Objectives The goal of this study was to systematically review the peripartum cardiomyopathy (PPCM) literature and determine the prevalence of preeclampsia (PE) in women with PPCM. Secondary analyses included evaluation of the prevalence of hypertensive disorders, multiple gestations, and multiparity. Background PPCM is a significant cause of maternal and infant morbidity and mortality worldwide, yet its etiology remains unknown. PE is often cited as a risk factor for the development of PPCM, and recent research suggests that PE and PPCM share mechanisms that contribute to their pathobiology. No comprehensive evaluation of the relationship between PE and PPCM exists. Methods A systematic predetermined search strategy was performed in multiple databases to identify studies describing ≥3 women with PPCM. Prevalence rates of PE, hypertension, multiple gestations, and multiparity were pooled. Results Data from 22 studies (979 patients) were included in this analysis. The pooled prevalence of 22% (95% confidence interval [CI] 16 to 28) was more than quadruple the 5% average worldwide background rate of PE in pregnancy (p < 0.001). There were no geographic or racial differences detected in the prevalence of PE in women with PPCM. The rates of hypertension during pregnancy (37% [95% CI 29 to 45) and multiple gestations (9% [95% CI 7 to 11]) were also elevated. Conclusions The prevalence of PE, hypertensive disorders, and multiple gestations in women with PPCM is markedly higher than that in the general population. These findings support the concept of a shared pathogenesis between PE and PPCM and highlight the need for awareness of the overlap between these 2 diseases.

Mutations or rearrangements in the gene encoding the receptor tyrosine kinase RET result in Hirschsprung disease, cancer and renal malformations. The standard model of renal development involves reciprocal signaling between the ureteric bud epithelium, inducing metanephric mesenchyme to differentiate into nephrons, and metanephric mesenchyme, inducing the ureteric bud to grow and branch. RET and GDNF (a RET ligand) are essential mediators of these epithelial-mesenchymal interactions. Vitamin A deficiency has been associated with widespread embryonic abnormalities, including renal malformations. The vitamin A signal is transduced by nuclear retinoic acid receptors (RARs). We previously showed that two RAR genes, Rara and Rarb2, were colocalized in stromal mesenchyme, a third renal cell type, where their deletion led to altered stromal cell patterning, impaired ureteric bud growth and downregulation of Ret in the ureteric bud. Here we demonstrate that forced expression of Ret in mice deficient for both Rara and Rarb2 (Rara(-/-)Rarb2(-/-)) genetically rescues renal development, restoring ureteric bud growth and stromal cell patterning. Our studies indicate the presence of a new reciprocal signaling loop between the ureteric bud epithelium and the stromal mesenchyme, dependent on Ret and vitamin A. In the first part of the loop, vitamin-A-dependent signals secreted by stromal cells control Ret expression in the ureteric bud. In the second part of the loop, ureteric bud signals dependent on Ret control stromal cell patterning.

Background--Obesity is a risk factor for various subtypes of cardiovascular disease (CVD), including coronary heart disease (CHD), heart failure (HF), and stroke. Nevertheless, there are limited comparisons of the associations of obesity with each of these CVD subtypes, particularly regarding the extent to which they are unexplained by traditional CVD mediators.Methods and Results--We followed 13 730 participants in the Atherosclerosis Risk in Communities (ARIC) study who had a body mass index ≥18.5 and no CVD at baseline (visit 1, 1987-1989). We compared the association of higher body mass index with incident HF, CHD, and stroke before and after adjusting for traditional CVD mediators (including systolic blood pressure, diabetes mellitus, and lipid measures). Over a median follow-up of 23 years, there were 2235 HF events, 1653 CHD events, and 986 strokes. After adjustment for demographics, smoking, physical activity, and alcohol intake, higher body mass index had the strongest association with incident HF among CVD subtypes, with hazard ratios for severe obesity (body mass index ≥35 versus normal weight) of 3.74 (95% CI 3.24-4.31) for HF, 2.00 (95% CI 1.67-2.40) for CHD, and 1.75 (95% CI 1.40-2.20) for stroke (P<0.0001 for comparisons of HF versus CHD or stroke). Further adjustment for traditional mediators fully explained the association of higher body mass index with CHD and stroke but not with HF (hazard ratio 2.27, 95% CI 1.94-2.64).Conclusions--The link between obesity and HF was stronger than those for other CVD subtypes and was uniquely unexplained by traditional risk factors. Weight management is likely critical for optimal HF prevention, and nontraditional pathways linking obesity to HF need to be elucidated. ( J Am Heart Assoc. 2016;5:e003921 doi: 10.1161/JAHA.116.003921) Key Words: coronary heart disease • epidemiology • heart failure • obesity • stroke O besity is a common risk factor for several subtypes of cardiovascular disease (CVD), including coronary heart disease (CHD), stroke, and heart failure (HF) [1][2][3][4] ; however, increasing evidence suggests that obesity leads to various subtypes of CVD through multiple distinct pathways. Some traditional risk factors, including hypertension, diabetes mellitus, and dyslipidemia, are established as mediators between obesity and atherosclerotic vascular disease. Although weight management is a fundamental component of CVD prevention, the majority of persons with obesity in the general population do not achieve sufficient and sustained weight loss. [5][6][7][8] Consequently, there is great emphasis on controlling the traditional CVD risk factors resulting from obesity as a strategy for reducing cardiovascular risk. Nevertheless, uniform approaches to the control of cardiovascular risk factors may not have the same impact on the likelihood of developing different subtypes of CVD. In this context, data conflict regarding whether the relationships of obesity with CHD and stroke are independent of established CVD mediators. Several prospective studies [9]...

Almost 1% of human infants are born with urogenital abnormalities, many of which are linked to irregular connections between the distal ureters and the bladder. During development, ureters migrate by an unknown mechanism from their initial integration site in the Wolffian ducts up to the base of the bladder in a process that we call ureter maturation. Rara(-/-) Rarb2(-/-) mice display impaired vitamin A signaling and develop syndromic urogenital malformations similar to those that occur in humans, including renal hypoplasia, hydronephrosis and mega-ureter, abnormalities also seen in mice with mutations in the proto-oncogene Ret. Here we show that ureter maturation depends on formation of the 'trigonal wedge', a newly identified epithelial outgrowth from the base of the Wolffian ducts, and that the distal ureter abnormalities seen in Rara(-/-) Rarb2(-/-) and Ret(-/-) mutant mice are probably caused by a failure of this process. Our studies indicate that formation of the trigonal wedge may be essential for correct insertion of the distal ureters into the bladder, and that these events are mediated by the vitamin A and Ret signaling pathways.

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Background Risk factors for obstructive sleep apnea (OSA) and development of subsequent cardiovascular (CV) complications differ by sex. We hypothesize that the relationship between OSA and high sensitivity troponin T (hs-TnT), cardiac structure, and CV outcomes differs by sex. Methods and Results 752 men and 893 women free of CV disease participating in both the Atherosclerosis Risk in the Communities and the Sleep Heart Health Studies were included. All participants (mean age 62.5±5.5 years) underwent polysomnography and measurement of hs-TnT. OSA severity was defined using established clinical categories. Subjects were followed for 13.6±3.2 years for incident coronary disease, heart failure, and CV and all-cause mortality. Surviving subjects underwent an echocardiography after 15.2±0.8 years. OSA was independently associated with hs-TnT among women (p=0.03) but not in men (p=0.94). Similarly, OSA was associated with incident HF or death in women (p=0.01) but not men (p=0.10). This association was no longer significant after adjusting for hs-TnT (p=0.09). Among surviving participants without an incident CV event, OSA assessed in mid-life was independently associated with higher left ventricle mass index only among women (p=0.001). Conclusions Sex-specific differences exist in the relationship between OSA and CV disease. OSA, assessed in mid-life, is independently associated with higher levels of concomitantly measured hs-TnT among women but not men, in whom other comorbidities associated with OSA may play a more important role. During 13-year follow-up, OSA was associated with incident HF or death only among women, and among those without an incident event, was independently associated with LV hypertrophy only in women.

Background: Despite growing evidence of cardiovascular complications associated with coronavirus disease 2019 , there are few data regarding the performance of transthoracic echocardiography (TTE) and the spectrum of echocardiographic findings in this disease.Methods: A retrospective analysis was performed among adult patients admitted to a quaternary care center in New York City between March 1 and April 3, 2020. Patients were included if they underwent TTE during the hospitalization after a known positive diagnosis for COVID-19. Demographic and clinical data were obtained using chart abstraction from the electronic medical record.Results: Of 749 patients, 72 (9.6%) underwent TTE following positive results on severe acute respiratory syndrome coronavirus-2 polymerase chain reaction testing. The most common clinical indications for TTE were concern for a major acute cardiovascular event (45.8%) and hemodynamic instability (29.2%). Although most patients had preserved biventricular function, 34.7% were found to have left ventricular ejection fractions # 50%, and 13.9% had at least moderately reduced right ventricular function. Four patients had wall motion abnormalities suggestive of stress-induced cardiomyopathy. Using Spearman rank correlation, there was an inverse relationship between high-sensitivity troponin T and left ventricular ejection fraction (r = À0.34, P = .006). Among 20 patients with prior echocardiograms, only two (10%) had new reductions in LVEF of >10%. Clinical management was changed in eight individuals (24.2%) in whom TTE was ordered for concern for acute major cardiovascular events and three (14.3%) in whom TTE was ordered for hemodynamic evaluation.Conclusions: This study describes the clinical indications for use and diagnostic performance of TTE, as well as findings seen on TTE, in hospitalized patients with COVID-19. In appropriately selected patients, TTE can be an invaluable tool for guiding COVID-19 clinical management.

Background Hospitalization for acute heart failure (HF) is associated with high rates of subsequent mortality and readmission. We assessed the influence of the time interval between prior HF hospitalization and randomization in the CHARM trials on clinical outcomes in patients with both reduced and preserved ejection fraction. Methods and Results CHARM enrolled 7,599 patients with NYHA class II-IV heart failure, of whom 5,426 had a history of prior HF hospitalization. Cox proportional hazards regression models were utilized to assess the association between time from prior HF hospitalization and randomization and the primary outcome of cardiovascular death or unplanned admission to hospital for the management of worsening HF over a median of 36.6 months. For patients with HF and reduced (HFrEF) or preserved (HFpEF) ejection fraction, rates of CV mortality and HF hospitalization were higher among patients with prior HF hospitalization than those without. The risk for mortality and hospitalization varied inversely with the time interval between hospitalization and randomization. Rates were higher for HFrEF patients within each category. Event rates for those with HFpEF and a HF hospitalization in the 6 months prior to randomization were comparable to the rate in HFrEF patients with no prior HF hospitalization. Conclusions Rates of CV death or HF hospitalization are greatest in those who have been previously hospitalized for HF. Independent of EF, rates of death and readmission decline as time from HF hospitalization to trial enrollment increased. Recent HF hospitalization identifies a high risk population for future clinical trials in HFrEF and HFpEF. Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00634400.