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BACKGROUNDSerelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. METHODSIn this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 μg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. RESULTSA total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P = 0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P = 0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. CONCLUSIONSIn this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778.

The incidence of pregnancy in women with cardiovascular disease is rising, primarily due to the increased number of women with congenital heart disease reaching childbearing age and the changing demographics associated with advancing maternal age. Although most cardiac conditions are well tolerated during pregnancy and women can deliver safely with favorable outcomes, there are some cardiac conditions that have significant maternal and fetal morbidity and mortality. The purpose of this paper is to review the available published reports and provide recommendations on the management of women with high-risk cardiovascular conditions during pregnancy.

Background-Because of the rarity of this condition, information on pregnancy-associated spontaneous coronary artery dissection is limited. We reviewed a large number of contemporary pregnancy-associated spontaneous coronary artery dissection cases in an attempt to define the clinical characteristics and provide management recommendations. Methods and Results-A literature search for cases of pregnancy-associated spontaneous coronary artery dissection reported between 2000 and 2015 included 120 cases; 75% presented with ST-segment-elevation myocardial infarction, and 80% had anterior myocardial infarction. Left anterior descending coronary artery was involved in 72% of cases, left main segment in 36%, and 40% had multivessel spontaneous coronary artery dissection. Ejection fraction was reduced to <40% in 44% of cases. Percutaneous coronary intervention was successful in only 50% of cases. Coronary artery bypass surgery was performed in 44 cases because of complex anatomy, hemodynamic instability, or failed percutaneous coronary intervention. Maternal complications included cardiogenic shock (24%), mechanical support (28%), urgent percutaneous coronary intervention (28%), urgent coronary artery bypass surgery (27.5%), maternal mortality (4%), and fetal mortality (2.5%). During follow-up for 305±111 days, there was a high incidence of symptoms because of persistent or new spontaneous coronary artery dissections, and 5 women needed heart transplantation or ventricular assist device implantation. Conclusions-Pregnancy-associated spontaneous coronary artery dissection is commonly associated with left anterior descending, left main, and multivessel involvement, which leads to a high incidence of reduced ejection fraction, and lifethreatening maternal and fetal complications. Percutaneous coronary intervention is associated with low success rate and high likelihood of complications, and coronary artery bypass surgery is often required. Recurrent ischemic events because of persistent or new spontaneous coronary artery dissection are common during long-term follow-up. (Circ Cardiovasc Interv. 2017;10:e004941.

Background— Pregnant women with a mechanical heart valve (MHV) are at a heightened risk of a thrombotic event, and their absolute need for adequate anticoagulation puts them at considerable risk of bleeding and, with some anticoagulants, fetotoxicity. Methods and Results— Within the prospective, observational, contemporary, worldwide Registry of Pregnancy and Cardiac disease (ROPAC), we describe the pregnancy outcome of 212 patients with an MHV. We compare them with 134 patients with a tissue heart valve and 2620 other patients without a prosthetic valve. Maternal mortality occurred in 1.4% of the patients with an MHV, in 1.5% of patients with a tissue heart valve ( P =1.000), and in 0.2% of patients without a prosthetic valve ( P =0.025). Mechanical valve thrombosis complicated pregnancy in 10 patients with an MHV (4.7%). In 5 of these patients, the valve thrombosis occurred in the first trimester, and all 5 patients had been switched to some form of heparin. Hemorrhagic events occurred in 23.1% of patients with an MHV, in 5.1% of patients with a tissue heart valve ( P <0.001), and in 4.9% of patients without a prosthetic valve ( P <0.001). Only 58% of the patients with an MHV had a pregnancy free of serious adverse events compared with 79% of patients with a tissue heart valve ( P <0.001) and 78% of patients without a prosthetic valve ( P <0.001). Vitamin K antagonist use in the first trimester compared with heparin was associated with a higher rate of miscarriage (28.6% versus 9.2%; P <0.001) and late fetal death (7.1% versus 0.7%; P =0.016). Conclusions— Women with an MHV have only a 58% chance of experiencing an uncomplicated pregnancy with a live birth. The markedly increased mortality and morbidity warrant extensive prepregnancy counseling and centralization of care.

Nonalcoholic fatty liver disease (NAFLD) is linked to the metabolic syndrome. The aim of the present study is to determine the effect of the metabolic syndrome on left ventricular (LV) geometry and function using as a model patients with NAFLD. Thirty-eight patients with NAFLD, less than 55 years of age and with a normal exercise test, were compared with an age and sex-matched control group. Patients with diabetes mellitus, hypertension, and body mass index>40 were excluded. A complete echocardiographic study including tissue Doppler imaging (TDI) was performed. The following parameters were assessed by echo Doppler: peak velocities of early (E) and late (A) diastolic filling, E/A ratio, flow propagation velocity (Vp). Using TDI early diastolic velocity (E'), and systolic velocity (S') of mitral annulus were obtained. The patients with NAFLD had a significantly higher body mass index (31.4+/-5 vs. 26.4+/-4 kg/m, P=0.01), higher glucose (100.6+/-13 vs. 83.0+/-10 mg/dL, P=0.01), and triglyceride levels (126.5+/-44 vs. 206.5+/-67 mg/dL, P<0.001). Increased thickness of the intraventricular septum, posterior wall (11.03+/-2.2 vs. 8.9+/-2.9 mm, P=0.001; 8.5+/-1.7 vs. 9.7+/-2.3 mm, P=0.04), and larger LV mass and LV mass/height (160.7+/-58.7 vs.115.3+/-35.4 g, P=0.001 and 92.6+/-29.5 vs. 69.2+/-19.8 g/m, P=0.001, respectively) were found in NAFLD group. LV systolic function was similar in both groups. Patients with NAFLD had a lower E (73.6+/-11.0 vs. 86.4+/-20.0 cm/s, P<0.006) and E/A ratio (1.0+/-0.3 vs. 1.76+/-0.8 P<0.0001). Moreover, the Vp and the E' on TDI were significantly lower compared with the control group (49.0+/-9.7 vs. 74.7+/-18.4 cm/s, P<0.0001 and 10.3+/-2.0 vs. 13.8+/-1.7 cm/s, P<0.0001, respectively). On multivariate analysis the E' on TDI was the only independent parameter associated with NAFLD. In conclusion, patients with NAFLD in the absence of morbid obesity, hypertension, and diabetes have mildly altered LV geometry and early features of left ventricular diastolic dysfunction. Early diastolic velocity on TDI was found to be the only index that could identify the patients with NAFLD and metabolic syndrome.