Use of Ventilatory Efficiency Slope as a Marker for Increased Mortality in Wild-Type Transthyretin Cardiac Amyloidosis.

Wild-type transthyretin amyloidosis (ATTRwt) results in an infiltrative cardiomyopathy often culminating in symptomatic heart failure. The use of cardiopulmonary exercise testing (CPET) in determining outcomes in ATTRwt cardiac amyloidosis is unknown. Given the emergence of novel therapies to treat transthyretin amyloidosis, we sought to investigate the utility of CPET on outcomes in patients with ATTRwt cardiomyopathy. Fifty-six patients, with biopsy and immunohistochemically proved ATTRwt, were enrolled between 2005 and 2015, as part of an NIH ATTRwt substudy at the Boston University Amyloidosis Center. Patients were prospectively studied, which included laboratory tests, electrocardiogram, echocardiography, in addition to CPET. In this cohort of ATTRwt patients who performed CPET were elderly, all were male, and predominantly white (69.9%). The overall median survival was 59.01 months (95% confidence interval [CI] 49.29 to 88.69). By multivariate analysis, C-reactive protein (CRP; hazard ratio [HR] 1.10 [1.03 to 1.18]), decreased sodium (HR 0.75 [0.58 to 0.97]), creatinine (HR 7.48 [2.44 to 22.98]) and VE/VCO2 (HR 1.10 [1.05 to 1.16]) were significant risk factors for mortality (p <0.05). Peak VO2 was insignificant by both univariate and multivariate analyses. ATTRwt patients with VE/VCO2 >40 had a worse median survival of 38.54 months (95% CI 32.63 to 51.47) versus 88.69 months (95% CI 56.26 to 89.49) than patients with VE/VCO2 slope ≤40. Receiver-operating characteristic curve showed that the combination of VE/VCO2, CRP, sodium, and creatinine (Area under the ROC Curve [AUC], 0.89) predicted 1-year mortality in ATTRwt cardiac amyloidosis. In conclusion, increased VE/VCO2, in combination with CRP, sodium, and creatinine, may identify patients at increased risk of death in ATTRwt cardiomyopathy. VE/VCO2 might have a role in objectively assessing therapeutic response in ATTRwt cardiac amyloidosis.

Effects of testosterone replacement therapy withdrawal and re-treatment in hypogonadal elderly men upon obesity, voiding function and prostate safety parameters.

Whether testosterone replacement therapy (TRT) is a lifelong treatment for men with hypogonadism remains unknown. We investigated long-term TRT and TRT withdrawal on obesity and prostate-related parameters. Two hundred and sixty-two hypogonadal patients (mean age 59.5) received testosterone undecanoate in 12-week intervals for a maximum of 11 years. One hundred and forty-seven men had TRT interrupted for a mean of 16.9 months and resumed thereafter (Group A). The remaining 115 patients were treated continuously (Group B). Prostate volume, prostate-specific antigen (PSA), residual voiding volume, bladder wall thickness, C-reactive protein (CRP), aging male symptoms (AMS), International Index of erectile function - erectile function (IIEF-EF) and International Prostate Symptoms Scores (IPSS) were measured over the study period with anthropometric parameters of obesity, including weight, body mass index (BMI) and waist circumference. Prior to interruption, TRT resulted in improvements in residual voiding volume, bladder wall thickness, CRP, AMS, IIEF-EF, IPSS and obesity parameters while PSA and prostate volume increased. TRT interruption reduced total testosterone to hypogonadal levels in Group A and resulted in worsening of obesity parameters, AMS, IPSS, residual voiding volume and bladder wall thickness, IIEF-EF and PSA while CRP and prostate volume were unchanged until treatment resumed whereby these effects were reversed. TRT interruption results in worsening of symptoms. Hypogonadism may require lifelong TRT.