Changes in echocardiographic parameters over time in paradoxical low-flow low-gradient aortic stenosis.

AIMS: To assess the progression of the disease and evolution of the main echocardiographic variables for quantifying AS in patients with severe low-flow low-gradient (LFLG) AS compared to other severe AS subtypes. METHODS AND RESULTS: Longitudinal, observational, multicenter study including consecutive asymptomatic patients with severe AS (aortic valve area, AVA < 1.0 cm²) and normal left ventricle ejection fraction (LVEF ≥ 50%). Patients were classified according to baseline echocardiography into: HG (high gradient; mean gradient ≥ 40 mmHg), NFLG (normal-flow low-gradient; mean gradient < 40 mmHg, indexed systolic volume (SVi) > 35mL/m2), or LFLG (mean gradient < 40 mmHg, SVi ≤ 35 mL/m²). AS progression was analyzed by comparing patients' baseline measurements and their last follow-up measurements or those taken prior to aortic valve replacement (AVR). Of the 903 included patients, 401 (44.4%) were HG, 405 (44.9%) NFLG, and 97 (10.7%) LFLG. Progression of the mean gradient in a linear mixed regression model was greater in low-gradient groups: LFLG vs. HG (regression coefficient 0.124, P = 0.005) and NFLG vs. HG (regression coefficient 0.068, P = 0.018). No differences were observed between the LFLG and NFLG groups (regression coefficient 0.056, P = 0.195). However, AVA reduction was slower in the LFLG group compared to the NFLG (P < 0.001). During follow-up, in conservatively-managed patients, 19.1% (n = 9) of LFLG patients evolved to having NFLG AS and 44.7% (n = 21) to having HG AS. In patients undergoing AVR, 58.0% (n = 29) of LFLG baseline patients received AVR with a HG AS. CONCLUSION: LFLG AS shows an intermediate AVA and gradient progression compared to NFLG and HG AS. The majority of patients initially classified as having LFLG AS changed over time to having other severe forms of AS, and most of them received AVR with a HG AS.

Predictors of cardiovascular outcomes after surgery in severe tricuspid regurgitation: clinical, imaging and hemodynamic prospective study.

INTRODUCTION AND OBJECTIVES: Severe tricuspid regurgitation (TR) is a prevalent valve disease with a high mortality rate. Current guidelines do not define specific thresholds at which patients should be considered for surgery or percutaneous procedures. Thus, patients are usually referred for intervention at a late stage of the disease. This study aimed to assess predictors of cardiovascular outcomes in a prospective cohort of patients with severe TR referred for surgery. METHODS: This was an observational, prospective, nonrandomized study. All patients underwent surgery for severe TR based on current clinical guidelines. Complete anamnesis, blood test, echocardiogram, cardiovascular magnetic resonance and right and left catheterization were performed. Patients were followed up in the outpatient department and a combined endpoint (hospitalization for heart failure and cardiovascular mortality) was registered. RESULTS: Forty-three consecutive patients were included (age: 66.9 ± 9.6 years, 67.4% female). Tricuspid annuloplasty was performed in all patients. After a median follow-up of 38 months, 12 patients (27.9%) showed the combined endpoint and 7 (16.3%) died. Above all clinical, blood and imaging data, the indexed right ventricular end-diastolic volume constituted the best predictor of the combined endpoint (HR, 1.1; P = .02) and cardiovascular mortality (HR, 1.1; P = .05). Furthermore, indexed right ventricular end-diastolic volume was associated with TR recurrence after surgery, with no impact on clinical outcomes. CONCLUSIONS: In patients with severe TR referred for surgery, right ventricular remodeling assessed by cardiovascular magnetic resonance constituted the best independent predictor of cardiovascular outcomes at follow-up.

The effect of benznidazole dose among the efficacy outcome in the murine animal model. A quantitative integration of the literature.

Despite more than 100 years since it was firstly described Chagas disease, only two drugs are available to treat Chagas disease: Nifurtimox launched by Bayer in 1965 and benznidazole launched by Roche in 1971. Drug discovery initiatives have been looking for new compounds as an alternative to these old drugs. Although new platforms have been used with the latest technologies, a critical step on that process still relies on the in vivo model. Unfortunately, to date, available animal models have limited predictive value and there is no standardization. With the aim to better understand the role of benznidazole, the current standard of care of Chagas disease, we performed this review. We intend to analyze the influence of the experimental design of the most used animal model, the murine model, in the assessment of the efficacy endpoint.