Forst, Beani

Preeclampsia (PE) is a multifactorial hypertensive disorder of pregnancy that significantly increases both short- and long-term cardiovascular risk for affected women. PE and cardiovascular disease (CVD) share common risk factors, including endothelial dysfunction, obesity, insulin resistance, and dyslipidemia. Women with a history of PE face a markedly elevated risk of chronic hypertension, heart failure, and adverse cardiac remodeling, with evidence suggestive of persistent vascular and myocardial changes after pregnancy. The complex pathophysiology of PE is multifactorial and is thought to involve a combination of abnormal placentation, immune dysregulation, and anti-angiogenic factors, which may induce permanent cardiovascular alterations. Genetic predispositions may further link PE with cardiomyopathies and peripartum cardiomyopathy. However, despite these well-established risks, standardized long-term surveillance and management strategies for women with prior PE remain lacking. Early identification and targeted intervention in women with a history of PE represent critical opportunities to mitigate future cardiovascular morbidity and mortality. This review highlights the urgent need for comprehensive, evidence-based strategies that incorporate personalized follow-up and risk stratification to improve cardiovascular outcomes in this high-risk population.

Abstract Introduction/Background Transthyretin amyloidosis (ATTR) is a debilitating disease that leads to progressive cardiac dysfunction. Tafamidis is the gold standard therapy for ATTR cardiomyopathy. In recent observational studies, sodium-glucose cotransporter-2 inhibitors (SGLT2-Is) have demonstrated cardiovascular benefits in ATTR cardiomyopathy, but their role in ATTR cardiomyopathy as combination therapy with tafamidis remains unclear. Purpose To investigate the impact of combination therapy with tafamidis and SGLT2-Is versus just tafamidis in patients with known ATTR cardiomyopathy. Methods This retrospective cohort study utilized data from the TriNetX multinational database. Patients diagnosed with ATTR cardiomyopathy who received tafamidis were identified and stratified into two cohorts based on SGLT2-I use. Outcomes were assessed over three years, including all-cause mortality, all-cause hospitalizations, acute myocardial infarction (AMI), acute heart failure (HF) hospitalizations, ischemic stroke, atrial fibrillation/flutter, end-stage renal disease (ESRD) or requirement for renal replacement therapy, and ventricular tachycardia. Propensity score matching was used to balance both cohorts based on clinical comorbidities, medication use, and laboratory data. Adjusted odds ratios (OR) were calculated by logistic regression models. Results After propensity score matching, 409 patients were included in each cohort with a follow-up duration of 722 days (SD 320.87) for the SGLT2-I cohort and and 755.90 days (SD 363.26) for the non-SGLT2-I cohort. SGLT2-Is were associated with significantly lower rates of all-cause hospitalizations (41.1% vs. 50.9%; OR 0.67 [p = 0.005]) and AMI (6.6% vs. 13.9%, OR 0.44 [p = 0.001]), which persisted by three years (all-cause hospitalizations: 52.1% vs. 61.4%, OR 0.67 [p = 0.006] and myocardial infarction: 11.2% vs. 18.3%, OR 0.56 [p = 0.004]). No significant differences among the two cohorts were observed for all-cause mortality, acute HF hospitalizations, ischemic stroke, atrial fibrillation/flutter, ventricular tachycardia, or ESRD/need for renal replacement therapy. Conclusions SGLT2-Is, in combination with tafamidis, are associated with decreased all-cause hospitalizations and AMI in ATTR cardiomyopathy. While a mortality benefit was not demonstrated, these results depict the magnitude of clinical benefit derived from combination therapy with tafamidis and SGLT2-Is as opposed to prior observational studies which investigated SGLT2-I single therapy

Background To compare the effectiveness of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) versus bariatric surgery on cardiovascular outcomes in patients with heart failure (HF) with preserved ejection fraction and obesity. Methods Using the TriNetX research network, we conducted a retrospective cohort study of adults (aged ≥18 years) with HF with preserved ejection fraction and obesity (body mass index >30 kg/m 2 ) from 2017 to 2022. Patients were categorized into 2 cohorts: those receiving GLP‐1 RAs (semaglutide or tirzepatide) and those who underwent bariatric surgery. Propensity score matching (1:1) was used to balance baseline characteristics. Primary outcomes included acute HF events and all‐cause hospitalizations. Secondary outcomes included all‐cause death, myocardial infarction, stroke, and follow‐up body mass index. Cox proportional hazard models were used to estimate hazard ratios (HRs). Results A total of 2747 patients were included per cohort (mean age, 68 years). GLP‐1 RA therapy was associated with lower incidence of acute HF events (38.9% versus 44.6%; HR, 0.78 [95% CI, 0.72–0.85]), all‐cause death (11.1% versus 14.8%; HR, 0.71 [95% CI, 0.61–0.82]), and all‐cause hospitalizations (66.4% versus 77.3%; HR, 0.62 [95% CI, 0.58–0.66]). Rates of myocardial infarction (13.8% versus 13.4%; HR 0.99 [0.86–1.14]) and stroke (9.7% versus 10.7%; HR, 0.87 [0.74–1.02]) were similar between groups. Mean body mass index at follow‐up was 38.0 in the GLP‐1 RA cohort versus 37.7 after bariatric surgery ( P =0.34). Hemoglobin A 1c at follow‐up was higher in the GLP‐1 RA group (7.4 versus 6.8; P <0.001). Conclusions In patients with HF with preserved ejection fraction and obesity, GLP‐1 RA therapy was associated with improved outcomes compared with bariatric surgery, supporting the need for prospective trials to evaluate GLP‐1 RAs as a therapeutic alternative.

Abstract Aims Left ventricular assist devices (LVADs) are a critical intervention for advanced heart failure (HF), serving as destination therapy or bridge to transplantation. Obesity and diabetes impact outcomes in patients with LVADs. Glucagon-like peptide-1 receptor agonists (GLP1-RAs) demonstrate cardiovascular benefits; however, their role in patients with LVADs remains underexplored. We evaluated the association of GLP1-RA therapy with cardiovascular outcomes in patients with LVADs. Methods This retrospective cohort study used the TriNetX database, a research network database from 98 healthcare organizations. We queried for all adult LVAD recipients (≥18 years) and were stratified into GLP1-RA users and non-users. Propensity score matching (PSM) (1:1) balanced demographics, comorbidities, medication use and laboratory data. Outcomes included heart transplantation rates, heart failure hospitalizations, all-cause mortality, all-cause hospitalizations and cardiovascular events. Logistic regression models were used to estimate adjusted odds ratios (aOR). Results After PSM, we included a total of 1036 adult LVAD recipients (518 GLP1-RA users, 518 matched non-users) with a mean follow-up time of 311.6 ± 98.4 days for the GLP1-RA cohort and 304.0 ± 111.5 days for the non-GLP1-RAs cohort. Mean age was 56.7 ± 12.2 years in the GLP1-RA cohort and 58.0 ± 12.5 years in the non-GLP1-RA cohort. Females comprised 28.0% of both cohorts while White patients represented 52.1% of the GLP1-RA group and 53.1% of the non-GLP1-RA group. GLP1-RA users had higher heart transplantation rates [n = 98 (18.9%) vs. n = 44 (8.5%); aOR 2.514 (95% CI: 1.720–3.673)]. Acute HF events and all-cause hospitalizations were lower among GLP1-RA users compared with non-users [n = 288 (55.6%) vs. n = 357 (68.9%); aOR 0.565 (95% CI: 0.438–728) and n = 324 (62.5%) vs. n = 390 (75.3%); aOR 0.548 (95% CI: 0.420–0.716)]. No differences were observed when comparing the GLP1-RA cohort with the non-GLP1-RA cohort in regard to all-cause mortality [n = 32 (6.2%) vs. n = 44 (8.5%); aOR 0.709 (95% CI: 0.442–1.138)], stroke [n = 42 (8.1%) vs. n = 58 (11.2%); aOR 0.700 (95% CI: 0.461–1.062)] or cardiac arrest [n = 18 (3.5%) vs. n = 17 (3.3%); aOR 1.061 (95% CI: 0.541–2.082)]. Conclusions GLP1-RA therapy in patients with advanced HF and LVADs is potentially associated with improved heart transplantation rates while decreasing hospitalization and acute HF event rates.

Introduction: Sex-based differences in outcomes among patients with heart failure with reduced ejection fraction (HFrEF) treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) remain underexplored. This study aimed to evaluate sex-specific differences in cardiovascular outcomes in patients with HFrEF receiving SGLT2 inhibitors alongside guidelinedirected medical therapy (GDMT). Methods: We conducted a retrospective cohort study using the TriNetX global research network. Adults with HFrEF treated with SGLT2is and GDMT were stratified by sex. Propensity score matching (PSM) was used to balance baseline demographics, comorbidities, medications, and laboratory data. Primary outcomes were all-cause mortality and acute heart failure (HF) events; secondary outcomes included hospitalizations, arrhythmias, renal outcomes, and advanced therapies. Results: After PSM, 17,408 male and 17,408 female patients were analyzed. Male patients had lower odds of acute HF events (aOR: 0.949; 95% CI: 0.909–0.991), all-cause hospitalizations (aOR: 0.933; 95% CI: 0.895–0.973), and renal failure (aOR: 0.915; 95% CI: 0.870–0.962). No significant differences were observed in all-cause mortality (aOR: 1.003; 95% CI: 0.926–1.087) or heart transplantation, although LVAD use was more frequent in males (aOR: 1.416; 95% CI: 1.053–1.905). Discussion: The findings highlighted potential sex-based disparities in outcomes for patients with HFrEF on SGLT2is. Differential prescribing patterns, comorbidity burden, or timing of therapy initiation may contribute to observed differences. Conclusion: Among HFrEF patients treated with SGLT2is, males experienced lower risks of HF events, hospitalizations, and renal failure compared to females, despite similar mortality. Further research is needed to understand and address sex-specific disparities in HFrEF management.

Cardiac cachexia (CC) is a severe complication of advanced heart failure (HF), characterized by involuntary weight loss and muscle wasting, leading to poor outcomes and higher mortality. Despite its severity, CC remains under-recognized and undertreated, lacking targeted therapies specifically addressing its pathophysiology. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), though beneficial in reducing cardiovascular risk in patients with HF, may exacerbate muscle wasting in cachectic patients, necessitating further investigation. Non-pharmacological strategies, including tailored nutritional support and exercise programs, have shown positive effects on body composition and quality of life in patients with CC. However, there remains a gap in recommendations tailored to preventive strategies and pharmacologic therapies for patients with CC and concomitant GLP-1RA use. This review highlights the multifactorial mechanisms underlying CC and current and emerging therapeutic approaches for mitigating HF-related sarcopenia while on GLP-1RAs.

Cardiogenic shock is the most common cause of mortality in patients with acute myocardial infarction with an increase in incidence over the last 15-years. Recent classification systems of cardiogenic shock (CS) have improved categorization of patients into subsets of acuity and begun to integrate phenotypes and etiologies in addition to risk modifiers. Early revascularization with PCI or CABG has been the most important advance in the management of AMI-CS patients with improvements in survival. Despite this initial progress, mortality remains high at approximately 40%, with a significant proportion of patients dying of neurological causes, especially in the cohort with cardiac arrest and multi-organ dysfunction despite cardiac recovery. Mechanical circulatory support devices are an attractive strategy to ameliorate the cardio-metabolic spiral but have thus far failed to show survival benefits in randomized trials during revascularization of AMI-CS patients with IABP and ECMO use, although many aspects of their use have yet to be studied, including their role as part of an escalation or bridging strategy along the continuum of CS care. Randomized trials in Impella percutaneous LVAD use are pending. Cardiac arrest patients represent an important cohort with specific challenges of care and familiarity with management including the use of mechanical CPR devices, temperature optimization, MCS use and pharmacotherapy issues are critical to successful outcomes.

Cerebrovascular accident (CVA) is one of the leading causes of death in the United States. Von Willebrand factor plays an important role in platelet activation and adhesion. It remains unclear whether Von Willebrand disease (vWD) is associated with a decreased risk of developing CVA. The study aimed to compare the relative risk (RR) of CVA in patients with and without vWD. We queried the National Inpatient Sample from 2009 to 2014 for discharge data and records for vWD and CVA using International Classification of Diseases, Ninth-Revision codes. The unadjusted and adjusted RR of CVA in patients with and without vWD were estimated using log-binomial model. Descriptive measures including means, medians, standard deviations, and range were presented based on normality test of continuous data. The prevalence of CVA was lower in patients with vWD than in those without vWD (1.31% vs 2.04%), with a RR of 0.64 (95% confidence interval (CI): 0.60–0.68). After adjusting for common CVA risk factors, the RR remained lower in vWD patients: 0.81 (95% CI: 0.76–0.86). vWD is associated with a lower RR of developing CVA. This suggests that deficiency of Von Willebrand factor is potentially protective against the development of CVA. To the best of our knowledge, this is the first study in humans to compare the RR of CVA in patients with and without vWD. Future studies are needed to explore causal relationships and therapeutic benefits.