Adverse Outcomes In Patients Research Articles

Investigating the combinatorial effects of radiofrequency ablation and anticoagulants in patients with atrial fibrillation and left atrial appendage thrombosis after successful thrombolysis.

The present study investigated the synergistic effects of radiofrequency ablation and various anticoagulants on adverse outcomes in patients with atrial fibrillation (AF) and left atrial appendage thrombosis following successful thrombolysis. Patients diagnosed with AF and left atrial appendage thrombosis post-successful thrombolysis (n=92) were retrospectively analysed. They were divided into two groups: Group A received radiofrequency ablation combined with an anticoagulant, while Group B received an anticoagulant alone and in combination with antiarrhythmic drugs. Subgroup analyses were conducted based on left atrial diameter (>45 mm), duration of AF (>1 year) and types of anticoagulants. Univariate and multivariate logistic regression analyses were performed to assess stroke and mortality risks in patients with AF with left atrial appendage thrombosis after dissolution. Multivariate logistic regression analysis identified AF duration (>1 year), left atrial diameter (>45 mm) and BNP level as significant risk factors for stroke (P<0.05). Compared with NOACs, the traditional anticoagulants (warfarin) demonstrated higher survival rates and lower stroke incidence in Group B (P<0.05); however, no significant difference was observed within Group A (P>0.05). Radiofrequency ablation combined with anticoagulants appeared to be more effective in treating AF with left atrial appendage thrombosis post-dissolution compared with anticoagulants alone. Attention to AF duration and left atrial diameter is crucial during early patient management. However, the choice between warfarin or NOACs for patients with AF and left atrial appendage thrombosis warrants further investigation.

Clinical effectiveness of nirmatrelvir plus ritonavir for patients with COVID-19 and preexisting psychiatric disorders

ABSTRACT Objectives This study assessed the clinical effectiveness of the combination of nirmatrelvir and ritonavir (NMV-r) in treating nonhospitalized patients with COVID-19 who have preexisting psychiatric disorders. Methods Patients diagnosed with COVID-19 and psychiatric disorders between 1 March 2020, and 1 December 2022, were included using the TriNetX network. The primary outcome was the composite outcome of all-cause emergency department (ED) visits, hospitalization, or death within 30 days. Results Propensity score matching yielded two cohorts of 20,633 patients each. The composite outcome of all-cause ED visits, hospitalization, or death within 30 days was 3.57% (737 patients) in the NMV-r cohort and 5.69% (1176) in the control cohort, resulting in a reduced risk in the NMV-r cohort (HR: 0.657; 95% confidence interval (CI): 0.599–0.720). The NMV-r cohort exhibited a lower risk of all-cause hospitalization (HR: 0.385; 95% CI: 0.328–0.451) and all-cause death (HR: 0.110; 95% CI: 0.053–0.228) compared with the control group. Conclusion NMV-r could mitigate the risk of adverse outcomes in nonhospitalized patients with COVID-19 and preexisting psychiatric disorders. However, only a limited number of patients in this population received adequate treatment, thus emphasizing the importance of promoting its appropriate use.

Machine learning approaches toward an understanding of acute kidney injury: current trends and future directions.

Acute kidney injury (AKI) is a significant health challenge associated with adverse patient outcomes and substantial economic burdens. Many authors have sought to prevent and predict AKI. Here, we comprehensively review recent advances in the use of artificial intelligence (AI) to predict AKI, and the associated challenges. Although AI may detect AKI early and predict prognosis, integration of AI-based systems into clinical practice remains challenging. It is difficult to identify AKI patients using retrospective data; information preprocessing and the limitations of existing models pose problems. It is essential to embrace standardized labeling criteria and to form international multi-institutional collaborations that foster high-quality data collection. Additionally, existing constraints on the deployment of evolving AI technologies in real-world healthcare settings and enhancement of the reliabilities of AI outputs are crucial. Such efforts will improve the clinical applicability, performance, and reliability of AKI Clinical Support Systems, ultimately enhancing patient prognoses.

Myocarditis in the modern era: analysing the impact of high-sensitivity troponin &amp; C-reactive protein in predicting the extent of myocarditis and LV systolic dysfunction on cardiac magnetic resonance

Abstract Background The diagnostic yield of acute myocarditis has improved considerably since the advent of high-sensitivity troponin (hs-Tn) assays and adoption of the 2018 Lake Louise criteria for cardiac magnetic resonance (CMR)-based imaging for myocardial oedema and injury (1). Yet, a seminal 1997 study, predating these technological advances, remains widely cited for highlighting an absence of troponin rise in two-thirds of myocarditis cases (2). We hypothesize that all cases of myocarditis exhibit hs-Tn rise. However, whether such elevations in hs-Tn or inflammatory markers correlate with the extent of myocardial injury and left ventricular systolic dysfunction (LVSD) on CMR remain unclear. To provide insight into this, we examined a contemporary cohort of cases between 2019-2023. Methods Two authors independently conducted case-notes reviews to verify the diagnosis of myocarditis. CMR findings were stratified into regional (e.g. inferolateral) and global myocarditis (e.g. subepicardial LGE in all segments). This classification aimed to explore potential correlations with LVSD severity, peak hs-Tn and other inflammatory markers. Receiver operating characteristics (ROC) curves was calculated to determine any cut-off value for predicting CMR findings and adverse patient outcomes. Results 103 inpatients were clinically coded as ‘myocarditis’ upon discharge, but subsequent CMR (within 4 weeks) reclassified 23 patients into other causes (Figure 1). Analysis of the myocarditis cohort revealed a predominantly male population (76%) with median age 53, commonly presenting with chest pain without a viral prodrome (Figure 2A-D). Elevated hs-Tn levels were observed universally, with a median peak hs-TnT of 610ng/L (IQR 1081.5ng/L) and hs-TnI of 3820ng/L (IQR 12416ng/L). In contrast, peak CRP ranged between 2mg/L (normal) and 600mg/L. Global myocarditis was detected in 11/80 patients (13.8%); however, this finding did not correlate with adverse patient outcomes which included all-cause mortality (9.6%) and cardiac re-admissions within 12 months (9.6%, namely for chest pains). No arrhythmic deaths were noted. COVID was present in 4% on admission. CRP cut-off of 140mg/L predicted the occurrence of global myocarditis with a sensitivity of 72.7% and specificity of 87.0% (AUC 0.74, 95% CI 0.52-0.96, p=0.014) (Figure 2E). However, neither hs-Tn or CRP levels correlated with the degree of LVSD (Figure 2F) or adverse outcomes. This is likely limited by the small sample. Conclusion Although all cases of myocarditis exhibited raised hs-Tn, this did not correlate with the degree of LV systolic impairment on CMR. Myocarditis with regional LV involvement can have normal CRP levels, while a CRP cut-off &amp;gt;140mg/L may predict the occurrence of global myocarditis. However, CMR stratification into regional and global was not associated with adverse patient outcome within 12 months. A larger sample size is required to verify this finding, including longer term follow-ups.Flowchart of patients included in studyMain findings

Comparative assessment of extracellular volume metrics in predicting adverse outcomes in patients with transthyretin amyloid cardiomyopathy

Abstract Introduction The indexed total extracellular volume of the myocardium (iECV) has recently been proposed to be superior in predicting adverse outcome in severe aortic stenosis as compared to conventional extracellular volume (ECV). So far, no study has assessed the comparative predictive performance of both measures in transthyretin amyloid cardiomyopathy (ATTR-CM). Aim We aimed to assess and compare the predictive performance of conventional ECV against iECV in determining adverse outcomes in patients with ATTR-CM. Methods From 2012 to 2023, patients with ATTR-CM undergoing contrast cardiac magnetic resonance (CMR) imaging prior to any specific treatment were enrolled. Both, conventional ECV and iECV were quantified on CMR alongside left ventricular volumetrics and late gadolinium enhancement. Adverse outcome was defined as a composite endpoint of hospitalization for heart failure and/or death. Results Analysis of 178 patients with ATTR-CM (82% males, mean age 77±8 years) revealed a mean conventional ECV of 47±13% and a mean iECV of 46±21 mL/m2, with a median follow-up of 2.5 years (IQR: 1.00-4.08 years). Conventional ECV was significantly associated with the composite endpoint (HR=1.03, 95%CI=1.01–1.05, p=0.006), outperforming iECV (HR=1.01, 95%CI=1.00–1.02, p=0.010). On multivariate analysis, adjusted for age, sex and left ventricular function, conventional ECV remained associated with the composite endpoint (p=0.002), while iECV demonstrated a slightly less significant association (p=0.003). Kaplan-Meier analysis, stratified by conventional ECV tertiles, revealed that patients in the highest tertile (ECV ≥53%) demonstrated the highest event rate (p = 0.043 by log rank test, see Figure 1A), in contrast to iECV (p=NS, Figure 1B). Conclusions High conventional ECV, among CMR fibrosis markers, is linked to heart failure hospitalizations and death in ATTR-CM, demonstrating superior prognostic value compared to iECV. Conventional ECV measurements may offer enhanced risk stratification for patients with ATTR-CM.

Hemoglobin/creatinine ratio as long- term prognostic marker in acute coronary syndromes: a praise registry study

Abstract Introduction Anemia and renal impairment are key determinants of adverse outcomes in patients with acute coronary syndrome (ACS). The hemoglobin/creatinine (Hb/Cr) ratio, a simple and universally accessible index that combines these two factors, was found to predict adverse outcomes in patients with cardiovascular disease. There is limited evidence on the performance of the Hb/Cr ratio in predicting long-term adverse outcomes in the specific setting of ACS. Purpose To evaluate the long-term prognostic impact of the Hb/Cr ratio in patients with ACS. Methods Out of the 23,270 ACS patients enrolled in the international PRAISE registry between 2003 and 2019, 3.465 were excluded due to missing data and 19.805 were included in this analysis. The primary endpoint was all-cause mortality at one year follow-up. Secondary endpoints were major bleeding and the composite of all-cause mortality or reinfarction at one year follow-up. A cut-point analysis according to Liu’s method was run to evaluate the best discriminative value of the Hb/Cr ratio for the prediction of all-cause mortality. Results The cut-point analysis showed that a cut-off value of 13.79 represented the most discriminative in predicting all-cause mortality at one year (CI 13.35–14.23; AUC 0.66), and that mortality increased exponentially when the ratio was &amp;lt;12.4. On the basis of this discriminative value, we divided our population into low vs. high Hb/Cr groups. The former included 5,874 (29.7%) patients, while the latter included 13,931 (70.3%). Patients in the low Hb/Cr group were older, more frequently female, and had a higher prevalence of cardiovascular risk factors, comorbidities, and history of coronary artery disease. Conversely, patients in the high Hb/Cr group were mostly men and more frequently admitted with a STEMI diagnosis. One year post-discharge from ACS, all-cause mortality (8.3% vs. 2.3%; p &amp;lt; 0.001), major bleeding (5.4% vs. 2.2%; p &amp;lt; 0.001) and the composite of all-cause mortality or reinfarction (11.6% vs. 4.7%; p &amp;lt; 0.001) were significantly higher in the low Hb/Cr group. Bivariate regression analysis showed that Hb/Cr ratio was inversely associated with all-cause mortality (OR 0.85; CI 0.84 – 0.86; p &amp;lt; 0.0001), major bleeding (OR 0.91; CI 0.89-0.92; p &amp;lt; 0.0001), and the composite of all-cause mortality or reinfarction (OR 0.89; CI 0.88-0.90; p &amp;lt; 0.0001). This association held strongly true even after an extensive adjustment for several covariates, including cardiovascular risk factors, comorbidities, and discharge medical therapy: all-cause mortality (OR 0.95; CI 0.92 – 0.97; p &amp;lt; 0.0001), major bleeding (OR 0.92; CI 0.89-0.95; p &amp;lt; 0.0001), composite of all-cause mortality or reinfarction (OR 0.96; CI 0.94-0.98; p &amp;lt; 0.0001). Conclusions HB/Cr ratio appears to be inversely associated with long-term adverse outcomes among ACS patients. Further research is warranted before routinely considering this index in clinical practice.

Is pulmonary vascular remodeling an intermediate link between hyperglycemia and adverse outcomes in patients with idiopathic pulmonary arterial hypertension? Insights from a multi-center cohort study

BackgroundHyperglycemia upon admission is associated with poor prognosis of many cardiovascular diseases. However, the relationship of stress hyperglycemia ratio (SHR), admission blood glucose (ABG), and hemoglobin A1c (HbA1c) with pulmonary hypertension has not been reported. This study aimed to explore the association of hyperglycemia indices with disease severity and long-term adverse outcomes in patients with idiopathic pulmonary arterial hypertension (IPAH).MethodsThis multi-center cohort study included 625 consecutive patients diagnosed with or treated for IPAH between January 2015 and June 2023. SHR was calculated using the followings: ABG (mmol/L)/(1.59 × HbA1c [%] − 2.59). The primary endpoint was defined as clinical worsening events. Multivariable Cox regression and restricted cubic spline analyses were employed to evaluate the association of SHR, ABG, and HbA1c with endpoint events. The mediating effect of pulmonary hemodynamics was evaluated to investigate the potential mechanism between hyperglycemia and clinical outcomes.ResultsDuring a mean follow-up period of 3.8 years, 219 (35.0%) patients experienced all-cause death or clinical worsening events. Hyperglycemia indices correlated with well-validated variables that reflected the severity of IPAH, such as the World Health Organization functional class, 6-min walk distance, and N-terminal pro-brain natriuretic peptide levels. Multivariable Cox regression analyses indicated that SHR (hazard ratio [HR] 1.328, 95% confidence intervals [CI]: 1.185, 1.489 per 0.1-unit increment, P < 0.001) and ABG (HR 1.317, 95% CI: 1.134, 1.529 per 1.0-unit increment, P < 0.001) were independent predictors of primary endpoint events. Mediation analysis indicated that pulmonary vascular resistance mediated 5.65% and 14.62% of the associations between SHR and ABG and clinical worsening events, respectively. The addition of SHR significantly improved reclassification, discrimination ability, and model fit beyond the clinical risk prediction model.ConclusionsSHR is positively associated with clinical worsening in patients with IPAH. The association appeared to be partially mediated through the pathway of pulmonary vascular remodeling, indicating that SHR may serve as a valuable indicator for providing additional risk information.

CMR-derived pulmonary artery to aorta ratio as a predictor of adverse outcome in patients with cardiac transthyretin amyloidosis

Abstract Introduction Cardiac transthyretin amyloidosis (ATTR) represents a heart failure phenotype often accompanied by pulmonary hypertension. The pulmonary artery to aorta ratio (PA/Ao), as assessed on cardiac computed tomography or cardiac magnetic resonance (CMR), has demonstrated to indicate risk for adverse events in a variety of cardiovascular diseases, particularly in heart failure and pulmonary hypertension. However, its prognostic value in cardiac ATTR remains unknown. Aim We aimed to investigate the prognostic value of the PA/Ao ratio in patients with cardiac ATTR. Methods Data of consecutive patients diagnosed with cardiac ATTR undergoing CMR were prospectively collected. PA/Ao ratios were measured from CMRs using axial images (Figure 1A). Adverse outcome, defined as heart failure related hospitalizations and/or mortality, was recorded during follow-up. Results Among the 190 confirmed cardiac ATTR patients (mean age 76±11 years, 79% males), encompassing hereditary transthyretin (vATTR, n=22) and senile (wtATTR, n=168) types, the median pulmonary artery diameter was 28mm (IQR 25-31) and the median ascending aorta diameter was 35mm (IQR 33-39). Over the median follow-up period of 28 months (IQR 11-50 months), 84 (44%) patients experienced an adverse event. Kaplan Meier curves demonstrated an increased risk for adverse outcome in patients with PA/Ao ratios above the median of ≥0.8 (p&amp;lt;0.001 by log rank test, see Figure 1B). In univariate analysis, a high PA/Ao ratio was associated with adverse outcome (HR=10.3, 95% CI=2.59–41.1, p&amp;lt;0.001). When adjusted for age, sex, body mass index and right ventricular function, the PA/Ao ratio remained significantly related to adverse outcome (adj. HR=10.8, 95% CI=1.76–65.8, p=0.010). Conclusion A PA/Ao ratio ≥0.8 on CMR is associated with heart failure hospitalization and death in patients with cardiac ATTR. This threshold, notably lower than the commonly reported ≥1.0 in other patient populations, holds promise for future risk stratification.

The gut-microbiome derived phenylacetylglutamine predicts adverse events in patients with acute coronary syndromes

Abstract Background and Introduction The gut microbiota-derived metabolite phenylacetylglutamine (PAG) is associated with incident cardiovascular events(1). Acute coronary syndromes (ACS) present a major health challenge, especially as population ages(2). Data from our group show increased PAG levels during aging in humans. However, the predictive potential of PAG for mortality and major adverse cardiovascular events (MACE) in patients (pts) with ACS is unknown. Purpose Here, we investigated the potential of PAG to predict ischemic and fatal events in pts with acute coronary syndromes (ACS). We also compared the predictive potential of PAG to another relevant gut-microbiota derived metabolite involved in CVD, namely Trimethylaminoxyde, (TMAO), and we evaluated their cumulative risk potential. Methods A total of 1’848 patients were enrolled in Cohort I of the SPUM-ACS study – a multi-center prospective ACS cohort study from Switzerland. Overall survival and incident MACE after 1 year follow-up were analyzed using Kaplan-Meier (KM) estimates and compared by log-rank test after patient stratification into PAG tertiles. Uni- and multivariable Cox-regression models were fit to calculate the hazard ratios for 1-year MACE in a crude model and adjusted model (adjusted for established confounders). Healthy controls served as additional controls. PAG plasma levels were quantified using LC-HRMS. Results The median PAG plasma level in the healthy control group was 1.76µM, whereas for the whole ACS patient population it was 1.92µM (Table 1). Pts in the third PAG tertile had a two times higher MACE rate and a four times higher mortality rate compared to pts in the first PAG tertile (p&amp;lt;0.001). (Table 2). PAG levels were significantly higher in pts who presented with MACE (2.63µM) or died (3.1µM) within the 1-year follow-up compared to the healthy control subjects (p&amp;lt;0.0001) (Figure 1A). Spearman correlation analysis revealed that plasma PAG levels were positively associated with age (r=0.43, p&amp;lt;0.0001), while a negative association with eGFR was observed (r=-0.51, p&amp;lt;0.0001) (Figure 1B). KM estimates indicated that pts in the highest PAG tertile had significantly higher 1-year MACE risk relative to those with low levels (Figure 1C; p&amp;lt;0.001 log rank). Following multivariable adjustment, PAG remained an independent predictor for MACE at 1-year follow-up with a hazard ratio (HR) of 1.8 (95% CI, 1.1–3.2, p=0.048) (Figure 1D). KM estimates of both, high levels of PAG and high levels of TMAO together, indicate that the combination of these two detrimental metabolites leads to an even higher risk of 1-year MACE relative to lower levels (Figure 1E). Conclusion PAG is a novel and independent predictor of adverse outcomes in patients with ACS. This study indicates the role of the gut-microbiome and its metabolites in predicting ischemic and fatal outcomes of pts with established CVD.

National early warning score predicts 90 days all-cause mortality among patients with acute heart failure

Abstract Background Acute heart failure (AHF) is defined as new-onset or worsening of symptoms and signs of heart failure including symptoms or signs related to congestion and volume overload. Patients presenting with AHF are a heterogeneous group as AHF is not a specific disease but a shared clinical presentation of different cardiac abnormalities. Due to the heterogeneity of the patient population, a prognostic tool is needed to identify AHF patients with a high risk of death. The National Early Warning Score (NEWS) is a system for scoring the vital signs that are measured at the patient's bedside and is developed to predict acute mortality within 24 hours. The NEWS has previously been used to evaluate all cost mortality for patients admitted to the Emergency Department (ED). There is limited data regarding the role of the NEWS in predicting adverse outcomes in patients with acute heart failure. Purpose To evaluate NEWS measured at the ED and clinical outcomes in patients with AHF. Methods This prospective, observational cohort study included consecutive patients with AHF admitted through the emergency department (ED) at a large public hospital from 10 March 2020 to 31 March 2022 and had a follow-up period of 365 days. Trained cardiologists assessed all patients for the presence of AHF. According to the cut-off value for the NEWS, high-risk groups are defined by a NEWS score &amp;gt; 7. The patients were categorized into two groups, high-risk and low-risk, depending on the scores they received from the NEWS assessment. The primary outcome was all-cause mortality at 90 days. We used multivariable Cox regression (hazard ratios [HRs]) to compare survival, adjusting for age, sex, smoking, known heart failure (HF), and lactate levels at admission. Results In the study period from March 10, 2020, to March 31, 2022, 408 patients were identified with AHF. Upon arrival to the ED, the median first NEWS was 4 (IQR 2-6). 323 patients were categorized in the low-risk group and 69 patients in the high-risk group. 16 patients had missing values upon arrival at the ED. The high-risk group exhibited significantly faster heart rate, lower saturation, and higher oxygen demand compared. A Kaplan-Meier plot revealed a statistically significant difference in all-cause mortality over 90 days between low-risk and high-risk groups among AHF patients (log rank, p-value &amp;lt; 0.001). After multivariable adjustment, NEWS&amp;gt;7 (HR, 1.69; CI, 1.18 to 2.45) (p-value= 0.004) and higher age (HR, 1.04; CI 1.03 to 1.07) were statistically associated with higher all-cause mortality (p &amp;lt;0.001). Conclusion In this prospective, observational cohort study of AHF patients presenting at the ED an initial NEWS &amp;gt;7 was associated with a significant all-cause mortality after 90 days.GRAPHIC ABSTRACT

Long-term outcomes of patients with apical hypertrophic cardiomyopathy: incorporation of a novel risk score

Abstract Background Apical hypertrophic cardiomyopathy (aHCM) is a subtype of HCM characterized by left ventricular hypertrophy predominantly in the apex. There is still limited data on factors associated with adverse outcomes in patients with aHCM. Objectives To a) describe the characteristics and b) develop a novel risk score associated with outcomes in aHCM patients. Methods A total of 462 patients (mean age 58±15 years, 68% male and 70% white) diagnosed with aHCM based on clinical, echocardiographic, and cardiac magnetic resonance (CMR) evaluation were included. The primary endpoint was all-cause death or aborted sudden cardiac death. Using the cox regression analysis, variables showing potential association with the composite endpoint were considered to develop an aHCM specific risk score. Results On echocardiography, the mean LV ejection fraction (LVEF) was 64±8%, and the mean LV mass was 223±72 g. A baseline CMR was performed in 246 (53%) patients, with delayed gadolinium enhancement in 170 (71%) patients with a mean percentage of 5±7%. Patients were followed-up for a mean of 68 months (range 1-248), with composite events occurring in 80 (17%) patients (death in 62 [13%] patients). Univariate Cox regression analysis identified age hazard ratio (HR) 1.06 (95% Confidence Interval or CI 1.04-1.08; p&amp;lt; 0.001), apical aneurysm HR 2.32 (95% CI 1.24-4.34 p=0.008), lower LVEF HR 0.96 (95% CI 0.94-0.99 p=0.002), higher right ventricular systolic pressure (RVSP) HR 1.04 (95% CI 1.02-1.06 p&amp;lt; 0.001), New York Heart Association Class IV HR 11.69 (95% CI 3.59-38.08 p&amp;lt; 0.001) and the presence of Atrial fibrillation HR 1.77 (95% CI 1.14-2.76 p=0.012). An aHCM specific risk score was subsequently created (Figure 1), with good discrimination (c-statistic=0.75) and good calibration with expected to observed ratio of 1.02 and a calibration slope of 0.91 (p-value for difference between expected and observed probabilities =0.22). The risk score ranges between 0 and 8 points, with higher score associated with a higher rate of composite events (Figure 2). Conclusion We developed a novel risk score which demonstrated incremental prognostic value for hard events in aHCM patients.Risk prediction modelKaplan Meier event-free survival curves

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&amp;gt;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

Endogen microvascular dysfunction is associated with worse outcomes in heart transplantation

Abstract Background Cardiac allograft vasculopathy (CAV) affects the health of both epicardial and microvascular blood vessels in heart transplants. Coronary microvascular dysfunction (CMD) has been associated with poor outcomes in the non-transplant population. Two patterns of microvascular dysfunction have been characterized, classical (low stress flow) and endogen (high rest flow). Whether these patterns of microvascular dysfunction are associated with outcomes in the transplant population has not been thoroughly evaluated. Purpose The purpose of the study was to assess the relationship between microvascular dysfunction and adverse outcomes in patients with heart transplants. Methods Patients with no history of angiographic CAV who underwent positron emission tomography myocardial perfusion imaging and were found to have normal perfusion (summed stress score = 0) were included in the study. Patients were then classified by microvascular dysfunction: normal (flow reserve ≥ 2.0) versus abnormal (flow reserve &amp;lt;2.0). Patients were further subclassified based on pattern of microvascular dysfunction, classical (stress myocardial flow &amp;lt;1.7 mL/min/g) and endogen (stress myocardial flow ≥1.7 mL/min/g). The two primary outcomes were all-cause mortality and a composite of death, heart failure hospitalization, acute coronary syndrome, and revascularization. Kaplan-Meier survival and Cox proportional regression were used to assess the relationship between microvascular function and outcomes. Results In total, 359 patients were enrolled in the study, of which 29 (8%) had classical CMD and 78 (22%) had endogen CMD. Patients with endogen CMD were more likely to be women (46%) compared to 31% for normal microvascular function and 24% for classical CMD. During a median follow up period of 2.0 years (Q1 1.7, Q3 2.3), 36 patients had an adverse event and 19 patients died. Endogen CMD was associated with a significantly higher risk of both the composite outcome, HR 2.30 (1.15 – 4.61), and all-cause mortality, 4.19 (1.64 – 10.73). Classical CMD was not associated with either the composite outcome, HR 0.88 (0.20 – 3.84) or death, HR 1.02 (0.12 – 8.33), however assessment of classical CMD was limited by small sample size. Conclusions Endogen-type CMD is associated with worse intermediate-term outcomes in transplant patients compared to normal microvascular function and classical-type CMD, although comparison to classical-type CMD was limited by small sample size.Table 1:DemographicsFigure 1:KM Survival Curves

Sex differences in left ventricular dilatation in patients with significant aortic regurgitation: prognostic implications

Abstract Background Left ventricular (LV) dilatation is a strong indicator of adverse outcome in patients with aortic regurgitation (AR). Accordingly, current guidelines recommend the use of LV end-systolic diameter index (LVESDi) as one of the criteria to trigger aortic valve surgery (AVS) in patients with severe AR, but with the same threshold regardless of gender. Purpose To assess sex differences in LV remodeling using both volumetric and linear measurements in a large cohort of patients with significant AR (moderate or greater) and to investigate their prognostic implications. Methods A total of 1070 patients (56 ± 18 years, 691 men) were included. The primary outcome was all-cause mortality. Results Women presented with older age (58 ± 19 vs. 55 ± 17, p=0.023) and more advanced heart failure (HF) symptoms than men (NYHA class III-IV 12% vs. 9%, p=0.017). Men showed significantly larger LVESDi (21 ± 5 vs. 20 ± 5 mm/m2, p=0.013) and LV end-systolic volume index (LVESVi 37 ± 28 vs. 26 ± 17 ml/m2 p&amp;lt;0.001). During a median follow-up of 89 (IQR, 54-132) months, 168 patients died. Women had lower survival rates at 3, 5, and 10 years of follow-up compared to men (92% vs. 94.3%; 85% vs. 89.7% and 75.3% vs. 84.1%, p=0.005) (Figure 1). Spline curve analysis revealed that the threshold of LVESDi associated with an increased risk of mortality was 20 mm/m2 for both sexes. In turn, the threshold for LVESVi was 40 ml/m2 for women and 45 ml/m2 for men. Univariable Cox regression models were constructed separately for men and women. The variables associated with all-cause mortality were age, NYHA class III-IV, and AVS as time-dependent covariate in women, and age, diabetes, AVS as time-dependent covariate, and LAVI (left atrial volume index) in men. These parameters were used as a basal multivariable Cox regression model on top of which LVESDi &amp;gt;20 mm/m2 (Model 1), LVESVi &amp;gt;40 ml/m2 for women and 45 ml/m2 for men (Model 2) were added (Table 1A). LVESVi &amp;gt;40 ml/m2 was not a significant univariate predictor in men. In women, LVESDi &amp;gt;20 mm/m2 (HR: 2.046, 95%CI 1.244-3.419; p=0.006) and LVESVi &amp;gt;40 ml/m2 (HR 1.758, CI 1.095-2.825; p=0.020) showed an independent association with all-cause mortality among other factors (Table 1A). In men, death was independently associated with LVESDi &amp;gt;20 mm/m2 (HR 1.979, 95%CI 1.255-3.121; p=0.003) and LVESVi &amp;gt;45 ml/m2 (HR 2.388, 1.522-3.746; p&amp;lt;0.001), among other factors (Table 1A). Moreover, when added to a basal model that included clinical and echocardiographic variables associated with prognosis, LV dilatation based on volumetric LV enlargement resulted in a greater discriminatory power for both genders (Table 1B). Conclusion Men and women have a similar LVESDi threshold of 20 mm/m2, which is associated with an increased risk of death. However, their respective cut-off values for LVESVi differ, with the optimal threshold for women being 40 ml/m2 and for men 45 ml/m2.

Association of osteopontin and shrunken pore syndrome with hospitalization for renal failure in acute heart failure patients

Abstract Background Shrunken pore syndrome (SPS) emerges as a distinctive manifestation of glomerular filtration dysfunction mainly manifested by the impairment of moderate-sized molecular filtration, distinguished by a variance in renal filtration between cystatin C and creatinine. SPS exhibits correlations with adverse prognosis of various cardiovascular diseases. A decline in renal function correlates with a poor prognosis among individuals with heart failure (HF). Osteopontin (OPN), a protein involved to bone mineralization, has been linked to deteriorating renal function and heightened risk for adverse outcomes in patients with chronic kidney disease. Purpose To explore if OPN and SPS are associated with hospitalization for renal failure in patients with acute HF. Methods Cystatin C and creatinine were analyzed in 395 hospitalized HF patients, of which 324 also had osteopontin (OPN) analyzed using a proximity extension assay. SPS was calculated using the CKD-EPI Equations for Glomerular Filtration Rate and defined as a cystatin C-based estimated glomerular filtration rate (eGFR) &amp;lt;60% of the creatinine based eGFR. Hospitalization for renal failure was extracted from regional registries using ICD10 codes N17-N19. Logistic and Cox regression models were deployed to explore a) OPN’s association with SPS; b) OPN’s association with hospitalization for renal failure; and c) SPS’s association with hospitalization for renal failure, adjusting for age, sex, systolic blood pressure and use of renin-angiotensin-aldosterone system (RAAS) inhibitors. Results The study population had a mean age of 74.8 (±12.0) years, 32.4% were women and 104 (26.5%) patients presented with SPS (Table 1). During the median follow-up period of 71 (interquartile range 56-88) months, 35 (8.9%) patients were hospitalized for renal failure. OPN was associated with the prevalence of SPS (OR 1.66; 95%CI 1.08-2.27; p=0.002), as well as with higher risk of hospitalization due to renal failure (HR 2.71; 95%CI 1.61-4.56; p&amp;lt;0.001). Further, also prevalent SPS was associated with higher risk of hospitalization due to renal failure (HR 2.44; 95%CI 1.14-5.24; p=0.022). Conclusions Here, we demonstrate that higher OPN levels are associated with a higher prevalence of SPS and an elevated risk of hospitalization due to renal failure among patients with HF. Additionally, the presence of SPS was associated with a higher risk of renal failure-related hospitalizations. These findings highlight the potential utility of OPN and SPS as biomarkers for identifying heart failure patients at risk of renal function decline, underscoring the importance of early risk stratification and targeted interventions in this population.

Mobile health technology integrated care in atrial fibrillation patients according to polypharmacy: an analysis of the mAFA-II clinical trial

Abstract Background Polypharmacy is common in patients with multiple chronic long-term conditions and has been associated with adverse outcome in patients with Atrial Fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway has been proposed to streamline an integrated care management of AF patients, and the Mobile Health Technology for Improved Screening and Optimized Integrated Care in AF (mAFA-II) prospective cluster randomised trial showed the efficacy of a mobile health (mHealth) implemented ‘ABC’ pathway (mAFA intervention) in improving prognosis of AF patients. Whether these benefits apply also to AF patients with polypharmacy is unclear. Purpose To evaluate the effect of mAFA intervention according to the presence of polypharmacy at baseline. Methods In the mAFA-II cluster randomised trial, between June 2018 and August 2019 adults with AF were enrolled in 40 centres in China; clusters were randomised in a 1:1 ratio to mAFA intervention or usual care. In this analysis, we defined polypharmacy as being treated with 5 or more drugs at baseline. The primary outcome was the composite of stroke, thromboembolism, all-cause death and rehospitalisation. We evaluated the interaction between the effect of mAFA intervention and the presence of polypharmacy at baseline on the risk of the primary outcome using multivariable Cox-regression analysis; results were expressed as adjusted Hazard Ratio (aHR) and 95% Confidence Intervals (95%CI). We also evaluated individual components of the primary outcomes as exploratory secondary endpoints. Results 3,324 patients were enrolled in the trial and included in this analysis; of these, 558 (16.8%) patients were polymedicated at baseline (mean age 71.9±12.6 years, females 44.3%); of these, 303 (54.3%) were allocated to mAFA intervention. 2,766 patients were not polymedicated (mean age 67.9±14.4 years, females 36.7%), of these 1,343 (48.5%) were allocated to mAFA intervention. Overall, patients in the polypharmacy group were older and with higher prevalence of most comorbidities and higher thromboembolic risk. The effect of mAFA intervention was similar among patients with vs. without polypharmacy on the reduction of the primary composite outcome, although with a diluted effect among polymedicated patients (adjusted Hazard Ratio [aHR] and 95% Confidence Interval [CI]: 0.34 [0.22-0.53] vs. 0.73 [0.27-1.99], p for interaction=0.166, Figure 1); similar results were observed for all-cause death and rehospitalizations. Conclusions A mHealth-technology implemented ABC pathway showed a similar effect on the reduction of the primary composite outcome among patients with and without polypharmacy. These findings support a broad application of the ABC pathway to improve outcomes in AF patients.Figure 1

Assessing stroke and mortality risk in heart failure: the CHA2DS2-VASc score's prognostic value in patients with and without atrial fibrillation - a systematic review and meta analysis

Abstract Background Heart failure (HF) is a common cardiovascular disorder that is linked to substantial morbidity and mortality. The CHA2DS2-VASc score, originally designed to assess the risk of stroke in patients with atrial fibrillation, has demonstrated potential as a prognostic indicator for adverse outcomes in patients with heart failure. This systematic review and meta-analysis aimed to assess the predictive accuracy of the CHA2DS2-VASc score in determining the occurrence of stroke and increased mortality rates in patients with heart failure. Methods A thorough search of electronic databases, such as PubMed, EMBASE, and the Cochrane Library, was performed to find pertinent papers published until the search cutoff date. Included studies examined the correlation between the CHA2DS2-VASc score and the likelihood of stroke or death in patients with heart failure. The assessment of the quality of the included studies was conducted using recognized criteria, and data were collected for quantitative synthesis. Findings The meta-analysis encompassed four studies (45864 patients), revealing a consistent and substantial correlation between elevated CHA2DS2-VASc scores and heightened risks of both stroke and mortality in heart failure patients. More precisely, patients with CHA2DS2-VASc scores ≥4 had a greater risk of stroke compared to those with scores &amp;lt;4 (odds ratio 0.38, 95% confidence interval 0.33-0.43, p-value &amp;lt; 0.00001). The combined data showed homogeneity (p-value = 0.24, I2 = 29%). Similarly, patients with CHA2DS2-VASc scores ≥4 had a higher risk of mortality compared to those with scores &amp;lt;4 (OR 0.49, 95% CI 0.30-0.80, P = 0.05). However, the combined data showed significant heterogeneity (P &amp;lt; 0.00001, I2 = 96%). Conclusion The CHA2DS2-VASc score is a useful predictive tool for identifying heart failure patients who are hospitalized and at a high risk of both stroke and high mortality. The results of this study provide evidence for the practicality of using the CHA2DS2-VASc score for risk stratification in patients with heart failure. Additional investigation is necessary to confirm these findings and examine the incorporation of the CHA2DS2-VASc score into risk assessment algorithms for tailored patient management.Figure:Risk of strokeFigure:Risk of mortality

One-year outcomes of patients with hypertrophic cardiomyopathy according to levels of inflammatory biomarkers

Abstract Background Hypertrophic cardiomyopathy (HCM) is a vastly heterogeneous sarcomere disorder unified by maximal left ventricular (LV) thickness increases. The lifetime relative risk of morbidity in HCM is four-fold higher than in the general population, primarily driven by arrhythmias and heart failure (HF). Numerous prognostic features have been identified, but our ability to identify high-risk patients of progression remains rudimentary. Small retrospective studies have shown that systemic inflammation is associated with adverse outcomes in patients with HF; others, small and single-center, have also shown associations between adverse outcomes and inflammation in HCM. Purpose We aimed to determine whether elevated levels of inflammatory biomarkers are associated with an increased risk of acute heart failure (AHF) and mortality at 1 year in a large cohort of patients with HCM across multiple centers in the United States (US). Methods In this retrospective study, using the US cohort of 60 healthcare organizations in the TriNetX database, we included more than 85,000 adult patients with HCM (ICD-10-CM codes I42.1 and I42.2) between 2004 and 2024. Patients were divided according to predetermined cut-offs of different inflammatory biomarkers (C-reactive protein [CRP], &amp;lt;2 mg/L vs. 2-100 mg/L; white blood cells [WBC], &amp;lt; vs. ≥ the median [8x10^3/µL]; neutrophils [Neu], &amp;lt; vs. ≥ the median [5x10^3/µL]). These cohorts were then 1:1 propensity score matched (PSM) for age, sex, and race. We used Kaplan-Meier survival curves to derive cumulative incidence curves (as 1 minus Kaplan-Meier survival estimates) for AHF (ICD-10-CM codes I50.21, I50.23, I50.31, I50.33, I50.41, I50.43) or death, and we compared them with the Log-rank (Mantel-Cox) test. We also derived Hazard Ratios (HR) with 95% Confidence Interval (CI) from Cox regression analysis to compare the outcomes within the groups at 1-year. Results After PSM, patients with HCM and CRP levels between 2-100 mg/L experienced higher rates of the composite outcome (19.6% vs. 12.2%, Log-rank p&amp;lt;0.001; HR 1.67, 95% CI [1.29-2.16]), as well as the separate outcomes of death (14.7% vs. 6.8%, Log-rank p&amp;lt;0.001; HR 2.23, 95% CI [1.68-2.98]) and AHF (10.9% vs. 7.5%, Log-rank p&amp;lt;0.001; HR 1.49, 95% CI [1.07-2.07]), compared to those with CRP &amp;lt;2 mg/L (Table 1)(Figure 1). Similarly, patients with Neu ≥5x10^3/µL reported higher incidences of the composite outcome (20.3% vs. 13.2%, Log-rank p&amp;lt;0.001; HR 1.62, 95% CI [1.55-1.68]) and the separates outcomes, compared to those with Neu &amp;lt;5x10^3/µL (Table 1) (Figure 1). Patients with WBC ≥8x10^3/µL also had increased rates of the composite outcome (19.4% vs. 14.1%, Log-rank p&amp;lt;0.001; HR 1.43, 95% CI [1.38-1.48]) and the separate outcomes, compared to those with WBC &amp;lt;8x10^3/µL (Table 1)(Figure 1). Conclusions In the first large 'real world' analysis of patients with HCM, elevated levels of inflammatory biomarkers were associated with worse outcomes of death and acute heart failure.

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

The association between elevated systemic inflammation response index and long-term mortality in patients with triple-vessel coronary disease

Abstract Background Inflammation is a critical factor in the development of coronary artery disease. The systemic inflammatory response index (SIRI) is a novel biomarker of inflammation. Studies have shown that SIRI is associated with the severity of coronary artery disease. However, there is currently a lack of research on the relationship between SIRI and adverse outcomes in patients with multivessel coronary artery disease. Our study aimed to investigate the correlation between SIRI and long-term mortality risk in patients with triple-vessel coronary disease (TVD) and explore the interaction between SIRI and treatment strategies. Methods After excluding patients with missing data or loss to follow-up, a total of 8559 patients with TVD were included in our study. Based on their SIRI levels during hospitalization, patients were evenly divided into three groups (SIRI-L, SIRI-M, and SIRI-H). All patients received appropriate treatment, including medical therapy alone (MT), percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG). The primary endpoint was all-cause death. SIRI was calculated by the formula: neutrophil counts × monocyte counts / lymphocyte counts. Results During a median follow-up of 6.58 years, a total of 1264 all-cause deaths (14.8%) were recorded. Elevated SIRI was significantly associated with increased mortality rates (11.1%, 14.6%, and 18.6% in the SIRI-L, SIRI-M, and SIRI-H groups, respectively). The risk of all-cause mortality was significantly higher in the SIRI-M and SIRI-H groups compared to the SIRI-L group (adjusted HR: 1.203, 95% CI: 1.037-1.395, p=0.015; adjusted HR: 1.400, 95% CI: 1.212-1.617, p&amp;lt;0.001; respectively). In elderly patients, the relationship between elevated SIRI and the risk of all-cause mortality was more pronounced, while it attenuated in younger patients. Additionally, it is noteworthy that there was an interaction between SIRI and treatment strategy (p=0.037). In patients of the SIRI-L group, there was no significant difference between PCI and CABG treatment. However, in patients of the SIRI-M and SIRI-H groups, CABG shows a significant survival advantage over PCI. Conclusion Evaluating SIRI may help identify high-risk groups among patients with triple-vessel coronary disease and guide the selection of treatment strategies.Kaplan-Meier curves