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.

Population genomic analyses reveal high diversity, recombination and nosocomial transmission among Candida glabrata (Nakaseomyces glabrata) isolates causing invasive infections.

Candida glabrata is a commensal yeast of the gastrointestinal tract and skin of humans. However, it causes opportunistic infections in immunocompromised patients, and is the second most common Candida pathogen causing bloodstream infections. Although there are many studies on the epidemiology of C. glabrata infections, the fine- and large-scale geographical nature of C. glabrata remain incompletely understood. Here we investigated both the fine- and large-scale population structure of C. glabrata through genome sequencing of 80 clinical isolates obtained from six tertiary hospitals in Qatar and by comparing with global collections. Our fine-scale analyses revealed high genetic diversity within the Qatari population of C. glabrata and identified signatures of recombination, inbreeding and clonal expansion within and between hospitals, including evidence for nosocomial transmission among coronavirus disease 2019 (COVID-19) patients. In addition to signatures of recombination at the population level, both MATa and MATα alleles were detected in most hospitals, indicating the potential for sexual reproduction in clinical environments. Comparisons with global samples showed that the Qatari C. glabrata population was very similar to those from other parts of the world, consistent with the significant role of recent anthropogenic activities in shaping its population structure. Genome-wide association studies identified both known and novel genomic variants associated with reduced susceptibilities to fluconazole, 5-flucytosine and echinocandins. Together, our genomic analyses revealed the diversity, transmission patterns and antifungal drug resistance mechanisms of C. glabrata in Qatar as well as the relationships between Qatari isolates and those from other parts of the world.

Device Interventions for Heart Failure.

Despite remarkable advances in drug therapy for heart failure (HF), the residual HF-related morbidity, mortality, and hospitalizations remain substantial across all HF phenotypes, and significant proportions of patients with HF remain symptomatic despite optimal drug therapy. Driven by these unmet clinical needs, the exponential growth of transcatheter interventions, and a recent shift in the regulatory landscape of device-based therapies, novel device-based interventions have emerged as a potential therapy for various phenotypes of HF. Device-based interventions can overcome some of the limitations of drug therapy (eg, intolerance, nonadherence, inconsistent delivery, and recurrent and long-term cost) and can target some HF-related pathophysiologic pathways more effectively than drug therapy. This paper reviews the current evolving landscape of device-based interventions in HF and highlights critical points related to implementation of these therapies in the current workflow of HF management.

Sodium-glucose cotransporter-2 inhibitors in heart failure: Potential decongestive mechanisms and current clinical studies.

Congestion is a key pathophysiological feature of heart failure (HF) syndrome that drives most of the clinical manifestations of acute HF and is related with poor quality of life and outcomes. Therefore, safe and effective decongestion is an important therapeutic target in the management of acute HF and despite the use of guideline-recommended loop diuretics, adequate decongestion is not always achieved in patients with acute HF. Recently, sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been shown to provide clinical benefits across a broad spectrum of patients with HF, including consistent reduction in the risk of acute HF episodes. While the exact mechanisms underlying these benefits remain a matter of debate, a growing body of evidence suggests that effective decongestion may be partly responsible, especially in the setting of acute HF. In this review, we discuss the potential decongestive mechanisms of SGLT-2 inhibitors, such as osmotic diuresis, natriuresis, preservation of glomerular filtration and facilitation of interstitial drainage, which can collectively translate into effective and safe decongestion. Furthermore, we provide a comprehensive review of up-to-date clinical data of SGLT-2 inhibitor use in the acute HF population.

Molecular characterization of Candida auris outbreak isolates in Qatar from patients with COVID-19 reveals the emergence of isolates resistant to three classes of antifungal drugs.

OBJECTIVES: During the COVID-19 pandemic in Qatar, many patients who were severely ill were colonized and infected by Candida auris, an invasive multidrug-resistant yeast pathogen that spreads through nosocomial transmission within healthcare facilities. Here, we investigated the molecular epidemiology of these C. auris isolates and the mechanisms associated with antifungal drug resistance. METHODS: Whole genomes of 76 clinical C. auris isolates, including 65 from patients with COVID-19 collected from March 2020 to June 2021, from nine major hospitals were sequenced on Illumina NextSeq. Single nucleotide polymorphisms were used to determine their epidemiological patterns and mechanisms for antifungal resistance. The data were compared with those published prior to the COVID-19 pandemic from 2018 to 2020 in Qatar. RESULTS: Genomic analysis revealed low genetic variability among the isolates from patients with and without COVID-19, confirming a clonal outbreak and ongoing dissemination of C. auris among various healthcare facilities. Based on antifungal susceptibility profiles, more than 70% (22/28) of isolates were resistant to both fluconazole and amphotericin B. Variant analysis revealed the presence of multi-antifungal resistant isolates with prominent amino acid substitutions: Y132F in ERG11 and V704L in CDR1 linked to reduced azole susceptibility and the emergence of echinocandin resistance samples bearing mutations in FKS1 in comparison with pre-COVID-19 pandemic samples. One sample (CAS109) was resistant to three classes of antifungal drugs with a unique premature stop codon in ERG3 and novel mutations in CDR2, which may be associated with elevated amphotericin B and azole resistance. DISCUSSION: Candida auris isolates from patients with COVID-19 and from most patient samples without COVID-19 in Qatar were highly clonal. The data demonstrated the emergence of multidrug-resistant strains that carry novel mutations linked to enhanced resistance to azoles, echinocandins, and amphotericin B. Understanding the epidemiology and drug resistance will inform the infection control strategy and drug therapy.

Intravenous iron infusion in patients with heart failure: a systematic review and study-level meta-analysis.

AIMS: There is considerable variability in the effect of intravenous iron on hard cardiovascular (CV)-related outcomes in patients with heart failure (HF) in randomized controlled trials (RCTs). We use a meta-analytic approach to analyse data from existing RCTs to derive a more robust estimate of the effect size of intravenous iron infusion on CV-related outcomes in patients with HF. METHOD AND RESULTS: PubMed/Medline was searched using the following terms: ('intravenous' and 'iron' and 'heart failure') from inception till 6 November 2022 for RCTs comparing intravenous iron infusion with placebo or standard of care in patients with HF and iron deficiency. Outcomes were the composite of CV mortality and first hospitalization for HF; all-cause mortality; CV mortality; first hospitalization for HF; and total hospitalizations for HF. Random effects risk ratio (RR) with 95% confidence intervals (CIs) were calculated. Ten RCTs with a total of 3438 patients were included. Intravenous iron resulted in a significant reduction in the composite of CV mortality and first hospitalization for HF [RR 0.0.85; 95% CI (0.77, 0.95)], first hospitalization for HF [RR 0.82; 95% CI (0.67, 0.99)], and total hospitalizations for HF [RR 0.74; 95% CI (0.60, 0.91)] but no statistically significant difference in all-cause mortality [RR 0.95; 95% CI. (0.83, 1.09)] or CV mortality [OR 0.89; 95% CI (0.75, 1.05)]. CONCLUSIONS: Intravenous iron infusion in patients with HF reduces the composite risk of first hospitalization for HF and CV mortality as well as the risks of first and recurrent hospitalizations for HF, with no effect on all-cause mortality or CV mortality alone.

Role of the Renal Lymphatic System in Heart Failure.

PURPOSE OF REVIEW: The lymphatic system plays a major but overlooked role in maintaining fluid homeostasis. Given the unique fluid homeostasis functions of the kidneys, dysregulation of the renal lymphatic system underlies the development of self-propagating congestive pathomechanisms. In this review, we outline the roles of the renal lymphatic system in heart failure (HF). RECENT FINDINGS: Studies have uncovered several pathomechanisms involving the renal lymphatic system in congestive states, such as impaired interstitial draining by the renal lymphatic system, impaired structure and valves of renal lymphatics, lymphatic-induced increase in renal reabsorption of water and sodium, and development of albuminuria with proteinuria-induced renal lymphangiogenesis. These self-propagating mechanisms result in "renal tamponade" with manifestations of cardiorenal syndrome and inappropriate renal response to diuretics. Dysregulation of the renal lymphatic system is integral to the development and progression of congestion in HF. Targeting renal lymphatics may provide a novel pathway to treat intractable congestion.

Gender Differences and Outcomes of Hypoattenuated Leaflet Thickening (HALT) Following Transcatheter Aortic Valve Replacement: A Meta-analysis of Randomized and Cohort Studies.

Subclinical leaflet thrombosis is characterized by hypoattenuated leaflet thickening (HALT) after transcatheter aortic valve replacement (TAVR) on computed tomography. However, given the low incidence of HALT after TAVR, the clinical significance of HALT is still being investigated. We sought to generate a more reliable estimate of the risk factors and adverse outcomes associated with HALT after TAVR by pooling data from randomized trials and cohort studies. PubMed/Medline database was systematically searched from inception until November 24, 2021, using the following terms: ("hypoattenuated leaflet thickening" and "transcatheter aortic valve replacement") and ("Subclinical leaflet thrombosis" and "transcatheter aortic valve replacement"). A random effects model meta-analysis was conducted using Mantel-Haenszel odds ratios (ORs) and the associated 95% confidence intervals (CIs), mean difference and the associated 95%. Ten studies with a total of 1462 patients were included, with follow-up ranging between 4 months and 3 years. HALT occurred in 14.4% of the patients undergoing TAVR. HALT was not associated with increased risk of stroke/TIA (OR 1.38; 95% CI [0.61-3.11]; I2=0%) or increased risk of all-cause mortality (OR 0.67; 95% CI [0.25-1.80]; I2=0). HALT was associated with a greater post-procedural mean aortic valve gradient (mean difference 2.31 mmHg; 95% CI [0.27, 4.35]; I2=71%). Interestingly, there was a trend of higher risk of HALT in men (OR 1.37; 95% CI [0.82-2.30]; I2=44%) while there was a trend towards lower risk of HALT in the presence of CKD (OR 0.76; 95% CI [0.49-1.19]; I2=0%); these trends did not reach statistical significance. This meta-analysis shows that the occurrence of HALT following TAVR is associated with a greater post-procedural mean aortic valve gradient but no excess risk of death or cerebrovascular events. The clinical significance of this higher post-procedural mean aortic valve gradient is uncertain and requires further investigations.

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.

Influence of Iron Deficiency on Clinical and Haemodynamic Parameters in Pulmonary Arterial Hypertension Cohorts.

BACKGROUND: Iron deficiency (Fedef) has been shown to be common in patients with group 1 or pulmonary arterial hypertension (PAH). Several studies have shown a negative impact of Fedef on clinical and haemodynamic parameters of the disease, but data from individual studies have not been strong enough to lead to incorporation of the finding of Fedef into prognostic or therapeutic algorithms. The goal of this meta-analysis was to combine data from available studies to better define any associations between Fedef and established variables of prognostic importance in PAH. METHODS: A literature search identified nine studies with extractable data relevant to the study questions. The impact of Fedef upon the following parameters was evaluated: 6-minute walk distance (6MWD), WHO-functional class, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, echocardiography, and findings from right heart catheterisation (RHC). Pooled results were reported as mean difference or risk difference with 95% confidence intervals utilising a random effects modeling approach. RESULTS: Fedef in the PAH population was common (47% of cases) and was associated with cardiovascular dysfunction (lower tricuspid annular plane systolic excursion [TAPSE], elevated NT-proBNP, and lower mixed venous oxygen saturation) and with reduction in functional capacity (lower 6MWD and higher functional class). CONCLUSION: This meta-analysis strengthens the relationships between Fedef and several markers of poor outcome in PAH. Fedef in patients with PAH warrants further scrutiny and merits consideration as a cause of clinical deterioration. Even though causation and longitudinal relationships between Fedef and PAH could not be identified, effect of Fedef on factors that affect disease prognosis is noteworthy and worthy of more focussed studies.

Diaphragmatic Function in Cardiovascular Disease: JACC Review Topic of the Week.

In addition to the diaphragm's role as the primary respiratory muscle, it also plays an under-recognized role in cardiac function. It serves as a pump facilitating venous and lymph return, modulating left ventricular afterload hemodynamics and pericardial pressures, as well as regulating autonomic tone. Heart failure (HF) is associated with diaphragmatic changes (ie, muscle fiber atrophy and weakness, increased ratio of type I to type II muscle fibers, and altered muscle metaboreflex) that lead to diaphragmatic dysfunction with subsequent symptomatic manifestations of HF. Herein, it is proposed that targeting the diaphragm in patients with HF via inspiratory muscle training or device-based stimulation can provide a novel treatment pathway for HF. Reviewed are several potential mechanisms through which therapies targeting the diaphragm can be beneficial in HF (ie, improving preload reserve, atrial and ventricular synchrony, and metaboreflex activity; reducing pericardial restraint; and restoring diaphragm strength).

Sodium-glucose Cotransporter 2 Inhibitors and Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a systemic disorder with cardiovascular manifestations; due to its complex and multifactorial pathophysiological mechanisms, no effective pharmacologic treatment has been identified to date. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated potentially favorable effects on NAFLD incidence and progression in preclinical and clinical studies. This review summarizes the evidence from preclinical and human studies supporting the use of SGLT2 inhibitors in NAFLD and proposes several mechanisms that may drive these favorable effects (ie, increasing insulin sensitivity, decreasing intrahepatic fat accumulation and lipotoxicity, decreasing oxidative stress and endoplasmic reticulum (ER) stress, improving autophagy, and inhibiting apoptosis).

Device Therapy for Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with few options for effective pharmacologic therapies. Numerous device-based approaches to HFpEF therapy have emerged, which aim to treat the clinical and pathophysiologic features common to the varied causes of this syndrome. This review summarizes the current landscape of device therapy in HFpEF with a focus on structural interventions, such as left-to-right atrial shunts; cardiac contractility modulation; autonomic modulation, such as baroreflex activation therapy and splanchnic nerve modulation; and respiratory modulation, such as phrenic nerve stimulation.

Post-recovery COVID-19 and incident heart failure in the National COVID Cohort Collaborative (N3C) study.

Cardiac involvement has been noted in COVID-19 infection. However, the relationship between post-recovery COVID-19 and development of de novo heart failure has not been investigated in a large, nationally representative population. We examined post-recovery outcomes of 587,330 patients hospitalized in the United States (257,075 with COVID-19 and 330,255 without), using data from the National COVID Cohort Collaborative study. Patients hospitalized with COVID-19 were older (51 vs. 46 years), more often male (49% vs. 42%), and less often White (61% vs. 69%). Over a median follow up of 367 days, 10,979 incident heart failure events occurred. After adjustments, COVID-19 hospitalization was associated with a 45% higher hazard of incident heart failure (hazard ratio = 1.45; 95% confidence interval: 1.39-1.51), with more pronounced associations among patients who were younger (P-interaction = 0.003), White (P-interaction = 0.005), or who had established cardiovascular disease (P-interaction = 0.005). In conclusion, COVID-19 hospitalization is associated with increased risk of incident heart failure.

Catheter-Based Management of Heart Failure: Pathophysiology and Contemporary Data.

Device therapy for severe heart failure (HF) has shown efficacy both in acute and chronic settings. Recent percutaneous device innovations have pioneered a field known as interventional HF, providing clinicians with a variety of options for acute decompensated HF that are centered on nonsurgical mechanical circulatory support. Other structural-based therapies are aimed at the pathophysiology of chronic HF and target the underlying etiologies such as functional mitral regurgitation, ischemic cardiomyopathy, and increased neurohumoral activity. Remote hemodynamic monitoring devices have also been shown to be efficacious for the ambulatory management of HF. We review the current data on devices and investigational therapies for HF management whereby pharmacotherapy falls short.

Trends and Characteristics of Hospitalizations in Patients With Heart Transplant.

There is limited data regarding the leading causes of hospitalization among heart transplant (HT) recipients and the characteristics of these hospitalizations. We conducted a retrospective analysis of the National Inpatient Sample weighted data between January 1, 2004, and December 31, 2018, which included hospitalized adults ≥18 years with a history of HT. Primary outcomes were the 10 most common primary causes of hospitalizations, clinical characteristics, inpatient mortality, length of stay, and inflation-adjusted care costs. We divided the study population in two period (2004-2014 and 2016-2018) to report the most common causes of hospitalizations. We identified a total of 209,771 weighted hospitalizations with a history of HT between January 1, 2004, and December 31, 2018. Between 2004 and 2014, pneumonia (6.21%), acute or unspecified renal failure (4.94%), complication of device, implant or graft (4.66%), sepsis (4.56%), and congestive heart failure (2.94%) were the most common causes of hospitalizations for HT recipient. Between 2016 and 2018, sepsis (9.03%), acute or unspecific renal failure (6.27%), complication of device, implant or graft (5.16%), pneumonia (4.92%), and complications of surgical procedure or medical device (3.86%) were the most common causes of hospitalizations for HT recipient. Sepsis had the highest inpatient mortality accounting for 11.32% of inpatient mortality in the 2004-2014 period and 6% in the 2016-2018 period. In summary, infections, acute renal failure, and other transplant complications are the leading causes of hospitalization among HT recipients. Sepsis carries the highest inpatient mortality.