Reporting of sex as a variable in cardiovascular studies using cultured cells: A systematic review.

Reporting the sex of biological material is critical for transparency and reproducibility in science. This study examined the reporting of the sex of cells used in cardiovascular studies. Articles from 16 cardiovascular journals that publish peer-reviewed studies in cardiovascular physiology and pharmacology in the year 2018 were systematically reviewed using terms "cultured" and "cells." Data were collected on the sex of cells, the species from which the cells were isolated, and the type of cells, and summarized as a systematic review. Sex was reported in 88 (38.6%) of the 228 studies meeting inclusion criteria. Reporting rates varied with Circulation, Cardiovascular Research and American Journal of Physiology: Heart and Circulatory Physiology having the highest rates of sex reporting (>50%). A majority of the studies used cells from male (54.5%) or both male and female animals (32.9%). Humans (31.8%), rats (20.4%), and mice (43.8%) were the most common sources for cells. Cardiac myocytes were the most commonly used cell type (37.0%). Overall reporting of sex of experimental material remains below 50% and is inconsistent among journals. Sex chromosomes in cells have the potential to affect protein expression and molecular signaling pathways and should be consistently reported.

Cardiac magnetic resonance imaging in heart transplant recipients with biopsy-negative graft dysfunction.

AIMS: Graft dysfunction (GD) after heart transplantation (HTx) can develop without evidence of cell- or antibody-mediated rejection. Cardiac magnetic resonance imaging (CMR) has an evolving role in detecting rejection; however, its role in biopsy-negative GD has not been described. This study examines CMR findings, evaluates outcomes based on CMR results, and seeks to identify the possibility of rejection missed through endomyocardial biopsy by using CMR in HTx recipients with biopsy-negative GD. METHODS AND RESULTS: HTx recipients with GD [defined as a decrease in left ventricular ejection fraction (LVEF) by >5% and LVEF < 50%] in the absence of rejection by biopsy or allograft vasculopathy and who underwent CMR were included in the study. The primary outcome was a composite of all-cause mortality, re-transplantation, or persistent LVEF < 50%. Overall, 34 HTx recipients developed biopsy-negative GD and underwent CMR. Left ventricular late gadolinium enhancement (LGE) on CMR was observed in 16 patients with two distinct patterns: diffuse epicardial (n = 13) and patchy (n = 3) patterns. Patients with LGE developed GD later after HTx [4 (1.4-6.8) vs. 0.8 (0.3-1.2) years, P < 0.001], were more often symptomatic (88% vs. 56%, P = 0.06), and had greater haemodynamic derangement (pulmonary capillary wedge pressure: 19 ± 7 vs. 13 ± 3 mmHg, P = 0.002) as compared with those without LGE. No significant difference was observed in the primary composite outcome between patients with LGE and those without LGE (50% vs. 38% of patients with events, P = 0.515). During a median follow-up of 3.8 years, mean LVEF improved similarly in the LGE-negative (37-55%) and LGE-positive groups (32-55%) (P = 0.16). CONCLUSIONS: Biopsy-negative GD occurs with and without LGE when assessed by CMR, indicative of possible rejection/inflammation occurring only in a subset of patients. Irrespective of LGE, LVEF improvement occurs in most GD patients, suggesting that other neurohormonal or immunomodulatory mechanisms may also contribute to GD development.

Racial and ethnic characteristics and cancer-specific survival in Primary Malignant Cardiac Tumors.

Background: There is limited insight into the epidemiological characteristics and effect of race and ethnicity on Primary Malignant Cardiac Tumors (PMCTs). Objectives: Comparison of clinical characteristics and cancer-specific survival outcomes of major races in the United States from the Surveillance, Epidemiology and End-Result (SEER) registry. Methods: ICD-O-3 codes were used to identify PMCTs for the years 1975 to 2015. Three major races were identified-"White", "Black", and "Asian/Pacific Islander". Cancer-specific survival outcomes were compared using Kaplan-Meier analysis across and amongst races, based on tumor histology. A subgroup analysis of cancer-specific survival was performed between "Hispanics" and "non-Hispanics." Results: Seven hundred and twenty patients were identified-47% females and 79% White, mean age at diagnosis (47 ± 20 years). Black patients were significantly younger (39 ± 18 years) and presented more commonly with angiosarcomas (53%). Non-angiogenic sarcomas and lymphomas were the most common tumors in the White (38%) and Asian/Pacific Islander (34%) cohorts. For a median follow-up period of 50 (IQR3-86) months, cancer-specific survival (mean ± SD, in months) was worse in Blacks (9 ± 3) as compared to Whites (15 ± 1) and Asian/Pacific Islander (14 ± 1) (p-value; Black vs. White <0.001; Black vs. Asian/Pacific Islanders = 0.017, White vs. Asian/Pacific Islanders = 0.3). Subgroup analysis with 116 (16%) Hispanics (40% females; mean age of 40 ± 20 years) showed a longer mean cancer-specific survival of 16.9 ± 2.4 months as compared to 13.6 ± 1.1 months in non-Hispanics (p = 0.011). Conclusion: Black and non-Hispanic patients have poorer cancer-specific survival in PMCTs.

Rare TBX4 Variant Causing Pulmonary Arterial Hypertension With Small Patella Syndrome in an Adult Man.

Small patella syndrome presents with small or absent patellae and may result in pulmonary arterial hypertension, typically in children. A pathogenic canonical splice site variant, c.1021+1G>A in the T-box transcription factor 4 (TBX4) gene, currently not included in commercial gene panel, was detected in an adult with pulmonary arterial hypertension and absent patellae. (Level of Difficulty: Advanced.).

Artificial Intelligence-Enabled Electrocardiography to Screen Patients with Dilated Cardiomyopathy.

Undiagnosed dilated cardiomyopathy (DC) can be asymptomatic or present as sudden cardiac death, therefore pre-emptively identifying and treating patients may be beneficial. Screening for DC with echocardiography is expensive and labor intensive and standard electrocardiography (ECG) is insensitive and non-specific. The performance and applicability of artificial intelligence-enabled electrocardiography (AI-ECG) for detection of DC is unknown. Diagnostic performance of an AI algorithm in determining reduced left ventricular ejection fraction (LVEF) was evaluated in a cohort that comprised of DC and normal LVEF control patients. DC patients and controls with 12-lead ECGs and a reference LVEF measured by echocardiography performed within 30 and 180 days of the ECG respectively were enrolled. The model was tested for its sensitivity, specificity, negative predictive (NPV) and positive predictive values (PPV) based on the prevalence of DC at 1% and 5%. The cohort consisted of 421 DC cases (60% males, 57±15 years, LVEF 28±11%) and 16,025 controls (49% males, age 69 ±16 years, LVEF 62±5%). For detection of LVEF≤45%, the area under the curve (AUC) was 0.955 with a sensitivity of 98.8% and specificity 44.8%. The NPV and PPV were 100% and 1.8% at a DC prevalence of 1% and 99.9% and 8.6% at a prevalence of 5%, respectively. In conclusion AI-ECG demonstrated high sensitivity and negative predictive value for detection of DC and could be used as a simple and cost-effective screening tool with implications for screening first degree relatives of DC patients.

Effect of CYP2C19 Genotype on Ischemic Outcomes During Oral P2Y12 Inhibitor Therapy: A Meta-Analysis.

OBJECTIVES: The aim of this study was to examine the effect of CYP2C19 genotype on clinical outcomes in patients with coronary artery disease (CAD) who predominantly underwent percutaneous coronary intervention (PCI), comparing those treated with ticagrelor or prasugrel versus clopidogrel. BACKGROUND: The effect of CYP2C19 genotype on treatment outcomes with ticagrelor or prasugrel compared with clopidogrel is unclear. METHODS: Databases through February 19, 2020, were searched for studies reporting the effect of CYP2C19 genotype on ischemic outcomes during ticagrelor or prasugrel versus clopidogrel treatment. Study eligibility required outcomes reported for CYP2C19 genotype status and clopidogrel and alternative P2Y12 inhibitors in patients with CAD with at least 50% undergoing PCI. The primary analysis consisted of randomized controlled trials (RCTs). A secondary analysis was conducted by adding non-RCTs to the primary analysis. The primary outcome was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia. Meta-analysis was conducted to compare the 2 drug regimens and test interaction with CYP2C19 genotype. RESULTS: Of 1,335 studies identified, 7 RCTs were included (15,949 patients, mean age 62 years; 77% had PCI, 98% had acute coronary syndromes). Statistical heterogeneity was minimal, and risk for bias was low. Ticagrelor and prasugrel compared with clopidogrel resulted in a significant reduction in ischemic events (relative risk: 0.70; 95% confidence interval: 0.59 to 0.83) in CYP2C19 loss-of-function carriers but not in noncarriers (relative risk: 1.0; 95% confidence interval: 0.80 to 1.25). The test of interaction on the basis of CYP2C19 genotype status was statistically significant (p = 0.013), suggesting that CYP2C19 genotype modified the effect. An additional 4 observational studies were found, and adding them to the analysis provided the same conclusions (p value of the test of interaction <0.001). CONCLUSIONS: The effect of ticagrelor or prasugrel compared with clopidogrel in reducing ischemic events in patients with CAD who predominantly undergo PCI is based primarily on the presence of CYP2C19 loss-of-function carrier status. These results support genetic testing prior to prescribing P2Y12 inhibitor therapy.

Post-discharge arrhythmic risk stratification of patients with acute myocarditis and life-threatening ventricular tachyarrhythmias.

AIMS: The outcomes of patients presenting with acute myocarditis and life-threatening ventricular arrhythmias (LT-VA) are unclear. The aim of this study was to assess the incidence and predictors of recurrent major arrhythmic events (MAEs) after hospital discharge in this patient population. METHODS AND RESULTS: We retrospectively analysed 156 patients (median age 44 years; 77% male) discharged with a diagnosis of acute myocarditis and LT-VA from 16 hospitals worldwide. Diagnosis of myocarditis was based on histology or the combination of increased markers of cardiac injury and cardiac magnetic resonance (CMR) Lake Louise criteria. MAEs were defined as the relapse, after discharge, of sudden cardiac death or successfully defibrillated ventricular fibrillation, or sustained ventricular tachycardia (sVT) requiring implantable cardioverter-defibrillator therapy or synchronized external cardioversion. Median follow-up was 23 months [first to third quartile (Q1-Q3) 7-60]. Fifty-eight (37.2%) patients experienced MAEs after discharge, at a median of 8 months (Q1-Q3 2.5-24.0 months; 60.3% of MAEs within the first year). At multivariable Cox analysis, variables independently associated with MAEs were presentation with sVT [hazard ratio (HR) 2.90, 95% confidence interval (CI) 1.38-6.11]; late gadolinium enhancement involving ≥2 myocardial segments (HR 4.51, 95% CI 2.39-8.53), and absence of positive short-tau inversion recovery (STIR) (HR 2.59, 95% CI 1.40-4.79) at first CMR. CONCLUSIONS: Among patients discharged with a diagnosis of myocarditis and LT-VA, 37.2% had recurrences of MAEs during follow-up. Initial CMR pattern and sVT at presentation stratify the risk of arrhythmia recurrence.