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Introduction: Anthracycline-induced left ventricular dysfunction is well documented in lymphoma patients. However, the impact of cardiovascular risk factors (CVRF) and obesity on the right ventricle (RV) remains poorly characterized. Hypothesis: How does baseline CVRF burden—including obesity—affect RV structure and function over time in lymphoma patients treated with doxorubicin-based chemotherapy? Methods: A prospective cohort of patients with Hodgkin or non-Hodgkin lymphoma treated with doxorubicin-based chemotherapy at Mayo Clinic between March 1, 2013, and December 31, 2024, underwent echocardiography prior to chemotherapy initiation (T0), at 3–6 months (T1) and 6-18 months (T2) after treatment completion. A dedicated RV 4-Chamber view was used for all measurements. Patients were stratified into five groups: BMI>30, BMI>35, no CVRF, 1 CVRF (hypertension, diabetes, dyslipidemia, or smoking status), and ≥2 CVRF. RV parameters included end-diastolic/systolic area, FAC, TAPSE, S′ velocity, TRV, RVSP, and RV free wall strain. Group and time differences were analyzed using the Kruskal–Walli’s test due to non-normal distribution. Results: Among of 356 lymphoma patients (mean age 59.2 years, IQR:46-69) predominantly male (63.7%), 39.3% met criteria for obesity. At T0, patients with BMI >35 had greater RV end-diastolic (20.4 ± 4.4 vs. 18.7 ± 3.5 mm; p=0.009) and end-systolic diameters (11.0 ± 2.1 vs. 9.9 ± 2.6 mm; p=0.024), higher TRV (2.5 ± 0.4 vs. 2.2 ± 0.3 m/s; p<0.001) vs. no CVRFs. TAPSE was reduced vs. >2 CVRF group (23.7 ± 4.2 vs. 22.1 ± 4.8 mm; p=0.032). At T1, BMI >35 patients showed increased RV end-diastolic (22.3 ± 3.6 mm; p<0.001) and end-systolic areas (12.8 ± 2.9 mm; p<0.001), and worsened RVFWS (−24.0 ± 4.7% vs. −26.1 ± 2.98%; p=0.001) vs. no CVRF. RVSP was higher in those with >2 CVRFs (32.3 ± 5.4 mmHg; p=0.001). At T2, RVFWS was reduced in obese patients (−22.9 ± 3.5% vs. −27.1 ± 4.0%; p<0.001). RVSP stayed elevated in BMI >35 (33.0 mmHg) and >2 CVRFs (30.7 mmHg) vs. no CVRFs (23.7 mmHg; p<0.001). FAC and S′ did not differ significantly. Conclusion: In lymphoma patients treated with anthracyclines, isolated obesity was associated with the most pronounced RV changes—greater than those seen in non-obese patients with other CVRFs. These early and persistent alterations underscore the need for dedicated cardio-oncology care regardless of additional risk factors.

Introduction: In patients with type 2 diabetes (T2D) at high cardiovascular risk, glucagon-like peptide-1 receptor agonists (GLP1-RAs) have been shown to reduce major adverse cardiovascular events. However, patients with valvular heart disease, including those undergoing transcatheter aortic-valve implantation (TAVI), have been largely excluded from randomized trials. Hypothesis: We investigated whether GLP1-RA use is associated with improved one-year cardiovascular outcomes in patients with T2D undergoing TAVI. Methods: We conducted a retrospective cohort study using the TriNetX network. Adults (≥18 years) with T2D who underwent TAVI between 2015 and 2023 were included and stratified based on GLP1-RA initiation within 14 days post-TAVI. Baseline characteristics, comorbidities, medications, and laboratory data were balanced using 1:1 propensity score matching (PSM). The primary outcome was a composite of all-cause mortality or hospitalization at 1 year. Secondary outcomes included acute heart failure (HF) exacerbation, acute myocardial infarction (AMI), cardiac arrest, and ischemic stroke. Outcomes were assessed from 1 month to 1 year after TAVI. Survival probabilities were estimated using Kaplan-Meier analysis, and hazard ratios (HRs) were calculated with Cox proportional hazards models. Results: Among 20,454 patients with T2D undergoing TAVI from 2015-2023, 937 received GLP1-RAs. After PSM, 930 patients were included in each cohort, with a mean age of 73 years and 37% female. The mean follow-up duration was 342 days for GLP1-RA users and 325 days for non-users. GLP1-RA cohort exhibited a higher 1-year survival probability (93.8%) compared to non-users (89.5%) (HR 0.573 [95% CI, 0.410-0.801]; p=0.001). GLP1-RA use was also associated lower rates of all-cause hospitalization (HR 0.762 [95% CI, 0.652-0.891]; p=0.001), acute HF exacerbation (HR 0.687 [95% CI, 0.566-0.834]; p<0.001), and cardiac arrest (HR 0.452 [95% CI, 0.213-0.960]; p=0.034). No differences were observed in AMI (HR 1.033 [95% CI, 0.750-1.423]; p=0.844), or ischemic stroke (HR 0.875 [95% CI, 0.659-1.162]; p=0.356). Conclusions: In patients with T2D undergoing TAVI, GLP1-RA use is associated with significant survival benefits and improved cardiovascular outcomes, including reductions in acute HF exacerbation, all-cause hospitalization, and cardiac arrest. These findings highlight the need for prospective clinical trials to confirm these results.

Background: Muscular dystrophies (MDs) may cause heart failure (HF), but outcomes specific to MD-related HF are not well characterized. Research Question: Do the outcomes of HF hospitalizations differ between patients with underlying MDs (MD-HF) vs. patients without MDs (non-MD-HF) in the United States? Methods: Discharge data from HF hospitalizations were abstracted from the Nationwide Readmissions Database (2016-2022) and stratified by the presence or absence of MD (MD-HF vs. non-MD-HF). 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. Propensity-score matching (PSM) was used to control baseline differences between the MD-HF and non-MD-HF cohorts. Odds ratios (OR) with associated 95% Confidence intervals (CI) and p-values were reported. Analyses were conducted via SAS v. 9.4, with statistical significance indicated by two-tailed p<.05. Results: 8,466,806 HF hospitalizations were included in the analysis, of which 3688 (0.04%) involved patients with MD. MD-HF hospitalizations involved younger patients (mean age 55.3 vs. 71.3 years, p<0.001) with higher rates of HF with reduced ejection fraction (HFrEF) compared to non-MD-HF hospitalizations (48.1% vs. 34.9%, p<0.001). Compared to non-MD-HF hospitalizations (2.01%), MD-HF hospitalizations (5.82%) were associated with significantly higher odds of inpatient mortality (OR 3.01, 95% CI: 2.03, 4.45); higher complications rate (OR 2.11, 95% CI, 1.77, 2.52) including cardiogenic shock (OR 2.61, 95% CI, 1.90, 3.59), cardiac arrest (OR 2.27, 95% CI, 1.17, 4.41), use of mechanical ventilation (OR 2.23, 95% CI, 1.82, 2.73); higher palliative care consultation (OR 4.52, 95% CI, 3.21, 6.36); as well as more extended hospital LOS (OR 1.18, 95% CI, 1.09, 1.29), higher total costs (OR 1.32, 95% CI, 1.24, 1.41), and higher odds of discharge to rehab facility (OR 2.46, 95% CI, 1.99, 3.03) and home healthcare (OR 1.85, 95% CI, 1.55, 2.21) (all p<0.001). MD was not associated with a significant difference in 30-day (OR 0.94, 95% CI, 0.78, 1.12) and 90-day (OR 0.98, 95% CI, 0.82, 1.17) all-cause readmission rates. Conclusion: MD-HF hospitalizations were associated with higher inpatient mortality, complication rates, resource utilization, discharge to rehab facility and home healthcare, and no difference in readmission rates compared to non-MD-HF hospitalizations.

Introduction: Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) arises from amyloidogenic aggregates of destabilized TTR protein in variant (ATTRv-CM) or acquired wild-type TTR (ATTRwt-CM). The p.V142I (V122I) variant is the most common pathogenic TTR allele in the USA and has higher mortality vs wild type. Acoramidis, an oral TTR stabilizer achieving ≥90% stabilization, is approved in USA, UK, Europe, and Japan for treating ATTR-CM in adults. In ATTRibute-CM (NCT03860935), acoramidis showed a reduction in all-cause mortality (ACM) or first cardiovascular-related hospitalization (CVH) vs placebo (PBO), with consistent benefit in ATTRwt-CM and ATTRv-CM (all variants). We report clinical outcomes in participants with p.V142I ATTRv-CM. Research Question: What was the efficacy of acoramidis for clinical outcomes (ACM, CVH) in participants with p.V142I ATTRv-CM in ATTRibute-CM? Methods: In ATTRibute-CM, 632 participants were randomized 2:1 to receive acoramidis HCl 800 mg or PBO twice daily for 30 months. All participants enrolled in open-label extension (OLE) received acoramidis only. Exploratory post hoc analyses were done in the p.V142I ATTRv-CM subgroup. Time-to-event analyses used a stratified Cox proportional hazards model using treatment group as an explanatory factor and baseline 6MWD as a covariate, stratified by randomization factors: serum NT-proBNP and eGFR. ACM was analyzed at Month 42 (ATTRibute-CM 30 months + 12 months OLE). Results: Of the 59 patients with ATTRv-CM reported at randomization, 35 (59.3%) had p.V142I (23 acoramidis, 12 PBO) with comparable baseline characteristics; 4 were homozygous for p.V142I (1 acoramidis, 3 PBO). Through Month 30, ACM/first CVH occurred in 43.5% (10/23) of acoramidis vs 83.3% (10/12) in PBO (HR 0.311; 95% CI 0.120–0.805; Figure 1 ). Through Month 42, ACM occurred in 26.1% (6/23) of continuous acoramidis vs 66.7% (8/12) in PBO to acoramidis (HR 0.307; 95% CI 0.097–0.973; Figure 2 ). Conclusions: In participants with p.V142I ATTRv-CM, acoramidis use was associated with 69% risk reduction in ACM/first CVH through Month 30 and ACM through Month 42 vs PBO. This is the first report of clinical benefit of this magnitude observed in this high-risk population. These findings have biologic plausibility and may reflect the near-complete stabilization observed experimentally with acoramidis in p.V142I ATTR fibrils. These observations require confirmation in larger cohort studies.

Introduction: Titin truncating variants (TTNtv) are a common cause of dilated (DCM) and non-dilated left ventricular cardiomyopathy (NDLVC). Mitral valve prolapse (MVP) occurs commonly in the general population and is characterized by myxomatous structural changes of the mitral valve apparatus. Both TTNtv-mediated DCMs and MVP have been associated independently with an increased risk of ventricular arrhythmias (VA) and sudden cardiac arrest/death (SCA/SCD). However, it remains unclear whether TTNtv-positive patients with co-existing MVP are at increased risk for major VA (MVA) events. Therefore, we sought to compare the prevalence of MVA events between TTNtv-positive patients with or without MVP in a large single-center cohort of genetic cardiomyopathy patients. Methods: Retrospective review of 1,230 ACM/DCM patients was used to identify those with a pathogenic/likely pathogenic (P/LP) TTNtv. Independent review of available imaging data was subsequently used to identify TTNtv-positive patients with co-existing MVP. The prevalence of non-SCA MVA and SCA/SCD was then compared between TTNtv-positive patients with and without MVP. Results: Overall, 253/1,230 (21%) of ACM/DCM patients were P/LP TTNtv-positive (43% female; mean age 44±17 years, mean LVEF 39±17%). Amongst these 253 TTNtv-positive patients, 15 (5.9%) had co-existing MVP (33% female, mean age 49±12 years, mean LVEF 48±12%). Collectively, TTNtv-positive patients with MVP were more likely to experience a MVA event than those without MVP [6/15 (40%) vs 41/238 (17%); p=0.03]. This included a higher risk of appropriate VT/VF-terminating ICD shocks [4/15 (27%) vs. 17/238 (7.1%); p=0.03] and SCA [3/15 (20%) vs 12/238 (5%); p=0.05]. However, despite the increased arrhythmic risk observed in TTNtv-positive patients with MVP, no deaths occurred in this subgroup and the overall cardiac mortality rate across the entire TTNtv-positive cohort was low [6/253 (2.4%)]. Conclusion: TTNtv-positive patients with concomitant MVP are at increased risk for MVA events, including SCA. Future studies are needed to i) better define the prognostic utility of MVP in the risk-stratification of TTN-NDLVC/DCM and other genetic cardiomyopathies and ii) determine whether some patients diagnosed with arrhythmogenic MVP syndrome may have TTNtv-mediated NDLVC exacerbated in a focal manner by the increased mechanical strain generated by the presence of the common and likely genetically unrelated myxomatous MVP.

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.