Aimen Shafiq

A patent foramen ovale (PFO) is present in approximately 25% of the general population. Its clinical significance is primarily in patients with cryptogenic stroke. Randomized trials have evaluated whether transcatheter PFO closure reduces recurrent stroke compared to medical therapy. Evidence outside stroke, including migraine, decompression illness, and platypneaorthodeoxia syndrome, is limited. We reviewed major randomized controlled trials and extended follow-up studies evaluating transcatheter PFO closure in patients with cryptogenic stroke. Key trials included RESPECT, REDUCE, CLOSE, DEFENSEPFO, and RESPECTLate. Study populations, procedural outcomes, and post-procedural management were summarized. Non-stroke indications were evaluated using available randomized and observational data. In the RESPECT trial (n=980; mean age 46±11 years; 38% female; median follow-up 5.9 years), recurrent ischemic stroke occurred in 3.6% of patients undergoing PFO closure vs 5.8% with medical therapy (HR 0.55; 95% CI, 0.31–0.999; p=0.046). The REDUCE trial (n=664; mean age 45±10 years; 42% female) demonstrated a 77% relative risk reduction in recurrent stroke with closure vs antiplatelet therapy alone (1.4% vs 5.4%; p=0.002). The CLOSE trial (n=663; mean age 45±11 years; 40% female) reported no recurrent strokes in the closure group vs 14 events (6%) in the anti-platelet group over 5.3 years (p<0.001). DEFENSEPFO (n=120; mean age 52±12 years; 45% female) showed stroke in 0% vs 12.9% with medical therapy at 2 years (p=0.013). RESPECTLate demonstrated sustained benefit over 10 years (HR 0.54; 95% CI, 0.29–0.999; p=0.046). Pooled analysis across trials indicated a 59% lower risk of recurrent stroke with closure (HR 0.41; 95% CI, 0.200.83). The benefit was most pronounced in patients with large shunts or atrial septal aneurysms. Post-procedural atrial fibrillation occurred in 35% of patients; serious procedural complications were <2%. Dual antiplatelet therapy was administered for 3–6 months, and successful shunt elimination exceeded 90%. Evidence for PFO closure in migraine with aura or decompression illness remains limited; closure in platypneaorthodeoxia syndrome shows symptomatic improvement based on small case series. Transcatheter PFO closure significantly reduces recurrent stroke in adults aged 1860 years with cryptogenic stroke and highrisk anatomical features. The procedure is generally safe, with low rates of serious complications. Nonstroke indications remain investigational, and patient selection with multidisciplinary evaluation is essential to maximize benefit and minimize risk.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly nonalcoholic fatty liver disease, is the most prevalent chronic liver disease worldwide, affecting more than 30% of adults and up to 70–90% of individuals with obesity or type 2 diabetes mellitus. Cardiovascular disease (CVD) represents the leading cause of mortality in this population. MASLD is increasingly recognized as an independent cardiovascular risk factor beyond traditional metabolic comorbidities. This narrative review summarizes epidemiologic, mechanistic, and clinical evidence linking MASLD with cardiovascular disease, with a focus on population-based cohort studies, imaging-based assessments of subclinical cardiovascular disease, and fibrosis-based risk stratification. Population-based cohorts, including the Framingham Heart Study and the Multi-Ethnic Study of Atherosclerosis, demonstrate that hepatic steatosis is associated with a 1.5–2.0-fold increased risk of incident cardiovascular events after adjustment for age, sex, body mass index, diabetes, and lipid levels. MASLD is characterized by insulin resistance, increased visceral adiposity, atherogenic dyslipidemia with elevated triglycerides, small dense low-density lipoprotein particles, and reduced high-density lipoprotein cholesterol. Patients exhibit systemic low-grade inflammation with elevated tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein, alongside altered adipokine and hepatokine signaling, including reduced adiponectin and increased leptin, resistin, fetuin-A, and fibroblast growth factor 21. Imaging studies identify higher carotid intima–media thickness, increased coronary artery calcium scores, and early left ventricular diastolic dysfunction in patients with MASLD compared with controls. Fibrosis stage has emerged as the strongest hepatic predictor of cardiovascular outcomes. Individuals with advanced fibrosis have significantly higher rates of cardiovascular events and mortality compared with those without fibrosis, independent of traditional risk factors. Emerging data also implicate gut–liver axis dysfunction and increased intestinal permeability in amplifying systemic inflammation and vascular injury. MASLD is closely linked to cardiovascular disease through shared metabolic, inflammatory, and fibrotic pathways. Cardiovascular risk in MASLD is driven primarily by fibrosis severity rather than steatosis burden. Incorporation of liver disease assessment, particularly fibrosis evaluation, into cardiovascular risk stratification may improve identification of high-risk individuals and support integrated cardiometabolic care.

Asymptomatic severe aortic stenosis (AS) has traditionally been managed with watchful waiting because of low annual sudden death rates (<1%) and concerns regarding procedural risk. Emerging randomized data indicate that irreversible myocardial injury may occur before symptom onset and that early aortic valve replacement (AVR) may improve outcomes. This review summarizes evidence from contemporary randomized controlled trials evaluating early surgical AVR (SAVR) or transcatheter AVR (TAVR) vs conservative management or surveillance in asymptomatic patients with severe AS and preserved left ventricular ejection fraction (LVEF). The RECOVERY trial randomized 145 asymptomatic patients with very severe AS (mean age 64 years) to early SAVR or conservative care. Over a median follow-up of 6.2 years, all-cause mortality occurred in 1% of the early surgery group vs 15% with conservative management (hazard ratio [HR] 0.09; 95% CI 0.01-0.67; p=0.003). The AVATAR trial included 157 asymptomatic patients with severe AS, preserved LVEF, and negative exercise testing (mean age approximately 67 years). Over a median follow-up of 32 months, the composite endpoint of all-cause death, myocardial infarction, stroke, or heart failure hospitalization occurred in 16.6% of patients assigned to early surgery compared with 32.9% in the conservative group (HR 0.46; 95% CI 0.23-0.90; p=0.02). The EARLY TAVR trial randomized 901 asymptomatic patients with severe AS and preserved LVEF to TAVR or clinical surveillance (mean age 75.8 years). After a median follow-up of 3.8 years, the primary composite outcome of death, stroke, or unplanned cardiovascular hospitalization occurred in 26.8% of the TAVR group versus 45.3% of the surveillance group (HR 0.50; 95% CI 0.40-0.63; p<0.001). Cardiovascular hospitalizations occurred in 20.9% vs 41.7%, all-cause mortality in 8.4% vs 9.2%, and stroke in 4.2% vs 6.7%, with no excess procedural complications in the early TAVR group. Randomized evidence demonstrates that early AVR, including both SAVR and TAVR, reduces mortality and major cardiovascular events in carefully selected asymptomatic patients with severe AS. The integration of clinical features with risk stratification tools, such as global longitudinal strain, cardiac magnetic resonance imaging, natriuretic peptides, and computed tomography-based valve calcification, supports timely intervention before irreversible myocardial damage occurs.

Background: Mechanical circulatory support (MCS) is critical in the management of cardiogenic shock (CS) complicating acute myocardial infarction (AMI), but racial/ethnic disparities in MCS utilization remain understudied. Methods: We extracted data from the National Inpatient Sample database for the years 2018 to 2020. Patients aged ≥18 years with AMI and CS listed as primary or secondary diagnosis were identified using ICD-10-CM. The primary outcome was in-hospital mortality. Secondary outcomes included MCS utilization, hospital length of stay (LOS), total hospital charges, acute kidney injury (AKI)/hemodialysis, and sepsis. Multivariable logistic and linear regression models were used to assess associations between race/ethnicity and in-hospital outcomes. Results: Among 89 125 hospitalizations for AMI and CS, Hispanics had lower in-hospital mortality than Whites (OR 0.86; 95% CI, 0.76–0.96). The MCS use was higher among Asians or Pacific Islanders (OR 1.35; 95% CI, 1.14–1.60) and Hispanics (OR 1.15; 95% CI, 1.01–1.30) than among Whites. Hispanics had longer LOS ( β = 1.3 days; 95% CI, 0.78–1.7), whereas Blacks had shorter stays ( β = −0.50 days; 95% CI,−0.91 to −0.10) than Whites. The rates of AKI/hemodialysis were higher among Hispanics (OR 1.26; 95% CI, 1.12–1.42), Blacks (OR 1.59; 95% CI, 1.40–1.79), and Asians or Pacific Islanders (OR 1.39; 95% CI, 1.18–1.64) than Whites. Sepsis rate was greater among Hispanics (OR 1.18; 95% CI, 1.04–1.34). Total hospital charges were higher among Hispanics ($53 770; 95% CI, $39 307–$68 233) and Asians or Pacific Islanders ($33 737; 95% CI, $8954–$58 520), than Whites. Conclusion: Racial and ethnic disparities in MCS use and clinical outcomes persist among patients with AMI and CS.

Background: Due to neurohormonal disturbances that occur following brain death, thyroid hormone therapy has been proposed as a means to enhance cardiac function in brain-dead organ donors. However, it remains unclear whether thyroid hormone administration improves clinical outcomes in potential heart donors. Methods: A comprehensive review of clinical trials was conducted to evaluate the impact of thyroid hormone therapy on heart viability and transplantation outcomes. A total of nine randomized controlled trials (RCTs) involving 1189 potential heart donors were included. Results: Thyroid hormone supplementation effectively restored circulating thyroid hormone levels in brain-dead donors. However, findings regarding improvements in cardiac function and transplantation outcomes were inconsistent across studies. While some RCTs reported marginal improvements in hemodynamic parameters and heart transplant viability, these results were not consistently replicated. Furthermore, most studies did not demonstrate a significant enhancement in recipient survival or graft function associated with thyroid hormone therapy. Conclusion: Although thyroid hormone therapy restores thyroid hormone levels in brain-dead donors, current evidence does not consistently support its effectiveness in improving donor heart viability or recipient outcomes. Further research is necessary to clarify the role of thyroid hormone therapy in donor management and its impact on long-term transplant success.

Background: Surgical aortic valve replacement (SAVR) is the commonly used approach for aortic valve replacement (AVR) in patients with aortic stenosis at low or intermediate surgical risk. However, transcatheter aortic valve replacement (TAVR) has emerged as an alternative to SAVR for AVR. This meta-analysis aims to assess the comparative efficacy and safety of TAVR versus SAVR in low-to-intermediate surgical risk patients by analyzing temporal trends in the outcomes of TAVR and SAVR at various follow-up intervals, providing a more detailed understanding. Methods: A thorough literature search was performed across PubMed/MEDLINE, Embase, and the Cochrane Library from their inception up to May 2024 to identify eligible randomized controlled trials (RCTs). Clinical outcomes were evaluated using a random-effects model to pool risk ratios (RRs) with 95% CIs. Results: A total of 17 studies reporting data at different follow-ups for nine trials were included (n=9092). No statistically significant difference was observed between TAVR and SAVR for reducing all-cause death at 30 days, 1 year, and 2 years but significantly increased risk with TAVR at 5 years or longer follow-up (RR=1.13, 95% CI: 1.03–1.23). However, TAVR was associated with a significantly decreased risk for cardiac death at 1-year follow-up (RR=0.79, 95% CI: 0.64–0.96) and comparable risk for cardiac death at 30 days, 2 years, and 5 years or longer follow-up when compared with SAVR. No statistically significant difference was observed between TAVR and SAVR for reducing the risk of myocardial infarction (MI) at 30 days, 1 year, 2 years, and 5 years or longer follow-up. TAVR was associated with a significantly lower risk of major bleeding events at 30 days (RR=0.38, 95% CI: 0.21–0.67); lower risk of acute kidney injury (AKI) at 30 days (RR=0.38, 95% CI: 0.26–0.54) and 1 year (RR=0.58, 95% CI: 0.41–0.82) and lower risk of new onset or worsening atrial fibrillation (AF) at 30 days (RR=0.25, 95% CI: 0.18–0.34), 1 year (RR=0.26, 95% CI: 0.16–0.41) and 2 years (RR=0.32, 95% CI: 0.20–0.49) when compared with SAVR. However, TAVR was associated with a significantly increased risk of permanent pacemaker implantation (PPI) at 30 days (RR: 2.62, 95% CI: 1.40–4.91), at 1 year (RR: 2.19, 95% CI: 1.24–3.87), at 2 years (RR: 2.74, 95% CI: 1.31–5.71), and beyond 5 years (RR: 1.95, 95% CI: 1.20–3.15). TAVR was also associated with a significantly increased risk of prosthetic valve thrombosis at 2 years (RR=2.70, 95% CI: 1.08–6.71), though no significant association was observed at 30 days, 1 year, or 5 years. Similarly, no significant differences were observed in aortic-valve reintervention rates at 30 days, 2 years, or 5 years, but TAVR showed a significantly increased risk at 1 year (RR=1.98, 95% CI: 1.21–3.24). TAVR was associated with a significantly increased risk of major vascular complications at 30 days (RR=2.37, 95% CI: 1.38–4.04) and a significantly increased risk of TIA at 2 years (RR: 1.43, 95% CI: 1.02–2.00, I ²=0%). The risk of hospitalizations was comparable between the groups. Conclusion: TAVR and SAVR demonstrated comparable rates of all-cause death up to 2 years of follow-up. However, at 5 years or longer follow-up, TAVR was associated with a higher risk of all-cause death. While TAVR showed certain procedural advantages, such as a lower risk of major bleeding, AKI, and new-onset or worsening AF, the choice between TAVR and SAVR in patients with low or intermediate surgical risk should consider long-term outcomes, with SAVR potentially being more favorable due to better survival observed on longer follow-up durations.

Background: Recent studies have focused on treating cardiac sarcoidosis (CS) with corticosteroids primarily mitigating symptoms and reducing the risk of mortality and other cardiovascular complications. A promising new treatment approach involves tumor necrosis factor (TNF) alpha inhibitors. Methodology: A systematic search was conducted on PubMed, the Cochrane Library, and Elsevier’s Science Direct databases to identify studies comparing TNF alpha inhibitors with other drugs in CS patients who had heart failure. The analyses were conducted using the random-effects model. Results: The study’s primary outcome is an increase in ejection fraction (EF), secondary outcomes include a reduction in the dose of prednisone at 6 and 12 months, maximum standardized uptake value by cardiac tissue, and fluorodeoxyglucose uptake by cardiac myocytes on positron emission tomography scan. The total number of pooled participants was 154 out of which 140 met the Heart Rhythm Society criteria for CS. The pooled analysis showed that treatment with the TNF alpha inhibitors was associated with a significant increase in EF [weighted mean difference (WMD), 46.272; 95% confidence interval (CI), 40.60–51.94, P < 0.001; I ², 75.74%], reduction in the dose of prednisone at 6 months (WMD, 9.20; 95% CI, 7.65–10.75; P < 0.001; I ², 13.33%) and at 12 months (WMD, 6.40; 95% CI, 4.74–8.07; P < 0.001; I ², 9.37%); decrease in myocardial maximum standardized uptake value (WMD, 1.99; 95% CI, 0.91–3.06; P < 0.001; I ²: 97%) and reduction in fluorodeoxyglucose uptake by cardiac myocytes (WMD, 1.55; 95% CI, 1.09–2.00; P < 0.001; I ², 32.29) on positron emission tomography scans. Conclusions: The research findings suggest that TNF alpha inhibitors improve EF, reduce required steroid dosage, and improve clinical outcomes. Nonetheless, further high-quality randomized controlled trials with large sample sizes are needed to assess other impacts of this therapy on patients with CS.

T cell lymphoma, a type of non-Hodgkin lymphomas is a rare form of malignancy with poor outcomes.