Background A population-based study to describe the impact of SARS-CoV-2 infection on pregnancy outcomes. Methods Prospective, population-based study including pregnant women consecutively attended at first/second trimester or at delivery at three hospitals in Barcelona, Spain. SARS-CoV-2 antibodies (IgG and IgM/IgA) were measured in all participants and nasopharyngeal RT-PCR was performed at delivery. The primary outcome was a composite of pregnancy complications in SARS-CoV-2 positive versus negative women: miscarriage, preeclampsia, preterm delivery, perinatal death, small-for-gestational age, neonatal admission. Secondary outcomes were components of the primary outcome plus abnormal fetal growth, malformation, intrapartum fetal distress. Outcomes were also compared between positive symptomatic and positive asymptomatic SARS-CoV-2 women. Results Of 2,225 pregnant women, 317 (14.2%) were positive for SARS-CoV-2 antibodies (n=314, 99.1%) and/or RT-PCR (n=36, 11.4%). Among positive women, 217 (68.5%) were asymptomatic, 93 (29.3%) had mild COVID-19 and 7 (2.2%) pneumonia, of which 3 required intensive care unit admission. In women with and without SARS-CoV-2 infection, the primary outcome occurred in 43 (13.6%) and 268 (14%), respectively [risk difference -0.4%, (95% CI: -4.1% to 4.1)]. As compared with non-infected women, women with symptomatic COVID-19 had increased rates of preterm delivery (7.2% vs. 16.9%, p=0.003) and intrapartum fetal distress (9.1% vs. 19.2%, p=0.004), while asymptomatic women had similar rates to non-infected cases. Among 143 fetuses from infected mothers, none had anti-SARS-CoV-2 IgM/IgA in cord blood. Conclusions The overall rate of pregnancy complications in women with SARS-CoV-2 infection was similar to non-infected women. However, symptomatic COVID-19 was associated with modest increases in preterm delivery and intrapartum fetal distress.

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Aims The prognostic value of biomarkers in patients with heart failure (HF) and mid-range (HFmrEF) or preserved ejection fraction (HFpEF) has not been widely addressed. The aim of this study was to assess whether the prognostic value of growth differentiation factor 15 (GDF-15) is superior to that of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with HFmrEF or HFpEF. Methods and results Heart failure patients with either HFpEF or HFmrEF were included in the study. During their first visit to the HF unit, serum samples were obtained and stored for later assessment of GDF-15 and NT-proBNP concentrations. Patients were followed up by the HF unit. The main endpoint was all-cause mortality. A total of 311 patients, 90 (29%) HFmrEF and 221 (71%) HFpEF, were included. Mean age was 72 ± 13 years, and 136 (44%) were women. No differences were found in GDF-15 or NT-proBNP concentrations between both HF groups. During a median follow-up of 15 months (Q1-Q3: 9-30 months), 98 patients (32%) died, most (71%) of cardiovascular causes. Patients who died had higher median concentrations of GDF-15 (4085 vs. 2270 ng/L, P < 0.0001) and NT-proBNP (1984 vs. 1095 ng/L, P < 0.0001). A Cox multivariable model identified New York Heart Association Functional Class III (P = 0.04), systolic blood pressure (P = 0.01), left atrial diameter (P = 0.03), age >65 years (P < 0.0001), and GDF-15 concentrations (P = 0.01) but not NT-proBNP as independent predictors of allcause mortality. The area under the curve was 0.797 for the basic model including NT-proBNP, and the area under the curve comparing the overall model was 0.819, P = 0.016 (DeLong's test). Integrated discrimination improvement index after the inclusion of GDF-15 in the model with the mortality risk factors was 0.033; that is, the ability to predict death increased by 3.3% (P = 0.004). Net reclassification improvement was 0.548 (P < 0.001); that is, the capacity to improve the classification of the event (mortality) was 54.8%. GDF-15 concentrations were divided in tertiles (<1625, 1625-4330, and >4330 ng/L), and survival curves were evaluated using the Kaplan-Meier technique. Patients in the highest tertile had the poorest 5 year survival, at 16%, whereas the lowest tertile had the best survival, of 78% (P < 0.001). Conclusions Growth differentiation factor 15 was superior to NT-proBNP for assessing prognosis in patients with HFpEF and HFmrEF. GDF-15 emerges as a strong, independent biomarker for identifying HFmrEF and HFpEF patients with worse prognosis.

Antecedents Cardiac allograft vasculopathy (CAV) is a frequent complication limiting the long-term (>1 year) survival after heart transplantation (HTx). CAV is initiated by endothelial dysfunction and can lead to severe cardiovascular (CV) complications. Since CAV is often clinically silent, biomarkers could help identifying HTx patients at risk of CAV and their severe complications. Aim Evaluate the clinical yield of high-sensitivity cardiac troponin T (hs-cTnT), marker of cardiomyocyte damage, and the soluble form of AXL (sAXL), biomarker of endothelial dysfunction, to assess the prognosis of long-term cardiovascular (CV) events occurring after HTx. Methods 96 patients were evaluated at least > 1 year after HTx. CAV was evaluated by coronary angiography or multisliced tomography, and hs-cTnT and sAXL measured 6 months before or after CAV evaluation. Patients were followed during 42 ± 15 months for a combined end point including cardiac death, angina or acute myocardial infarction, left ventricular ejection fraction < 50%, or heart failure not due to an acute rejection. Results 51 patients (53%) presented CAV at evaluation; 21 of them had CV events. Hs-cTnT (56 ± 45 versus 20 ± 18 ng/L; p = 0.04) and sAXL concentrations (98 ± 51 versus 26 ± 26 ng/L; p = 0.01) were significantly higher in patients with CV events. Hs-cTnT (HR 1.03; 95% CI 1.015–1.042, p = 0.0001) and sAXL (HR 1.01; 95% CI 1.001–1.019, p = 0.02) were independent predictors of CV events. A hs-cTnT concentration < 21 ng/L, detected by AUC ROC, predicted the absence of CV events with a predictive value of 91%; sAXL did not add more predictive value to hs-cTnT. Survival free of CV events was 92% in patients with hs-cTnT < 21 ng/L and 57% in those with hs-cTnT > 21 ng/L (p < 0.001). Conclusion Hs-cTnT, but not sAXL, measured during the long-term follow-up of HTx patients appears as a helpful biomarker to identify patients at low risk of adverse CV outcomes.

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Background Cardiovascular diseases (CVD) are cause of increased morbidity and mortality in spite of advances for diagnosis and treatment. Changes during pregnancy affect importantly the maternal CV system. Pregnant women that develop preeclampsia (PE) have higher risk (up to 4 times) of clinical CVD in the short- and long-term. Predominance of an anti-angiogenic environment during pregnancy is known as main cause of PE, but its relationship with CV complications is still under research. We hypothesize that angiogenic factors are associated to maternal cardiac dysfunction/remodeling and that these may be detected by new cardiac biomarkers and maternal echocardiography. Methods Prospective cohort study of pregnant women with high-risk of PE in first trimester screening, established diagnosis of PE during gestation, and healthy pregnant women (total intended sample size n = 440). Placental biochemical and biophysical cardiovascular markers will be assessed in the first and third trimesters of pregnancy, along with maternal echocardiographic parameters. Fetal cardiac function at third trimester of pregnancy will be also evaluated and correlated with maternal variables. Maternal cardiac function assessment will be determined 12 months after delivery, and correlation with CV and PE risk variables obtained during pregnancy will be evaluated. Discussion The study will contribute to characterize the relationship between anti-angiogenic environment and maternal CV dysfunction/remodeling, during and after pregnancy, as well as its impact on future CVD risk in patients with PE. The ultimate goal is to improve CV health of women with high-risk or previous PE, and thus, reduce the burden of the disease. Trial registration NCT04162236

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N-terminal pro-brain natriuretic peptide (NT-proBNP) and uric acid are elevated in pregnancies with preeclampsia (PE). Short-term prediction of PE using angiogenic factors has many false-positive results. Our objective was to validate a machine-learning model (MLM) to predict PE in patients with clinical suspicion, and evaluate if the model performed better than the sFlt-1/PlGF ratio alone. A multicentric cohort study of pregnancies with suspected PE between 24+0 and 36+6 weeks was used. The MLM included six predictors: gestational age, chronic hypertension, sFlt-1, PlGF, NT-proBNP, and uric acid. A total of 936 serum samples from 597 women were included. The PPV of the MLM for PE following 6 weeks was 83.1% (95% CI 78.5–88.2) compared to 72.8% (95% CI 67.4–78.4) for the sFlt-1/PlGF ratio. The specificity of the model was better; 94.9% vs. 91%, respectively. The AUC was significantly improved compared to the ratio alone [0.941 (95% CI 0.926–0.956) vs. 0.901 (95% CI 0.880–0.921), p < 0.05]. For prediction of preterm PE within 1 week, the AUC of the MLM was 0.954 (95% CI 0.937–0.968); significantly greater than the ratio alone [0.914 (95% CI 0.890–0.934), p < 0.01]. To conclude, an MLM combining the sFlt-1/PlGF ratio, NT-proBNP, and uric acid performs better to predict preterm PE compared to the sFlt-1/PlGF ratio alone, potentially increasing clinical precision.