Cardiomyocytes undergo proliferation, differentiation, and hypertrophy during fetal development. Current techniques struggle to distinguish cardiomyocyte proliferation from alternative cell fates. In this study, we combined flow cytometry measures of cardiomyocyte ploidy (DAPI) and in vivo DNA replication (EdU) over a 24-h period to evaluate the trajectories of cardiomyocytes from normally growing control fetal sheep and fetuses affected by placental insufficiency and fetal growth restriction (FGR) at 0.9 gestation. We categorized ∼100,000 cardiomyocytes from the left and right ventricles (LV and RV) of each animal as proliferating (2C EdU+), differentiated (4C EdU-), or endoreplicating and polyploid (6C+ EdU+). Compared with controls, FGR hearts had 25%-50% fewer cardiomyocytes that replicated DNA (EdU+) (LV: P = 0.02, RV: P = 0.002). The fraction of proliferating cardiomyocytes, indicated by the population of newly synthesized 2C EdU+ daughter cells, was ∼20% lower in FGR fetuses (LV: P = 0.006, RV: P = 0.02). Instead, the percentage of endoreplicating cardiomyocytes (6C+ EdU+) in FGR hearts was double that of controls (LV: P = 0.004, RV: P = 0.002). Although total EdU+ was not a strong predictor of cardiac growth, LV and RV mass correlated positively with the percentage of 2C EdU+ cardiomyocytes and negatively with 6C+ EdU+ cardiomyocytes across all fetuses. LV mass also correlated positively with the percentage of differentiated cardiomyocytes (4C EdU-), which was lower in FGR hearts compared with controls (P = 0.008). This study is the first to characterize cardiomyocyte fate following DNA replication in fetal sheep. Our findings suggest that FGR cardiomyocytes differentially prioritize their cycling capacity in favor of polyploidization instead of proliferation.NEW & NOTEWORTHY Knowledge of cardiac development has been limited by available methodologies. We used a novel flow cytometry approach to measure DNA replication in utero and distinguish between cardiomyocyte proliferation, differentiation, and endoreplication in growth-restricted (FGR) and normally growing fetal sheep. FGR cardiomyocytes have lower proliferation rates but increased endoreplication compared with controls. Endoreplication and polyploidy are negatively correlated with ventricular mass. Our findings provide insight into fetal cardiac development and how cardiomyocyte fate is altered by FGR.

The orphan receptor GPRC5B promotes macrophage infiltration and an inflammatory plaque phenotype in atherosclerosis.

Background: Arterial hypertension (AH) remains a global health concern due to its multifactorial etiology, limited therapeutic success, and high cardiovascular risk. In this context, plant-derived compounds such as essential oils have gained attention as alternative strategies. The monoterpene (-)-linalool (LIN) demonstrates antihypertensive effects. However, its clinical application is hampered by poor solubility and low bioavailability. Methods: This study aimed to investigate the chronic cardiovascular effects of free LIN and its inclusion complex with β-cyclodextrin (LIN/β-CD) in spontaneously hypertensive rats (SHR) and normotensive Wistar rats. Results: Pharmacokinetic analysis showed that complexation with β-CD markedly improved LIN plasma exposure, increasing systemic bioavailability by approximately 20-fold and prolonging its circulation time. In acute assays, intravenous LIN and LIN/β-CD (50 mg/kg) reduced blood pressure in SHR, LIN induced bradycardia, and LIN/β-CD elicited a mild, non-significant tachycardia. Orally administered LIN/β-CD exerted superior antihypertensive effects compared to free LIN. In a 60-day chronic regimen, LIN/β-CD consistently maintained reduced arterial pressure, achieving levels comparable to normotensive controls, while free LIN produced transient effects. LIN/β-CD also significantly reduced the cardiac mass index in SHR, suggesting attenuation of hypertrophic remodeling. Vascular reactivity assays revealed enhanced endothelium-dependent and -independent relaxation and diminished vasoconstriction in LIN/β-CD-treated animals, indicating improved endothelial and smooth muscle function. Histological analyses confirmed the absence of cardiac or vascular injury in both treatment groups. Conclusions: In conclusion, the LIN/β-CD complex improves the pharmacokinetic profile and enhances the arterial morphology, antihypertensive and cardioprotective effects of linalool. These findings support its translational potential as a safe and effective oral formulation for the long-term management of hypertension and associated cardiovascular dysfunction.

Patients with nephrotic syndrome develop albuminuria, hyperlipidemia and heart failure, but the pathomechanisms underlying this interconnection are unclear. We previously found that fibroblast growth factor 23 (FGF23) promotes cardiac hypertrophy in animal models of chronic kidney disease (CKD). Since patients with nephrotic syndrome have elevated FGF23, we hypothesized that FGF23 also contributes to heart damage in nephrotic syndrome. We previously developed a mouse model with the inducible and podocyte-specific overexpression of a constitutively active NFATc1 mutant variant (NFATc1nuc), which within one week develops a nephrotic syndrome-like phenotype. Here we conducted serological analyses of phosphate and lipid metabolism, and we studied the cardiac phenotype after one week and three months of albuminuria. After one week, mice presented with albuminuria, hyperlipidemia and elevated serum FGF23 levels, as well as reductions in cardiac function and cardiac hypertrophy on a cellular level without significant increases in cardiac mass or fibrosis. Under physiologic conditions and in CKD, elevations in systemic phosphate levels, also called hyperphosphatemia, induce FGF23 production in the bone. However, in NFATc1nuc mice we could detect neither increases in serum phosphate levels nor in FGF23 expression in the bone. Instead, nephrotic mice had FGF23 elevations in the heart, and our in vitro studies showed that free fatty acids induced FGF23 expression in cardiac myocytes resulting in hypertrophy. We also found that mice with prolonged NFATc1nuc expression transition into a CKD-like phenotype with hyperphosphatemia and further FGF23 elevations, as well as cardiac hypertrophy and fibrosis and a reduced lifespan. Our study suggests that NFATc1nuc mice serve as a model of nephrotic syndrome that progresses to CKD with pathologic cardiac remodeling. Our findings indicate that hyperlipidemia might contribute to heart failure in nephrotic syndrome by inducing FGF23 expression in the heart, which then drives cardiac hypertrophy.

We report the case of a 53-year-old male patient who presented to the cardiology department with presyncope and atypical chest pain. The transthoracic echocardiography revealed a homogeneous hypoechoic mass measuring 2.5 × 5.7 cm at the level of the anterolateral wall of the right ventricle. In order to further characterize the identified right-ventricle-adjacent mass, we performed a cardiac computed tomography, which confirmed the presence of a homogeneous hypodense mass with a single wall, without septation. Cardiac magnetic resonance imaging demonstrated a serous fluid mass capping the right atrium, right atrial appendage, and coronary sinus, without evidence of myocardial invasion. The multimodality imaging performed clarified the diagnosis of an uncomplicated pericardial cyst. The patient was managed conservatively with every 6 months echocardiographic evaluation. At a 2-year follow-up, he presented no recurrent symptoms, and the pericardial cyst maintained the same characteristics. The cornerstone of this case report was relying on multimodality imaging in order to characterize the adjacent cardiac mass and to arrive at the diagnosis of an uncomplicated pericardial cyst, which established the prognosis and management of the patient.

IntroductionThis study examined cardiac adaptations in futsal athletes to determine how sport-specific training influences cardiac morphology and function across different competitive levels.MethodsMale athletes from under-18, under-20, and adult categories underwent electrocardiogram, transthoracic echocardiogram, and cardiopulmonary exercise testing. Measured parameters included VO₂max, ventricular and atrial dimensions, wall thickness, and cardiac mass index. Group differences were analyzed using one-way ANOVA with Tukey's post-hoc test (p < 0.05).ResultsUnder-20 athletes showed significantly higher VO₂max compared to adults (mean difference: +4.87 mL·kg−1·min−1; p = 0.014). Adult players exhibited greater interventricular septal (+0.68 mm; p = 0.048) and inferolateral left ventricular wall thickness (+0.75 mm; p = 0.016), alongside higher left atrial volume (+27.4 mL vs. U18; p < 0.001) and indexed left atrial volume (+14.6 mL/m² vs. U18; p < 0.001). Conversely, the right ventricular end-diastolic diameter was larger in under-18 athletes compared to under-20 (+10.9 mm; p < 0.001) and adult players (+14.3 mm; p < 0.001). Ejection fraction, left ventricular end-diastolic diameter, and ventricular mass index remained consistent among groups, confirming preserved systolic function across all athletes.ConclusionProgressive futsal training promotes selective cardiac remodeling characterized by increased wall thickness and chamber dilation in adult athletes without compromising function. These adaptations reflect physiological remodeling associated with chronic high-intensity intermittent training, emphasizing the need for longitudinal monitoring to distinguish normal adaptation from early pathological changes.

Cardiac metabolism is highly adaptive, and distinct maladaptive remodeling processes may contribute to the development of cardiac dysfunction. Here, we compared the metabolic, structural, and functional adaptations of two murine models: C57BL/6J mice fed a high-fat, carbohydrate-free diet and New Zealand Obese mice maintained on a standard diet. Cardiac function was assessed by echocardiography, plasma metabolite profiles were analyzed, and cardiac proteomes were quantified by mass spectrometry. Proteomic data were computationally integrated into a kinetic model of cardiac central metabolism (CARDIOKIN1) to predict changes in substrate utilization and ATP production capacities under physiological nutrient conditions. Diet-induced metabolic stress led to cardiac dysfunction with preserved ejection fraction, characterized by mitochondrial dysfunction, impaired ATP production, inflammation, and reduced cardiac mass. Conversely, genetically induced obesity resulted in cardiac impairment with reduced ejection fraction associated with mild fibrosis, maintained ATP production, and substrate switching favoring fatty acid utilization. Proteomic and computational analyses revealed a coordinated downregulation of metabolic networks involved in oxidative phosphorylation, substrate transport, and energy production in both models, but with distinct profiles of metabolic inflexibility and mitochondrial efficiency. This study provides insights of how dietary versus genetic metabolic stress reprograms cardiac metabolism and structure, offering mechanistic insights into the diverse pathways leading to cardiac dysfunction. These insights may guide future strategies for metabolic intervention in heart failure subtypes.

Background: Chronic heart failure (HF) is a significant public health issue. The principal risk factors for left ventricular diastolic dysfunction (LVDD) include older age, female sex, obesity, hypertension, smoking, and diabetes, among others, all of which can reduce physical activity. Additionally, peripheral factors such as skeletal muscle mass (SMM) abnormalities decrease maximal oxygen consumption. In elderly HF patients, the prevalence of sarcopenia is higher than in those without HF; however, the relationship between sarcopenia and HF remains insufficiently explained, particularly in right HF (RHF). Our objective was to describe the echocardiographic alterations between sarcopenic and non-sarcopenic subjects with RHF. Methods: A cross-sectional study was conducted. Outpatients aged 18 years or older with a confirmed diagnosis of RHF were included. Sarcopenia was defined according to EWGSOP2. Results: A total of 183 patients were included; 24.5% had sarcopenia. The mean age was 64.34 ± 13.97 years. Echocardiographic characteristics revealed evidence of LVDD in sarcopenic subjects, as indicated by lower E wave velocity, E/A ratio, and e’ lateral and medial values, as well as lower right ventricular (RV) wall thickness compared with non-sarcopenic subjects. The multivariate model showed that sarcopenia subjects had lower RV wall thickness (B: −1.36 mm, 95% CI: −2.30 to −0.42), e’ medial (B: −1 cm/s, 95% CI: −1.99 to −0.02), and e’ lateral (B: −1.78 cm/s, 95% CI: −2.97 to −0.60). Conclusions: The prevalence of sarcopenia in RHF patients was 24.6%, which was associated with LVDD and lower RV wall thickness, suggesting a loss of cardiac muscle mass.

Minimally Invasive Diagnosis of a Cardiac Mass: Resolving Clinical-Imaging Discordance.

IntroductionNumerous studies have established the potential of nicorandil in alleviating myocardial fibrosis subsequent to myocardial infarction. Nevertheless, the precise mechanism underlying this effect remains incompletely elucidated. This study aims to investigate whether nicorandil can mitigate myocardial inflammation and oxidative stress during post-infarction remodeling in mice through animal experiments, thereby shedding light on its mechanism for ameliorating myocardial fibrosis after myocardial infarction by inhibiting inflammation and oxidative stress.MethodsThe male C57BL/6J mice were randomly allocated into the following groups: Sham group, MI group, Nic group and Nic + Glib group. The left anterior descending coronary artery (LAD) was ligated to induce myocardial infarction. The intervention lasted for 4 weeks after modeling in each group. Cardiac function was evaluated by echocardiography and cardiac mass index. Serum hs-CRP was quantified using ELISA. The oxidative stress level of myocardial tissue was determined using an oxidative stress detection box. HE staining and Masson staining were employed to evaluate the inflammatory response and fibrosis in myocardial tissue. Immunohistochemical staining was utilized to detect the inflammatory response and fibrosis markers in local myocardial tissue: IL-1β,TNF-α,IL-6,α-SMA and CollagenⅠ.ResultsNicorandil can improve left ventricular fractional shortening (LVFS%), left ventricular ejection fraction (LVEF%), and heart mass index after myocardial infarction, and reduce serum hs-CRP and the expression of IL-1β, TNF-α, IL-6, α-SMA, and collagenⅠ in myocardial tissue. In addition, it can increase SOD and GSH-Px levels and reduce MDA content in myocardial tissue. In addition, HE and Masson staining showed that nicorandil could inhibit myocardial and perivascular fibrosis to a certain extent, and reduce the level of local inflammatory response. These beneficial effects of nicorandil were inhibited to some extent by glibenclamide.ConclusionNicorandil attenuates myocardial inflammation, oxidative stress and myocardial fibrosis levels by activating ATP-sensitive potassium channels (K-ATP), thereby improving post-MI cardiac remodeling and preserving cardiac function.

ObjectiveNon-compaction cardiomyopathy (NCC) is a genetic disorder characterized by the presence of an extensive layer of trabecular myocardium with intertrabecular recesses communicated with the ventricular cavity. The aim of this work is to evaluate the clinical and morphological characteristics of patients with NCC with and without systolic dysfunction assessed by cardiac magnetic resonance imaging (Cardiac MRI). Material and MethodsTwenty patients with NCC diagnosis were retrospectively included. End- diastolic volume (LVEDV) and end-systolic volume, end-diastolic diameter (LVEDD) and end- systolic diameter, ejection fraction (LVEF), cardiac mass and LV trabeculations were determined. The distribution of NC myocardium was carried out with the model of 17 myocardial segments. ResultsThe average thickness of NC myocardium and normal myocardium was 13.1 ± 3.3 mm and 3.6 ± 0.6 mm respectively. LVEDD, LVEDV, global, compacted and trabecular left ventricular mass were significantly increased in patients with ventricular dysfunction. LVEF had a negative linear correlation with the trabecular myocardial mass (MM)/m2 (R = 0.67, p = 0.001), LVEDV/m2 (R = .77, p &lt;0.001) and LVEDD/ m2 (R = 0.7, p &lt;0.001). There was also a negative linear correlation between MM/m2 and LVEDV/m2 (R = 0.76, p &lt;0.001). ConclusionsThere are two ways of presenting the disorder, a subtle or mild with preserved systolic function and another associated to a ventricular dysfunction that behaves as dilated cardiomyopathy.

Primary cardiac sarcomas are exceedingly rare, with a very low incidence in the general population. A variety of sarcoma subtypes can originate in the heart, including angiosarcoma, rhabdomyosarcoma, leiomyosarcoma, fibrosarcoma, and osteosarcoma. These tumors are typically classified based on histological characteristics, most often determined following surgical excision or biopsy. Among them, primary cardiac osteosarcoma is one of the rarest forms, with fewer than 60 cases reported in the literature to date. This narrative review aims to provide an overview of primary cardiac osteosarcoma, including its epidemiology, clinical presentation, and current management strategies. Additionally, we highlight several remarkable case reports to illustrate the variability and complexity of this rare malignancy. # Summary The clinical presentation of primary cardiac osteosarcoma often mimics other cardiac conditions such as heart failure, mitral stenosis, or coronary artery disease, making diagnosis challenging. Transthoracic echocardiography (TTE) is typically the first imaging modality to detect a cardiac mass. Due to the rarity of the tumor, established treatment protocols are limited. Surgical resection is generally the preferred initial approach for localized disease without metastasis. Chemotherapy and radiation therapy may also be used, but their application must be carefully considered given the heart's sensitivity to these treatments. Despite advances in imaging, surgical techniques, and adjuvant therapies that have improved survival in some cases, the overall prognosis for primary cardiac osteosarcoma remains poor. # Conclusion Because primary cardiac osteosarcoma is so rare, establishing standardized treatment guidelines remains challenging. By reviewing historical cases and examining current clinical management strategies, we aim to contribute to a better understanding of this aggressive malignancy and ultimately improve patient outcomes.

Cardiac hemangiomas (CHs) are rare benign vascular tumors, which can develop in any cardiac chamber or layer. Large right atrial hemangioma causing compression of the pulmonary vein is exceedingly rare and complete surgical resection may be needed. A 52-year-old asymptomatic male was incidentally found to have a cardiac mass during a routine health examination. A well-defined, low-metabolism mass compressing the pulmonary vein was confirmed by PET-CT. The tumor was completely resected, and the histopathology and immunohistochemistry confirmed the diagnosis of cavernous hemangioma. The patient recovered uneventfully and was discharged in stable condition. Although rare, cardiac hemangiomas should be considered in the differential diagnosis of intracardiac masses. Complete surgical resection is feasible and leads to favorable outcomes, even in cases with complex anatomical relationships.

Background: Adolescence has been identified as a critical time point when physiological adaptations deviate into pathological cardiometabolic disease processes. Large-scale prospective evidence on the direct impact of increasing fat mass from adolescence with alterations in cardiac structure among apparently healthy adolescents is limited. Adolescent dyslipidaemia and elevated blood pressure (BP) have been established as independent predictors of premature cardiac damage. However, understanding the mechanism through which fat mass alters cardiac indices will be crucial for public health intervention and preventive cardiology. Purpose: To examine the longitudinal associations of total fat mass and trunk fat mass with progressive cardiac remodelling and examine the role of low-density lipoprotein cholesterol (LDL-c), systolic BP, and inflammation on the relationships. Methods: From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 1803 adolescents aged 17 years who had repeated dual-energy Xray absorptiometry-measured fat mass at ages 17 and 24 years clinic visits were included. Echocardiography at 17 and 24 years assessed left ventricular mass indexed for height 2.7 (LVM). Repeated-measure longitudinal multivariate-adjusted analyses were conducted with generalized linear mixed-effect models with identity links. Structural equation model causal mediation analysis assessed the proportion of the association between fat mass and cardiac mass during ages 17 to 24 years mediated by LDL-c, systolic BP, or high-sensitivity C-reactive protein (hsCRP). Results: Each unit increase of total fat mass from age 17–24 years ( β = 0.12g/m 2.7 [95% CI, 0.09 – 0.15], p&lt;0.001) and trunk fat mass (0.23g/m 2.7 [0.18 – 0.28], p&lt;0.001) were independently associated with increased LVM over the 7-year growth period. Increased LDL-c, systolic BP, and hsCRP partly mediated (7.9%, 10.6%, and 7.4% mediation, respectively) the longitudinal associations between increased fat mass and increased cardiac mass during growth from adolescence to young adulthood (Figure 1). Conclusions: Increased total and trunk fat mass in adolescence was associated with cardiac structural remodelling, partially explained by altered cardiometabolic and inflammatory indices. Trunk fat mass may have a two-fold worse deleterious effect on cardiac mass than total fat mass.

A 65-year-old male with history of coronary artery disease with percutaneous coronary intervention six months earlier presented with one month of fevers, night sweats, chest pain, muscle aches, fatigue, dyspnea on exertion and palpitations. CT chest revealed a 9x5cm mass in the right atrium and right ventricle, which was confirmed on TTE. He had a TTE two weeks earlier without evidence of a mass. Cardiac MRI further revealed a large pericardial effusion and the cardiac mass encasing the right coronary artery and superior vena cava causing near occlusion of the distal SVC. A biopsy and pericardiocentesis revealed acute leukemia of ambiguous lineage, but bone marrow biopsy and serial lumbar punctures were negative for disease. The patient underwent treatment with intravenous and intrathecal chemotherapy. His course was complicated by atrial fibrillation with rapid ventricular response requiring a rate control strategy as his chemotherapy-induced thrombocytopenia prevented anticoagulation. Initial restaging scans one to three months after chemotherapy showed resolution of uptake and reduction in mass size. However, subsequent scans one month after prior scans showed the mass to have increased uptake and size, so partial resection was performed with repeat pathology confirming acute leukemia of ambiguous lineage. Initial plans for bone marrow transplant were placed on hold given local recurrence. Currently, he is receiving palliative radiation as a bridge with hope for more targeted therapy. Acute undifferentiated leukemia is exceedingly rare and is defined as an absence of definitive myeloid or lymphoid lineage markers. There has never been a reported case of acute undifferentiated leukemia presenting as an isolated cardiac mass as seen in this case. Cardiac involvement in leukemia is rare, and it is usually associated with a distinct myeloid or lymphoid lineage if discovered. Patients with cardiac involvement are frequently asymptomatic and cardiac involvement may only be noted during autopsy. Overall, outcomes for cardiac hematologic malignancies are poor but are slightly more favorable in leukemias. Cardiac hematologic malignancies are exceedingly rare and can progress quickly. It is important to recognize them quickly and initiate definitive treatment plans as soon as possible to prevent local and metastatic recurrence. More research is needed to understand the progression of acute undifferentiated leukemia presenting as a cardiac mass.

Introduction: While previous studies have quantified the community prevalence of Cardiovascular-Kidney-Metabolic (CKM) Stages, limited data exist regarding the expected progression of CKM Stages in mid-life. Methods: Among participants in the population-sampled Dallas Heart Study (DHS) longitudinal cohort, we estimated the prevalence of CKM Stages at Visit 1 (DHS1; 2000-2002) and Visit 2 (DHS2, 2007–2009). Protocol measurements of body composition, lipids, fasting blood sugar, serum creatinine, NT-proBNP, hs-cTnT, urinary albumin and creatinine, coronary artery calcium by cardiac CT (CAC), and cardiac function and mass by cardiac MRI were conducted at both visits. To account for Visit 2 non-attendance, we performed additional sensitivity analysis using inverse probability of attrition weights (IPAW) with the following DHS1 variables as predictors of DHS2 attendance: age, sex, race, obesity, income, education level, eGFR, ejection fraction, cardiovascular risk score, and history of heart failure, coronary heart disease, or stroke. Results: Among 2,991 participants at DHS1, 2030 also attended DHS2 and had an age of 44±10 years at DHS1 and 52±10 years at DHS2, 58% were female, and 50% reported non-Hispanic Black race/ethnicity. Over the median 6.8 (IQR 6.3-7.3) years between DHS1 and DHS2, the prevalence of CKM Stage 1 decreased from 14.7 to 10.8%; while the prevalence of CKM Stage 4 increased from 6% to 13%. Overall, 32% had progression in CKM Stage ( Figure) . Among the 280 (14%) participants who improved their CKM Stage, 206 (74%) derived from Stage 3 at DHS1, primarily meeting these criteria due to elevated troponin. Similar findings were observed in analyses incorporating IPAW to account for DHS2 non-attendance. Conclusion: In a community-based cohort, CKM Stages progressed in nearly one-third over 7 years in mid-life. The prevalence of advanced CKM Stages (i.e., Stage 3 and 4) increased from 28% to 34%. The role and criteria of cardiac biomarkers in defining Stage 3 CKM warrant further study.

Regular vigorous exercise brings about cardiovascular adaptations, but the relationship between cardiac magnetic resonance-derived T1 and T2 mapping and physical fitness is not fully understood, with conflicting literature results. This study aims to define the associations between cardiorespiratory fitness evaluated using cardiopulmonary exercise testing (CPET) and cardiac remodelling using cardiac magnetic resonance (CMR), including T1 and T2 mapping. We enrolled elite, healthy athletes undergoing pre-participation screening (including personal and family history, physical examination, and 12-lead ECG) who volunteered for maximal CPET and non-contrast CMR with a 1.5T scanner, performed no more than 31 days apart. Our study population comprised 125 athletes: median age 19 [16-24.5] years; 65% males; median hours of training 20 [15-24.5]; 9% power, 36% endurance, 55% mixed. Overall, female athletes showed less pronounced cardiorespiratory and cardiac morphological remodelling compared to their male counterparts, and endurance athletes exhibited the highest levels of cardiorespiratory fitness and the most pronounced cardiac remodelling of the sport types considered. Greater overall fitness was associated with larger cardiac volumes and mass, and lower T1 and T2 values. In multivariate analysis, sex, sport type, LVMi, EDWT, VO2 max, and peak lactate collectively explained ∼27% of the variation in T1 values. Cardiac remodelling in athletes appears to be influenced by training load, sex, and sport type. In this study, we demonstrate for the first time an association between myocardial tissue characteristics, assessed by mapping, and cardiopulmonary fitness, evaluated through CPET. This finding suggests a potential link between aerobic adaptation and tissue-level myocardial properties. Further studies are warranted to validate these associations and to clarify their role in distinguishing physiological athletic remodelling from early pathological changes.

Background: The recent AHA presidential advisory on Cardiovascular-Kidney-Metabolic Syndrome (CKM) proposed a novel staging scheme, but limited data exist regarding the associations of CKM Stages with incident cardiovascular events and mortality. Methods: We included participants in the Dallas Heart Study, a population-sampled cohort from Dallas County, who attended study Visit 1 (2000-2002) and underwent protocol measurement of body composition, lipids, fasting blood sugar, serum creatinine, NT-proBNP, hs-cTnT, urinary albumin and creatinine, coronary artery calcium by cardiac CT (CAC), and cardiac function and mass by cardiac MRI. CKM Stages were defined as per AHA CKM definitions: Stage 0 – no CKM risk factors; 1 – excess or dysfunctional adiposity; 2 – metabolic risk factors and/or chronic kidney disease; 3 – subclinical cardiovascular diseases [CAC, left ventricular hypertrophy or dysfunction by cardiac MRI, elevated cardiac biomarkers (NT-proBNP or hs-cTnT), high AHA-PREVENT or KDIGO scores]; 4 – prevalent cardiovascular diseases [coronary heart disease (CHD), heart failure (HF), atrial fibrillation, stroke]. Participants were followed for fatal and non-fatal clinical outcomes, including CHD, HF, and stroke through December 31 th 2018. Multivariable Cox proportional hazard models were used to assess the relationship of the CKM Stage with incident events compared to absent CKM or Stage 1, adjusting for age, sex, and race. Results: Among the 2,991 participants (age 44±10 years, 56% female, 50% reported non-Hispanic Black race), CKM stage prevalence was 9% Stage 0, 14% Stage 1, 47% Stage 2, 22% Stage 3, and 7% Stage 4. Over a median follow-up of 16.9 (IQR 16.4 -17.6) years, 19% died or developed CHD, HF, or stroke. No significant differences in risk were observed between Stage 0 and Stage 1 for composite and individual outcomes. Compared to those with Stage 0 or 1 CKM, a graded association was observed between greater CKM Stage 2-4 and heightened risk of composite CHD, HF, stroke, or death [HR 1.8 (95% CI 1.3-2.5), 3.5 (2.5-4.8), 5.4 (3.8-7.8), respectively] in adjusted model. Similar trends were observed for each component of the composite ( Figure) . Conclusion: Over 17 years of follow-up, individuals with CKM Stage 1 did not experience worse outcomes than those free of CKM Stage. CKM Stages 2, 3, and 4 were associated with a stepwise higher risk of all cause mortality and incident CHD, HF, and stroke compared to those with Stage 0 or 1 CKM.

The following manuscript documents the management of a middle-aged male, who underwent surgical resection of a large, right atrial cardiac lipoma. The patient presented with an extensive oncologic history including osteogenic sarcoma, melanoma and pulmonary neoplasm, suggesting that his cardiac mass was part of a syndromic presentation. In this case, surgical resection was pursued both to treat his increased symptom burden and to obtain definitive tissue diagnosis. Hence, this case report demonstrates how a syndromic presentation of cardiac lipoma requires a lower threshold for surgical resection, especially when considering heightened malignancy risk.

Abstract Introduction/Objective Cardiac tumors are rare, with myxomas being the most common primary cardiac tumor. Low-grade neuroendocrine tumors (NETs) are neoplasms arising from neuroendocrine cells, and they are most frequently found in the gastrointestinal tract and lungs. Historically, they were referred to as “carcinoid” tumors. NETs are relatively rare, with an estimated incidence ranging from 2.5 to 5 cases per 100,000 population per year. Involvement of the heart by NETs is exceedingly rare and almost universally represents metastasis from a distant primary. Cardiac metastasis from carcinoid tumors occurs in approximately 4% of patients, many of which have advanced disease and carcinoid syndrome. Primary neuroendocrine tumors of the heart are even rarer, with limited cases described in the literature, and their occurrence within the interventricular septum is virtually unknown. This report highlights a unique case of a low-grade neuroendocrine tumor presenting as a cardiac mass, with a unique natural history. Methods/Case Report A 56-year-old woman with a history of mitral valve minimally invasive surgical repair in 2015 presented with new-onset dyspnea on exertion, dizziness, and a recent presyncopal episode, but no chest pain, orthopnea, flushing, diarrhea, or lower extremity edema. Transthoracic echocardiography revealed a 4 cm spherical mass (size 4 cm) attached to the apex of the interventricular septum, protruding into the right ventricle. Cardiac CT angiography confirmed a well circumscribed mass with no invasion. Whole-body PET-CT showed increased radiotracer uptake localized to the cardiac mass, with no evidence of abnormal uptake elsewhere in the body. The initial impression was a cardiac myxoma. Surgical resection was performed. Gross examination revealed a rounded firm, tan yellow mass measuring 4.0 cm. Histologically, the tumor consisted of a neuroendocrine tumor composed of uniform cells with low-grade features, with no mitotic activity or necrosis. Immunohistochemical stains were positive for Pancytokeratin (AE1/AE3), Chromogranin, and Synaptophysin, supporting the diagnosis of a neuroendocrine tumor. The Ki-67 proliferation index was approximately 1%, indicative of a low-grade tumor. Immunohistochemical stains for Cytokeratin 7, Cytokeratin 20, TTF-1, PAX8, and GATA3 were negative. Of note, immunohistochemical stain for CDX2 was diffusely positive, strongly suggesting origin from a primary tumor in the midgut. Results NA Conclusion Neuroendocrine tumors of the heart are exceedingly rare and often present with non-specific symptoms or no symptoms at all. Imaging findings may mimic more common cardiac tumors, such as myxomas. Histopathologic evaluation and immunohistochemical profiling are essential for definitive diagnosis. CDX2 positivity by immunohistochemistry within metastatic carcinoid tumors is strongly associated with a small intestinal primary, even in the absence of a detectable primary lesion. This case demonstrates the necessity of considering alternate diagnoses other than myxoma for tumors in the ventricle. It also highlights the unique natural history of some of these lesions that present as metastases before detection of a primary tumor, and without the clinical features of carcinoid syndrome.