Cardiovascular Impact of Metabolic Surgery Across Patient and Surgery Subgroups: A Systematic Review and Meta-Analysis.

Highlights From the Circulation Family of Journals.

ObjectiveTo evaluate the prognosis of unrecognised myocardial infarction determined by electrocardiography (UMI-ECG) or cardiac magnetic resonance imaging (UMI-CMR).DesignSystematic review and meta-analysis of prospective studies.Data sourcesElectronic databases, including PubMed, Embase, and Google Scholar.Study selectionProspective cohort studies were included if they reported adjusted relative risks, odds ratios, or hazard ratios and 95% confidence intervals for all cause mortality or cardiovascular outcomes in participants with unrecognised myocardial infarction compared with those without myocardial infarction.Data extraction and synthesisThe primary outcomes were composite major adverse cardiac events, all cause mortality, and cardiovascular mortality associated with UMI-ECG and UMI-CMR. The secondary outcomes were the risks of recurrent coronary heart disease or myocardial infarction, stroke, heart failure, and atrial fibrillation. Pooled hazard ratios and 95% confidence intervals were reported. The heterogeneity of outcomes was compared in clinically recognised and unrecognised myocardial infarction.ResultsThe meta-analysis included 30 studies with 253 425 participants and 1 621 920 person years of follow-up. UMI-ECG was associated with increased risks of all cause mortality (hazard ratio 1.50, 95% confidence interval 1.30 to 1.73), cardiovascular mortality (2.33, 1.66 to 3.27), and major adverse cardiac events (1.61, 1.38 to 1.89) compared with the absence of myocardial infarction. UMI-CMR was also associated with increased risks of all cause mortality (3.21, 1.43 to 7.23), cardiovascular mortality (10.79, 4.09 to 28.42), and major adverse cardiac events (3.23, 2.10 to 4.95). No major heterogeneity was observed for any primary outcomes between recognised myocardial infarction and UMI-ECG or UMI-CMR. The absolute risk differences were 7.50 (95% confidence interval 4.50 to 10.95) per 1000 person years for all cause mortality, 11.04 (5.48 to 18.84) for cardiovascular mortality, and 27.45 (17.1 to 40.05) for major adverse cardiac events in participants with UMI-ECG compared with those without myocardial infarction. The corresponding data for UMI-CMR were 32.49 (6.32 to 91.58), 37.2 (11.7 to 104.20), and 51.96 (25.63 to 92.04), respectively.ConclusionsUMI-ECG or UMI-CMR is associated with an adverse long term prognosis similar to that of recognised myocardial infarction. Screening for unrecognised myocardial infarction could be useful for risk stratification among patients with a high risk of cardiovascular disease.

Introduction Transthyretin cardiac amyloidosis (ATTR-CA) results from the deposition of amyloid fibrils in the myocardium, leading to restrictive cardiomyopathy and reduced myocardial contractile reserve. This progressive process often results in symptomatic chronic heart failure (HF) and, eventually, death. Objectives Identify predictors of extended major adverse cardiovascular events (MACE) in patients (pts) with ATTR-CA followed at a Cardiomyopathy Clinic (CC) in a regional hospital in Portugal. Methods Retrospective single-center study of pts diagnosed with wild-type ATTR-CA per ESC algorithm from 2018 to 2024. Clinical, echocardiographic, electrocardiographic and analytical data were collected at the time of diagnosis (table 1). The occurrence of extended MACE, defined as cardiovascular (CV) mortality, myocardial infarction, stroke and HF hospitalizations, was assessed 18 months after diagnosis. Pts who suffered MACE (group 1) were compared with those who did not (group 2). Results 45 pts were included (80±6 yrs, 91% male), of whom 20 (44%) had MACE (group 1). Group 1 pts more frequently had atrial fibrillation (AF) (95 vs 48%, p<0.001), chronic kidney disease (CKD) (80 vs 44%, p=0.014) and chronic obstructive pulmonary disease (COPD) (40 vs 12%, p=0.041). After multivariate logistic regression of these 3 comorbidities, only AF (OR 24.83, CI 95% 2.31-266.46, p=0.008) and CKD (OR 7.55, CI 95% 1.51-37.66, p=0.014) remained independent predictors of MACE. Regarding echocardiographic variables, group 1 pts demonstrated lower left atrial (LA) reservoir strain (LASr) [5.5 (IQR 3) vs 7.0% (IQR 8); p=0.039] and LA contractile strain (LASct) [0.0 (IQR 2) vs -3.0% (IQR 6); p=0.026]. Additionally, group 1 more often had atrioventricular block (40 vs 4%, p=0.012) and showed significantly higher NT-proBNP levels (5655±3006 vs 4030±2927 pg/mL, p=0.028). ROC analysis identified cut-offs for predicting MACE in ATTR-CA pts: creatinine ≥1.25 mg/dl (AUC 0.764, sensitivity (S) 85%, specificity (E) 64%), NT-proBNP ≥3220 pg/ml (AUC 0.705, S 90%, E 52%), and LASct ≥-2.5% (AUC 0.675, S 80%, E 52%). The primary driver of 18-month MACE was HF hospitalizations (86%), followed by CV mortality (14%). Conclusions In this ATTR-CA population, pts with extended MACE had lower LASr and LASct values and higher NT-proBNP levels at diagnosis. Assessing these parameters may help predict adverse outcomes. Additionally, AF and CKD were identified as independent risk factors for MACE.

Background:Obesity is associated with a significant predisposition towards cardiovascular events and acts as an important risk factor for mortality. Herein, we conducted a comprehensive meta-analysis to estimate the protective effect of bariatric surgery on disease-specific mortality and major adverse cardiovascular events (MACEs) in patients with severe obesity.Methods:PubMed and Embase were searched from inception to 4 June 2022. Eligible studies were age, sex, and BMI-matched cohort studies. The protocol for this meta-analysis was registered on PROSPERO (ID: CRD42022337319).Results:Forty matched cohort studies were identified. Bariatric surgery was associated with a lower risk of disease-specific mortality including cancer mortality [hazard ratio with 95% confidence interval: 0.46 (0.37–0.58)], cardiovascular mortality [0.38 (0.29–0.50)], and diabetes mortality [0.25 (0.11–0.57)]. Bariatric surgery was associated with a lower incidence of MACEs [0.58 (0.51–0.66)] and its components including all-cause mortality [0.52 (0.47–0.58)], atrial fibrillation [0.79 (0.68–0.92)], heart failure [0.52 (0.42–0.65)], myocardial infarction [0.55 (0.41–0.74)], and stroke [0.75 (0.63–0.89)]. According to subgroup analysis on all-cause mortality, patients with severe obesity and type 2 diabetes benefited more from bariatric surgery than those with severe obesity only (heterogeneity between groups: P=0.001), while different surgical approaches brought similar benefits (heterogeneity between groups: P=0.87).Conclusions:This meta-analysis of 40 matched cohort studies supports that bariatric surgery reduces disease-specific mortality and incidence of both MACEs and its components in patients with severe obesity compared with nonsurgical subjects. Bariatric surgery deserves a more aggressive consideration in the management of severe obesity.

Background: Serum magnesium (Mg) has been reported to be inversely associated with the risk of atrial fibrillation (AF), coronary artery disease (CAD), and major adverse cardiovascular events (MACE). However, whether high serum Mg is associated with a lower risk of MACE, heart failure (HF), stroke, and all-cause mortality among AF patients remains unclear. Methods: We evaluated prospectively 503 participants of the Atherosclerosis Risk in Communities (ARIC) Study with available serum Mg and a diagnosis of AF at the time of Mg measurement participating in visit 2 (1990-1992, n = 90) or visit 5 (2011-2013, n = 403). Serum Mg was modeled in tertiles and as a continuous variable in standard deviation units. Endpoints (HF, MI, stroke, cardiovascular (CV) death, all-cause mortality, and MACE) were identified and modeled separately using Cox proportional hazard regression adjusting for potential confounders. Results: During a mean follow-up of 7.0 years, there were 105 HF, 50 MI, 36 stroke, 119 CV deaths, 160 total deaths, and 285 MACE. After adjustment for demographic and clinical variables, participants in the 2 nd and 3 rd tertiles of serum Mg had lower rates of most endpoints, with the strongest inverse association for the incidence of MI (Table). Serum Mg modeled linearly as a continuous variable did not show clear associations with endpoints. Due to limited number of events, precision of most estimates of association was relatively low. Conclusion: Higher serum Mg was associated with lower risk of developing incident MI and, to a lesser extent, other cardiovascular endpoints. Further studies in larger AF patient cohorts are needed to evaluate the role of serum Mg in preventing adverse CV outcomes in these patients.

Cardiovascular risk with DPP-4 inhibitors: latest evidence and clinical implications.

AimsBeta blockers are associated with improved outcomes for selected patients with cardiovascular disease. We assessed long-term utilization of beta blockers after coronary artery bypass grafting (CABG) and its association with outcome.Methods and resultsAll 35 184 patients in Sweden who underwent first-time isolated CABG between 1 January 2006 and 31 December 2017 and were followed for at least 6 months were included in a nationwide observational study. Multivariable Cox regression models using time-updated data on dispensed prescriptions were used to assess associations between different types of beta blockers and outcomes. The primary outcome was major adverse cardiovascular events (MACEs), a composite of all-cause mortality, stroke, and myocardial infarction (MI). Subgroup analyses were performed in patients with and without previous MI, heart failure, and reduced left ventricular ejection fraction (LVEF). Median follow-up was 5.2 years (range 0–11). At baseline, 33 159 (94.2%) patients were dispensed beta blockers, 30 563 (92.2%) of which were cardioselective beta blockers. After 10 years, the dispensing of cardioselective beta blockers had declined to 73.7% of all patients. Ongoing treatment with cardioselective beta blockers was associated with a slight reduction in MACEs [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.89–0.98, P = 0.0063]. The reduction was largely driven by a reduced risk of MI (HR 0.83, 95% CI 0.75–0.92, P = 0.0003), while there was no significant reduction in all-cause mortality (HR 0.99, 95% CI 0.93–1.05) and stroke (HR 0.96, 95% CI 0.87–1.05). The reduced risk for MI was consistent in all the investigated subgroups.ConclusionOngoing treatment with cardioselective beta blockers after CABG is associated with a reduction in MACEs, mainly because of reduced long-term risk for MI. The association between cardioselective beta blockers and MI was consistent in patients with and patients without previous MI, heart failure, atrial fibrillation, or reduced LVEF.

Introduction: Orthostatic hypotension (OH) is a debilitating condition commonly observed in patients with impaired vascular tone upon positional changes, often due to neurogenic disorders, liver disease, hypovolemia, or advanced HF. While fludrocortisone has been associated with adverse outcomes—particularly HF-related complications—compared to midodrine in HF populations, direct comparative data between these two therapies in the general population with OH is seldom. Hypothesis: This study aims to compare cardiovascular and renal outcomes in patients with OH treated with fludrocortisone (without midodrine) versus those treated with midodrine (without fludrocortisone). Methods: A retrospective cohort study was conducted using data from the TriNetX collaborative research network from January 2007 to May 2025. Patients aged 18 or older diagnosed with OH were included. After propensity score matching for demographics, comorbidities, and medications, two cohorts were analyzed: cohort 1 included 33,101 patients treated with fludrocortisone (excluding midodrine), and cohort 2 included 33,101 treated with midodrine (excluding fludrocortisone). Mean age was 62 years; 51% were female and 47% male. Risk ratios (RR) and hazard ratios (HR) with 95% confidence intervals and p-values were calculated using TriNetX. The outcomes assessed included all cause mortality, syncope/collapse, stroke, heart failure (HF), acute myocardial infarction (AMI), atrial fibrillation (AF), and ventricualr fibrillation (VF). Results: Though mortality risk was higher in cohort 1 (26.85% vs. 22.12%, RR 1.214, 95% CI 1.181–1.247; p<0.0001), HR was 0.938 (95% CI 0.91–0.968; p<0.0001). Syncope was more frequent in cohort 1 (25.84% vs. 21.77%, RR 1.187; p<0.0001; HR 1.034; p=0.025), as was stroke (8.09% vs. 7.09%, RR 1.142; HR 0.939; p=0.0375). AMI (6.05% vs. 6.92%, RR 0.873; HR 0.694; p<0.0001), HF (17.81% vs. 22.99%, RR 0.775; HR 0.636; p<0.0001), AF (18.50% vs. 22.54%, RR 0.821; HR 0.695; p<0.0001), and VF (0.34% vs. 0.62%, RR 0.544; HR 0.435) were all lower in cohort 1. AKI/CKD risk was similar (30.43% vs. 30.66%, RR 0.993; p=0.5213), though HR favored fludrocortisone (0.846; p<0.0001). Conclusion: In OH patients, midodrine was linked to lower all-cause mortality risk, but fludrocortisone showed better survival and lower risks of HF, AMI, AF, VF, and cardiovascular mortality. Syncope and cerebrovascular events were more common with fludrocortisone.

BackgroundSince 2005, the cardioprotective effects of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have garnered attention. The cardioprotective effect could be an added benefit to the use of GLP-1 RA. This systematic review and meta-analysis aimed at summarizing observational studies that recruited type 2 diabetes individuals with fewer cardiovascular (CV) events before enrolling in the research.MethodsSystematically, the databases were searched for observational studies reporting compound CV events and deaths in type 2 diabetics without having the risk of cardiovascular diseases (CVDs) compared to other glucose-lowering agents. A meta-analysis was carried out using random effects model to estimate the overall hazard ratio (HR) with a 95% confidence interval (CI). Five studies were found eligible for the systematic review including a total of 64,452 patients receiving either liraglutide (three studies) or exenatide (two studies).ResultsThe pooled HR for major adverse cardiac event (MACE) and extended MACE was 0.72 (95% CI: 0.65 - 0.93, I2 = 68%) and 0.93 (95% CI: 0.89 - 0.98, I2 = 29%), respectively. The pooled HR for hospitalization due to heart failure (HHF) and occurrence of HF was 0.84 (95% CI: 0.77 - 0.91, I2 = 79%) and 0.83 (95% CI: 0.75 - 0.94, I2 = 95%), respectively. For stroke, GLP-1 RA was associated with a significant risk reduction of 0.86 (95% CI: 0.75 - 0.98, I2 = 81%). There was no significant myocardial infarction (MI) risk reduction with GLP-1 RA. As for all-cause mortality, the pooled HR for the occurrence of all-cause mortality was 0.82 (95% CI: 0.76 - 0.88, I2 = 0%). The pooled HR for the occurrence of CV death was 0.75 (95% CI: 0.65 - 0.85, I2 = 38%). GLP-1 RA therapy was associated with a significantly low risk of MACE, extended MACE, all-cause mortality, and CV mortality. Except for MACE, the heterogenicity among the studies was low.ConclusionWe conclude that GLP-1 RA is associated with a low risk of CV events composites and mortality. The findings support the cardioprotective effect of GLP-1 RA.

We evaluated data on blacks and whites with acute ST-segment-elevation myocardial infarction treated with either fibrinolysis or primary percutaneous coronary intervention from the National Registry of Myocardial Infarction (NRMI)-4 and -5 participating centers between July 2000 and December 2006 to determine race-related differences in bleeding and outcomes. We found that among patients with ST-segment-elevation myocardial infarction receiving fibrinolysis, the bleeding rates were higher for blacks (n2283) than whites (n42 243; 10.9% versus 10.3%; adjusted odds ratio, 1.21; 95% confidence interval, 1.02-1.43). Similarly, in patients receiving primary percutaneous coronary intervention, the bleeding rates were higher in blacks (n2826) than whites (n46 332; 10.3% versus 7.8%; adjusted odds ratio, 1.33; 95% confidence interval, 1.13-1.56). Bleeding was associated with a higher risk of death in both ethnic groups. However, there was no overall racial difference in in-hospital mortality among those with bleeding or without bleeding treated with either fibrinolysis or primary percutaneous coronary intervention. We concluded that race-related differences existed in bleeding risk among patients with ST-segmentelevation myocardial infarction receiving reperfusion therapy that portend poor prognosis. Thus, the efficacy and safety of many new drugs or treatment strategies for any disease observed in clinical trials that enroll predominantly white patients may not be similar in other ethnic groups that are underrepresented in these trials.

Background: Previous literature shows that metabolic surgery effectively decreases the risk of cardiovascular disease (CVD) events in patients with obesity. The use of metabolic surgery has, however, been limited in people with obesity and pre-existing CVD due to concerns of poor post-operative cardiovascular outcomes. This study aims to determine the effectiveness and safety of metabolic surgery in patients with pre-existing CVD. Methods: A search of electronic databases, PubMed, Cochrane Central and SCOPUS was conducted from their inception till May 2024. The study was conducted adhering to the PRISMA guidelines. Outcomes of interest were risk of all-cause mortality, major adverse cardiovascular events (MACE), risk of myocardial infarction (MI), and cerebrovascular events in patients with and without prior CVD undergoing bariatric surgery. Data was pooled as generic inverse variance using a random effects model, and presented as hazard ratios (HR) with their 95% confidence intervals (CI). Results: We included four studies in our analysis (n = 5,244). Our pooled analysis shows that metabolic surgery leads to significant reduction in risk of all-cause mortality (HR = 0.51, 95% CI: [0.42, 0.61]; p<0.01). We also observed a significant risk reduction of 43% in MACE with metabolic surgery (HR = 0.57, 95% CI: [0.5, 0.64]; p<0.01). Metabolic surgery was not associated with a significant reduction in the risk of MI (HR = 0.53, 95% CI: [0.24, 1.18]; p = 0.12, I2 = 83%). Similarly, a non-significant decrease in risk of cerebrovascular events was observed with metabolic surgery (HR = 0.89, 95% CI: [0.65, 1.22]; p = 0.48) Conclusion: Metabolic surgery is associated with decreased risk of all-cause mortality and MACE in patients with obesity and established CVD. These results are thought to be mediated through reduction in risk factors such as obesity, but also by reducing inflammatory mediators and having other beneficial effects on cardiac structure and left ventricular workload.

<i>Circulation:</i> Clinical Summaries

SummaryBackgroundWarfarin use and associated outcomes in patients with heart failure and atrial fibrillation and a cardiovascular implantable electronic device have not been described previously.HypothesisWe hypothesized that warfarin is underused and is associated with lower risks of mortality, thromboembolic events, and myocardial infarction.MethodsUsing data from a clinical registry linked with Medicare claims, we examined warfarin use at discharge and 30-day and 1-year Kaplan-Meier estimates of all-cause mortality and cumulative incidence rates of mortality, thromboembolic events, myocardial infarction, and bleeding events in patients 65 years or older with a history of atrial fibrillation and a cardiovascular implantable electronic device admitted with heart failure between 2001 and 2006 who were naïve to anticoagulation therapy at admission. We compared outcomes between patients who were or were not prescribed warfarin at discharge and tested associations between treatment and outcomes.ResultsOf 2586 eligible patients in 252 hospitals, 2049 were discharged without a prescription for warfarin. At 1 year, the group discharged without warfarin had a higher mortality rate after discharge (37.4% vs 28.8%; P < .001) but similar rates of thromboembolism, myocardial infarction, and bleeding events. After adjustment, treatment with warfarin was associated with lower risk of all-cause death 1 year after discharge (hazard ratio, 0.76; 95% confidence interval, 0.63–0.92).ConclusionAmong older patients with heart failure and atrial fibrillation and a cardiovascular implantable electronic device, 4 of 5 were discharged without a prescription for warfarin. Warfarin nonuse was associated with a higher risk of death 1 year after discharge.

Digoxin in patients with permanent atrial fibrillation: data from the RACE II study.

Factors Associated With Major Adverse Cardiovascular Events After Liver Transplantation Among a National Sample.