Adverse Cardiovascular Outcomes In Patients Research Articles

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.

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.

Elevated levels of plasma inactive stromal cell derived factor-1α predict poor long-term outcomes in diabetic patients following percutaneous coronary intervention

BackgroundSince the complication of diabetes mellitus (DM) is a risk for adverse cardiovascular outcomes in patients with coronary artery disease (CAD), appropriate risk estimation is needed in diabetic patients following percutaneous coronary intervention (PCI). However, there is no useful biomarker to predict outcomes in this population. Although stromal cell derived factor-1α (SDF-1α), a circulating chemokine, was shown to have cardioprotective roles, the prognostic impact of SDF-1α in diabetic patients with CAD is yet to be fully elucidated. Moreover, roles of SDF-1α isoforms in outcome prediction remain unclear. Therefore, this study aimed to assess the prognostic implication of three forms of SDF-1α including total, active, and inactive forms of SDF-1α in patients with DM and after PCI.MethodsThis single-center retrospective analysis involved consecutive patients with diabetes who underwent PCI for the first time between 2008 and 2018 (n = 849). Primary and secondary outcome measures were all-cause death and the composite of cardiovascular death, non-fatal myocardial infarction, and ischemic stroke (3P-MACE), respectively. For determining plasma levels of SDF-1α, we measured not only total, but also the active type of SDF-1α by ELISA. Inactive isoform of the SDF-1α was calculated by subtracting the active isoform from total SDF-1α.ResultsUnadjusted Kaplan–Meier analyses revealed increased risk of both all-cause death and 3P-MACE in patients with elevated levels of inactive SDF-1α. However, plasma levels of total and active SDF-1α were not associated with cumulative incidences of outcome measures. Multivariate Cox hazard analyses repeatedly indicated the 1 higher log-transformed inactive SDF-1α was significantly associated with increased risk of all-cause death (hazard ratio (HR): 2.64, 95% confidence interval (CI): 1.28–5.34, p = 0.008) and 3P-MACE (HR: 2.51, 95% CI: 1.12–5.46, p = 0.02). Moreover, the predictive performance of inactive SDF-1α was higher than that of total SDF-1α (C-statistics of inactive and total SDF-1α for all-cause death: 0.631 vs 0.554, for 3P-MACE: 0.623 vs 0.524, respectively).ConclusionThe study results indicate that elevated levels of plasma inactive SDF-1α might be a useful indicator of poor long-term outcomes in diabetic patients following PCI.Trial registration: This study describes a retrospective analysis of a prospective registry database of patients who underwent PCI at Juntendo University Hospital, Tokyo, Japan (Juntendo Physicians’ Alliance for Clinical Trials, J-PACT), which is publicly registered (University Medical Information Network Japan—Clinical Trials Registry, UMIN-CTR 000035587).

Dapagliflozin in patients with heart failure and previous myocardial infarction: A participant-level pooled analysis of DAPA-HF and DELIVER.

Patients with heart failure (HF) and history of myocardial infarction (MI) face a higher risk of disease progression and clinical events. Whether sodium-glucose cotransporter 2 inhibitors may modify clinical trajectory in such individuals remains incompletely understood. The DAPA-HF and DELIVER trials compared dapagliflozin with placebo in patients with symptomatic HF with left ventricular ejection fraction (LVEF) ≤40% and > 40%, respectively. In this pooled participant-level analysis, we assessed efficacy and safety outcomes by history of MI. The primary outcome in both trials was the composite of cardiovascular death or worsening HF. Of the total of 11 007 patients, 3731 (34%) had a previous MI and were at higher risk of the primary outcome across the spectrum of LVEF in covariate-adjusted models (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.02-1.24). Dapagliflozin reduced the risk of the primary outcome to a similar extent in patients with (HR 0.83, 95% CI 0.72-0.96) and without previous MI (HR 0.76, 95% CI 0.68-0.85; pinteraction = 0.36), with consistent benefits on key secondary outcomes as well. Serious adverse events did not occur more frequently with dapagliflozin, irrespective of previous MI. History of MI confers increased risks of adverse cardiovascular outcomes in patients with HF across the LVEF spectrum, even among those with preserved ejection fraction. Dapagliflozin consistently and safely reduces the risk of cardiovascular death or worsening HF, regardless of previous MI.

A high level of uric acid is associated with long-term adverse cardiovascular outcomes in patients who received fractional flow reserve with coronary intermediate stenosis

Background and aimsThe role of fractional flow reserve (FFR) in coronary intermediate lesions is widely recommended by guidelines. The effect of uric acid (UA) on cardiovascular events is also well known. However, the relationship between UA and long-term cardiovascular outcomes in patients who received FFR with intermediate lesions remains unknown. Methods and resultsWe retrospectively included 428 patients who underwent both coronary angiography (CAG) and FFR. Participants were stratified into two groups based on the median UA. The primary endpoint was the composite of major adverse cardiovascular and cerebrovascular events (MACCEs), including repeat revascularization, nonfatal stroke, nonfatal myocardial infarction, and all-cause death. A Cox proportional hazards model was utilized to analyze the association between UA and the prevalence of MACCEs. During a median follow-up of 5.8 years, a higher MACCEs rate occurred in the high UA group compared to the low UA group (16.8% vs. 5.1%, p log-rank<0.01). Elevated UA was independently linked to a higher incidence of MACCEs, whether UA was treated as a categorical or continuous variable (hazard ratio [HR] 2.76, 95% confidence interval [CI] 1.27–6.03 or HR 1.01, 95% CI 1.01–1.02). The restricted cubic spline (RCS) analysis illustrated that the HR for MACCEs increased with increasing UA. ConclusionThe present study demonstrates that UA is associated with MACCEs risk and suggests that UA is a reliable predictor of long-term cardiovascular events in coronary intermediate stenosis patients.

Clonal hematopoiesis of indeterminate potential (CHIP) and cardiovascular toxicity from androgen deprivation therapy in men with prostate cancer.

312 Background: Androgen deprivation therapy (ADT) with agonists of the gonadotropin releasing hormone (GnRH) receptor (e.g. leuprolide) is associated with coronary artery disease and major adverse cardiovascular (CV) events. CHIP, an age-related expanded somatic blood cell clone without other hematologic abnormalities, is associated with inflammation and accelerated atherosclerosis. Whether CHIP is associated with adverse CV outcomes in patients receiving ADT is unknown. Methods: Twenty-five men with localized prostate cancer pursuing radiotherapy plus ≥ 6 months of leuprolide were enrolled on a prospective biorepository. Using pre-treatment blood samples, whole exome sequencing libraries were generated; identified variants were filtered to retain &lt;1% MAF variants found amongst the three most common CHIP genes ( DNMT3A, TET2, ASXL1). Pre-treatment and 6-month blood samples from each patient subsequently were analyzed using a commercially available, validated 4-protein risk score that is predictive of 4-year major adverse CV events (Prevencio Inc HART CVE, Seattle WA). Multivariable logistic regression measured the association of CHIP with increased CV risk after initiation of leuprolide, defined as a clinically significant rise in 4-protein risk score at six months compared with baseline. Results: Median age was 70 years (IQR 65-76), 10 men (40%) were Black, and 4 men (16%) had a history of myocardial infarction. CHIP gene variants were found in 7 men (28%). Amongst the men with CHIP variants, 6 (85.7%) were Black. Amongst the entire cohort, 11/25 (44%) men had a clinically significant rise in CV risk score after six months of ADT. These men, compared with those who did not experience a rise in CV risk, were more often Black (72.7% versus 14.3%), on anti-hypertensive medication (72.7% versus 14.3%), and had higher baseline LDL cholesterol level (median 98 versus 81 mg/dL). On univariate analysis, harboring ≥1 CHIP variant was associated with a significantly increased odds of having an elevated CV risk score after 6 months of ADT. On multivariable analysis, after adjusting for race, anti-hypertensive medication use, and baseline LDL cholesterol, harboring ≥1 CHIP variant was associated with increased odds of having an elevated CV risk score after 6 months of ADT (adjusted OR 1.44, 95% CI 0.88-1.83), which did not meet statistical significance but limited by small sample size. Conclusions: Six months of GnRH-agonist leuprolide resulted in a rise in CV risk score in 44% of this cohort. CHIP variants, identified in 28% of this cohort, was associated with increased odds of experiencing a rise in CV risk score. Notably, Black men were more likely to harbor CHIP and experience increased CV risk after 6 months of leuprolide, respectively. Larger studies are underway to determine if CHIP variants may serve as a biomarker of ADT-induced CV risk, especially in older Black men.

Blood pressure levels and adverse cardiovascular outcomes in heart failure: A systematic review and meta-analysis.

Existing data on the association between blood pressure levels and adverse cardiovascular outcomes in patients with heart failure (HF) are inconsistent. The optimal blood pressure targets for patients with HF remain uncertain. This study sought to assess the associations between blood pressure (systolic and diastolic blood pressure, SBP and DBP) levels and adverse cardiovascular disease (CVD) outcomes in patients with HF. A systematic review and meta-analysis were conducted using MEDLINE, Embase, the Cochrane Library, and Web of Science databases up to 5 May 2023. The outcomes of interest included adverse cardiovascular events and all-cause mortality. Pooled relative risks (RRs) with corresponding 95% confidence intervals (CIs) were calculated. Forty-three unique observational cohort studies, comprising 120 643 participants with HF, were included. The pooled RRs (95% CIs) for SBP thresholds of ≥140 mmHg vs <140 mmHg were 0.92 (0.83-1.01) for all-cause mortality, 0.83 (0.67-1.04) for CVD death, and 0.98 (0.80-1.21) for HF hospitalization. The pooled RR (95% CI) for SBP thresholds of ≥160 mmHg vs <160 mmHg and all-cause mortality was 0.67 (0.62-0.74). SBP levels below <130, <120, and < 110 mmHg were each associated with an increased risk of various cardiovascular endpoints and all-cause mortality. The pooled RR (95% CI) for DBP thresholds of ≥80 mmHg vs <80 mmHg and all-cause mortality was 0.86 (0.67-1.10). A 10 mmHg increase in SBP or DBP was associated with a reduction in all-cause mortality and other cardiovascular endpoints. The findings suggest that lower and normal baseline SBP levels (<130, <120, and < 110 mmHg) may be associated with future risk of worse outcomes in patients with HF. Optimal baseline blood pressure levels for these patients may lie within the range of ≥140 mmHg for SBP. In the absence of observational studies with repeated blood pressure measurements or definitive trials evaluating optimal blood pressure targets, individualized blood pressure targets based on patients' unique circumstances are warranted in HF management.

Psychological Distress and the Risk of Adverse Cardiovascular Outcomes in Patients With Coronary Heart Disease

BackgroundPsychological distress is a recognized risk factor in patients with coronary heart disease (CHD), but its clinical significance is unclear. ObjectivesThe purpose of this study was to determine if an index of psychological distress is independently associated with adverse outcomes and significantly contributes to risk prediction. MethodsPooled analysis of 2 prospective cohort studies of patients with stable CHD (N = 891). A psychological distress score was constructed using measures of depression, anxiety, anger, perceived stress, and post-traumatic stress disorder, measured at baseline. The study endpoint included cardiovascular death or first or recurrent nonfatal myocardial infarction or hospitalization for heart failure at 5.9 years. ResultsIn both cohorts, first and recurrent events occurred more often among those in the highest tertile of distress score than those in the lowest tertile. After combining the 2 cohorts, compared with the lowest tertile, the hazards ratio for having a distress score in the highest tertile was 2.27 (95% CI: 1.69-3.06), and for the middle tertile, it was 1.52 (95% CI: 1.10-2.08). Adjustment for demographics and clinical risk factors only slightly weakened the associations. When the distress score was added to a traditional clinical risk model, C-statistic, net reclassification index, and integrative discrimination index all significantly improved. ConclusionsAmong patients with CHD, a composite measure of psychological distress was significantly associated with an increased risk of adverse events and significantly improved risk prediction.

Immune Activation Mediates the Association of Advanced Hepatic Fibrosis With Adverse Outcomes in Patients With Coronary Artery Disease.

Literature suggests a bidirectional association between advanced hepatic fibrosis (AHF) and coronary artery disease (CAD). We evaluated the association of AHF with immune activation, systemic inflammation, and adverse outcomes in patients with CAD. A fibrosis-4 index cutoff value ≥2.67 was used to define AHF. Circulating levels of soluble urokinase plasminogen activator receptor and hsCRP (high-sensitivity C-reactive protein) were measured as markers for immune activation and systemic inflammation, respectively. The relationship of AHF with soluble urokinase plasminogen activator receptor, hsCRP, and adverse cardiovascular outcomes was evaluated. Among 3406 participants with CAD, 479 had AHF. Participants with AHF were older; were less likely to be Black individuals; and had a lower body mass index, worse renal function, and a prior history of heart failure. In multivariable linear regression models adjusted for clinical and demographic confounders, participants with AHF had 15.6% higher soluble urokinase plasminogen activator receptor and 24.0% higher hsCRP levels. They were more likely to experience the following adverse outcomes: all-cause death (adjusted hazard ratio [HR], 1.57 ([95% CI, 1.29-1.92]; P<0.001) and cardiovascular death: (subdistribution HR, 1.50 [95% CI, 1.14-1.95]; P=0.003). Mediation analysis showed that 47.0% (95% CI, 13.6%-81.2%]; P=0.006) of the indirect effect of AHF on cardiovascular death was mediated by circulating soluble urokinase plasminogen activator receptor levels. AHF is independently associated with immune activation, systemic inflammation, and adverse cardiovascular outcomes in patients with CAD. The association of AHF with adverse outcomes is partly mediated by immune activation, and targeting this pathway may help reduce the residual risk in patients with CAD.

Myelofibrosis Is Associated with Poor Cardiovascular Outcomes after Heart Failure Hospitalization

Background: Myeloproliferative neoplasms (MPN), including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are at high risk of cardiovascular (CV) disease including heart failure (HF). Prior studies have suggested patients with MPN are at increased risk of HF. Among patients with MPN, those with MF have the most aggressive disease with significantly shortened survival. However, data on CV outcomes among patients with MF are sparse. Therefore, we examined CV outcomes among patients with MPN hospitalized for HF. Methods: This was a retrospective cohort analysis of the National Readmission Database (NRD) of adult patients with a primary diagnosis of HF from 2017 and 2018 with a history of MPN (N = 4632), which were identified using ICD-10 codes. The primary outcome was 90-day unplanned CV-related readmission (readmission for HF, arterial thrombotic event [ATE], or venous thromboembolism [VTE]). Secondary outcomes were index hospitalization death and 90-day any-cause unplanned readmission. Propensity scores (PS) for estimating probability of MF were calculated using non-parsimonious multivariable logistic regression that included all baseline patient characteristics examined. PS weighting (PSW) was utilized to adjust for potential confounders. Patients with MF were compared with patients with ET or PV and standardized mean difference (SMD) was calculated for variables before and after PSW. Imbalances between groups were significant if SMD for a given covariable was ≥ 0.10. Hazard ratios (HR) were estimated for 90-day readmission outcomes using Cox proportional hazards regression and odds ratio (OR) for estimating index hospitalization death were calculated using logistic regression. Results: A total of 3748 patients with ET or PV (2639 ET, 1109 PV) and 884 with MF were included. Prior to PSW, patients with MF were older (mean age 77.7 vs 74.3 years), more likely to have anemia (53.8% vs 47.2%) and less likely to be female (44.9% vs 56.1%), have systolic HF (39.9% vs 46.1%), and cardiogenic shock (1.6% vs 3.4%) compared with ET/PV, Table. After PSW, baseline characteristics were well balanced between groups. After PSW, MF was associated with increased risk of 90-day CV readmission (HR 1.18, 95% CI 1.08 - 1.30), index hospitalization death (OR 1.67, 95% CI 1.38 - 2.01), and 90-day any-cause readmission (HR 1.26, 95% CI 1.17 - 1.35). Additionally, MF was associated with increased risk of 90-day HF readmission (HR 1.24, 95% CI 1.12 - 1.38) but not ATE (HR 0.62, 95% CI 0.47 - 0.81) or VTE-readmission (HR 0.72, 95% CI 0.43 - 1.19), Figure. Conclusions: Patients with MPN admitted with HF have high rates of 90-day CV-related and any-cause readmissions. MF was associated with higher risk of 90-day CV-related, HF, and any-cause readmission compared with patients with ET or PV. Patients with MF had higher risk of index HF hospitalization mortality compared with ET or PV. More investigation is needed in order to identify risk factors for adverse CV outcomes in patients with MPNs with HF, particularly those with MF. Although preventing thrombotic complications and managing CV risk are part of routine care for ET and PV patients, this study highlights the importance of incorporating CV risk management in MF patients.

Association Between Self-Rated Medication Adherence and Adverse Cardiovascular Outcomes in Patients With Hypertension.

Background Medication nonadherence contributes to poor health outcomes but remains challenging to identify. This study assessed the association between self-rated adherence and systolic blood pressure, low-density lipoprotein cholesterol levels, cardiovascular events, and all-cause mortality in SPRINT (Systolic Blood Pressure Intervention Trial). Methods and Results A total of 9361 patients randomized to 2 systolic blood pressure target groups, <120 mm Hg (intensive) and <140 mm Hg (standard), self-rated their medication adherence at each visit by marking a scale, ranging from 0% to 100%. Lower and high adherence were defined as scores ≤80% and >80%, respectively. Linear mixed effect regression models and Cox proportional hazard models were used to evaluate the association between self-rated adherence and systolic blood pressure and low-density lipoprotein cholesteroland cardiovascular events and all-cause mortality, respectively. A total of 9278 participants (mean age 68±9.4 years, 35.6% female) had repeated self-rated adherence measurements available, with a mean of 15±4 measurements per participant over 3.8 years follow-up. Of these, 2694 participants (29.0%) had ≥1 adherence measurements ≤80%. Compared with high-adherent patients, patients with lower adherence had significantly higher estimated on-treatment systolic blood pressure at 2-year follow-up: 128.7 (95% CI, 127.6-129.9) versus 120.0 (95% CI, 119.7-120.2) mm Hg in the intensive arm; and 139.8 (95% CI 138.4-141.1) versus 135.0 (95% CI 134.7-135.2) in the standard arm. Moreover, lower adherence was associated with an estimated 11 mg/dL higher low-density lipoprotein cholesterol level, more cardiovascular events (hazard ratio [HR], 1.69 [95% CI, 1.20-2.39]), and higher all-cause mortality (HR, 1.63 [95% CI, 1.16-2.31]). Conclusions Self-rated adherence allows identification of lower medication adherence and correlates with blood pressure control, low-density lipoprotein cholesterol levels, and adverse outcomes.

Catheter ablation for atrial fibrillation in patients with heart failure with reduced versus preserved ejection fraction; a systematic review and meta-analysis

Abstract Background Catheter ablation is superior to pharmacological therapies for lowering adverse cardiovascular outcomes in patients with both atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF). Yet, it is uncertain whether patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF) derive the same treatment benefit from catheter ablation. Purpose This systematic review and meta-analysis aimed to assess whether the efficacy of AF catheter ablation in reducing all-cause mortality and heart failure events is different in patients with HFrEF versus HFpEF. Methods We searched MEDLINE, Embase, and Cochrane Central to September 2022 for randomized controlled trials in patients with heart failure comparing catheter ablation for AF with medical therapy (defined as rate or rhythm control with medications, device implantation, and/or cardioversion). The outcomes of interest were all-cause mortality and heart failure events (i.e. hospitalization or worsening). Pairs of reviewers systematically screened the eligible studies and used random-effects models to combine data. We contacted authors of eligible studies to obtain unpublished data on heart failure subgroups. We used an interaction p-value to test the statistical significance of difference between subgroups with HFrEF and HFpEF. Results A total of 8 studies (2118 participants, mean age: 65.6 years, 28.1% women) assessed the effect of catheter ablation on all-cause mortality in patients with AF and heart failure. We found no statistical evidence of a different effect for AF catheter ablation in reducing all-cause mortality in patients with HFrEF (196 events, RR 0.67, 95% CI: 0.50-0.90) compared to those with HFpEF (77 events, RR 0.95, 95% CI: 0.39-2.30) – p for subgroup differences=0.46. In addition, 7 studies (2057 participants, mean age: 65.8 years, 29% women) evaluated the effect of catheter ablation on heart failure events in patients with AF and heart failure. As compared to conventional medical therapies, AF catheter ablation significantly reduced the risk of heart failure events in patients with HFrEF (285 events, RR 0.59, 95% CI: 0.48-0.72); however, it had little or no effect on heart failure events in those with HFpEF (106 events, RR 0.93, 95% CI: 0.65-1.32). Interaction analysis showed significant effect modification for AF catheter ablation in patients with HFpEF – p for subgroup differences=0.03. Conclusion Catheter ablation is superior to conventional medical therapies for reducing all-cause mortality in patients with AF and heart failure. However, its beneficial effect on heart failure events may be limited to patients with HFrEF. The available evidence on patients with HFpEF is insufficient for a definitive conclusion. Future trials are warranted to study the prognostic effect of catheter ablation in patients with AF and HFpEF.All-cause MortalityHeart Failure Events

Kidney function by creatinine and cystatin c and adverse cardiovascular outcomes in patients with atrial fibrillation

Abstract Background Atrial fibrillation (AF) patients with chronic kidney disease are at an increased risk for ischemic and bleeding events and all-cause mortality. Accurate kidney function estimation is key for risk assessment. Creatinine is commonly used to calculate the Glomerular Filtration Rate (GFR). However, cystatin c has been described to be more sensitive than creatinine independent of muscle mass, autoimmune disease, inflammation or consuming diseases. Thus, cystatin C might be superior for risk assessment in patients with AF. Aim We aimed to investigate the associations between kidney function, assessed by creatinine and cystatin c, and major adverse cardiovascular events (MACE), its individual components, and major bleedings. Methods We enrolled 3865 AF patients into two prospective, multicenter cohort studies. Creatinine and cystatin c were measured at baseline and clinical outcome events were assessed yearly. We calculated GFR using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula based on either creatinine (GFRcr), cystatin c (GFRcy) or both (GFRc2). Primary outcome was MACE, defined as a composite of stroke or systemic embolism, myocardial infarction and cardiovascular death. Secondary outcomes were the individual components of MACE and major bleeding. Multivariable adjusted Cox regression analyses were built to investigate the associations between kidney function and adverse outcome events. Results Mean age was 71 ± 10 years and 28% were female. Mean creatinine and cystatin levels were 103 ± 32 μmol/l and 1.2 ± 0.4 mg/l, respectively, translating to a GFRc2 of 63.8 ± 21.7 ml/min/1.73 m2. Over a median follow-up of 6 years, the incidence rates for MACE (per 100 person-years) across quartiles (Q1-Q4) of GFRc2 were 22.0, 19.6, 17.4 and 15.9, respectively (Figure). When using multivariable adjusted Cox regression analysis, MACE was significantly associated with GFRcr (per 1 standard deviation: HR 0.87 (95%CI 0.77; 0.97) p=0.01), GFRcy (HR 0.68 (CI 0.58; 0.78), p&amp;lt;0.001) and GFRc2 (HR 0.75 (CI 0.66; 0.86), p&amp;lt;0.001). This association was mainly driven by cardiovascular death (Table). Major bleeding was associated with GFRcy (HR 0.73 (0.60-0.88) p=0.001) and GFRc2 (HR 0.80 (0.67-0.95), p=0.01), but not with GFRcr (HR 0.91 (95% CI 0.78-1.07) p=0.25). Conclusion Among AF patients, GFR equations including cystatin c were associated both with MACE and bleeding events, while creatinine based GFR equations were only associated with MACE. Therefore, Cystatin c based GFR equations might offer more comprehensive risk stratification in AF patients.Figure 1Table 1

Natural course and prognostic impact of lead-related tricuspid regurgitation

Abstract Aim Direct injury from Cardiac Implantable Electrical Device (CIED) leads is one of the most common causes of tricuspid regurgitation (TR), with a reported prevalence up to 40%. Little is known about the natural history of CIED-related TR and the prognostic impact of worsening TR detected at different time points after CIED implantation. Methods The CIED-IT registry retrospectively included patients who underwent CIED implantation in a tertiary referral center in Italy, as long as they had been performed repeated transthoracic echocardiograms (TTE) and at least one chest CT after the implantation. TR severity was graded using a pre-specified 4-class grading scheme: mild, moderate, severe and massive. The primary endpoint for outcome analysis was major adverse clinical events (MACE), defined as the composite of all-cause death or heart failure (HF) hospitalizations. Results 249 patients undergoing CIED implantation from January 2015 to December 2021 were included. Median time to last available TTE was 1593 days (IQR 857-2089). TR prevalence was 71.8% (178/248) at baseline and 88.7% (220/248, p&amp;lt;0.001) at last available TTE. Worsening TR was observed in 48.4% (120/248) of cases. Mean age was 74.5±10.1 years, 35% of patients were females, 45.6% had atrial fibrillation and 41.9% had a LVEF &amp;lt;40%. Baseline RV dysfunction was present in 23.8% of patients, while a worsening RV function was observed in 24.2% of patients with worsening TR and 10.1% of those without worsening TR (p=0.003). Median follow-up time was 4.2 years (IQR: 2.4-5.6). At Kaplan Maier analysis, the cumulative 5-year MACE incidence was 39.4% (95% CI: 30.4-50%) in patients with worsening TR and 18.9% (95% CI: 12.5-28.1%) in those with no worsening TR (Log-Rank p = 0.01). This difference was mainly driven by a higher rate of heart failure hospitalizations in the worsening TR group (36.5% vs, 10 at 5y, Log-Rank p&amp;lt;0.001), while the rate of all-cause death was comparable between the two groups (Log-Rank p=0.313). At multivariable stepwise Cox regression analysis, worsening TR was an independent predictor of both MACE (HR 1.89, 95% CI: 1.15-3.11, p=0.012) and HF hospitalizations (HR 2.77, 95% CI: 1.49-5.16, p=0.001). In a subgroup analysis including patients who also received a 1-year TTE (median time 182 days, IQR: 74-286), worsening TR at last available TTE was still an independent MACE predictor (HR 1.75, 95% CI: 1.0-3.1, p=0.05), while worsening TR at 1y was not (HR 1.66, 95% CI: 0.9-3.06). Conclusions CIED-related TR is a strong determinant of long-term adverse cardiovascular outcomes in patients undergoing CIED implantation. Lead-induced injury is sometimes not evident in the first months after the procedure and might require years to develop clinically significant TR. Serial echocardiographic assessments are therefore pivotal to implement risk stratification, while further knowledge of the pathophysiology of CIED-related TR is required to prevent its occurrence.Kaplan Maier Curves for MACEKaplan Maier curves for HHF

Abstract 13155: Safety and Efficacy of Anti-Hypertensive Medications in Patients With Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta-Analysis

Introduction: Hypertension (HTN) is a co-morbidity that is commonly associated with heart failure (HF) with preserved ejection fraction (HFpEF). This meta-analysis aims to evaluate the association of anti-hypertensive medications (AHM) therapy with cardiovascular (CV) outcomes in patients with HFpEF. Hypothesis: Treatment of HTN in HFpEF patients is associated with improved CV outcomes. Methods: Performed a database search (OVID Medline, Web of Science, and Embase) for studies reporting the association of AHM with CV outcomes in patients with HFpEF. The primary endpoint was all-cause mortality. Secondary endpoints include CV mortality, worsening HF, CV hospitalization, and major adverse CV events (MACE). Results: A total of 15 studies with 17507 HFpEF participants (8732 treated with medical therapy vs 8775 treated with placebo) met inclusion criteria. Use of AHM was not associated with lower all-cause mortality or CV mortality compared to treatment with placebo (OR 1.01, 95% CI 0.80-1.27; p=0.95, OR 0.97, 95% CI 0.86-1.08; p=0.53). Use of AHM was associated with a statistically significant lower risk of MACE and CV hospitalization (OR 0.90, 95% CI 0.83-0.97; p&lt;0.01, OR 0.89, 95% CI 0.81-0.97; p&lt;0=0.04). Subgroup analysis demonstrated this to be primarily driven by studies with mixed HFpEF patients with or without HTN, not HFpEF patients with HTN. There was a non-significant trend toward lower risk of worsening HF in patients treated with AHM, and was driven by HFpEF patients with or without HTN, not HFpEF patients with HTN (OR 0.87, 95% CI 0.78-0.97; p=0.02 versus OR 0.57, 95% CI 0.18-1.86; p=0.35). Conclusion: While treatment with anti-hypertensives was not associated with lower risk of all-cause mortality, their use may be associated with reduced risk of adverse CV outcomes in patients with HFpEF regardless of whether they have HTN. Further studies are needed to clarify this association and determine the effect based on specific classes of medications.

Abstract 18437: Efficacy and Safety of Dapagliflozin in Patients With Heart Failure and Previous Myocardial Infarction

Introduction: Patients with HF and history of myocardial infarction (MI) may represent a distinct subpopulation with unique pathways of disease progression and elevated risk of clinical events. Whether SGLT2 inhibitors may modify disease trajectory in such individuals is uncertain. Methods: The DAPA-HF and DELIVER trials compared dapagliflozin with placebo in patients with symptomatic HF with LVEF ≤40% and &gt;40%, respectively. In this pooled participant-level analysis, we assessed efficacy and safety outcomes by history of MI. The primary outcome in both trials was the composite of cardiovascular (CV) death or worsening HF. Results: Of the total of 11,007 patients, 3,731 (34%) had a prior MI and were at higher risk of the primary outcome across the spectrum of LVEF in covariate-adjusted models (HR 1.12 [95% CI 1.02-1.24]; Left Panel ). Dapagliflozin reduced the risk of the primary outcome to a similar extent in patients with (HR 0.83 [95% CI 0.72-0.96]) and without prior MI (HR 0.76 [95% CI 0.68-0.85]; P i nteraction =0.36), with consistent benefits on key secondary outcomes as well ( Right Panel ). Serious adverse events did not occur more frequently with dapagliflozin, irrespective of prior MI. Conclusions: History of MI confers increased risks of adverse cardiovascular outcomes in patients with HF across the spectrum of ejection fraction. Dapagliflozin consistently and safely reduces the risk of adverse cardiovascular outcomes, regardless of previous MI. Ongoing trials are actively examining SGLT2 inhibitors when introduced early after acute MI.

Associations of Inflammatory Biomarkers With the Risk of Morbidity and Mortality After Cardiac Surgery: A Systematic Review and Meta-analysis.

Although inflammatory biomarkers have been associated with cardiovascular events in nonsurgical settings, these associations have not been systematically addressed in patients undergoing cardiac surgery. This review aimed to evaluate the relationships of inflammatory markers with mortality and adverse cardiovascular events in patients undergoing cardiac surgery. Medline, Embase, and Central databases were systematically searched for studies reporting pre- or postoperative levels of inflammatory biomarkers in patients undergoing cardiac surgery. Outcomes of interest were postoperative mortality, nonfatal myocardial infarction, stroke, congestive heart failure, and major adverse cardiovascular events (MACE). Studies reporting multivariable adjusted risk estimates were included. Risk estimates were pooled with the use of random-effects models and reported as summary odds ratios (ORs). Among 14,465 citations identified, 29 studies including 29,401 participants met the eligibility criteria. The average follow-up time after surgery was 31 months. Preoperative C-reactive protein (CRP) levels were associated with an increased risk of all-cause mortality (OR 1.88, 95% CI 1.60-2.20; I2= 19%; 11 studies) and MACE (OR 1.73, 95% CI 1.34-2.24; I2= 0%; 3 studies). CRP levels measured on postoperative day 6 (OR 7.4, 95% CI 2.90-18.88, 1 study) and day 10 (OR 11.8, 95% CI 3.50-39.78, 1 study) were associated with a higher risk of all-cause mortality. Less, but overall similar, information was available for other inflammatory biomarkers. In this large meta-analysis, inflammatory biomarkers measured before or after cardiac surgery were associated with mortality and adverse cardiovascular outcomes in patients undergoing cardiac surgery.

Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients.

This study attempted to identify exosomal circular RNAs (circRNAs) as diagnostic and prognostic biomarkers for patients with ST-segment elevation myocardial infarction (STEMI). The differentially expressed exosomal circRNAs (DEECs) were screened from microarray dataset (GSE160717 and GSE197137) and RNA-Seq dataset (GSE208194), and the expression levels of DEECs in patients with STEMI were validated using reverse transcription and quantitative real-time PCR. The diagnostic value of DEECs was assessed using receiver operating characteristic curves. The major adverse cardiovascular event (MACE)-free 1-year survival rate was evaluated using the Kaplan-Meier method, and the factors affecting prognosis were determined using Cox regression model analysis. Results showed that four DEECs were screened including exo-circ-0001490, exo-circ-0020887, exo-circ-0009590, and exo-circ-0055440, and only upregulated exo-circ-0020887 and exo-circ-0009590 expression was validated in patients with STEMI. The exo-circ-0020887 and exo-circ-0009590 expression was positively correlated with hs-CRP, LDL-C, cTnI, and CK-MB. The exo-circ-0020887 and exo-circ-0009590 showed good diagnostic efficacy to distinguish STEMI patients from healthy controls (area under the curves: 0.85 and 0.80). STEMI patients with high levels of exo-circ-0020887 and exo-circ-0009590 had lower MACE-free 1-year survival rate, and exo-circ-0020887 and exo-circ-0009590 expression was independent risk factors for adverse prognosis. In summary, upregulation of plasma exo-circ-0020887 and exo-circ-0009590 might act as potential biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in patients with STEMI.