Intravenous iron therapy for heart failure and iron deficiency: An updated meta-analysis of randomized clinical trials.

Heart failure (HF) patients frequently exhibit iron deficiency, which is associated with a poor prognosis. Although various trials have been conducted, it is uncertain if intravenous (IV) iron replenishment improves clinical outcomes in HF patients with iron deficiency. A comprehensive literature search was conducted using PubMed/MEDLINE, Embase, and the Cochrane Library from inception till 15 September 2023 to retrieve randomized controlled trials (RCTs) that compared IV iron therapy with placebo or standard of care in patients with HF and iron deficiency. Clinical outcomes were assessed by generating forest plots using the random-effects model and pooling odds ratios (ORs) or weighted mean differences (WMDs). Fourteen RCTs with 6651 patients were included. IV iron therapy showed a significantly reduced incidence of the composite of first heart failure hospitalization (HHF) or cardiovascular (CV) mortality as compared with the control group (OR = 0.73, 95% CI: 0.58 to 0.92). The IV iron therapy resulted in a trend towards lower CV mortality (OR = 0.88, 95% CI: 0.76 to 1.01), 1-year all-cause mortality (OR = 0.85, 95% CI: 0.71 to 1.02), and first HHF (OR = 0.73, 95% CI: 0.51 to 1.05), and an improved left ventricular ejection fraction (LVEF) (MD = 4.54, 95% CI: -0.13 to 9.21). Meta-regression showed a significant inverse moderating effect of baseline LVEF on the first HHF or CV death. In patients with HF and iron deficiency, IV iron therapy reduced the incidence of composite of first HHF or CV mortality. There was a trend of lower overall CV and 1-year all-cause mortality, first HHF, and improved LVEF with IV iron therapy.

Ongoing and Future Clinical Trials of Pharmacotherapy for Heart Failure.

Increasing knowledge of the processes leading to heart failure (HF) has allowed significant developments in therapies for HF over the past few decades. Despite the evolution of HF treatment, it still places a large burden on patients and health care systems across the world.We used clinicaltrials.gov to gather information about clinical trials as of August 2023 studying pharmacotherapy for HF. We included interventional trials that were "active, not recruiting", "recruiting", or looking for participants but "not yet recruiting". In total, 119 studies met our criteria of ongoing clinical trials studying novel as well as currently approved HF pharmacotherapies. The major interventions were novel medications/already approved medications for other diseases 29 % (34 trials), sodium-glucose co-transporter inhibitors 21 % (25 trials), angiotensin receptor blocker-neprilysin inhibitors 10 % (12 trials), diuretics 14 % (17 trials) and mineralocorticoid receptor antagonists 5 % (6 trials). Ongoing research will aid in reducing the impact of HF and we summarize clinical trials leading the way to better HF treatment in this review.

Sex-Based Differences in Patients With Left Ventricular-Assisted Devices and Strokes.

Background: Sex-based differences in clinical outcomes among patients with stroke related to left ventricular assist devices (LVADs) are not well described. Objectives: In this study, the authors examined differences in clinical characteristics and outcomes in men and women who had a stroke during LVAD hospitalization. Methods: The National Inpatient Sample from 2010 and 2019 was used to identify patients with stroke during LVAD hospitalization. Outcomes of interest include inpatient mortality and clinical complications among men vs women. Weighted logistic regression was used to determine the association of sex and outcomes. Adjustments were made for age and the Elixhauser comorbidity index. Results: In total, 35,820 patients underwent LVAD implantation (77% men), and 6.12% (n = 2,192) of patients experienced stroke. Women who had stroke were younger than men who had stroke (mean age in women was 51 years vs men 59 years, P < 0.001). Men with strokes had a higher burden of comorbidities than women. While there were no differences in the odds of ischemic stroke, women had higher odds of hemorrhagic stroke compared to men (OR: 1.49 [95% CI: 1.02-2.18]). Mortality in patients with LVAD who had stroke was significantly higher than in those without stroke. Between 2010 and 2019, stroke rates significantly increased among men, while the trend remained variable among women. Conclusions: In this national cohort, men had a higher comorbidity burden and had worsening stroke trends over the last decade compared to women. Women had fewer LVAD implants and a higher incidence of hemorrhagic stroke. Understanding the factors that contribute to sex-related outcome disparities among LVAD stroke patients is crucial in addressing these diverging trends.

Highlights of Cardiovascular Disease Prevention Studies Presented at the 2024 American College of Cardiology Conference.

PURPOSE OF REVIEW: To summarize selected late-breaking science on cardiovascular (CV) disease prevention presented at the 2024 Scientific Session of the American College of Cardiology (ACC) conference. RECENT FINDINGS: The LIBerate-HR trial showed the efficacy and safety of lerodalcibep, a subcutaneous injection that prevents binding of Pro-Protein Convertase Subtilisin/Kexin (PCSK) 9 to low-density lipoprotein (LDL)-receptors resulting in LDL-cholesterol (LDL-C) lowering in patients at very high risk or high risk of atherosclerotic CV disease (ASCVD). The AEGIS-II randomized patients with type 1 myocardial infarction (MI) with multivessel coronary artery disease and additional CV risk factors and found no benefit in major adverse CV events (MACE) with CSL112, an apolipoprotein A1 infusion shown to increase cholesterol efflux capacity. The Bridge-TIMI 73a trial showed a significant reduction in triglyceride (TG) levels with olezarsen, an antisense mRNA, in patients with moderate hyperTG with elevated CV risk. The BE ACTIVE trial showed significant improvement in step counts in patients given behavioral and financial incentives. The DRIVE study showed a significant increase in the prescription of either sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus (T2DM) at elevated CV or renal risk with a remote team-based, non-licensed navigator and clinical pharmacist approach. The TACTiC trial showed increased and sustained use of statin therapy by patient-driven use of a web-based portal that calculated the ASCVD risk score and gave prompts. The VICTORIAN-INITIATE trial showed efficacy and safety in early use of inclisiran in patients with ASCVD who did not reach target LDL-C < 70 mg/dL despite maximally tolerated statin therapy. The ARISE-HF trial showed no difference in change of peak oxygen consumption with the use of an oral aldose reductase inhibitor, AT-001, in patients with well-controlled T2DM and diabetic cardiomyopathy with high-risk features compared to placebo. The PREVENT trial showed a significant reduction in target vessel failure at 2 years in patients with non-flow limiting vulnerable plaques with percutaneous coronary intervention and optimal medical therapy (OMT) compared to OMT alone. The late-breaking clinical science presented at the 2024 Scientific Session of the ACC paves the way for an evidence-based alternative to statin therapy and provides data on several common clinical scenarios encountered in daily practice.

Has mortality in the United States returned to pre-pandemic levels? An analysis of provisional 2023 data.

BACKGROUND: The COVID-19 pandemic, which started in 2020, resulted in greater all-cause mortality in 2020 and in subsequent years. Whether all-cause mortality remains elevated in 2023 compared to pre-pandemic numbers is unknown. METHODS AND RESULTS: The United States (US) Center for Disease Control Wide-Ranging, Online Data for Epidemiologic Research database was used to compare mortality rates between 2019 and provisional data for 2022 and 2023. Age-adjusted mortality rates (AAMRs) for all-cause as well as top causes of mortality were collected. Mortality based on subgroups by sex, age, and ethnicity was also collected. All-cause AAMRs between 2018 and 2023 per 100,000 individuals were 723.6, 715.2, 835.4, 879.7, (provisionally) 798.8, and (provisionally) 738.3, respectively, with AAMRs in 2023 remaining above 2019 pre-pandemic levels. Similar trends were noted in subgroups based on sex, ethnicity, and most age groups. Mortality attributed directly to COVID-19 peaked in 2021 as the 3rd leading cause of death and dropped to the 10th leading cause in 2023. Provisional mortality rate trends for 2023 suggest that rates for diseases of the heart increased during the pandemic but appear to have returned to or dipped below pre-pandemic levels. CONCLUSION: Provisional 2023 all-cause mortality rates in the US have decreased from the 2021 peak associated with the COVID-19 pandemic but remain above the pre-pandemic baseline. Mortality from some conditions, including diseases of the heart, appears to have recovered from the impact of the COVID-19 pandemic.

Unraveling the enigma of long COVID: novel aspects in pathogenesis, diagnosis, and treatment protocols.

Long COVID, now unmistakably identified as a syndromic entity encompassing a complex spectrum of symptoms, demands immediate resolution of its elusive pathogenic underpinnings. The intricate interplay of diverse factors presents a complex puzzle, difficult to resolve, and thus poses a substantial challenge. As instances of long COVID manifest by repeated infections of SARS-CoV-2 and genetic predisposition, a detailed understanding in this regard is needed. This endeavor is a comprehensive exploration and analysis of the cascading pathogenetic events driven by viral persistence and replication. Beyond its morbidity, long COVID, more disabling than fatal, exacts one of the most substantial tolls on public health in contemporary times, with the potential to cripple national economies. The paper introduces a unified theory of long COVID, detailing a novel pathophysiological framework that interlinks persistent SARS-CoV-2 infection, autoimmunity, and systemic vascular pathology. We posit a model where viral reservoirs, immune dysregulation, and genetic predispositions converge to perpetuate disease. It challenges prevailing hypotheses with new evidence, suggesting innovative diagnostic and therapeutic approaches. The paper aims to shift the paradigm in long COVID research by providing an integrative perspective that encapsulates the multifaceted nature of the condition. We explain the immunological mechanisms, hypercoagulability states, and viral reservoirs in the skull that feed NeuroCOVID in patients with long COVID. Also, this study hints toward a patient approach and how to prioritize treatment sequences in long COVID patients in hospitals and clinics.

Global burden of cardiovascular disease attributable to smoking, 1990-2019: an analysis of the 2019 Global Burden of Disease Study.

AIMS: This study aims to investigate the trends in the global cardiovascular disease (CVD) burden attributable to smoking from 1990 to 2019. METHODS AND RESULTS: Global Burden of Disease Study 2019 was used to analyse the burden of CVD attributable to smoking (i.e. ischaemic heart disease, peripheral artery disease, stroke, atrial fibrillation and flutter, and aortic aneurysm). Age-standardized mortality rates (ASMRs) per 100 000 and age-standardized disability-adjusted life year rates (ASDRs) per 100 000, as well as an estimated annual percentage change (EAPC) in ASMR and ASDR, were determined by age, sex, year, socio-demographic index (SDI), regions, and countries or territories. The global ASMR of smoking-attributed CVD decreased from 57.16/100 000 [95% uncertainty interval (UI) 54.46-59.97] in 1990 to 33.03/100 000 (95% UI 30.43-35.51) in 2019 [EAPC -0.42 (95% UI -0.47 to -0.38)]. Similarly, the ASDR of smoking-attributed CVD decreased between 1990 and 2019. All CVD subcategories showed a decline in death burden between 1990 and 2019. The burden of smoking-attributed CVD was higher in men than in women. Significant geographic and regional variations existed such that Eastern Europe had the highest ASMR and Andean Latin America had the lowest ASMR in 2019. In 2019, the ASMR of smoking-attributed CVD was lowest in high SDI regions. CONCLUSION: Smoking-attributed CVD morbidity and mortality are declining globally, but significant variation persists, indicating a need for targeted interventions to reduce smoking-related CVD burden.

The burden of cardiovascular disease (CVD) attributed to smoking declined worldwide between 1990 and 2019. The burden of smoking-attributed CVD was higher in men than in women in 2019. There were significant variations between different countries and regions such that Eastern Europe had the highest death rate and Andean Latin America had the lowest death rate in 2019. Also, countries with high socio-economic status had lower death rates from smoking-attributed CVD. This highlights the need for targeted interventions to reduce the burden of smoking-attributed CVD. The overall age-adjusted deaths from CVD attributed to smoking declined from 57.16/100 000 in 1990 to 33.03/100 000 in 2019.In 2019, ischaemic heart disease was the leading cause of smoking-attributed CVD deaths.

Brief report: Effect of cardiac multi-morbidity on COVID hospitalization outcomes.

BACKGROUND: The COVID-19 pandemic has stretched healthcare resources thin and led to significant morbidity and mortality. There have been no studies utilizing national data to investigate the role of cardiac risk factors on outcomes of COVID hospitalizations. The aim of this study was to examine the effect of cardiac multimorbidity on healthcare utilization and outcomes among COVID hospitalizations during the first year of the pandemic. METHODS: Using the national inpatient sample (NIS), we identified all adult hospital admissions with a primary diagnosis of COVID in 2020, using International Classification of Diseases, Tenth Revision, Clinical Modification codes (ICD010-CM). Coronary artery disease, diabetes mellitus, heart failure, peripheral vascular disease, previous stroke, and atrial fibrillation were then identified as cardiac comorbidities using ICD-10-CM codes. Multivariable logistic regression was used to evaluate the effect of cardiac multimorbidity on mortality and mechanical ventilation. RESULTS: We identified 1,005,040 primary COVID admissions in 2020. Of these admissions, 216,545 (20.6%) had CAD, 413,195 (39.4%) had DM, 176,780 (16.8%) had HF, 159,700 (15.2%) had AF, 30735 (2.9%) had PVD, and 25,155 (2.4%) had a previous stroke. When stratified by number of comorbidities, 428390 (40.8%) had 0 comorbidities, 354960 (33.8%) had 1, 161225 (15.4%) had 2, and 105465 (10.0%) had 3+ comorbidities. COVID hospitalizations with higher cardiac multimorbidity had higher mortality rates (p<0.001) higher MV rates (p<0.001). In our multivariable regression, these associations remained with increasing odds for mortality with each stepwise increase in cardiac multimorbidity (1: OR 1.48 (1.45-1.50); 2: OR 2.13 (2.09-2.17); 3+: OR 2.43 (2.38-2.48), p<0.001, all). CONCLUSIONS: Our study is the first national examination of the impact of cardiac comorbidities on COVID outcomes. A higher number of cardiac comorbidities was associated with significantly higher rates of MV and in-hospital mortality, independent of age. Future, more granular, and longitudinal studies are needed to further examine these associations.

Highlights of Cardiovascular Disease Prevention Studies Presented at the 2023 American Heart Association Scientific Sessions.

PURPOSE OF REVIEW: Focused review highlighting ten select studies presented at the 2023 American Heart Association (AHA) Scientific Sessions. RECENT FINDINGS: Included studies assessed semaglutide and cardiovascular outcomes in overweight or obese patients without diabetes (SELECT); dapagliflozin in patients with acute myocardial infarction without diabetes (DAPA-MI); effects of dietary sodium on systolic blood pressure in middle-aged individuals (CARDIA-SSBP); long-term blood pressure control after hypertensive pregnancy with physician guided self-management (POP-HT); effect and safety of zilebesiran, an RNA interference therapy, for sustained blood pressure reduction (KARDIA-1); recaticimab add-on therapy in patients with non-familial hypercholesterolemia and mixed hyperlipidemia (REMAIN-2); efficacy and safety of lepodisiran an extended duration short-interfering RNA targeting lipoprotein(a); safety and pharmacodynamic effects of an investigational DNA base editing medicine that inactivates the PCSK9 gene and lowers LDL cholesterol (VERVE-101); automated referral to centralized pharmacy services for evidence-based statin initiation in high-risk patients; and effects of intensive blood pressure lowering in reducing risk of cardiovascular events (ESPRIT). Research presented at the 2023 AHA Scientific Sessions emphasized innovative strategies in cardiovascular disease prevention and management.

Sex differences in heart transplantation - analysis of the national inpatient sample 2012-2019.

INTRODUCTION: Advanced heart failure therapies and heart transplantation (HT) have been underutilized in women. Therefore, we aimed to explore the clinical characteristics and outcomes of HT by sex. METHODS: We conducted a retrospective analysis of adult discharges from the National Inpatient Sample (NIS) between 2012 and 2019. International Classification of Disease (ICD) procedure codes were used to identify those who underwent HT. RESULTS: A total of 20,180 HT hospitalizations were identified from 2012-2019. Among them, 28 % were female. Women undergoing HT were younger (mean age 51 vs. 54.5 years, p<0.001). HT hospitalizations among men were more likely to have atrial fibrillation, diabetes, hypertension, renal failure, dyslipidemia, smoking, and ischemic heart disease. HT hospitalizations among women were more likely to have hypothyroidism and valvular heart disease. HT hospitalizations in women were associated with no significant difference in risk of in-hospital mortality (adjusted odds ratio [OR] 0.82; 95 % confidence interval [CI] 0.58-1.16, p=0.271), no significant difference in length of stay or inflation-adjusted cost. Men were more likely to develop acute kidney injury during HT hospitalization (69.2 % vs. 59.7 %, adjusted OR 0.71, 95 % CI 0.61-0.83, p<0.001). CONCLUSIONS: HT utilization is lower in women. However, most major in-hospital outcomes for HT are similar between the sexes. Further studies are need to explore the causes of lower rates of HT in women.

Disparities in heart failure between White, Black, and Hispanic young adults: insights from the National Health and Nutrition Examination Survey.

BACKGROUND: The prevalence of heart failure (HF) is increasing among young adults in the United States with pervasive racial and ethnic differences in this population. OBJECTIVE: To evaluate contemporary associations between race and ethnicity, clinical comorbidities, and outcomes among young to middle-aged adults with HF. METHODS: A retrospective analysis was performed using the National Health and Nutrition Examination Survey. All participants with a self-report of HF aged 20-64 years from 2005 to 2018 were included and stratified by race and ethnicity [non-Hispanic (NH) Whites, NH Blacks, and Hispanics]. Data on baseline characteristics including age, sex, marital status, citizenship, education level, body mass index, insurance, waist circumference, cigarette smoking, marijuana use, and relevant clinical comorbidities were included. Weighted logistic regression was performed to estimate adjusted odds ratios (aOR) to determine the association of race and ethnicity with HF. Cox proportional-hazards models were used to assess the association of race and ethnicity with all-cause and cardiac mortality. RESULTS: A total of 1,940,447 young to middle-aged adults had self-reported HF between 2005 and 2018, of whom 61% were NH White, 40% were NH Black, and 22% were Hispanic. When compared with NH White adults, NH Black adults had higher odds of HF adjusted for age, sex, insurance status, marital status, education level, citizenship status, and clinical comorbidities (adjusted aOR 2.63, 95% CI: 1.71-4.05, p < 0.001). There was no significant difference in the odds of HF between Hispanic and NH White adults (aOR 1.18, 95% CI: 0.64-2.18, p = 0.585). NH Black adults had higher mean systolic and diastolic blood pressure, and a comparable or lower burden of cardiovascular and non-cardiovascular clinical comorbidities compared with NH White and Hispanic adults. No statistical significance was noted by race and ethnicity for all-cause and cardiac mortality during a follow-up of 5 years. CONCLUSION: NH Black young to middle-aged adults were more likely to have HF which may be related to higher blood pressure given the largely similar burden of clinically relevant comorbidities compared with other racial and ethnic groups.

Racial and ethnic disparities in cardiovascular disease - analysis across major US national databases.

BACKGROUND: There are several studies that have analyzed disparities in cardiovascular disease (CVD) health using a variety of different administrative databases; however, a unified analysis of major databases does not exist. In this analysis of multiple publicly available datasets, we sought to examine racial and ethnic disparities in different aspects of CVD, CVD-related risk factors, CVD-related morbidity and mortality, and CVD trainee representation in the US. METHODS: We used National Health and Nutrition Examination Survey, National Ambulatory Medical Care Survey, National Inpatient Sample, Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research, United Network for Organ Sharing, and American Commission for Graduate Medical Education data to evaluate CVD-related disparities among Non-Hispanic (NH) White, NH Black and Hispanic populations. RESULTS: The prevalence of most CVDs and associated risk factors was higher in NH Black adults compared to NH White adults, except for dyslipidemia and ischemic heart disease (IHD). Statins were underutilized in IHD in NH Black and Hispanic patients. Hospitalizations for HF and stroke were higher among Black patients compared to White patients. All-cause, CVD, heart failure, acute myocardial infarction, IHD, diabetes mellitus, hypertension and cerebrovascular disease related mortality was highest in NH Black or African American individuals. The number of NH Black and Hispanic trainees in adult general CVD fellowship programs was disproportionately lower than NH White trainees. CONCLUSION: Racial disparities are pervasive across the spectrum of CVDs with NH Black adults at a significant disadvantage compared to NH White adults for most CVDs.

Association between neighborhood household income and inpatient atrial fibrillation outcomes.

BACKGROUND: The impact of socioeconomic status on the clinical outcomes of patients admitted to the hospital for atrial fibrillation (AF) is not well described. OBJECTIVE: The purpose of this study was to determine the association between median neighborhood household income (mNHI) and clinical outcomes among patients admitted to the hospital for AF. METHODS: We retrospectively analyzed primary AF hospitalizations from the United States National Inpatient Sample between 2016 and 2020. The analyzed sample was divided into quartiles based on the mNHI in the zip code of the patient's residence. The lowest quartile was used as the reference category. Study outcomes included inpatient procedure utilization (ablation, cardioversion, percutaneous left atrial appendage closure), length of stay, cost, mortality, and disposition. Weighted multivariable logistic and linear regression, adjusting for multiple patient and hospital-level characteristics, was performed. RESULTS: Patients in the highest mNHI quartile had lower comorbidity burden, lower in-hospital mortality (odds ratio [OR] 0.78; 95% confidence interval [CI] 0.7-0.87; P <.001), lower discharges to care facility (OR 0.86; 95% CI 0.83-0.9; P <.001), shorter length of stay (adjusted mean difference -0.26; 95% CI -0.30 to -0.22; P <.001), higher procedure utilization, and higher health care costs ($12,124 vs $10,018) compared to the lowest mNHI quartile patients. CONCLUSION: We identified significantly higher in-hospital mortality and lower procedural/resource utilization in patients living in lower-income neighborhoods compared to higher-income neighborhoods. Further research is needed to better understand the drivers of these disparities and the strategies to improve health care disparities between socioeconomic groups.

Temporal Trends in Substance Use and Cardiovascular Disease-Related Mortality in the United States.

BACKGROUND: There are limited data on substance use (SU) and cardiovascular disease (CVD)-related mortality trends in the United States. We aimed to evaluate SU+CVD-related deaths in the United States using the Centers for Disease Control and Prevention Wide-Ranging, Online Data for Epidemiologic Research database. METHODS AND RESULTS: The Multiple Cause-of-Death Public Use record death certificates were used to identify deaths related to both SU and CVD. Crude, age-adjusted mortality rates, annual percent change, and average annual percent changes with a 95% CI were analyzed. Between 1999 and 2019, there were 636 572 SU+CVD-related deaths (75.6% men, 70.6% non-Hispanic White individuals, 65% related to alcohol). Age-adjusted mortality rates per 100 000 population were pronounced in men (22.5 [95% CI, 22.6-22.6]), American Indian or Alaska Native individuals (37.7 [95% CI, 37.0-38.4]), nonmetropolitan/rural areas (15.2 [95% CI, 15.1-15.3]), and alcohol-related death (9.09 [95% CI, 9.07 to 9.12]). The overall SU+CVD-related age-adjusted mortality rates increased from 9.9 (95% CI, 9.8-10.1) in 1999 to 21.4 (95% CI, 21.2-21.6) in 2019 with an average annual percent change of 4.0 (95% CI, 3.7-4.3). Increases in SU+CVD-related average annual percent change were noted across all subgroups and were pronounced among women (4.8% [95% CI, 4.5-5.1]), American Indian or Alaska Native individuals, younger individuals, nonmetropolitan areas, and cannabis and psychostimulant users. CONCLUSIONS: There was a prominent increase in SU+CVD-related mortality in the United States between 1999 and 2019. Women, non-Hispanic American Indian or Alaska Native individuals, younger individuals, nonmetropolitan area residents, and users of cannabis and psychostimulants had pronounced increases in SU+CVD mortality.