Clinical outcomes and the impact of valve morphology for transcatheter aortic valve replacement in bicuspid aortic valves: A systematic review and meta-analysis.

BACKGROUND: Bicuspid aortic valve (BAV) is present in approximately 0.5%-2% of the general population, causing significant aortic stenosis (AS) in 12%-37% of affected individuals. Transcatheter aortic valve replacement (TAVR) is being considered the treatment of choice in patients with symptomatic AS across all risk spectra. AIM: Aim Our study aims to compare TAVR outcomes in patients with BAV versus tricuspid aortic valves (TAV). METHODS: A comprehensive literature search was performed in PubMed, Web of Science, and Cochrane trials. Studies were included if they included BAV and TAV patients undergoing TAVR with quantitative data available for at least one of our predefined outcomes. Meta-analysis was performed by the random-effects model using Stata software. RESULTS: Fifty studies of 203,288 patients were included. BAV patients had increased 30-day all-cause mortality (odds ratio [OR] = 1.23 [1.00-1.50], p = 0.05), in-hospital stroke (OR = 1.39 [1.01-1.93], p = 0.05), in-hospital and 30-day PPI (OR = 1.13 [1.00-1.27], p = 0.04; OR = 1.16 [1.04-1.13], p = 0.01) and in-hospital, 30-day and 1-year aortic regurgitation (AR) (OR = 1.48 [1.19-1.83], p < 0.01; OR = 1.79 [1.26-2.52], p < 0.01; OR = 1.64 [1.03-2.60], p = 0.04). Subgroup analysis on new-generation valves showed a reduced 1-year all-cause mortality (OR = 0.86 [CI = 0.75-0.98], p = 0.03), despite higher in-hospital and 30-day PPI (OR = 0.1.21 [1.04-1.41], p = 0.01; OR = 1.17 [1.05-1.31], p = 0.01) and in-hospital AR (OR = 1.62 [1.14-2.31], p = 0.01) in the BAV group. The quality of included studies was moderate-to-high, and only three analyses presented high heterogeneity. CONCLUSION: TAVR is associated with comparable outcomes in patients with BAV and TAV. Careful selection of BAV cases by preprocedural assessment of valve anatomy and burden of calcification, pre- and post-procedural dilation, and implementing newer generations of valves may improve the safety and efficacy of TAVR in BAV patients.

Baxdrostat: A Novel Aldosterone Synthase Inhibitor for Treatment Resistant Hypertension.

Hypertension is a global epidemic, affecting around 30.4% of the population and being the leading preventable risk factor for death. Despite the availability of numerous antihypertensive agents, less than 20% of individuals have their blood pressure controlled. Resistant hypertension poses a challenge, but a new class of medication, aldosterone synthase inhibitors (ASI), shows promise. ASI reduces aldosterone production by inhibiting aldosterone synthase. This review article focuses on Baxdrostat, a highly potent ASI currently in phase 3 trials. It discusses the drug's biochemical pathway, efficacy trials in animals and humans, and its potential in uncontrolled hypertension, chronic kidney disease, and primary aldosteronism.

Role of Influenza Vaccination in Cardiovascular Disease: Systematic Review and Meta-Analysis.

Influenza vaccination has shown great promise in terms of its cardioprotective effects. The aim of our analysis is to provide evidence regarding the protective effects of influenza vaccination in patients with cardiovascular disease. We conducted a systematic literature search to identify trials assessing the cardiovascular outcomes of influenza vaccination. Summary effects were calculated using a DerSimonian and Laird fixed effects and random effects model as odds ratio with 95% confidence intervals (CIs) for all the clinical endpoints. Fifteen studies with a total of 745,001 patients were included in our analysis. There was lower rates of all-cause mortality [odds ratio (OR) = 0.74, 95% CI 0.64-0.86], cardiovascular death (OR = 0.73, 95% CI 0.59-0.92), and stroke (OR = 0.71, 95% CI 0.57-0.89) in patients who received the influenza vaccine compared to placebo. There was no significant statistical difference in rates of myocardial infarction (OR = 0.91, 95% CI 0.69-1.21) or heart failure hospitalizations (OR = 1.06, 95% CI 0.85-1.31) in the 2 cohorts. In patients with cardiovascular disease, influenza vaccination is associated with lower all-cause mortality, cardiovascular death, and stroke.

Early Coronary Angiography in Patients With Out-of-Hospital Cardiac Arrest Without ST-Segment Elevation: A Systematic Review, Meta-Analysis, and Comparative Analysis of Studies.

Out-of-hospital cardiac arrest has a high mortality rate. Unlike ST-elevation myocardial infarction, the results of performing early coronary angiography (CAG) in non-ST-elevation myocardial infarction patients are controversial. This study aimed to compare early and nonearly CAG in this population, in addition to the identification of differences between randomized controlled trials (RCTs) and observational studies conducted in this regard. A systematic search in PubMed, Embase, and Cochrane library was performed to identify the relevant studies. Random-effect meta-analysis was done to calculate the pooled effect size of early versus nonearly CAG outcomes in all studies in addition to each of the RCT and observational subgroups of the studies. The relative risk ratio (RR), along with its 95% confidence interval (CI), was used as a measure of difference. A total of 16 studies including 5234 cases were included in our analyses. Compared with observational cohorts, RCT studies had patients with higher baseline comorbidities (older age, hypertension, diabetes, and coronary artery disease). Random-effect analysis revealed a lower rate of in-hospital mortality in the early-CAG group (RR, 0.79; 95% CI, 0.65-0.97; P = 0.02); however, RCT studies did not find a statistical difference in this outcome (RR, 1.01; 95% CI, 0.83-1.23; P = 0.91). Moreover, mid-term mortality rates were lower in the early-CAG group (RR, 0.87; 95% CI, 0.78-0.98; P = 0.02), mostly due to observational studies. There was no significant difference between the groups in other efficacy and safety outcomes. Although early CAG was associated with lower in-hospital and mid-term mortality in overall analyses, no such difference was confirmed by the results obtained from RCTs. Current evidence from RCTs may not be representative of real-world patients and should be interpreted within its limitation.

Effect of BMI on patients undergoing transcatheter aortic valve implantation: A systematic review and meta-analysis.

BACKGROUND: The relationship of body mass index (BMI) and an "obesity paradox" with cardiovascular risk prediction is controversial. This systematic review and meta-analysis aims to compare the associations of different BMI ranges on transcatheter aortic valve implantation (TAVI) outcomes. METHODS: International databases, including PubMed, the Web of Science, and the Cochrane Library, were systematically searched for observational and randomized controlled trial studies investigating TAVI outcomes in any of the four BMI categories: underweight, normal weight, overweight, and obese with one of the predefined outcomes. Primary outcomes were in-hospital, 30-day, and long-term all-cause mortality. Random-effects meta-analysis was performed to calculate the odds ratio (OR) or standardized mean differences (SMD) with 95% confidence interval (CI) for each paired comparison between two of the BMI categories. RESULTS: A total of 38 studies were included in our analysis, investigating 99,829 patients undergoing TAVI. There was a trend toward higher comorbidities such as hypertension, diabetes, and dyslipidemia in overweight patients and individuals with obesity. Compared with normal-weight, patients with obesity had a lower rate of 30-day mortality (OR 0.42, 95% CI 0.25-0.72, p < 0.01), paravalvular aortic regurgitation (OR 0.63, 95% CI 0.44-0.91, p = 0.01), 1-year mortality (OR 0.48, 95% CI 0.24-0.96, p = 0.04), and long-term mortality (OR 0.69, 95% CI 0.51-0.94, p = 0.02). However, acute kidney injury (OR 1.16, 95% CI 1.04-1.30, p = 0.01) and permanent pacemaker implantation (OR 1.25, 95% CI 1.05-1.50, p = 0.01) odds were higher in patients with obesity. Noteworthy, major vascular complications were significantly higher in underweight patients in comparison with normal weight cases (OR 1.62, 95% CI 1.07-2.46, p = 0.02). In terms of left ventricular ejection fraction (LVEF), patients with obesity had higher post-operative LVEF compared to normal-weight individuals (SMD 0.12, 95% CI 0.02-0.22, p = 0.02). CONCLUSION: Our results suggest the presence of the "obesity paradox" in TAVI outcomes with higher BMI ranges being associated with lower short- and long-term mortality. BMI can be utilized for risk prediction of patients undergoing TAVI.

Comparative Safety and Effectiveness of Loading Doses of P2Y12 Inhibitors in Patients Undergoing Elective PCI: a Network Meta-analysis.

PURPOSE: Effective platelet inhibition prior to elective percutaneous coronary intervention (PCI) reduces the risk of ischemic complications. Newer P2Y12 inhibitors are preferred agents over clopidogrel for patients presenting with the acute coronary syndrome. However, the comparative efficacy and safety of them over clopidogrel in elective PCI is unclear. We performed a network meta-analysis to compare the safety and efficacy of loading strategies of P2Y12 inhibitors in patients undergoing elective PCI. METHODS: We conducted a systematic review of randomized controlled trials (RCT) up to June 2021 to compare the safety and effectiveness of different loading strategies of P2Y12 inhibitors before elective PCI. The endpoints of interest were overall mortality, rates of myocardial infarction (MI), stroke, revascularization, and major bleeding. Random effects model using the frequentist approach was used to perform a network meta-analysis using R software. RESULTS: Five trials with a total of 5194 patients were included in our analysis. For ischemic outcomes, including MI, stroke, and revascularization, prasugrel had the most favorable trend. However, clopidogrel had the highest probability of being most effective for major bleeding and all-cause mortality. None of these trends was statistically significant due to lack of power for each outcome. CONCLUSION: Although prasugrel and ticagrelor are known as more potent antiplatelet agents, their effects in preventing MI and stroke are marginal and do not translate into improved overall mortality and bleeding compared with clopidogrel.

Protease-Activated Receptor Antagonist for Reducing Cardiovascular Events - A Review on Vorapaxar.

Acute Coronary Syndrome (ACS) is a term that describes pathologies related to myocardial ischemia, and is comprised of unstable angina, non-ST elevation myocardial infarction, and ST elevation myocardial infarction. Urgent management of ACS is typically necessary to prevent future morbidity and mortality. Current medical recommendations of ACS management involve use of dual antiplatelet therapy, typically with aspirin and clopidogrel. However, newer therapies are being designed and researched to improve outcomes for patients with ACS. Vorapaxar is a novel antiplatelet therapy that inhibits thrombin-mediated platelet aggregation to prevent recurrence of ischemic events. It has been Food and Drug Administration approved for reduction of thrombotic cardiovascular events in patients with a history of MI or peripheral arterial disease with concomitant use of clopidogrel and/or aspirin, based upon the findings of the TRA 2°P-TIMI 50 trial. However, Vorapaxar was also found to have a significantly increased risk of bleeding, which must be considered when administering this drug. Based upon further subgroup analysis of both the TRA 2°P-TIMI 50 trial and TRACER trial, Vorapaxar was found to be potentially beneficial in patients with peripheral artery disease, coronary artery bypass grafting, and ischemic stroke. There are current trials in progress that are further evaluating the use of Vorapaxar in those conditions, and future research and trials are necessary to fully determine the utility of this drug.

Vericiguat: A Novel Soluble Guanylate Cyclase Stimulator for Use in Patients With Heart Failure.

Heart failure (HF) affects 6.2 million Americans and is increasing annually in its frequency. Treatment of HF has been at the forefront of medical advancements due to the financial burden on our health care system. As such, changes to the guidelines regarding standard of care have been evolving over the last decade with the recent additions of sacubitril-valsartan and sodium glucose co-transporter-2 inhibitors to standard of care in the treatment of HF. Despite the aforementioned expansions in treatment options, HF continues to have a significant impact on the American health care system. Most recently, a novel drug vericiguat that targets an unprecedented pathway for the treatment of HF was Food and Drug Administration approved for the management of patients with HF with a reduced ejection fraction with a recent hospitalization or need for outpatient intravenous diuretics. In clinical trials, vericiguat was associated with a reduction in death from cardiovascular causes and first hospitalization in comparison to placebo. The aim of this review is to provide a comprehensive literature analysis of the various trials surrounding the approval of vericiguat and to both inform and synthesize the data surrounding the clinical use of vericiguat. The introduction of Vericiguat should be considered as a treatment option in patients to decrease the mortality/morbidity of HF with reduced ejection fraction and to increase the quality of life.

COVID-19 Cardiovascular Connection: A Review of Cardiac Manifestations in COVID-19 Infection and Treatment Modalities.

The coronavirus pandemic has crippled healthcare system since its outbreak in 2020, and has led to over 2.6 million deaths worldwide. Clinical manifestations of COVID-19 range from asymptomatic carrier to severe pneumonia, to life-threatening acute respiratory distress syndrome (ARDS). The early efforts of the pandemic surrounded treating the pulmonary component of COVID-19, however, there has been robust data surrounding the cardiac complications associated with the virus. This is suspected to be from a marked inflammatory response as well as direct viral injury. Arrhythmias, acute myocardial injury, myocarditis, cardiomyopathy, thrombosis, and myocardial fibrosis are some of the observed cardiac complications. There have been high morbidity and mortality rates in those affected by cardiac conditions associated with COVID-19. Additionally, there have been documented cases of patients presenting with typical cardiac symptoms who are subsequently discovered to have COVID-19 infection. In those who test positive for COVID-19, clinical awareness of the significant cardiac components of the virus is pertinent to prevent morbidity and mortality. Unfortunately, treatment and preventative measures developed for COVID-19 have been shown to be also be associated with cardiac complications. This is a comprehensive review of the cardiac complications and manifestations of COVID-19 infection in addition to those associated with both treatment and vaccination.

Growing role of SGLT2i in heart failure: evidence from clinical trials.

INTRODUCTION: : There is an unmet need for therapies that improve overall mortality and morbidity for patients with preserved ejection fraction, who comprise roughly half of all heart failure (HF) cases. The growing role of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in cardiovascular outcomes provides a paradigm shift in the treatment of HF. AREAS COVERED: : This review article provides a general overview of the growing role of SGLT2is and summarizes the mechanism of action, side effects, and contraindications for the treatment of HF. We also discuss recent clinical trials measuring the effects of different SGLT2is as possible treatment options for HF with reduced ejection fraction and HF with mid-range and preserved EF. We conducted a review of all the randomized, controlled studies with SGLT2is in patients with known heart failure with and without type-2 diabetes (T2DM). We performed a literature search in PubMed, Google Scholar, the Web of Science, and the Cochrane Library while screening results by the use of titles and abstracts. EXPERT OPINION: : The promising pathophysiological profile of SGLT2i and their role in cardioprotective effects demonstrate an invaluable discovery in the management of patients with HF irrespective of their diabetes status.

Effect of Genotype-Guided Oral P2Y12 Inhibitor Selection After Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Clopidogrel is the most frequently used P2Y12 inhibitor as a component of the dual antiplatelet regimen in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Prior studies have shown the variable efficacy of clopidogrel due to genotypic differences in the CYP2C19 enzyme function, which converts clopidogrel to its active metabolite. The aim of this meta-analysis is to evaluate the effectiveness of genotype testing-guided P2Y12 inhibitor prescription therapy to patients after PCI for ACS compared to non-genotype guided conventional treatment. METHODS: A comprehensive literature search was performed in PubMed, Embase, and Cochrane to identify relevant trials. Summary effects were calculated using a DerSimonian and Laird random-effects model as odds ratio with 95% confidence intervals for all the clinical endpoints. RESULTS: Seven studies with 9617 patients were included. Genotype-guided strategy arm included prasugrel or ticagrelor prescription to patients with loss of function (LOF) of CYP219 alleles (most commonly alleles being *2 and *3) and clopidogrel prescription to those without the LOF allele. The conventional arm included patients treated with clopidogrel without genotype testing. Comparison of genotype arm with conventional arm showed decreased major adverse cardiovascular events (MACE), improved cardiovascular (CV) mortality, and reduced incidence of myocardial infarction (MI) in the genotype arm, and a similar stroke incidence in the two arms. Regarding adverse events, the incidence of stent thrombosis was lower in the genotype arm than the conventional arm. CONCLUSION: Our analysis illustrates the possible advantages of genotype-guided P2Y12 inhibitor prescription strategy compared to non-genotype-guided strategy with reductions in MACE, CV mortality, MI, and stent thrombosis. This analysis can be used as a stepping stone to conducting further trials determining the efficacy of this treatment strategy in various ACS subtypes.

Next-Day Discharge vs Early Discharge After Transcatheter Aortic Valve Replacement: Systematic Review and Meta-Analysis.

With the growing utilization of transcatheter aortic valve replacement (TAVR) as an alternative option to surgical valve replacement (SAVR) in patients considered to be suboptimal for surgery, there is a need to explore the possibility of next day discharge (NDD) and its potential outcomes. The aim of our study is to compare outcomes and complications following NDD vs the standard early discharge (ED) (less than 3 days). A comprehensive literature search was performed in PubMed, Embase, and Cochrane to identify relevant trials. Summary effects were calculated using a DerSimonian and Laird random effects model as odds ratio with 95% confidence intervals for all the clinical endpoints. Studies comparing same-day or next-day discharge vs discharge within the next three days were included in our analysis. 6 studies with 2,672 patients were identified. The risk of bleeding and vascular complications was significantly lower in patients with NDD compared to ED (OR 0.10, P < 0.00001 and OR 0.22, P = 0.002 respectively). The incidence of permanent pacemaker (PPM) implants was significantly lower in patients who had NDD compared to ED (OR 0.21, P = 0.0005). The incidence of 30 day mortality, stroke, AKI and readmission rates was not different between the two groups. NDD after TAVR allows for reduction in hospital stay and can mitigate hospital costs without an increased risk of complications. Our analysis shows that complication rate is comparable to ED, NDD is a reasonable option for certain patients with severe aortic stenosis who undergo TAVR. Further studies are needed to elucidate whether higher risk patients who would benefit from an extended inpatient monitoring post TAVR.

Firibastat: A Novel Brain Aminopeptidase Inhibitor - A New Era of Antihypertensive therapy.

Global incidence and prevalence of hypertension continues to increase and remains a significant challenge. The ever-increasing number of cases are due to comorbid conditions such as obesity and diabetes, as well as lifestyle indiscretions such as excessive salt intake. Hypertension, congestive heart failure, and kidney disease are all conditions resulting from abnormal Renin-Angiotensin-Aldosterone activation and adverse remodeling. Firibastat, a novel Brain Aminopeptidase inhibitor, may be able to help achieve blood pressure control in those with resistant hypertension. In this review article, we will discuss the biochemical pathway of firibastat and various trials assessing drug efficacy in animals and humans. This drug has the potential to curb the risk of uncontrolled hypertension and help improve long term cardiovascular morbidity and mortality.

Valvular Heart Disease in Pregnancy: Anticoagulation and the Role of Percutaneous Treatment.

Valvular heart disease is present in about 1% of pregnancies, and it poses a management challenge as both fetal and maternal lives are at risk of complications. Pregnancy is associated with significant hemodynamic changes, which can compromise the cardiac status in women with underlying valvular disorders. Management of valvular heart diseases has undergone considerable innovation and advancement with newer techniques, approaches and devices being employed. The decision regarding the management of anticoagulation, especially in patients with prosthetic valves, raises distinct questions and challenges. In this review, we describe the management of common valvular heart diseases encountered during pregnancy, role of percutaneous catheter based therapeutic interventions, the importance of a team-based approach, and the challenges given existing gaps in the literature.