Vera Lennie

Background: Sodium-glucose cotransporter 2 inhibitors reduce the risk of heart failure hospitalization and cardiovascular death in patients with heart failure and reduced ejection fraction (HFrEF). However, their effects on cardiac structure and function in HFrEF are uncertain. Methods: We designed a multicenter, randomized, double-blind, placebo-controlled trial (the SUGAR-DM-HF trial [Studies of Empagliflozin and Its Cardiovascular, Renal and Metabolic Effects in Patients With Diabetes Mellitus, or Prediabetes, and Heart Failure]) to investigate the cardiac effects of empagliflozin in patients in New York Heart Association functional class II to IV with a left ventricular (LV) ejection fraction ≤40% and type 2 diabetes or prediabetes. Patients were randomly assigned 1:1 to empagliflozin 10 mg once daily or placebo, stratified by age (<65 and ≥65 years) and glycemic status (diabetes or prediabetes). The coprimary outcomes were change from baseline to 36 weeks in LV end-systolic volume indexed to body surface area and LV global longitudinal strain both measured using cardiovascular magnetic resonance. Secondary efficacy outcomes included other cardiovascular magnetic resonance measures (LV end-diastolic volume index, LV ejection fraction), diuretic intensification, symptoms (Kansas City Cardiomyopathy Questionnaire Total Symptom Score, 6-minute walk distance, B-lines on lung ultrasound, and biomarkers (including N-terminal pro-B-type natriuretic peptide). Results: From April 2018 to August 2019, 105 patients were randomly assigned: mean age 68.7 (SD, 11.1) years, 77 (73.3%) male, 82 (78.1%) diabetes and 23 (21.9%) prediabetes, mean LV ejection fraction 32.5% (9.8%), and 81 (77.1%) New York Heart Association II and 24 (22.9%) New York Heart Association III. Patients received standard treatment for HFrEF. In comparison with placebo, empagliflozin reduced LV end-systolic volume index by 6.0 (95% CI, –10.8 to –1.2) mL/m 2 ( P =0.015). There was no difference in LV global longitudinal strain. Empagliflozin reduced LV end-diastolic volume index by 8.2 (95% CI, –13.7 to –2.6) mL/m 2 ( P =0.0042) and reduced N-terminal pro-B-type natriuretic peptide by 28% (2%–47%), P =0.038. There were no between-group differences in other cardiovascular magnetic resonance measures, diuretic intensification, Kansas City Cardiomyopathy Questionnaire Total Symptom Score, 6-minute walk distance, or B-lines. Conclusions: The sodium-glucose cotransporter 2 inhibitor empagliflozin reduced LV volumes in patients with HFrEF and type 2 diabetes or prediabetes. Favorable reverse LV remodeling may be a mechanism by which sodium-glucose cotransporter 2 inhibitors reduce heart failure hospitalization and mortality in HFrEF. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03485092.

BACKGROUND: Pulmonary arterial hypertension (PAH) is uncommon among HIV-positive patients. However, it is a potentially life-threatening condition. Transthoracic echocardiography (TTE) is a noninvasive tool validated for PAH screening. The aim of our study was to establish the prevalence and factors associated with PAH in HIV-infected patients. METHODS: Consecutive HIV-infected individuals attended at one HIV reference clinic in Madrid, Spain, during year 2011 were examined. Demographics and clinical data were recorded and a Doppler echocardiography was performed in all individuals. PAH was considered when right ventricular pressure was more than 35 mmHg (mild if <40 mmHg, moderate if 40-65 mmHg, and severe if >65 mmHg). RESULTS: Three hundred and ninety-two individuals were examined (83.4% men, median age 47 years, 53% were men who have sex with men and 53% former intravenous drug addicts). Overall, 84% were on HAART, 76% had undetectable HIV viral load and median CD4 cell counts were 577 cells/μl. Cardiovascular risk factors were smoking 50%, arterial hypertension 16% and diabetes mellitus 9%. A total of 28.5 and 4.8% had chronic hepatitis C (CHC) and 4.8% chronic hepatitis B, respectively. PAH was diagnosed in 9.9% of patients (6.4% mild, 2.8% moderate and 0.8% severe). Multivariate logistic regression analysis [odds ratio (OR), 95% confidence interval (CI)] showed that detectable plasma HIV-RNA [OR, 3.3; 95% CI, 1.04-10], CHC [OR, 3.1; 95% CI 1.2-8.2] and female sex [OR, 2.9; 95% CI, 1.04-8.3] were independently associated with PAH. CONCLUSION: The prevalence of PAH HIV-infected patients on regular follow-up approaches 10%, being moderate-severe in nearly 4% of cases. Patients with CHC and/or uncontrolled HIV replication exhibit a higher risk of PAH.

BACKGROUND AND AIMS: The epidemiology of peripartum cardiomyopathy (PPCM) in Europe is poorly understood and data on long-term outcomes are lacking. A retrospective, observational, population-level study of validated cases of PPCM in Scotland from 1998 to 2017 was conducted. METHODS: Women hospitalized with presumed de novo left ventricular systolic dysfunction around the time of pregnancy and no clear alternative cause were included. Each case was matched to 10 controls. Incidence and risk factors were identified. Morbidity and mortality were examined in mothers and children. RESULTS: The incidence of PPCM was 1 in 4950 deliveries. Among 225 women with PPCM, obesity, gestational hypertensive disorders, and multi-gestation were found to be associated with having the condition. Over a median of 8.3 years (9.7 years for echocardiographic outcomes), 8% of women with PPCM died and 75% were rehospitalized for any cause at least once. Mortality and rehospitalization rates in women with PPCM were ∼12- and ∼3-times that of controls, respectively. The composite of all-cause death, mechanical circulatory support, or cardiac transplantation occurred in 14%. LV recovery occurred in 76% and, of those who recovered, 13% went on to have a decline in LV systolic function despite initial recovery. The mortality rate for children born to women with PPCM was ∼5-times that of children born to controls and they had an ∼3-times greater incidence of cardiovascular disease over a median of 8.8 years. CONCLUSIONS: PPCM affected 1 in 4950 women around the time of pregnancy. The condition is associated with considerable morbidity and mortality for the mother and child. There should be a low threshold for investigating at-risk women. Long term follow-up, despite apparent recovery, should be considered.