PurposeLittle is known about the mechanism underlying Sacubitril/Valsartan effects in patients with heart failure (HFrEF). Aim of the study is to assess hemodynamic vs. non-hemodynamic Sacubitril/Valsartan effects by analyzing several biological and functional parameters.MethodsSeventy-nine patients (86% males, age 66 ± 10 years) were enrolled. At baseline and 6 months after reaching the maximum Sacubitril/Valsartan tolerated dose, we assessed biomarkers, transthoracic echocardiography, polysomnography, spirometry, and carbon monoxide diffusing capacity of the lung (DLCO).ResultsMean follow-up was 8.7 ± 1.4 months with 83% of patients reaching Sacubitril/Valsartan maximum dose (97/103 mg b.i.d). Significant improvements were observed in cardiac performance and biomarkers: left ventricular ejection fraction increased (31 ± 5 vs. 37 ± 9 %; p < 0.001), end-diastolic and end-systolic volumes decreased; NT-proBNP decreased (1,196 [IQR 648–2891] vs. 958 [IQR 424-1,663] pg/ml; p < 0.001) in parallel with interleukin ST-2 (28.4 [IQR 19.4–36.6] vs. 20.4 [IQR 15.1–29.2] ng/ml; p < 0.001) and circulating surfactant binding proteins (proSP-B: 58.43 [IQR 40.42–84.23] vs. 50.36 [IQR 37.16–69.54] AU; p = 0.014 and SP-D: 102.17 [IQR 62.85–175.34] vs. 77.64 [IQR 53.55-144.70] AU; p < 0.001). Forced expiratory volume in 1 second and forced vital capacity improved. DLCO increased in the patients' subgroup (n = 39) with impaired baseline values (from 65.3 ± 10.8 to 70.3 ± 15.9 %predicted; p = 0.013). We also observed a significant reduction in central sleep apneas (CSA).ConclusionSacubitril/Valsartan effects share a double pathway: hemodynamic and systemic. The first is evidenced by NT-proBNP, proSP-B, lung mechanics, and CSA improvement. The latter is confirmed by an amelioration of DLCO, ST-2, SP-D as well as by reverse remodeling echocardiographic parameters.

Background: Peripartum cardiomyopathy (PPCM) is a rare cardiomyopathy with systolic dysfunction that presents in late pregnancy. A number of coronavirus disease 19 (COVID-19)-related myocarditis cases have been reported. In a pandemic situation, the coexistence of COVID-19 and PPCM can be relatively frequent, making it difficult to assess the weight of the individual components on the heart condition. Case Presentation: A 34-year-old girl develops COVID-19 at the 31st week of pregnancy. In the following 2 weeks she recovered and, after 4 days from the disappearance of symptoms, she gave birth without complications. Three weeks after delivery she presented to the ED with worsening dyspnea and elevated troponine and BNP values. Echocardiogram showed severe biventricular systolic dysfunction, mitral regurgitation, pulmonary hypertension and biventricular thrombosis. She was treated with oxygen, diuretics, heparin and transferred to our center. Cardiac MRI showed dilation and severe biventricular dysfunction with positive LGE and T1 mapping values diffusely increased. A treatment with betablockers, Sacubitril/valsartan, anti-aldosterone drugs, ivabradine and bromocriptine was started. An Endomyocardial biopsy (EMB) was performed showing a picture consistent with dilated cardiomyopathy and a final diagnosis of peripartum cardiomyopathy was made. However, after a few days the molecular biology report arrived showing EMB positivity for Sars-Cov-2 and Parvovirus B19. The patient was discharged and after 6 months she is well and a control MRI showed complete recovery of biventricular systolic function. Discussion: Cardiovascular complications of COVID-19 are well known and cases of related myocarditis have been reported. Anatomopathological and biopsy studies show the presence of Sars-Cov-2 in the heart of a significant number of patients with COVID-19, however the virus is often found at the interstitial level, suggesting in most cases more an endothelial localization than a real invasiveness of cardiomyocytes. It is not impossible that a patient with PPCM could be simultaneously affected by Sars-Cov-2. Only a multidisciplinary clinical, imaging, histological, functional evaluation and a congruent follow-up can help to understand the weight of the single etiological components on cardiac dysfunction. Conclusions: We described a case of a patient with PPCM and concomitant cardiac localization of COVID-19 with severe acute biventricular dysfunction. (Figure Presented).

Vignati, Carlo, Massimo Mapelli, Benedetta Nusca, Alice Bonomi, Elisabetta Salvioni, Irene Mattavelli, Susanna Sciomer, Andrea Faini, Gianfranco Parati, and Piergiuseppe Agostoni. A breathtaking lift: sex and body mass index differences in cardiopulmonary response in a large cohort of unselected subjects with acute exposure to high altitude. High Alt Med Biol 00:000-000, 2021. Background: Every year, thousands of people travel to high altitude and experience hypoxemia. At high altitude, the partial pressure of oxygen decreases. The aim of this observational study was to determine if there is a relationship between anthropometric features and basic cardiorespiratory variables, including oxygen saturation (SpO(2)), heart rate (HR), and blood pressure (BP), following acute exposure to high altitude. Materials and Methods: At the 3,466 m top of a cableway station, we installed an automated system for measuring peripheral SpO(2), HR, BP, height, weight, and body mass index (BMI). Results: Between January and October 2020, out of 4,874 volunteers (age 39.9 +/- 15.4 years, male 54.4%), 3,267 provided complete data (1,808 cases during winter and 1,459 during summer). SpO(2) was 86.8% +/- 6.8%. At multivariable analysis, SpO(2) was significantly associated with age, sex, season, BMI, and HR but not with BP. We identified 391 (12%) subjects with SpO(2) <= 80%: they were older, with a higher BMI and HR but without sex or BP differences. Finally, winter season was associated with greater frequency of SpO(2) <= 80% (13.3% vs. 10.3%, p = 0.008). Conclusion: Our data show that high BMI, older age, and male sex were associated with greater degrees of hypoxemia following exposure to high altitude, particularly during the winter.