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Purpose: Pulmonary arterial hypertension (PAH) is a disorder characterized by elevated pulmonary arterial pressure which leads to cardiac hypertrophy and dysfunction. Current treatments have marginal impact and additional therapies are required. Melatonin is a natural product shown to be cardioprotective against hypertension and myocardial ischemia. We propose that melatonin treatment may be cardioprotective in a model of monocrotaline (MCT) induced PAH.Methods: Male Long Evans rats (150-175g) were injected with MCT (80mg/kg) which induced PAH after 28 days. Melatonin (6mg/kg) was added in drinking water after 14 days of PAH development, until day 28 (n>5). Cardiac hypertrophy was confirmed with a ratio of the right ventricle weight over left ventricle plus septal weight (RVW/LV+S). Cardiac functional parameters were assessed at day 28, using isolated heart perfusion and echocardiography including right ventricular systolic (RVSP), developed pressure (RVDP) and left ventricular end diastolic volume (LVEDV). We also assessed plasma levels of oxidative stress (TBARS).Results: Melatonin reduced RVW/LV+S (0.56 ± 0.03 vs. 0.34 ± 0.03, p < 0.0006), RVSP (92.74 ± 5.13 mmHg vs. 79.82 ± 0.51mmHg, p < 0.0001) and RVDP (81.22 ± 2.75mmHg vs. 71.39 ± 0.57mmHg, p < 0.025). Melatonin also improved LVEDV (0.173 ± 0.01mL vs. 0.65± 0.08mL, p< 0.0002) and plasma TBARS (2.07 ± 0.28μM/mg protein vs. 1.25 ± 0.06μM/mg protein, p< 0.019).Conclusions: Our data suggest that melatonin improves cardiac function in far progressed experimental PAH by decreasing oxidative stress. Melatonin may represent a novel therapeutic approach in the treatment of PAH. [ABSTRACT FROM PUBLISHER]

18 F-flurodeoxyglycose (FDG)/ 13 N-ammonia positron emission tomography/computed tomography (PET/CT) is frequently utilized to evaluate cardiac sarcoidosis (CS) but findings can reflect other forms of myocardial inflammation or altered myocardial metabolic activity. Herein, we present five cases where cardiac PET findings suggested CS, but right ventricular endomyocardial biopsy samples revealed ATTR-type cardiac amyloidosis., (© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Objective: Endomyocardial biopsy (EMB) is a useful diagnostic tool though the yield may be limited in many myocardial diseases. Data on the diagnostic yield and prognostic significance of EMB guided by abnormal electrograms (EGM-Bx) in suspected cardiac sarcoidosis (CS) are scarce., Methods: Seventy-nine patients (mean age: 56 ± 12 years; 61% men) with suspected CS based on clinical and imaging features underwent right or left ventricular EGM-Bx guided by electroanatomic mapping. Tissue samples were obtained from sites with abnormal EGMs and/or abnormal cardiac imaging. The diagnostic yield of EGM-Bx was evaluated in reference to histopathologic analysis. Left ventricular assist device (LVAD) and transplantation-free survival were compared between patients with positive and negative EGM-Bx for CS., Results: A total of 254 samples were obtained from abnormal EGM sites, and 126 samples from normal EGM sites guided by pre-procedure imaging findings. Abnormal histopathology was noted in 65 (26%) and 10 (8%) samples from abnormal and normal EGM sites, respectively. Histopathology confirmed CS in 16 (20%) patients, while an alternative tissue diagnosis emerged in 10 (13%) patients. Abnormal EGMs at the biopsy site had sensitivity 89% and specificity 33% for a histopathologic diagnosis of CS. LVAD and transplantation-free survival were not significantly associated with the EGM-Bx result (log-rank p = .91)., Conclusion: In patients with suspected CS, abnormal EGM-Bx has high sensitivity and low specificity for establishing a definite CS diagnosis. Consideration of substrate abnormalities apparent on preprocedural imaging as an adjunct for selection of biopsy sites may further improve EGM-Bx yield., (© 2021 Wiley Periodicals LLC.)

Aims: Cardiovascular disease is a major threat to maternal health, with cardiomyopathy being among the most common acquired cardiovascular diseases during pregnancy and the postpartum period. The aim of our study was to evaluate the effectiveness of an electrocardiogram (ECG)-based deep learning model in identifying cardiomyopathy during pregnancy and the postpartum period., Methods and Results: We used an ECG-based deep learning model to detect cardiomyopathy in a cohort of women who were pregnant or in the postpartum period seen at Mayo Clinic. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. We compared the diagnostic probabilities of the deep learning model with natriuretic peptides and a multivariable model consisting of demographic and clinical parameters. The study cohort included 1807 women; 7%, 10%, and 13% had left ventricular ejection fraction (LVEF) of 35% or less, <45%, and <50%, respectively. The ECG-based deep learning model identified cardiomyopathy with AUCs of 0.92 (LVEF ≤ 35%), 0.89 (LVEF < 45%), and 0.87 (LVEF < 50%). For LVEF of 35% or less, AUC was higher in Black (0.95) and Hispanic (0.98) women compared to White (0.91). Natriuretic peptides and the multivariable model had AUCs of 0.85 to 0.86 and 0.72, respectively., Conclusions: An ECG-based deep learning model effectively identifies cardiomyopathy during pregnancy and the postpartum period and outperforms natriuretic peptides and traditional clinical parameters with the potential to become a powerful initial screening tool for cardiomyopathy in the obstetric care setting., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The etiology of peripartum cardiomyopathy remains unknown. One hypothesis is that an increase in the 16-kDa form of prolactin is pathogenic and suggests that breastfeeding may worsen peripartum cardiomyopathy by increasing prolactin, while bromocriptine, which blocks prolactin release, may be therapeutic. An autoimmune etiology has also been proposed. The authors investigated the impact of breastfeeding on cellular immunity and myocardial recovery for women with peripartum cardiomyopathy in the IPAC (Investigations in Pregnancy Associated Cardiomyopathy) study. Women who breastfed had elevated prolactin, and prolactin levels correlated with elevations in CD8 + T cells. However, despite elevated prolactin and cytotoxic T cell subsets, myocardial recovery was not impaired in breastfeeding women.

Purpose of Review: Hypertensive disorders of pregnancy (HDP) often result in cardiac dysfunction and have been variably included as a risk factor for peripartum cardiomyopathy (PPCM). However, there is debate regarding the relationship between the two entities., Recent Findings: Diastolic dysfunction appears to be more predominant among gravidas with HDP, while systolic dysfunction predominates in PPCM. However, this finding is not consistent in all studies. Recent examinations of mortality and morbidity associated with PPCM in the setting of HDP do not demonstrate a predominant pattern with a mixture of results. Further, right ventricular dysfunction is identified to be a common theme in both populations. From a basic science perspective, there is evidence to demonstrate a predominantly anti-angiogenic milieu in both PPCM and HDP. PPCM and HDP associated cardiomyopathy overlap significantly. As such, unifying theories for their pathophysiology should be investigated.

Background: Epidemiology, aetiology, management and outcome data for various forms of pulmonary hypertension (PH) in Africa are scarce., Methods: A prospective, multinational cohort registry of 220 consecutive patients (97% of African descent) from 9 specialist centres in 4 African countries. The antecedents, characteristics and management of newly diagnosed PH plus 6-month survival were studied., Results: There were 209 adults (median age 48years [IQR 35, 64]) and 11 children (age range 1 to 17years). Most adults had advanced disease - 66% WHO Functional Class III-IV, median 6-minute walk test distance of 252m (IQR 120, 350) and median right ventricular systolic pressure 58mmHg (IQR 49, 74). Adults comprised 16% pulmonary arterial hypertension, 69% PH due to left heart disease, 11% PH due to lung disease and/or hypoxia, 2% chronic thromboembolic pulmonary hypertension, and 2% PH with unclear multifactorial mechanism. At 6-months, 21% of adults with follow-up data had died. On an adjusted basis (independent of sub-groups) mortality was associated with increasing functional impairment (p=0.021 overall - WHO Class IV versus I, OR 1.68 [95% CI 0.13, 4.36]) and presence of combined right atrial and ventricular hypertrophy (46% - OR 2.88, 95% CI 1.45, 5.72). Children commonly presented with dyspnoea, fatigue, cough, and palpitations with six and three children, respectively diagnosed with concurrent PH associated congenital heart disease and left heart disease., Conclusions: These data provide new insights into PH from an African perspective, with clear opportunities to improve its prevention, treatment and outcomes., Trial Registration: ClinicalTrials.gov (NCT02265887)., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Pulmonary hypertension (PH) is characterized by elevated pulmonary arterial pressure, which leads to right ventricular (RV) hypertrophy and failure. The pathophysiological mechanisms of PH remain unclear but oxidative stress is believed to contribute to RV dysfunction. Melatonin is a powerful antioxidant and is cardioprotective against ischemia-reperfusion injury and hypertension. Therefore, we hypothesized that a chronic treatment with melatonin, given as a curative or preventive therapy, may confer cardiovascular benefits in PH. PH was induced in Long Evans rats (n ≥ 6 per group), with a single subcutaneous injection of monocrotaline (MCT, 80 mg/kg). Melatonin was given daily in the drinking water, with the treatment starting either on the day of the injection of MCT (dose testing: melatonin 75 ng/L and 6 mg/kg), 14 days after the injection of MCT (curative treatment: 6 mg/kg), or 5 days before the injection (preventive treatment: 6 mg/kg). The development of PH was assessed by measuring RV hypertrophy, RV function, cardiac interstitial fibrosis, and plasma oxidative stress. Compared with controls, MCT-treated rats displayed RV hypertrophy and dysfunction, increased interstitial fibrosis, and elevated plasma oxidative stress. A chronic melatonin treatment (75 ng/L or 6 mg/kg) reduced RV hypertrophy, improved RV function and reduced plasma oxidative stress. Curative and preventive treatment improved RV functional and plasma oxidative stress parameters and reduced cardiac interstitial fibrosis. Our data demonstrate that melatonin confers cardioprotection in this model of PH. As melatonin is an inexpensive and safe drug, we propose that clinical investigation of the effects of melatonin on RV function in patients with PH should be considered., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Pulmonary hypertension (PH) is a devastating, progressive disease with increasingly debilitating symptoms and usually shortened overall life expectancy due to a narrowing of the pulmonary vasculature and consecutive right heart failure. Little is known about PH in Africa, but limited reports suggest that PH is more prevalent in Africa compared with developed countries due to the high prevalence of risk factors in the region., Methods and Analysis: A multinational multicentre registry-type cohort study was established and tailored to resource-constraint settings to describe disease presentation, disease severity and aetiologies of PH, comorbidities, diagnostic and therapeutic management, and the natural course of PH in Africa. PH will be diagnosed by specialist cardiologists using echocardiography (right ventricular systolic pressure >35 mm Hg, absence of pulmonary stenosis and acute right heart failure), usually accompanied by shortness of breath, fatigue, peripheral oedema and other cardiovascular symptoms, ECG and chest X-ray changes in keeping with PH as per guidelines (European Society of Cardiology and European Respiratory Society (ESC/ERS) guidelines). Additional investigations such as a CT scan, a ventilation/perfusion scan or right heart catheterisation will be performed at the discretion of the treating physician. Functional tests include a 6 min walk test and the Karnofsky Performance Score. The WHO classification system for PH will be applied to describe the different aetiologies of PH. Several substudies have been implemented within the registry to investigate specific types of PH and their outcome at up to 24 months. Data will be analysed by an independent institution following a data analyse plan., Ethics and Dissemination: All local ethics committees of the participating centres approved the protocol. The data will be disseminated through peer-reviewed journals at national and international conferences and public events at local care providers., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Few data describe the case burden of heart disease and cardiovascular risk factors relative to other conditions in urban Africans seeking primary health care., Methods: A clinical registry captured data on 1311 consecutive primary care patients (99% African) from two primary care clinics in Soweto, South Africa. Those with suspected sub-clinical heart disease had more advanced cardiologic assessment., Results: Overall, 862 women (66%, 41 ± 16 years) and 449 men (38 ± 14 years) were studied. Whilst more men were smokers (47% vs. 14%; OR 5.23, 95% CI 4.01-6.82), more women were obese (42% vs. 14%; OR 4.54, 95% CI 3.33-5.88); blood glucose levels doubling with age in obese women. Although 33% were hypertensive, only 4.9% had type 2 diabetes (n=45), heart disease (n=10) and/or cerebrovascular disease (n=12). Overall, 16% (n=205) had an abnormal 12-lead ECG with more men than women showing a major abnormality (24% vs. 11%; OR 2.63, 95% CI 1.89-3.46). Of 99 cases (7.6%) subject to advanced cardiologic assessment, 29 (2.2%) had newly diagnosed heart disease: including hypertensive heart failure (13 women vs. 2 men, OR 4.51 95% CI 1.00-21.2), coronary artery disease (n=3), valve disease (n=3), dilated cardiomyopathy (n=3) and 2 cases of acute myocarditis., Conclusions: These data demonstrate a relatively low burden of heart disease in urban African patients seeking primary health care. Alternatively, high antecedent risk, particularly among obese women, highlights a key role for enhanced primary prevention., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Outcome of bioprosthetic valve replacement in the tricuspid position in patients with kidney failure is unknown. The authors describe a case of accelerated bioprosthetic tricuspid valve calcification leading to critical stenosis in a patient on chronic dialysis and with poorly controlled hyperparathyroidism. He required a second valve replacement in less than 3 years from the initial tricuspid replacement surgery. Both renal failure and its associated hyperparathyroidism have been implicated in native heart valve calcification. This case suggests that bioprosthetic valves could also be at risk for rapid calcification; more frequent monitoring of prosthetic valve function may be necessary.