In-hospital evolution of secondary mitral regurgitation in acutely decompensated heart failure.

AIMS: Secondary mitral regurgitation (MR) negatively affects prognosis in acutely decompensated heart failure (ADHF), but can be rapidly sensitive to changes in volume status and medical interventions. We sought to assess the evolution of secondary MR in patients hospitalized for ADHF and its prognostic implications. METHODS: We retrospectively enrolled 782 patients admitted for ADHF with at least two in-hospital echocardiographic evaluations of MR. We classified MR severity as none-mild or moderate-severe. Based on MR evolution, patients were divided into 'persistent moderate-severe MR', 'improved MR' (from moderate-severe to none-mild) and 'persistent none-mild MR'. RESULTS: Four hundred and forty patients (56%) had moderate-severe MR at first evaluation, of whom 144 (33% of patients with baseline moderate-severe MR) had 'improved MR', while 296 (67%) had 'persistent moderate-severe MR'. Patients with improved MR had better clinical, laboratory and echocardiographic parameters of decongestion at discharge compared with those with persistent moderate-severe MR and showed a higher up-titration of recommended therapies. Left ventricular volume, ejection fraction and serum urea were the predictors of improved MR at multivariable analysis. After adjustment, no differences in 5-years survival (primary outcome) were observed according to baseline MR severity. When patients were stratified according to the in-hospital changes in MR severity, improved MR was associated with lower risk of 5-years mortality, compared with both persistent none-mild MR [hazard ratio (HR) = 0.505, P = 0.032] and persistent moderate-severe MR (HR = 0.556, P = 0.040). CONCLUSIONS: The severity of MR frequently improved during hospitalization for ADHF; the extent and the changes in MR severity during the in-hospital stay identified distinct patient phenotypes, and seemed to portend different long-term outcomes, with higher 5-years survival associated with improvement in MR.

Dynamic evolution of tricuspid regurgitation during hospitalization in patients with acute decompensated heart failure.

AIMS: Secondary tricuspid regurgitation (TR) is associated with poor prognosis in acute decompensated heart failure (ADHF). However, its dynamic evolution in response to volume status and treatment has never been previously investigated. In this study, we sought to explore the in-hospital evolution of TR in ADHF patients and to assess its prognostic implications. METHODS AND RESULTS: We retrospectively enrolled patients admitted for ADHF with ≥2 in-hospital echocardiographic evaluations of TR. Patients were categorized, according to TR evolution, into persistent moderate-severe TR, improved TR (from moderate-severe to trivial-mild) and persistent trivial-mild TR. The primary endpoint was a composite of 5-year all-cause mortality and heart failure hospitalization (HFH). A total of 1054 patients were included. Of 318 patients (30%) with moderate-severe TR at admission, 49% improved TR severity and showed better trends of decongestion, whereas those who maintained persistent moderate-severe TR had characteristics of more severe heart failure at admission and discharge. Atrial fibrillation, previous heart failure and higher dosage of loop diuretics before admission were associated with a lower probability of improved TR. After adjustment, improved TR was associated with lower risk of 5-year all-cause mortality/HFH compared with persistent moderate-severe TR (hazard ratio [HR] 0.524, p = 0.008) and no different from persistent trivial-mild TR (HR 0.878, p = 0.575). Results were consistent across all subgroups of in-hospital variation of mitral regurgitation. CONCLUSION: Among ADHF patients with moderate-severe TR at admission, 49% had an in-hospital improvement in TR severity, which was associated with a reduction in risk of 5-year all-cause mortality and morbidity outcomes.

Phenotype and outcomes according to loop diuretic use in pulmonary arterial hypertension.

AIMS: The use of loop diuretics in pulmonary arterial hypertension (PAH) is less frequent compared with heart failure. The clinical and prognostic characteristics of PAH patients according to loop diuretic use remain unexplored. In this study, we retrospectively analysed the characteristics and survival of PAH patients requiring different doses of loop diuretics. METHODS AND RESULTS: Patients diagnosed with PAH between 2001 and 2022 at seven European centres for the management of PAH. According to the median equivalent dose of furosemide in the overall cohort, patients were divided into two subgroups: no/low-dose loop diuretic and high-dose loop diuretic. Primary outcome was 5 year all-cause mortality. Among the 397 patients included, 227 (57%) were treated with loop diuretics. Median daily furosemide equivalent dose was 25 mg, and accordingly patients were divided in no/low dose (i.e. ≤25 mg, n = 257, 65%) vs. high dose (i.e. >25 mg, n = 140, 35%). Patients in the high-dose group were older, more likely to have comorbidities, and had a more severe disease according to the ESC/ERS risk category. Crude 5 year survival was significantly shorter in patients in the high-dose group, but after adjustment for age, sex, and risk category, high loop diuretic dose was not significantly associated with the primary outcome. CONCLUSIONS: Use of high dose of loop diuretics in PAH is associated with a higher burden of comorbidities, more severe disease, and worse survival. However, in PAH, the need of high loop diuretic dose is a marker of disease severity and not an independent prognostic factor.

Frequency, characteristics and risk assessment of pulmonary arterial hypertension with a left heart disease phenotype.

AIM: To obtain real-world evidence about the features and risk stratification of pulmonary arterial hypertension (PAH) with a left heart disease (LHD) phenotype (PAH-LHD). METHODS AND RESULTS: By reviewing the records of consecutive incident PAH patients at 7 tertiary centers from 2001 to 2021, we selected 286 subjects with all parameters needed to determine risk of death at baseline and at first follow-up with COMPERA and COMPERA 2.0 scores. Fifty seven (20%) had PAH-LHD according to the AMBITION definition. Compared with no-LHD ones, they were older, had higher BMI, more cardiovascular comorbidities, higher E/e' ratio and left atrial area, but lower BNP concentrations and better right ventricular function and pulmonary hemodynamics. Survival was comparable between PAH-LHD and no-LHD patients, although the former were less commonly treated with dual PAH therapy. Both COMPERA and COMPERA 2.0 discriminated all-cause mortality risk of PAH-LHD at follow-up, but not at baseline. Risk profile significantly improved during follow-up only when assessed by COMPERA 2.0. At multivariable analysis with low-risk status as reference, intermediate-high and high-risk, but not LHD phenotype, were associated with higher hazard of all-cause mortality. Results were comparable in secondary analyses including patients in the last 10 years and atrial fibrillation and echocardiographic abnormalities as additional criteria for PAH-LHD. CONCLUSIONS: In real life, PAH-LHD patients are frequent, have less severe disease and are less likely treated with PAH drug combinations than no-LHD. The COMPERA 2.0 model may be more appropriate to evaluate their mortality risk during follow-up and how it is modulated by therapy.

A very rare cause of pre-capillary pulmonary hypertension: The PAMI syndrome.

We report the first known case of PAMI syndrome associated with pulmonary arterial hypertension (PAH) with a positive response to cyclophosphamide and pulmonary vasodilators. The patient's history began at 7 months with severe pancytopenia and fever. As time progressed, migrating arthritis, hepatosplenomegaly, and a growth deficit manifested without a plausible explanation. At the age of 17, worsening dyspnea led to a diagnosis of severe pre-capillary pulmonary hypertension and, after a multidisciplinary evaluation, a dual therapy with both vasoactive and immunosuppressive agents led to rapid clinical improvement. After a decade of stability, stopping sildenafil caused deterioration, reversed upon reintroduction. Thirty years after the onset of signs and symptoms, a genetic test identified the underlying condition known as PAMI syndrome. As PAMI syndrome involves intense systemic inflammation similar to PAH related to systemic lupus erythematosus (SLE), parameters and functional autonomy appropriately responded to early immunosuppressive and vasoactive therapy. PAMI syndrome, a rare autoinflammatory disease, is linked to precapillary pulmonary hypertension but the exact cause and optimal treatment approach are not fully understood, requiring further research for clarification and improved treatment options.

Association of Tricuspid Regurgitation With Outcome in Acute Heart Failure.

BACKGROUND: Tricuspid regurgitation (TR) is common in chronic heart failure (HF) and is associated with negative prognosis. However, evidence on prognostic implications of TR in acute HF is lacking. We sought to investigate the association between TR and mortality and the interaction with pulmonary hypertension (PH) in patients admitted for acute HF. METHODS: We enrolled 1176 consecutive patients with a primary diagnosis of acute HF and with available noninvasive estimation of TR and pulmonary arterial systolic pressure. RESULTS: Moderate-severe TR was present in 352 patients (29.9%) and was associated with older age and more comorbidities. The prevalence of PH (ie, pulmonary arterial systolic pressure >40 mm Hg), right ventricular dysfunction, and mitral regurgitation was higher in moderate-severe TR. At 1 year, 184 (15.6%) patients died. Moderate-severe TR was associated with higher 1-year mortality risk after adjustment for other echocardiographic parameters (pulmonary arterial systolic pressure, left ventricle ejection fraction, right ventricular dysfunction, mitral regurgitation, left and right atrial indexed volumes; hazard ratio, 1.718; P=0.009), and the association with outcome was maintained when clinical variables (eg, natriuretic peptides, serum creatinine and urea, systolic blood pressure, atrial fibrillation) were added to the multivariable model (hazard ratio, 1.761; P=0.024). The association between moderate-severe TR and outcome was consistent in patients with versus without PH, with versus without right ventricular dysfunction, and with versus without left ventricle ejection fraction <50%. Patients with coexistent moderate-severe TR and PH had 3-fold higher 1-year mortality risk compared with patients with no TR or PH (hazard ratio, 3.024; P<0.001). CONCLUSIONS: In patients hospitalized for acute HF, the severity of TR is associated with 1-year survival, regardless of the presence of PH. The coexistence of moderate-severe TR and estimated PH was associated with a further increase in mortality risk. Our data must be interpreted in the context of potential underestimation of pulmonary arterial systolic pressure in patients with severe TR.