Development of a Left Ventricular Diastolic Stress Test

Abstract

Left ventricular diastolic dysfunction is an important predictor of morbidity and mortality, and a major source of dyspnea upon exertion. Abnormal diastolic function, particularly during activities of daily living, is therefore an important contributor to reduced exercise tolerance and quality of life. Until recently, assessment of diastolic function has been limited to the resting condition, which often fails to recapitulate that which is experienced during daily activities. Accordingly, we sought to develop a simple— but effective— diastolic stress test which could easily be implemented into the clinical setting and differentiate patients with varying levels of diastolic dysfunction. For this investigation, we focused our attention on two known cardiovascular stressors: (a) isometric handgrip exercise (IHG), and (b) the cold pressor test (CPT). Both of these stressors are associated with robust and reproducible elevations in heart rate (HR) and arterial blood pressure (BP), without major changes in body and lung movement which are likely to be seen during dynamic exercise. We hypothesized that augmentation of the sympathetic nervous system and its associated cardiovascular response, would serve as a powerful diastolic discriminant. To test this hypothesis, we recruited six young, healthy women (age: 23 ± 4, BMI: 23.0 ± 2.8) and five elderly women without overt heart disease (age: 74 ± 7; BMI: 27.5 ± 3.0; two with Hypertension and one with Hypercholesterolemia). Heart rate, BP, Doppler mitral inflow velocities and annular tissue velocities were assessed at rest, following two minutes of IHG at 40% of maximum voluntary contraction, and following two minutes of a CPT. The major novel findings were two‐fold: First, IHG caused an increase in HR (ΔHR: 26 vs. 20bpm, young vs. old), and systolic BP (ΔSBP: 32 vs. 21mmHg, young vs. old), while the E/E′ ratio (a surrogate measure of left ventricular filling pressure) rose in the elderly population, with very little change in the young subjects (ΔE/E′: 0.87 vs. 1.80, young vs. old). Second, the CPT also increased HR (ΔHR: 6 vs. 10bpm, young vs. old) and systolic BP (ΔSBP: 17 vs. 42mmHg, young vs. old), while similarly differentiating the diastolic response in young vs. older participants (ΔE/E′: −0.07 vs. 1.47, young vs. old). Taken together, these preliminary data demonstrate both feasibility and efficacy of this novel diastolic stress test. More work is needed to apply this work to individuals at risk for or with heart failure and compare this approach to existing stress modalities.Support or Funding InformationThis work was supported by AHA 16SDG27260115 and the Harry S. Moss Heart Trust.