Acute pleiotropic effects of dapagliflozin in type 2 diabetic patients with heart failure with reduced ejection fraction: a crossover trial.

AIMS: This study aimed to explore the rapid effects of dapagliflozin in heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: We studied the functional, echocardiographic, electrophysiological, lung ultrasound, ambulatory blood pressure (BP), microvascular and macrovascular function, and biochemical effects of 2 week treatment with dapagliflozin in 19 type 2 diabetic HFrEF patients in a double-blind, crossover, placebo-controlled trial. Dapagliflozin had no significant effect on clinical, functional, or quality of life parameters. Dapagliflozin reduced systolic BP [114 (105, 131) vs. 106 (98, 113) mmHg, P < 0.01] and diastolic BP [71 (61, 78) vs. 62 (55, 70) mmHg, P < 0.01]. There was no effect on cardiac chamber size, ventricular systolic function, lung ultrasound, or arterial wave reflection. Dapagliflozin increased creatinine [117 (92, 129) vs. 122 (107, 135) µmol/L, P < 0.05] and haemoglobin [135 (118, 138) vs. 136 (123, 144) g/L, P < 0.05]. There was a reduction in ventricular ectopy [1.4 (0.1, 2.9) vs. 0.2 (0.1, 1.4) %, P < 0.05] and an increase in standard deviation of normal heart beat intervals [70 (58, 90) vs. 74 (62, 103), P < 0.05]. Unexpectedly, dapagliflozin increased high-sensitivity troponin T [25 (19, 37) vs. 28 (20, 42) ng/L, P < 0.01] and reduced reactive hyperaemia index [1.29 (1.21, 1.56) vs. 1.40 (1.23, 1.84), P < 0.05]. CONCLUSIONS: After 2 weeks, while multiple parameters supported BP reduction and haemoconcentration with dapagliflozin, reduction in cardiac filling pressure, lung water, and functional improvement was not shown. Reduced ventricular ectopic burden suggests an early antiarrhythmic benefit. The small increase in troponin T and the reduction in the reactive hyperaemia index warrant further mechanistic exploration in this treatment of proven mortality benefit in HFrEF.

The Spectrum of Change in the Elite Athlete's Heart.

BACKGROUND: Extreme levels of both strength and aerobic training result in increased left ventricular (LV) and right ventricular (RV) volumes and LV mass, a key component of athletes' heart. The aim of this study was to document temporal changes in the hearts of elite professional athletes (Australian Football League players) over a 2- to 6-year period. METHODS: Thirty-six Australian Football League players with 3.5 ± 2.7 years of professional training at enrollment prospectively underwent echocardiography in the preseasons of 2009, 2013, and 2015. At each time point, LV dimension and contractility and RV dimension, area, and contractility were measured using two-dimensional echocardiography. LV volumes, ejection fraction, and mass were measured using three-dimensional echocardiography. RESULTS: The mean age at baseline was 21.8 ± 2.6 years (range, 18-29 years). Most players (n = 20) had increases in fitness between studies (mean maximal oxygen uptake, 62.3 ± 3.6 vs 64.3 ± 2.1 mL/kg/min). In these players, there were increases in both LV and RV size and in LV mass. Players who were >25 years of age at their baseline scans demonstrated a trend toward increases in RV size and a decline in RV global longitudinal strain. Fitness level and playing position also affected the degree of physiological athletic cardiac remodeling. CONCLUSIONS: Australian football is a sport that involves both strength and aerobic training. This study, unique in its length and detail, demonstrates that remodeling in the athlete's heart is a continuous spectrum of change. This remodeling occurs over time in response to high levels of exercise, with proportional increase in LV mass and LV dimensions.

Side effects of high-dose dobutamine are not prevented by normal saline infusion in dobutamine stress echocardiography.

High-dose dobutamine used in dobutamine stress echocardiography (DSE) has hemodynamically based side effects due to a variable combination of beta1 (inotropic) and beta2 (vasodilator) effects. Of concern is the development of an "empty ventricle syndrome" associated with intracavitary or outflow tract obstruction and resultant symptomatic hypotension. This study was undertaken to determine whether the concurrent administration of normal saline (N/S) would decrease symptoms, limit the development of left ventricular outflow tract (LVOT) obstruction and hypotension by maintaining left ventricular volume. One hundred patients, mean age 66 years +/- 12, presenting for a DSE were randomized into two groups. One group (n = 50) received N/S at a rate of 800 ml/hour during the test, the second group received dobutamine alone. Patients were instructed to report and quantify symptoms on a scale of 1 to 10. Echocardiographic measurements of end systolic volume (ESV) and LVOT gradients were taken prior to dobutamine and at peak dose. There was no difference in symptom scores (3.5 +/- 5.1(N/S) vs. 3.0 +/- 4.7, P = 0.6), change in systolic blood pressure (BP) (-0.74 mmHg +/- 33 (N/S) vs. -0.89 +/- 35, P = 0.9) maximum LVOT gradient at peak (16.4 mmHg +/- 16.1 (N/S) vs. 13.9 mmHg +/- 9, P = 0.4), or ESV at peak (17.9 mL +/- 13.4 (N/S) vs. 15.5 ml +/- 10.6, P = 0.37). Furthermore, there was no difference in the number of patients (10/50 (20%) in both groups) who developed a significant LVOT gradient, defined as greater than 20 mmHg at peak dose. Despite the sound theoretical basis of N/S infusion to protect against "empty ventricle syndrome" during DSE this randomized trial does not demonstrate any symptomatic or hemodynamic benefit.