to 8-32 mg/L meropenem MIC values (i.e. ≥ × 4 MIC). In the assessment of in vivo efficacy of meropenem, at the 4-day follow-up, mortality rates were 96.7% (untreated), 83.3% (ceftazidime-avibactam-treated) and 13.3% (meropenem-treated) (P < 0.05). Univariate Cox regression analysis showed significantly lower risk in the meropenem group compared to untreated group [HR 0.02 (95% CI: 0.01-0.05)]. These pre-clinical results might support use of meropenem as a potential alternative for treatment of infections due to KPC-variant producers displaying in vitro susceptibility to meropenem.

Long-term prognosis and predictors of death in chronic Chagas cardiomyopathy in women and men

Abstract Background Chronic Chagas cardiomyopathy (CCC) is one of the leading causes of heart failure (HF) in Latin America and carries high morbidity and mortality. Previous studies showed conflicting results in epidemiological and clinical evidence of a gender-associated risk of death in patients with HF due to CCC. Purpose This study analysed the long-term prognosis and the main predictors of death in women and men with HF due to CCC. Methods From March 2009 to January 2023, we followed a cohort of outpatients with HF due to CCC. Specific serological tests diagnosed Chagas disease. Baseline data included clinical characteristics and echocardiographic findings. Statistical analyses were performed using the Kaplan-Meier (K-M) method to analyse time-to-event data and Cox proportional hazards methods to search for predictors of death. Results We studied 739 patients, with a mean age of 57.0 ± 12.1 years, 387 (52%) male. Women had a higher mean age (58.4 ± 11.7 vs. 55.8 ± 12.3 years; p=0.001), had a higher mean baseline left ventricular ejection fraction (LVEF) (44.3±14.5 % vs. 37.0±14.5%; p&amp;lt;0.001) and a smaller left ventricular diastolic diameter (LVDD) (56.8±8.9 vs. 62.5±9.4 mm; p&amp;lt;0.001). Over a median follow-up period of 10 years, 213 (56%) men and 169 (44%) women died (K-M: log-rank p=0.043; Figure). Men received more beta-blocker therapy (52.4% vs. 47.6%; p=0.040) and had a higher prevalence of chronic kidney disease (CKD) (p=0.003) and stroke (p=0.007). HFpEF was more prevalent in women and HFrEF in men (p&amp;lt;0.001). Device implantation and transplant were similar between women and men. Cox regression analysis for death adjusted for age, sex, myocardial infarction, diabetes, CKD, stroke, atrial fibrillation (AF), and LVEF showed LVEF (HR= 0.98;95%CL:0.97-0.98), age (HR=1.03;95%CL1.02-1.04) and CKD (HR= 1.32;95%CL:1.10-1.64) as the main predictors of death. In men, the main predictors were age (HR=1.02;95%CL:1.01-1.04), CKD (HR=1.409;95%CL:1.07-1.86), and LVEF (HR=0.98;95%CL:0.97-0.99), and in women AF (HR=1.41;95%CL:1.03-1.91), age (HR=1.03;95%CL:1.01-1.04), and LVEF (HR=0.97;95%CL:0.96 -0.98). Conclusion women had a better prognosis than men, but gender was not an independent predictor of death. Prevention of comorbidities, especially CKD in men and AF in women, and higher beta-blocker therapy can significantly reduce the death rate in women and men with HF from CCC.

Prognostic significance of the estimated pulse wave velocity in critically ill patients with coronary heart disease

Abstract Background The estimated pulse wave velocity (ePWV) has emerged as an alternative measurement of arterial stiffness which has been suggested as a potential marker for mortality and cardiovascular risk. Nonetheless, its prognostic significance in critically ill patients with coronary heart disease (CHD) remains uncertain. Methods Patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) were grouped into quartiles according to the ePWV levels. We conducted logistic and Cox regression analyses to examine the association between ePWV and both in-hospital and 1-year all-cause mortality among critically ill patients with CHD. Additionally, we employed restricted cubic spline (RCS) analysis to explore the relationship between ePWV as a continuous variable and mortality. Results A total of 11001 patients (men: 63.6%, age: 71.94 [IQR: 62.69-81.31]) were included in this study. In-hospital mortality and 1-year mortality rates were 9.1% and 25.1%, respectively. Multivariable logistic regression models demonstrated that ePWV was independently associated with an elevated risk of in-hospital mortality (OR 1.27; 95%CI [1.14-1.41]; p&amp;lt;0.001) and 1-year mortality (OR 1.49; 95% CI [1.38-1.60]; p&amp;lt;0.001]. The restricted cubic splines regression model revealed a linear relationship between ePWV and both in-hospital and 1-year mortality (p for non-linearity = 0.098 and p for non-linearity = 0.156, respectively). Conclusion Our findings indicate a linear association between ePWV levels and short- and long-term mortality in critically ill patients with CHD.

Prognostic value of echocardiographic parameters in predicting major adverse cardiac events one year following st-segment elevation myocardial infarction

Abstract Approximately 50% of patients who survive an ST-segment elevation myocardial infarction (STEMI) experience irreversible damage to the heart muscle, which increases long-term risk of developing heart failure. Moreover, cardiovascular mortality constitutes half of all deaths. This research aimed to determine the best combination of patient data collected during a one-year follow-up period to enhance the accuracy of outcome predictions for patients with STEMI. Methods In this study, 246 patients who experienced STEMI and older than 18 were prospectively monitored. All participants received primary percutaneous coronary intervention treatment. The study's primary outcomes, observed over the year following hospital discharge, included cardiovascular death, recurrent myocardial infarction, newly diagnosed heart failure, and arrhythmias or conduction issues. Of the patients, 18% of patients reached the primary outcomes. Two-dimensional transthoracic echocardiography was conducted 3-5 days after the initial event to assess left ventricular global longitudinal strain (GLS) using 2D speckle-tracking echocardiography on the apical four-chamber, two-chamber, and long-axis views. Left ventricular mechanical dispersion was calculated as the standard deviation of the time from the Q/R wave onset to peak GLS across 17 segments of the left ventricle. Results The findings revealed that the overall GLS was -10.70 (-12.61 to -8.40), but in patients who met the study's primary outcomes, GLS was significantly lower at -7.83 (-8.70 to -6.90), compared to -12.02 (-13.11 to -10.17) in those who did not, with a significant difference (p=0.00001). Mechanical dispersion was 40.24±26.56 in the entire cohort but significantly higher at 65.62±22.57 in the outcome group compared to 25.79±14.81 in the non-outcome group (p=0.00001). The ejection fraction averaged 48.97±7.69% across all patients, 47.22±7.16% in those with outcomes, and 49.92±7.84% in those without, with a statistically significant difference (p=0.039). Cox regression analysis identified key predictors of major adverse cardiac events (MACE) within one year after STEMI, including global longitudinal strain (p=0.0006), left atrium volume index (p=0.0448), left ventricular end-diastolic diameter (p=0.045), and mechanical dispersion (p&amp;lt;0.0001). A multivariate logistic regression analysis demonstrated that a combination of GLS, left ventricular end-systolic volume (LVESV), mechanical dispersion, and ejection fraction could predict 1-year MACE with high accuracy (χ2 = 85.18; p&amp;lt;0.0001, AUC=0.961 [0.903-0.989]). In conclusion, this study identifies crucial metrics, such as global longitudinal strain, left ventricular end-systolic volume, mechanical dispersion, and ejection fraction, as predictive factors for MACE one year following STEMI. This predictive model is straightforward, reproducible, and can be easily implemented in cardiology practice.

Elevated mitral valve pressure gradient following transcatheter edge-to-edge repair is independently associated with inferior outcomes in atrial, but not in ventricular secondary mitral regurgitation

Abstract Background In transcatheter mitral valve edge-to-edge repair (M-TEER), the goal of optimizing post-procedural residual mitral regurgitation inadvertently carries the risk of generating relevant mitral stenosis, resulting in an elevated mean mitral valve pressure gradient (MPG). In patients with primary mitral regurgitation, an elevated post-procedural MPG has been found to independently predict impaired outcomes. However, the effect of elevated post-procedural MPG on outcome after M-TEER in patients with secondary mitral regurgitation (SMR) has yet to be fully elucidated. This study investigated the impact of elevated MPG on outcome in the EuroSMR registry, a large, multi-center real-world cohort of patients with SMR. Methods This retrospective study included patients who underwent M-TEER for SMR between 2009 and 2021 in 12 centers. Patients were stratified into two groups based on SMR etiology: (1) ventricular SMR (vSMR), and (2) atrial SMR (aSMR). The etiology was considered as vSMR in patients with a left ventricular ejection fraction (LV-EF) &amp;lt;50% and aSMR in subjects with preserved left ventricular function (LV-EF ≥50%) and a markedly dilated left atrium (Left Atrial Volume Index [LAVi] ≥40ml/m2). According to the proposed M-VARC threshold, post-procedural MPG was assessed by discharge transthoracic echocardiography and was considered elevated if &amp;gt;5 mmHg. The primary endpoint was all-cause mortality after 5 years, with statistical analysis conducted using Kaplan-Meier and uni- and multivariable Cox Regression analysis. Results Among the 1703 patients in the study (vSMR: n=1420; aSMR: n=283), elevated post-procedural MPG was observed in 9.4% (n=133) of vSMR and 19.1% (n=54) of aSMR patients. Atrial fibrillation was significantly more prevalent in aSMR (78.4% vs. 57.1%, p&amp;lt;0.001). Patients with vSMR had a higher median surgical risk assessed by the EuroScore II (aSMR vs. vSMR: 7.0% [IQR 4.0, 13.1] vs. 4.9% [IQR 2.9, 8.5], p&amp;lt;0.001). Kaplan-Meier analyses for all-cause mortality after 5 years demonstrated significant differences in aSMR patients (low vs. elevated MPG: 48.9% vs. 69.8%, log-rank p&amp;lt;0.01), while there was no difference in vSMR patients (55.7% vs. 60.8%, log-rank p=0.66) (Figure 1). This observed effect remained significant even after accounting for common confounding factors: elevated MPG was an independent predictor for all-cause mortality in aSMR patients (HR=1.86; 95%-CI: 1.14-3.02, p=0.013) but not in vSMR patients (HR=1.00; 95%-CI: 0.74-1.35, p=0.99). Conclusion Our findings suggest that elevated post-procedural MPG is an independent predictor of adverse outcomes in patients with aSMR, but not in those with vSMR. This effect may partially be explained by a reduced left atrial function and higher rates of atrial fibrillation.Figure 1.Study flowchart

Effect of pre-procedural blood pressure on one-year cardiovascular events after percutaneous coronary intervention in patients with acute myocardial infarction

Abstract Background Although high systolic blood pressure (SBP) and low diastolic blood pressure (DBP) are associated with adverse cardiovascular outcomes in coronary artery disease, their impact on patients with acute myocardial infarction (AMI) remains unclear. Methods This multicenter prospective study included 874 AMI patients undergoing percutaneous coronary intervention (PCI) with pre-procedural blood pressure recorded. Patients with cardiogenic shock and missing blood pressure data were excluded. The patients were categorized based on SBP (high ≥120 mmHg, low &amp;lt;120 mmHg) and DBP (high ≥70, low &amp;lt;70 mmHg) into four groups: high SBP and high DBP (HSHD), high SBP and low DBP (HSLD), low SBP and high DBP (LSHD), and low SBP and low DBP (LSLD) group. The primary endpoint was a composite of all-cause mortality, myocardial infarction, stroke, and major bleeding. Results The average age of the patients was 68.9 years, with a mean pulse pressure of 58 ± 19 mmHg. The Kaplan-Meier curves showed significant differences in the primary endpoints among the four groups (Log-rank test, p &amp;lt;0.001). At 12 months, the primary endpoint occurrence was highest in the HSLD group (13.3%) and lowest in the LSHD group (2.4%). Additionally, multivariate Cox regression analysis revealed that the HSLD group, compared to the HSHD group, was independently correlated with an increased risk of cardiovascular events (hazard ratio 2.43, 95% confidence interval 1.16-5.11; p = 0.019). Conclusion Pre-procedural HSLD serves as an independent predictor and is associated with one-year adverse cardiovascular outcomes in AMI patients.Patient diagramKaplan-Meier one-year outcome

Left ventricular ejection fraction and clinical outcomes after transcatheter aortic valve implantation

Abstract Background Reduced left ventricular ejection fraction (LVEF ≤50%) has been associated with poor prognosis in patients with severe aortic stenosis treated medically or with aortic valve replacement. However, less is known regarding the impact of different degrees of LVEF including moderately to severely reduced LVEF after transcatheter aortic valve replacement (TAVR). Purpose To examine the association between baseline LVEF and clinical outcomes after TAVR. Methods Patients undergoing TAVR between 2008-2021 from the Swedish Transcatheter Cardiac Intervention Registry (SWENTRY) were included. LVEF was estimated from echocardiography before TAVR and categorized as ≥50%, 40-49%, 30-39% and &amp;lt;30%. SWENTRY was linked to the National Patient Registry and Cause of Death Registry for outcome variables. Patients were followed for a median of 3.2 years for the primary outcome heart failure hospitalizations and the secondary outcome all-cause mortality. Cox regression analyses adjusted for age, sex, BMI, atrial fibrillation, eGFR class, diabetes, hypertension, frailty, chronic pulmonary disease and coronary artery disease were performed for the association between LVEF groups and outcome. Results In total, 8686 patients were included (mean age 81 years, 47% female) of whom 5904 (68%) patients had LVEF ≥50%, 1342 (15%) had LVEF 40-49%, 906 (10%) had LVEF 30-39% and 534 (6%) had LVEF &amp;lt;30%. Significant differences were observed across the LVEF groups in the cumulative incidence rates of heart failure hospitalizations (19, 30, 37 and 43%; p&amp;lt;0.001) and all-cause mortality (41, 54, 55, 57%; p&amp;lt;0.001) at five years. In adjusted analyses there was a stepwise increase in the risks of heart failure hospitalizations (Figure 1A) and all-cause mortality (Figure 1B) for each respective LVEF category. Conclusion Reduced LVEF, especially LVEF &amp;lt;30%, was associated with a dramatically increased long-term risk of heart failure hospitalizations and all-cause mortality in patients undergoing TAVR. LVEF should be considered in risk stratification and patient selection for TAVR.

Comparative analysis of a novel preoperative stratification method versus traditional scores in patients with severe aortic stenosis undergoing aortic valve surgery

Abstract Introduction It is crucial to consider factors that complicate the indication of transcatheter aortic valve replacement (TAVR) in patients with aortic stenosis (AS), such as narrow valve ring, extensive calcification or inadequate vascular access. (1-4) Thus, aortic valve replacement surgery (SAVR) remains a recommended indication, with its pre-surgical stratification being a challenge. (1-3) Despite the widespread use of scores like the STS and EuroSCORE II, they exhibit limitations, being validated primarily for populations outside Latin America and focusing predominantly on individual factors while often neglecting structural parameters like left ventricular hypertrophy, diastolic dysfunction, or left atrium volume. (3-5) Purpose This study aimed to assess whether a novel modified Généreux stratification method offers superior predictive value for postoperative mortality in AS patients compared to traditional scoring systems. Methods We conducted a retrospective, single-center study involving patients with confirmed severe AS who underwent aortic valve replacement surgery between January 2017 and December 2021. The new stratification method categorized patients into three stages based on echocardiographic parameters (see Figure 1). Univariate and multivariate Cox regression analyses were conducted to identify predictors of mortality, with survival analysis performed using Kaplan-Meier curves. A p-value &amp;lt;0.05 was considered statistically significant. Results A total of 508 patients were included in the study. Stage 1 patients had a lower median age (62 years vs. 67 years in stages 2 and 3). The median EuroSCORE and STS were 2.75 and 2.62%, respectively, with stage 3 showing significantly higher scores (p ≤0.001). Over a median follow-up of 81 months, 56 deaths occurred (11%). Kaplan-Meier curve analysis revealed significant differences in all-cause mortality among the three groups (HR 4.073, log-rank p≤0.001), as illustrated in Figure 1. Multivariate analysis identified the three preoperative stages (HR 3.22, [95% CI 1.44-7.20], p=0.004) and mean transaortic gradient (HR 0.96, [95% CI 0.92-0.99], p=0.021) as independent predictors of mortality. The new stages demonstrated a superior area under the ROC curve of 0.758 compared to traditional scores (see Figure 1). Conclusions The novel three-stage preoperative classification and low transaortic gradient serve as significant predictors of mortality in patients undergoing SAVR. These stages exhibit robust predictive capability for mortality compared to EuroSCORE II and STS.Baseline and multivariate analysisKaplan-meier and ROC curve

Peak VO2 is associated with cardiac functional response and long-term survival in patients with heart failure and atrial fibrillation undergoing catheter ablation

Abstract Background Contemporary guidelines recommend Catheter Ablation (CA) in patients with persistent Atrial Fibrillation (AF) with Heart Failure with reduced ejection fraction (HFrEF). It is challenging to prospectively predict who will respond. We have previously described the long-term survival outcomes of patients in this cohort.(1) However, the clinical characteristics associated with HF response and long-term clinical outcomes have not been reported. Objective To evaluate the association of HF parameters with cardiac functional response to CA and long-term survival after CA. Methods Post-hoc, long-term follow-up of mortality was undertaken in patients enrolled in the CAMTAF and ARC-HF RCTs. Both studies enrolled patients with persistent AF and HFrEF between 2005 and 2012 and randomised to first-time CA or medical therapy alone. Left ventricular ejection fraction (LVEF) and peak VO2 were measured in both studies at baseline and 12-month follow-up. The Universal Definition of HF response (LVEF improves by &amp;gt;10% points or to an LVEF &amp;gt;50%) was used.(2,3) Multi-variate logistic regression was used to determine features associated with HF response and Cox proportional hazards modelling for survival. Results 102 patients underwent randomisation with 52 assigned to CA. The mean age was 60.2 ±10.7 years with 93 (91.2%) male. The mean Baseline LVEF was 31 ±11% and peak VO2 was 1815 ±642mlmin-1. Baseline LVEF did not correlate significantly with Minnesota Living with Heart Failure (MLWHF) score (r=-0.11, p=0.29) whereas baseline peak VO2 did (r=-0.28, p&amp;lt;0.01). In patients randomised to CA, the median (IQR) improvement in LVEF was +8.4% (0, 15%). 22/52 (42.3%) patients were classified as Responders based on the Universal Criteria. Responders were younger (54.7 ±10.6 years vs 61.8 ±11.4, p=0.03) and had a higher mean HR on baseline Holter monitoring (89 ±14bpm vs 79 ±11bpm p&amp;lt;0.01) than non-responders. There was no significant difference in sex, baseline MLWHF scores, BNP levels or LVEF between groups (28±9% vs 31 ±9%, p=0.19). Responders had a significantly higher peak VO2 at baseline than Non-Responders (1972 ±668mlmin-1 vs 1556 ±580mlmin-1, p=0.03). On multivariate analysis, mean heart rate on Holter monitoring and peak VO2 were significantly associated with Responder status post-ablation. (Table 1a) During a median follow-up of 7.8 (3.9 –9.9) years, 34 (33.3%) patients died, including 17 (32.7%) patients in the CA arm. On univariate analysis, baseline peak VO2 was significantly greater of survivors at 5 years (1867 ±624 mlmin-1 vs 1259 ±497 mlmin-1, p&amp;lt;0.01). On multivariate Cox regression analysis, the peak VO2 at baseline was the only significant predictor of survival (Table 1b). Conclusion Peak VO2 at baseline was associated with baseline symptom status, the short-term LVEF response to CA and long-term survival and may be a useful stratification tool to aid patient selection for CA.1a. Regression for 6-month LVEF response1b. Regression for long-term mortality

Changes and prognostic impact of right ventricular-to-pulmonary artery coupling after transcatheter aortic valve replacement

Abstract Background The ratio of tricuspid annular plane systolic excursion to systolic pulmonary artery pressure (TAPSE/sPAP), a good noninvasive approach for right ventricular to pulmonary artery (RV/PA) coupling, is of prognostic significance in many cardiovascular diseases. Yet, data regarding RV/PA coupling in transcatheter aortic valve replacement (TAVR) remain sparse. Aims: To assess the change in TAPSE/sPAP between pre- and post-TAVR as well as its long-term prognostic value. Methods: All patients who underwent TAVR for severe aortic stenosis between 2002 and 2022 at a university hospital, with an available TAPSE/sPAP assessed by echocardiography before and after procedure were included in this study. When available, TAPSE/sPAP was correlated with invasive right heart catheterization data. The primary endpoint was 5-years all-cause death or hospitalization for acute heart failure. C-tree analysis was used to find the best TAPSE/sPAP cut-off to be associated with the primary outcome. Results: Two hundred and sixty-nine patients were included in this analysis (median age 85 years, 57% women, 63% NYHA III-IV). Balloon expandable valves was implanted in 90% of cases. TAPSE/sPAP was significantly improved by TAVR (0.52 vs 0.58 mm/mmHg, p=0.02). The lower the TAPSE/sPAP, the higher the NYHA functional class (p=0.0017), the higher the NTproBNP level (p &amp;lt;0.001) and the higher the logistic EuroSCORE (p&amp;lt;0.001). TAPSE/sPAP had a good correlation with pulmonary artery elastance (r=-0.61, p&amp;lt;0.001). Using C-tree analysis, TAPSE/sPAP ≤0.55 mm/mmHg was the best cut-off associated with the primary outcome (p=0.002). In multivariable Cox regression analysis, TAPSE/sPAP remained independently associated with the primary outcome even after adjustment with echocardiography, comorbidities or logistic EuroSCORE (Table 1). Both from baseline and follow-up assessment, patients with TAPSE/sPAP ≤0.55 mm/mmHg had worse event-free survival (Figure 1A-B). Interestingly, change in TAPSE/sPAP provided important prognostic value (Figure 1C). Conclusion: This study emphasizes the prognostic value of TAPSE/sPAP in the field of TAVR and suggest considering RV/PA coupling assessment not only before or after procedure but also the change in TAPSE/sPAP to identify patients at higher risk of worse outcome.Table1.Multivariable Cox analysisFig1.Kaplan meier curves

Comprehensive remote myocardium characterisation using T1 mapping in patients with ST-segment elevation myocardial infarction

Abstract Background Myocardial tissue injury due to acute myocardial infarction (AMI) does not only occur in the myocardium that is supplied by the culprit lesion, but can also extend to the remote, non-infarcted myocardium. The prognostic implications of remote myocardium changes assessed by cardiac magnetic resonance (CMR) are not fully understood. The aim was to investigate the prognostic relevance of remote myocardium alterations assessed by CMR T1 mapping (native T1 and extracellular volume (ECV)) in patients after ST-segment elevation myocardial infarction (STEMI). Methods This study analyzed 491 STEMI patients treated with primary percutaneous coronary intervention (PCI) that were included in the prospective MARINA-STEMI study (NCT04113356). CMR imaging was performed 4 (Interquartile range [IQR]: 3-5) days after PCI. CMR images were analyzed for left ventricular (LV) function, standard infarct characteristics as well as native remote T1 and remote ECV. The primary clinical endpoint was the composite of all-cause mortality, re-infarction and new congestive heart failure (Major adverse cardiovascular events, MACE). Results Remote native T1 (median: 1009 [IQR: 979-1044] ms) was associated with female sex, peak NT-pro-BNP levels, peak hs-cTnT elevations, TIMI-risk score, admission Killip class, anterior infarct location, post-interventional TIMI-flow, LV ejection fraction and microvascular injury. Remote ECV (median: 26.37 [IQR: 24.28-29.27] %) was associated with age, female sex, peak NT-pro-BNP levels, diabetes, TIMI-risk score, admission Killip class, anterior infarct location, LV ejection fraction and microvascular injury. Over a median follow-up of 12 months (IQR: 12-13) after STEMI, 42 MACE outcomes occurred. Higher native remote T1-times (1018.5 [IQR: 997.0-1064.0] ms vs. 1007.0 [IQR: 977.0-1041.5] ms, p=0.033) as well as a higher remote ECV-values (28.07 vs. 26.27 %, p=0.009) were observed in patients with MACE. Multivariable Cox regression analysis demonstrated that remote ECV (hazard ratio (HR): 1.53 [confidence interval (CI): 1.07-2.19], p=0.020) but not native remote T1 associated with MACE. Conclusions A comprehensive assessment of the remote myocardium with native T1 and ECV provides prognostic information in a contemporary cohort of low risk STEMI patients. Remote ECV, but not remote native T1, was found to be an independent predictor of MACE.

Cardiac magnetic resonance (CMR) height-based allometric scaling in Southeast Asians; implications in the diagnosis and prognosis of left ventricular hypertrophy (LVH): the REMODEL study

Abstract Background Left ventricular hypertrophy (LVH) is a strong predictor of adverse cardiovascular outcomes (1). Although normalizing LV mass (LVM) to height exponents has been shown to reduce variability from body size, specific recommendations for height exponents are lacking due to the scarcity of normal cohorts to define appropriate height exponents (2). Cardiac magnetic resonance (CMR) is increasingly used in assessing LVM, and the existing body of research is based primarily on the MESA cohort (3). While the MESA cohort is ethnically diverse, the intrinsic effects of ethnicity may not fully be discerned if certain ethnic groups are under-represented. Purpose We aimed to demonstrate the diagnostic and prognostic implications of establishing height exponents specific to sex in a Southeast Asian cohort. Methods Non-overweight/obese Southeast Asian healthy volunteers (n=416) were used to establish appropriate height exponents and normal reference ranges of LVM. The impact of these height exponents was examined in a separate cohort of Southeast Asians with hypertension (n=878). All individuals underwent standardized cardiovascular magnetic resonance imaging (CMR). Primary outcome was a composite of acute coronary syndrome, heart failure hospitalization, stroke, and cardiovascular mortality. Cox regression analysis of various LVH measures were adjusted for 24-hour systolic blood pressure, diabetes, and hyperlipidemia. Results The height exponents for healthy females and males were 1.57 and 2.33, respectively. In patients with hypertension, sex-specific height exponents significantly increased the detection of LVH compared with body surface area (BSA) indexing (47% [n=409/878] versus 27% [n= 236/878], p&amp;lt;0.001). Most individuals re-classified to LVH with sex-specific height exponents were overweight (33.1%, n=58/175) or obese (64.6%, n=113/175). There were 37 primary events over 60 [37-73] months of follow-up. Regardless of indexing method, LVH was independently associated with increased adverse events (sex-specific height exponent hazard ratio (HR): 2.8 [1.25-6.29], P=0.013). The prediction ability of LVH diagnosis by sex-specific height exponents was similar to BSA indexing (HR: 5.43 [2.49-11.8], P&amp;lt;0.001). Conclusions Reference ranges specific to the ethnicity, sex and imaging modality are necessary to establish appropriate height exponents. Although utilizing sex-specific height exponents to index LVM resulted in significantly more LVH reclassification when compared with BSA indexing, this did not translate to a notable improvement in event prediction. Further research into alternative methods of LVM indexing is warranted.Abstract SummaryPredictive Ability of LVH Measures

Risk factors of all-cause mortality in heart failure with mildly reduced ejection fraction patients with different post-discharge left ventricular ejection fraction variation patterns

Abstract Background The identification of risk factors for all-cause mortality in patients diagnosed with heart failure with mildly reduced ejection fraction (HFmrEF) and exhibiting varying post-discharge left ventricular ejection fraction (LVEF) patterns remains incomplete. This study aimed to determine the independent risk factors of all-cause mortality among HFmrEF patients with different LVEF variation patterns post-discharge. Methods This retrospective study analyzed data from 807 HFmrEF patients admitted to our hospital between January 2015 and August 2020. Patients were categorized into three groups based on LVEF variation patterns within 6 months to one year post-discharge: Group A (transitioning to heart failure with reduced ejection fraction [HFrEF], n=225), Group B (remaining as HFmrEF, n=335), and Group C (reverting to heart failure with preserved ejection fraction [HFpEF], n=227). Patients were followed up for a mean of 33 months, with all-cause mortality as the primary endpoint. Multivariate Cox regression analysis was conducted to identify independent risk factors for all-cause mortality in each group. Results The mortality rates for Groups A, B, and C were 43.11%, 23.94%, and 24.67%, respectively (P&amp;lt;0.001). Independent risk factors for all-cause mortality in Group A included age (HR=1.04, P=0.007), obesity (HR=1.76, P=0.040), higher creatinine (&amp;gt;100 µmol/L, HR=1.83, P=0.029), higher E/e’ (HR=1.06, P=0.001), absence of PCI (HR=0.51, P=0.019), and non-use of ACEI/ARB (HR=0.039, P=0.006). In Group B, independent risk factors for all-cause mortality were age (HR=1.06, P&amp;lt;0.001), higher NT-proBNP (&amp;gt;2505 pg/ml, HR=2.50, P=0.002), and absence of PCI (HR=0.040, P=0.005). Group C exhibited age (HR=1.04, P=0.002), pleural effusion (HR=2.38, P=0.007), higher creatinine (&amp;gt;100 µmol/L, HR=2.84, P&amp;lt;0.001), and non-use of ACEI/ARB (HR=0.42, P=0.021) as significant independent risk factors associated with increased all-cause mortality risk. Conclusion This study highlights distinct risk factors associated with all-cause mortality in HFmrEF patients exhibiting different post-discharge LVEF variation patterns. Age emerged as a consistent risk factor across all groups, underscoring the importance of age-related considerations in managing HFmrEF patients. Additionally, factors such as obesity, renal function, echocardiographic parameters, and medication adherence played varying roles in influencing mortality risk depending on the evolution of LVEF following discharge. These findings emphasize the need for personalized risk stratification and tailored management strategies for HFmrEF patients to improve outcomes and reduce mortality rates.

Safety and efficacy of immune checkpoint inhibitors in patients with pre-treatment reduced left ventricular function

Abstract Background Immune checkpoint inhibitors (ICIs) have revolutionized the clinical outcomes of cancer. Nevertheless, the response varies across populations and their use may lead to ICIs-related adverse events (irAEs), including cardiovascular (CV) irAEs, which can be life-threatening. Limited evidence exists regarding the safety and efficacy of ICIs therapy in patients presenting with pre-treatment reduced left ventricular ejection fraction (LVEF). Objectives To evaluate the safety and efficacy of ICIs therapy in patients with pre-treatment reduced LVEF. Methods Retrospective single center cohort of patients treated with ICIs therapy, who performed pre-treatment LVEF assessment. The primary endpoint was to evaluate the safety of ICIs among this population, assessed by CV irAEs (composite of myocarditis, acute coronary syndrome, heart failure, and arrhythmia). The secondary endpoint was to evaluate the efficacy of ICIs, assessed by all-cause mortality and progression-free survival (PFS). Results The cohort included 307 patients with 30 (10%) patients presenting with pre-treatment reduced LVEF, with a mean LVEF of 39±7%. While a significantly higher prevalence of CV irAEs was observed in the reduced LVEF group (37% vs. 14%, p=0.004), following a multivariable cox regression analysis including baseline cardiovascular diseases and risk factors, pre-treatment reduced LVEF did not remain a significant predictor (p=0.635). No significant differences were observed between the groups regarding all-cause mortality and PFS. Conclusions Pre-treatment reduced LVEF was found to be safe with no significant impact on efficacy among patients treated with ICIs.

Increased risk of infective endocarditis following transurethral resection of the prostate (TUR-P)

Abstract Background Transient bacteremia is a well-known complication of transurethral resection of the prostate (TUR-P). Still, the associated risk of bacteremia and subsequent infective endocarditis (endocarditis) after TUR-P has been sparsely examined. Purpose To examine the risk of bacteremia and infective endocarditis following TUR-P. Methods We identified all patients who underwent TUR-P between 2010-2020 with ICD-10 codes from Danish nationwide registries. Patients were compared to an age-matched cohort of males from the general population (1:1 match-ratio). We defined a 6-month exposure window following TUR-P and examined the risk of bacteremia and endocarditis within the first 6 months and compared with the following 6-12 months after TUR-P. Microbiology findings were based on complete data on blood culture results. Incidences of bacteremia and endocarditis were calculated, and groups were compared with cumulative incidences. To account for predisposing endocarditis risk factors, multivariable time-dependent Cox regression analyses were performed on the associated risk of bacteremia and endocarditis. Results In total, 25.781 patients underwent TUR-P. Median age was 70.7 years (IQR: 64.9-76.3). Incidence of bacteremia was higher in the TUR-P group than the control group (727.47 [681.49-776.56] per 10,000 person years vs 84.75 [95% CI: 70.19-102.35)] per 10,000 person years). Incidence of endocarditis was also higher in the TUR-P group than the control group (34.64 [95% CI: 25.78-46.55] per 10,000 person years vs 3.14 [95% CI: 1.18-8.35] per 10,000 person years). In 72.7% of endocarditis-cases, Enterococcus Faecalis was the disease-causing pathogen in the TUR-P group. As compared with an age-matched control group, we found an increased associated risk of bacteremia in patients undergoing TUR-P within the first 6 months from the procedure (adj. HR: 7.72 [95% CI: 6.25-9.53]) and the increased risk persisted within the following 6-12 months (adj. HR 2.31 [95% CI: 1.83-2.91]). TUR-P was also associated with endocarditis within 6 months from the procedure (8.16 [95% CI 3.06-21.79]), but not significantly the following 6-12 months after (2.15 [95% CI: 0.91-5.07]) as compared with the age-matched control group. Conclusion Transurethral resection of the prostate (TUR-P) is associated with an almost 8 times increased risk of bacteremia and an 8 times increased risk of infective endocarditis. Our findings emphasize the necessity for development of better preventive strategies against infective endocarditis after TUR-P.Risk of endocarditis post-TUR-P

Prosthesis-patient mismatch is associated with long-term mortality following surgical aortic valve replacement

Abstract Background Prosthesis-patient mismatch (PPM) refers to a situation where the indexed effective orifice area (iEOA) of an implanted prosthetic valve is too small relative to the patient's body size, resulting in hemodynamic compromise. Studies examining the long-term consequences of PPM after surgical aortic valve replacement (SAVR) have yielded conflicting results. Purpose To evaluate the impact of PPM on long-term outcomes in patients undergoing primary isolated SAVR. Methods All patients who underwent isolated first-time SAVR from 1990-2014 were included in this observational, single-center study. PPM was defined as a predicted iEOA &amp;lt;0.85 cm2/m2 and severe PPM was defined as an iEOA &amp;lt;0.65 cm2/m2. Patient demographics, surgical details, and in-hospital outcomes were prospectively collected in our institutional database. Cases were linked to provincial administrative databases at an independent, non-profit research institute whose legal status allows it to collect and analyze health care and demographic data. The primary outcome of interest was all-cause mortality. Secondary outcomes were aortic valve reoperation (surgical or transcatheter) and post-operative hospitalization for heart failure. Multivariable Cox regression analysis identified risk factors for long-term mortality. Kaplan-Meier curves were generated for long-term survival and cumulative incidence functions for aortic valve reoperation and heart failure hospitalization. Results A total of 1,798 patients were included (no PPM: 770 [43%]; moderate PPM: 943 [52%]; and severe PPM: 85 [5%]). Mean age was 64±13 years, and 750 (42%) were female. 451 (25%) patients received a mechanical valve, and 1347 (75%) received a stented bioprosthetic valve. Concomitant aortic root enlargement was performed in 492 (27%) patients. At 20 years, survival was 47.8% (95% CI: 43.2%–52.2%) in the "no PPM group" compared with 29.5% (95% CI: 25.6%–33.5%) and 24.7% (95% CI: 12.7%–38.8%) in the moderate and severe PPM groups, respectively (p&amp;lt;0.001) (Figure 1). On multivariable analysis, iEOA was independently associated with long-term mortality (HR 0.95 per 0.10 increase in iEOA, 95% CI [0.91–0.98]; p=0.007). In a pre-specified subgroup analysis, iEOA was found to be associated with late mortality in patients younger than 65 years (p&amp;lt;0.001) but not in patients 65 years and older (p=0.23). Readmission for heart failure was more frequent among patients who had PPM than those who did not (Figure 2). There was no difference in aortic valve reintervention in patients with or without PPM (p=0.654). Conclusions Prosthesis-patient mismatch is common after SAVR and is associated with late mortality and hospitalization for heart failure. The deleterious impact of PPM on survival appears more pronounced in young patients. These findings may have important implications for the lifetime management of patients with aortic valve disease.Survival post SAVRHeart failure hospitalization post SAVR