Peripartum cardiomyopathy (PPCM) is a cause of pregnancy-associated heart failure. It typically develops during the last month of, and up to 6 months after, pregnancy in women without known cardiovascular disease. The present position statement offers a state-of-the-art summary of what is known about risk factors for potential pathophysiological mechanisms, clinical presentation of, and diagnosis and management of PPCM. A high index of suspicion is required for the diagnosis, as shortness of breath and ankle swelling are common in the peripartum period. Peripartum cardiomyopathy is a distinct form of cardiomyopathy, associated with a high morbidity and mortality, but also with the possibility of full recovery. Oxidative stress and the generation of a cardiotoxic subfragment of prolactin may play key roles in the pathophysiology of PPCM. In this regard, pharmacological blockade of prolactin offers the possibility of a disease-specific therapy.--

Background-Heart failure with preserved left ventricular (LV) ejection fraction (EF) is increasingly recognized and usually referred to as diastolic heart failure (DHF). Its pathogenetic mechanism remains unclear, partly because of a lack of myocardial biopsy material. Endomyocardial biopsy samples obtained from DHF patients were therefore analyzed for collagen volume fraction (CVF) and sarcomeric protein composition and compared with control samples. Single cardiomyocytes were isolated from these biopsy samples to assess cellular contractile performance. Methods and Results-DHF patients (nϭ12) had an LVEF of 71Ϯ11%, an LV end-diastolic pressure (LVEDP) of 28Ϯ4 mm Hg, and no significant coronary artery stenoses. DHF patients had higher CVFs (7.5Ϯ4.0%, PϽ0.05) than did controls (nϭ8, 3.8Ϯ2.0%), and no conspicuous changes in sarcomeric protein composition were detected. Cardiomyocytes, mechanically isolated and treated with Triton X-100 to remove all membranes, were stretched to a sarcomere length of 2.

Abstract-High diastolic stiffness of failing myocardium results from interstitial fibrosis and elevated resting tension (F passive ) of cardiomyocytes. A shift in titin isoform expression from N2BA to N2B isoform, lower overall phosphorylation of titin, and a shift in titin phosphorylation from N2B to N2BA isoform can raise F passive of cardiomyocytes. In left ventricular biopsies of heart failure (HF) patients, aortic stenosis (AS) patients, and controls (CON), we therefore related F passive of isolated cardiomyocytes to expression of titin isoforms and to phosphorylation of titin and titin isoforms. Biopsies were procured by transvascular technique (44 HF, 3 CON), perioperatively (25 AS, 4 CON), or from explanted hearts (4 HF, 8 CON). None had coronary artery disease. Isolated, permeabilized cardiomyocytes were stretched to 2.2-m sarcomere length to measure F passive . Expression and phosphorylation of titin isoforms were analyzed using gel electrophoresis with ProQ Diamond and SYPRO Ruby stains and reported as ratio of titin (N2BA/N2B) or of phosphorylated titin (P-N2BA/P-N2B) isoforms. F passive was higher in HF (6.1Ϯ0.4 kN/m 2 ) than in CON (2.3Ϯ0.3 kN/m 2 ; PϽ0.01) or in AS (2.2Ϯ0.2 kN/m 2 ; PϽ0.001). Titin isoform expression differed between HF (N2BA/N2Bϭ0.73Ϯ0.06) and CON (N2BA/N2Bϭ0.39Ϯ0.05; PϽ0.001) and was comparable in HF and AS (N2BA/N2Bϭ0.59Ϯ0.06). Overall titin phosphorylation was also comparable in HF and AS, but relative phosphorylation of the stiff N2B titin isoform was significantly lower in HF (P-N2BA/P-N2Bϭ0.77Ϯ0.05) than in AS (P-N2BA/P-N2Bϭ0.54Ϯ0.05; PϽ0.01). Relative hypophosphorylation of the stiff N2B titin isoform is a novel mechanism responsible for raised

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The increased Ca(2+)-responsiveness of the contractile apparatus in end-stage failing human hearts cannot be explained by a shift in contractile protein isoforms, but results from the complex interplay between changes in the phosphorylation status of MLC-2 and TnI.