Search

Empagliflozin reduces the risk of heart failure (HF) hospitalizations but not all-cause mortality when started within 14 days of acute myocardial infarction (AMI). This study sought to evaluate the association of left ventricular ejection fraction (LVEF), congestion, or both, with outcomes and the impact of empagliflozin in reducing HF risk post-AMI. In the EMPACT-MI (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction) trial, patients were randomized within 14 days of an AMI complicated by either newly reduced LVEF<45%, congestion, or both, to empagliflozin (10 mg daily) or placebo and were followed up for a median of 17.9 months. Among 6,522 patients, the mean baseline LVEF was 41 ± 9%; 2,648 patients (40.6%) presented with LVEF <45% alone, 1,483 (22.7%) presented with congestion alone, and 2,181 (33.4%) presented with both. Among patients in the placebo arm of the trial, multivariable adjusted risk for each 10-point reduction in LVEF included all-cause death or HF hospitalization (HR: 1.49; 95% CI: 1.31-1.69; P < 0.0001), first HF hospitalization (HR: 1.64; 95% CI: 1.37-1.96; P < 0.0001), and total HF hospitalizations (rate ratio [RR]: 1.89; 95% CI: 1.51-2.36; P < 0.0001). The presence of congestion was also associated with a significantly higher risk for each of these outcomes (HR: 1.52, 1.94, and RR: 2.03, respectively). Empagliflozin reduced the risk for first (HR: 0.77; 95% CI: 0.60-0.98) and total (RR: 0.67; 95% CI: 0.50-0.89) HF hospitalizations, irrespective of LVEF or congestion, or both. The safety profile of empagliflozin was consistent across baseline LVEF and irrespective of congestion status. In patients with AMI, the severity of left ventricular dysfunction and the presence of congestion was associated with worse outcomes. Empagliflozin reduced first and total HF hospitalizations across the range of LVEF with and without congestion. (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction [EMPACT-MI]; NCT04509674) [Display omitted] [ABSTRACT FROM AUTHOR]

Aims Methods Conclusion Heart failure (HF), a global pandemic affecting millions of individuals, calls for adequate predictive guidance for improved therapy. Congestion, a key factor in HF‐related hospitalizations, further underscores the need for timely interventions. Proactive monitoring of intracardiac pressures, guided by pulmonary artery (PA) pressure, offers opportunities for efficient early‐stage intervention, since haemodynamic congestion precedes clinical symptoms.The BioMEMS study, a substudy of the MONITOR‐HF trial, proposes a multifaceted approach integrating blood biobank data with traditional and novel HF parameters. Two additional blood samples from 340 active participants in the MONITOR‐HF trial were collected at baseline, 3‐, 6‐, and 12‐month visits and stored for the BioMEMS biobank. The main aims are to identify the relationship between temporal biomarker patterns and PA pressures derived from the CardioMEMS‐HF system, and to identify the biomarker profile(s) associated with the risk of HF events and cardiovascular death.Since the prognostic value of single baseline measurements of biomarkers like N‐terminal pro‐B‐type natriuretic peptide is limited, with the BioMEMS study we advocate a dynamic, serial approach to better capture HF progression. We will substantiate this by relating repeated biomarker measurements to PA pressures. This design rationale presents a comprehensive review on cardiac biomarkers in HF, and aims to contribute valuable insights into personalized HF therapy and patient risk assessment, advancing our ability to address the evolving nature of HF effectively. [ABSTRACT FROM AUTHOR]

Background Aim Methods Results Conclusions Several studies have evaluated the role of QRS duration (QRSd) or QRS narrowing as a predictor of response to cardiac resynchronization therapy (CRT) to reduce nonresponders.Our study aimed to determine the correlation between the relative change in QRS index (QI) compared to clinical outcome and prognosis in patients who underwent CRT implantation.A three‐centers study involving 398 patients with a CRT device was conducted. Clinical, echocardiographic and pharmacological variables, QRSd before and after CRT implantation and QI were measured.In a 6‐month follow‐up, a significant improvement in left ventricular ejection fraction (LVEF), left ventricular end‐diastolic and systolic volumes (LVEDV and LVESV) were observed. QI was related to reverse remodeling (multiple r‐squared: 0.48, adjusted r‐squared: 0.43, p = .001), and the cut‐off value that best predicted LV reverse remodeling after 6 months of CRT was 12.25% (AUC 0.7, p = .001). At 24 months, a statistically significant difference was found between patients with a QI ≤ 12.25% and those with a QI > 12.25% regarding NYHA class worsening (p = .04). The mean of the QI of patients who died from cardiovascular causes was lower than patients who died of other causes (p = .0179). A correlation between pre‐CRT QRSd/LVEDV and QI was observed (r = + 0.20; p = .0003). A higher QRSd/LVEDV ratio was associated with an improved LVEF, LVEDV, and LVESV (p < .0001) at follow‐up.QI narrowing after CRT was related to greater echocardiographic reverse remodeling and a lower rate of adverse events (death or cardiovascular hospitalizations). The QI can improve the prediction of adverse events in a population with CRT regardless of comorbidities according to the Charlson Comorbidity Index. QI could be used to predict CRT response. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Hospital readmissions following left ventricular assist device (LVAD) remain a frequent comorbidity, associated with decreased quality of life and increased resources utilization. This study sought to determine causes, predictors, and impact on survival of hospitalizations during HeartMate 3 (HM3) support.All patients implanted with HM3 between November 2014 to December 2019 at Columbia University Irving Medical Center were consecutively enrolled in the study. Demographics and clinical characteristics from the index admission and the first outpatient visit were collected and used to estimate 1‐year and 900‐day readmission‐free survival and overall survival. Multivariable analysis was performed for subsequent readmissions.Of 182 patients who received a HM3 LVAD, 167 (92%) were discharged after index admission and experienced 407 unplanned readmissions over the median follow up of 727 (interquartile range (IQR): 410.5, 1124.5) days. One‐year and 900‐day mean cumulative number of all‐cause unplanned readmissions was 0.43 (95%CI, 0.36, 0.51) and 1.13 (95%CI, 0.99, 1.29). The most frequent causes of rehospitalizations included major infections (29.3%), bleeding (13.2%), device‐related (12.5%), volume overload (7.1%), and other (28%). One‐year and 900‐day survival free from all‐cause readmission was 38% (95%CI, 31–46%) and 16.6% (95%CI, 10.3–24.4%). One‐year and 900‐day freedom from 2, 3, and ≥4 readmissions were 60.7%, 74%, 74.5% and 26.2%, 33.3%, 41.3%. One‐year and 900‐day survival were unaffected by the number of readmissions and remained >90%. Male sex, ischemic etiology, diabetes, lower serum creatinine, longer duration of index hospitalization, and a history of readmission between discharge and the first outpatient visit were associated with subsequent readmissions.Unplanned hospital readmissions after HM3 are common, with infections and bleeding accounting for the majority of readmissions. Irrespective of the number of readmissions, one‐year survival remained unaffected. [ABSTRACT FROM AUTHOR]

Cardiac remodelling involves structural, cellular and molecular alterations in the heart after injury, resulting in progressive loss of heart function and ultimately leading to heart failure. Circular RNAs (circRNAs) are a recently rediscovered class of non‐coding RNAs that play regulatory roles in the pathogenesis of cardiovascular diseases, including heart failure. Thus, a more comprehensive understanding of the role of circRNAs in the processes governing cardiac remodelling may set the ground for the development of circRNA‐based diagnostic and therapeutic strategies. In this review, the current knowledge about circRNA origin, conservation, characteristics and function is summarized. Bioinformatics and wet‐lab methods used in circRNA research are discussed. The regulatory function of circRNAs in cardiac remodelling mechanisms such as cell death, cardiomyocyte hypertrophy, inflammation, fibrosis and metabolism is highlighted. Finally, key challenges and opportunities in circRNA research are discussed, and orientations for future work to address the pharmacological potential of circRNAs in heart failure are proposed. [ABSTRACT FROM AUTHOR]

Purpose Added layers of remote management in heart failure (HF) have become available for patients with an implantable cardioverter defibrillator (ICD). The aim of this study was to investigate the impact of pharmacist-managed HF monitoring in patients with a multisensor-capable ICD. Methods This was a retrospective, data-only, single-arm study that compared primary outcome events individually in the preactivation and postactivation periods at a single center. The primary outcomes were the total number of all-cause and HF-related hospitalizations and all-cause emergency department (ED) visits and the median length of stay for all-cause and HF-related hospitalizations. The secondary outcome quantified medication utilization. Results In total, 132 patients completed the 1-year follow-up period. Overall, there was a 49% reduction in the number of patients with an all-cause hospitalization, a 77% reduction in the number of patients with an HF-related hospitalization, and a 36% reduction in the number of patients with an ED visit. More patients were hospitalized, visited the ED (P < 0.005), and had a longer median length of stay for all-cause hospitalizations in the preactivation period (P < 0.05). Overall medication utilization increased in the postactivation period. Conclusion A pharmacist-led remote monitoring program, utilizing a multisensor diagnostic, was effective at significantly reducing hospitalizations, ED visits, and length of stay. [ABSTRACT FROM AUTHOR]

The Kidney Disease Improving Global Outcomes (KDIGO) classification integrates both estimated glomerular filtration rate and urine-albumin-creatinine ratio to stratify risk more comprehensively in patients with chronic kidney disease. There are limited data assessing whether this classification system is associated with prognosis and treatment response in heart failure populations. The aim of this study was to evaluate the relative treatment effects of sacubitril/valsartan across the KDIGO risk categories in patients with HFrEF. PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) was a global randomized controlled trial evaluating sacubitril/valsartan vs enalapril in patients with heart failure with reduced ejection fraction (HFrEF). Patients were classified according to low, moderate, and high/very high KDIGO risk. Treatment responses were assessed according to baseline KDIGO risk. The primary outcome was a composite of cardiovascular (CV) death or heart failure hospitalization. A renal composite outcome was defined as sustained decline in estimated glomerular filtration rate by ≥40% or end-stage kidney disease. Among 1,910 (23% of total) participants with available data, 42%, 32%, and 26% were classified as low, moderate, and high/very high KDIGO risk, respectively. Patients in the highest KDIGO risk categories experienced the highest rates of the primary composite outcome (7.6 per 100 person-years [95% CI: 6.5-9.0 per 100 person-years], 9.4 per 100 person-years [95% CI: 7.9-11.2 per 100 person-years], and 14.9 per 100 person-years [95% CI: 12.7-17.6 per 100 person-years]; P < 0.001). Sacubitril/valsartan had a similar safety profile and demonstrated consistent effects on the risk of both the primary outcome (P Interaction = 0.31) and the renal composite outcome (P Interaction = 0.50) across the spectrum of KDIGO risk. One in 4 patients with HFrEF were classified as at least high KDIGO kidney risk; these individuals faced concordantly the highest risks of CV events. Sacubitril/valsartan exhibited consistent CV and kidney protective benefits as well as safety across the spectrum of baseline kidney risk. These data further support initiation of sacubitril/valsartan in HFrEF across a broad range of kidney risk. (This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure [PARADIGM-HF]; NCT01035255) [Display omitted] [ABSTRACT FROM AUTHOR]

Arrhythmias frequently accompany heart failure and left ventricular dysfunction. Tachycardias, atrial fibrillation, and premature ventricular contractions can induce a reversible form of dilated cardiomyopathy (CM) known as arrhythmia-induced CM (AiCM). The intriguing question is why certain individuals are more susceptible to AiCM, despite similar arrhythmia burdens. The primary challenge is determining the extent of arrhythmias' contribution to left ventricular systolic dysfunction. AiCM should be considered in patients with a mean heart rate of >100 beats/min, atrial fibrillation, or a PVC burden of >10%. Confirmation of AiCM occurs when CM reverses upon eliminating the responsible arrhythmia. Therapy choice depends on the specific arrhythmia, patient comorbidities, and preferences. After left ventricular function is restored, ongoing follow-up is essential if an abnormal myocardial substrate persists. Accurate diagnosis and treatment of AiCM have the potential to enhance patients' quality of life, improve clinical outcomes, and reduce hospital admissions and overall health care costs. [Display omitted] • Tachycardia, AF, and PVCs can result in cardiomyopathy or AiCM. • Ambulatory ECG monitoring and CMR are key to establishing the diagnosis of AiCM. • Appropriate treatment of AiCM can reverse ventricular systolic dysfunction and potentially decrease morbidity and mortality. • A better understanding of the pathophysiological mechanisms and predictors of AiCM is needed to develop preventive strategies. [ABSTRACT FROM AUTHOR]

Early cardiac rehabilitation using non-invasive ventilation (NIV) and aerobic exercise may reduce the length of hospital stay in patients with heart failure (HF), however, there is still no evidence of this effect on patients in the intensive care unit (ICU). to investigate the effects of aerobic exercise (AE) performed simultaneously with non-invasive ventilation (NIV) on the length of intensive care stay (LICUS) in patients diagnosed with decompensated heart failure (HF) admitted to the intensive care units (ICU). Twenty-eight patients admitted to the intensive care unit (ICU) because of decompensation of HF were randomised into two groups: the intervention group (AE + NIV), and a control group. The intervention group's treatment strategy involved simultaneous AE with NIV daily. The control group performed non-simultaneous AE and NIV daily during their ICU stay. The primary outcome was LICUS. The secondary outcomes were the length of hospital stay, peripheral and respiratory muscle strength, functional status, functional classification, and exercise tolerance. The mean LICUS was shorter in AE + NIV than in the control group (6.3 ± 4.7 days vs 8.3 ± 3.6 days, respectively; p = 0.015). Secondary outcomes were similar between groups, except for exercise hemodynamics, which was improved in AE + NIV, as showed by the decreased diastolic blood pressure immediately after the exercise tolerance test. The use of AE simultaneous with NIV reduced the LICUS of patients admitted to the ICU because of decompensated HF. This innovative approach is a promising tool for accelerating ICU discharge during the in-hospital rehabilitation of patients with HF. [ABSTRACT FROM AUTHOR]

The article explores ethical challenges related to deactivating left ventricular assist devices (LVADs), highlighting the need for clear communication with patients and families, the role of palliative care, and conflicts arising from differing views on the benefits and burdens of LVAD therapy.

Background: Patients with hidradenitis suppurativa (HS) often suffer from comorbid diabetes, metabolic syndrome, and hyperlipidemia and, therefore, are susceptible to the development of cardiovascular diseases (CVDs). Moreover, systemic inflammation plays a vital role in the development of atherosclerosis. The creation of atherosclerotic plaque is characterized by endothelial dysfunction driven by elevated concentrations of interleukin (IL)‐1, IL‐6, and IL‐18 among others, as well as tumor necrosis factor (TNF) alpha. Methods: This study aimed to assess the risk of HS patients developing CVDs. We performed a large‐scale, propensity‐matched global retrospective cohort study analyzing the risk of development of CVDs in patients suffering from HS. The analysis included 144,100 HS patients with 144,100 healthy controls (HC). The cohorts were matched regarding demographics and history of diseases relevant to CVDs, e.g., diabetes, obesity, and nicotine dependence. A total of 90 cardiovascular disorders were identified. The identification of cardiovascular disorders was based on ≥1% appearance of the event, based on absolute numbers, in both cohorts. Results: Before the matching, HS patients displayed a higher frequency in excess weight or obesity (25 vs. 14.4%, respectively), nicotine dependence, and diabetes mellitus, but lower odds of primary hypertension in comparison to healthy controls. A total of 47 CVDs are associated with an increased risk of onset in HS patients. Although the highest hazard ratio (HR; 2.1; 95% CI: 1.95–2.269) was found for unspecified heart failure, the HS cohort was exceptionally predisposed to developing myocardial infarction (HR: 2.06; 95% CI: 1.88–2.27) and an acute embolism and deep vein thrombosis of the lower extremity (HR: 1.93; 95% CI: 1.74–2.14). Conclusions: This is the most extensive study on the association of HS with CVDs. We demonstrated that HS patients are at significantly greater risk of developing various CVDs compared to matched controls, with heart failure being the most common one. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is characterised by breathlessness and fatigue that impacts negatively on patients' intentions to prioritise physical activity (PA). Healthcare professionals (HCPs) experience challenges when motivating patients to increase PA. It is essential to develop an understanding of how to support HCPs to deliver PA interventions. We aimed to identify active ingredients of HCP training interventions to enable delivery of PA interventions to HF patients. Nine databases were searched. Data were extracted on study characteristics, active ingredients, outcomes, and fidelity measures. Data were synthesised narratively, and a promise analysis was conducted on intervention features. Ten RCTs, which reported a training intervention for HCPs were included (N = 22 HCPs: N = 1,414 HF patients). Two studies reported the use of theory to develop HCP training. Seven behaviour change techniques (BCTs) were identified across the 10 training interventions. The most 'promising' BCTs were 'instruction on how to perform the behaviour' and 'problem solving'. Two studies reported that HCP training interventions had been formally evaluated. Fidelity domains including study design, monitoring and improving the delivery of treatment, intervention delivery, and provider training were infrequently reported. Future research should prioritise theory-informed development and robust evaluation of training interventions for HCPs to enable faithful and quality delivery of patient interventions. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is a widely used chemotherapeutic agent that can cause serious cardiotoxic side effects, leading to heart failure (HF). Impaired mitochondrial function is thought to be key factor driving progression into HF. We have previously shown in a rat model of DOX-HF that heart failure with reduced ejection fraction correlates with mitochondrial loss and dysfunction. Adenosine monophosphate-dependent kinase (AMPK) is a cellular energy sensor, regulating mitochondrial biogenesis and energy metabolism, including fatty acid oxidation. We hypothesised that AMPK activation could restore mitochondrial function and therefore be a novel cardioprotective strategy for the prevention of DOX-HF. Consequently, we set out to assess whether 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR), an activator of AMPK, could prevent cardiac functional decline in this chronic intravenous rat model of DOX-HF. In line with our hypothesis, AICAR improved cardiac systolic function. AICAR furthermore improved cardiac mitochondrial fatty acid oxidation, independent of mitochondrial number, and in the absence of observable AMPK-activation. In addition, we found that AICAR prevented loss of myocardial mass. RNAseq analysis showed that this may be driven by normalisation of pathways associated with ribosome function and protein synthesis, which are impaired in DOX-treated rat hearts. AICAR furthermore prevented dyslipidemia and excessive body-weight loss in DOX-treated rats, which may contribute to preservation of myocardial mass. Though it is unclear whether AICAR exerted its cardioprotective effect through cardiac or extra-cardiac AMPK-activation or via an AMPK-independent effect, these results show promise for the use of AICAR as a cardioprotective agent in DOX-HF to both preserve cardiac function and mass. [Display omitted] • AICAR is partially cardioprotective in DOX-induced heart failure in rats • AICAR improves dyslipidemia and cardiac mitochondrial fatty acid metabolism • AICAR also attenuates loss of cardiac mass by normalizing protein synthesis pathways [ABSTRACT FROM AUTHOR]

COVID-19 has disproportionately affected racialized populations, with particular impact among individuals of Black individuals. However, it is unclear whether disparities in venous thromboembolic (VTE) complications exist between Black individuals and those belonging to other racial groups with confirmed SARS-CoV2 infections. To summarize the prevalence and moderators associated with VTE among Black COVID-19 patients in minoritized settings, and to compare this to White and Asian COVID-19 patients according to sex, age, and comorbid health conditions (heart failure, cancer, obesity, hypertension). A systematic search of MEDLINE, Embase, CINAHL and CENTRAL for articles or reports published from inception to February 15, 2023. Reports on VTE among Black individuals infected with SARS-CoV2, in countries where Black people are considered a minority population group. Study characteristics and results of eligible studies were independently extracted by 2 pairs of reviewers. VTE prevalence was extracted, and risk of bias was assessed. Prevalence estimates of VTE prevalence among Black individuals with COVID19 in each study were pooled. Where studies provided race-stratified VTE prevalence among COVID19 patients, odds ratios were generated using a random-effects model. Prevalence of VTE, comprising of deep vein thrombosis and pulmonary embolism. Ten studies with 66,185 Black individuals reporting the prevalence of COVID-19 associated VTE were included. Weighted median age of included studies was 47.60. Pooled prevalence of COVID-19 associated VTE was 7.2 % (95 % CI, 3.8 % – 11.5 %) among Black individuals. Among individuals with SARS-CoV2 infections, Black population had higher risks of VTE compared to their White (OR = 1.79, [95 % CI 1.28–2.53], p <.001) or Asian (OR = 2.01, [95 % CI, 1.14–3.60], p =.017) counterparts, or patients with other racial identities (OR = 2.01, [95 % CI, 1.39, 2.92]; p <.001). Black individuals with COVID-19 had substantially higher risk of VTE compared to White or Asian individuals. Given racial disparities in thrombotic disease burden related to COVID-19, medical education, research, and health policy interventions are direly needed to ensure adequate disease awareness among Black individuals, to facilitate appropriate diagnosis and treatment among Black patients with suspected and confirmed VTE, and to advocate for culturally safe VTE prevention strategies, including pre-existing inequalities to the COVID-19 pandemic that persist after the crisis. • Black individuals with COVID-19 are particularly at risk of developing Venous thromboembolism (VTE). • Black individuals with COVID-19 had substantially higher risk of VTE compared to White or Asian individuals. • Male participants with COVID-19 presented a higher risk of VTE compared to women. [ABSTRACT FROM AUTHOR]

Hyperkalaemia is an electrolyte imbalance that impairs muscle function and myocardial excitability, and can potentially lead to fatal arrhythmias and sudden cardiac death. The prevalence of hyperkalaemia is estimated to be 6%–7% worldwide and 7%–10% in Asia. Hyperkalaemia frequently affects patients with chronic kidney disease, heart failure, and diabetes mellitus, particularly those receiving treatment with renin‐angiotensin‐aldosterone system (RAAS) inhibitors. Both hyperkalaemia and interruption of RAAS inhibitor therapy are associated with increased risks for cardiovascular events, hospitalisations, and death, highlighting a clinical dilemma in high‐risk patients. Conventional potassium‐binding resins are widely used for the treatment of hyperkalaemia; however, caveats such as the unpalatable taste and the risk of gastrointestinal side effects limit their chronic use. Recent evidence suggests that, with a rapid onset of action and improved gastrointestinal tolerability, novel oral potassium binders (e.g., patiromer and sodium zirconium cyclosilicate) are alternative treatment options for both acute and chronic hyperkalaemia. To optimise the care for patients with hyperkalaemia in the Asia–Pacific region, a multidisciplinary expert panel was convened to review published literature, share clinical experiences, and ultimately formulate 25 consensus statements, covering three clinical areas: (i) risk factors of hyperkalaemia and risk stratification in susceptible patients; (ii) prevention of hyperkalaemia for at‐risk individuals; and (iii) correction of hyperkalaemia for at‐risk individuals with cardiorenal disease. These statements were expected to serve as useful guidance in the management of hyperkalaemia for health care providers in the region. [ABSTRACT FROM AUTHOR]

Purpose: Vericiguat reduced clinical endpoints in patients experiencing worsening heart failure in clinical trials, but its implementation outside trials is unclear. Methods: This retrospective analysis of longitudinally collected data was based on the IQVIA™ LRx database, which includes ~ 80% of the prescriptions of the 73 million people covered by the German statutory health insurance. Results: Between September 2021 and December 2022, vericiguat was initiated in 2916 adult patients. Their mean age was 73 ± 13 years and 28% were women. While approximately 70% were uptitrated beyond 2.5 mg, only 36% reached 10 mg. Median time to up-titration from 2.5 mg to 5 mg was 17 (quartiles: 11–33) days, and from 2.5 to 10 mg 37 (25–64) days, respectively. In 87% of the patients, adherence to vericiguat was high as indicated by a medication possession ratio of ≥ 80%, and 67% of the patients persistently used vericiguat during the first year. Women and older patients reached the maximal dose of 10 mg vericiguat less often and received other substance classes of guideline-recommended therapy (GDMT) less frequently. The proportion of patients receiving four pillars of GDMT increased from 29% before vericiguat initiation to 44% afterwards. Conclusion: In a real-world setting, despite higher age than in clinical trials, adherence and persistence of vericiguat appeared satisfactory across age categories. Initiation of vericiguat was associated with intensification of concomitant GDMT. Nevertheless, barriers to vericiguat up-titration and implementation of other GDMT, applying in particular to women and elderly patients, need to be investigated further. [ABSTRACT FROM AUTHOR]

Background: The PARADIGM HF trial showed sacubitril/valsartan (SV) to be superior to enalapril in patients with reduced ejection fraction (HFrEF). Since its publication, several other randomized trials have compared SV to either an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) in HFrEF which showed conflicting results regarding mortality, hospitalizations, and quality of life scoring. Objective: To review randomized comparative trials of SV to either ACEI or ARB in patients with HFrEF. Methods: PubMed and Embase databases were used to identify randomized comparative trials. The text terms sacubitril, angiotensin neprilysin, and LCZ696 were used for both searches. Meta-analysis, retrospective, adhoc, and cohort studies were excluded. Results: 1476 and 3983 citations were reviewed on PubMed and Embase, respectively. Of these, 11 randomized comparative trials to either ACEI or ARB were included for analysis. The mortality/quality of life benefits of SV over enalapril in the PARADIGM HF were not corroborated in any of the other trials. The effect of hospitalizations for heart failure was inconsistent among trials. Exercise tolerance was not improved with SV versus enalapril. Conclusion: The results of the PARADIGM HF trial have largely not been confirmed in subsequent randomized comparative trials. [ABSTRACT FROM AUTHOR]

Echocardiography frequently serves as the first-line treatment of diagnostic imaging for several pathological entities in cardiology. Artificial intelligence (AI) has been growing substantially in information technology and various commercial industries. Machine learning (ML), a branch of AI, has been shown to expand the capabilities and potential of echocardiography. ML algorithms expand the field of echocardiography by automated assessment of the ejection fraction and left ventricular function, integrating novel approaches such as speckle tracking or tissue Doppler echocardiography or vector flow mapping, improved phenotyping, distinguishing between cardiac conditions, and incorporating information from mobile health and genomics. In this review article, we assess the impact of AI and ML in echocardiography. Plain Language Summary: Echocardiography is the most common test in cardiovascular imaging and helps diagnose multiple different diseases. Machine learning, a branch of artificial intelligence (AI), will reduce the workload for medical professionals and help improve clinical workflows. It can rapidly calculate a lot of important cardiac parameters such as the ejection fraction or important metrics during different phases of the cardiac cycle. Machine learning algorithms can include new technology in echocardiography such as speckle tracking, tissue Doppler echocardiography, vector flow mapping, and other approaches in a user-friendly manner. Furthermore, it can help find new subtypes of existing diseases in cardiology. In this review article, we look at the current role of machine learning and AI in the field of echocardiography. [ABSTRACT FROM AUTHOR]

Heart failure poses a global health challenge affecting millions of individuals, and access to guideline-directed medical therapy is often limited. This limitation is frequently attributed to factors such as drug availability, slow adoption, clinical inertia, and delayed diagnosis. Despite international recommendations promoting the use of guideline-directed medical therapy for heart failure management, personalized approaches are essential in settings with resource constraints. In India, crucial treatments like angiotensin II receptor blocker neprilysin inhibitors and sodium-glucose co-transporter 2 inhibitors are not fully utilized despite their established safety and efficacy. To address this issue, an expert consensus involving 150 specialists, including cardiologists, nephrologists, and endocrinologists, was convened. They deliberated on patient profiles, monitoring, and adverse side effects and provided tailored recommendations for guideline-directed medical therapy in heart failure management. Stressing the significance of early initiation of guideline-directed medical therapy in patients with heart failure, especially with sodium-glucose co-transporter 2 inhibitors, the consensus also explored innovative therapies like vericiguat. To improve heart failure outcomes in resource-limited settings, the experts proposed several measures, including enhanced patient education, cardiac rehabilitation, improved drug access, and reforms in healthcare policies. [ABSTRACT FROM AUTHOR]

Introduction: There are limited data on the burden of newly diagnosed patients with heart failure (HF) in Thailand. Thus, this study aimed to fully understand the hospitalization, rehospitalization, mortality rates, demographics and characteristics, and quality of care in these patients. Method: A retrospective review of all eligible adult patients' medical records from 2018 and 2019 was conducted at five hospitals. The patients were newly diagnosed with HF, as indicated by the International Classification of Diseases (ICD)-10 code "I50." Descriptive statistics was used to investigate patients' hospital burden and clinical outcome data. Results: There were 1134 patients newly diagnosed with HF, classified as HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), and HF with mildly reduced ejection fraction (HFmrEF) (44.0, 40.0, and 16.0%, respectively). The male-to-female ratios in HFmrEF and HFpEF were similar. In contrast, the proportion of men with HFrEF was greater. The mean age of all patients was 66.0 years. The hospitalization rate was 1.3. Rehospitalization rates for HF-related issues were 0.1, 0.2, 0.4, and 0.5 at 30 days, 60 days, 180 days, and 1 year, respectively. The percentage of deaths from all causes among these patients was 9.8%, while the percentage of deaths from cardiovascular-related causes was 8.5%. Only a small proportion of patients received a target dose of guideline-directed medical therapy (GDMT). Conclusions: The study revealed that the characteristics, hospitalization rate for HF, and in-hospital mortality rate among newly diagnosed patients with HF were higher compared to similar studies conducted in Thailand and other countries. Moreover, a high quality of care is needed to improve the morbidity and mortality associated with HF in Thailand. [ABSTRACT FROM AUTHOR]

Introduction: Heart failure (HF) is one of the leading causes of hospitalization worldwide. In Thailand, data on HF burden remains limited. This study aimed to describe comprehensive evidence detailing the HF prevalence, hospital admission rates, in-hospital mortality, and overall mortality rates at the hospital level. Method: All eligible adult patients' medical records from 2018 and 2019 were analyzed retrospectively at five hospitals in different regions. The patients were diagnosed with HF, as indicated by the International Classification of Diseases (ICD)-10 code I50. Descriptive statistics were used to examine the hospital burden as well as patients' clinical and outcome data. Results: A total of 7384 patients with HF were identified from five tertiary hospitals. Around half of the patients were male. The mean age was 67 years, and the main health insurance scheme was the Universal Coverage Scheme. The prevalence of HF was 0.1% in 2018 and 0.2% in 2019. Heart failure with preserved ejection fraction (HFpEF) was the most common type of HF in both visits, followed by heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF). The proportion of HF hospitalizations was 1.2% in 2018 and 1.5% in 2019. The proportion of HF rehospitalizations versus hospitalizations in patients with HF was 22.7% in 2018 and 23.9% in 2019. The risk of rehospitalization was highest at 180 days after hospital discharge (87.8%). Among the patients with HF, the proportion of all-cause mortality was 9.1% in 2018 and 8.0% in 2019. Most of the deaths occurred within 30 days after hospitalization. Conclusion: Our study demonstrated that the burden of HF in terms of hospitalization and in-hospital mortality was notably high when compared to similar studies conducted in Thailand and other countries. [ABSTRACT FROM AUTHOR]

Radiation therapy (RT) is an essential component in the treatment of many pediatric malignancies. Thoracic RT may expose the heart to radiation dose and thereby increase the risk of late cardiac disease. This comprehensive review from the Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative focused on late cardiac disease in survivors of childhood cancer treated with RT. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. We identified 1496 articles; 4 were included for dose-response modeling between mean cardiac radiation dose and risk of late coronary artery disease, heart failure (HF), valvular disease, and any cardiac disease. For each 10-Gy increase in corrected mean cardiac radiation dose in 1.8- to 2.0-Gy fractions, we estimated a hazard ratio of 2.01 (95% confidence interval [CI], 1.79-2.25) for coronary artery disease, of 1.87 (95% CI, 1.70-2.06) for HF, of 1.87 (95% CI, 1.78-1.96) for valvular disease, and of 1.88 (95% CI, 1.75-2.03) for any cardiac disease. From the same model, for each 100-mg/m2 increase in cumulative anthracycline dose, the hazard ratio for the development of HF was 1.93 (95% CI, 1.58-2.36), equivalent to an increase in mean heart dose of approximately 10.5 Gy. Other nontreatment factors were inconsistently reported in the analyzed articles. Radiation dose to the heart increases the risk of late cardiac disease, but survivors of childhood cancer who receive a mean dose <10 Gy at standard fractionation are at low absolute risk (<∼2% approximately 30 years after exposure) of late cardiac disease in the absence of anthracycline exposure. Minimizing cardiac radiation dose is especially relevant in children receiving anthracyclines. When cardiac sparing is not possible, we recommend prioritizing target coverage. It is likely that individual cardiac substructure doses will be a better predictor of specific cardiac diseases than mean dose, and we urge the pediatric oncology community to further study these relationships. [ABSTRACT FROM AUTHOR]

Background: Substantial focus has been placed on atrial fibrillation (AF) treatment and associated stroke prevention rather than preventing AF itself. We employed Mendelian randomization (MR) approach to examine the causal relationships between 50 modifiable risk factors (RFs) and AF. Methods: Instrumental variables for genetically predicted exposures were derived from corresponding genome‐wide association studies (GWASs). Summary‐level statistical data for AF were obtained from a GWAS meta‐analysis (discovery dataset, N = 1,030,836) and FinnGen (validation dataset, N = 208,594). Univariable and multivariable MR analyses were performed, primarily using inverse variance weighted method with a series of robust sensitivity analyses. Results: Genetic predisposition to insomnia, daytime naps, apnea, smoking initiation, moderate to vigorous physical activity and obesity traits, including body mass index, waist–hip ratio, central and peripheral fat/fat‐free mass, exhibited significant associations with an increased risk of AF. Coffee consumption and ApoB had suggestive increased risks. Hypertension (odds ratio (OR) 95% confidence interval (CI): 5.26 (4.42, 6.24)), heart failure (HF) (OR 95% CI, 4.77 (2.43, 9.37)) and coronary artery disease (CAD) (OR 95% CI: 1.20 (1.16, 1.24)) were strongly associated with AF, while college degree, higher education attachment and HDL levels were associated with a decreased AF risk. Reverse MR found a bidirectional relationship between genetically predicted AF and CAD, HF and ischemic stroke. Multivariable analysis further indicated that obesity‐related traits, systolic blood pressure and lower HDL levels independently contributed to the development of AF. Conclusions: This study identified several lifestyles and cardiometabolic factors that might be causally related to AF, underscoring the importance of a holistic approach to AF management and prevention. [ABSTRACT FROM AUTHOR]

Fabry disease (FD) is a rare, X-linked lysosomal storage disorder that can result in fatal end-stage renal disease, heart failure, and cerebro-occlusive events. Vague clinical symptoms and rarity often mean diagnosis and potential treatment is delayed. Ophthalmic findings in FD patients can be helpful in establishing an early diagnosis and timely treatment. Spectral domain optical coherence tomography (SD-OCT) imaging in FD patients shows hyper-reflective foci (HRF) in characteristic patterns within the inner retinal layers. We found that the HRF was localised in linear distributions at the deep and superficial borders of the retinal inner nuclear layer, likely reflecting anatomic vascular plexuses and FD-related sphingolipid deposition within the vessel walls. These results highlight the potential use of SD-OCT in FD and how it may aid diagnosis in undifferentiated patients, prognostication, and disease monitoring. [ABSTRACT FROM AUTHOR]

Socioeconomic deprivation is associated with a lower likelihood of referral for advanced heart failure (HF) evaluation, but it is not known whether it influences rates of advanced HF therapies independently of key hemodynamic measures and comorbidity following advanced HF evaluation in a universal healthcare system. We linked data from a single-center Danish clinical registry of consecutive patients evaluated for advanced HF with patient-level information on socioeconomic status. Patients were divided into groups based on the level of education (low, medium, and high), combined degree of socioeconomic deprivation (low, medium, and high), and household income quartiles. Rates of the combined outcome of left ventricular assist device implantation or heart transplantation (advanced HF therapy) with death as a competing risk were estimated with cumulative incidence functions, and Cox proportional hazards models adjusted for age, sex, central venous pressure, cardiac index, and comorbidities. We included 629 patients, median age 53 years, of whom 77% were men. During a median follow-up of 5 years, 179 (28%) underwent advanced HF therapy. The highest level of education was associated with higher rates (high vs low, adjusted HR 1.81 95% CI 1.14–2.89, p = 0.01), whereas household income quartile groups (Q4 vs Q1, adjusted HR 1.37 95% CI 0.76–2.47, p = 0.30) or groups of combined socioeconomic deprivation (high vs low degree of deprivation, adjusted HR 0.86 95% CI 0.50–1.46, p = 0.56) were not significantly associated with rates of advanced HF therapy. Patients with a lower level of education might be disfavored for advanced HF therapies and could require specific attention in the advanced HF care center. [ABSTRACT FROM AUTHOR]

There is no FDA-approved left ventricular assist device (LVAD) for smaller children permitting routine hospital discharge. Smaller children supported with LVADs typically remain hospitalized for months awaiting heart transplant—a major burden for families and a challenge for hospitals. We describe the initial outcomes of the Jarvik 2015, a miniaturized implantable continuous flow LVAD, in the NHLBI-funded Pumps for Kids, Infants, and Neonates (PumpKIN) study, for bridge-to-heart transplant. Children weighing 8 to 30 kg with severe systolic heart failure and failing optimal medical therapy were recruited at 7 centers in the United States. Patients with severe right heart failure and single-ventricle congenital heart disease were excluded. The primary feasibility endpoint was survival to 30 days without severe stroke or non-operational device failure. Of 7 children implanted, the median age was 2.2 (range 0.7, 7.1) years, median weight 10 (8.2 to 20.7) kilograms; 86% had dilated cardiomyopathy; 29% were INTERMACS profile 1. The median duration of Jarvik 2015 support was 149 (range 5 to 188) days where all 7 children survived including 5 to heart transplant, 1 to recovery, and 1 to conversion to a paracorporeal device. One patient experienced an ischemic stroke on day 53 of device support in the setting of myocardial recovery. One patient required ECMO support for intractable ventricular arrhythmias and was eventually transplanted from paracorporeal biventricular VAD support. The median pump speed was 1600 RPM with power ranging from 1–4 Watts. The median plasma free hemoglobin was 19, 30, 19 and 30 mg/dL at 7, 30, 90 and 180 days or time of explant, respectively. All patients reached the primary feasibility endpoint. Patient-reported outcomes with the device were favorable with respect to participation in a full range of activities. Due to financial issues with the manufacturer, the study was suspended after consent of the eighth patient. The Jarvik 2015 LVAD appears to hold important promise as an implantable continuous flow device for smaller children that may support hospital discharge. The FDA has approved the device to proceed to a 22-subject pivotal trial. Whether this device will survive to commercialization remains unclear because of the financial challenges faced by industry seeking to develop pediatric medical devices. (Supported by NIH/NHLBI HHS Contract N268201200001I, clinicaltrials.gov 02954497). [ABSTRACT FROM AUTHOR]

Temporary mechanical circulatory support as well as multidisciplinary team approach in a regional care organization might improve survival of cardiogenic shock. No study has evaluated the relative effect of each temporary mechanical circulatory support on mortality in the context of a regional network. Prospective observational data were retrieved from patients consecutively admitted with cardiogenic shock to the intensive care units in 3 centers organized into a regional cardiac assistance network. Temporary mechanical circulatory support indication was decided by a heart team, based on the initial shock severity or if shock was refractory to medical treatment within 24 hours of admission. A propensity score for circulatory support use was used as an adjustment co-variable to emulate a target trial. The primary endpoint was in-hospital mortality. Two hundred and forty-six patients were included in the study (median age: 59.5 years, 71.9% male): 121 received early mechanical assistance. The main etiologies were acute myocardial infraction (46.8%) and decompensated heart failure (27.2%). Patients who received early mechanical assistance had more severe conditions than other patients. Their crude in-hospital mortality was 38% and 22.4% in other patients but adjusted in-hospital mortality was not different (hazard ratio 0.91, 95% CI:0.65–1.26). Patients with mechanical assistance had a higher rate of complications than others with longer Intensive Care Unit and hospital stays. In the conditions of a cardiac assistance regional network, in-hospital mortality was not improved by early mechanical assistance implantation. A high incidence of complications of temporary mechanical circulatory support may have jeopardized its potential benefit. [ABSTRACT FROM AUTHOR]

Aim: To determine the effects of collaborative health management of congestive heart failure through the rigorous evaluation and extraction of evidence. Background: Over the past two decades, cardiovascular disease has been the leading cause of death worldwide. Multidisciplinary team intervention for congestive heart failure has increased with population ageing and congestive heart failure incidence rate as well as cost of care. However, the effectiveness and feasibility of collaborative health management need to be explored. Design: Systematic review and meta‐analysis. Methods: We conducted systematic literature searches in the Cochrane Library, PubMed, CINAHL and Medline for articles published between 2002 and 2022. After screening based on the inclusion and exclusion criteria, 13 articles were included in a rigorous review and evidence extraction process, evaluated methodological quality using the Jadad Quality Scale. Statistical heterogeneity was evaluated using Review Manager (RevMan Version 5.4) for the meta‐analysis. Results: In this study, a systematic review and meta‐analysis were performed on 13 studies regarding the collaborative health management of people with congestive heart failure. The common result is that the collaborative health management model enables the enhancement of self‐care and monitoring abilities, the strengthening of cardiac function, the alleviation of physiological and psychological symptoms and the improvement of readmission rates, mortality rate and quality of life. Conclusion: The congestive heart failure collaborative health management model could decrease the hospitalization rate related to congestive heart failure, all‐cause mortality rate, and all‐cause hospitalization rate, and improve the quality of life. Implications for Practice: The collaborative health management model could effectively coordinate interdisciplinary team cooperation and provide information, which decreases hospitalization and mortality risks and improves their quality of life. No patient or Public Contribution: Our paper is a systematic review and meta‐analysis, and such details do not apply to our work. What does this paper contribute to the wider global clinical community?: The Collaborative Health Management Model provides in‐depth insights, aiding in the design tailored to the specific circumstances of each country. Highlighting its critical role in the context of a global shortage of nursing staff, the model emphasizes the integration of multidisciplinary professional roles and the strengthening of collaboration as essential elements in addressing challenges posed by workforce shortages.Implementation of the Collaborative Health Management Model not only enhances patient care outcomes but also relieves pressure on healthcare systems, lowers medical costs, and addresses challenges arising from the shortage of nursing staff. Consequently, this model not only contributes to individual patient care improvement but also holds broader implications for enhancing the efficiency and sustainability of global healthcare systems. Trial and Protocol Registration: The detailed study protocol can be found on the PROSPERO website. [ABSTRACT FROM AUTHOR]

Objectives: Patients with severe stroke are at high risk of developing acute respiratory distress syndrome (ARDS), but this severe complication was often under-diagnosed and rarely explored in stroke patients. We aimed to investigate the prevalence, early predictors, and outcomes of ARDS in severe stroke. Methods: This prospective study included consecutive patients admitted to neurological intensive care unit (neuro-ICU) with severe stroke, including acute ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. The incidence of ARDS was examined, and baseline characteristics and severity scores on admission were investigated as potential early predictors for ARDS. The in-hospital mortality, length of neuro-ICU stay, the total cost in neuro-ICU, and neurological functions at 90 days were explored. Results: Of 140 patients included, 35 (25.0%) developed ARDS. Over 90% of ARDS cases occurred within 1 week of admission. Procalcitonin (OR 1.310 95% CI 1.005–1.707, P = 0.046) and PaO2/FiO2 on admission (OR 0.986, 95% CI 0.979–0.993, P < 0.001) were independently associated with ARDS, and high brain natriuretic peptide (OR 0.994, 95% CI 0.989–0.998, P = 0.003) was a red flag biomarker warning that the respiratory symptoms may be caused by cardiac failure rather than ARDS. ARDS patients had longer stays and higher expenses in neuro-ICU. Among patients with ARDS, 25 (62.5%) were moderate or severe ARDS. All the patients with moderate to severe ARDS had an unfavorable outcome at 90 days. Conclusions: ARDS is common in patients with severe stroke, with most cases occurring in the first week of admission. Procalcitonin and PaO2/FiO2 on admission are early predictors of ARDS. ARDS worsens both short-term and long-term outcomes. The conflict in respiratory support strategies between ARDS and severe stroke needs to be further studied. [ABSTRACT FROM AUTHOR]

Background and purpose: The transition to adult services, and subsequent glucocorticoid management, is critical in adults with Duchenne muscular dystrophy. This study aims (1) to describe treatment, functional abilities, respiratory and cardiac status during transition to adulthood and adult stages; and (2) to explore the association between glucocorticoid treatment after loss of ambulation (LOA) and late‐stage clinical outcomes. Methods: This was a retrospective single‐centre study on individuals with Duchenne muscular dystrophy (≥16 years old) between 1986 and 2022. Logistic regression, Cox proportional hazards models and survival analyses were conducted utilizing data from clinical records. Results: In all, 112 individuals were included. Mean age was 23.4 ± 5.2 years and mean follow‐up was 18.5 ± 5.5 years. At last assessment, 47.2% were on glucocorticoids; the mean dose of prednisone was 0.38 ± 0.13 mg/kg/day and of deflazacort 0.43 ± 0.16 mg/kg/day. At age 16 years, motor function limitations included using a manual wheelchair (89.7%), standing (87.9%), transferring from a wheelchair (86.2%) and turning in bed (53.4%); 77.5% had a peak cough flow <270 L/min, 53.3% a forced vital capacity percentage of predicted <50% and 40.3% a left ventricular ejection fraction <50%. Glucocorticoids after LOA reduced the risk and delayed the time to difficulties balancing in the wheelchair, loss of hand to mouth function, forced vital capacity percentage of predicted <30% and forced vital capacity <1 L and were associated with lower frequency of left ventricular ejection fraction <50%, without differences between prednisone and deflazacort. Glucocorticoid dose did not differ by functional, respiratory or cardiac status. Conclusion: Glucocorticoids after LOA preserve late‐stage functional abilities, respiratory and cardiac function. It is suggested using functional abilities, respiratory and cardiac status at transition stages for adult services planning. [ABSTRACT FROM AUTHOR]

Background: With the emergence of cytotoxic T lymphocyte‐associated protein‐4 (CTLA‐4) inhibitors, the outcomes of patients with malignant tumors have improved significantly. However, the incidence of cardiovascular adverse events has also increased, which can affect tumor treatment. In this study, we evaluated the incidence and severity of adverse cardiovascular events caused by CTLA‐4 inhibitors by analyzing reported trials that involved CTLA‐4 inhibitor therapy. Methods: Randomized clinical trials published in English from January 1, 2013, to November 30, 2022, were searched using the Cochrane Library and PubMed databases. All included trials examined all grade and grades 3–5 cardiac and vascular adverse events. These involved comparisons of CTLA‐4 inhibitors to placebo, CTLA‐4 inhibitors plus chemotherapy to chemotherapy alone, CTLA‐4 inhibitors combined with PD‐1/PD‐L1 inhibitors to PD‐1/PD‐L1 inhibitors alone, and CTLA‐4 inhibitors plus target agent to PD‐1/PD‐L1 inhibitors plus target agent. The odds ratio (OR) and corresponding 95% confidence intervals (CIs) were calculated using the Mantel‐Haenszel method. Results: Overall, 20 trials were included. CTLA‐4 inhibitors significantly increased the incidence of all‐grade cardiovascular toxicity (OR = 1.33, 95% CI: 1.00–1.75, p = 0.05). The incidence of all‐grade cardiovascular toxicity increased in malignant tumor patients who received single‐agent CTLA‐4 inhibitors (OR = 1.73, 95% CI: 1.13–2.65, p = 0.01), as well as the incidence rate of grades 3–5 cardiovascular adverse events (OR = 2.00, 95% CI: 1.08–3.70, p = 0.03). Compared with the non‐CTLA‐4 inhibitor group, CTLA‐4 inhibitors plus chemotherapy, PD‐1/PD‐L1 inhibitors, or target agent did not significantly affect the incidence of cardiac and vascular toxicity. The incidence of grades 3–5 cardiac failure, hypertension, pericardial effusion, myocarditis, and atrial fibrillation were much higher among patients exposed to CTLA‐4 inhibitor, but the data were not statistically significant. Conclusion: Our findings suggest that the incidence rate of all cardiovascular toxicity and severe cardiovascular toxicity increased in patients who were administered CTLA‐4 inhibitors. In addition, the risk of serious cardiovascular toxic events was independent of the type of adverse event. From these results, physicians should assess the benefits and risks of CTLA‐4 inhibitors when treating malignancies. [ABSTRACT FROM AUTHOR]

With the increasing frequency of heart failure (HF) in elderly patients, polypharmacy has become a major concern owing to its adverse outcomes. However, reports on the clinical impact of polypharmacy and discharge medications in hospitalized super-aged patients with acute HF are rare. Data from 682 patients aged 80 years or older, hospitalized for treating acute HF, were analyzed. We recorded the number of medications at discharge and classified them into three groups: HF, non-HF cardiovascular, and non-cardiovascular medications. We investigated the correlation of polypharmacy, defined as daily administration of 10 or more medications at discharge, and the use of discharge medications with post-discharge prognosis. Polypharmacy was recorded in 24.3% of enrolled patients. Polypharmacy was not an independent predictor of all-cause mortality, the incidence of cardiac-related death, or HF-associated rehospitalization; however, the number of non-cardiovascular medications, multiple usage of potentially inappropriate medications, use of mineralocorticoid receptor antagonists, and doses of loop diuretics were associated with poor prognosis. Polypharmacy was significantly associated with higher mortality in patients with Barthel index ≥ 60 at discharge; hence, physical function at discharge was useful for the stratification of prognostic impacts of polypharmacy. The current study demonstrated that polypharmacy was not essentially associated with poor prognosis in super-aged patients with acute HF. Appropriate medications that consider the patient's physical function, rather than polypharmacy itself, are important for the management of HF. [ABSTRACT FROM AUTHOR]

Guidelines advocate for integrating palliative care into the management of heart failure (HF) and of children with life-limiting disease. The potential impact of palliative care integration into pediatric HF on patient-centered outcomes is poorly understood. The present study sought to assess the association of programmatic implementation of palliative care into the heart transplant evaluation process with hospital-free days (HFD) and end of life (EOL) treatment choices. The study included patients less than 19 years of age who underwent a heart transplant evaluation between February 2012 and April 2020 at a single center. Patients evaluated in the programmatic palliative care (PPC) era (January 2016–April 2020) were compared to patients evaluated in the pre-PPC era (February 2012–December 2015). The study included 188 patients, with 91 (48%) in the PPC era and 97 (52%) in the pre-PCC era. Children < 1 year of age at the time of the evaluation represented 32% of the cohort. 52% of patients had single ventricle physiology. PPC was not significantly associated with increased HFD (IRR 0.94 [95% CI 0.79–1.2]). PPC was however associated with intensity of EOL care with decreased mechanical ventilation (OR 0.12 [95% CI 0.02–0.789], p = 0.03) and decreased use of ionotropic support (OR 0.13 [95% CI 0.02-0.85], p =0.03). PPC in pediatric heart transplant evaluations may be associated with less invasive interventions at EOL. [ABSTRACT FROM AUTHOR]

There are strong associations between oxygen desaturations and cardiovascular outcomes. Additionally, oxygen resaturation rates are linked to excessive daytime sleepiness independent of oxygen desaturation severity. No studies have yet looked at the independent effects of comorbidities or medications on resaturation parameters. The Sleep Heart Health Study data was utilised to derive oxygen saturation parameters from 5804 participants. Participants with a history of comorbidities or medication usage were compared against healthy participants with no comorbidity/medication history. 4293 participants (50.4% female, median age 64 years) were included in the analysis. Females recorded significantly faster resaturation rates (mean 0.61%/s) than males (mean 0.57%/s, p < 0.001), regardless of comorbidities. After adjusting for demographics, sleep parameters, and desaturation parameters, resaturation rate was reduced with hypertension (-0.09 (95% CI -0.16, -0.03)), myocardial infarction (-0.13 (95% CI -0.21, -0.04)) and heart failure (-0.19 (95% CI -0.33, -0.05)), or when using anti-hypertensives (-0.10 (95% CI -0.17, -0.03)), mental health medications (-0.18 (95% CI -0.27, -0.08)) or anticoagulants (-0.41 (95% CI -0.56, -0.26)). Desaturation to Resaturation ratio for duration was decreased with mental health (-0.21 (95% CI -0.34, -0.08)) or diabetic medications (-0.24 (95% CI -0.41, -0.07)), and desaturation to resaturation ratio for area decreased with heart failure (-0.25 (95% CI -0.42, -0.08)). Comorbidities and medications significantly affect nocturnal resaturation parameters, independent of desaturation parameters. However, the causal relationship remains unclear. Further research can enhance our knowledge and develop more precise and safer interventions for individuals affected by certain comorbidities. • Oxygen resaturation rate is faster in females (0.61 %/s) than in males (0.57 %/s). • Oxygen resaturation rate is slowed with hypertension or myocardial infarction. • Mental health medications and anticoagulants significantly slowed resaturation rates. • Resaturation rate was not associated with ESS scores. [ABSTRACT FROM AUTHOR]

B-lines assessed by lung ultrasound (LUS) outperform physical exam, chest radiograph, and biomarkers for the associated diagnosis of acute heart failure (AHF) in the emergent setting. The use of LUS is however limited to trained professionals and suffers from interpretation variability. The objective was to utilize transfer learning to create an AI-enabled software that can aid novice users to automate LUS B-line interpretation. Data from an observational AHF LUS study provided standardized cine clips for AI model development and evaluation. A total of 49,952 LUS frames from 30 patients were hand scored and trained on a convolutional neural network (CNN) to interpret B-lines at the frame level. A random independent evaluation set of 476 LUS clips from 60 unique patients assessed model performance. The AI models scored the clips on both a binary and ordinal 0–4 multiclass assessment. A multiclassification AI algorithm had the best performance at the binary level when applied to the independent evaluation set, AUC of 0.967 (95% CI 0.965–0.970) for detecting pathologic conditions. When compared to expert blinded reviewer, the 0–4 multiclassification AI algorithm scale had a reported linear weighted kappa of 0.839 (95% CI 0.804–0.871). The multiclassification AI algorithm is a robust and well performing model at both binary and ordinal multiclass B-line evaluation. This algorithm has the potential to be integrated into clinical workflows to assist users with quantitative and objective B-line assessment for evaluation of AHF. [ABSTRACT FROM AUTHOR]

Proper protein degradation is required for cellular protein homeostasis and organ function. Particularly, in post-mitotic cells, such as cardiomyocytes, unbalanced proteolysis due to inflammatory stimuli and oxidative stress contributes to organ dysfunction. To ensure appropriate protein turnover, eukaryotic cells exert two main degradation systems, the ubiquitin-proteasome-system and the autophagy-lysosome-pathway. It has been shown that proteasome activity affects the development of cardiac dysfunction differently, depending on the type of heart failure. Studies analyzing the inducible subtype of the proteasome, the immunoproteasome (i20S), demonstrated that the i20S plays a double role in diseased hearts. While i20S subunits are increased in cardiac hypertrophy, atrial fibrillation and partly in myocarditis, the opposite applies to diabetic cardiomyopathy and ischemia/reperfusion injury. In addition, the i20S appears to play a role in autophagy modulation depending on heart failure phenotype. This review summarizes the current literature on the i20S in different heart failure phenotypes, emphasizing the two faces of i20S in injured hearts. A selection of established i20S inhibitors is introduced and signaling pathways linking the i20S to autophagy are highlighted. Mapping the interplay of the i20S and autophagy in different types of heart failure offers potential approaches for developing treatment strategies against heart failure. [Display omitted] • Impaired immunoproteasome (i20S) activity differently affects heart failure types. • i20S is increased in cardiac hypertrophy, atrial fibrillation and in myocarditis. • i20S is decreased in diabetic cardiomyopathy and ischemia/reperfusion injury. • i20S can directly impact autophagy via Atg5 degradation and Akt/mTOR activation. • Lack of i20S increases mitochondrial fission and decreases AMPK activity. [ABSTRACT FROM AUTHOR]

Background: There is no standard approach for managing the use or dose of loop diuretics after initiating sacubitril/valsartan. Objective: To investigate longitudinal trends in loop diuretic therapy use and doses during the initial 6 months following sacubitril/valsartan initiation. Methods: This retrospective cohort study included adult patients who were initiated on sacubitril/valsartan in cardiology clinics. Inclusion criteria were patients diagnosed with heart failure with reduced ejection fraction (ejection fraction ≤40%) and initiated on sacubitril/valsartan in an outpatient setting. We investigated longitudinal trends in the prevalence of loop diuretic use and furosemide equivalent dose at baseline, 2 weeks, 1 month, 3 month and 6 months following sacubitril/valsartan initiation. Results: A total of 427 patients were included in the final cohort. Compared to the baseline loop diuretic use and dose, there were no significant longitudinal changes in the prevalence of loop diuretic use or the furosemide equivalent dose over the 6 months following sacubitril/valsartan initiation. The use of sacubitril/valsartan was not significantly associated with reductions in the use or dose of loop diuretics over a 6-month follow-up period. Conclusion: The use of sacubitril/valsartan did not significantly change the use or dose of loop diuretics over 6-month follow-up period. Initiation of sacubitril/valsartan may not need a pre-emptive loop diuretic dose reduction. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to improve outcomes in patients with heart failure (HF) and are now included in guideline-directed medical therapy. Trials reporting the change in loop diuretic dose following SGLT2i initiation have indicated conflicting results. There is no clear guidance on whether reducing loop diuretic doses following SGLT2i initiation is appropriate. Objective: The purpose of this study is to assess the impact of SGLT2i initiation on diuretic adjustment in hospitalized patients with known or new HF. Methods: This was a retrospective, single health-system study assessing the change in loop diuretic dose in the 60 days following discharge for patients with HF initiated on SGLT2i therapy during a hospital admission or upon discharge. Secondary outcomes assessed effect on renal function and discontinuation of SGLT2i within the 60 day follow up period. Results: Forty percent of patients required loop diuretic dose adjustment, with 29% requiring a dose reduction within the 60 days following discharge. There was minimal change in serum creatinine or blood urea nitrogen. The SGLT2i was discontinued in 6 patients. Conclusions: After inpatient initiation of SGLT2is, approximately one-third of patients required a reduction in loop diuretic dose within 60 days following hospital discharge. Further study is recommended to confirm if empiric diuretic dose adjustments are appropriate in this HF population. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) is an important, emerging risk factor for dementia, but it is not clear whether HFpEF contributes to a specific pattern of neuroanatomical changes in dementia. A major challenge to studying this is the relative paucity of datasets of patients with dementia, with/without HFpEF, and relevant neuroimaging. We sought to demonstrate the feasibility of using modern data mining tools to create and analyze clinical imaging datasets and identify the neuroanatomical signature of HFpEF-associated dementia. We leveraged the bioinformatics tools at Vanderbilt University Medical Center to identify patients with a diagnosis of dementia with and without comorbid HFpEF using the electronic health record. We identified high resolution, clinically-acquired neuroimaging data on 30 dementia patients with HFpEF (age 76.9 ± 8.12 years, 61% female) as well as 301 age- and sex-matched patients with dementia but without HFpEF to serve as comparators (age 76.2 ± 8.52 years, 60% female). We used automated image processing pipelines to parcellate the brain into 132 structures and quantify their volume. We found six regions with significant atrophy associated with HFpEF: accumbens area, amygdala, posterior insula, anterior orbital gyrus, angular gyrus, and cerebellar white matter. There were no regions with atrophy inversely associated with HFpEF. Patients with dementia and HFpEF have a distinct neuroimaging signature compared to patients with dementia only. Five of the six regions identified in are in the temporo-parietal region of the brain. Future studies should investigate mechanisms of injury associated with cerebrovascular disease leading to subsequent brain atrophy. [ABSTRACT FROM AUTHOR]

Aim Methods and results Conclusion The role of malnutrition among patients with severe heart failure (HF) is not well established. We evaluated the incidence, predictors, and prognostic impact of malnutrition in patients with severe HF.Nutritional status was measured using the geriatric nutritional risk index (GNRI), based on body weight, height and serum albumin concentration, with malnutrition defined as GNRI ≤98. It was assessed in consecutive patients with severe HF, defined by at least one high‐risk ‘I NEED HELP’ marker, enrolled at four Italian centres between January 2020 and November 2021. The primary endpoint was all‐cause mortality. A total of 510 patients with data regarding nutritional status were included in the study (mean age 74 ± 12 years, 66.5% male). Among them, 179 (35.1%) had GNRI ≤98 (malnutrition). At multivariable logistic regression, lower body mass index (BMI) and higher levels of natriuretic peptides (B‐type natriuretic peptide [BNP] > median value [685 pg/ml] or N‐terminal proBNP > median value [5775 pg/ml]) were independently associated with a higher likelihood of malnutrition. Estimated rates of all‐cause death at 1 year were 22.4% and 41.1% in patients without and with malnutrition, respectively (log‐rank p < 0.001). The impact of malnutrition on all‐cause mortality was confirmed after multivariable adjustment for relevant covariates (adjusted hazard ratio 2.03, 95% confidence interval 1.43–2.89, p < 0.001).In a contemporary, real‐world, multicentre cohort of patients with severe HF, malnutrition (defined as GNRI ≤98) was common and independently associated with an increased risk of mortality. Lower BMI and higher natriuretic peptides were identified as predictors of malnutrition in these patients. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions Implications for nursing practice To identify characteristics associated with an intention to complete advance directives (ADs) and end‐of‐life treatment preferences for outpatients with heart failure (HF).A cross‐sectional, analytical study. Sociodemographic and clinical data were collected from 108 patients with HF in an outpatient clinic in São Paulo, SP, Brazil. Quality of life (QoL) was assessed using the Minnesota Living with Heart Failure Questionnaire; knowledge about HF and the intention to complete ADs were assessed using a script. The relationships among variables were assessed through the chi‐square and Mann–Whitney tests, with p < 0.05 considered significant.The intention to complete ADs was significantly associated with reporting adherence to pharmacological recommendations (99% vs. 88.1%, p = 0.02), worse QoL (29.7 ± 18.2 vs. 20.9 ± 11.0; p = 0.0336), perceived knowledge about HF (89.7% vs. 63.6%, p = 0.0495), not wishing the healthcare providers would decide about treatment (27.3% vs. 2.15, p = 0.0026), and considering ADs useful (91.8% vs. 27.3%, p < 0.001). End‐of‐life treatment preferences included living as long as possible (50.5%), not being sedated (37.1%), and staying close to family and friends for as long as possible (32.0%).Characteristics associated with an intention to complete ADs and end‐of‐life treatment preferences were identified in patients with HF.These results can help facilitate patients’ completion of their ADs or activate their intention to maximize opportunities to exercise autonomy. [ABSTRACT FROM AUTHOR]

Aims: We assessed eligibility for omecamtiv mecarbil (OM) in a real-world cohort with heart failure with reduced ejection fraction (HFrEF) according to the selection criteria of the GALACTIC-HF trial (trial scenario) and selected trial´s criteria more likely to impact real-world use (pragmatic scenario). Methods and results: We included 31,015 patients with HFrEF lasting ≥3 months and registered in the Swedish HF registry between 2000–2021. Trial eligibility was calculated by applying all the GALACTIC-HF selection criteria. The pragmatic scenario considered only the New York Heart Association class, history of worsening HF, N-terminal pro-B-type natriuretic peptides (NT-proBNP), blood pressure and renal failure criteria defined as in the trial. Eligibility for OM in chronic HFrEF was 21% and 36% in the trial and pragmatic scenarios, respectively. Eligibility was higher in those with EF<30% (trial: 27%, pragmatic: 44%), in-patients (trial:30%, pragmatic:57%), severe HF (trial: 35%, pragmatic: 60%), NYHA class III-IV (trial: 26%, pragmatic: 45%), and NT-proBNP≥5,000pg/mL (trial: 30%, pragmatic: 51%). The criteria that most limited eligibility were history of a recent worsening HF event (60% eligible in chronic HFrEF), elevated NT-proBNP (82% eligible), and deviating blood pressure (82% eligible). Overall, eligible patients were characterized by more severe HF and higher CV event-rates in both scenarios, and higher comorbidity burden in the pragmatic scenario. Conclusion: Approximately 21% of real-world chronic HFrEF patients would be eligible for OM according to the GALACTIC-HF selection criteria, and 36% according to the criteria more likely to affect OM use in clinical practice. Criteria in both scenarios identified a patient-group with severe HF and high CV event-rates. [ABSTRACT FROM AUTHOR]

Objectives: To analyze diaphragmatic thickness, at end-inspiration and end-expiration, diaphragmatic thickening index and mobility via US under two different modalities of inspiratory muscle loading, in two different modalities of inspiratory muscle loading and different load intensities at full-vital capacity maneuvers and the relationship between diaphragmatic thickness with pulmonary function tests in participants with HF. Methods: This randomized crossover trial, enrolled with 17 HF subjects, evaluated diaphragm thickness (Tdi, mm), fractional thickness (TFdi, %), and mobility (mm) US during low and high intensities (30% and 60% of maximal inspiratory pressure—MIP) with two modalities of inspiratory muscle loading mechanical threshold loading (MTL) and tapered flow-resistive loading (TFRL). Results: Both MTL and TFRL produced a increase in Tdi, but only with high intensity loading compared to baseline—2.21 (0.26) vs. 2.68 (0.33) and 2.73 (0.44) mm; p =.01. TFdi was greater than baseline under all conditions, except during low intensity of TFRL. Diaphragm mobility was greater than baseline under all conditions, and high intensity of TFRL elicited greater mobility compared to all other conditions. Additionally, baseline Tdi was moderately correlated with pulmonary function tests. Conclusions: MTL and TFRL modalities elicit similar increases in diaphragm thickness at loads, but only during high intensity loading it was greater than baseline. Diaphragm mobility was significantly greater than baseline under both loads and devices, and at high intensity compared to low intensity, although TFRL produced greater mobility compared to modalities of inspiratory muscle loading. There is an association between diaphragm thickness and pulmonary function tests. [ABSTRACT FROM AUTHOR]

Background: The real-world tuberculosis (TB) surveillance data was generally incomplete due to underreporting and underdiagnosis. The inventory study aimed to assess and quantify the incompletion of surveillance systems in southwestern China. Methods: The inventory study was conducted at randomly selected health facilities (HF) by multi-stage stratified cluster sampling. The participants were included in the period between August of 2020 in province-level and prefecture-level HF, and in the period between June to December of 2020 in other categories of HF respectively. The clinical committee confirmed medical records were matched to the National Notifiable Disease Reporting System (NNDRS) and the Tuberculosis Information Management System (TBIMS) to define the report and register status. The underreporting and under-register rates were evaluated based on the matched data, and factors associated with underreport and under-register were assessed by the 2-level logistic multilevel model (MLM). Results: We enrolled 7,749 confirmed TB cases in the analysis. The province representative overall underreport rate to NNDRS was 1.6% (95% confidence interval, 95% CI, 1.3 − 1.9), and the overall under-register rate to TBIMS was 9.6% (95% CI, 8.9–10.3). The various underreport and under-register rates were displayed in different stratifications of background TB disease burden, HF level, HF category, and data source of the medical record in HF among prefectures of the province. The intraclass correlation coefficient (ICC) was 0.57 for the underreporting null MLM, indicating the facility-level cluster effect contributes a great share of variation in total variance. The two-level logistic MLM showed the data source of medical records in HF, diagnostic category of TB, and type of TB were associated with underreporting by adjusting other factors (p < 0.05). The ICC for under-register was 0.42, and the HF level, HF category, data source of medical records in HF, diagnostic category of TB and type of TB were associated with under-register by adjusting other factors (p < 0.05). Conclusion: The inventory study depicted incomplete TB reporting and registering to NNDRS and TBIMS in southwestern China. It implied that surveillance quality improvement would help advance the TB prevention and control strategy. [ABSTRACT FROM AUTHOR]

Background: Renal impairment is a predictor of coronavirus disease (COVID-19) severity. No studies have compared COVID-19 outcomes in patients with chronic kidney disease (CKD) and patients with impaired renal function without a prior diagnosis of CKD. This study aimed to identify the impact of pre-existing impaired renal function without CKD on COVID-19 outcomes. Methods: This retrospective study included 3,637 patients with COVID-19 classified into three groups by CKD history and estimated glomerular filtration rate (eGFR) on referral: Group 1 (n = 2,460), normal renal function without a CKD history; Group 2 (n = 905), impaired renal function without a CKD history; and Group 3 (n = 272), history of CKD. We compared the clinical characteristics of these groups and assessed the effect of CKD and impaired renal function on critical outcomes (requirement for respiratory support with high-flow oxygen devices, invasive mechanical ventilation, or extracorporeal membrane oxygen, and death during hospitalization) using multivariable logistic regression. Results: The prevalence of comorbidities (hypertension, diabetes, and cardiovascular disease) and incidence of inflammatory responses (white blood counts, and C-reactive protein, procalcitonin, and D-dimer levels) and complications (bacterial infection and heart failure) were higher in Groups 2 and 3 than that in Group 1. The incidence of critical outcomes was 10.8%, 17.7%, and 26.8% in Groups 1, 2, and 3, respectively. The mortality rate and the rate of requiring IMV support was lowest in Group 1 and highest in Group 3. Compared with Group 1, the risk of critical outcomes was higher in Group 2 (adjusted odds ratio [aOR]: 1.32, 95% confidence interval [CI]: 1.03–1.70, P = 0.030) and Group 3 (aOR: 1.94, 95% CI: 1.36–2.78, P < 0.001). Additionally, the eGFR was significantly associated with critical outcomes in Groups 2 (odds ratio [OR]: 2.89, 95% CI: 1.64–4.98, P < 0.001) and 3 (OR: 1.87, 95% CI: 1.08–3.23, P = 0.025) only. Conclusions: Clinicians should consider pre-existing CKD and impaired renal function at the time of COVID-19 diagnosis for the management of COVID-19. [ABSTRACT FROM AUTHOR]

Randomized controlled trials (RCTs) show a reduction in acute kidney injury, renal impairment and acute renal failure after initiation of a sodium glucose cotransporter‐2 inhibitor. Observational literature on the association is conflicting, but important to understand for populations with a higher risk of medication‐related adverse renal events. We aimed to systematically review the literature to summarize the association between sodium glucose cotransporter‐2 inhibitor use and acute kidney injury, renal impairment and acute renal failure in three at‐risk groups: older people aged >65 years, people with heart failure and people with reduced renal function. A systematic search of Embase (1974 until 23 February 2024) and PubMed (1946 until 23 February 2024) was performed. RCTs were included if they reported numbers of acute kidney injury or acute renal failure in people using sodium glucose cotransporter‐2 inhibitors compared to other diabetic therapies. Studies needed to report results by level of renal function, heart failure status or age. Of 922 results, eight studies were included. The absolute risk of acute kidney injury or acute renal failure was higher in people >65 years compared to those <65 years, higher in people with heart failure (vs without) and higher in people with reduced kidney function (vs preserved kidney function), but insufficient evidence to determine if the relative effect of sodium glucose cotransporter‐2 inhibitors on this risk was similar for each group. At‐risk cohorts are associated with a higher incidence of acute kidney problems in users of sodium glucose cotransporter‐2 inhibitors. [ABSTRACT FROM AUTHOR]

Background: Heavy menstrual bleeding (HMB) is a common menstrual disorder associated with multiple risk factors of cardiovascular disease (CVD) in women. In addition, HMB is often present with irregular menstruation (IM) which is a risk factor for CVD outcomes. However, the relationship between HMB and CVD outcomes is unexplored in the presence or absence of IM. We determined the association of HMB with multiple CVD outcomes using a nationally representative sample of female hospitalizations in the US. Methods: All hospitalizations of females with HMB diagnosis and normal menstrual cycles from ages of 18 to 70 years were extracted from the National Inpatient Sample Database, 2017. The HMB was defined using the International Classification of Diseases (ICD)-10 for excessive and frequent menstruation bleeding and included any current or history of HMB diagnosis. Outcomes including major adverse cardiovascular events (MACE), coronary heart disease (CHD), stroke, heart failure (HF), atrial fibrillation (AF) or arrhythmia, myocardial infarction (MI), and diabetes (DM) were defined using ICD-10 codes. Adjusted logistic regression and prosperity scores-matched logistic regression analyses were conducted to summarize adjusted associations with an odds ratio (OR) and a 95% confidence interval (CI). Results: Among 2,430,851 hospitalizations, HMB was observed in 7762 (0.68%) females with age ≤ 40 years and 11,164 (0.86%) females with age > 40 years. Among hospitalizations with age ≤ 40 years, HMB was significantly associated with increased odds of CVD outcomes including MACE (OR = 1.61; 95% CI: 1.25, 2.08), CHD (OR = 1.72; 95% CI: 1.10, 2.71), stroke (OR = 1.95; 95% CI: 1.12, 3.40), HF (OR = 1.53; 95% CI: 1.15, 2.03), and AF/arrhythmia (OR = 1.84; 95% CI: 1.34, 2.54). These associations were confirmed in multiple sensitivity analyses. In contrast, HMB was not robustly associated with CVD events among hospitalizations of women with age > 40 years. HMB without IM was strongly associated with DM, HF, AF, and MACE outcomes while HMB with IM was strongly associated with CHD and AF outcomes in hospitalizations of young women. Conclusions: HMB is associated with CVD events among US hospitalizations of young women. A routine investigation and screening of menstrual disorders, especially HMB, is useful for CVD risk stratification and management in young women. [ABSTRACT FROM AUTHOR]