Mortality Events Research Articles

Radial versus femoral access for rotational atherectomy angioplasty

Abstract Introduction The transfemoral approach (TFA) is a potentially advantageous acess site for complicated and prolonged percutaneous coronary angioplasty like rotational atherectomy (RA). Despite this, there is mounting data that suggests the transradial approach (TRA), an alternative to the TFA acess, is linked to reduced rates of mortality and access site complications. Aim This study was conducted with the aim of providing a quantitative appraisal of clinical outcomes of TRA for patients undergoing RA procedure. Methods In this retrospective study, we analyzed all RA procedures performed from March 2013 to June 2019 at our single center institution. Primary endpoints were procedural success, in-hospital mortality, and major adverse cardiovascular events (MACE) during hospitalization. Results Of the 98 patients undergoing RA, the TRA approach was chosen for 79% patients, and the TFA approach for 21% patients. No significant difference in procedural success rates was observed (94% vs. 91%, p=0.19). The use of RA via TRA correlated with a lower contrast volume (p=0.027) and a decreased post-procedure hospital stay (p=0.005). After multivariate adjustment, TRA demonstrated a noteworthy reduction in in-hospital mortality odds (OR: 0.62; 95% CI: 0.44 to 0.87; p = 0.003), major bleeding (OR: 0.48; 95% CI: 0.33 to 0.70; p < 0.001), MACE (OR: 0.68; 95% CI: 0.51 to 0.89; p = 0.015), and 30-day mortality (OR: 0.68; 95% CI: 0.51 to 0.89; p = 0.015). Conclusions Even though RA is a complex procedure, employing radial access (TRA) might be associated with favorable outcomes. These include a lower contrast volume, shorter hospital stay, and reduced odds of in-hospital mortality, major bleeding, MACE, and 30-day mortality compared to femoral access (TFA).

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<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<0.0001) (Figure 1A). Spearman correlation analysis revealed that plasma PAG levels were positively associated with age (r=0.43, p<0.0001), while a negative association with eGFR was observed (r=-0.51, p<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<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.

Early- and mid-term outcomes following redo aortic surgeries: a retrospective cohort study

BackgroundRedo aortic surgeries are complex procedures known to be associated with increased morbidity and mortality compared to patients who undergo de novo aortic procedures. We aimed to report the survival and outcomes following redo aortic surgeries in our centre. We performed a retrospective cohort study of 77 patients who underwent redo aortic surgery between January 1st, 2018, and August 30th, 2023. The primary outcome of interest was operative mortality. Other secondary outcomes of interest included overall mortality, survival rates, and other peri-operative major adverse events. Survival analysis was performed and Cox- proportional hazard regression models were fitted to explore the relationship between exposure variables and outcomes of interest in the total cohort of patients.ResultsThe mean age of the total cohort was 64.22 ± 12.22 years with majority being males (n = 57, 69.3%). The most common indication for redo surgery was aortic aneurysm (n = 41, 53.2%) and majority of the patients had a first redo aortic surgery (n = 69, 89.6%). The rate of freedom from in-hospital mortality was 63.1% (95% confidence interval (CI) 35.4–100%). Overall survival rate during the 5-year study period was 73.1% (95% CI 62.6–85.4%) in the whole cohort. The factors found to be predictive of overall mortality were priority of surgery hazard ratio (HR) 3.48 (95% CI 1.20–10.05, p = 0.02), time to re-operation HR 0.89 (95% CI 0.81–0.99, p = 0.025), pre-operative chronic kidney disease HR 3.16 (95% CI 1.18–8.43, p = 0.022), need for mechanical circulatory support HR 12.7 (95% CI 4.23–38.12, P < 0.001), post-operative renal dysfunction requiring hemofiltration HR 4.03 (95% CI 1.50–10.79, p = 0.006), and post-op re-exploration HR 47.82 (95% CI 13.9–164.4, p < 0.001).ConclusionsOur study shows that short-term and mid-term outcomes following redo aortic surgery are favourable. The factors found to be associated with overall mortality include post-op re-exploration, renal dysfunction, use of post-op mechanical circulatory support, priority of surgery, and time to re-operation.Graphical Summary of outcomes following redo aortic surgery over a 5-year period (2018–2013). CI, confidence interval; HR, hazard ratio; CKD, chronic kidney disease, AKI, acute kidney injury, MCS, mechanical circulatory support.

The impact of daily step count with mobile health apps on clinical outcomes among general population

Abstract Background/Introduction Numerous studies have investigated the correlation between daily step count and the reduction of all-cause mortality and cardiovascular events. However, the optimal daily step count for the general population remains controversial. Purpose This study aims to assess cardiovascular risk based on individual step counts using a large cohort that includes step count data from mHealth Apps (Kencom), health checkups databases, and Japanese insurance claims databases. Methods We analyzed data from 85,204 users registered with Kencom between January 2016 and September 2021. The mean step count during one year before and after baseline data collection was used to define each individual's step count. We divided participants into low (N=45,539) and high (N=39,665) step count groups based on their mean step counts. Additionally, we categorized users into five groups based on their step counts (&amp;lt;4000; 4000-5999; 6000-7999; 8000-9999; and ≥10000) to evaluate cardiovascular events. The primary outcome was the occurrence of cardiovascular events, including myocardial infarction, stroke, angina pectoris, heart failure, and atrial fibrillation, as classified by the International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10). The cumulative incidence was estimated over 5 years. Results The high step count group was generally younger and predominantly male. No significant differences in cardiovascular risk factors such as hypertension, dyslipidemia, diabetes mellitus, and current smoking status were found between the two groups. Stratifying baseline characteristics by step count revealed significant differences among the five groups, with the exception of sex. The cumulative incidence of cardiovascular events was significantly lower in the high step count group compared to the low step count group (6.5% vs. 7.5%, log-rank P=0.005, Figure 1). After adjusting for confounding factors, the risk reduction of the high step count group remained significant (HR: 0.92, 95% CI: 0.87-0.98, P=0.005). Among the five step count groups, the incidence of primary outcome significantly differed, with only Group 5 (≥10000 steps) showing a significant reduction in the risk of cardiovascular events compared to Group 1 (&amp;lt;4000 steps) after adjustment (HR: 0.87, 95% CI: 0.77-0.99, P=0.03). Subgroup analyses based on sex indicated that the risk reduction was significant in males in Group 5 but not in females. Conclusion The risk of cardiovascular events was higher in the low step count group compared to the high step count group. After adjusting for confounders, only the highest step count group (≥10,000 steps/day) showed a significant reduction in cardiovascular event risk compared to the lowest step count group.

Systemic inflammation and risk of death in patients with atherosclerotic cardiovascular disease and chronic kidney disease

Abstract Background Atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease stage 3 - 4 (CKD) affects 7% and 10% of the Danish population, respectively. Systemic inflammation (SI) contributes to destabilisation of atherosclerotic plaques and is characterized by elevated levels of C-reactive protein (CRP) in the blood. CKD is associated with SI and is independently associated with an increased risk of ASCVD. CRP levels ≥2 mg/L have been identified as a risk factor for mortality and major adverse cardiovascular events (MACE). Purpose To provide real-world evidence on the clinical burden of SI in patients diagnosed with ASCVD and CKD, using national health registers. Method Data from the Danish National Patient Registry from 1994-2022 was used to identify ASCVD patients by ICD-10 codes. CKD was identified by eGFR test results in the range [15 -59mL/min/1.73m2], in the Register of Laboratory Results for Research (RLRR). The latter diagnosis of ASCVD and CKD was set as index date. CRP-test results were extracted from RLRR and only individuals with at least two CRP tests were included. If two CRP-test results ≥2mg/L to &amp;lt; 20mg/L were observed less than six month apart, and within two years of index date, the individual was classified to have SI. The eGFR data from RLRR was available from 2011 onwards, with some regional differences in reporting. Individuals observed with CKD or ASCVD in the first year of eGFR availability were excluded to ensure a study of incident individuals. Individuals using select medications or diagnosed with selected chronic conditions thought to influence CRP levels were excluded. Additional population characteristics were extracted from corresponding national health and administrative registers. Hazard of all-cause mortality and MACE was analysed in a Cox proportional risk regression. Results From 2012 to 2022, a total of 19,162 individuals were eligible for the study population (SI: 13,039, No SI: 6,123). Median follow-up time was 4.1 and 8.2 years for individuals with or without SI, respectively. Median CRP two years before and after index date in the two groups was 7mg/L and 1mg/L. No clinically significant differences were found for demographic or socioeconomic characteristics. Patients with SI had more frequent history of hypertension, atrial fibrillation, COPD, heart failure and Type 2 diabetes before index, and higher risk of hypertension, atrial fibrillation, stroke, heart failure and type 2 diabetes after index. SI population had significantly increased hazard of mortality in a crude model (HR: 2.35, 95% CI: [2.22 – 2.50]), and in adjusted analysis HR: 2.06 ([1.92 - 2.21]). The corresponding hazard ratios for MACE were 1.9 ([1.81 – 2.01]) and 1.66 ([1.57 – 1.77]). The results were consistent across different model specifications and subgroups. Conclusion SI is associated with a significantly higher clinical burden of disease and a higher risk of all-cause mortality.Flowchart of inclusion/exclusionHazard ratio, overall and by subgroup

Diabetes mellitus and adverse clinical events in patients with atrial fibrillation: implications of insulin treatment: a report from the GLORIA-AF Registry Phase III

Abstract Background Atrial Fibrillation (AF) and diabetes mellitus (DM) are both associated with adverse clinical events, but the associations has not been fully elucidated, especially in relation to insulin use. Purpose To analyze the associations between DM and the risk of clinical adverse events in patients with AF, and second, explore the impact of insulin treatment in these patients. Methods We studied patients with AF from the prospective Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry with 3-years follow-up. Clinical events included all-cause death, major bleeding, myocardial infarction (MI), stroke, thromboembolism (TE), and major adverse cardiovascular events (MACE). MACE was defined as a composite of stroke, MI and major bleeding. Kaplan-Meier curves were used to estimate the cumulative incidence of clinical events. Multivariable cox regression models with subgroups were used to estimate the association between DM and the risk of mortality and clinical events. Results A total of 15,861 AF patients were included (mean age 70.00 ± 10,21 years old; 55% male, 20% Asia), of which 3,666 had DM (mean age 70.04 ± 9.54 years old; 59% male, 21% Asia). Kaplan-Meier curves showed that AF patients with DM had higher cumulative hazard of all outcomes, including all-cause death (OR: 1.56, 95%CI: 1.38-1.77), CVD (OR: 1.72, 95%CI: 1.44-2.06), major bleeding (OR: 1.4, 95%CI: 1.17-1.67), stroke (OR: 1.29, 95%CI: 1.04-1.61), TE (OR: 1.26, 95%CI:1.02-1.56), MI (OR: 1.88, 95%CI: 1.48-2.39) and MACE (OR: 1.61, 95%CI: 1.41-1.84). After adjustment by prior disease and drugs, the outcomes of stroke (OR: 1.19, 95%CI: 0.95-1.49) and TE (OR: 1.22, 95%CI: 0.98-1.52) showed not significant. Subgroup analysis found that increased risks of stroke were found in female (OR: 1.43, 95%CI: 1.03-1.98, Pinteraction = 0.062) and non-Asian patients (OR: 1.39, 95%CI: 1.06-1.82, Pinteraction = 0.175) with DM. For all cause death, subgroup results were similar with overall patients. In addition, insulin use increased the risk of all cause death (OR: 1.82, 95%CI: 1.45-2.29), CVD (OR: 1.70, 95%CI: 1.22-2.37), major bleeding (OR: 1.54, 95%CI: 1.08-2.18), MI (OR: 1.72, 95%CI: 1.12-2.64), MACE (OR: 1.65, 95%CI: 1.28-2.11) in patients with AF and DM. Multivariable model showed similar result. Conclusions DM was independently associated with higher risk of all-cause death, CVD, MI, major bleeding, and MACE in patients with AF. Insulin use was associated with higher risk of all-cause death, CVD, MI, major bleeding, and MACE in patients with AF and DM.Figure 1Figure 2

The safety and efficacy of treprostinil for the treatment of pulmonary arterial hypertension: a systematic review and meta-analysis of randomized controlled trials

Abstract Introduction Pulmonary arterial hypertension (PAH) is a severe and life-threatening condition characterized by increased pulmonary vascular resistance and elevated mean pulmonary artery pressure. Treprostinil, a prostacyclin analog, has vasodilatory and anti-remodeling effects on pulmonary arterial smooth muscle cells, indicating promising benefits in enhancing exercise capacity, improving hemodynamics, and reducing morbidity in patients with PAH. Aim The primary objective of this systematic review and Meta-analysis is to assess the efficacy and safety of Treprostinil in patients with PAH. Methods We systematically searched PubMed, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov from inception until July 2023. Randomized controlled trials comparing Treprostinil with Placebo were selected. We used the mean values to compare continuous data and odds ratio (OR) for dichotomous outcomes with their 95% confidence interval (CI). Results We included 7 studies with a total of 2,447 patients. The Treprostinil group was favored over the control group in terms of 6-minute walk distance (6MWD) (Mean difference (MD), meters (m)) (MD = 15.16 m, 95% confidence interval (CI) (10.42 – 19.90 )). Subgroup analysis based on the route of administration revealed a 6MWD of (MD = 13.55 m (95% CI (7.82 – 19.28)) for oral administration and (MD = 17.49 m, 95% CI (6.01 – 28.89)) for intravenous (IV)/subcutaneous (SC) administration, indicating enhanced exercise capacity. When evaluating the efficacy of Treprostinil for oral administration, there was a slight but non-significant trend toward functional improvement (Odds Ratio (OR): 1.36; 95% CI: 0.95 to 1.93) and no significant change in maintaining functional status (OR: 0.94; 95% CI: 0.59 to 1.51). In terms of functional deterioration, the risk was also not significantly reduced (OR: 0.84; 95% CI: 0.36 to 1.98). Safety assessment of the drug was based on clinical, mortality, and adverse events outcomes. Clinically, Treprostinil demonstrated a protective effect against disease progression, evidenced by a reduced risk of clinical worsening (OR: 0.69; 95% CI: 0.52 to 0.91). Mortality rates were not significantly impacted by Treprostinil addition (OR: 0.95; 95% CI: 0.57 to 1.58 for oral, 0.80; 95% CI: 0.32 to 1.98 for IV/SC). However, the incidence of adverse events was notably higher among Treprostinil-treated patients, particularly with oral administration. Conclusion The addition of Treprostinil therapy for patients with PAH significantly improved exercise capacity, as evidenced by an increase in the 6MWD compared to control groups and demonstrated a reduced risk of clinical worsening. The incidence of adverse events was higher among Treprostinil-treated patients, especially with oral administration, potentially impacting quality of life.Forest plot of the 6MWD

AI-enhanced detection of coronary inflammation predicts 10-year risk for cardiac mortality and MACE in individuals with no or minimal coronary atherosclerosis on routine CCTA

Abstract Background Coronary CT angiogram (CCTA) is one of the first line investigations for patients with chest pain suspected of coronary artery disease (CAD). Current CCTA interpretations mainly focus on luminal obstruction, which is identified in the minority of patients, whereas the majority who have no or minimal atherosclerotic plaques visible on CCTA are often provided with reassurance. However, residual risk from inflammation that drives atherosclerosis and plaque vulnerability are not captured with luminal stenoses alone. Fat attenuation index (FAI) Score quantifies coronary inflammation on routine CCTA, and integrate with clinical risk factors/plaque burden in an artificial intelligence enabled risk algorithm (AI-Risk) that could help to risk stratify this patient group. Purpose To evaluate the prognostic value or FAI Score and AI-Risk in the risk stratification of patients with no or minimal atherosclerosis. Methods In a nested cohort within the Oxford Risk Factors and Non-invasive imaging (ORFAN) study, consecutive patients (n=3,393) who underwent routine clinical CCTA were followed up over a median(IQR) 7.7(6.4-9.1) years for cardiac mortality and major adverse cardiac events (MACE, including myocardial infarction, new onset heart failure, cardiac mortality). CADRADS 2.0 classification 0 or 1 were used to define no or minimal luminal stenoses. FAI Score was calculated for each of the 3 epicardial coronary arteries. Results A total of 1,678 patients had no or minimal atherosclerosis on CCTA [median (IQR) age 53(45-63), 49.8% male]. Cardiac mortality occurred in 3.1% and MACE occurred in 8.8% of the patients during the follow-up period. Patients at the lowest quartile of FAI Score or low/medium AI-Risk classification showed very low event rate during follow up. Patients with the highest quartile of LAD FAI Score showed 9 times higher risk of cardiac mortality (Panel A) and 5 times higher risk of MACE (Panel B) compared to those at lowest quartile. Similar findings were observed for LCX and RCA. Finally, integrating coronary inflammation with clinical risk factors and plaque burden, patients at very high AI-Risk classification showed 5 times higher risk of cardiac mortality (Panel C), and 4 times higher risk of MACE (Panel D) compared to those with low/medium risk classification. Conclusion Coronary artery inflammation measured by FAI Score could stratify the risk of patients with no or minimal coronary atherosclerosis on CCTA, and could help to guide early preventative treatments.

High-Sensitivity Troponin-T and heart failure risk in individuals with suspected acute coronary syndrome

Abstract Background In individuals with suspected acute coronary syndrome (ACS), serial assessments of high-sensitivity cardiac troponin-T (hsTnT) levels demonstrate associations with both short- and long-term mortality and recurrent ischemic events. Nonetheless, the relationship with subsequent heart failure remains inadequately characterized. Purpose We investigated the association between single and serial hsTnT levels and subsequent hospitalization or outpatient medical encounters related to heart failure in individuals presenting with suspected ACS. Methods Utilizing Danish national registries from 2012 to 2019, we identified individuals without known heart failure who underwent dual hsTnT assessments ( 99th percentile upper reference limit: 13.5 ng/l), spaced 1-7 hours apart during hospitalization for myocardial infarction (MI), unstable angina, observation for suspected MI, or chest pain. Participants were categorized based on their hsTnT concentration patterns from the first to the second measurement (primary groups: normal, rising, persistently elevated, or falling) and the extent of hsTnT concentration alterations (secondary groups: &amp;lt;20%, &amp;gt;20 to 50%, or &amp;gt;50% in either direction). Additionally, they were grouped into quartiles based on the initial hsTnT measurement (&amp;lt;=9 ng/l, 10-15 ng/l, 16-66 ng/l, &amp;gt;=67 ng/l) to assess whether heightened hsTnT concentrations correlated with an increased risk of heart failure. Standardized risks of hospitalization or outpatient contacts for heart failure were computed using multivariable logistic regression with average treatment effect modeling. Results The study encompassed 26,835 individuals, of whom 38.9% received discharge diagnoses of MI, 5.1% were diagnosed with unstable angina, and 56.1% with observation for suspected MI or chest pain. Median age was 64.2 years, with 59.5% males. Prevalence of known cardiovascular disease included coronary disease in 18.1% of cases, prior revascularization in 7.2%, atrial fibrillation or flutter in 7.9%, and a history of stroke in 6.3%. Within the initial 30 days, 628 persons received a heart failure diagnosis, with an additional 960 diagnosed between days 31-365. Subjects displaying two normal hsTnT values exhibited the lowest standardized absolute risk (0.39% in days 0-30; 0.58% in days 31-365), while those with persistently elevated concentrations demonstrated the highest risk (6.45% in days 0-30; 7.05% in days 31-365) (Figure). Notably, the magnitude of hsTnT within each primary group did not affect heart failure risk. Conversely, heart failure risk exhibited a positive association with hsTnT concentrations measured in the initial sample. Conclusions In individuals presenting with suspected ACS, subjects with a sustained elevation in hsTnT levels showed the highest risk of subsequent heart failure events. Moreover, a dose-response association was observed between hsTnT concentrations and heart failure risk.Figure

Tafamidis treatment for transthyretin amyloid cardiomyopathy: results from an open-label, early-access, long-term study extension in an all-comers population

Abstract Background In the pivotal Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT NCT01994889), tafamidis significantly reduced mortality and cardiovascular hospitalization in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Given the high clinical unmet need and the favorable benefit-to-risk profile of tafamidis, there was a justification to provide patients with an option for early access to treatment as part of the ATTR-ACT long-term extension study (LTE; NCT02791230). Purpose To assess long-term safety in an all-comers population receiving early access to tafamidis. Methods Following protocol amendment (20 July 2018), patients with ATTR-CM, not previously enrolled in ATTR-ACT, and without commercial access to tafamidis, were enrolled in the LTE early-access study arm in 13 countries. Patients received open-label, once-daily tafamidis free acid 61 mg for up to 60 months, until they gained product access by prescription or study discontinuation by the sponsor. All-cause and cardiovascular (CV)-related mortality, CV-related hospitalization, and treatment-emergent adverse events (TEAEs) were assessed. Results Of 1481 patients enrolled in the early-access cohort, 1476 received at least one dose of tafamidis and were included in the analysis. Mean (SD) age at enrollment was 76.5 (7.8) years old, 37.5% were ≥80 years old, and 88.8% were male. Most patients (85.6%) had wild-type ATTR-CM, and 14.9%, 52.9%, 30.8%, and 1.3% were in New York Heart Association (NYHA) Class I, II, III, and IV, respectively. Over a mean (SD) follow-up period of 17.7 (13.8) months, all-cause and CV-related mortality rates were 23.4% and 13.8%, respectively (Table). Mean frequency of CV-related hospitalization per year was 0.28 (0.60). Serious TEAEs and TEAEs leading to discontinuation of the study were observed in 0.6% of patients (both); no new safety signals were identified. Conclusions Findings from the early-access cohort of the ATTR-ACT LTE highlight the safety of tafamidis treatment in an all-comers ATTR-CM patient population.

Ten-year outcomes in patients with hypertension and primary hyperaldosteronism undergoing surgical adrenalectomy versus medical therapy: data from the multinational collaborative network TriNetX

Abstract Background Surgical adrenalectomy for resection of adenomas has been the standard approach for treating patients with secondary hypertension due to primary hyperaldosteronism. However, few studies explored long-term outcomes in patients treated with adrenalectomy when compared to patients treated with conservative management. Purpose To compare ten-year mortality and cardiovascular outcomes in patients with primary hyperaldosteronism treated with surgical adrenalectomy versus patients with primary hyperaldosteronism treated with medical therapy alone. Methods This retrospective cohort study used real-world data from healthcare organizations participating in the global health research collaborative network TriNetX. We performed propensity score matching for demographic and clinical characteristics and calculated hazard ratios, comparing 2.397 patients in each group. The outcomes were all-cause death, heart failure, and the composite endpoint ischemic stroke, hemorrhagic stroke, myocardial infarction, unstable angina, and aorta aneurysm or dissection (major adverse vascular events) during the 10-year follow-up. Results Patients undergoing surgical adrenalectomy had a lower incidence of all-cause death (3.0%) when compared with patients in medical therapy (5.0%) ( hazard ratio 0.60, 95% CI 0.45-0.81). Patients in the surgical group had a 4.6% incidence of heart failure and the medical therapy had an 8.6% incidence of heart failure (hazard ratio 0.54, 95% CI 0.42-0.69). The incidence of major adverse vascular events was lower in the surgical group (10.9%) compared to the medical therapy group (14. 1%) ( hazard ratio 0.76, 95% CI 0.65-0.90). Conclusion In patients with hypertension and primary hyperaldosteronism, surgical adrenalectomy was associated with lower 10-year mortality, heart failure, and major adverse vascular events compared to medical therapy alone.

Growth differentiation factor-15 and 5-years cardiovascular risk in chest pain patients presenting to the emergency department: a multicenter cohort study

Abstract Background Growth differentiation factor 15 (GDF-15) has been explored as a prognostic biomarker in multiple disease entities, including ischemic heart disease and heart failure (HF), but its role as a prognostic marker in chest pain patients presenting to the emergency department (ED) is unknown. Purpose To investigate the association between GDF-15 and 5-year all-cause mortality, cardiovascular mortality, and major adverse cardiac events (MACE), and to evaluate its prognostic incremental value. Methods Patients presenting to the ED with acute chest pain were prospectively enrolled in an international multicenter diagnostic study. GDF-15 concentrations were measured in a blinded fashion upon ED presentation. Follow-ups were performed at 3 months, 1-, 2- and 5-years. MACE was defined as the composite of cardiovascular mortality, acute myocardial infarction, stroke, and HF rehospitalization. Associations between GDF-15 and each prognostic outcome were modeled using multivariable Cox proportional hazard regression fitting restricted cubic splines to continuous variables. The magnitude of the effect of each GDF-15 unit change on multivariable-adjusted models was assessed graphically using dose-response plots. To compute an HR for the dose-response plots we chose a GDF-15 value of 1200 pg/mL as a reference value as this has been chosen in previous literature1. For the restricted cubic splines three knots were used. The added prognostic value of GDF-15 was evaluated by the increase in the C-statistic between a base and an extended model and the fraction of new information (FNI) provided by GDF-15. Results A total of 4779 chest pain patients had baseline GDF-15 values available. The median age was 61 [48-74] and 33% were female. Higher GDF-15 levels were more strongly associated with heart failure, kidney dysfunction, older age, hypertension, diabetes and coronary artery disease. GDF-15 was independently associated with 5-years all-cause mortality, cardiovascular mortality and MACE (Figure). When adding GDF-15 to a rich-for-prior-information base model which included age, sex, cardiovascular risk factors, creatinine, cardiac troponin and NT-proBNP, GDF-15 provided relevant incremental prognostic discrimination for 5-years all-cause death and cardiovascular death. (Table). Conclusions In chest pain patients presenting to the emergency department, GDF-15 concentration on admission was associated with 5-years all-cause mortality, cardiovascular mortality, and MACE. In addition, it provided relevant incremental prognostic information when added on top of troponin and NT-proBNP, the two current prognostic gold standard biomarkers.FigureTable

Real-life impact of complete revascularization of non-ST elevation myocardial infarction during index hospitalization

Abstract Introduction patients with non-ST elevation acute myocardial infarction (NSTEMI) frequently present multivessel disease (MVD) with significant stenosis in non-infarct-related arteries (non-IRA). Unlike for ST elevation acute myocardial infarction, there is a paucity of studies evaluating the prognostic impact of complete revascularization in these patients. In fact, recommendation for complete revascularization is based in observational and non-randomized studies suggesting a possible benefit regarding mortality and major cardiovascular events. Purpose to evaluate the prognostic impact of complete revascularization during the index hospitalization in the Portuguese patients with NSTEMI and MVD. Methods patients hospitalized for NSTEMI with MVD included in a national multicentre retrospective study between October 2010 and December 2022 were divided into two groups: group 1 was submitted to complete percutaneous revascularization during the index hospitalization (IRA and non-IRA with diameter stenosis ≥50% on angiography), and group 2 performed IRA-only revascularization. The impact of complete revascularization on the probability of cardiovascular re-hospitalization, as well as on in-hospital and one-year mortality rates was evaluated. Results a total of 3084 patients was included, 74.8% were males, with a mean age of 67.8±11.9 years. Most patients were submitted to IRA-only revascularization (72.9%). From the remaining, 81.4% performed complete revascularization during the index procedure and 18.6% staged during index hospitalization. Group 1 patients were younger (65.5±11.8 vs. 68.6±11.8 years, p&amp;lt;0.001), with fewer comorbidities and slightly higher left ventricular ejection fraction (55±11 vs. 51±11%, p&amp;lt;0.001). On the other hand, group 2 patients revealed a significantly higher percentage of previous, revascularization (14.8% vs. 1.6%), mostly surgical. Besides overall similar incidence of in-hospital complications, including recurrence of acute myocardial infarction, patients submitted to complete revascularization showed a non-significant trend to an inferior in-hospital mortality rate (0.7 vs. 1.6%, p=0.06). Also, 1-year mortality rate was similar between groups (4.2 vs. 5.0%, p=0.54). However, complete revascularization appeared to result in a long-term prognostic benefit, halving the incidence of unplanned cardiovascular re-hospitalizations at one year of follow-up (9.3 vs. 18.8%, p&amp;lt;0.001). Conclusion complete revascularization led to an overall long-term benefit, mainly due to a reduction in cardiovascular re-hospitalizations, without a significant impact on 1-year mortality rate.

Effect of triglycerides on cardiovascular risk in patients with a first vs. recurrent acute coronary syndrome

Abstract Background Triglyceride (TG) levels have gained increasing interest in the prevention of cardiovascular disease although there is divergent evidence that might be explained by confounding factors. Methods We performed a multicenter and retrospective study using the ongoing registries of acute coronary syndrome (ACS) patients of 7 hospitals from Spain. TG were measured during the hospitalization, and mortality and major adverse cardiovascular events (MACE) were analyzed through follow-up. Results We included 14,483 patients discharged after an ACS, mean age 67.5 (13.3), 28.1% women, and 30.4% with an ST-elevation ACS; 2,378 (16.4%) patients had a previous ACS and were classified as recurrent ACS. Median triglyceride level was 120.5 (interquartile range [IQRS] 90-197) mg/dL and was slightly higher in patients with recurrent ACS (135 IQR 98-186 vs. 129 IQR 95-175; p&amp;lt;0.01). Patients with first vs. recurrent ACS received ticagrelor or prasugrel more frequently at discharge (14.8% vs. 7.4%; p&amp;lt;0.01), but no other differences in medical treatments were observed. Median follow-up was 1223 (interquartile range 570-2040) days. All-cause mortality was 15.0% (n= 2,166), and 34.71% (n=5,019) of the patients experienced a first MACE during follow-up. Patients with recurrent ACS had higher mortality (32.9% vs. 11.4%; p&amp;lt;0.01) and MACE (46.5% vs. 32.4%; p&amp;lt;0.01) rates. Multivariate analysis, adjusted for age, sex, diabetes, previous heart failure, and medical treatments at discharge showed that TG levels were not associated with higher risk of mortality (p=0.29) but with higher risk of MACE (p=0.04). A significant interaction (p=0.01) was observed for TG and previous ACS for both endpoints and, therefore, analyses were performed separately (Figure 1). As shown in Figure 2, TG were associated with higher risk of death in patients with first ACS (p=0.02) but not in patients with recurrent ACS (p=0.48); in contrast, TG were associated with higher risk of MACE (p=0.024) in patients with a recurrent ACS but not in patients with a first ACS (p=0.25). Conclusions Previous ACS modifies the risk of TG on mortality and MACE in patients discharged after an ACS. TG might be considered a target for treatment in patients after a first or recurrent ACS, although the exact impact on outcomes might be different.

Outcomes of post-acute coronary syndrome patients enrolled in a phase 2 cardiac rehabilitation program

Abstract Introduction Cardiac rehabilitation (CR) is a class I recommendation in the management of patients with acute coronary syndrome (ACS), namely ST-elevation myocardial infarction (STEMI) and non-ST acute coronary syndrome (NST-ACS). Reported mortality and recurrent cardiovascular (CV) events are still unacceptably high in these patients. Purpose To assess CV outcomes of patients enrolled in a CR program and its association with ACS presentation. Methods Single-center, retrospective observational study that included all consecutive post-ACS patients enrolled in a phase 2 CR program in 2017, with a follow-up of 24 months. Group 1 were patients with STEMI; group 2 were patients with NST-ACS. Major adverse cardiovascular events (MACE) were defined as a composite of death, non-fatal ACS, non-fatal stroke, and unplanned revascularization. Results Of the 202 ACS patients who attended the CR program in 2017, 4 were excluded due to missing data. Of the 198 patients analyzed (age 60.3±10.7 years, 82% male), 101 patients had a STEMI and 97 NST-ACS. STEMI patients were significantly younger (57±9.5 vs. 63±10, p&amp;lt;0.001), with fewer CV risk factors (diabetes 16% vs. 32%, p=0.008; hypertension 51% vs. 72%, p=0.002; obesity 17% vs. 31%, p=0.020; dyslipidemia 54% vs. 77%, p&amp;lt;0.001), except for active smoking (53% vs. 29%, p=0.001), and were less likely to have previous history of coronary artery disease (9% vs. 31%, p&amp;lt;0.001). During the 3-month CR program, both groups achieved significant reduction in body mass index, LDL-Cholesterol, functional capacity, and smoking cessation rates. At 3-, 12-, and 24-months evaluation, both groups showed no differences in risk factor management, nor differences in lipid-lowering therapy, namely percentage of high-intensity statin and ezetimibe use. STEMI patients were treated more frequently with ticagrelor (86% vs. 67%, p=0.001) at baseline. MACE occurrence was significantly lower in STEMI patients (11% vs. 28%, p=0.003), driven mainly by recurrent ACS (4% vs. 15%, p=0.006). Conclusions In our study, NST-ACS patients had significantly higher CV disease burden and worse outcomes at 24-month follow-up. Despite the heightened CV risk in this group, secondary prevention treatment intensity was similar in both groups.

1-year outcomes of patients presenting with acute coronary syndromes in Western Cape, South Africa: findings from the PERFUSION ACS registry

Abstract Background Cardiovascular disease(CVD), particularly acute myocardial infarction(MI), has emerged as a public health challenge in South Africa(SA), however, there is a paucity of data regarding long-term clinical outcomes such as CVD mortality, heart failure, stroke and recurrence of MI in this region. Purpose To determine 1-year major adverse cardiac outcomes among individuals discharged alive following admission for troponin-positive Acute Coronary Syndromes(ACS) in Western Cape, SA. Methods Between February 2021 and May 2022, 838 adults(≥18 years) with a diagnosis of ACS were prospectively enrolled into the investigator-initiated, multi-center PrEsentation, Rationale, and impact of reperFUSION for Acute Coronary Syndromes (PERFUSION ACS) registry. Participants were enrolled at a tertiary-care referral center and four secondary-level healthcare facilities. Key data elements were measured at index admission, including baseline demographics, risk factors, clinical presentation, complications, laboratory tests, revascularization strategies, and discharge medication. Survivors at discharge provided consent for 30-day and 12-month telephonic evaluations for major adverse cardiovascular events(MACE), which were captured on a web-based system that was centrally managed and analyzed. Results Of 838 participants, 39% were female, one-third were &amp;lt;55 years of age, 76% had a history of smoking, 74% had hypertension, 58% had dyslipidemia, and 56% were obese. STEMI accounted for 51% of cases, with NSTEMI in 49%. Baseline data for the cohort, stratified into two categories of MI, are provided in Table 1. Median duration from symptom onset to hospital presentation was 10.42 (±15.26) hours, with a majority(80%) presenting first to a non-PCI-capable facility. Among STEMI cases, two-thirds received thrombolysis(65%), primarily with Streptokinase; 49% underwent angiography via a pharmacoinvasive strategy, and 3% received primary percutaneous coronary intervention(PCI). Overall, 57% of patients with NSTEMI were treated with an invasive approach. The one-year all-cause mortality was 21%, with 88% attributable to cardiovascular disease-related death. Cumulative MACE rate at one year was 57%. Event rates for the individual MACE components were 32% for heart failure, 19% for non-fatal MI, and 6% for non-fatal stroke. 6% of participants died in-hospital, while 30-day mortality was 9%. There were no significant differences in all-cause mortality between STEMI and NSTEMI at 1 year. Conclusion Troponin-positive ACS are associated with a high rate of 12-month mortality and non-fatal major adverse cardiac events in Western Cape, SA. The concerning registry findings emphasize the need to prioritize ischemic heart disease prevention and management, and highlight important gaps in care which can serve as targets for improvement throughout the country.PERFUSION: Table 1PERFUSION: All-cause mortality and MACE

Right atrial and ventricular function in risk stratification of patients with pulmonary artery hypertension

Abstract Background Right atrial (RA) phasic function was proved to be impaired in individuals with pulmonary arterial hypertension (PAH), the awareness of the nonnegligible involvement of RA in the clinical course of PAH was raised. However, evidence for the clinical significance of the RA strain in prognostication and risk stratification for PAH patients was limited. Method Participants diagnosed with PAH from June 2013 to December 2022 in West China Hospital were prospectively and continuously recruited. The primary endpoint was all-cause mortality, and the second endpoint was a combination of all-cause mortality and heart failure-related repeat hospitalization. Cox regression analysis and Kaplan Meier survival analysis were performed to identify the association between variables and outcomes. C-index, 1-year mortality, and annual event rate were performed to confirm the value of RA strain in PAH patients’ risk stratification. Result A total of 283 participants (mean age, 38 ± 14 years, 84 male) were finally included, following a median follow-up duration of 31.5 months (interquartile range: 15.1-53.9 months). Significant decreases in RA reservoir (p&amp;lt;.001), conduit (p&amp;lt;.001), booster pump function (p&amp;lt;.001), right ventricular global longitudinal strain (RVGLS, p&amp;lt;.001), and free-wall longitudinal strain (RV-FWLS, p&amp;lt;.001) were observed in participants with all-cause mortality than those who survived. Using 16.1% and 23.6% as thresholds for RA reservoir strain, PAH patients could be divided into low-, intermediate, and high-risk groups well, with calculated 1-year mortality of 1.8%, 6.9%, and 21.4%. Moreover, RA reservoir strain presented with better 1-year mortality predictive performance than RV-FWLS (C-index, 0.82 [0.72-0.92] vs 0.72 [0.62-0.82], p&amp;lt;.001). The addition of RA reservoir strain had significantly increased the power of both REVEAL Lite2 and Comparative, Prospective Registry of Newly initiated Therapies for Pulmonary Hypertension (COMPERA) models (both p&amp;lt;.001). Conclusion RA reservoir strain was an independent predictor of all-cause mortality in individuals with pulmonary arterial hypertension and could be used to stratify participants into different risk stratification stratum.

Study of lipoprotein(a) and its impact on atherosclerotic cardiovascular disease: design, rationale, and first results of the Zabrze-Lip(a)R Registry

Abstract Aims Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease. Increased Lp(a) concentration &amp;gt;30 mg/dl may cause faster atherosclerosis. There is a need to characterize further the clinical phenotypes in patients at risk for ASVD with high Lp(a) levels. Material The Zabrze-Lip(a)R Registry was created on the basis of data from 2,001 patients with high- and very high cardiovascular risk treated in a tertiary hospital, and the Registry patients will be followed for many years. Mortality and cardiovascular events, such as known death, MI, and stroke, will be assessed. Results The median Lp(a) concentration in the entire population was 6.6 mg/dl (mean 14.3 ± 19.4 mg/dl). Preliminary results of the study group showed that 540 (27%) patients had elevated Lp(a) levels above 30 mg/dl, mainly in patients with established ASCVD after MI and/or coronary revascularization. Patients with elevated Lp(a) levels are older and have higher hematocrit and NT-proBNP and CRP levels. Conclusions Extensive observational studies are essential for further work that objectively collects information on the risks associated with Lp(a) values and cardiovascular disease. Additionally, developing a deeper understanding of the impact of Lp(a) on prognosis will be valuable in how Lp(a) interacts with other established risk factors in improving cardiovascular risk prediction.Distribution of Lp(a) concentrationsComparison of pts with different Lp(a)

Paracetamol and adverse cardiovascular outcomes in patients with heart failure

Abstract Background Paracetamol is the most widely used pain killer worldwide, yet its potential influence on cardiovascular events among patients with heart failure (HF) remains unclear. Thus, this study aims to investigate both the short-term and long-term effects of paracetamol use on all-cause mortality and cardiovascular events in HF patients. Methods Using the previously validated territory-wide clinical information registry, paracetamol use was identified among all eligible patients with HF (N = 211,409) from 2000 to 2020. A case-crossover design was used to investigate the associations between short-term use of paracetamols and all-cause mortality and cardiovascular outcomes. Defined daily dose (DDD) was used to evaluate the dose-response relationship. Additionally, the marginal structural design was applied to model paracetamol use as a time-varying exposure and evaluate its long-term effects during the follow-up period. Results Of all eligible subjects, the mean age was 73.2±12.3 years, and 43.6% was male. Over a median follow-up of 10.5 years (interquartile range: 5.7-15.8), 113,258 (53.6%) patients were re-hospitalised for HF, HF-related death occurred in 11,892 (5.6%) patients, incident myocardial infarction (MI) in 28223 (13.3%) patients, incident stroke in 26458 (12.5%) patients, cardiovascular death (CVD) in 72,175 (34.1%) patients and all-cause death in 123,505 (58.4%) patients. Associating HF rehospitalisation to previous paracetamol exposure using the case-crossover design displayed an elevated risk (OR 3.62, 95% CI 3.53-3.71). Associations were similar for MI (OR 5.77, 95% CI 5.50-6.05), stroke (OR 2.37, 95% CI 2.25-2.49), HF-related death (OR 1.86, 95% CI 1.75-1.98), CVD (OR 3.64, 95% CI 3.55-3.73), and all-cause mortality (OR 3.32, 95% CI 3.26-3.39). Moreover, compared with paracetamol users taking the reference dose, users of low, medium and high doses of paracetamol had 16%, 17% and 52% higher risk of HF rehospitalisation. During the long-term follow-up, the average weighted hazard ratio (HR) for HF rehospitalisation in paracetamol users was 2.48 (95% CI 2.46–2.50) as compared with paracetamol non-users after accounting for all-cause mortality as a competing risk. Similarly, the average weighted HR for incident MI or stroke was 2.71 (2.62-2.81) and 3.45 (3.34-3.57), respectively. However, neutral results were shown for HF-related death, CVD and all-cause mortality. Conclusion The use of paracetamol among patients with HF is common. Paracetamol was associated with adverse cardiovascular outcomes both in short-term and long-term follow-up with a dose-response relationship, while its impact on long-term mortality remained neutral. Future randomized controlled trials or experimental studies are warranted to gain a comprehensive understanding of the underlying mechanisms driving such associations between paracetamol and adverse cardiovascular outcomes.

Clustering analysis based on clinically available data for improving risk stratification and outcome prediction of hypertension

Abstract Background Hypertension (HTN) is a heterogeneous condition with several factors contributing to adverse outcomes. Machine learning can harness complex data to unveil outcome predictors and guide prevention. Purpose To use clustering analysis on clinical data to identify HTN risk profiles and their associations with cardiovascular abnormalities and clinical outcomes. Methods A cohort of 14,840 UK Biobank hypertensive participants without pre-existing heart failure (HF) who underwent cardiovascular magnetic resonance (CMR) assessment was examined using K-means clustering on 79 clinical attributes. The clusters’ association with incident HF, mortality, atrial fibrillation (AF), and major adverse cardiovascular events (MACE) were evaluated, alongside imaging characteristics, with mediation analysis probing the role of imaging in risk differentiation. All post-hoc analyses were adjusted for vascular risk factors (VRFs), including diabetes, hypercholesterolaemia, previous myocardial infarction. Results Three distinct clusters differing considerably in lifestyle habits, cardiovascular risk factors, electrocardiographic parameters, and cardiometabolic profiles were identified. Cluster 1 (lowest risk), predominantly females, exhibited the most favourable metabolic profile and outcomes. Cluster 2 (highest risk), predominantly males, had the most adverse metabolic and cardiovascular profiles, and the highest risk of all adverse outcomes, especially AF and HF (hazard ratio (HR) 1.80 [1.45–2.25] and 1.85 [1.39–2.46]; p &amp;lt;0.005). This group was associated with more eccentric LV hypertrophy (LVH), overall poorer left atrial emptying function (LAEF), bi-ventricular systolic function and LV mechanics, and higher systemic vascular resistance (Figure 1). Cluster 3 (intermediate risk) was a more heterogeneous group with the highest burden of diabetes and adiposity and a moderate rise in AF and MACE risk (HR 1.61 [1.12-2.32] and 1.30 [1.07-1.58]; p &amp;lt;0.05). This cluster was associated with concentric LV remodelling and better indices of cardiac mechanics, but greater impairment in LA booster pump function (active LAEF) than Cluster 2 (Figure 1). Cluster 2's effect on MACE was mostly mediated through LV mass increase (proportion mediated, 67%), followed by changes (reducing) in LV global longitudinal strain (33%), and ejection fraction (25.4%). The indirect effect of CMR changes in the association between cluster 3 and MACE was much smaller with the highest proportion of the effects mediated through increased myocardial wall thickness (26%) but not LV mass, and changes in all the components of LA function. Conclusions Clinical data clustering provides insight into distinct HTN risk profiles, each with specific imaging characteristics and clinical trajectories, hinting at different pathophysiological mechanisms. Enhanced phenotyping can facilitate tailored interventions based on the disease subtype and improve clinical outcomes.Figure 1.