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This study tested the hypothesis that early left ventricular (LV) relaxation is impaired in older obese patients with heart failure with preserved ejection fraction (HFpEF), and related to decreased peak exercise oxygen uptake (peak VO2). LV strain and strain rate were measured by feature tracking of magnetic resonance cine images in 79 older obese patients with HFpEF (mean age: 66 yr; mean body mass index: 38 kg/m²) and 54 healthy control participants. LV diastolic strain rates were indexed to cardiac preload as estimated by echocardiography derived diastolic filling pressures (E/e0), and correlated to peak VO2. LV circumferential early diastolic strain rate was impaired in HFpEF compared with controls (0.93 ± 0.05/s vs. 1.20 ± 0.07/s, P = 0.014); however, we observed no group differences in early LV radial or longitudinal diastolic strain rates. Isolating myocardial relaxation by indexing all three early LV diastolic strain rates (i.e. circumferential, radial, and longitudinal) to E/e0 amplified the group difference in early LV diastolic circumferential strain rate (0.08 ± 0.03 vs. 0.13 ± 0.05, P < 0.0001), and unmasked differences in early radial and longitudinal diastolic strain rate. Moreover, when indexing to E/e0, early LV diastolic strain rates from all three principal strains, were modestly related with peak VO2 (R =0.36, 0.27, and 0.35, respectively, all P < 0.01); this response, however, was almost entirely driven by E/e0 itself, (R = 0.52, P < 0.001). Taken together, we found that although LV relaxation is impaired in older obese patients with HFpEF, and modestly correlates with their severely reduced peak exercise VO2, LV filling pressures appear to play a much more important role in determining exercise intolerance. [ABSTRACT FROM AUTHOR]

Chronic heart failure (CHF) is a major contributor to cardiovascular disease and is the leading cause of hospitalization for those over the age of 65, which is estimated to account for close to seventy billion dollars in healthcare costs by 2030 in the US alone. The successful therapies for preventing and reversing CHF progression are urgently required. One strategy under active investigation is to restore dysregulated myocardial calcium (Ca2+), a hallmark of CHF. It is well established that intracellular Ca2+ concentrations are tightly regulated to control efficient myocardial systolic contraction and diastolic relaxation. Among the many cell surface proteins and intracellular organelles that act as the warp and woof of the regulatory network controlling intracellular Ca2+ signals in cardiomyocytes, sarco/endoplasmic reticulum Ca2+ ATPase type 2a (SERCA2a) undoubtedly plays a central role. SERCA2a is responsible for sequestrating cytosolic Ca2+ back into the sarcoplasmic reticulum during diastole, allowing for efficient uncoupling of actin-myosin and subsequent ventricular relaxation. Accumulating evidence has demonstrated that the expression of SERCA2a is downregulated in CHF, which subsequently contributes to severe systolic and diastolic dysfunction. Therefore, restoring SERCA2a expression and improving cardiomyocyte Ca2+ handling provides an excellent alternative to currently used transplantation and mechanical assist devices in the treatment of CHF. Indeed, advancements in safe and effective gene delivery techniques have led to the emergence of SERCA2a gene therapy as a potential therapeutic choice for CHF patients. This mini-review will succinctly detail the progression of SERCA2a gene therapy from its inception in plasmid and animal models, to its clinical trials in CHF patients, highlighting potential avenues for future work along the way. [ABSTRACT FROM AUTHOR]

Cardiac stress testing improves detection and risk assessment of heart disease. Magnetic resonance imaging (MRI) is the clinical gold-standard for assessing cardiac morphology and function at rest; however, exercise MRI has not been widely adapted for cardiac assessment because of imaging and device limitations. Commercially available magnetic resonance ergometers, together with improved imaging sequences, have overcome many previous limitations, making cardiac stress MRI more feasible. Here, we aimed to demonstrate clinical feasibility and establish the normative, healthy response to supine exercise MRI. Eight young, healthy subjects underwent rest and exercise cinematic imaging to measure left ventricular volumes and ejection fraction. To establish the normative, healthy response to exercise MRI we performed a comprehensive literature review and meta-analysis of existing exercise cardiac MRI studies. Results were pooled using a random effects model to define the left ventricular ejection fraction, end-diastolic, end-systolic, and stroke volume responses. Our proof-of-concept data showed a marked increase in cardiac index with exercise, secondary to an increase in both heart rate and stroke volume. The change in stroke volume was driven by a reduction in end-systolic volume, with no change in end-diastolic volume. These findings were entirely consistent with 17 previous exercise MRI studies (226 individual records), despite differences in imaging approach, ergometer, or exercise type. Taken together, the data herein demonstrate that exercise cardiac MRI is clinically feasible, using commercially available exercise equipment and vendor-provided product sequences and establish the normative, healthy response to exercise MRI.