Reversing the Cardiac Effects of Sedentary Aging in Middle Age—A Randomized Controlled Trial

BackgroundPoor fitness in middle age is a risk factor for heart failure, particularly heart failure with a preserved ejection fraction. The development of heart failure with a preserved ejection fraction is likely mediated through increased left ventricular (LV) stiffness, a consequence of sedentary aging. In a prospective, parallel group, randomized controlled trial, we examined the effect of 2 years of supervised high-intensity exercise training on LV stiffness.MethodsSixty-one (48% male) healthy, sedentary, middle-aged participants (53±5 years) were randomly assigned to either 2 years of exercise training (n=34) or attention control (control; n=27). Right heart catheterization and 3-dimensional echocardiography were performed with preload manipulations to define LV end-diastolic pressure-volume relationships and Frank-Starling curves. LV stiffness was calculated by curve fit of the diastolic pressure-volume curve. Maximal oxygen uptake (Vo2max) was measured to quantify changes in fitness.ResultsFifty-three participants completed the study. Adherence to prescribed exercise sessions was 88±11%. Vo2max increased by 18% (exercise training: pre 29.0±4.8 to post 34.4±6.4; control: pre 29.5±5.3 to post 28.7±5.4, group×time P<0.001) and LV stiffness was reduced (right/downward shift in the end-diastolic pressure-volume relationships; preexercise training stiffness constant 0.072±0.037 to postexercise training 0.051±0.0268, P=0.0018), whereas there was no change in controls (group×time P<0.001; pre stiffness constant 0.0635±0.026 to post 0.062±0.031, P=0.83). Exercise increased LV end-diastolic volume (group×time P<0.001), whereas pulmonary capillary wedge pressure was unchanged, providing greater stroke volume for any given filling pressure (loading×group×time P=0.007).ConclusionsIn previously sedentary healthy middle-aged adults, 2 years of exercise training improved maximal oxygen uptake and decreased cardiac stiffness. Regular exercise training may provide protection against the future risk of heart failure with a preserved ejection fraction by preventing the increase in cardiac stiffness attributable to sedentary aging.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT02039154

Improving risk prediction in heart failure using machine learning

Background: Predicting mortality is important in patients with heart failure (HF). However, current strategies for predicting risk are only modestly successful, likely because they are derived from statistical analysis methods that fail to capture prognostic information in large data sets containing multi-dimensional interactions. Methods and results: We used a machine learning algorithm to capture correlations between patient characteristics and mortality. A model was built by training a boosted decision tree algorithm to relate a subset of the patient data with a very high or very low mortality risk in a cohort of 5822 hospitalized and ambulatory patients with HF. From this model we derived a risk score that accurately discriminated between low and high-risk of death by identifying eight variables (diastolic blood pressure, creatinine, blood urea nitrogen, haemoglobin, white blood cell count, platelets, albumin, and red blood cell distribution width). This risk score had an area under the curve (AUC) of 0.88 and was predictive across the full spectrum of risk. External validation in two separate HF populations gave AUCs of 0.84 and 0.81, which were superior to those obtained with two available risk scores in these same populations. Conclusions: Using machine learning and readily available variables, we generated and validated a mortality risk score in patients with HF that was more accurate than other risk scores to which it was compared. These results support the use of this machine learning approach for the evaluation of patients with HF and in other settings where predicting risk has been challenging

Effect of closed loop stimulation versus accelerometer on outcomes with cardiac resynchronization therapy: the CLASS trial.

Chronotropic incompetence (CI) in patients with heart failure is common and associated with impaired exercise intolerance and adverse outcomes. This study sought to determine the effects of closed loop stimulation (CLS) rate-adaptive pacing on functional capacity in patients with heart failure with reduced ejection fraction (HFrEF) and CI implanted with cardiac resynchronization therapy (CRT) devices.A randomized, blinded, cross-over designed trial enrolled patients with HFrEF and CI implanted with a Biotronik CRT-D to complete a quality of life questionnaire, 6-min walk distance (6MWD), and cardiopulmonary exercise testing after two programmed periods: 1-week period of CLS and 1-week period of standard accelerometer (DDDR).Nine patients (6 males, mean age 71.4 years, 7 with New York Heart Association Class III, mean ejection fraction 39 ± 8%) were enrolled. Quality of life trended higher in CLS as compared to DDDR (550.8 ± 123.9 vs 489.3 ± 164.9, p = 0.06). There were no differences between CLS and DDDR in 6MWD (293.1 ± 90.2 m vs 315.1 ± 95.5 m, p = 0.52), peak heart rate (HR) 110.7 ± 14.7 bpm vs 109.7 bpm ± 14.1, p = 0.67), or peak VO2 (12.3 ± 4.9 ml/kg/min vs 12.9 ± 5.9, p = 0.47). As tests were submaximal as indicated by low respiratory exchange ratios (0.98 ± 0.11 vs 1.0 ± 0.8, p = 0.35), VE/VCO2 slope also showed no difference between CLS and DDDR (35.8 ± 5.6 vs 35.4 ± 5.7, p = 0.65). Five patients (56%) preferred CLS programming (p = 1.0).In patients with HFrEF and CI implanted with a CRT-D, peak HR, peak VO2, and 6MWD were equivalent, while there was a trend toward improved quality of life in CLS as compared to DDDR.URL: https://www.clinicaltrials.gov . Unique identifier: NCT02693262

Effect of closed loop stimulation versus accelerometer on outcomes with cardiac resynchronization therapy: the CLASS trial.

Chronotropic incompetence (CI) in patients with heart failure is common and associated with impaired exercise intolerance and adverse outcomes. This study sought to determine the effects of closed loop stimulation (CLS) rate-adaptive pacing on functional capacity in patients with heart failure with reduced ejection fraction (HFrEF) and CI implanted with cardiac resynchronization therapy (CRT) devices.A randomized, blinded, cross-over designed trial enrolled patients with HFrEF and CI implanted with a Biotronik CRT-D to complete a quality of life questionnaire, 6-min walk distance (6MWD), and cardiopulmonary exercise testing after two programmed periods: 1-week period of CLS and 1-week period of standard accelerometer (DDDR).Nine patients (6 males, mean age 71.4 years, 7 with New York Heart Association Class III, mean ejection fraction 39 ± 8%) were enrolled. Quality of life trended higher in CLS as compared to DDDR (550.8 ± 123.9 vs 489.3 ± 164.9, p = 0.06). There were no differences between CLS and DDDR in 6MWD (293.1 ± 90.2 m vs 315.1 ± 95.5 m, p = 0.52), peak heart rate (HR) 110.7 ± 14.7 bpm vs 109.7 bpm ± 14.1, p = 0.67), or peak VO2 (12.3 ± 4.9 ml/kg/min vs 12.9 ± 5.9, p = 0.47). As tests were submaximal as indicated by low respiratory exchange ratios (0.98 ± 0.11 vs 1.0 ± 0.8, p = 0.35), VE/VCO2 slope also showed no difference between CLS and DDDR (35.8 ± 5.6 vs 35.4 ± 5.7, p = 0.65). Five patients (56%) preferred CLS programming (p = 1.0).In patients with HFrEF and CI implanted with a CRT-D, peak HR, peak VO2, and 6MWD were equivalent, while there was a trend toward improved quality of life in CLS as compared to DDDR.URL: https://www.clinicaltrials.gov . Unique identifier: NCT02693262