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Abstract Aims Right ventricular (RV) allograft dysfunction is present in half of all heart transplant (HT) recipients. Non‐invasive assessment of RV function in the setting of rejection is not well described. We outline an echocardiographic technique, short‐axis fractional area change (SAXFAC), to evaluate RV function in the HT population and correlate this with the grade of pathologic rejection. Methods and results We retrospectively reviewed the electronic medical records of 110 people who received a HT between 1 January 2015 and 29 February 2020 and had no evidence of rejection. One hundred eighty‐two transthoracic echocardiograms (TTEs) completed up to 1 year from the date of transplantation were analysed for the target acoustic window, the parasternal mid‐ventricular short‐axis view. Sixty‐one TTEs from 23 healthy transplants were deemed appropriate for SAXFAC determination. Thirty‐three organ recipients with at least grade 1R allograft rejection were also identified, and their TTEs screened for SAXFAC analysis. Two expert readers independently calculated SAXFAC as follows: RV end‐diastolic area minus end‐systolic area divided by end‐diastolic area. Using commercially available software (Epsilon, Ann Arbor, Michigan), we quantified RV radial strain, longitudinal strain, and apical fractional area change (FAC). Twenty‐eight transplant recipients with grade 0R or 1R rejection and nine patients with clinically significant rejection completed the study analysis. SAXFAC demonstrated significant variability in the entire population with an inverse relationship to severity of allograft rejection (P ≤ 0.01). Radial strain and FAC were also associated with clinically significant rejection (P ≤ 0.01). Conclusions Short‐axis fractional area change is a simple two‐dimensional technique to assess RV function in HT recipients and showed no significant inter‐observer variability. In our small, single‐centre, retrospective case series, lower SAXFAC values were associated with clinically significant allograft rejection. The small sample size and infrequent occurrence of rejection make our observations hypothesis‐generating only. We advocate dedicated RV SAXFAC imaging planes be included when assessing allograft function.

BackgroundCardiac tumors are usually metastatic. Melanoma is the tumor with the highest rate of cardiac metastasis. Clinicians need to be aware of the metastatic involvement of the left ventricular apex as a differential diagnosis of apical hypertrophic cardiomyopathy.Case summaryA 74-year-old woman presented for evaluation of fatigue. The initial electrocardiogram and echocardiogram showed features of apical hypertrophic cardiomyopathy. The patient reported a lesion on her right forearm that had been present for many years, leading to its biopsy, which showed melanoma. Further evaluation with a chest-computed tomography (CT) scan showed left lung nodules and nodular thickening of the left ventricular apex. Positron emission tomography showed an increased uptake of fluorodeoxyglucose in the left lung nodule and left ventricular apex, suggestive of metastatic spread of the melanoma. A CT-guided biopsy of the left lung nodule revealed melanoma. The patient was treated with ipilimumab initially, followed by paclitaxel with poor response to treatment, and later passed under hospice care.ConclusionMetastatic tumors involving the left ventricular apex should be considered in the differential diagnosis of apical hypertrophic cardiomyopathy, especially in patients with a history of melanoma, and advanced cardiac imaging, including cardiac magnetic resonance imaging, CT, and/or positron emission tomography (PET) may help with narrowing down the differential diagnosis.

Chronic exposure to silica is a recognized health hazard. Manifestations of pulmonary and extrapulmonary silicosis are well described. Secondary pulmonary arterial hypertension and pericardial involvement are described, but myocardial involvement has not been reported. In this case of newly diagnosed pulmonary silicosis, ventricular tachycardia results are shown from pathological involvement of ventricular myocardium. (Level of Difficulty: Beginner.)

Background Age‐related heart diseases are significant contributors to increased morbidity and mortality. Emerging evidence indicates that mitochondria within cardiomyocytes contribute to age‐related increased reactive oxygen species (ROS) generation that plays an essential role in aging‐associated cardiac diseases. Methods and Results The present study investigated differences between ROS production in cardiomyocytes isolated from adult (6 months) and aged (24 months) Fischer 344 rats, and in cardiac tissue of adult (18–65 years) and elderly (>65 years) patients with preserved cardiac function. Superoxide dismutase inhibitable ferricytochrome c reduction assay (1.32±0.63 versus 0.76±0.31 nMol/mg per minute; P=0.001) superoxide and H2O2 production, measured as dichlorofluorescein diacetate fluorescence (1646±428 versus 699±329, P=0.04), were significantly higher in the aged versus adult cardiomyocytes. Similarity in age‐related alteration between rats and humans was identified in mitochondrial‐electron transport chain‐complex‐I‐associated increased oxidative‐stress by MitoSOX fluorescence (53.66±18.58 versus 22.81±12.60; P=0.03) and in 4‐HNE adduct levels (187.54±54.8 versus 47.83±16.7 ng/mg protein, P=0.0063), indicative of increased peroxidation in the elderly. These differences correlated with changes in functional enrichment of genes regulating ROS homeostasis pathways in aged human and rat hearts. Functional merged collective network and pathway enrichment analysis revealed common genes prioritized in human and rat aging‐associated networks that underlay enriched functional terms of mitochondrial complex I and common pathways in the aging human and rat heart. Conclusions Aging sensitizes mitochondrial and extramitochondrial mechanisms of ROS buildup within the heart. Network analysis of the transcriptome highlights the critical elements involved with aging‐related ROS homeostasis pathways common in rat and human hearts as targets.

Vagal nerve stimulators are devices used to treat medically refractory epilepsy. Here, we present a rare, unique, and life-threatening side effect of vagal nerve stimulator placement. (Level of Difficulty: Advanced.)

Abstract Aims Fibroblast to myofibroblast trans‐differentiation with altered bioenergetics precedes cardiac fibrosis (CF). Either prevention of differentiation or promotion of de‐differentiation could mitigate CF‐related pathologies. We determined whether 3‐hydroxy‐3‐methyl‐glutaryl‐coenzyme A (HMG‐CoA) reductase inhibitors—statins, commonly prescribed to patients at risk of heart failure (HF)—can de‐differentiate myofibroblasts, alter cellular bioenergetics, and impact the human ventricular fibroblasts (hVFs) in HF patients. Methods and results Either in vitro statin treatment of differentiated myofibroblasts (n = 3–6) or hVFs, isolated from human HF patients under statin therapy (HF + statin) vs. without statins (HF) were randomly used (n = 4–12). In vitro, hVFs were differentiated by transforming growth factor‐β1 (TGF‐β1) for 72 h (TGF‐72 h). Differentiation status and cellular oxygen consumption rate (OCR) were determined by α‐smooth muscle actin (α‐SMA) expression and Seahorse assay, respectively. Data are mean ± SEM except Seahorse (mean ± SD); P

Bidirectional ventricular tachycardia (BDVT), a rare ventricular arrhythmia, is commonly caused by digitalis toxicity or channelopathies and is rarely caused by aconite toxicity, myocarditis, infarction, or sarcoidosis. This paper describes a patient with BDVT, recurrent syncope, myocardial disarray, and interstitial fibrosis on histology but normal results on echocardiography with variants in the TTN, KCNH2, and GATA4 genes. (Level of Difficulty: Advanced.)

BackgroundThe risk of thromboembolism and bleeding before initiation of oral anticoagulant (OAC) in atrial fibrillation patients is estimated by CHA2DS2-VASc and HAS-BLED scoring system, respectively. Patients' socioeconomic status (SES) could influence these risks, but its impact on the two risk scores' predictive performance with respect to clinical events remains unknown. Our objective was to determine if patient SES defined by area deprivation index (ADI), in conjunction with CHA2DS2-VASc and HAS-BLED scores, could guide oral anticoagulation therapy.Methods and findingsThe study cohort included newly diagnosed patients with AF who were treated with warfarin. The cohort was stratified by the time in therapeutic range of INR (TTR), ADI, CHA2DS2-VASc, and HAS-BLED risk scores. TTR and ischemic and bleeding events during the first year of therapy were compared across subpopulations. Among 7274 patients, those living in the two most deprived quintiles (ADI ≥60%) had a significantly higher risk of ischemic events and those in the most deprived quintile (ADI≥80%) had a significantly increased risk of bleeding events. ADI significantly improved the predictive performance of CHA2DS2-VASc but not HAS-BLED risk scores.ConclusionADI can predict increased risk for ischemic and bleeding events in the first year of warfarin therapy in patients with incident AF.

Delayed perforation of the coronary artery and extraluminal migration of coronary stent is a rare phenomenon. We report a case in which the stent was documented to perforate the coronary artery at least 1 year after the intervention and migrated within the pericardium without any symptom. (Level of Difficulty: Intermediate.)

Excessive cardiac fibrosis, characterized by increased collagen-rich extracellular matrix (ECM) deposition, is a major predisposing factor for mechanical and electrical dysfunction in heart failure (HF). The human ventricular fibroblast (hVF) remodeling mechanisms that cause excessive collagen deposition in HF are unclear, although reports suggest a role for intracellular free Ca2+ in fibrosis. Therefore, we determined the association of differences in cellular Ca2+ dynamics and collagen secretion/deposition between hVFs from failing and normal (control) hearts. Histology of left ventricle sections (Masson trichrome) confirmed excessive fibrosis in HF versus normal. In vitro, hVFs from HF showed increased secretion/deposition of soluble collagen in 48 h of culture compared with control [85.9±7.4 µg/106 cells vs 58.5±8.8 µg/106 cells, P

PurposeHigh calorie intake leads to obesity, a global socio-economic and health problem, reaching epidemic proportion in children and adolescents. Saturated and monounsaturated fatty acids from animal (lard) fat are major components of the western-pattern diet and its regular consumption leads to obesity, a risk factor for cardiovascular disease. However, no clear evidence exists whether consumption of diet rich in saturated (SFAs) and monounsaturated (MUFAs) fatty acids has detrimental effects on cardiac structure and energetics primarily due to excessive calories. We, therefore, sought to determine the impact of high calories versus fat content in diet on cardiac structure and mitochondrial energetics.MethodsSix-week-old C57BL/6J mice were fed with high calorie, high lard fat-based diet (60% fat, HFD), high-calorie and low lard fat-based diet (10% fat, LFD), and lower-calorie and fat diet (standard chow, 12% fat, SCD) for 10 weeks.ResultsThe HFD- and LFD-fed mice had higher body weight, ventricular mass and thickness of posterior and septal wall with increased cardiomyocytes diameter compared to the SCD-fed mice. These changes were associated with a reduction in the mitochondrial oxidative phosphorylation (OXPHOS) complexes I and III activity compared to the SCD-fed mice without significant differences between the HFD- and LFD-fed animals. The HFD-fed animals had higher level of malondialdehyde (MDA) than LFD and SCD-fed mice.ConclusionsWe assume that changes in cardiac morphology and selective reduction of the OXPHOS complexes activity observed in the HFD- and LFD-fed mice might be related to excessive calories with additional effect of fat content on oxidative stress.