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Cardiovascular Diabetology Jun 2024Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) are glucose-lowering agents used for the treatment of type 2 diabetes mellitus, which also improve heart failure and...
BACKGROUND
Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) are glucose-lowering agents used for the treatment of type 2 diabetes mellitus, which also improve heart failure and decrease the risk of cardiovascular complications. Epicardial adipose tissue (EAT) dysfunction was suggested to contribute to the development of heart failure. We aimed to elucidate a possible role of changes in EAT metabolic and inflammatory profile in the beneficial cardioprotective effects of SGLT-2i in subjects with severe heart failure.
METHODS
26 subjects with severe heart failure, with reduced ejection fraction, treated with SGLT-2i versus 26 subjects without treatment, matched for age (54.0 ± 2.1 vs. 55.3 ± 2.1 years, n.s.), body mass index (27.8 ± 0.9 vs. 28.8 ± 1.0 kg/m, n.s.) and left ventricular ejection fraction (20.7 ± 0.5 vs. 23.2 ± 1.7%, n.s.), who were scheduled for heart transplantation or mechanical support implantation, were included in the study. A complex metabolomic and gene expression analysis of EAT obtained during surgery was performed.
RESULTS
SGLT-2i ameliorated inflammation, as evidenced by the improved gene expression profile of pro-inflammatory genes in adipose tissue and decreased infiltration of immune cells into EAT. Enrichment of ether lipids with oleic acid noted on metabolomic analysis suggests a reduced disposition to ferroptosis, potentially further contributing to decreased oxidative stress in EAT of SGLT-2i treated subjects.
CONCLUSIONS
Our results show decreased inflammation in EAT of patients with severe heart failure treated by SGLT-2i, as compared to patients with heart failure without this therapy. Modulation of EAT inflammatory and metabolic status could represent a novel mechanism behind SGLT-2i-associated cardioprotective effects in patients with heart failure.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Heart Failure; Middle Aged; Male; Female; Pericardium; Adipose Tissue; Treatment Outcome; Inflammation Mediators; Severity of Illness Index; Stroke Volume; Anti-Inflammatory Agents; Ventricular Function, Left; Diabetes Mellitus, Type 2; Metabolomics; Biomarkers; Epicardial Adipose Tissue
PubMed: 38943140
DOI: 10.1186/s12933-024-02298-9 -
BMC Cardiovascular Disorders Jun 2024Pulmonary transit time (PTT) can be measured automatically from arterial input function (AIF) images of dual sequence first-pass perfusion imaging. PTT has been...
BACKGROUND
Pulmonary transit time (PTT) can be measured automatically from arterial input function (AIF) images of dual sequence first-pass perfusion imaging. PTT has been validated against invasive cardiac catheterisation correlating with both cardiac output and left ventricular filling pressure (both important prognostic markers in heart failure). We hypothesized that prolonged PTT is associated with clinical outcomes in patients with heart failure.
METHODS
We recruited outpatients with a recent diagnosis of non-ischaemic heart failure with left ventricular ejection fraction (LVEF) < 50% on referral echocardiogram. Patients were followed up by a review of medical records for major adverse cardiovascular events (MACE) defined as all-cause mortality, heart failure hospitalization, ventricular arrhythmia, stroke or myocardial infarction. PTT was measured automatically from low-resolution AIF dynamic series of both the LV and RV during rest perfusion imaging, and the PTT was measured as the time (in seconds) between the centroid of the left (LV) and right ventricle (RV) indicator dilution curves.
RESULTS
Patients (N = 294) were followed-up for median 2.0 years during which 37 patients (12.6%) had at least one MACE event. On univariate Cox regression analysis there was a significant association between PTT and MACE (Hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.08-1.25, P = 0.0001). There was also significant association between PTT and heart failure hospitalisation (HR 1.15, 95% CI 1.02-1.29, P = 0.02) and moderate correlation between PTT and N-terminal pro B-type natriuretic peptide (NT-proBNP, r = 0.51, P < 0.001). PTT remained predictive of MACE after adjustment for clinical and imaging factors but was no longer significant once adjusted for NT-proBNP.
CONCLUSIONS
PTT measured automatically during CMR perfusion imaging in patients with recent onset non-ischaemic heart failure is predictive of MACE and in particular heart failure hospitalisation. PTT derived in this way may be a non-invasive marker of haemodynamic congestion in heart failure and future studies are required to establish if prolonged PTT identifies those who may warrant closer follow-up or medicine optimisation to reduce the risk of future adverse events.
Topics: Humans; Heart Failure; Male; Female; Middle Aged; Aged; Predictive Value of Tests; Time Factors; Prognosis; Ventricular Function, Left; Myocardial Perfusion Imaging; Stroke Volume; Risk Factors; Pulmonary Circulation; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Artery; Risk Assessment; Ventricular Function, Right; Magnetic Resonance Imaging
PubMed: 38943084
DOI: 10.1186/s12872-024-04003-w -
American Heart Journal Jun 2024It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can...
PCSK9 Inhibitor Added to High-Intensity Statin Therapy to Prevent Cardiovascular Events in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Randomized, Double- Blind, Placebo-Controlled, Multicenter SHAWN Study.
BACKGROUND
It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions.
METHODS
This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at one-year follow-up between two groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance.
CONCLUSION
The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.
PubMed: 38942221
DOI: 10.1016/j.ahj.2024.06.004 -
Metabolism: Clinical and Experimental Jun 2024Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic conditions affect populations across economic strata. Nevertheless, there are...
Disparities in metabolic dysfunction-associated steatotic liver disease and cardiometabolic conditions in low and lower middle-income countries: systematic analysis from the global burden of disease study 2019.
OBJECTIVE
Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic conditions affect populations across economic strata. Nevertheless, there are limited epidemiological studies addressing these diseases in low (LICs) and lower-middle-income countries (lower MICs). Therefore, an analysis of the trend of MASLD and cardiometabolic conditions in these countries is necessary.
METHODS
From 2000 to 2019, jointpoint regression analysis was employed to calculate the prevalence, mortality, and disability-adjusted life years (DALYs) for cardiometabolic conditions including MASLD, type 2 diabetes mellitus (T2DM), dyslipidemia (DLP), hypertension (HTN), obesity, peripheral artery disease (PAD), atrial fibrillation and flutter (AF/AFL), ischemic heart disease (IHD), stroke, and chronic kidney disease from HTN and T2DM, in LICs and lower MICs (according to the World Bank Classification 2019) using the Global Burden of Disease 2019 data.
RESULTS
Among the eleven cardiometabolic conditions, MASLD (533.65 million), T2DM (162.96 million), and IHD (76.81 million) had the highest prevalence in LICs and Lower MICs in 2019. MASLD represented the largest proportion of global prevalence in these countries (43 %). From 2000 to 2019, mortality in LICs and lower MICs increased in all cardiometabolic conditions, with obesity-related mortality having the highest increase (+134 %). During this timeframe, there were increased age-standardized death rates (ASDR) from obesity, PAD, and AF/AFL. From all conditions, the DALYs-to-prevalence ratio was higher in LICs and lower MICs than the global average.
CONCLUSION
The burden of MASLD and cardiometabolic conditions is increasing worldwide, with LICs and lower MICs experiencing higher disability per prevalence. As these conditions are preventable, counteracting these trends requires not only the modification of ongoing actions but also the strategizing of immediate interventions.
PubMed: 38942169
DOI: 10.1016/j.metabol.2024.155958 -
Europace : European Pacing,... Jun 2024Anticoagulation can prevent stroke and prolong lives in patients with atrial fibrillation (AF); However, anticoagulated patients with AF remain at risk of death. The aim...
AIMS
Anticoagulation can prevent stroke and prolong lives in patients with atrial fibrillation (AF); However, anticoagulated patients with AF remain at risk of death. The aim of this study was to investigate the causes of death and factors associated with all-cause and cardiovascular death in the XANTUS population.
METHODS AND RESULTS
Causes of death occurring within a year after rivaroxaban initiation in patients in the XANTUS program studies were adjudicated by a central adjudication committee and classified following international guidance.Baseline characteristics associated with all-cause or cardiovascular death were identified. Of 11,040 patients, 187 (1.7%) died. Almost half of these deaths were due to cardiovascular causes other than bleeding (n = 82, 43.9%), particularly heart failure (n = 38, 20.3%) and sudden or unwitnessed death (n = 24, 12.8%). Fatal stroke (n = 8, 4.3%), which was classified as a type of cardiovascular death, and fatal bleeding (n = 17, 9.1%) were less common causes of death. Independent factors associated with all-cause or cardiovascular death included age, AF type, body mass index, left ventricular ejection fraction, hospitalization at baseline, rivaroxaban dose, and anaemia.
CONCLUSION
The overall risk of death due to stroke or bleeding was low in XANTUS. Anticoagulated patients with AF remain at risk of death due to heart failure and sudden death. Potential interventions to reduce cardiovascular deaths in anticoagulated patients with AF, require further investigation, e.g. early rhythm control therapy and AF ablation.
PubMed: 38941511
DOI: 10.1093/europace/euae183 -
Interdisciplinary Cardiovascular and... Jun 2024Less invasive surgery has emerged as an option for aortic pathologies. The current study compared our experience on early postoperative results of patients with aortic...
OBJECTIVES
Less invasive surgery has emerged as an option for aortic pathologies. The current study compared our experience on early postoperative results of patients with aortic surgery between partial upper sternotomy (PUS) and full sternotomy (FS).
METHODS
We performed a retrospective analysis of the data of patients undergoing aortic root surgery with concomitant ascending aorta and hemiarch replacement. Exclusion criteria were type A aortic dissection and other concomitant major cardiac surgery. After propensity-score matching, we compared the perioperative outcomes of patients undergoing surgery with PUS vs FS.
RESULTS
161 patients operated on between January 2013 and September 2022 met the inclusion criteria (PUS: n = 22, FS: n = 139). Propensity score matching yielded 22 pairs with a balanced distribution of propensity scores and covariates between the compared groups. There was no evidence that PUS affects cardiopulmonary bypass [108(67-119) vs 113(87-148) min, p = 0.154; PUS vs FS] and circulatory arrest duration [9(7-10) vs 9(8-13) min, p = 0.264; PUS vs FS]. There was a reduced cross-clamp duration in the PUS group [88(58-96) vs 92(71-122) min, p = 0.032]. Cumulative sum charts (CUSUM) have shown consistently low cross-clamp and circulatory arrest duration for two experienced surgeons who performed 20 of the procedures in the PUS group (10 each). Perioperative mortality and morbidity were low, with no in-hospital mortality in the PUS group [0 vs 1(4.5%), p > 0.999] and absence of strokes in both groups.
CONCLUSIONS
In summary, our initial experience suggests that less invasive aortic root, ascending aorta, and hemiarch replacement via partial upper sternotomy could be performed in our patient cohort as safely as via full sternotomy. Advantages for the patient are reduced surgical trauma, improved cosmetic results, and-presumably-less pain.
PubMed: 38941507
DOI: 10.1093/icvts/ivae120 -
Clinical Cardiology Jul 2024Chronic heart failure (CHF) has always posed a significant threat to human survival and health. The efficacy of thiamine supplementation in CHF patients remains... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic heart failure (CHF) has always posed a significant threat to human survival and health. The efficacy of thiamine supplementation in CHF patients remains uncertain.
HYPOTHESIS
Receiving supplementary thiamine may not confer benefits to patients with CHF.
METHODS
A comprehensive search was conducted across the Cochrane Library, PubMed, EMBASE, ClinicalTrials.gov, and Web of Science databases up until May 2023 to identify articles investigating the effects of thiamine supplementation in CHF patients. Predefined criteria were utilized for selecting data on study characteristics and results.
RESULTS
Seven randomized, double-blind, controlled trials (five parallel trials and two crossover trials) involving a total of 274 patients were enrolled. The results of the meta-analysis pooling these studies did not reveal any significant effect of thiamine treatment compared with placebo on left ventricular ejection fraction (WMD = 1.653%, 95% CI: -1.098 to 4.405, p = 0.239, I = 61.8%), left ventricular end-diastolic volume (WMD = -6.831 mL, 95% CI: -26.367 to 12.704, p = 0.493, I = 0.0%), 6-min walking test (WMD = 16.526 m, 95% CI: -36.582 to 69.634, p = 0.542, I = 66.3%), N-terminal pro-B type natriuretic peptide (WMD = 258.150 pg/mL, 95% CI: -236.406 to 752.707, p = 0.306, I = 21.6%), or New York Heart Association class (WMD = -0.223, 95% CI: -0.781 to 0.335, p = 0.434, I = 87.1%). However, it effectively improved the status of thiamine deficiency (TD).
CONCLUSIONS
Our meta-analysis indicates that thiamine supplementation does not have a direct therapeutic effect on CHF, except for correcting TD.
Topics: Humans; Heart Failure; Thiamine; Randomized Controlled Trials as Topic; Dietary Supplements; Chronic Disease; Ventricular Function, Left; Stroke Volume; Vitamin B Complex; Treatment Outcome
PubMed: 38940395
DOI: 10.1002/clc.24309 -
Stroke Jun 2024Angioedema without concomitant urticaria is a well-known complication of treatment with the recombinant tissue-type plasminogen activator (r-tPA) alteplase and its...
Angioedema without concomitant urticaria is a well-known complication of treatment with the recombinant tissue-type plasminogen activator (r-tPA) alteplase and its genetically modified variant tenecteplase. It is potentially lethal when causing airway obstruction and can require intubation. The latest guideline for the early management of patients with acute ischemic stroke from the American Heart Association/American Stroke Association advises to treat this complication initially by interfering with the histamine pathway. This article aims to clarify the pathophysiological mechanism of r-tPA-induced angioedema and provides several arguments that this condition is primarily bradykinin-mediated and hence should be treated initially by intervening with the bradykinin pathway. Second, other-less frequently reported-adverse symptoms after r-tPA therapy and their proposed pathophysiological mechanisms leading to specific treatment are described. This manuscript describes the need for an update of the section "3.5 IV alteplase" from the American Heart Association/American Stroke Association guideline to treat this r-tPA-induced angioedema adequately and prevent potentially fatal outcomes.
PubMed: 38939926
DOI: 10.1161/STROKEAHA.124.047060 -
JACC. Advances Apr 2024Major adverse cardiovascular events (MACE) are a leading cause of morbidity and mortality among adults with type 2 diabetes. Currently, available MACE prediction models...
BACKGROUND
Major adverse cardiovascular events (MACE) are a leading cause of morbidity and mortality among adults with type 2 diabetes. Currently, available MACE prediction models have important limitations, including reliance on data that may not be routinely available, narrow focus on primary prevention, limited patient populations, and longtime horizons for risk prediction.
OBJECTIVES
The purpose of this study was to derive and internally validate a claims-based prediction model for 1-year risk of MACE in type 2 diabetes.
METHODS
Using medical and pharmacy claims for adults with type 2 diabetes enrolled in commercial, Medicare Advantage, and Medicare fee-for-service plans between 2014 and 2021, we derived and internally validated the annualized claims-based MACE estimator (ACME) model to predict the risk of MACE (nonfatal acute myocardial infarction, nonfatal stroke, and all-cause mortality). The Cox proportional hazards model was composed of 30 covariates, including patient age, sex, comorbidities, and medications.
RESULTS
The study cohort comprised 6,623,526 adults with type 2 diabetes, mean age 68.1 ± 10.6 years, 49.8% women, and 73.0% Non-Hispanic White. ACME had a concordance index of 0.74 (validation index range: 0.739-0.741). The predicted 1-year risk of the study cohort ranged from 0.4% to 99.9%, with a median risk of 3.4% (IQR: 2.3%-6.5%).
CONCLUSIONS
ACME was derived in a large usual care population, relies on routinely available data, and estimates short-term MACE risk. It can support population risk stratification at the health system and payer levels, participant identification for decentralized clinical trials of cardiovascular disease, and risk-stratified observational studies using real-world data.
PubMed: 38939660
DOI: 10.1016/j.jacadv.2024.100852 -
JACC. Advances Nov 2023Sex differences in the clinical presentation and outcomes of DeBakey type I/II (Stanford type A) acute aortic dissection (AAD) remain unclear.
BACKGROUND
Sex differences in the clinical presentation and outcomes of DeBakey type I/II (Stanford type A) acute aortic dissection (AAD) remain unclear.
OBJECTIVES
The authors aimed to determine the impact of sex on the clinical presentation and in-hospital outcomes of surgically or medically treated patients with type I/II AAD.
METHODS
We studied 3,089 patients with type I/II AAD enrolled in multicenter Japanese registry between 2013 and 2018. The patients were divided into 2 treatment groups: surgical and medical. Multivariable logistic regression was used to examine the association between sex and in-hospital mortality.
RESULTS
In the entire cohort, women were older and more likely to have hyperlipidemia, previous stroke, altered consciousness, and shock/hypotension at presentation than men. Women had higher proportions of intramural hematomas and type II dissections than men. In the surgical group (n = 2,543), men had higher rates of preoperative end-organ malperfusion ( = 0.003) and in-hospital mortality ( = 0.002) than women. Multivariable analysis revealed that male sex was associated with higher in-hospital mortality after surgery (OR: 1.71; 95% CI: 1.24-2.35; < 0.001). In the medical group (n = 546), women were older and had higher rates of cardiac tamponade ( = 0.004) and in-hospital mortality ( = 0.039) than men; no significant association between sex and in-hospital mortality was found after multivariable adjustment (OR: 0.95; 95% CI: 0.56-1.59; = 0.832).
CONCLUSIONS
Male sex was associated with higher in-hospital mortality for type I/II AAD in the surgical group but not in the medical group. Further research is needed to understand the mechanisms responsible for worse surgical outcomes in men.
PubMed: 38938720
DOI: 10.1016/j.jacadv.2023.100661