Abstract Objectives We aimed to determine whether body mass index (BMI) is a prognostic indicator for long-term, all-cause mortality in patients undergoing transcatheter aortic valve implantation ...(TAVI). Background Obesity in patients with established cardiovascular disease has previously been identified as an indicator of good prognosis, a phenomenon known as the “obesity paradox”. The prognostic significance of BMI in patients with severe aortic stenosis (AoS) undergoing TAVI is a matter of current debate, as published studies are scarce and their results conflicting. Methods This is an observational, retrospective study involving 770 patients who underwent TAVI for AoS. The cohort was divided into three groups based on their BMI: normal weight (≥ 18.5 to < 25 kg/m2 ), overweight (≥ 25 to < 30 kg/m2 ) and obese (≥ 30 kg/m2 ). The predictive effect of BMI on all-cause mortality 3 years following TAVI intervention was analysed using a Cox regression. Results 155 patients died during follow-up. The overweight group ( n = 302, 38.97%), experienced a lower mortality rate compared to the normal weight and obese groups (15.9% vs 25.7% and 21.0%, respectively log-rank p -value = 0.036). After adjustment by logistic EuroSCORE, being overweight was found to be an independent protective factor against mortality (HR: 0.63 95% CI: 0.42 to 0.94, p = 0.024). This was not the case for obesity (HR: 0.92 95% CI: 0.63 to 1.35, p = 0.664). We therefore describe for the first time, a “J-shaped” regression curve describing the relationship between BMI and mortality. Conclusions BMI is a predictive factor of all-cause mortality in AoS patients undergoing TAVI. This relationship takes the form of a “J-shaped” curve in which overweight patients are associated with the lowest mortality rate at follow-up.
Among patients undergoing transcatheter aortic valve replacement (TAVR), prognosis is impacted by nutritional status, but the influence of the nutritional risk index (NRI) is unknown. Here we ...calculated the NRI to determine the prevalence and prognostic impact in terms of mortality of malnutrition in TAVR patients.
This retrospective multicenter study included 941 patients who underwent TAVR between 2008 and 2016 (mean age, 80.7 ± 6.5 years; 57% female). The NRI was calculated as 1.519 × albumin (g/L) + 41.7 × (real weight kg / ideal weight kg). The mean NRI was 98.1 ± 7.0%. The patients were stratified into the following groups based on malnutrition risk: severe (NRI < 83.5; n = 83; 8.82%), moderate (83.5 ≥ NRI < 97.5; n = 370; 39.32%), mild (97.5 ≥ NRI < 100; n = 102; 10.84%), and no risk (NRI ≥ 100; n = 386; 41.02%). During the follow-up period (2.1 ± 1.1 years), 186 patients died, representing 19.8% of the total cohort. Cox regression models were used to analyze the relationship between NRI and mortality during follow-up. Compared to patients with no or mild nutritional risk, those with moderate or severe nutritional risk had a 45% greater risk of mortality during follow-up (adjusted HR, 1.45; 95% CI, 1.05–1.99; P = 0.021).
Malnutrition is common among TAVR patients. Our present data indicated that the NRI was independently associated with increased risk of death during long-term follow-up after TAVR. Based on its potential to improve risk prediction, NRI appears to be a promising tool for the clinical assessment of patients who are candidates for TAVR.
•Malnutrition, assessed by the NRI, is common among TAVR patients.•NRI was independently associated with mortality during long-term follow-up after TAVR.•NRI as a tool for detection of malnutrition should be included in the evaluation process of TAVR patients.
In our study we describe for the first time a "J"-shaped regression, that relates the BMI with long-term mortality (figure 1). ...patients at the extremes of the curve (underweight and extreme ...obesity) has the worst prognosis, whereas patients who are overweight have the most favorable prognosis.
Our objective was to evaluate progression-free survival (PFS) and distant metastasis-free survival (DMFS) as surrogate end points for overall survival (OS) in randomized trials of chemotherapy in ...loco-regionally advanced nasopharyngeal carcinomas (NPCs).
Individual patient data were obtained from 19 trials of the updated Meta-Analysis of Chemotherapy in Nasopharyngeal Carcinoma (MAC-NPC) plus one additional trial (total = 5144 patients). Surrogacy was evaluated at the individual level using a rank correlation coefficient ρ and at the trial level using a correlation coefficient R
between treatment effects on the surrogate end point and OS. A sensitivity analysis was performed with two-year PFS/DMFS and five-year OS.
PFS was strongly correlated with OS at the individual level (ρ = 0.93, 95% confidence interval CI = 0.93 to 0.94) and at the trial level (R
= 0.95, 95% CI = 0.47 to 1.00). For DMFS, too, the individual-level correlation with OS was strong (ρ = 0.98, 95% CI = 0.98 to 0.98); at trial level, the correlation was high but the regression adjusted for measurement error could not be computed (unadjusted R
= 0.96, 95% CI = 0.94 to 0.99). In the sensitivity analysis, two-year PFS was highly correlated with five-year OS at the individual level (ρ = 0.89, 95% CI = 0.88 to 0.90) and at the trial level (R
= 0.85, 95% CI = 0.46 to 1.00); two-year DMFS was highly correlated with five-year OS at the individual level (ρ = 0.95, 95% CI = 0.94 to 0.95) and at the trial level (R
= 0.78, 95% CI = 0.33 to 1.00).
PFS and DMFS are valid surrogate end points for OS to assess treatment effect of chemotherapy in loco-regionally advanced NPC, while PFS can be measured earlier.
Purpose
HFpEF (heart failure with preserved ejection fraction) is a major consequence of diabetic cardiomyopathy with no effective treatments. Here, we have characterized Akita mice as a preclinical ...model of HFpEF and used it to confirm the therapeutic efficacy of the mitochondria-targeted dicarbonyl scavenger, MitoGamide.
Methods and Results
A longitudinal echocardiographic analysis confirmed that Akita mice develop diastolic dysfunction with reduced E peak velocity, E/A ratio and extended isovolumetric relaxation time (IVRT), while the systolic function remains comparable with wild-type mice. The myocardium of Akita mice had a decreased ATP/ADP ratio, elevated mitochondrial oxidative stress and increased organelle density, compared with that of wild-type mice. MitoGamide, a mitochondria-targeted 1,2-dicarbonyl scavenger, exhibited good stability in vivo, uptake into cells and mitochondria and reactivity with dicarbonyls. Treatment of Akita mice with MitoGamide for 12 weeks significantly improved the E/A ratio compared with the vehicle-treated group.
Conclusion
Our work confirms that the Akita mouse model of diabetes replicates key clinical features of diabetic HFpEF, including cardiac and mitochondrial dysfunction. Furthermore, in this independent study, MitoGamide treatment improved diastolic function in Akita mice.
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