Adverse Cardiovascular Outcomes In Patients Research Articles

Abstract 4137695: Bundle Branch Block(BBB) is Independently Associated With Adverse Cardiovascular Outcomes in Patients With Heart Failure With Preserved Ejectionfraction(HFPEF): A Propensity Score Matched Analysis

Background: Ventricular dyssynchrony due to BBB can cause adverse cardiovascular(CV) outcomes in HF with reduced EF and is known to occur in HFpEF but its independent impact on is unclear. Objective: To determine if BBB is an independent risk factor for adverse HF outcomes in HFpEF and the impact of atrial fibrillation (AF).. Methods: We studied the impact of BBB in HFpEF utilizing propensity score(PS) matched cohorts without and with BBB from the TOPCAT Americas trial to account for confounding by other co-morbidities. Outcomes analyzed included the TOPCAT primary outcome, CV death&hospitalization (CVH), sudden death, pump failure death (PFD), HF hospitalizations(H), and progression of HF. The impact of concomitant AF ( defined as any AF or AF on ECG) on these outcomes with and without BBB was analyzed. Results: 329 pts with HFpEF&BBB were PS matched for 24 demographic&disease state variables, BNP strata and AF status with a cohort of 329 pts with HFpEF without BBB. BBB was associated with increased risk of the TOPCAT primary outcome (Hazard ratio{HR} 1.44, 95% confidence intervals {CI} 1.10-1.89, p=0.008), increased risk of HF hospitalizations by 41%(HR 1.41 95% CI 1.04-1.91 p=0.0248) but not CVH (HR 1.18, 95% CI 0.93-1.49, p=..169), but not sudden death (HR 1.40, 95% CI 0.70-2.82, p=0.342) or CV death (HR 1.26, 95% CI 0.84-1.89, p=0.257). Risk of pump failure death (PFD) with BBB was significantly higher in HFpEF subjects without a history of AF (Figure left panel .Kaplan Meier Log rank p=0.0478, HR: 4.22, 95% CI: 0.89 to 19.87, p=0.0689) but not in AF (p=0.138). PFD risk was markedly higher in AF subjects without BBB ( Figure right, Kaplan Meier Log rank p=.0012, HR:7.99, 95% CI:1.80 to 35.41,p = 0.0063) than those with BBB (p=0.91) Conclusion: Ventricular dysynchrony induced by BBB independently worsens HFH risk in HFpEF. Its adverse impact on PFD iis seen in the absence of AF. Increase in PFD risk with AF in HFpEF subjects is most prominent in those with normal intraventricular conduction. Mechanical dyssynchrony induced by BBB may have a role in HFpEF subgroups with preserved atrioventricular filling, leading to these adverse HF outcomes

ABLE-SCORE: a simplified risk score for major adverse cardiovascular outcomes in patients with left ventricular noncompaction

Abstract Background Left ventricular noncompaction (LVNC) is a heterogeneous entity with life-threatening complications and variable prognosis [1,2]. However, there are limited prediction models available to identify individuals at high risk of adverse outcomes, and the current risk score in LVNC is comparatively complex for clinical practice [3,4]. Purpose To develop and validate a simplified risk score to predict major adverse cardiovascular events (MACE) in LVNC. Methods This multicenter longitudinal cohort study consecutively enrolled morphologically diagnosed LVNC patients between January 2009 and December 2020 at a single national-level medical center (derivation cohort n=300; internal validation cohort n=129), and between January 2014 and December 2022 at two national-level medical centers (external validation cohort n=95). The derivation/internal validation cohorts and the multicenter external validation cohort were followed annually until December 2022 and December 2023, respectively. MACE was defined as a composite of all-cause mortality, heart transplantation/left ventricular assist device implantation, cardiac resynchronization therapy, malignant ventricular arrhythmia, and thromboembolism. A simplified risk score, the ABLE-SCORE, was developed based on independent risk factors for MACE in the multivariable Cox regression predictive model, and underwent both internal and external validation to confirm its discrimination (Harrell’s C-index), calibration (calibration plots), and clinical applicability (decision curve analysis). Results A total of 524 LVNC patients (43.5 ± 16.6 years, 65.8% male) were included in the study. At the end of the follow-up, 97 (32.3%), 38 (29.5%), and 20 (21.1%) individuals in the derivation, internal validation, and external validation cohort experienced at least one endpoint of MACE. The ABLE-SCORE was established using four easily accessible clinical variables: age at diagnosis, N-terminal pro-brain natriuretic peptide levels, left atrium enlargement and left ventricular ejection fraction≤40% measured by echocardiography. The risk score showed excellent performance in discrimination, with Harrell’s C-index of 0.821 (95%CI 0.772-0.869), 0.786 (95%CI 0.703-0.869), and 0.750 (95%CI 0.644-0.856) in the derivation, internal validation, and external validation cohort, respectively. Calibration plots of the three datasets suggested accurate agreement between the predicted and observed 5-year risk of MACE in LVNC. According to decision curve analysis, the ABLE-SCORE displayed greater net benefit than the currently existing risk score for MACE in LVNC [3], indicating its strength in clinical applicability. Conclusions Derived from readily available laboratory and echocardiographic variables, a simplified and efficient risk score for MACE was developed and validated using a large LVNC cohort, making it a reliable and convenient tool for the risk stratification and clinical management of patients with LVNC.Development of the ABLE-SCOREValidation of the ABLE-SCORE

Implementation of sodium-glucose co-transporter 2 inhibitors in patients with heart failure through a new digital strategy (EMAIL-HF): a randomised clinical trial study design

Abstract Introduction Delayed implementation of new medical discoveries remains a global healthcare challenge and is mainly due to the complexity of cross-institutional patient care. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors is the latest medical discovery in heart failure (HF) and have recently been added to clinical guidelines as they have proven to reduce the risk of adverse cardiovascular outcomes in patients with HF across the ejection fraction spectrum. Whether a new digital strategy can optimise and accelerate the implementation of SGLT2 inhibitors in patients living with HF is of great importance for public health. Purpose To evaluate whether a new and streamlined digital strategy can optimise and accelerate the implementation of SGLT2 inhibitors in patients with HF. Design and methods: The trial is a multicentre, parallel group, register-based randomised clinical study, evaluating the effect and potential of a new digital strategy to implement new guideline therapies to patients living with a chronic disease, specifically SGLT2 inhibitors to patients with HF (figure 1). The setup employs data from nationwide health registers and official digital letters to inform patients about the new therapy option and invite them to have their eligibility evaluated by a HF specialist and start therapy. A total of ~10,000 patients with HF across the ejection fraction spectrum (with and without diabetes), who have not yet been started on SGLT2 inhibitors, are identified through Danish nationwide health registers, and randomised 1:1 to receive the digital letter (figure 2). The primary outcome is the proportion of patients redeeming a prescription of a SGLT2 inhibitor within six months. Secondary outcome is a composite HF endpoint consisting of all-cause death or HF hospitalisation. Other outcome measures are renal failure, stroke and myocardial infarction, safety outcomes, adherence to therapy and proportion of vulnerable patient groups initiating therapy including immigrants, elderly, frail patients, patients with lower socioeconomic level and lower educational level. A total of 4689 patients have been randomised (February 2024) and data will be presented in 2025. Conclusions The trial will determine the efficacy and safety of a new and streamlined digital strategy to implement SGLT2 inhibitors to patients with chronic HF. The setup has the potential to be used in a broad spectrum of patients living with chronic diseases and is expected to be highly cost-effective.Figure 1.Study hypothesisFigure 2.Study design

Association of cardiac amyloidosis with cardiovascular outcomes after aortic valve replacement in patients with severe aortic stenosis: a systematic review and meta-analysis

Abstract Introduction Aortic stenosis (AS) and cardiac amyloidosis (CA) frequently coexist and is commonly observed in older individuals referred for aortic valve replacement (AVR). However, the association of CA with adverse outcomes after AVR has not been well established. Purpose This meta-analysis aimed to evaluate the association of CA with adverse cardiovascular outcomes in patients with severe AS after undergoing AVR. Methods A literature search was performed for studies evaluating patients with severe AS undergoing AVR, comparing clinical endpoints on follow-up for patients with and without CA. The clinical endpoints included all-cause mortality and heart failure (HF) hospitalization. Databases searched included Ovid MEDLINE, Embase, and Web of Science. Subgroup analysis was performed for short term (<30 days) and long term (>30 days) mortality. The search was not restricted to time or publication status. Results Five studies including 1,105 patients with severe AS (111 with concurrent CA, 904 without CA) met inclusion criteria. The mean follow-up duration was 24.6 months, mean age was 81.2 years and 55.4% were men. Mean echocardiographic aortic valve parameters included valve area of 0.715cm2, mean gradient of 41.8 mmHg, and peak velocity of 4.2m/s. The mean left ventricular ejection fraction was 58%. All except 1 study included only patients with ATTR CA while excluding other causes of CA. There was no statistically significant difference in all-cause mortality between patients with and without CA following AVR, both in short-term (OR 0.94; 95% CI 0.17-5.31; p=0.95) and long-term (OR 1.72; 95% CI 0.75-3.91; p=0.20) follow-up. However, patients without CA demonstrated a significantly lower risk of heart failure hospitalization post-AVR compared to those with CA (OR 2.49; 95% CI 1.18–5.23; p = 0.02). Conclusion In the context of patients with severe AS undergoing AVR, the presence of CA does not appear to significantly impact short-term or long-term all-cause mortality. Notably, patients without CA exhibited a lower risk of heart failure hospitalization following AVR. These findings underscore the importance of considering cardiac amyloidosis in the clinical management of severe AS and highlight potential differences in outcomes based on its presence or absence. Additional studies are needed to elucidate outcome differences for CA patients who undergo surgical versus transcatheter AVR.Figure 1

Effect of physical activity level on the association of LBBB, heart failure, and mortality

Abstract Background The beneficial effect of physical activity (PA) on adverse cardiovascular outcomes in patients with heart failure (HF) and left bundle branch block (LBBB) is well established. Yet, the impact of PA on individuals with LBBB without evident HF remains unexplored. Our objective is to investigate how PA modifies the outcomes of new-onset LBBB patients concerning HF-related hospitalizations and mortality. Methods Among the UK Biobank participants without a diagnosis of HF, we identified individuals with new-onset LBBB and available PA quantification. Patients were dichotomized into normal QRS and LBBB groups, following by stratification according to summed minutes of PA per week. The primary outcome was all-cause mortality, and HF-related hospitalizations. Cox proportional hazard model and Kaplan-Meier survival analysis were applied. Results The final cohort comprised 367,934 individuals, with a mean age of 56.6±8.2 years and 47% male. Among them, 3,427 (0.9%) developed new-onset LBBB, characterized by advanced age, male predominance, and higher rates of comorbidities. Median summed PA minutes per week were 100 (IQR: 125-180), with no significant difference between normal QRS and LBBB patients. Over a median follow-up of 13.8 years (IQR: 13-14.5), 26,304 patients (7.15%) died. Kaplan-Meier analysis revealed higher mortality risk with reduced PA level and/or LBBB (log-rank p<0.001 for both). Multivariate Cox analysis adjusted for age, sex, and comorbidities showed LBBB patients had over 3.5-fold increased risk of death (HR 3.67, 95% CI 3.39-3.97, p<0.001) compared to normal QRS. The association of LBBB with mortality was modified by weekly PA minutes; those with <150 minutes had nearly 40% higher risk compared to those with ≥150 minutes (HR 3.78, 95% CI 3.43–4.15, p<0.001; HR 3.4, 95% CI 2.93–3.95, p<0.001; p for interaction=0.035). The protective effect of PA was 6% among normal QRS patients, compared to 22% among individuals with LBBB (HR 0.94, 95% CI 0.91 – 0.96, p<0.001 vs. HR 0.78, 95% CI 0.66 – 0.93, p=0.004). Similar findings were observed for HF hospitalizations. Conclusions Although the correlation between LBBB and adverse cardiovascular outcomes remained consistent across both levels of physical activity (PA), it was more pronounced among patients with low PA levels. When assessing the risk in patients with newly diagnosed LBBB, particular attention should be directed towards their PA status.

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.

The value of coronary calcium score in predicting clinical outcomes in patients with chronic coronary syndrome

BackgroundCoronary artery atherosclerosis and calcification are the precursors to the development of coronary artery disease and its complications. Coronary artery calcium scoring (CACS) is useful as a risk-stratification tool in coronary artery disease.ObjectiveThe current study was designed to identify the relationship between CACS and major adverse cardiovascular outcomes in patients with stable coronary artery disease.MethodsThe study was conducted on 435 patients with stable ischemic heart disease. The patients were classified into two groups according to their coronary artery calcium score (CACS): group I (n = 220 patients), whose calcium score was mild to moderate (< 400), and group II (n = 215 patients), whose calcium score was high (≥ 400). All patients were closely monitored for two years to assess major adverse cardiovascular events (MACE).ResultsAfter 2 years of follow-up, MACE drastically increased in Group II in the form of unstable angina, myocardial infarction, demand for percutaneous coronary intervention, and heart failure. Multivariate regression analysis showed that age ≥ 55 years, Framingham risk score > 10, CACS ≥ 400, body mass index ≥ 30 kg/m2, and the proximal lesions of the vessels were the independent risk factors for major cardiac events.ConclusionThe coronary calcium score is a distinct feature of coronary atherosclerosis, and a score of 400 or higher is a reliable, noninvasive predictor of the progression of coronary artery diseases and their consequences, including MACE.

Cardiovascular outcomes in Parkinson’s disease patients from a retrospective cohort study

Parkinson’s disease (PD) reports high rates of morbidity and mortality, but the risk of adverse cardiovascular outcomes in patients with PD has not been fully elucidated. This bi-center retrospective cohort study using the electronic health records (EHR) database of two tertiary hospitals screened a total of 327,292 subjects who visited the outpatient clinic, and 1194 patients with PD were propensity score-matched with a control population. The primary outcome was the occurrence of major adverse cardiovascular events (MACE). Key secondary outcomes included all-cause death, cardiovascular (CV) death, stroke, myocardial infarction (MI), heart failure hospitalization and 30-day CV death. After PS matching, MACE occurrence was not significantly different between PD and non-PD groups (18.2% vs. 17.5%, log-rank p = 0.98). Key secondary outcomes were also similar between the two groups. In patients with PD, MACE rate, and also CV risk score, were higher in patients with more severe PD (according to Hoehn and Yahr scale and unified Parkinson’s disease rating scale), and after multivariable analysis, PD severity was not an independent predictor of MACE. Patients with PD are at an increased risk of adverse cardiovascular outcomes, but the contribution from other common CV risk factors cannot be ignored. The management of prevalent CV risk factors is therefore important in mitigating adverse outcomes among patients with PD.

P160 MODELLING CARDIOVASCULAR TOXICITY IN CELLULO ASSOCIATED WITH ANTITUMORALS

Background and Objective: Gastrointestinal cancer (GIC) stands as a leading cause of cancer-related mortality worldwide. Currently combination chemotherapy, particularly metal-based drugs, often induces side effects, limiting their clinical efficacy. Cardiotoxicity, a common complication associated with various therapeutic agents, manifests through vascular endothelial dysfunction, a hallmark of ischemic coronary disease. Our aim is to design novel metal-based drugs with enhanced efficacy, specificity, and mitigated off-target cytotoxicity. We identified the isomers trans and cis-[PtI2(isopropylamine)2] (I5 and I6, respectively), as promising candidates against GIC, both in vitro and in vivo 1. RNA seq was performed in 6 different GIC cells. The Gene Set Enrichment Analysis (GSEA) revealed a significant enrichment of inflammation-related genes and downregulation of angiogenesis-associated pathways in treated cells. Our objective now is to develop preclinical studies of the cardiovascular toxicity of I5 and I6. Methods: Cardiovascular effects of these drugs were studies using a in cellulo model system (AC16, HUVEC cell lines). Biological and biochemistry approaches and techniques were used to assess senescence, mitochondrial respiration, viability by MTS and wound healing assays. Results: Our findings indicate that both I5 and I6 decrease cellular viability, induce senescence (as evidenced by β-galactosidase activity), and generate reactive oxygen species compared to commonly used cisplatin. Additionally, I5 impact oxidative phosphorylation (OXPHOS) and glycolysis metabolism. Furthermore, a wound healing assay suggests that the migration of cells is modulated in response to treatment with these compounds. Conclusions: Accurate preclinical assessment of the effects of novel drugs on the vascular endothelium is imperative to address treatment-induced endothelial dysfunction before envisioning clinical trials. Understanding the impact of anti-cancer agents on the vascular endothelium will not only inform therapeutic strategies to prevent or reverse treatment-induced cardiotoxicity but may also serve as a vital tool for predicting, monitoring, and preventing adverse cardiovascular outcomes in patients undergoing cancer treatment. 1 Commun Biol 7, 353, doi:10.1038/s42003-024-06052-5 (2024).

Abstract Mo033: Circulating Long Noncoding RNA Expression Signature Predicts Adverse Cardiovascular Outcomes in Patients with Coronary Artery Disease

Background: Patients with coronary artery disease (CAD) have increased risks of subsequent major adverse cardiovascular events (MACE). Currently, there are no reliable tools to predict recurrent MACE in CAD patients. Objective: To determine if circulating long noncoding RNA (lncRNA) expression signature predicts recurrent MACE in CAD patients. Methods: As part of the Taiwan Biosignature Study, this prospective nested case-control study included 168 CAD patients who experienced MACE during the follow-up and another 108 CAD patients who remained free of MACE after a≥24-month follow-up. Plasma lncRNAs were profiled to determine their prognostic values for MACE in CAD patients. Results: Initially, RNA sequencing in 59 CAD patients (41 with recurrent MACE) revealed that a total of 124 plasma lncRNAs were dysregulated in CAD patients with recurrent MACE. Subsequent analyses showed that the expression signature of these lncRNAs classified CAD patients with vs. without recurrent MACE with an accuracy of 93%. Elevated levels of plasma lnc-NCF1-1, BRE-AS1, lnc-ZFAT-6, lnc-SLC46A3-5, lnc-CXCL3-2 and lnc-EBF3-4 were associated with increased risks of recurrent MACE. Additional studies in the remaining 217 CAD patients (127 with recurrent MACE) validated that increased plasma levels of lnc- NCF1-1, BRE-AS1, lnc-ZFAT-6, and lnc-EBF3-4 were significant predictors of recurrent MACE. In addition, lnc-SCORE, an index calculated from MACE-associated plasma lncRNA levels, was shown to be a strong independent predictor (adjusted HR, 2.70 [95% CI 1.78-4.09]) of recurrent MACE in CAD patients. BRE-AS1 and lnc-ZFAT-6 , two endothelium-enriched MACE-associated lncRNAs, were specifically dysregulated in cardiomyopathy of ischemic, but not of non-ischemic, origin, suggesting their potential contribution to the development of myocardial ischemia. Moreover, knocking BRE-AS1 reversed hypoxia-induced upregulation of VCAM-1 in human aortic endothelial cells, suggesting its functional contribution to vascular inflammation upon ischemia. Conclusions: This study shows the prognostic roles of circulating lncRNAs in predicting recurrent MACE in CAD patients. Endothelium-enriched lncRNA BRE-AS1 is involved in ischemia-induced vascular inflammation.

Catheter-based ablation to improve outcomes in patients with atrial fibrillation and heart failure with preserved ejection fraction: Rationale and design of the CABA-HFPEF-DZHK27 trial.

Atrial fibrillation (AF) is common in heart failure (HF) and negatively impacts outcomes. The role of ablation-based rhythm control in patients with AF and HF with preserved (HFpEF) or mildly reduced ejection fraction (HFmrEF) is not known. The CABA-HFPEF-DZHK27 (CAtheter-Based Ablation of atrial fibrillation compared to conventional treatment in patients with Heart Failure with Preserved Ejection Fraction) trial will determine whether early catheter ablation for AF can prevent adverse cardiovascular outcomes in patients with HFpEF or HFmrEF. CABA-HFPEF-DZHK27 (NCT05508256) is an investigator-initiated, prospective, randomized, open, interventional multicentre strategy trial with blinded outcome assessment. Approximately 1548 patients with paroxysmal or persistent AF diagnosed within 24 months prior to enrolment and HFpEF or HFmrEF will be randomized to early catheter ablation within 4 weeks after randomization or to usual care. All patients receive anticoagulation, rate control, and HF management according to current guideline recommendations. Usual care can include rhythm control in symptomatic patients. Patients will be followed until the end of the trial for the primary outcome, a composite of cardiovascular death, stroke, and total unplanned hospitalizations for HF or acute coronary syndrome. The safety outcome comprises complications of catheter ablation and death. The trial is powered for a rate ratio of 0.75 (two-sided alpha = 0.05, 1-beta = 0.8). CABA-HFPEF-DZHK27 will define the role of systematic and early catheter ablation in patients with AF and HFpEF or HFmrEF.

Natural history of initially asymptomatic severe aortic stenosis: a one-stage meta-analysis.

Current guidelines on the management strategy for patients with asymptomatic severe aortic stenosis (AS) remain unclear. This uncertainty stems from the lack of data regarding the natural history of these patients. To address this gap, we performed a systematic review and meta-analysis examining the natural history of asymptomatic severe AS patients receiving conservative treatment. The PubMed, Cochrane, and Embase databases were searched from inception to 24 January 2024 using the keywords "asymptomatic" AND "aortic" AND "stenosis". We included studies examining patients with asymptomatic severe AS. In interventional trials, only data from conservatively managed arms were collected. A one-stage meta-analysis was conducted using individual patient data reconstructed from published Kaplan-Meier curves. Sensitivity analysis was performed for major adverse cardiovascular outcomes in patients who remained asymptomatic throughout follow-up. A total of 46 studies were included (n = 9545). The median time to the development of symptoms was 1.11years (95% CI 0.90-1.53). 49.36% (40.85-58.59) of patients who were asymptomatic had suffered a major adverse cardiovascular event by 5years. The median event-free time for heart failure hospitalization (HFH) was 5.50years (95% CI 5.14-5.91) with 36.34% (95% CI 33.34-39.41) of patients experiencing an HFH by year 5. By 5years, 79.81% (95% CI 69.26-88.58) of patients developed symptoms (angina, dyspnoea, syncope and others) and 12.36% (95% CI 10.01-15.22) of patients died of cardiovascular causes. For all-cause mortality, the median survival time was 9.15years (95% CI 8.50-9.96) with 39.43% (CI 33.41-36.40) of patients dying by 5years. The median time to AVR was 4.77years (95% CI 4.39-5.17), with 52.64% (95% CI 49.85-55.48) of patients requiring an AVR by 5years. Our results reveal poor cardiovascular outcomes for patients with asymptomatic severe AS on conservative treatment. A significant proportion eventually requires an AVR. Further research is needed to determine if early intervention with AVR is more effective than conservative treatment.

Assessment of left atrial function provides incremental value: the left atrial volumetric/mechanical coupling index in patients with chronic kidney disease.

Heart failure is a common cause of adverse cardiovascular outcomes in patients with chronic kidney disease (CKD). Left atrial (LA) characteristics are thought to be involved in the development of heart failure. However, LA assessment is complex. Though a variety of parameters have been defined, there is no single parameter that best defines LA function. Pilot data indicate that left atrial volumetric/mechanical coupling index (LACI) may be useful, but data with CKD are lacking. The objective of this study was to define LACI in a cohort of patients with CKD and to assess its value in evaluating LA function and predicting heart failure. A cohort of patients with CKD was enrolled at our hospital between 2021 and 2023. Follow-up was performed for heart failure. LACI is a volumetric to mechanical coupling index, calculated as the ratio of the LA volume index to the tissue-Doppler myocardial velocity at atrial contraction. Spearman's rank correlation or Pearson's correlation was used to calculate the correlation between LACI and echocardiographic/hemodynamic variables. Receiver operating characteristic curve (ROC) analysis was utilised to derive the area under the curve (AUC) for LACI, LVGLS, LASr, LASct and LASI for the detection of heart failure. Kaplan-Meier survival curves were employed to compare clinical outcomes based on LACI thresholds. A multivariable logistic regression analysis was employed to assess the relationship between risk factors and elevated LACI. Cox proportional hazards regression was used to identify risk factors for heart failure. LACI showed a positive correlation with NT-proBNP, CK-MB, LAVI, E/e' and LASI (r = 0.504, 0.536, 0.856, 0.541 and 0.509, p < 0.001); and a negative correlation with LASr (r = -0.509, p < 0.001). On the ROC analysis for the determination of heart failure, the AUC of LACI was comparable to those of LVGLS (0.588 vs. 509, p = 0.464), LASr (0.588 vs. 0.448, p = 0.132), LASct (0.588 vs. 0.566, p = 0.971) and LASI (0.588 vs. 0.570, p = 0.874). The cardiovascular risk factors increased by LACI were age, BMI, diabetes, triglycerides, LA size, LASr, LASI, E/A, E/e' and EF (p < 0.05). During a median follow-up of 16 months (range, 6-28 months), the event-free survival curves demonstrated a higher risk of heart failure in the group with LACI > 5.0 (log-rank test: P < 0.001). LACI > 5.0 was an independent predictor of heart failure [OR: 0.121, 95% CI (0.020-0.740), p = 0.022]. LACI may prove to be a valuable tool for assessing LA function in patients with CKD, and could be integrated into the routine assessment of LA for the purpose of prognostic assessment and clinical decision-making in patients with CKD.

The Association between Platelet Lymphocyte Ratio and In-Hospital Outcomes in Patients with First Attack of Acute ST-elevation Myocardial Infraction following Thrombolysis with Streptokinase in a Tertiary Care Hospital

Introduction: Platelet Lymphocyte ratio (PLR) has been found to be a good predictor of future adverse cardiovascular outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Aim: Investigation was done in the aim to detect the role of Platelet Lymphocyte ratio (PLR) in predicting in-hospital adverse cardiac events in patients with STEMI thrombolysed with streptokinase in a tertiary care hospital. Methods: This cross sectional descriptive study carried out in the Department of Cardiology, Mymensingh Medical College Hospital, Mymensingh for fifteen-month duration from January, 2018 to March, 2019, in STEMI patients, who were thrombolysed with inj. Streptokinase (STK) had blood samples at admission, analyzed complete blood counts for PLR calculation. They were grouped into two, low and high PLR, taking 150 as cut-off. Chi square test was used to compare rate of adverse events and death in hospital stay. Logistic regression analysis was used to estimate predictive ability of PLR for in-hospital cardiac events. Results: A total of 79 patients among 217 patients had complications. Patients in high PLR group had higher rate of complications (63.6% vs. 21.4%, p &lt;0.001) in hospital than those in low PLR group. Arrhythmias (13.0% vs. 5.0%, p &lt;0.036), Heart failure (45.5% vs. 15.0%, p=0.001), Cardiogenic shock (10.4% vs.3.6%, p &lt;0.001), Death (9.1% vs. 6.4%, p=0.473), occurred more in high PLR group. Mean PLR was significantly different between Group-I and Group-II (96.21±27.79 vs. 233.21±88.20, p&lt;0.001). Multivariate regression analysis showed PLR an independent predictor of in-hospital adverse cardiac events (at 10% level of significance, p = 0.001). Conclusion: High admission PLR is an independent predictor for in-hospital adverse cardiac events in patients hospitalized for STEMI thrombolysed with streptokinase.

Adverse Cardiovascular Outcomes in Patients With Obstructive Sleep Apnea and Obesity: Metabolic Surgery vs Usual Care

BackgroundNo therapy has been shown to reduce the risk of major adverse cardiovascular events (MACE) and death in patients with obstructive sleep apnea (OSA). ObjectivesThe authors sought to investigate the long-term relationship between metabolic surgery and incident MACE in patients with OSA and obesity. MethodsAdult patients with a body mass index 35 to 70 kg/m2 and moderate-to-severe OSA at a U.S. health system (2004-2018) were identified. Baseline characteristics of patients who underwent metabolic surgery were balanced with a nonsurgical control group using overlap-weighting methods. Multivariable Cox regression analysis estimated time-to-incident MACE. Follow-up ended in September 2022. ResultsA total of 13,657 patients (7,496 [54.9%] men; mean age 52.0 ± 12.4 years; median body mass index 41.0 kg/m2 [Q1-Q3: 37.6-46.2 kg/m2]), including 970 patients in the metabolic surgery group and 12,687 patients in the nonsurgical group, with a median follow-up of 5.3 years (Q1-Q3: 3.1-8.4 years) were analyzed. The mean between-group difference in body weight at 10 years was 26.6 kg (95% CI: 25.6-27.6 kg) or 19.3% (95% CI: 18.6%-19.9%). The 10-year cumulative incidence of MACE was 27.0% (95% CI: 21.6%-32.0%) in the metabolic surgery group and 35.6% (95% CI: 33.8%-37.4%) in the nonsurgical group (adjusted HR: 0.58 [95% CI: 0.48-0.71]; P < 0.001). The 10-year cumulative incidence of all-cause mortality was 9.1% (95% CI: 5.7%-12.4%) in the metabolic surgery group and 12.5% (95% CI: 11.2%-13.8%) in the nonsurgical group (adjusted HR: 0.63 [95% CI: 0.45-0.89]; P = 0.009). ConclusionsAmong patients with moderate-to-severe OSA and obesity, metabolic surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident MACE and death.

Metabolomics and Cardiovascular Risk in Patients with Heart Failure: A Systematic Review and Meta-Analysis.

The associations of plasma metabolites with adverse cardiovascular (CV) outcomes are still underexplored and may be useful in CV risk stratification. We performed a systematic review and meta-analysis to establish correlations between blood metabolites and adverse CV outcomes in patients with heart failure (HF). Four cohorts were included, involving 83 metabolites and 37 metabolite ratios, measured in 1158 HF patients. Hazard ratios (HR) of 42 metabolites and 3 metabolite ratios, present in at least two studies, were combined through meta-analysis. Higher levels of histidine (HR 0.74, 95% CI [0.64; 0.86]) and tryptophan (HR 0.82 [0.71; 0.96]) seemed protective, whereas higher levels of symmetric dimethylarginine (SDMA) (HR 1.58 [1.30; 1.93]), N-methyl-1-histidine (HR 1.56 [1.27; 1.90]), SDMA/arginine (HR 1.38 [1.14; 1.68]), putrescine (HR 1.31 [1.06; 1.61]), methionine sulfoxide (HR 1.26 [1.03; 1.52]), and 5-hydroxylysine (HR 1.25 [1.05; 1.48]) were associated with a higher risk of CV events. Our findings corroborate important associations between metabolic imbalances and a higher risk of CV events in HF patients. However, the lack of standardization and data reporting hampered the comparison of a higher number of studies. In a future clinical scenario, metabolomics will greatly benefit from harmonizing sample handling, data analysis, reporting, and sharing.

Insulin resistance, coronary artery lesion complexity and adverse cardiovascular outcomes in patients with acute coronary syndrome

BackgroundInsulin resistance (IR) is linked to both the complexity of coronary artery lesions and the prognosis of acute coronary syndrome (ACS). However, the precise extent of this correlation and its impact on adverse cardiovascular outcomes in ACS patients remain unclear. Therefore, this study aims to investigate the intricate relationship between IR, coronary artery lesion complexity, and the prognosis of ACS through a cohort design analysis.MethodA total of 986 patients with ACS who underwent percutaneous coronary intervention (PCI) were included in this analysis. IR was assessed using the triglyceride-glucose (TyG) index, while coronary artery lesion complexity was evaluated using the SYNTAX score. Pearson’s correlation coefficients were utilized to analyze the correlations between variables. The association of the TyG index and SYNTAX score with major adverse cardiovascular events (MACEs) in ACS was investigated using the Kaplan-Meier method, restricted cubic splines (RCS), and adjusted Cox regression. Additionally, a novel 2-stage regression method for survival data was employed in mediation analysis to explore the mediating impact of the SYNTAX score on the association between the TyG index and adverse cardiovascular outcomes, including MACEs and unplanned revascularization.ResultsDuring a median follow-up of 30.72 months, 167 cases of MACEs were documented, including 66 all-cause deaths (6.69%), 26 nonfatal myocardial infarctions (MIs) (2.64%), and 99 unplanned revascularizations (10.04%). The incidence of MACEs, all-cause death, and unplanned revascularization increased with elevated TyG index and SYNTAX score. Both the TyG index (non-linear, P = 0.119) and SYNTAX score (non-linear, P = 0.004) displayed a positive dose-response relationship with MACEs, as illustrated by the RCS curve. Following adjustment for multiple factors, both the TyG index and SYNTAX score emerged as significant predictors of MACEs across the total population and various subgroups. Mediation analysis indicated that the SYNTAX score mediated 25.03%, 18.00%, 14.93%, and 11.53% of the correlation between the TyG index and MACEs in different adjusted models, respectively. Similar mediating effects were observed when endpoint was defined as unplanned revascularization.ConclusionElevated baseline TyG index and SYNTAX score were associated with a higher risk of MACEs in ACS. Furthermore, the SYNTAX score partially mediated the relationship between the TyG index and adverse cardiovascular outcomes.

Safety and Efficacy of Anti-Hypertensive Medications in Patients with Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-analysis.

Hypertension (HTN) is a co-morbidity that is commonly associated with heart failure with preserved ejection fraction (HFpEF). However, it remains unclear whether treatment of hypertension in HFpEF patients is associated with improved cardiovascular outcomes. The purpose of this meta-analysis is to evaluate the association of anti-hypertensive medical therapy with cardiovascular outcomes in patients with HFpEF. We performed a database search for studies reporting on the association of anti-hypertensive medications with cardiovascular outcomes and safety endpoints in patients with HFpEF. The databases searched include OVID Medline, Web of Science, and Embase. The primary endpoint was all-cause mortality. Secondary endpoints include cardiovascular (CV) mortality, worsening heart failure (HF), CV hospitalization, composite major adverse cardiovascular events (MACE), hyperkalemia, worsening renal function, and hypotension. A total of 12 studies with 14062 HFpEF participants (7010 treated with medical therapy versus 7052 treated with placebo) met inclusion criteria. Use of anti-hypertensive medications was not associated with lower all-cause mortality, CV mortality or CV hospitalization compared to treatment with placebo (OR 1.02, 95% CI 0.77-1.35; p=0.9, OR 0.88, 95% CI 0.73-1.06; p=0.19, OR 0.99, 95% CI 0.87-1.12; p=0.83, OR 0.90, 95% CI 0.79-1.03; p=0.11). Anti-hypertensive medications were not associated with lower risk of subsequent acute myocardial infarction (AMI) (OR 0.53, 95% CI 0.07-3.73; p=0.5). Use of anti-hypertensive medications was associated with a statistically significant lower risk of MACE (OR 0.90, 95% CI 0.83-0.98; p=0.02). While treatment with anti-hypertensive medications was not associated with lower risk of all-cause mortality, their use may be associated with reduce risk of adverse cardiovascular outcomes in patients with HFpEF regardless of whether they have HTN. Additional high quality studies are required to clarify this association and determine the effect based on specific classes of medications.

ECHOCARDIOGRAPHIC AND ELECTROCARDIOGRAPHIC PREDICTORS OF NEW ATRIAL FIBRILLATION IN END-STAGE RENAL DISEASE PATIENTS WITH PRESERVED LEFT VENTRICULAR SYSTOLIC FUNCTION

Objective: We investigated the echocardiographic and electrocardiographic predictors for future development of AF in patients with ESRD and preserved LV EF who had never diagnosed AF. Design and method: Atrial fibrillation (AF) is a common cause which leads to adverse cardiovascular outcome in patients with end-stage renal disease (ESRD). AF is common arrhythmia in patients with reduced left ventricular (LV) ejection fraction (EF). It is unclear the predictor of new AF in patients with preserved LV EF. We enrolled 226 patients with ESRD who has performed transthoracic echocardiography. We excluded the 1) 16 patients who has been received a diagnosis of AF, and 2) 19 patients with LV EF &lt; 50%, and 191 patients (121 males, mean 62 ± 14 years) Results: During a mean follow-up period of 885 ± 720 days, AF occurred in 20 (10.5%) patients. The patients with AF development was older (69 ± 12 vs. 61 ± 14 years, p=0.023). There were no differences in history of hypertension, diabetes, stroke and coronary artery disease between two groups. In univariate Cox regression analysis, left atrial volume index (LAVI), right ventricular systolic pressure, age and QRS duration were associated with future AF events. After multivariate Cox regression analysis, age (HR: 1.015, 95% CI: 1.008-1.105, p value: 0.022) and QRS duration (HR: 1.025, 95% CI: 1.001-1.049, p value: 0.043) significantly predicted the future development of AF. Conclusions: QRS duration is well known predictor of cardiovascular outcome in patients with reduced LV EF. In this study, we demonstrated QRS duration predicted new AF events in ESRD patients with preserved LV EF.

Prediabetes is associated with increased cardiac events in patients with cancer who are prescribed anthracyclines.

Prediabetes, which is a precedent of overt diabetes, is a known risk factor for adverse cardiovascular outcomes. Its impact on adverse cardiovascular outcomes in patients with cancer who are prescribed anthracycline-containing chemotherapy (ACT) is uncertain. The objective of this study was to evaluate the association of prediabetes with cardiovascular events in patients with cancer who are prescribed ACT. The authors identified patients with cancer who received ACT from 2000 to 2019 from Clinical Data Analysis Reporting System of Hong Kong. Patients were divided into diabetes, prediabetes, and normoglycemia groups based on their baseline glycemic profile. The Primary outcome, a major adverse cardiovascular event (MACE), was the composite event of hospitalization for heart failure and cardiovascular death. Among 12,649 patients at baseline, 3997 had prediabetes, and 5622 had diabetes. Over median follow-up of 8.7 years, the incidence of MACE was 211 (7.0%) in the normoglycemia group, 358 (9.0%) in the prediabetes group, and 728 (12.9%) in the diabetes group. Compared with normoglycemia, prediabetes (adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.01-1.43) and diabetes (adjusted HR, 1.46; 95% CI, 1.24-1.70) were associated with an increased risk of MACE. In the prediabetes group, 475 patients (18%) progressed to overt diabetes and exhibited a greater risk of MACE (adjusted HR, 1.76; 95% CI, 1.31-2.36) compared with patients who remained prediabetic. In patients with cancer who received ACT, those who had prediabetes at baseline and those who progressed to diabetes at follow-up had an increased risk of MACE. The optimization of cardiovascular risk factor management, including prediabetes, should be considered in patients with cancer who are treated before and during ACT to reduce cardiovascular risk. Patients with cancer who have preexisting diabetes have a higher risk of cardiovascular events, and prediabetes is often overlooked. In this study of 12,649 patients with cancer identified in the Clinical Data Analysis Reporting System of Hong Kong who were receiving treatment with anthracycline drugs, prediabetes was correlated with increased deaths from cardiovascular disease and/or hospitalizations for heart failure. Patients who progressed from prediabetes to diabetes within 2 years had an increased risk of combined hospitalization for heart failure and death from cardiovascular disease. These findings indicate the importance of paying greater attention to cardiovascular risk factors, including how prediabetes is managed, in patients who have cancer and are receiving chemotherapy with anthracyclines, emphasizing the need for surveillance, follow-up strategies, and consideration of prediabetes management in cancer care.