Intravascular Imaging-Guided Versus Angiography-Guided Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Trials.

BACKGROUND: Despite the initial evidence supporting the utility of intravascular imaging to guide percutaneous coronary intervention (PCI), adoption remains low. Recent new trial data have become available. An updated study-level meta-analysis comparing intravascular imaging to angiography to guide PCI was performed. This study aimed to evaluate the clinical outcomes of intravascular imaging-guided PCI compared with angiography-guided PCI. METHODS AND RESULTS: A random-effects meta-analysis was performed on the basis of the intention-to-treat principle. The primary outcomes were major adverse cardiac events, cardiac death, and all-cause death. Mixed-effects meta-regression was performed to investigate the impact of complex PCI on the primary outcomes. A total of 16 trials with 7814 patients were included. The weighted mean follow-up duration was 28.8 months. Intravascular imaging led to a lower risk of major adverse cardiac events (relative risk [RR], 0.67 [95% CI, 0.55-0.82]; P<0.001), cardiac death (RR, 0.49 [95% CI, 0.34-0.71]; P<0.001), stent thrombosis (RR, 0.63 [95% CI, 0.40-0.99]; P=0.046), target-lesion revascularization (RR, 0.67 [95% CI, 0.49-0.91]; P=0.01), and target-vessel revascularization (RR, 0.60 [95% CI, 0.45-0.80]; P<0.001). In complex lesion subsets, the point estimate for imaging-guided PCI compared with angiography-guided PCI for all-cause death was a RR of 0.75 (95% CI, 0.55-1.02; P=0.07). CONCLUSIONS: In patients undergoing PCI, intravascular imaging is associated with reductions in major adverse cardiac events, cardiac death, stent thrombosis, target-lesion revascularization, and target-vessel revascularization. The magnitude of benefit is large and consistent across all included studies. There may also be benefits in all-cause death, particularly in complex lesion subsets. These results support the use of intravascular imaging as standard of care and updates of clinical guidelines.

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.

SGLT2 inhibitors in hypertension: Role beyond diabetes and heart failure.

Type 2 Diabetes Mellitus (T2DM) is a pandemic that affects millions of patients worldwide. Diabetes affects multiple organ systems leading to comorbidities including hypertension. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) recently have been approved for the treatment of T2DM and heart failure with reduced and preserved ejection fraction. Retrospective analyses of clinical trials have noted SGLT2 inhibitors to have a promising effect on blood pressure. Moreover, the observed blood pressure reduction is not just an acute effect of treatment initiation but has been shown to have a long-term impact on both systolic and diastolic blood pressure. The mechanism of action leading to the blood pressure reduction is still unclear; however, proposed mechanisms are related to the natriuretic effect, modification of the renin-angiotensin-aldosterone system, and/or the reduction in the sympathetic nervous system, SGLT2i should be considered as second-line medication in those patients with diabetes or heart disease and concomitant hypertension. This article reviews the pharmacology, side effect profile, and clinical trials surrounding the use of SGLT2i for the treatment of hypertension.

Pharmacotherapies in Heart Failure With Preserved Ejection Fraction: A Systematic Review and Network Meta-Analysis.

Various pharmacotherapies exist for heart failure with preserved ejection fraction (HFpEF), but with unclear comparative efficacy. We searched EMBASE, Medline, and Cochrane Library from inception through August 2021 for all randomized clinical trials in HFpEF (EF >40%) that evaluated beta-blockers, mineralocorticoid receptor antagonist (MRA), angiotensin-converting enzyme inhibitors (ACE), angiotensin receptor blockers (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), and sodium-glucose cotransporter-2 inhibitors (SGLT2i). Outcomes assessed were cardiovascular mortality, all-cause mortality, and HF hospitalization. A frequentist network meta-analysis was performed with a random-effects model. We included 22 randomized clinical trials (30,673 participants; mean age = 71.7 ± 4.2 years; females = 49.3 ± 7.7%; median follow-up = 24.4 ± 11.1 months). Compared with placebo, there was no statistically significant difference in cardiovascular mortality [beta-blockers; odds ratio (OR) 0.79 (0.46-1.34), MRA; OR 0.90 (0.70-1.14), ACE OR 0.95 (0.59-1.53), ARB; OR 1.02 (0.87-1.19), ARNI; OR 0.97 (0.74-1.26) and SGLT2i; OR 1.00 (0.84-1.18)] or all-cause mortality [beta blockers; OR 0.75 (0.54-1.04), MRA; OR 0.90 (0.75-1.08) ACE; OR 1.05 (0.71-1.54), ARB; OR 1.03 (0.91-1.15), ARNI; OR 0.99 (0.82-1.20) and SGLT2i; OR 1.00 (0.89-1.13)]. The certainty in these estimates was low or very low. There was a significantly reduction in HF hospitalization with the use of SGLT2i [OR 0.71 (0.62-0.82), moderate certainty], ARNI [OR 0.77 (0.63-0.94), low certainty], and MRA [OR 0.81 (0.66-0.98), moderate certainty]; with corresponding P scores of 0.84, 0.68, and 0.58, respectively. In HFpEF, the use of beta-blockers, MRA, ACE/ARB/ARNI, or SGLT2i was not associated with improved cardiovascular or all-cause mortality. SGLT2i, ARNI, and MRA reduced the risk of HF hospitalizations.

Coronary Intravascular Lithotripsy.

Coronary artery calcification is strongly associated with adverse cardiac events and can impede the success of percutaneous coronary intervention (PCI) due to challenges with delivery of equipment and expansion of stents. Current treatment modalities for mitigation of coronary calcification have limitations and inherent risk of complications. Coronary intravascular lithotripsy (IVL) is a novel technique to modify coronary artery calcification via acoustic pressure waves. IVL utilizes an easy-to-use device, which does not require a steep learning curve. Prospective studies have shown this technique to be safe and effective and can be used to adequately modify calcified coronary stenoses in preparation for PCI and stent deployment and optimization. IVL has unique features that can be used alone or as an adjunctive therapy to other available calcium modification tools. As compared to the currently established modalities of calcium modification, IVL has the potential to facilitate successful PCI with fewer serious procedural complications. In this review article, we discuss the importance of coronary artery calcification, the role of IVL, its mechanism, the current clinical data behind its use and future directions. Overall, coronary IVL is a promising technology for the treatment of severely calcified coronary stenoses, with a need for, long-term clinical outcome data of IVL-facilitated PCI.

Finerenone: A New Era for Mineralocorticoid Receptor Antagonism and Cardiorenal Protection.

The renin-angiotensin-aldosterone system is a neurohormonal system responsible for maintaining homeostasis of fluid regulation, sodium balance, and blood pressure. The complexity of this pathway enables it to be a common target for blood pressure and volume-regulating medications. The mineralocorticoid receptor is one of these targets, and is found not only in the kidney, but also tissues making up the heart, blood vessels, and adipose. Mineralocorticoid receptor antagonists have been shown to slow progression of chronic kidney disease, treat refractory hypertension and primary aldosteronism, and improve morbidity and mortality in management of heart failure with reduced ejection fraction. The more well-studied medications were derived from steroid-based compounds, and thus come with a distinct side-effect profile. To avoid these adverse effects, developing a mineralocorticoid receptor antagonist (MRA) from a non-steroidal base compound has gained much interest. This review will focus on the novel non-steroidal MRA, Finerenone, to describe its unique mechanism of action while summarizing the available clinical trials supporting its use in patients with various etiologies of cardiorenal disease.

Trends in 10-Year Predicted Risk of Cardiovascular Disease Associated With Food Insecurity, 2007-2016.

Introduction: Consumption of a healthy diet improves cardiovascular (CV) risk factors and reduces the development of cardiovascular disease (CVD). Food insecure (FIS) adults often consume an unhealthy diet, which can promote obesity, type 2 diabetes mellitus (T2DM), hypertension (HTN), and hyperlipidemia (HLD). The Supplemental Nutrition Assistance Program (SNAP) is designed to combat food insecurity by increasing access to healthy foods. However, there is a paucity of data on the association of SNAP participation among FIS adults and these CVD risk factors. Methods: The National Health and Nutrition Examination Survey (NHANES) is a publicly available, ongoing survey administered by the Centers for Disease Control and Prevention and the National Center for Health Statistics. We analyzed five survey cycles (2007-2016) of adult participants who responded to the CVD risk profile questionnaire data. We estimated the burden of select CVD risk factors among the FIS population and the association with participation in SNAP. Results: Among 10,449 adult participants of the survey, 3,485 (33.3%) identified themselves as FIS. Food insecurity was more common among those who were younger, female, Hispanic, and Black. Among the FIS, SNAP recipients, when compared to non-SNAP recipients, had a lower prevalence of HLD (36.3 vs. 40.1% p = 0.02), whereas rates of T2DM, HTN, and obesity were similar. Over the 10-year survey period, FIS SNAP recipients demonstrated a reduction in the prevalence of HTN (p < 0.001) and HLD (p < 0.001) which was not evident among those not receiving SNAP. However, obesity decreased only among those not receiving SNAP. The prevalence of T2DM did not change over the study period in either group. Conclusion: Over a 10-year period, FIS adults who received SNAP demonstrated a reduction in the prevalence of HTN and HLD, which was not seen among those not receiving SNAP. However, the prevalence of obesity and T2DM did not decline among SNAP recipients, suggesting that additional approaches are required to impact these important CVD risk factors.

The role of serial right heart catheterization in risk stratification and management of pulmonary arterial hypertension.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial blood pressure secondary to increased pulmonary vascular resistance. AREAS COVERED: Invasive hemodynamic assessment by heart catheterization (RHC) remains the gold standard to confirm the diagnosis, to determine the severity of right ventricular dysfunction and to test for pulmonary vasoreactivity. After diagnosis and initiation of therapy, many PAH centers continue to perform RHC at regular intervals to monitor for disease progression and alter management. We discuss the importance of risk stratification in PAH, the role of RHC in the evaluation and treatment of these patients and compare non-invasive risk assessment tools to that of RHC. EXPERT OPINION: RHC is useful for diagnosis of PAH, assessing the risk of mortality and morbidity, directing the escalation and de-escalation of therapy, and monitoring for disease progression. In the current era of improved non-invasive cardiac hemodynamic assessment, the role for routine follow-up serial RHC in patients with PAH needs to be reassessed in future studies. With the availability of non-invasive risk assessment tools such as REVEAL Lite 2, it may be reasonable to reconsider the role of annual or protocoled RHC, and instead, move on to an "as needed" and individual approach.

Impact of Body Mass Index on Mortality in Hospitalized Patients With Hypertrophic Cardiomyopathy.

Although obesity is associated with increased phenotypic expression in patients with hypertrophic cardiomyopathy (HC), the effect of body mass index (BMI) on in-hospital mortality in hospitalized patients with HC has not been established. We evaluated the National Inpatient Sample in the United States to identify all adults with HC hospitalized for cardiac illnesses between 2008 and 2017. Using International Classification of Diseases codes, the study cohort was stratified into underweight (BMI ≤19.9 kg/m2), normal weight (BMI 20.0 to 24.9 kg/m2), overweight (BMI 25.0 to 29.9 kg/m2), class I (BMI 30.0 to 34.9 kg/m2), class II (BMI 35.0 to 39.9 kg/m2), and class III (BMI ≥40.0 kg/m2) obesity. Multiple logistic regression analysis was used to analyze the independent association of various BMI categories and mortality. The study included a total of 2,392,325 hospitalizations (mean age-66.1 ± 12.2 years; 42.0% female). The patients with class III obesity (adjusted mortality rate [AMR] 3.3%, adjusted odds ratio [AOR] 1.53, 95% confidence interval [CI] 1.29 to 1.82, p <0.001) and underweight patients (AMR 4.4%, AOR 2.07, 95% CI 1.74-2.46, p <0.001) had higher in-hospital mortality whereas overweight patients (AMR 1.6%, AOR 0.26, 95% CI 0.19 to 0.34, p <0.001), patients with class I obesity (AMR 0.8%, AOR 0.35, 95% CI 0.27 to 0.45, p <0.001) and patients with class II obesity (AMR 0.8%, AOR 0.34, 95% CI 0.26 to 0.45, p <0.001) had lower mortality compared with patients with normal BMI (AMR 2.9%). In conclusion, BMI has a nonlinear U-shaped relation with in-hospital mortality in patients with HC. The patients who were underweight and morbidly obese had significantly higher mortality, whereas those patients with overweight, class I, and class II obesity had lower mortality than normal BMI.

Heart failure with preserved ejection fraction: key stumbling blocks for experimental drugs in clinical trials.

INTRODUCTION: Heart failure with preserved ejection fraction (HFpEF) is a disease with a high prevalence. Accounting for more than 50% of all heart failure cases, it carries a significant mortality. There is a lack of therapeutic options that show improvement in morbidity and mortality. Certain novel therapies have shown a decrease in heart failure hospitalizations; however, this beneficial effect was more pronounced for heart failure patients with mildly reduced ejection fraction (EF). AREAS COVERED: This review summarizes the pathophysiology of the disease to help elucidate the differences between heart failure with reduced ejection fraction (HFrEF), and HFpEF, which could explain why therapies are successful in one (rather than the other). This review focuses on non-standardized nomenclature across major trials, the challenges of finding a therapeutic agent for such a heterogeneous population, and identification of specific phenotypes that have different outcomes and could be a target for future therapies. EXPERT OPINION: Lack of standardized diagnostic criteria, associated with population heterogeneity, might explain why trials have failed to improve outcomes for patients with HFpEF. Standardizing phenotypes, recapitulating these phenotypes in animal models, and understanding the mechanisms of the disease at the molecular level could be the first steps in identifying promising therapeutic options.

Mental health disorders and readmissions following acute myocardial infarction in the United States.

Hospital readmissions following an acute myocardial infarction (MI) are associated with increased mortality and morbidity. The aim of this study was to investigate if there is a significant association between specific mental health disorders (MHD) and risk of hospital readmission after an index hospitalization for acute MI. We analyzed the U.S. National Readmission Database for adult acute MI hospitalizations from 2016 to 2017. Co-morbid diagnoses of MHD were obtained using appropriate ICD-10-CM diagnostic codes. The primary outcome of interest was 30-day all-cause unplanned readmission. Cox-regression analysis was used to identify the association of various MHD and risk of 30-day readmission adjusted for demographics, medical and cardiac comorbidities, and coronary revascularization. We identified a total of 1,045,752 hospitalizations for acute MI; patients had mean age of 67 ± 13 years with 37.6% female. The prevalence of any MHD was 15.0 ± 0.9%. After adjusting for potential confounders, comorbid diagnosis of major depression [HR 1.11 (95% CI 1.07-1.15)], bipolar disorders [1.32 (1.19-1.45)], anxiety disorders [1.09 (1.05-1.13)] and schizophrenia/other psychotic disorders [1.56 (1.43-1.69)] were independently associated with higher risk of 30-day readmission compared to those with no comorbid MHD. We conclude that MHD are significantly associated with a higher independent risk of 30-day all-cause hospital readmissions among acute MI hospitalizations.

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.

Extracorporeal Membrane Oxygenation in Patients With COVID-19.

Coronavirus disease 2019 (COVID-19) is characterized by a clinical spectrum of diseases ranging from asymptomatic or mild cases to severe pneumonia with acute respiratory distress syndrome (ARDS) requiring mechanical ventilation. Extracorporeal membrane oxygenation (ECMO) has been used as rescue therapy in appropriate patients with COVID-19 complicated by ARDS refractory to mechanical ventilation. In this study, we review the indications, challenges, complications, and clinical outcomes of ECMO utilization in critically ill patients with COVID-19-related ARDS. Most of these patients required venovenous ECMO. Although the risk of mortality and complications is very high among patients with COVID-19 requiring ECMO, it is similar to that of non-COVID-19 patients with ARDS requiring ECMO. ECMO is a resource-intensive therapy, with an inherent risk of complications, which makes its availability limited and its use challenging in the midst of a pandemic. Well-maintained data registries, with timely reporting of outcomes and evidence-based clinical guidelines, are necessary for the careful allocation of resources and for the development of standardized utilization protocols.