Standard Therapy Research Articles

Introduction: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a class of medications that reduce blood glucose levels by inhibiting glucose reabsorption in the proximal convoluted tubules of nephrons to promote glucose excretion. These agents have demonstrated cardioprotective and renoprotective effects, particularly in heart failure and chronic kidney disease (CKD), respectively. However, they are not currently considered standard therapy for patients following myocardial infarction (MI). In this study, we hypothesize that the addition of SGLT2i to standard post-MI therapy reduces mortality in patients with a history of MI and advanced CKD (stages IV or V), despite concerns that SGLT2i are less effective at the low eGFR levels seen in late-stage CKD. Methods: We conducted a retrospective cohort study using de-identified patient data from the TriNetX platform, a global electronic health record (EHR) database comprising 120 healthcare systems worldwide. Two cohorts were established: Cohort A, including patients with a history of MI and stage IV or V CKD who were not taking an SGLT2i, and Cohort B, including similar patients who were taking an SGLT2i in addition to standard post-MI therapy. Propensity score matching was applied to balance baseline comorbidities between cohorts, including hypertension, hyperlipidemia, dyslipidemia, obesity, diabetes, and tobacco use. Results: The five-year mortality rate among patients with prior MI and stage IV or V CKD not receiving an SGLT2i was 33.02% (N=13,637; 4,503 deaths), compared to 21.05% (N=13,632; 2,870 deaths) in those receiving an SGLT2i (P<0.0001; 95% CI [10.92%, 12.01%]; absolute risk difference: 11.97%). The risk ratio was 1.57 (95% CI [1.51, 1.63]), and the odds ratio was 1.85 (95% CI [1.75, 1.95]). Conclusion: This study found a significant reduction in five-year mortality among patients with prior MI and stage IV or V CKD who received SGLT2i in addition to standard post-MI therapy, which includes ACE inhibitors/ARBs, beta-blockers, antiplatelet agents, and high-intensity statins. Although SGLT2i are often avoided in advanced CKD due to perceived diminished efficacy at low eGFR levels, our retrospective analysis of EHR data suggests a novel role for these medications in post-MI management among patients with late-stage CKD. While these findings are promising, they are limited by the retrospective nature of the analysis, and should be confirmed with prospective trials.

Background: Transthyretin Amyloid Cardiomyopathy (ATTR-CM) is a progressive, infiltrative disease caused by deposition of misfolded transthyretin (TTR) amyloid fibrils in the myocardium. TTR-targeted therapies, including TTR stabilizers and gene silencers, have shown clinical benefit in randomized clinical trials. However, data on cardiovascular outcomes associated with these therapies in real-world settings remain limited. Methods: This retrospective cohort study utilized electronic health record data from the TriNetX Research Network (2019–2025). Adults with a diagnosis of ATTR-CM were categorized into three groups based on prescription records: TTR stabilizers (e.g., tafamidis, acoramidis), TTR gene silencers (e.g., vutrisiran, eplontersen, patisiran, inotersen), or standard medical therapy. The primary outcome was a composite of ventricular tachycardia (VT), ventricular fibrillation (VF), cardiac arrest, or all-cause mortality. Cox proportional hazards models with inverse probability weighting (IPW) were used to estimate adjusted associations. Results: Among 10,888 patients with ATTR-CM (34.8% female; median age 73 years [IQR 64–80]), 4,301 received a TTR stabilizer, 356 received a TTR gene silencer, and 6,231 were managed with standard therapy. In adjusted analyses using IPW, TTR stabilizer use was associated with a lower risk of the composite outcome compared with standard therapy (HR = 0.81; 95% CI: 0.72–0.92; p = 0.001). A non-significant association was observed for TTR gene silencers relative to standard therapy (HR = 0.81; 95% CI: 0.59–1.12; p = 0.205). (Table 1, Figure 1) Conclusions: In this large, real-world analysis of patients with ATTR-CM, use of TTR stabilizers was associated with a lower incidence of major cardiovascular events compared with standard care. TTR gene silencers showed a similar directional association, though limited by a smaller sample size. These findings support further investigation in prospective studies to better understand the relationship between TTR-targeted therapies and clinical outcomes.

Background: Hypertrophic obstructive cardiomyopathy (HOCM) is usually treated with standard therapy: beta-blockers (BBs) and/or non-dihydropyridine calcium channel blockers (CCBs). Mavacamten, a selective cardiac myosin inhibitor, has shown efficacy in improving functional status and reducing obstruction. Research Question: Does the addition of Mavacamten to standard therapy with calcium channel blockers and beta-blockers improve functional status and reduce mortality in patients with HOCM? Aims: The aim of this study was to assess the efficacy of Mavacamten plus standard therapy versus standard therapy alone in improving functional status and reducing mortality in HOCM patients. Methods: This retrospective cohort analysis used the TriNetX database to compare adult patients who were prescribed mavacamten plus standard therapy (CCBs and/or BBs) after being diagnosed with HOCM (intervention group), while the control group included patients treated with standard therapy alone. A 1:1 propensity score-matched (PSM) analysis controlled for 76 baseline demographic and clinical characteristics. Outcomes were analyzed over a 365-day period post-index date and were assessed through the odds ratio (OR) and 95% confidence interval (CI) Results: The intervention group included 405 patients, while the control group included 15,871. After PSM, 381 patients were included in each group; 59.3% and 62.2% were female, respectively. The mean age was 62.6 (SD ± 14.4) and 63.9 (SD ± 16) years, respectively. The addition of mavacamten was associated with a significant reduction in all-cause hospitalizations (OR 0.583, CI 0.433-0.787, P < .0001), emergency hospitalizations (OR 0.669, CI 0.467-0.961, P = 0.029), cardiac-related hemodynamic instability (OR 0.433, CI 0.269-0.696, P < .0001), and acute myocardial infarction (OR 0.266, CI 0.130-0.546, P < .0001), and enhanced left ventricular ejection fraction (LVEF > 50%) (OR 2.680, CI 1.703-4.217, P < .0001). Other analyzed outcomes, such as mortality, new-onset systolic or diastolic heart failure, were comparable between the two groups Conclusion: Mavacamten plus CCBs/BBs reduced hospitalizations, improved cardiac biomarkers, and showed favorable trends in mortality and heart failure, supporting its use in clinical practice and the need for long-term studies.

Background: Vericiguat, a soluble guanylate-cyclase stimulator, has been shown in randomized trials to reduce the composite risk of cardiovascular death or heart-failure hospitalization. Its broader effect on major adverse cardiovascular events (MACE) and arrhythmia in routine practice, however, remains uncertain. Research Question: Among adults with heart failure with reduced ejection fraction (HFrEF), does initiating vericiguat alter one-year risks of MACE, malignant ventricular arrhythmia, and all-cause mortality compared with standard therapy? Methods: Using the TriNetX Global Collaborative Network, we identified adults with HFrEF between 2021 and 2024. Patients who received vericiguat formed the exposure cohort; those without vericiguat exposure served as comparators. One-to-one propensity-score matching balanced demographics, comorbidities, concomitant medications (including guideline-directed medical therapies for heart failure), and laboratory values, yielding 1,397 patients per group. Outcomes were assessed from the day after the index date through 12 months of follow-up. The primary endpoint was MACE—a composite of acute myocardial infarction, stroke, pulmonary embolism, cardiac arrest, and acute systolic heart-failure decompensation. Secondary endpoints were incident malignant ventricular arrhythmia (ventricular fibrillation or flutter) and all-cause mortality. Hazard ratios with 95 % confidence intervals were computed. Results: A total of 2,794 matched patients (1,397 per group) were analyzed. Median follow-up was 357 days in the vericiguat cohort and 321 days in controls. MACE occurred in 23.9 % vs 26.8 % of patients (hazard ratio [HR] 0.83, 95 % confidence interval [CI] 0.71–0.96; p = 0.012). All-cause mortality was 10.5 % vs 10.9 % (HR 0.93, 95 % CI 0.74–1.16; p = 0.50). Malignant ventricular arrhythmia occurred in 1.7 % vs 1.0 % (HR 1.76, 95 % CI 0.89–3.47; p = 0.10). Conclusion: In this large, real-world, propensity-matched HFrEF cohort, vericiguat initiation was associated with a 17 % relative reduction in the hazard of one-year MACE, without a statistically significant reduction in mortality or malignant ventricular arrythmia. These findings support vericiguat as an effective adjunct to guideline-directed therapy for mitigating composite cardiovascular events in HFrEF and highlight the need for prospective studies to confirm its long-term effectiveness and safety.

Introduction: Osimertinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that is crucial in the treatment of EGFR-mutant non-small cell lung cancer (NSCLC). It exerts its effect by selectively binding to mutant EGFR and inhibiting downstream signaling pathways involved in cell proliferation and survival. However, emerging evidence has raised concerns about its potential cardiovascular toxicity. This meta-analysis evaluates the incidence and relative risk of cardiac adverse events in NSCLC patients treated with Osimertinib. Methods: We conducted a comprehensive literature search using MEDLINE and EMBASE databases from inception through May 31st, 2025. Phase III randomized controlled trials (RCTs) utilizing Osimertinib in NSCLC reporting cardiac adverse events were included. The Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR) with a 95% confidence interval (CI). Heterogeneity was assessed with Cochran’s Q-statistic. The random effects model was applied. Results: A total of 2,863 patients from six phase III RCTs (MARIPOSA n=849, LAURA n=216, AURA3 n=415, FLAURA n=556, ADAURA n=680, NCT02959749 n=147) were included in the analysis. QT prolongation of any grade occurred in 4.83% of patients receiving Osimertinib versus 1.50 % in controls (RR 3.32; 95% CI: 2.06-5.34; P<0.00001). High-grade QT prolongation was reported in 1.24% of the Osimertinib group compared to 0.30% of the control group (RR 3.25; 95% CI: 1.16-9.12; P=0.02 ). Any grade of decreased ejection fraction was documented at 2.35 % in the Osimertinib arm versus 1.05 % in the control arm (RR 2.25; 95% CI: 1.23-4.11; P=0.008). The incidence of high-grade cardiac failure in the Osimertinib groups was 1.70% compared to 0.53% in the control groups (RR 3.02; 95% CI: 1.32-6.95; P=0.009). There was no statistically significant difference in the incidence of high-grade decreased ejection fraction (0.85% vs. 0.15%; RR 3.40; 95% CI: 0.95–12.15; P=0.06) and high-grade pericardial effusion (0.33% vs. 0.38%; RR 1.01; 95% CI: 0.31–3.28; P=0.98). Conclusions: This study demonstrated a higher risk of QT prolongation, reduced ejection fraction, and high-grade cardiac failure with Osimertinib versus placebo or other standard therapies, highlighting the need for careful cardiac monitoring for early recognition and intervention to improve quality of life and clinical outcomes.

Background: Ventricular tachycardia (VT) is a life-threatening arrhythmia often seen in patients with structural heart disease. While antiarrhythmic drugs (AADs) have long been standard therapy, catheter ablation has emerged as a preferred treatment strategy. The comparative efficacy and safety of ablation versus AADs as first-line therapy remain uncertain. Methods: A systematic literature search was conducted across multiple databases, including PubMed, Embase, and Web of Science, to identify randomized controlled trials (RCTs) comparing catheter ablation to AAD therapy in adults with structural heart disease and sustained ventricular tachycardia. The primary outcome was VT reoccurrence. Secondary outcomes included all-cause mortality, VT storm, hospitalizations, and major adverse cardiovascular events (MACE). Results: Six randomized controlled trials were selected comprising 1,072 patients that met the inclusion criteria. 552 patients were treated with catheter ablation, and 520 received AAD therapy. Antiarrhythmic drugs used were amiodarone, sotalol, mexiletine, and procainamide, with earlier studies using a wide array of therapies and later often using only amiodarone and sotalol. The average follow-up duration was 24.8 months, with an average age of 65 years and approximately 89.5% of male patients. Catheter ablation was associated with a significant reduction in recurrent VT (OR: 0.69; 95% CI: 0.50–0.95; P = 0.02), VT storm (OR: 0.62; 95% CI: 0.47–0.80; P = 0.0003), hospitalizations (OR: 0.74; 95% CI: 0.56–0.98; P = 0.03), and a trend toward reduced MACE (OR: 0.76; 95% CI: 0.54–1.07; P = 0.12). No significant difference was observed in all-cause mortality (OR: 0.91; 95% CI: 0.66–1.26; P = 0.58). Conclusion: Catheter ablation significantly reduces the risk of VT recurrence, VT storm, and hospitalizations compared to AAD therapy in patients with structural heart disease. Although no mortality benefit was observed, these findings support catheter ablation as a potentially superior initial strategy for VT management in this population. More high-quality studies are warranted to clarify the long-term safety and effectiveness of this procedure.

Background: Kawasaki disease (KD) is the leading cause of acquired heart disease in children in developed countries. Although IVIG is the standard therapy, ~17% of patients in Japan are IVIG-resistant and at high risk for coronary artery aneurysms (CAAs). No reliable biomarkers currently exist to predict IVIG resistance before treatment. Extracellular vesicles (EVs), especially endothelial microparticles (EMPs), carry miRNAs that reflect vascular inflammation and immune dysregulation. Objective: To develop and validate a diagnostic scoring system using EV-encapsulated miRNAs for early identification of IVIG-resistant KD patients. Methods: Fifty acute KD patients (median age: 37 months; 13 IVIG-resistant) and 50 controls (25 febrile non-KD and 25 healthy children) were enrolled. Serum EVs were isolated by ultracentrifugation and profiled using Affymetrix® GeneChip® miRNA 4.0. Discriminative miRNAs were identified via PLS-DA, VIP scoring, and random forest analysis. A diagnostic score was derived from selected miRNAs and validated internally. In situ hybridization in autopsy tissue confirmed the localization of miRNA. Functional assays in THP-1 monocytes were used to evaluate cytokine induction. Results: EV-miRNA profiles stratified IVIG responders, non-responders, and febrile controls. Two miRNAs— hsa-miR-145-5p and hsa-miR-320a —were enriched in EMPs from KD patients with CAAs and showed endothelial localization. Both miRNAs induced the expression of IL-6 and TNF-α in monocytes. The diagnostic score based on these miRNAs achieved 100% sensitivity and specificity for predicting IVIG resistance, with a cut-off of -0.63. Conclusion: We introduce a novel EV-miRNA-based diagnostic platform that enables early, pre-treatment identification of IVIG-resistant KD patients. This approach supports precision-guided therapy and may reduce coronary complications by enabling timely intervention.

Human metapneumovirus (hMPV) is a well-known paramyxovirus that has primarily been associated with respiratory illness. Extrapulmonary complications, such as pericarditis and pericardial effusion, are exceptionally uncommon. We report a case of hMPV-associated pericarditis in an immunocompetent patient with a solitary kidney, where standard anti-inflammatory therapy was contraindicated. A 77-year-old man with a history of renal oncocytoma status post unilateral nephrectomy presented with six days of exertional dyspnea followed by midsternal chest pain with radiation to the left shoulder. Labs revealed mild leukocytosis, baseline renal dysfunction, elevated NT-proBNP and elevated inflammatory markers. High-sensitivity troponin on three serial measurements remained stable. ECG with ST elevations in multiple leads initially raised suspicion of acute coronary syndrome. Given the pleuritic nature of the pain and a stable low-level troponin elevation, urgent catheterization was deferred. CT pulmonary angiogram was negative for PE but showed a pericardial effusion. Transthoracic echocardiogram confirmed small to moderate circumferential pericardial effusion without tamponade physiology. A respiratory viral PCR returned positive for hMPV infection. Though the patient developed acute atrial fibrillation with rapid ventricular response, he remained hemodynamically stable and did not meet criteria for pericardiocentesis. After nephrology and cardiology consultation, NSAIDs and colchicine were avoided due to renal risk. He was initiated on high-dose aspirin and experienced symptomatic improvement after only 4 doses. He was discharged in stable condition with a plan for two-week taper and outpatient follow-up. While viral pericarditis is not uncommon, hMPV is rarely identified as the causative agent. A literature review reveals only a handful of reported cases of hMPV-induced pericarditis, with even fewer occurring in the context of impaired renal reserve. This case underscores the importance of including hMPV in the differential diagnosis of viral pericarditis. It also highlights a critical management challenge: while NSAIDs and colchicine remain first-line therapies for pericarditis, renal dysfunction may preclude their use and necessitate alternative treatment strategies. Our patient achieved clinical improvement with aspirin monotherapy alone, demonstrating its potential utility in patients with contraindications to standard therapy.

Background: Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is a rare autoinflammatory condition associated with recurrent episodes of fever, chest pain, and serositis responsive to anti-inflammatory therapies. We present a case of COVID-induced TRAPS with clinical and radiographic resolution of coronary microvascular dysfunction (CMD) from anti-interleukin-1 (IL-1) treatment. Case: A previously healthy 40-year-old male marathon runner developed COVID infection in 2022 followed by recurrent episodes of fevers, myalgias, and arthralgias. In March 2023, rheumatology diagnosed him with an unspecified autoinflammatory disorder due to elevated inflammatory markers with a negative infectious and autoimmune workup. He had mild relief with prednisone and hydroxychloroquine but then developed dyspnea and chest pain in July 2023. Echocardiogram showed a newly reduced ejection fraction to 35-40%. Stress cardiac magnetic resonance imaging (cMRI) revealed a localized perfusion defect concerning for ischemia with globally abnormal stress perfusion curves suggestive of multivessel obstructive epicardial diseases versus CMD. Coronary angiogram revealed only luminal irregularities. Cardiac positron emission tomography (cPET) findings were consistent with CMD. Given the patient's refractoriness to antianginal and anti-inflammatory therapies with TRAPS phenotype, he was initiated on anakinra, an IL-1 receptor antagonist. His angina resolved within 1 month, as well as normalization of myocardial perfusion on cPET and cMRI at 3 and 4 months, respectively. Discussion: Due to the patient’s angina and new cardiomyopathy in the setting of a prior viral infection, a stress cMRI was pursued to evaluate for inflammatory and ischemic etiologies; findings were concerning for ischemia. cPET raised the likelihood of CMD given the absence of obstructive disease on the coronary angiogram. The patient met clinical criteria for TRAPS, likely triggered by COVID infection, with angina refractory to standard medical therapy, so he was trialed on anakinra with remarkable clinical response and radiographic evidence of CMD resolution. Conclusion: TRAPS is due to an enhanced inflammatory response that can be triggered by viral infections, but, to date, no known cases have been reported of COVID-induced TRAPS in adults. TRAPS can cause chronic inflammation that predisposes individuals to CMD with resultant angina, which can be treated by targeting the systemic inflammation.

Background: Sacubitril/valsartan (Sac/Val) has been shown to reduce N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with acute heart failure (AHF), yet the therapeutic response may differ according to underlying cardiac phenotype. Hypothesis: We hypothesized that specific baseline echocardiographic parameters may modify the NT-proBNP-lowering effect of Sac/Val in this population. Aims: This study aimed to explore whether baseline echocardiographic markers could identify patients with AHF, who will experience greater reductions in NT-proBNP following Sac/Val therapy. Methods: This was a sub-analysis of the multicenter, physician-initiated, prospective, randomized, open-label PREMIER study (NCT05164653), in which the clinical effects of early initiation of Sac/Val, compared to the standard renin-angiotensin system inhibitor therapy (control), were evaluated in Japanese inpatients stabilized after hospitalization for AHF. Participants were stratified according to echocardiographic characteristics at baseline, including LVEDVI, LVESVI, LVMI, LVOT-VTI, E/e′, LAVI, and TRV. The proportional change in geometric mean NT-proBNP from baseline to 8 weeks was compared between the Sac/Val and control groups within each stratum. Results: Among 206 patients with echocardiographic data (median age, 76 years; 31% female; median left ventricular ejection fraction, 39%), 94 were assigned to the sacubitril/valsartan (Sac/Val) group and 112 to the control group. Overall, Sac/Val treatment led to a significantly greater reduction in NT-proBNP than control (group ratio 0.75; 95% CI, 0.60 to 0.93). Among the echocardiography-based subgroups, the treatment effect was more evident in subgroups with elevated LVMI (LVMI ≥123.7 g/m 2 ; group ratio, 0.56; 95% CI, 0.40 to 0.77) and reduced LVOT-VTI (LVOT-VTI <13 cm; group ratio, 0.59; 95% CI, 0.43 to 0.80), compared to each corresponding counterpart (P for interaction = 0.009 and 0.045, respectively) ( Figure ). In contrast, no significant between-group differences in the treatment effect were observed in subgroups stratified by other echocardiographic parameters (all P for interaction >0.1). Conclusions: Baseline LVMI and LVOT-VTI values may help identify the optimal patients who derive greater benefit from early initiation of Sac/Val therapy after an AHF episode, supporting a phenotype-guided approach to individualized treatment in this population.

Case Presentation: A previously healthy 33-year-old woman developed acute pericarditis with early tamponade physiology following a Coxsackievirus B infection contracted from her child. Despite urgent pericardiocentesis (550 mL) and standard anti-inflammatory therapy with NSAIDs and colchicine, she progressed to incessant pericarditis necessitating corticosteroids. Clinical Course and Timeline: Day 1: Initial presentation with tamponade physiology; Coxsackie B serology positive Days 9–10: Escalating NSAID therapy failed to control symptoms Week 2: Prednisone (30 mg/day) initiated with temporary symptom relief Week 3: Relapse during taper, resulting in rehospitalization Week 7: Recurrence despite slow taper to prednisone 5 mg Rilonacept was initiated at week 7 due to persistent steroid dependence. Within 4–6 weeks, the patient achieved complete clinical remission, normalization of inflammatory markers, and resolution of echocardiographic abnormalities. Corticosteroids were successfully discontinued over a 3-month taper while maintaining remission on rilonacept at 21-week follow-up. Discussion: This case underscores the pathophysiological relevance of IL-1β in viral pericarditis. Coxsackievirus infection induces myocardial inflammation via IL-1–mediated cytokine cascades. Traditional steroid dependence—affecting 15-30% of pericarditis patients—represents a major therapeutic challenge with significant morbidity. By acting as a soluble decoy receptor, rilonacept interrupts this pathway, offering a targeted therapeutic strategy beyond traditional broad-spectrum immunosuppression. Key Insights: 1. IL-1–mediated inflammation was a critical driver in disease persistence 2. Steroid dependence emerged despite optimal guideline-directed therapy 3. Rilonacept enabled sustained steroid-free remission Clinical Significance: IL-1 inhibition with rilonacept represents a paradigm shift in managing steroid-refractory pericarditis, especially in virally mediated cases. This case supports the growing role of biologics in cardiac inflammation and raises important questions about earlier IL-1 blockade to preempt steroid dependence. Conclusion: This case illustrates the efficacy of IL-1–targeted therapy in a complex, steroid-dependent pericarditis case and advocates for broader clinical consideration of rilonacept in viral pericarditis. Further investigation is warranted to define optimal timing and patient selection for IL-1 blockade in this setting.

Introduction: Atrial fibrillation(AF) following coronary artery bypass graft is a prevalent complication often occurring 2-4 days postoperatively, characterised by brief asymptomatic episodes. It increases morbidity, hospital stay, risk of stroke and mortality. The pathophysiology involves triggers that act on a susceptible remodelled-atrium. Risk factors include age, heart failure, hypertension and atrial enlargement. Emerging evidence indicates Sodium-Glucose Transport Protein 2 Inhibitors (SGLT2i) like empagliflozin may prevent post-Coronary Artery Bypass Graft Surgery (CABGs) associated AF by reducing sympathetic outflow, atrial remodelling and inflammation. Considering these mechanisms and existing data we have developed this study to assess the potential of SGLT2i in preventing postoperative atrial fibrillation in patients undergoing coronary artery bypass graft. Methodology: The review conducted follows the PRISMA guidelines and major medical databases, which include PUBMED, Google Scholar and Science-Direct, were extensively searched using a comprehensive search term to identify and retrieve available articles. The articles that included the assessment of the efficacy of SGLT2i in the prevention of AF post-CABGs were considered for the final analysis. The data was analysed using the Meta, Metadata and the Metafor packages of R Studio. The Odds Ratio of occurrence of Atrial Fibrillation was assessed as the primary outcome. The Mantel-Haenszel method (Common effect model) and the Inverse variance method (Random effects model) were utilized to analyse the odds ratio. The I^2 test was used to assess the heterogeneity. Results: The review included a total of 4 articles with a standard control and SGLT2i therapy to prevent the occurrence of AF in post-CABGs patients. A total of 6011 patients out of which 2002 patients received SGLT2i therapy and 3998 patients belonged to the control groups. The occurrence of AF was significantly lower in the SGLT2i in comparison to the Control Groups (OR = 0.74, 95% CI [0.64; 0.85], p = 0.2901]. Conclusion: This review highlights the potential of SGLT2 inhibitors in reducing the risk of atrial fibrillation following coronary artery bypass graft surgery. Compared to standard care, patients receiving SGLT2i therapy experienced a significantly lower incidence of postoperative AF. These findings support the growing evidence for the cardioprotective effects of SGLT2 inhibitors, reinforcing their role in post-surgical cardiac care.

Objective: As an integral component of complementary and alternative medicine systems, Traditional Chinese Medicine (TCM) has presented novel therapeutic possibilities for the clinical management of chronic heart failure (HF). This trial investigates the clinical efficacy and safety profile of Xinfuli Granules (XFLG), a Chinese herbal formulation, in patients diagnosed with HF with reduced ejection fraction. Methods: This single-center, randomized controlled trial enrolled 444 HF patients (NT-pro BNP ≥ 450 pg/mL and LVEF ≤ 45%) at Fuwai Hospital between October 2021 and December 2024. Participants were randomized (1:1) to receive either XFLG plus standard care or standard care alone. The primary endpoint was the composite of all-cause mortality and HF-related hospitalization. Secondary outcomes included changes in LVEF, NT-pro BNP, NYHA functional class, Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, TCM syndrome score, Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scores. Results: A total of 356 participants (178 per group) completed the trial, with median ages of 58 years (IQR: 50-67) in the XFLG group and 60 years (IQR: 52.75-69) in controls. At 12 weeks, the XFLG group demonstrated a significantly lower incidence of the primary composite outcome compared to the control group (11.24% vs. 18.54%; HR, 0.566; 95%CI: 0.325-0.988; P =0.042). In secondary endpoint analyses, the XFLG group demonstrated superior improvement in LVEF compared with controls (4% vs 3%; P =0.047). For NT-pro BNP levels, XFLG group showed significantly greater median absolute reductions (413 pg/mL vs 256 pg/mL; P =0.048) and relative reductions (42.02% vs 25.84%; P =0.01). NT-pro BNP reduction (>30%) was achieved by more patients in the XFLG arm (59.5% vs 44.1%; P =0.008). Significant advantages were observed in NYHA class improvement (efficacy rate: 53.8% vs 41.4%, P =0.031) and TCM syndrome scores (efficacy rate: 74.05% vs 37.24%, P <0.001). Quality of life assessments showed marked improvements in the MLHFQ, PHQ-9, and GAD-7 scores (differences: -15 vs -4; -2 vs 0; -1 vs 0 respectively; P <0.001), with comparable safety profiles between groups. Conclusions: XFLG combined with standard HF therapy significantly reduced the risk of all-cause mortality and HF-related hospitalization composite outcome, improved cardiac function, and quality of life, alleviated depressive and anxiety states in HF patients, with a favorable safety profile.

Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that requires effective management strategies to optimize long-term health outcomes. While metformin is the standard first-line therapy, many patients require second-line treatments to achieve adequate glycemic control. Newer drug classes, such as Sodium-Glucose Cotransporter-2 (SGLT-2) inhibitors and Glucagon-Like Peptide-1 (GLP-1) receptor agonists (RA), offer better and more physiologic control of blood sugar along with added cardiovascular benefits. Still, their cost-effectiveness remains uncertain compared to traditional therapies. Objective: This study uses Markov modeling and microsimulation approach to evaluate the long-term health outcomes, costs, and cost-effectiveness of SGLT-2 inhibitors, GLP1 RAs, and traditional second-line therapies. Methods: A Markov model using TreeAge Pro software was constructed to simulate T2DM progression over a 40-year horizon, incorporating transitions between key health states: no history of cardiovascular disease (CVD), history of CVD, and death. Cost effectiveness analysis (CEA) was performed with a willingness-to-pay (WTP) threshold of $100,000 per quality-adjusted life year (QALY). Microsimulation and sensitivity analyses assessed the robustness of findings. Results: The analysis provides insights into the comparative cost-effectiveness of SGLT2 inhibitors and GLP-1 RAs versus traditional second-line therapies. Our findings indicate that while newer therapies offer substantial cardiovascular benefits, their cost effectiveness depends on drug pricing and other parameters. Using the current estimated costs and a WTP of $100,000, neither of the new medicines are cost-effective compared to traditional medicines. Conclusion: The present study highlights the importance of economic evaluation in selecting second-line therapies for T2DM. The results of our analyses could help formulate future healthcare decision-making and policy development to optimize patient outcomes while managing healthcare costs effectively.

Background: The optimal management of minor ischemic stroke without clearly disabling neurologic deficits remains controversial. Despite the widespread use of intravenous thrombolytic agents in acute ischemic stroke, their role in patients presenting with minor, non-disabling symptoms (National Institutes of Health Stroke Scale [NIHSS] score ≤5) is unclear. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing intravenous thrombolysis with standard antithrombotic therapy without thrombolysis in patients with minor non-disabling ischemic stroke (NIHSS ≤5) through May 2025. The review protocol was registered in PROSPERO (CRD420251064220). The primary efficacy outcome was excellent functional recovery, defined as modified Rankin Scale (mRS) score 0–1 at 90 days. Secondary efficacy outcomes included functional independence (mRS 0–2) and all-cause death at 90 days. The primary safety outcome was symptomatic intracranial hemorrhage (sICH) within 36 hours of intervention. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using a random-effects model. Results: A total of five RCTs involving 3,391 patients were included (mean age, 65.8±11.2 years, 36.5% female). Three trials used alteplase (PRISMS, ARAMIS, MINOR), one tenecteplase (TEMPO-2), and one prourokinase (PUMICE). Pooled analysis showed that compared with no thrombolysis, thrombolysis was associated with a lower likelihood of excellent functional outcome (mRS 0–1) (83.0% vs. 85.3%; OR 0.83, 95% CI 0.69–1.00) and functional independence (mRS 0–2) (90.3% vs. 92.8%; OR 0.71, 95% CI 0.55–0.91). Thrombolysis, compared with no thrombolysis, was also associated with higher rates of all-cause mortality (2.5% vs. 1.0%; OR 2.36, 95% CI 1.33–4.19) and sICH (1.3% vs. 0.2%; OR 4.97, 95% CI 1.77–13.96) (Figure). Conclusion: In patients with minor non-disabling ischemic stroke, thrombolysis was associated with significantly worse clinical outcomes, including reduced functional recovery, higher risk of sICH, and increased mortality. These findings argue against the routine use of thrombolysis in this patient population.

Background: Chronic refractory edema in the lower extremities is a disabling condition characterized by persistent swelling and venous stasis skin changes, despite standard conservative therapies. Research Question: What are the underlying etiologies of chronic refractory lower extremity edema, and how effective is a structured, integrated diagnostic protocol in improving etiologic classification and guiding targeted management? Study Design and Methods: This was a single-center, retrospective analysis of 58 prospectively enrolled patients with chronic, refractory lower extremity edema persisting for ≥1 year, all of whom underwent a standardized diagnostic protocol. Superficial and deep venous insufficiency were assessed using duplex ultrasonography with reflux testing. Central venous anatomy was evaluated with iliocaval ultrasonography to detect potential obstructions in the inferior vena cava or iliac veins. Right heart catheterization was performed to assess for pulmonary hypertension, a possible contributor to chronic venous hypertension in the lower extremities. Iliocaval venography and intravascular ultrasound were employed to confirm or exclude obstructive pathology of the central veins. Right heart catheterization and invasive venous assessments were conducted concurrently. Etiologies were categorized as cardiopulmonary (pulmonary hypertension [PH]), central (non-thrombotic iliac vein lesion [NIVL]), peripheral (superficial venous insufficiency [SVI]), or multifactorial. Results: Of the 58 patients, 51.7% had a single identifiable etiology, while 41.4% had multifactorial causes. Non-thrombotic iliac vein lesion (NIVL) was the most common etiology, identified in 55.2% of cases, followed by pulmonary hypertension (PH) in 48.3%, and superficial venous insufficiency (SVI) in 43.1%. Among patients with multifactorial etiologies, NIVL frequently coexisted with either PH or SVI. Unknown etiology, not attributable to any of the specified categories (NIVL, PH, or SVI), was identified in 6.7% of patients. Endovascular intervention for iliocaval obstruction (n = 23) and venous ablation for isolated SVI (n = 10) led to sustained clinical improvement, with no recurrence or procedural complications observed during follow-up. Interpretation: This pathophysiology-based diagnostic algorithm enabled accurate etiologic classification and informed individualized treatment strategies for patients with chronic refractory edema and chronic venous skin changes of the lower extremities.

Malignant brain tumors are a highly complex and heterogeneous group of neoplasms, with glioblastoma being the most aggressive and treatment-resistant form. Standard therapies remain insufficient, largely due to poor drug penetration across the blood-brain barrier and tumor heterogeneity. Lipid-based nanoemulsions have emerged as promising nanocarriers capable of enhancing drug solubility, protecting unstable compounds, and facilitating targeted delivery across the blood-brain barrier. This scoping review analyzed 19 studies focused on lipid-based nanoemulsions for brain tumor therapy, particularly those incorporating synthetic drugs, natural compounds, and nucleic acids. Key formulation strategies, preparation methods, and physicochemical characteristics were outlined. The majority of studies demonstrated in vitro cytotoxicity against rat C6 and human U87MG glioma cell lines. Particularly, nanoemulsions loaded with temozolomide, and siRNA targeting CD73 reduced tumor growth in glioma-bearing rats, especially via nasal administration. Natural products such as kaempferol and honokiol also showed antiglioma effects in vitro when delivered through nanoemulsions. These findings highlight the potential of nanoemulsions in neuro-oncology, particularly for noninvasive nose-to-brain delivery and gene silencing therapies. Further research is needed to standardize formulations and validate their efficacy and safety in clinical settings.

Introduction: Cardiogenic shock is a life-threatening complication of decompensated heart failure, with elevated in-hospital mortality rates despite advances in treatment. Pulmonary artery catheterization (PAC) provides detailed hemodynamic data that may guide therapy in shock states, yet its routine use has declined following neutral trials in broader heart failure populations. The benefit of PAC in patients with cardiogenic shock remains uncertain. Research question: In patients with cardiogenic shock, does the use of pulmonary artery catheter compared to standard therapy reduce in-hospital mortality? Methods: We conducted a systematic review and meta-analysis including both observational studies and randomized controlled trials that compared the use of PAC versus no PAC in patients with cardiogenic shock. A comprehensive search was carried out in PubMed, Scopus, Cochrane CENTRAL, and Web of Science databases. Data were pooled using a random-effects model, and the certainty of the evidence was assessed using the GRADE approach. Primary outcomes included mortality, while secondary outcomes were length of hospital stay and procedure-related complications. Results: Nine studies including over 1.1 million patients with cardiogenic shock were analyzed. PAC was not associated with reduced in-hospital mortality compared to no PAC (RR 1.25, 95% CI 0.62–2.49; p=0.48). No significant differences were found in the use of vasoactive agents (RR 1.12, 95% CI 0.94–1.34; p=0.13), renal replacement therapy (RR 1.06, 95% CI 0.25–4.53; p=0.90), intra-aortic balloon pump (RR 2.00, 95% CI 0.84–4.73; p=0.09), ECMO (RR 1.03, 95% CI 0.40–2.64; p=0.95), or durable ventricular assist device implantation (RR 2.48, 95% CI 0.45–13.70; p=0.21). All outcomes showed high heterogeneity and wide prediction intervals, indicating substantial variability and uncertainty in treatment effects across studies. Conclusion: PAC was not associated with significant benefits in mortality or major clinical endpoints. These findings suggest that PAC use should be individualized, and highlight the need for prospective trials to better define which patients may derive benefit from invasive hemodynamic monitoring.

Background: Tafamidis is the standard therapy for transthyretin cardiac amyloidosis, but the role of adjunctive medications such as SGLT2 inhibitors, mineralocorticoid receptor antagonists, GLP-1 receptor agonists, and sacubitril/valsartan on patient outcomes remains uncertain. Objective: To assess associations between these therapies and clinical outcomes in patients with cardiac amyloidosis receiving tafamidis. Methods: Using the TriNetX Research Network, we conducted a multicenter retrospective cohort study of adults initiating tafamidis from January 2019 to April 2025. Exposure to each drug class within 90 days of tafamidis initiation defined treatment groups. Propensity score matching was used. The primary outcome was all-cause mortality at one and five years. Secondary outcomes included heart failure hospitalization or death, major adverse cardiovascular events (MACE), emergency visits, atrial fibrillation, and acute kidney injury. Results: Among 5,683 patients, SGLT2 inhibitor use was associated with lower mortality at one year (hazard ratio 0.563; 95% confidence interval 0.416–0.762) and five years (hazard ratio 0.615; 95% confidence interval 0.483–0.782), and with lower odds of heart failure hospitalization or death (odds ratio 0.547; 95% confidence interval 0.454–0.659) and MACE (odds ratio 0.704; 95% confidence interval 0.591–0.839) at five years. Sacubitril/valsartan use was associated with fewer emergency visits (odds ratio 0.744; 95% confidence interval 0.575–0.964) and reduced MACE (odds ratio 0.751; 95% confidence interval 0.575–0.981) at five years. Mineralocorticoid receptor antagonist use was linked to higher odds of atrial fibrillation, acute kidney injury, emergency visits, and MACE at both one and five years. GLP-1 receptor agonist use was associated with fewer emergency visits at one year (odds ratio 0.554; 95% confidence interval 0.318–0.965). Conclusions: In patients with cardiac amyloidosis receiving tafamidis, adjunctive use of SGLT2 inhibitors and sacubitril/valsartan was associated with favorable clinical outcomes. Conversely, mineralocorticoid receptor antagonists were linked to increased risks of arrhythmia, renal events, and healthcare utilization.

Background: Heart transplantation (HTx) is the gold standard therapy for refractory class IV NYHA heart failure. While it has been widely observed that donor ejection fraction (EF) at the time of procurement has little to no significant impact on recipient survival, particularly when ischemic time is less than 4-hours, there are few studies which investigate the role of post-transplant EF. Namely, it has not been fully established how serial changes in follow-up EF impact HTx outcomes. Research question: Do serial changes in post-transplant EF impact HTx recipient survival, and if so, which pattern of change has the highest risk of mortality? Goals: Our study seeks to evaluate the role of post-transplant EF changes and its impact on HTx recipient survival. By addressing this gap in knowledge, clinicians may better identify and treat hazardous EF trajectories earlier in their course. Methods: The UNOS thoracic database was analyzed for first-time, isolated orthotopic HTx patients (≥18yrs) between 2000-2023. The absolute difference between EF values at 1- (EF1) and 2-years (EF2) post-HTx was analyzed; patients with missing data in EF1 or EF2 were excluded. Recipients were stratified into 5 groups: severe reduction in EF: <-10% points (n=1403), mild reduction in EF: -5.1 to -10% (n=2381), stable EF: -5 to +5% (n=19194), mild increase in EF: +5.1 to +10% (n=2414), and substantial increase in EF: >+10% (n=1314). Survival was assessed utilizing Kaplan-Meier curves, log-rank test, and Cox regression modelling. Results: In total, 26706 patients were included in this study. Kaplan-Meier curves are displayed in Figure 1, with median survival estimates for each EF group as follows: severe reduction (10.6yrs), mild reduction (14.3yrs), stable (14.4yrs), mild increase (14.5yrs), and substantial increase (14.2yrs). There was a significant difference in survival based on log-rank test (p<0.001). Cox regression modelling found the following mortality risk results with reference to a stable EF: severe EF reduction (HR=1.88, p<0.001), mild EF reduction (HR=1.11, p=0.035), mild EF increase (HR=1.04, p=0.426), and substantial EF increase (HR=1.24, p<0.001). Conclusion: Our investigation found a significant increase in mortality risk for HTx recipients who develop a reduction or substantial increase in EF. Special attention and care should be given to such recipients – particularly those who are observed to have a drop in their EF of >10%, as their risk for mortality may increase by 88%.