Zolt Arany

Comparison of Clinical Characteristics and Outcomes of Peripartum Cardiomyopathy Between African American and Non–African American Women

Importance Peripartum cardiomyopathy (PPCM) disproportionately affects women of African ancestry, but well-powered studies to explore differences in severity of disease and clinical outcomes are lacking. Objective To compare the clinical characteristics, presentation, and outcomes of PPCM between African American and non–African American women. Design, Setting, and Participants This retrospective cohort study using data from January 1, 1986, through December 31, 2016, performed at the University of Pennsylvania Health System, a tertiary referral center serving a population with a high proportion of African American individuals, included 220 women with PPCM. Main Outcomes and Measures Demographic and clinical characteristics and echocardiographic findings at presentation, as well as clinical outcomes including cardiac recovery, time to recovery, cardiac transplant, persistent dysfunction, and death, were compared between African American and non–African American women with PPCM. Results A total of 220 women were studied (mean [SD] age at diagnosis, 29.5 [6.6] years). African American women were diagnosed with PPCM at a younger age (27.6 vs 31.7 years, P < .001), were diagnosed with PPCM later in the postpartum period, and were more likely to present with a left ventricular ejection fraction less than 30% compared with non–African American women (48 [56.5%] vs 30 [39.5%], P = .03). African American women were also more likely to worsen after initial diagnosis (30 [35.3%] vs 14 [18.4%], P = .02), were twice as likely to fail to recover (52 [43.0%] vs 24 [24.2%], P = .004), and, when they did recover, recovery took at least twice as long (median, 265 vs 125.5 days; P = .02) despite apparent adequate treatment. Conclusions and Relevance In a large cohort of women with well-phenotyped PPCM, this study demonstrates a different profile of disease in African American vs non–African American women. Further work is needed to understand to what extent these differences stem from genetic or socioeconomic differences and how treatment of African American patients might be tailored to improve health outcomes.

Metabolic Regulation of Angiogenesis in Diabetes and Aging

Impaired angiogenesis and endothelial dysfunction are hallmarks of diabetes and aging. Clinical efforts at promoting angiogenesis have largely focused on growth factor pathways, with mixed results. Recently, a new repertoire of endothelial intracellular molecules critical to endothelial metabolism has emerged as playing an important role in regulating angiogenesis. This review thus focuses on the emerging importance and therapeutic potential of these proteins and of endothelial bioenergetics in diabetes and aging.

Myocardial performance index in hypertensive disorders of pregnancy: The relationship between blood pressures and angiogenic factors

ABSTRACT Objective: To study the association between cardiac function measured by myocardial performance index (MPI), blood pressures and angiogenic factors measured at the time of echocardiography in patients with and without hypertensive disorders of pregnancy (HDP). Methods: We prospectively studied 189 pregnant women and evaluated whether changes in cardiac function observed on echocardiography were correlated with higher blood pressures and whether higher blood pressures were associated with antiangiogenic proteins (soluble fms-like tyrosine kinase, sFlt1; soluble endoglin, sEng). Comprehensive echocardiograms, including measurement of MPI, were performed on all patients. sFlt1 and sEng levels were measured using enzyme-linked immunosorbent assay. Results: Overall, 189 patients were divided into tertiles based on mean arterial pressure (MAP). The MPI was worst in tertile 3 (0.50 ± 0.15) compared to tertile 1 (0.42 ± 0.10), p = 0.0004. sFlt1 (pg/ml) and sEng (ng/ml) were highest in tertile 3 compared to tertile 1: 15055.37 vs. 1623.01 and 33.06 vs. 8.15, respectively, with p-value <0.001. In crude multivariate regression analysis, MAP was positively correlated with MPI (r = 0.32, p < 0.001), GLS (r = 0.54, p < 0.001), sFlt1 (r = 0.60, p < 0.001) and sEng (r = 0.61, p < 0.001). After adjustment for confounders, these relationships persisted between MAP and MPI (r = 0.31, p = 0.0003), GLS (r = 0.46, p < 0.001), sFlt1 (r = 0.56, p < 0.001) and sEng (r = 0.58, p < 0.001). Conclusion: Mean arterial pressure correlates with worsening cardiac function as measured by MPI and serum levels of angiogenic factors. Further studies are needed to evaluate whether a reduction in blood pressure will reverse changes in MPI or reduce levels of angiogenic proteins seen among women with HDP.

Mitochondria Cripple without Krüppel

Proper mitochondrial biogenesis and removal is crucial in maintaining a healthy heart. Liao et al now show key roles for cardiac KLF4 in mitochondrial homeostasis via its interaction with the ERR/PGC-1 module, and mitochondrial clearance via regulation of mitophagy. Disruption of KLF4 leads to profoundly injured mitochondria and cardiac failure.

Does Endothelium Buffer Fat

Endothelial cells (ECs) are the metabolic gatekeepers of the body. All tissues require nutrients for growth and function, and those nutrients must pass the endothelial layer. In some tissues like the liver, the endothelium is discontinuous and marked by “fenestrae” (from the Latin for “window”), dedicated transcellular openings that allow free movement of nutrients. But in most tissues such as the heart, muscle, and brain, endothelia lack fenestrae, and nutrients must traverse the endothelial wall directly. The list of nutrients that must do so is long and includes sugars, amino acids, and fats. Of those, the latter have received the least attention, although organs like the heart consume copious fatty acids for the generation of ATP. Article, see p 1289 Fatty acids travel the blood stream largely in 2 forms: esterified as triglycerides in lipoprotein particles, including chylomicrons and VLDL (very-low–density lipoprotein), or unesterified and noncovalently bound to albumin. Esterified fatty acids are liberated by lipoprotein lipase, which, importantly, is located on the luminal side of the endothelium. Therefore, all fatty acids must traverse the endothelial layer before reaching underlying parenchyma. Recent work has demonstrated that paracrine factors, both proteins and metabolites, secreted by parenchymal cells can promote adjacent endothelium to transport fats. For example, VEGFB (vascular endothelial growth factor B), a VEGF family member, is secreted from fat-consuming oxidative skeletal and heart muscles to promote transendothelial fat transport, thereby coordinating myocyte metabolism with nutrient delivery.1 Similarly, 3-hydroxy-isobutyrate, a metabolite of valine catabolism, is secreted from skeletal muscle to promote transendothelial fatty acid transport, and it may contribute to muscle lipotoxicity and insulin resistance.2 How does the endothelium handle and transport fats in response to these and other signals? Surprisingly little is known about how this process inside ECs occurs. Several mechanisms have been proposed: diffusion within endothelial …