Citations

Introduction: Preeclampsia is a multisystem progressive disease of pregnancy, characterized by a new onset of hypertension (≥ 140/90 mm Hg) with proteinuria after the 20th week of gestation. There is a conflict between United States guidelines that recommend Low-dose aspirin (LDA) and United Kingdom guidelines that recommend High-dose aspirin (HDA) for the prevention of preeclampsia in high-risk pregnant women. After the latest study that recommends HDA and the absence of pairwise meta-analyses comparing two doses, we aimed to conduct a comprehensive pairwise meta-analysis to assess whether HDA is better than LDA in the prevention of preeclampsia. Methods: We conducted a systematic search on PubMed, Scopus, Cochrane Central, and Web of Science (WOS) from inception until June 2025. All randomized controlled trials (RCTs) comparing LDA and HDA in high-risk pregnant women were included. Our primary outcome was the incidence of preeclampsia (PE), while secondary outcomes were Placental abruption, Pre-term delivery, and Intrauterine Growth Restriction (IUGR). Using random-effects models, we calculated risk ratios (RR) with 95% confidence intervals (CIs). Results: A total of 8 RCTs with 1,290 patients from the United States, Canada, England, and different Asian countries were included, among whom 642 (49.8%) patients were randomized to HDA. All studies compared HDA (≥ 150 mg) and LDA (75 mg to 81 mg). Patients with LDA had a higher risk of Preeclampsia (RR: 1.71, 95% CI: 1.19 to 2.44, p<0.001) compared to HDA. There was no significant difference between the LDA and HDA regarding Placental abruption, Pre-term delivery, and IUGR. With a pooled RR with a 95% CI (1.8, [0.91 to 3.54], P = 0.09), (1.25, [0.79 to 1.97], P = 0.34), (1.5, [0.93 to 2.42], P = 0.1), respectively. Conclusion: Among high-risk pregnant women, LDA was associated with a 71% higher incidence of preeclampsia than HDA. These results support the use of HDA as a preventive medication for preeclampsia in high-risk pregnant women.

Background: Left atrial (LA) strain, measured by two-dimensional speckle tracking (2D-STE), has not been explored in lymphoma patients before anthracycline treatment as a prognostic marker for predicting future major adverse cardiovascular effects (MACE), heart failure, cardiotoxicity, and all-cause mortality after treatment. Hypothesis: Can an abnormal baseline LA peak reservoir strain (LA RS) measured before anthracycline chemotherapy predict MACE, heart failure, cardiotoxicity, and all-cause mortality in lymphoma patients? Methods: A retrospective cohort study was conducted including 104 patients diagnosed with Hodgkin and non-Hodgkin lymphoma, enrolled and followed from January 1, 2013, to June 30, 2023. LA RS was measured in a dedicated 4 chamber view (TomTec Imaging Systems, Unterschleissheim, Germany), abnormal values defined as less than 35%. Univariate Cox regression analyses were performed to assess whether the LA RS was associated with the development of MACE, cardiotoxicity, heart failure, and all-cause mortality. Multivariable Cox regression models were used to adjust for comorbidities. Associations with outcomes were evaluated using the Kaplan-Meier method and Cox regression. Results: Among 104 patients (mean age of 59 years; [IQR], 49–70), 69 (66.3%) were male and 102 (98.1%) were white. MACE occurred in 19 patients, heart failure in 14 patients, and cardiotoxicity was observed in 4 patients. Additionally, all-cause mortality was found in 19 patients (18.3%). Abnormal LA RS was significantly associated with increased all-cause mortality (HR 3.12, 95% CI 1.02–9.53, p=0.0454) (Figure c), even after adjusting for hypertension, dyslipidemia, smoking status, gender and age (Figure d). No significant associations were found between LA RS and MACE (HR 1.42, 95% CI 0.56-3.62, p=0.4604) (Figure a), heart failure (HR 1.12, 95% CI 0.38-3.24, p=0.8299), or cardiotoxicity (HR 3.23, 95% CI 0.33-31.47, p=0.3128) (Figure b). Conclusions: Abnormal baseline LA strain measured by echocardiography is an independent predictor of all-cause mortality in lymphoma patients. These findings support the use of LA strain assessment into initial risk stratification protocols, providing particular value in identifying patients at increased risk of mortality.

Introduction: Apolipoprotein B (ApoB) and coronary artery calcium score (CAC) are well-established risk factors for coronary heart disease (CHD). However, the interaction between these risk factors on CHD risk has not been well-studied. We investigated the association between ApoB levels and CAC with CHD risk. Methods: We analyzed 4,649 participants from the Multiethnic Study of Atherosclerosis cohort (median follow-up 13.9 years) without baseline CHD or statin use. High ApoB was defined as ≥120 mg/dL. Participants were divided into 6 groups; group 1: CAC = 0 with normal ApoB, group 2: CAC = 0 with high ApoB, group 3: CAC 1-99 with normal ApoB, group 4: CAC 1-99 with high ApoB, group 5: CAC ≥100 with normal ApoB, group 6: CAC ≥100 with high ApoB. CHD was defined as myocardial infarction, resuscitated cardiac arrest, or CHD death. Survival analysis using Kaplan-Meier and multivariable Cox proportional hazard models were performed to assess the relationship between ApoB, CAC, and time to first CHD event. Results: In an adjusted model, high ApoB, CAC (1-99), and CAC (≥100) were independently associated with CHD (HR: 1.48; 95% CI: 1.04, 2.11; HR: 2.54; 95% CI: 1.78, 3.64; and HR: 4.41; 95% CI: 3.08, 6.31, respectively). Compared to group 1 (CAC 0 with normal ApoB), CAC 0 and high ApoB (group 2) was not associated with increased risk of CHD (HR: 1.15; 95% CI: 0.59, 2.23). However, a statistically significant greater risk of CHD was observed in those with CAC 1-99 and normal ApoB (group 3) (HR: 2.12; 95% CI: 1.37, 3.28), CAC 1-99 and high ApoB (group 4) (HR: 4.12; 95% CI: 2.42, 7.00), CAC ≥100 and normal ApoB (group 5) (HR: 4.20; 95% CI: 2.78, 6.34), CAC ≥100 and high ApoB (group 6) (HR: 5.72; 95% CI: 3.40, 9.63). Conclusions: In this analysis, ApoB and CAC are independently associated with CHD risk. Individuals with high ApoB and CAC ≥100 had the highest risk of CHD. In contrast, individuals with CAC = 0 and high ApoB had no significant increase in CHD risk compared to individuals with normal ApoB levels. These findings suggest that ApoB and CAC may be complementary tools for CHD risk stratification in the context of primary prevention.

Background: Programmed Cell Death 4 (PDCD4) is a tumor suppressor known for promoting apoptosis and inhibiting growth and protein translation in cancer cells. However, the role of PDCD4 in the heart remains elusive. This study explores PDCD4's regulation and function in the heart through genetic manipulation. Methods: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), neonatal mouse cardiomyocytes, and transgenic mice with constitutive cardiomyocyte-specific PDCD4 overexpression were used in this study. In vitro, PDCD4 expression was manipulated by plasmid-based overexpression or siRNA-mediated knockdown, and confirmed by Western blot. Subcellular localization of PDCD4 was assessed by immunofluorescence staining. Apoptosis was evaluated using cleaved-PARP immunoblotting and TUNEL staining. Cardiac function in mice was assessed by echocardiography. Results: In hiPSC-CMs and isolated neonatal cardiomyocytes, expression of PDCD4 is predominantly found in the nucleus, suggesting a possible role in nuclear signaling or gene regulation. Treatment of hiPSC-CMs with 1 μM doxorubicin (DOX) for 3 days significantly reduced PDCD4 expression. Functionally, PDCD4 overexpression attenuated DOX-induced apoptosis, as evidenced by decreased cleaved-PARP levels and fewer TUNEL-positive cells, whereas PDCD4 knockdown increased cell death, indicating a protective role under chemotherapeutic stress. PDCD4 expression decreased in mouse hearts during postnatal development. Transgenic mice with cardiomyocyte-specific PDCD4 overexpression showed normal heart weight, size, and function, without induced apoptosis under baseline conditions. We are currently investigating the potential cardioprotection of PDCD4 transgene against DOX induced acute and chronic cardiotoxicities. Conclusion: PDCD4 has a pro-apoptotic function in cancer cells but demonstrates an anti-apoptotic role in cardiomyocytes during chemotherapeutic stress in vitro. These observations indicate a context-dependent role for PDCD4 in cardioprotection, presenting it as a potential therapeutic target for reducing cardiotoxicity during cancer treatment.

Background: Heart failure (HF) continues to be a major cause of morbidity and mortality worldwide, placing a significant burden on healthcare systems. Differences in the outcomes of HF hospitalizations for adults in teaching vs. non-teaching hospitals in urban settings are uncertain. Research Question: Do outcomes of HF hospitalizations differ between patients hospitalized in urban teaching vs. non-teaching hospitals in the United States? Methods: HF hospitalizations were abstracted from the 2016 through 2022 Nationwide Readmissions Database and stratified into urban teaching vs. urban non-teaching hospital settings. Propensity-score matching was used to control for baseline differences between teaching and non-teaching hospital cohorts. Logistic regression and lognormal models were estimated to assess differences in inpatient mortality, length of stay (LOS), total costs, complications, and 30-day and 90-day all-cause readmissions. Odds ratios (OR) with associated 95% Confidence intervals (CI) and p-values were reported. Analyses were conducted via SAS v. 9.4. Results: A total of 7,558,299 weighted HF hospitalizations were included in the analysis, of which 76.3% involved urban teaching hospitalizations. Compared to urban non-teaching, HF hospitalizations in urban teaching hospitals were associated with higher odds of in-hospital mortality (OR 1.24, 95% CI:1.21-1.27); had higher complications, including cardiogenic shock (OR 2.58, 95% CI, 2.46, 2.70), cardiac arrest (OR 1.31, 95% CI, 1.27, 1.36), CPR (OR 1.28, 95% CI, 1.22, 1.34), and use of extracorporeal membrane oxygenation (OR 20.13, 95% CI, 13.0, 31.2), intra-aortic balloon pump (OR 4.46, 95% CI, 3.90, 5.10) and mechanical ventilation (OR 1.27, 95% CI, 1.23, 1.33); higher hospitalization cost (Ratio 1.18, 95% CI: 1.17,1.20), longer length of stay (OR 1.16, 95% CI: 1.15, 1.17) and a greater palliative care consultation rate (Ratio 1.35 (95% CI 1.30, 1.40) (all p<0.001) ( Figure 1 ). 30-day (OR 1.03, 95% CI: 1.02, 1.04) and 90-day (OR 1.05, 95% CI: 1.02, 1.07) all-cause readmission rates were also statistically higher (p<0.001), though the difference was clinically non-significant ( Figure 2 ). The home discharge rate was similar for teaching and non-teaching hospitals ( Figure 2 ). Conclusion: HF hospitalizations in urban teaching hospitals were associated with higher inpatient mortality, complication rates, resource utilization, and palliative care consult rates than urban non-teaching hospitals.

Background: The efficacy of different conventional ventilation during automated head-up (AHUP) CPR using active decompression and impedance threshold device with head and torso elevation is unknown. We sought to determine the central and peripheral hemodynamics while using the 10:1 versus the 30:2 positive pressure ventilation (PPV). Research Question: Does the PPV delivery method affect the hemodynamics during AHUP-CPR? Methods: Ventricular fibrillation was induced in anesthetized pigs (n=5), followed by AHUP-CPR initiation with positive pressure ventilations applied using an automated bag compressor to deliver 10ml/kg of tidal volume over 1 sec at a rate of 10 breaths/min. After 15 minutes of CPR using a 10:1 ratio, ventilation was changed to a 30:2 ratio for 2 minutes with 2 PPV delivered consecutively. Thereafter 10:1 ratio was resumed followed by another 2-minute round of 30:2 PPV mode. Intraventricular pressures and volumes using conductance catheters placed in the right ventricle (RV), along with other hemodynamic parameters were recorded continuously, during the 2-minute intervals between PPV delivery. A mixed-effects model was used to evaluate the effects of PPV mode on pressure-volume (PV) loop parameters while using a Spearman correlation to explore the relationship between PV loop indices. Results: There was no statistically significant difference between RV stroke volume (SV) with 10:1 versus 30:2 PPV mode (Table 1). Throughout 2 minutes, 30:2 ventilation mode resulted in a significantly higher end-tidal CO2 (ETCO2), and higher pressures with a higher pulmonary elastance (Ea) imposed on RV (p<0.05). Higher Ea was strongly correlated with lower SV and ETCO2 (Spearman's rho correlation confidence of -0.97 and -0.83, respectively). No significant differences were observed between the two ventilation modes in any other hemodynamic parameters, including intrathoracic, aortic and right atrial pressures, as well as coronary and cerebral perfusion pressures. Conclusion: No significant difference was found for right ventricular stroke volume when comparing one breath after 10 chest compressions to two breaths after 30 compressions during automated head-up CPR. Delivering two consecutive breaths after 30 continuous compressions led to an overall higher ETCO2, but it also imposed greater ventricular pressure and afterload, which were significantly correlated with reduced SV and ETCO2.

Background: Ventricular tachycardia (VT) is a potentially life-threatening arrhythmia frequently observed in structural heart diseases, including cardiac laminopathy, a genetic cardiomyopathy associated with a high risk of sudden cardiac death (SCD) and progressive systolic dysfunction caused by pathogenic variants in LMNA -encoded lamin A/C. While catheter ablation is a key therapeutic strategy for VT management, its efficacy in cardiac laminopathy remains poorly defined. Objective: This systematic review and single-arm meta-analysis aims to synthesize the available evidence in the literature on the role of VT ablation for patients with cardiac laminopathy. Methods: A single-arm meta-analysis was conducted following PRISMA guidelines, systematically searching PubMed, Embase, and Cochrane databases for studies investigating VT ablation outcomes in patients with cardiac laminopathy. We applied an inverse variance random-effects model for a meta-analysis of proportions. Results: We included 6 cohort studies and 1 abstract comprising 62 patients with LMNA-related cardiomyopathy (mean age at 53.2 ± 9.7 years, 85% males, and 88% with an ICD). The predominant ablation strategy was endocardial/endo-epicardial in 93% of cases. Acute success rate following VT ablation was 37% (95% CI: 14 to 63%) and 28% of the patients required multiple procedures. Over a median follow-up of 26 (9-35) months, VT recurrence rate after ablation was 91% (95% CI: 76 to 100%; Figure A ). The all-cause mortality rate was 54% (95% CI: 39% to 70%; Figure B ), primarily driven by cardiac causes 51% (95% CI: 25 to 76%; Figure C ). There was an elevated rate of heart transplantation 14% (95% CI: 1 to 34%), highlighting overall poor outcomes in this patient population. Conclusion: Catheter ablation in cardiac laminopathy is associated with limited long-term efficacy, with high rates of VT recurrence, cardiovascular mortality and heart transplantation. These findings underscore the importance of ICD implantation for primary prevention and the pressing need to develop alternative treatment strategies. Further research is necessary to determine whether specific LMNA variants influence ablation outcomes and to explore emerging therapies targeting the underlying molecular mechanisms of cardiac laminopathy.

Background: Group 1 pulmonary artery hypertension (PAH) is treated with three main drug classes: prostacyclin analogs (PCAs), endothelin receptor antagonists, and nitric oxide pathway drugs. PCAs may be administered via parenteral (intravenous (IV), subcutaneous (SQ)) or oral/inhaled routes. The role of parenteral versus non-parenteral PCAs in contemporary PH practice remains unclear. Objectives: To compare contemporary hemodynamic and survival outcomes between parenteral and non-parenteral PCA use. Methods: This retrospective study included patients with WHO Group 1 PAH, who underwent a right heart catheterization (RHC) at Mayo Clinic. Diagnosis required mPAP was ≥25 mm Hg, documented chart diagnosis and initiation of PAH therapy. Echocardiographic and repeat RHC parameters were collected and only patients started on PCA therapy were included. Patients were grouped based on intiiated PCA route: parenteral (IV/SQ) vs non-parenteral routes (oral/inhaled). Hemodynamic changes (post-pretreatment) were compared using t-tests and ANOVA for parenteral vs non-parenteral PCA. Survival was assessed using Kaplan-Meier curves, and Cox proportional hazards models. Results: Of 144 patients initiated on PCA after the first RHC, 89 (62%) received parenteral and 55 (38%) non-parenteral PCA.. At baseline, patients who started on parenteral PCA had more severe disease with higher mean PAP, RAP and PVR. On follow-up, parenteral PCAs led to greater reductions in mean PAP and RAP, with no differences in PVR, TPR, or CO changes. Survival was worse with parenteral PCA use even after adjusting for comorbidities and baseline hemodynamics (HR 1.93; 95% CI 1.17-3.18; p=0.009). Discussion: Parenteral PCAs were more often used in patients with more severe pulmonary vascular disease. Despite greater hemodynamic improvements, parenteral PCAs were associated with worse survival, likely due to more severe disease at baseline. Further research is needed to understand the role of PCA route in guiding treatment strategies.

Background: MELAS is a rare mitochondrial disorder characterized by multisystem involvement, including stroke-like episodes, seizures, and cardiomyopathy. Cardiac involvement in MELAS may include left ventricular dysfunction, arrhythmias, and structural abnormalities, yet the occurrence of cardioembolic stroke as a direct consequence of these manifestations is exceedingly rare. To date, no literature has clearly described this association. Case Presentation: A male in his twenties with known MELAS syndrome, epilepsy, and heart failure with reduced ejection fraction (EF 25%) presented with acute right hemiparesis and aphasia. Investigations: CT angiography and CT perfusion revealed reduced opacification in the left MCA bifurcation and a left M2 thrombus (Figure 1A). The contrast echocardiogram showed a normal-sized left ventricle with severely reduced ejection fraction (25%, down from 30% six months prior), diffuse hypokinesis, grade III diastolic dysfunction, and a left ventricular thrombus, with no patent foramen ovale. Treatment: Given the high suspicion for cardioembolic stroke, the patient received intravenous tenecteplase within the 3-hour window. Mechanical thrombectomy was planned but aborted due to spontaneous recanalization. Post-thrombolytic angiography confirmed reperfusion of the left MCA with residual distal M3 thrombus (Figure 1B).MRI confirmed infarcts in the left MCA distribution and right precentral gyrus, with no evidence of hemorrhagic transformation. Anticoagulation was initiated for secondary prevention. Statins were withheld due to concerns about mitochondrial toxicity. Follow-up: On a 3-month follow-up, the patient remained neurologically stable and continued oral anticoagulation without recurrent events. Discussion: The clinical scenario posed a diagnostic challenge—stroke-like episodes in MELAS are metabolic and typically non-territorial. However, an LV thrombus, territorial infarction, and perfusion mismatch pointed to an ischemic etiology. Timely thrombolysis led to significant neurological recovery. This case highlights the importance of distinguishing cardioembolic stroke from mitochondrial stroke-like events, especially in patients with known cardiac involvement. Conclusion: In MELAS patients with cardiac dysfunction, cardioembolic stroke must be considered when clinical and imaging findings suggest a vascular event. Early recognition and intervention, including thrombolysis, can lead to favorable outcomes.

Background: Etripamil nasal spray is a fast-acting, calcium channel blocker in development for the conversion of paroxysmal supraventricular tachycardia (PSVT) outside of a health-care setting. Studies have demonstrated the favorable safety and efficacy of self-administered etripamil in restoring sinus rhythm (SR) and reducing emergency department visits. Purpose: This report analyzes the efficacy, safety, and test-dose tolerability of etripamil across PSVT clinical studies. Methods: We systemically examined randomized, controlled and open-label trials evaluating etripamil in patients with PSVT. Efficacy measures included the proportion of patients converting from PSVT to SR within 30 minutes and the median times to conversion across all Phase 3 studies. Safety data for treatment-emergent adverse events (TEAEs), serious AEs, and test dose tolerability from Phase 2/3 studies were summarized descriptively. Results: NODE-1, NODE-301 Part 1, NODE-301 Part 2 (RAPID, including RAPID Extension, RAPID Open Label, RAPID Open Label Extension periods), NODE-302, and NODE-303 studies were analyzed (Table 1). The Kaplan-Meier estimate of etripamil exposed patients converting to SR within 30 minutes (n= 622) was 59.6% (range, 53.6% to 64.3%) with a median time to conversion of 18.5 minutes (95% CI, 15.7 to 21.0). The proportions of RCT placebo group patients converting from SVT to SR by 30 minutes ranged from 26.7% to 34.7%. Estimates of conversion of SVT to SR with etripamil at 60 minutes for individual studies ranged from 63.2% to 73.5% (Figure). Combined analysis showed mainly the occurrence of mild, transient TEAEs, primarily nasal discomfort, nasal congestion, rhinorrhea, throat irritation, and epistaxis (Table 2). 1,107 patients took at least one etripamil test dose while in SR; no significant change in average baseline heart rate or blood pressure was observed within 45 minutes of administration, and test dose failure occurred in only 16 patients (1.4%). Conclusions: Across multiple clinical studies of acute PSVT management, self-administered etripamil consistently demonstrated robust efficacy and a favorable safety profile for acute PSVT management. Safety data and the low rate of test dose failures indicate favorable tolerability, suggesting no need for a pretreatment test dose. These findings support the potential of etripamil as a patient-administered therapy for PSVT, which may reduce reliance on emergency care.