Primary Prevention of Cardiovascular Disease in Women.

Cardiovascular disease (CVD) remains a leading cause of mortality in women, necessitating innovative primary prevention strategies. Contemporary guidelines on primary prevention of CVD highlight the increasing prevalence of CVD risk factors and emphasize the significance of female-specific risk enhancers that substantially augment the future risk of CVD. These risk factors occur throughout a woman's life cycle, such as hormonal contraception, hypertensive disorders of pregnancy, and menopause, all of which confer an added layer of risk in women beyond the conventional risk factors. Despite this, current methods may not fully capture the nuanced vulnerabilities in women that increase their risk of CVD. In this review, we highlight gender-specific risk enhancers and subsequent prevention as well as strategies to improve primary prevention of CVD in women.

Epidemiology and Prognostic Implications of Coronary Artery Calcium in Asymptomatic Individuals With Prediabetes: A Multicohort Study.

OBJECTIVE: To describe the epidemiology and prognostic value of coronary artery calcium (CAC) in individuals with prediabetes. RESEARCH DESIGN AND METHODS: We pooled participants free of clinical atherosclerotic cardiovascular disease (ASCVD) from four prospective cohorts: the Multi-Ethnic Study of Atherosclerosis, Heinz Nixdorf Recall Study, Framingham Heart Study, and Jackson Heart Study. Two definitions were used for prediabetes: inclusive (fasting plasma glucose [FPG] ≥100 to <126 mg/dL and hemoglobin A1c [HbA1c] ≥5.7% to <6.5%, if available, and no glucose-lowering medications) and restrictive (FPG ≥110 to <126 mg/dL and HbA1c ≥5.7% to <6.5%, if available, among participants not taking glucose-lowering medications). RESULTS: The study included 13,376 participants (mean age 58 years; 54% women; 57% White; 27% Black). The proportions with CAC ≥100 were 17%, 22%, and 37% in those with euglycemia, prediabetes, and diabetes, respectively. Over a median (25th-75th percentile) follow-up time of 14.6 (interquartile range 7.8-16.4) years, individuals with prediabetes and CAC ≥100 had a higher unadjusted 10-year incidence of ASCVD (13.4%) than the overall group of those with diabetes (10.6%). In adjusted analyses, using the inclusive definition of prediabetes, compared with euglycemia, the hazard ratios (HRs) for ASCVD were 0.79 (95% CI 0.62, 1.01) for prediabetes and CAC 0, 0.70 (0.54, 0.89) for prediabetes and CAC 1-99, 1.54 (1.27, 1.88) for prediabetes and CAC ≥100, and 1.64 (1.39, 1.93) for diabetes. Using the restrictive definition, the HR for ASCVD was 1.63 (1.29, 2.06) for prediabetes and CAC ≥100. CONCLUSIONS: CAC ≥100 is frequent among individuals with prediabetes and identifies a high ASCVD risk subgroup in which the adjusted ASCVD risk is similar to that in individuals with diabetes.

Bridging gaps and optimizing implementation of guideline-directed medical therapy for heart failure.

Despite robust scientific evidence and strong guideline recommendations, there remain significant gaps in initiation and dose titration of guideline-directed medical therapy (GDMT) for heart failure (HF) among eligible patients. Reasons surrounding these gaps are multifactorial, and largely attributed to patient, healthcare professionals, and institutional challenges. Concurrently, HF remains a predominant cause of mortality and hospitalization, emphasizing the critical need for improved delivery of therapy to patients in routine clinical practice. To optimize GDMT, various implementation strategies have emerged in the recent decade such as in-hospital rapid initiation of GDMT, improving patient adherence, addressing clinical inertia, improving affordability, engagement in quality improvement registries, multidisciplinary clinics, and EHR-integrated interventions. This review highlights the current use and barriers to optimal utilization of GDMT, and proposes novel strategies aimed at improving GDMT in HF.

Cardiovascular Outcomes of Transcatheter Aortic Valve Implantation in Patients With Chronic Kidney Disease in Octogenarian Population.

Limited data are available regarding in-hospital outcomes of transcatheter aortic valve implantation (TAVI) in the octogenarian population with chronic kidney disease (CKD). We sought to study the cardiovascular outcomes of TAVI in CKD hospitalization with different stages at the national cohort registry. We used the National Inpatient Sample database to compare TAVI CKD low-grade (LG) (stage I to IIIa, b) versus TAVI CKD high-grade (HG) (stage IV to V) in octogenarians. Outcomes such as inpatient mortality, cardiogenic shock, new permanent pacemaker implantation, acute kidney injury), sudden cardiac arrest, mechanical circulatory support, major bleeding, transfusion, and resource utilization were compared between the 2 cohorts. A total of 74,766 octogenarian patients (TAVI CKD-HG n = 12,220; TAVI CKD-LG n = 62,545) were included in our study. On matched analysis, TAVI CKD-HG had higher odds of in-hospital mortality (adjusted odds ratio [aOR] 2.18, 95% confidence interval [CI] 1.0-2.5, p <0.0001), cardiogenic shock (aOR 1.22, 95% CI 1.07 to 1.39, p = 0.0019), permanent pacemaker implantation (aOR 1.14, 95% CI 1.06 to 1.23, p = 0.0006), acute kidney injury (aOR 1.19, 95% CI 1.13 to 1.27, p <0.0001), sudden cardiac arrest (aOR 1.32, 95% CI 1.09 to 1.61, p = 0.004), major bleeding (aOR 1.1, 95% CI 1.006 to 1.22, p <0.0368) and higher rates of blood transfusion (aOR 1.62, 95% CI 1.5 to 1.75, p <0.0001) when compared with the TAVI CKD-LG cohort. However, there was no statistically significant difference in the odds of cerebrovascular accident and mechanical circulatory support use between the 2 groups.

Meta-analysis on performance of ABC and GARFIELD-AF compared to CHA2DS2-VASc and HAS-BLED in anticoagulated atrial fibrillation patients.

BACKGROUND: When high thromboembolic and bleeding risks coexist, the former tends to influence physicians' decision making for anti-coagulation therapy. However, the ideal is to weigh the risk of major bleeding and stroke together to ensure effective anti-coagulation treatment, which is a limitation of traditional guideline recommended CHA2DS2-VASc and HAS-BLED. This meta-analysis assesses the performance of the two new scores - ABC and GARFIELD-AF compared to CHA2DS2-VASc and HAS-BLED for major bleeding and stroke outcomes in patients with atrial fibrillation (AF) on anticoagulation therapy. METHODS: MEDLINE and Cochrane central were searched from 2010 to February 2023 that compared GARFIELD-AF and/or ABC with CHA2DS2-VASc and/or HAS-BLED scores using C-statistics to assess their discriminative ability. RESULTS: 12 studies were included in this meta-analysis. When assessing stroke risk prediction, GARFIELD-AF stroke (C-Statistic: 0.71; 95 % CI: 0.70-0.72; I2 = 0 %, p < 0.05) was found to be significantly better than ABC-stroke (C-Statistic: 0.67; 95 % CI: 0.65-0.68; I2 = 0 %, p < 0.05), and CHA2DS2-VASc (C-Statistic: 0.64; 95 % CI: 0.60-0.67; I2 = 92 %, p < 0.05). Additionally, when assessing bleeding risk prediction, ABC-bleeding (C-Statistic: 0.66; 95 % CI: 0.61-0.70; I2 = 84 %, p < 0.05), GARFIELD-AF (C-Statistic: 0.64; 95 % CI: 0.60-0.68; I2 = 95 %, p < 0.05), and HAS-BLED (C-Statistic: 0.64; 95 % CI: 0.62-0.66; I2 = 85 %, p < 0.05) all showed equivalent performances. CONCLUSION: The GARFIELD-AF stroke score showed superior performance to the well-established CHA2DS2-VASc score as well as the ABC-stroke score. Therefore, new guidelines should favor GARFIELD-AF use in clinical practice.

Effectiveness of Emergency versus Nonemergent Coronary Angiography After Out-of-Hospital Cardiac Arrest without ST-Segment Elevation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The optimal timing of coronary angiography (CAG) in patients after out-of-hospital cardiac arrest (OHCA) without ST-segment elevation remains controversial. Therefore, we conducted a meta-analysis of randomized control trials to investigate the effectiveness of emergency CAG versus delayed CAG in OHCA patients with a non-ST-segment elevated rhythm. PubMed, Scopus, CINAHL, Cochrane CENTRAL, and JBI databases were searched from inception to September 7, 2022. Our primary end point was survival with a good neurological outcome, whereas the secondary outcomes included short-term survival, mid-term survival, recurrent arrhythmias, myocardial infarction after hospitalization, major bleeding, acute kidney injury, and left ventricular ejection fraction. Nine randomized control trials involving 2,569 patients were included in this analysis. Our meta-analysis showed no significant difference in the improvement of neurological outcome (RR 0.96, 95% Confidence Interval [CI] [0.87, 1.06]), short-term survival (risk ratio [RR] 0.98, 95% CI [0.89, 1.08]), mid-term survival (RR 0.98, 95% CI [0.87, 1.10]), recurrent arrhythmias (RR 1.02, 95% CI [0.50, 2.06]), myocardial infarction (RR 0.66, 95% CI [0.13, 3.30]), major bleeding (RR 0.96, 95% CI [0.55, 1.69]), acute kidney injury (RR 1.20, 95% CI [0.32, 4.49]) and left ventricular ejection fraction (RR 0.89, 95% CI [0.69, 1.15]) in patients who underwent emergency CAG compared with delayed CAG patients. In conclusion, our analysis revealed that emergency CAG had no prognostic superiority over delayed CAG in patients with OHCA without ST-segment elevation.

Meta-Analysis Evaluating Risk of Hyperkalemia Stratified by Baseline MRA Usage in Patients with Heart Failure Receiving SGLT2 Inhibitors.

BACKGROUND: Both mineralocorticoid receptor antagonists (MRAs) and sodium-glucose co-transporter type 2 inhibitors (SGLT2is) have demonstrated beneficial reductions in cardiovascular outcomes. However, the risk of precipitating hyperkalemia with their concomitant usage remains unclear. METHODS: MEDLINE and Cochrane were searched from inception through March 2022. Randomized controlled trials on patients with heart failure (HF) evaluating the effect of SGLT2is on clinical outcomes between MRA users and non-users were considered for inclusion. Outcomes of interest were mild and moderate/severe hyperkalemia, for which hazard ratios (HR) were pooled using a random effects model. RESULTS: From the 972 articles retrieved from the initial search, three RCTs (n = 14,462 patients) were included in our meta-analysis. Pooled analysis demonstrated no significant difference in the incidence of mild hyperkalemia between MRA users (HR 0.82 [0.70-0.97]) and non-users (HR 0.95 [0.77-1.17]) (P-interaction = 0.28). The risk of severe hyperkalemia was significantly decreased in MRA users (HR 0.59 [0.44-0.78]; p = 0.0002; I2 = 0%) but not in non-users (HR 0.76 [0.56-1.02]; p = 0.07; I2 = 0%) (P-interaction = 0.22). Sensitivity analysis including patients with HF with reduced ejection fraction (HFrEF) revealed similar results across all subgroups, but no significant reduction in the incidence of mild hyperkalemia (HR 0.89 [0.76-1.04] was noted in MRA users with HFrEF. CONCLUSION: MRAs reduced the risk of mild or moderate/severe hyperkalemia, when added to SGLT2is. Future clinical trials should target scrupulous assessment of the risk of mild and moderate/severe hyperkalemia when used concomitantly with MRAs.

Albuminuria and Heart Failure: JACC State-of-the-Art Review.

Although chronic kidney disease is characterized by low glomerular filtration rate (GFR) or albuminuria, estimated GFR (eGFR) is more widely utilized as a marker of risk profile in cardiovascular diseases, including heart failure (HF). The presence and magnitude of albuminuria confers a strong prognostic association in forecasting risk of incident HF as well as its progression, irrespective of eGFR. Despite the high prevalence of albuminuria in HF, whether it adds incremental prognostic information in clinical practice and serves as an independent risk marker, and whether there are any therapeutic implications of assessing albuminuria in patients with HF is less well-established. In this narrative review, we assess the potential role of albuminuria in risk profiling for development and progression of HF, strengths and limitations of utilizing albuminuria as a risk marker, its ability to serve in HF risk prediction models, and the implications of adopting albuminuria as an effective parameter in cardiovascular trials and practice.

Association of Non-Alcoholic Fatty Liver Disease With in-Hospital Outcomes in Primary Heart Failure Hospitalizations With Reduced or Preserved Ejection Fraction.

Recent studies focusing on the prevalence, characteristics, and outcomes of primary heart failure (HF) with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) in non-alcoholic fatty liver disease (NAFLD) are sparse. We sought to assess these using a nationally-representative population. We used the 2016-2018 National Inpatient Sample database to study the prevalence, characteristics, clinical risk profiles, morbidity, mortality, cost, and resource utilization among primary HFpEF and HFrEF hospitalizations with and without NAFLD. In the period from January 1, 2016, to December 31, 2018, there were 3,522,459 admissions of patients aged ≥18 years with a diagnosis of primary HF. Of these, 82,585 (2.3%) hospitalizations had secondary diagnosis of NAFLD. Admissions with NAFLD and HFrEF were associated with higher rates of in-hospital mortality (aOR 1.84, CI 1.66-2.04, P < 0.001) compared to admissions of HFrEF without NAFLD. Similarly, hospitalizations with HFpEF-NAFLD were associated with higher rates of in hospital mortality (aOR 1.65 CI 1.43-1.9, P < 0.001) compared to HFpEF admissions without NAFLD. Pressors use, cardiogenic shock, AKI with or without dialysis use, cardiac arrest, LOS and hospitalization cost were higher in admissions of HFrEF and HFpEF with NAFLD compared to those without NAFLD. In-hospital mortality, was higher in primary HFrEF and HFpEF admissions with NAFLD compared to without NAFLD. Physicians must be aware of the worse clinical outcomes of HFrEF and HFpEF in patients with NAFLD. Further clinical research is needed to address the knowledge gap and treatment options available for the patients with HF and NAFLD.

Mechanisms of current therapeutic strategies for heart failure: more questions than answers?

Heart failure (HF) is a complex, multifactorial and heterogeneous syndrome with substantial mortality and morbidity. Over the last few decades, numerous attempts have been made to develop targeted therapies that may attenuate the known pathophysiological pathways responsible for causing the progression of HF. However, therapies developed with this objective have sometimes failed to show benefit. The pathophysiological construct of HF with numerous aetiologies suggests that interventions with broad mechanisms of action which simultaneously target more than one pathway maybe more effective in improving the outcomes of patients with HF. Indeed, current therapeutics with clinical benefits in HF have targeted a wider range of intermediate phenotypes. Despite extensive scientific breakthroughs in HF research recently, questions persist regarding the ideal therapeutic targets which may help achieve maximum benefit. In this review, we evaluate the mechanism of action of current therapeutic strategies, the pathophysiological pathways they target and highlight remaining knowledge gaps regarding the mode of action of these interventions.

Outcomes of concomitant aortic valve procedures and left ventricular assist device implantation: A systematic review and meta-analysis.

BACKGROUND: Left ventricular assist device (LVAD) implantation is frequently employed in patients with end-stage heart failure. The outcomes of addressing the repair of all substantial aortic valvular disease at the time of LVAD implantation remain unclear. We sought to assess the clinical outcomes in patients undergoing LVAD implantation concomitant with aortic valve procedures (AVPs) compared with isolated LVAD implantation. METHODS: A literature search was performed using PubMed, Embase, and Cochrane library from inception till June 2022. Primary outcomes included short-term mortality and long-term survival. Random effects models were used to compute mean differences and odds ratios with 95% confidence intervals (CIs). RESULTS: A total of 14 observational studies (N = 52 693) met our inclusion criteria. Concomitant LVAD implantation and AVPs were associated with higher short-term mortality (OR = 1.61 [95% CI, 1.06-2.42]; p = 0.02) and mean CPBt (MD = 43.25 [95% CI, 22.95-63.56]; p < 0.0001), and reduced long-term survival (OR = 0.70 [95% CI, 0.55-0.88]; p = 0.003) compared with isolated LVAD implantation. No difference in the odds of cerebrovascular accident (OR = 1.05 [95% CI, 0.79-1.39]; p = 0.74) and mean length of hospital stay (MD = 2.89 [95% CI, -4.04 to 9.82]; p = 0.41) was observed between the two groups. On adjusted analysis, short-term mortality was significantly higher in the LVAD group with concurrent AVPs when compared with the isolated LVAD group (aHR = 1.50 [95% CI, 1.20-1.87]; p = 0.0004). CONCLUSIONS: Concurrent AVPs were associated with higher short-term mortality and reduced long-term survival in patients undergoing LVAD implantation compared with isolated LVAD implantation.

Inconsistent Outcome Reporting in Heart Failure Randomized Controlled Trials.

BACKGROUND: Randomized controlled trials (RCTs) may report outcomes different from those prespecified on trial-registration websites, protocols and statistical analysis plans (SAPs). This study sought to investigate the prevalence and characteristics of heart failure (HF) RCTs that report outcomes different from those prespecified. METHODS AND RESULTS: MEDLINE via PubMed was searched to include phase II-IV HF RCTs in 9 high-impact journals from 2010 to 2020. Outcomes reported in trial publications were compared with prespecified outcomes in protocols, registration websites and SAPs. We used the χ2 or Fisher exact test to analyze correlations between trial characteristics and inconsistencies. Among 216 trials, 32 inconsistencies were observed in 28 trials (13.0%). Among 32 inconsistencies, 2 (6.3%) pertained to omission of prespecified primary outcomes, 4 (12.5%) to omission of prespecified secondary outcomes, 2 (6.3%) to changing prespecified primary outcomes to secondary outcomes, and 2 (6.3%) to changing prespecified secondary outcomes to primary outcomes. Of the inconsistencies, 3 (9.4%) pertained to addition of new primary outcomes, 17 (53.1%) to addition of new secondary outcomes, and 2 (6.3%,) to changes in the timing of assessment of primary outcomes. The majority of the inconsistencies favored statistically significant findings; 78 (36.1%) were registered retrospectively. Single-center recruitment was associated with outcome inconsistencies (ß = -0.14; 95% CI, -0.22 - -0.01; P = 0.035). CONCLUSIONS: More than 1 in 10 trials reported outcomes inconsistent with those specified in trial registration websites, SAPs and protocols. An action plan is warranted to minimize selective reporting and improve transparency.

Reporting and Definition of Kidney Death in Heart Failure Clinical Trials.

Current kidney death definitions across heart failure (HF) trials are ambiguous and lack standardization. The interlinked shared pathways of HF and kidney failure makes it difficult to adjudicate the cause versus effect relationship of worsening HF and kidney failure events and raises concerns whether 'kidney death' is an affirmative or exclusionary diagnosis. Universally standardized definition of kidney death is therefore of utmost importance to accurately ascertain if kidney death is due to kidney failure itself or due to complications associated with it. Conceptually comprehensive and applicable definition(s) would be beneficial for clinicians and investigators in comparing data across trials and for shared decision making. Herein, we review the current definitions of kidney death, the frequency of reporting it across HF trials and the limitations associated with it. Additionally, we propose clinically relevant and comprehensive definitions pertaining kidney organ death which may aid clinicians and researchers alike in accurately distinguishing kidney death from a non-kidney death event.

Performance of current risk stratification models for predicting mortality in patients with heart failure: a systematic review and meta-analysis.

AIMS: There are several risk scores designed to predict mortality in patients with heart failure (HF). This study aimed to assess performance of risk scores validated for mortality prediction in patients with acute HF (AHF) and chronic HF. METHODS AND RESULTS: MEDLINE and Scopus were searched from January 2015 to January 2021 for studies which internally or externally validated risk models for predicting all-cause mortality in patients with AHF and chronic HF. Discrimination data were analysed using C-statistics, and pooled using generic inverse-variance random-effects model. Nineteen studies (n = 494 156 patients; AHF: 24 762; chronic HF mid-term mortality: 62 000; chronic HF long-term mortality: 452 097) and 11 risk scores were included. Overall, discrimination of risk scores was good across the three subgroups: AHF mortality [C-statistic: 0.76 (0.68-0.83)], chronic HF mid-term mortality [1 year; C-statistic: 0.74 (0.68-0.79)], and chronic HF long-term mortality [≥2 years; C-statistic: 0.71 (0.69-0.73)]. MEESSI-AHF [C-statistic: 0.81 (0.80-0.83)] and MARKER-HF [C-statistic: 0.85 (0.80-0.89)] had an excellent discrimination for AHF and chronic HF mid-term mortality, respectively, whereas MECKI had good discrimination [C-statistic: 0.78 (0.73-0.83)] for chronic HF long-term mortality relative to other models. Overall, risk scores predicting short-term mortality in patients with AHF did not have evidence of poor calibration (Hosmer-Lemeshow P > 0.05). However, risk models predicting mid-term and long-term mortality in patients with chronic HF varied in calibration performance. CONCLUSIONS: The majority of recently validated risk scores showed good discrimination for mortality in patients with HF. MEESSI-AHF demonstrated excellent discrimination in patients with AHF, and MARKER-HF and MECKI displayed an excellent discrimination in patients with chronic HF. However, modest reporting of calibration and lack of head-to-head comparisons in same populations warrant future studies.

Evaluation and Treatment of Central Sleep Apnea in Patients with Heart Failure.

Sleep-disordered breathing (SDB) is a common comorbidity in patients with heart failure (HF). Prevalence of the most common subtypes of SDB, central sleep apnea (CSA) and obstructive sleep apnea (OSA), is increasing, which is concerning due to the association of SDB with increased mortality in patients with HF. Despite an increasing burden of CSA in HF, it is difficult to detect using current diagnostic tools and the treatment modalities are limited by variable efficacy and patient adherence. Though positive airway pressure therapies remain the cornerstone of OSA treatment, the management of CSA in the setting of HF continues to evolve. The association of the presence of CSA with worse prognosis in HF patients warrants the need for routine screening for signs and symptoms of CSA in this population. In this review, we examine the connection between CSA and HF, and highlight advancements in timely diagnostics, treatment modalities, and strategies to promote facilitation of compliance in this high-risk cohort.

DOACs or VKAs or LMWH - What is the optimal regimen for cancer-associated venous thromboembolism? A systematic review and meta-analysis.

Background: Clinical guidelines have supported the use of direct anticoagulants (DOACs) for the treatment of cancer-associated venous thromboembolism (Ca-VTE). However, recent trials have reported increased bleeding risks associated with DOACs usage, raising concerns regarding its efficacy. Objectives: The authors conducted a meta-analysis to study the efficacy and safety of DOACs for the treatment of VTE in cancer patients, compared with Low-weight molecular heparin (LMWH) and Vitamin-K antagonists (VKAs). Methods: PubMed, EMBASE, Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL) were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines from inception to June 17th, 2021.The primary outcomes studied were VTE recurrence and major bleeding. Results: A total of 8 randomized controlled trials (RCTs) enrolling almost 7000 patients were included. Direct oral anticoagulants significantly reduced VTE Recurrence in cancer patients when compared to patients treated with LMWH or VKAs (Hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.46-0.83; P = 0.002; I2 = 26%). There were no statistically significant differences for major bleeding (HR 0.86, 95% confidence interval [CI] 0.56-1.33; P = 0.50; I2 = 34%), clinically relevant non-major bleeding (HR 1.23, 95% confidence interval [CI] 0.79-1.91; P = 0.35; I2 = 66%), pulmonary embolism (HR 0.71, 95% confidence interval [CI] 0.47-1.06; P = 0.10; I2 = 7%), and all-cause mortality (HR 0.98, 95% confidence interval [CI] 0.86-1.12; P = 0.78; I2 = 1%), between DOACs and LMWH. Conclusion: This analysis shows that DOACs are the optimal regimen to treat Ca-VTE. They have a similar to slightly increased bleeding risk compared with LMWH and are a safer alternative to VKAs.