Association between testosterone replacement therapy and cardiovascular outcomes: A meta-analysis of 30 randomized controlled trials.

BACKGROUND: The Cardiovascular safety of testosterone replacement therapy (TRT) among men with hypogonadism is not well established to date. Hence, we sought to evaluate the cardiovascular disease (CVD) outcomes among patients receiving testosterone therapy by using all recently published randomized controlled trials. METHODS: We performed a systematic literature search on PubMed, EMBASE, and Clinicaltrial.gov for relevant randomized controlled trials (RCTs) from inception until September 30th, 2023. RESULTS: A total of 30 randomized trials with 11,502 patients were included in the final analysis. The mean age was ranging from 61.61 to 61.82 years. Pooled analysis of primary and secondary outcomes showed that the incidence of any CVD events (OR, 1.12 (95%CI: 0.77-1.62), P = 0.55), stroke (OR, 1.01 (95%CI: 0.68-1.51), P = 0.94), myocardial infarction (OR, 1.05 (95%CI: 0.76-1.45), P = 0.77), all-cause mortality (OR, 0.94 (95%CI: 0.76-1.17), P = 0.57), and CVD mortality (OR, 0.87 (95%CI: 0.65-1.15), P = 0.31) was comparable between TRT and placebo groups. CONCLUSION: Our analysis indicates that for patients with hypogonadism, testosterone replacement therapy does not increase the CVD risk and all-cause mortality.

Immediate vs. multistage revascularization of non-infarct coronary artery(-ies) in patients with hemodynamically stable multivessel disease acute myocardial infarction: a systematic review and meta-analysis.

BACKGROUND: Untreated multivessel disease (MVD) in acute myocardial infarction (AMI) has been linked to a higher risk of recurrent ischemia and death within one year . Current guidelines recommend percutaneous coronary intervention (PCI) for significant non-infarct artery (-ies) (non-IRA) stenosis in hemodynamically stable AMI patients with MVD, either during or after successful primary PCI, within 45-days. However, deciding the timing of revascularization for non-IRA in cases of MVD is uncertain. METHODS: This meta-analysis was performed based on PRISMA guidelines after registering in PROSPERO (CRD42023472652). Databases were searched for relevant articles published before 10 November 2023. Pertinent data from the included studies were extracted and analyzed using RevMan v5.4. RESULTS: Out of 640 studies evaluated, there were 13 RCTs with 5144 patients with AMI with MVD. The immediate non-IRA PCI is associated with a significantly lower occurrence of unplanned ischemia-driven PCI (OR 0.60; confidence interval [CI] 0.44-0.83) and target-vessel revascularization (OR 0.72; CI 0.53-0.97) . Although there is a favorable trend for major adverse cardiovascular and cerebrovascular events (MACCE), nonfatal AMI, cerebrovascular events, and major bleeding in the immediate non-culprit artery (-ies) PCI, those were statistically non-significant. Similarly, all-cause mortality, cardiovascular mortality, stent thrombosis, and acute renal insufficiency did not show significant differences between two groups. CONCLUSION: Among hemodynamically stable patients with multivessel AMI, the immediate PCI strategy was superior to the multistage PCI strategy for the unplanned ischemia-driven PCI and target-vessel revascularization while odds are favorable in terms of MACCE, nonfatal AMI, cerebrovascular events, and major bleeding at longest follow-up.

Transcarotid versus trans-axillary/subclavian transcatheter aortic valve replacement (TAVR): A systematic review and meta-analysis.

BACKGROUND: Transcatheter Aortic Valve Replacement (TAVR) is the treatment of choice in patients with severe aortic stenosis. Transcarotid (TCa) or Trans-axillary/subclavian (TAx/Sc) are safer and less invasive non-femoral approaches, where transfemoral access is difficult or impossible to obtain. METHODS: This meta-analysis was performed based on PRISMA guidelines after registering in PROSPERO (CRD42023482842). This meta-analysis was performed to compare the safety of the transcarotid and trans-axillary/subclavian approach for TAVR including studies from inception to October 2023. RESULTS: Seven studies with a total of 6227 patients were included in the analysis (TCa: 2566; TAx/Sc: 3661). Transcarotid TAVR approach had a favorable trend for composite of stroke and all-cause mortality (OR 0.79, CI 0.60-1.04), all-cause mortality, stroke, major vascular complication, and new requirement of permanent pacemaker though those were statistically insignificant. On sub-analysis of the results of the studies based on the territory (USA vs French), composite outcome of all cause mortality, stroke and major bleeding (OR 0.54, CI 0.54-0.81), composite of stroke and all cause mortality (OR 0.64, CI 0.50-0.81), and stroke/TIA (OR 0.53, CI 0.39-0.73) showed lower odds of occurrence among patient managed with TCa approach in the American cohort. CONCLUSION: Overall, transcarotid approach had favorable though statistically insignificant odds for composite (stroke and all-cause mortality) and individual outcomes (stroke, all-cause mortality, etc.). There are significant variations in observed outcomes based on study's geographic location. Large prospective randomized clinical trials comparing the two approaches with representative samples are necessary to guide the clinicians in choosing among these approaches.

Implantable cardioverter defibrillators for primary prevention in patients with ischemic and non-ischemic cardiomyopathy: A meta-analysis.

BACKGROUND: Ischemic and nonischemic cardiomyopathy (NICM) are one of the leading causes of sudden cardiac death (SCD). Evidence supporting Implantable Cardioverter Defibrillator (ICD) for the prevention of SCD and mortality has shown conflicting results to date. OBJECTIVE: We aim to evaluate the impact of ICD therapy with conventional care for the primary prevention of death of various causes in adults with ICM and NICM. METHODS: We performed a systematic literature search on the electronic database for relevant articles from inception until 30th May 2023. Pooled odds ratios (OR) were calculated using a random effect model, and a p-value of <0.05 was considered statistically significant. RESULTS: A total of 13 randomized controlled trials involving 7857 patients were included in the study. Pooled analysis showed that ICD therapy was associated with a significant reduction in the incidence of all-cause mortality (OR, 0.69 (95%CI:0.55-0.87), P = 0.001), with a similar trend among ICM and NICM compared with the control group. ICD therapy also reduces the incidence of SCD (OR, 0.32(95%CI: 0.24-0.43), P<0.00001) with a similar trend in ICM and NICM, as well as death due to arrhythmia (OR, 0.35(95%CI: 0.19-0.64), P<0.001). However, the incidence of cardiovascular mortality in the ICD group (OR, 0.77(95%CI: 0.58-1.02), P=0.07) was comparable to the control group. CONCLUSION: ICD therapy was associated with a reduction in the incidence of all-cause mortality, sudden cardiac death, and death due to arrhythmia among ischemic and nonischemic cardiomyopathy patients.

Cardiovascular and Cerebrovascular Outcomes With Vitamin D Supplementation: A Systematic Review and Meta-Analysis.

Vitamin D supplementation has seen a sharp increase in the primary healthcare setting but its efficacy in decreasing the risk of cardiovascular and cerebrovascular events is yet to be reliably established. We aim to determine whether vitamin D supplementation can significantly impact the risk of cardiovascular and cerebrovascular events. An extensive literature search of PubMed, Embase, and Cochrane CENTRAL was conducted from inception till August 2023 to include all the articles comparing vitamin D and placebo. Cardiovascular and cerebrovascular outcomes were presented as risk ratios (RR) with 95% confidence intervals (CIs) and pooled using a random effects model. Thirty-six trials consisting of 493,389 participants were included in our analysis. Our pooled analysis demonstrated no significant difference between vitamin D supplementation and placebo for the risk of cardiovascular mortality (RR 1.01, 95% CI 0.94-1.08; P = 0.80), stroke or cerebrovascular events (RR 1.03, 95% CI 0.95-1.11; P = 0.48), myocardial infarction (MI) (RR 0.98, 95% CI 0.91-1.06; P = 0.65), cerebrovascular mortality (RR 1.00, 95% CI 0.68-1.46; P = 0.99), arrhythmias (RR 0.98, 95% CI 0.66-1.44; P = 0.90) and hemorrhagic or ischemic stroke. There was no significant heterogeneity between the studies in any analysis. There was no significant difference in the risk of cardiovascular and cerebrovascular outcomes with vitamin D supplementation or placebo. Additional large high-powered studies focused on high-risk and vitamin D-deficient populations are required to resolve the current discrepancy in the literature and provide a definitive conclusion to this end.

Association Between Catheter Ablation and Dementia Among Patients With Atrial Fibrillation: A Systematic Review and Meta-analysis.

Atrial fibrillation (AF) is associated with an increased risk of Dementia. However, the association between catheter ablation (CA) in patients with atrial fibrillation and the risk of dementia is not well established, with conflicting results to date. We aimed to evaluate the association between CA patients and the risk of Dementia. We performed a systematic literature search using the PubMed, Embase, Scopus, and Cochrane libraries for relevant articles from inception until 10th May 2023. Hazard ratios (HR) were pooled using a random-effect model, and a P-value of < 0.05 was considered statistically significant. A total of 5 studies with 125,649 patients (30,192 in the CA group and 95,457 in the non-CA group) were included. The mean age of patients among CA and non-CA groups was comparable (58.7 vs 58.18). The most common comorbidity among CA and non-CA groups was hypertension (18.49% vs 81.51%), respectively. Pooled analysis of primary outcome showed that CA was associated with a significant reduction in the risk of Dementia (HR, 0.63 [95% CI: 0.52-0.77], P < 0.001). Similarly, pooled analysis of secondary outcomes showed that the patients with CA had a lower risk of Alzheimer's disease (HR, 0.78 [95% CI: 0.66-0.92], P < 0.001) compared with the non-CA group. However, there was no statistically significant difference in the risk of vascular dementia (HR, 0.63 [95% CI: 0.38-1.06], P = 0.08) between both groups of patients. Our study suggested that catheter ablation reduced the risk of dementia and Alzheimer's disease compared to the nonablation group of patients.

Trends in Rheumatic Heart Disease-Related Mortality in the United States from 1999 to 2020.

There is a lack of mortality data on rheumatic heart disease (RHD) in the United States (US). In light of this, a retrospective analysis was conducted to investigate the temporal, sex-based, racial, and regional trends in RHD-related mortality in the US, ranging from 1999 to 2020. The Center for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC-WONDER) dataset was analyzed, where crude and age-adjusted mortality rates (AAMR) were identified, along with annual percentage changes (APCs) determined by Joinpoint regression. Through the period of 1999 to 2020, there were 141,137 RHD-related deaths reported, with a marginal decline from 4.05/100,000 in 1999 to 3.12/100,000 in 2020. However, the recent rise in AAMR from 2017 to 2020 has created a source of concern (APC: 6.62 [95% CI, 3.19-8.72]). Similar trends were observed in the Black or African American race from 2017 to 2020 (APC: 10.58 [95% CI, 6.29-17.80]). Moreover, the highest percentage change from 2018 to 2020 was observed in residents of large metropolitan areas (APC: 7.6 [95% CI, 2.8-10.5]). A prominent disparity was observed among states, with values ranging from 1.74/100,000 in Louisiana to 5.27/100,000 in Vermont. States within the top 90th percentile of RHD-related deaths included Alaska, Minnesota, Washington, Wyoming, and Vermont. In conclusion, it is imperative to delve deeper into the evidently rising trends of RHD-related mortality and outline the possible sources of social determinants within US healthcare in order to provide equal and quality medical care throughout the nation.

Angiotensin-Neprilysin inhibition in heart failure with preserved ejection fraction: A meta-analysis of randomized controlled trials.

BACKGROUND: The effect of sacubitril/valsartan on patients with heart failure (HF) with preserved ejection fraction (HFpEF) is a topic of ongoing debate. METHODS: Medline was queried from inception through the last week of May 2023 for randomized studies assessing the effects of sacubitril/valsartan in patients with HFpEF. For continuous outcomes, we pooled either the geometric mean ratios (gMR) or weighted mean difference (WMD) with 95% confidence intervals (CI). For dichotomous outcomes, we pooled Risk ratios (RR) with 95% CI. RESULTS: Four trials were included (N=8,129). Compared to the control, sacubitril/valsartan was associated with a reduction in NT-proBNP levels (gMR: 0.84, 95% CI 0.80, 0.88) and improvement in KCCQ score (WMD: 0.85, 95% CI: 0.02, 1.67). We observed no differences for HF hospitalization (RR: 0.90, 95% CI: 0.79, 1.01), cardiovascular mortality (RR: 0.83, 95% CI: 0.52, 1.32), all-cause mortality (RR: 0.99, 95% CI: 0.86-1.13) and improvement (RR: 1.15, 95% CI: 0.93, 1.42) or worsening (RR: 0.92, 95% CI: 0.78, 1.09) of NYHA class between the sacubitril/valsartan and comparator group. Sacubitril/valsartan was generally safe, and patients were less likely to have a ≥50% decline in eGFR compared to control (RR: 0.60, 95% CI: 0.39, 0.92). CONCLUSION: Pooled analysis suggests that sacubitril/valsartan reduces natriuretic peptide levels and improves the quality of life in patients with HFpEF, which may translate into better clinical outcomes as observed by a numerical trend towards improvement in major HF outcomes with sacubitril/valsartan therapy.

Bivalirudin versus heparin in STEMI after BRIGHT-4 trial: an updated meta-analysis.

BACKGROUND: The use of bivalirudin-based anticoagulation over heparin-based anticoagulation for coronary percutaneous intervention has been debated for a long time. Multiple trials have shown promising benefits of bivalirudin over heparin therapy with the most recent addition being the BRIGHT-4 trial. We performed a meta-analysis to assess evidence from these trials, focusing on the coronary intervention of the STEMI population. METHODS: This meta-analysis was performed based on PRISMA guidelines after registering in PROSPERO (CRD42023394701). Databases were searched for relevant articles published before January 2023. Pertinent data from the included studies were extracted and analyzed using RevMan v5.4. RESULTS: Out of 2375 studies evaluated, 13 randomized control trials with 24 360 acute ST-elevation myocardial infarction patients were included for analysis. The bivalirudin-based anticoagulation reduced the net clinical events (OR 0.75, CI 0.61-0.92), major adverse cardiac or cerebral events (OR 0.85, CI 0.74-0.98), any bleeding (OR 0.61, CI 0.45-0.83), major bleeding (OR 0.54, CI 0.39-0.75), all-cause mortality (OR 0.79, CI 0.67-0.92) and cardiac mortality (OR 0.78, CI 0.65-0.93) significantly without increasing the risk of any stent thrombosis (OR 0.92, 95% CI 0.52-1.61), definite stent thrombosis (OR 1.17, 95% CI 0.62-2.22) and acute stent thrombosis (OR 2.06, 95% CI 0.69-6.09) significantly at 30 days. CONCLUSION: Based on this meta-analysis, bivalirudin plus a post-PCI high-dose infusion-based anticoagulation during STEMI PCI has significant benefits over heparin therapy for cardiovascular outcomes without a significant increase in the risk of thrombotic outcomes.

Artificial intelligence in cardiac computed tomography.

Artificial Intelligence (AI) is a broad discipline of computer science and engineering. Modern application of AI encompasses intelligent models and algorithms for automated data analysis and processing, data generation, and prediction with applications in visual perception, speech understanding, and language translation. AI in healthcare uses machine learning (ML) and other predictive analytical techniques to help sort through vast amounts of data and generate outputs that aid in diagnosis, clinical decision support, workflow automation, and prognostication. Coronary computed tomography angiography (CCTA) is an ideal union for these applications due to vast amounts of data generation and analysis during cardiac segmentation, coronary calcium scoring, plaque quantification, adipose tissue quantification, peri-operative planning, fractional flow reserve quantification, and cardiac event prediction. In the past 5 years, there has been an exponential increase in the number of studies exploring the use of AI for cardiac computed tomography (CT) image acquisition, de-noising, analysis, and prognosis. Beyond image processing, AI has also been applied to improve the imaging workflow in areas such as patient scheduling, urgent result notification, report generation, and report communication. In this review, we discuss algorithms applicable to AI and radiomic analysis; we then present a summary of current and emerging clinical applications of AI in cardiac CT. We conclude with AI's advantages and limitations in this new field.

An incidental danger: Left ventricular thrombus in takotsubo syndrome.

Takotsubo cardiomyopathy is a potentially lethal condition characterized by transient regional systolic dysfunction in the absence of coronary artery ischemia. This syndrome predominantly affects postmenopausal women and is often preceded by physical or emotional stress and often presents with symptoms of acute coronary syndrome, chest pain, and shortness of breath. Although the effects can be transient, takotsubo cardiomyopathy still results in an 8-12% rate of in-hospital mortality, with cardiogenic shock being the most common cause of death. There are known risk factors that increase the likelihood of a patient developing a left ventricular thrombus during the clinical course. The management of these cases is discussed in this report.

A Case of Ticagrelor-Induced Sinus Pause.

Ticagrelor is an oral antiplatelet agent commonly used following percutaneous coronary intervention (PCI). There have been many reports describing bradyarrhythmias in the setting of ticagrelor use, most notably sinus pauses. This process is thought to be related to ticagrelor's inhibition of human equilibrative nucleoside transporter (hENT1), which reduces cellular uptake of adenosine. We present a case of a 58-year-old male who experienced prolonged sinus pauses 38 hours after starting ticagrelor following ST-elevation myocardial infarction with subsequent PCI and stent placement.

Factors associated with bleeding events in patients on rivaroxaban for non-valvular atrial fibrillation: A real-world experience.

BACKGROUND: Rivaroxaban is a direct oral anticoagulant (DOAC) approved for the treatment of non-valvular atrial fibrillation (NVAF). Data related to the risk factors associated with rivaroxaban-induced bleeding in patients with NVAF remain scarce in the community setting. We sought to investigate these bleeding risk factors in a racially diverse patient population. METHODS: We conducted a single-center, retrospective study based on a chart review of patients who received rivaroxaban from our outpatient pharmacy from January 2015 to April 2018 for NVAF. Any reported bleeding event (BE) was recorded as either major or minor bleeding event. Demographic and clinical data were collected and analyzed. RESULTS: Of the 327 patients included in our analysis, 105 (32%) were female, and the mean age was 62 ± 12 years. Among the included patients, 176 (54%) patients were black, 71 (22%) were white, 51 (15.6%) were Hispanic, 13 (4%) were Asian, and 15 (4.6%) belonged to other races. 89 (27.2%) of the patients had co-prescription of aspirin. A total of 24 (7.3%) patients developed BE, out of which 9 (2.7%) patients had a major BE, and 15 (4.5%) patients had minor BE. Non-fatal gastrointestinal bleeding and epistaxis were the most common type of BE. On multivariable analysis, concurrent aspirin use (81 to 325 mg) (P = 0.03; odds ratio (OR) 2.60 [1.08-6.28]) and increasing age (P = 0.00; OR 1.06 [1.01-1.11]) were independent predictors of BE. CONCLUSION: In community practice, aspirin co-prescription is common among NVAF patients prescribed rivaroxaban. Increasing age and concurrent aspirin use are independent predictors of BE.

Troponin Levels at Presentation Before Coronary Angiogram and Their Association With Cost, Mortality, and Readmission.

Background and objective In patients undergoing coronary angiogram, the degree of cardiac enzyme elevation at presentation has been thought of as a strong and independent predictor of in-hospital mortality and readmission. Recent studies, however, have suggested a lack of clarity regarding this speculation, particularly with regard to troponin elevations. Additionally, the impact of troponin levels (TnI) at presentations on cost is poorly understood. In this study, we aimed to evaluate the association of Tnl at initial presentation with 30-day all-cause readmission and all-cause mortality as well as admission costs. Methods This study was a retrospective analysis of 7,388 patients who underwent coronary angiogram at our facility from 2015 to 2017. Patients were identified from a local CathPCI Registry® registry, and a subsequent chart review was performed for readmission and mortality data. Cost data were provided by our in-facility finance department. We excluded patients with incomplete records and those who required coronary artery bypass grafting (CABG). After the exclusion of patients deemed ineligible, the final sample size eligible for analysis was 1,163. Patients were divided into two groups based on Tnl at presentation with a cut-off value of 0.04 ng/ml. Adjusted regression and multivariate analysis were used for clinical outcomes. Primary outcomes were 30-day readmission and mortality. The secondary outcome was the admission cost. Results Within our cohort, the average participant age was 64.6 years (SD: 12.7), and the majority of them were male (70.7%). Of these patients, 207 had lower TnI (<0.04 ng/ml), while 956 had higher TnI at presentation. The high TnI (≥0.04 ng/ml) group had a significantly higher number of patients with a family history of coronary artery disease (CAD) (13.8% vs. 7.7%: p=0.017) and those on dialysis (3.2% vs. 0.5%: p=0.028) compared to the low Tnl group. Additionally, we did not find any significant difference in 30-day mortality or readmission between the two groups in our cohort. On average, each patient in the high TnI group spent $936 more for hospital admissions compared to patients in the low Tnl group. However, this difference was not statistically significant. Conclusions Tnl at admission did not reveal a significant impact on 30-day mortality or readmission, which is consistent with the findings of previous studies. A high Tnl at admission increased the cost of admission; however, the difference was not statistically significant in our cohort.