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Due to the bleeding risk of full-dose systemic thrombolysis and the lack of major trials focusing on the clinical benefits of catheter-directed treatment, heparin antiocoagulation remains the standard of care for patients with intermediate-high-risk pulmonary embolism (PE). The Higher-Risk Pulmonary Embolism Thrombolysis (HI-PEITHO) study (ClinicalTrials.gov Identifier: NCT04790370) is a multinational multicenter randomized controlled parallel-group comparison trial. Patients with: (1) confirmed acute PE; (2) evidence of right ventricular (RV) dysfunction on imaging; (3) a positive cardiac troponin test; and (4) clinical criteria indicating an elevated risk of early death or imminent hemodynamic collapse, will be randomized 1:1 to treatment with a standardized protocol of ultrasound-facilitated catheter-directed thrombolysis plus anticoagulation, vs anticoagulation alone. The primary outcome is a composite of PE-related mortality, cardiorespiratory decompensation or collapse, or non-fatal symptomatic and objectively confirmed PE recurrence, within 7 days of randomization. Further assessments cover, apart from bleeding complications, a broad spectrum of functional and patient-reported outcomes including quality of life indicators, functional status and the utilization of health care resources over a 12-month follow-up period. The trial plans to include 406 patients, but the adaptive design permits a sample size increase depending on the results of the predefined interim analysis. As of May 11, 2022, 27 subjects have been enrolled. The trial is funded by Boston Scientific Corporation and through collaborative research agreements with University of Mainz and The PERT Consortium. Regardless of the outcome, HI-PEITHO will establish the first-line treatment in intermediate-high risk PE patients with imminent hemodynamic collapse. The trial is expected to inform international guidelines and set the standard for evaluation of catheter-directed reperfusion options in the future.

In acute pulmonary embolism (PE), overt right ventricular (RV) failure with cardiogenic shock indicates a poor prognosis. However, normotensive patients with acute RV dysfunction on echocardiography or computed tomography and with myocardial troponin elevation may also have an adverse outcome. Thrombolysis rapidly reverses RV pressure overload in PE, but it remains unclear whether it may improve the early and long-term clinical outcome of selected normotensive patients. The Pulmonary EmbolIsm THrOmbolysis (PEITHO) trial is a prospective, multicenter, international, randomized (1:1), double-blind comparison of thrombolysis with tenecteplase vs placebo in normotensive patients with confirmed PE, an abnormal right ventricle on echocardiography or computed tomography, and a positive troponin I or T test result. Both treatment groups receive standard anticoagulation. The primary efficacy outcome is the composite of death from any cause or hemodynamic collapse within 7 days of randomization. Safety outcomes include ischemic/hemorrhagic strokes and other major bleeding episodes. In addition, 180-day clinical and echocardiographic follow-up will be performed. The study is expected to enroll approximately 1,000 patients. By determining the benefits vs risks of thrombolysis in submassive or intermediate-risk PE, this trial is expected to answer a long-standing query on the management of this patient population.

Abstract Aims To analyse the predictive value of advanced markers of right ventricular (RV) function and RV-pulmonary arterial (PA) coupling in forecasting long-term left ventricular (LV) improvement in de novo heart failure with reduced ejection fraction (HFrEF). Methods and results 260 patients (mean age 57 years, 68% men) from the PROLONG-II study were included. PROLONG-II analysed patients with new-onset HFrEF receiving a wearable cardioverter-defibrillator. For this substudy, RV free wall longitudinal strain (RVFWS), tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and right ventricular-pulmonary artery (RV-PA) coupling ratios [RVFWS/systolic pulmonary artery pressure (PASP), TAPSE/PASP and FAC/PASP] at baseline and 3-month follow-up (early follow-up) were examined. LV improvement and non-improvement were defined as an LV ejection fraction (LVEF) of >35% or ≤35% at last available (long-term) follow-up. The median follow-up was 31.5 months (IQR: 18.2–45.4), and 151 (58%) patients experienced LV improvement in the long term. No significant differences of RV function and markers of RV-PA coupling were observed at baseline; however, the subgroup of patients with long-term LVEF improvement showed better RV function at early follow-up (RVFWS −20.9 ± 4.3 vs. −18.5 ± 5.1%, TAPSE 19.7 ± 5.1 vs. 17.4 ± 4.9 mm, FAC 39.7 ± 8.5 vs. 35.2 ± 9.4%, all P < 0.01). In multivariable analysis, RVFWS at early follow-up was shown to be an independent predictor of later LV recovery [odds ratio 1.078 (95% confidence interval 1.010–1.150), P < 0.05]. The non-improvers exhibited worse RV-PA coupling at early follow-up [RVFWS/PASP 0.82 ± 0.35 vs. 0.65 ± 0.35%/mmHg, TAPSE/PASP 0.71 (0.55–1.00) vs. 0.54 (0.35–0.75) mm/mmHg, FAC/PASP 1.54 ± 0.61 vs. 1.24 ± 0.75%/mmHg, all P < 0.01]. RVFWS/PASP identified RV-PA uncoupling was associated with a higher risk of all-cause mortality (hazard ratio 4.64, 95% confidence interval 1.34–16.09, P = 0.033). Conclusions Persistent RV dysfunction, as indicated by both standard and advanced echocardiographic markers during the early follow-up period, implies a reduced potential for long-term LV recovery in patients with newly diagnosed HFrEF.

Objective To analyse the incidence and the impact on outcome of right ventricular failure (RVF) in patients with acute respiratory distress syndrome (ARDS). Patients and methods A total of 145 ARDS patients included in the previously published French Pulmonary Artery Catheter (PAC) study were randomly assigned to receive a PAC. All patients were ventilated according to a strategy aimed at limiting plateau pressure. The RVF was defined by the concomitant presence of: (1) a mean pulmonary artery pressure (MPAP) > 25 mmHg, (2) a central venous pressure (CVP) higher than pulmonary artery occlusion pressure (PAOP) and (3) a stroke volume index < 30 mL m −2 . Results Right ventricular failure was present in 9.6% of patients. Mortality was 68% at day-90 with no difference between patients with RVF (RVF+) and without RVF (71 vs. 67%, respectively). SAPS II, PaO 2 /FiO 2 and PaCO 2 were similar in both groups. Tidal volume and I/E ratio were significantly higher in RVF+ (9.7 ± 2.8 vs. 8.6 ± 1.8 ml m −2 and 0.7 ± 0.5 vs. 0.5 ± 0.2). Plateau pressure tended to be higher in RVF+ (28 ± 6 vs. 25 ± 6 cmH 2 O, NS). In multivariate analysis, PaO 2 /FiO 2 , mean arterial pressure, arterial pH, SvO 2 , MPAP and presence of CVP > PAOP, but not RVF, were independently associated with day-90 mortality. Conclusion In this group of patients investigated early in the course of ARDS and ventilated according to a strategy aimed at limiting plateau pressure, the presence of RVF was about 10%. Unlike MPAP and the presence of CVP > PAOP, RVF at this early stage did not appear as an independent factor of mortality.

Abstract Rationale Patients with pulmonary hypertension due to left heart disease (PH-LHD) and a diastolic pulmonary vascular pressure gradient ≥7 mm Hg, representing PH out of proportion to pulmonary arterial wedge pressure, have pulmonary vascular disease and increased mortality. Little information exists on this condition, recently labeled as “combined pre- and post-capillary PH” (Cpc-PH). Objectives To investigate epidemiology, risk factors, right ventricular function, and outcomes in patients with chronic heart failure and Cpc-PH. Methods The study population was identified from a retrospective chart review of a clinical database of 3,107 stable patients who underwent first diagnostic right heart catheterization and from a prospective cohort of 800 consecutive patients at a national university-affiliated tertiary center. Measurements and Main Results The retrospective cohort had 664 patients with systolic heart failure (SHF) and 399 patients with diastolic heart failure (DHF), 12% of whom were classified as Cpc-PH. The prospective cohort had 172 patients with SHF (14% Cpc-PH) and 219 patients with DHF (12% Cpc-PH). Chronic obstructive pulmonary disease (P = 0.034) and the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio (P = 0.015) predicted Cpc-PH in SHF. Younger age (P = 0.004), valvular heart disease (P = 0.046), and the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio predicted Cpc-PH in DHF (P = 0.016). Right ventricular–pulmonary vascular coupling was worse in Cpc-PH patients (end-systolic elastance to effective arterial elastance [Ees/Ea]: SHF: 1.05 ± 0.25; P = 0.002; DHF: 1.17 ± 0.27; P = 0.027) than in those with isolated post-capillary PH (Ees/Ea: SHF: 1.52 ± 0.51; DHF: 1.45 ± 0.29). Conclusions Cpc-PH is rare in chronic heart failure. Right ventricular–pulmonary vascular coupling is poor in Cpc-PH and could be one explanation for dismal outcomes.

A new infectious outbreak sustained by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now spreading all around the world. The aim of this study was to evaluate the prognostic value of left ventricular global longitudinal strain (LV-GLS) and right ventricular longitudinal strain (RV-LS) in patients with coronavirus disease 2019 (COVID-19). In this prospective, single-center study, data were gathered from patients treated for COVID-19 between April 15 and April 30, 2020. Two-dimensional echocardiography (2-DE) and speckle tracking echocardiography (STE) images were obtained for all patients. Patients were divided into three groups: those with severe COVID-19 infection, those with non-severe COVID-19 infection, and those without COVID-19 infection (the control group). Data regarding clinical characteristics and laboratory findings were obtained from electronic medical records. The primary endpoint was in-hospital mortality. A total of 100 patients hospitalized for COVID-19 were included in this study. The mean age of the severe group (n = 44) was 59.1 ± 12.9, 40% of whom were male. The mean age of the non-severe group (n = 56) was 53.7 ± 15.1, 58% of whom were male. Of these patients, 22 died in the hospital. In patients in the severe group, LV-GLS and RV-LS were decreased compared to patients in the non-severe and control groups (LV-GLS: − 14.5 ± 1.8 vs. − 16.7 ± 1.3 vs. − 19.4 ± 1.6, respectively [p < 0.001]; RV-LS: − 17.2 ± 2.3 vs. − 20.5 ± 3.2 vs. − 27.3 ± 3.1, respectively [p < 0.001]). The presence of cardiac injury, D-dimer, arterial oxygen saturation (SaO2), LV-GLS (OR 1.63, 95% confidence interval [CI] 1.08–2.47; p = 0.010) and RV-LS (OR 1.55, 95% CI 1.07–2.25; p = 0.019) were identified as independent predictors of mortality via multivariate analysis. LV-GLS and RV-LS are independent predictors of in-hospital mortality in patients with COVID-19.

Inclusion criteria included group 1 PAH (7) (not associated with connective tissue disease, human immunodeficiency virus, portal hypertension, or schistosomiasis), age >18 years, and symptomatic RV failure (objective findings of RV dysfunction by echocardiography [RV diastolic diameter >4.3 cm, fractional area change <35%, or tricuspid annular plane systolic excursion <1.5 cm] with New York Heart Association class II or III heart failure symptoms) despite optimal PAH therapy. [...]scheduling conflicts prevented two patients from completing baseline testing, and one patient was hospitalized for urosepsis before enrollment. [...]seven patients were enrolled in the study, in which they provided signed consent (approved by the institutional review board) and received anakinra 100 mg subcutaneously daily for 14 days, which is the dose approved by the U.S. Food and Drug Administration for the treatment of rheumatoid arthritis. Baseline testing before treatment included biomarkers (high-sensitivity C-reactive protein [hsCRP], IL-6, and N-terminal pro B-type natriuretic peptide [NTproBNP]), quality-of-life questionnaires (Duke Activity Severity Index and Minnesota Living with Heart Failure Questionnaire), transthoracic echocardiography, and cardiopulmonary exercise testing for measurement of peak oxygen consumption and ventilatory efficiency (Ve:Vco2 slope) (8). In CANTOS (Canakinumab Antiinflammatory Thrombosis Outcome Study), a recently published trial of IL-1 blockade in patients after myocardial infarction, overall rates of composite cardiovascular events were reduced with canakinumab, a monoclonal antibody to IL-1ß (10), especially in those patients who achieved hsCRP levels <2.0 mg/L (11). [...]in addition to being hindered by a small sample size, this study may have been underpowered to detect changes in surrogate markers of improved clinical status (cardiopulmonary exercise testing parameters) because of a failure to achieve the desired degree of inflammatory suppression.

COVID-19 patients with cardiac involvement have a high mortality rate. The aim of this study was to investigate the echocardiographic features in COVID-19 patients between severe and non-severe groups. For this single-center study, data from patients who were treated for COVID-19 between March 25, 2020 and April 15, 2020 were collected. Two-dimensional echocardiography (2DE) images were obtained for all patients. Patients were divided into two groups based on the severity of their COVID-19 infections. 2DE parameters indicating right ventricular (RV) and left ventricular (LV) functions were compared between the two groups. A total of 90 patients hospitalized for COVID-19 were included in this study. The mean age of the severe group (n = 44) was 63.3 ± 15.7 years, and 54% were male. The mean age of non-severe group (n = 46) was 49.7 ± 21.4 years, and 47% were male. In the severe group, RV and LV diameters were larger (RV, 36.6 ± 5.9 mm vs. 33.1 ± 4.8 mm, p = 0.003; LV 47.3 ± 5.8 mm vs. 44.9 ± 3.8 mm, p = 0.023), the LE ejection fraction (LVEF) and the RV fractional area change (RV-FAC) were lower (LVEF, 54.0 ± 9.8% vs. 61.9 ± 4.8%, p < 0.001; RV-FAC, 41.4 ± 4.1% vs. 45.5 ± 4.5%, p < 0.001), and pericardial effusions were more frequent (23% vs. 0%) compared to patients in the non-severe group. A multiple linear regression analysis determined that LVEF, right atrial diameter, high-sensitivity troponin I, d-dimer, and systolic pulmonary artery pressure, were independent predictors of RV dilatation. The results demonstrate that both right and left ventricular functions decreased due to COVID-19 infection in the severe group. 2DE is a valuable bedside tool and may yield valuable information about the clinical status of patients and their prognoses.

ObjectiveA 45% threshold of right ventricular ejection fraction (RVEF) is proposed clinically relevant in patients with pulmonary arterial hypertension (PAH). We aim to determine treatment response, long-term right ventricular (RV) functional stability and prognosis of patients with PAH reaching or maintaining the RVEF 45% threshold.MethodsIncident, treatment-naive, adult PAH patients with cardiac magnetic resonance imaging at baseline and first follow-up were included (total N=127) and followed until date of censoring or death/lung transplantation. Patients were categorised into two groups based on 45% RVEF. Baseline predictors, treatment response and prognosis were assessed with logistic regression analyses, two-way analysis of variance and log-rank tests.ResultsPatients were 50±17 years old, 73% female, of which N=75 reached or maintained the 45% RVEF threshold at follow-up (RVEF≥45%@FU), while N=52 patients did not (RVEF<45%@FU). RV end-diastolic volume and N-terminal pro-B-type natriuretic peptide at baseline were multivariable predictors of an RVEF ≥45% at follow-up. A 40% pulmonary vascular resistance (PVR) reduction resulted in greater improvement in RV function (ΔRVEF 17±11 vs. 5±8; pinteraction<0.001) compared to a PVR reduction <40%, but did not guarantee an RVEF ≥45%. Finally, the 45% RVEF threshold was associated with stable RV function during long-term follow-up and better survival (HR: 1.91 (95% CI: 1.11 to 3.27)). Patients failing to reach or maintain the 45% RVEF threshold at first follow-up mostly stayed below this threshold over the next consecutive visits.ConclusionAfter treatment initiation, 60% of patients with PAH reach or maintain the 45% RVEF threshold, which is associated with a long-term stable RV function and favourable prognosis.