Heart Rate Dependence of the Pulmonary Resistance x Compliance (RC) Time and Impact on Right Ventricular Load

Abstract

BackgroundThe effect of heart rate (HR) and body surface area (BSA) on pulmonary RC time and right ventricular (RV) load is unknown.MethodsTo determine the association of HR and BSA with the pulmonary RC time and measures of RV load, we studied three large patient cohorts including subjects with 1) known or suspected pulmonary arterial hypertension (PAH) (n = 1008), 2) pulmonary hypertension due to left heart disease (n = 468), and 3) end-stage heart failure with reduced ejection fraction (n = 150). To corroborate these associations on an individual patient level, we performed an additional analysis using high-fidelity catheters in 22 patients with PAH undergoing right atrial pacing.ResultsA faster HR inversely correlated with RC time (p<0.01 for all), suggesting augmented RV pulsatile loading. Lower BSA directly correlated with RC time (p<0.05) although the magnitude of this effect was smaller than for HR. With incremental atrial pacing, cardiac output increased and total pulmonary resistance (TPR) fell. However, effective arterial elastance, its mean resistive component (TPR/heart period; 0.60±0.27 vs. 0.79±0.45;p = 0.048), and its pulsatile component (0.27±0.18 vs 0.39±0.28;p = 0.03) all increased at faster HR.ConclusionHeart rate and BSA are associated with pulmonary RC time. As heart rate increases, the pulsatile and total load on the RV also increase. This relationship supports a hemodynamic mechanism for adverse effects of tachycardia on the RV.

Smooth muscle cytochrome b5 reductase 3 deficiency accelerates pulmonary hypertension development in sickle cell mice

“…Anemia-driven increases in heart rate can adversely affect RV afterload, with increased work for the RV spurring compensatory remodeling. 47 The augmented RV end diastolic pressure observed in SS chimeras with 3 weeks of SMC CYB5R3 knockdown is consistent with an elevated RV preload that one expects with anemia. 48,49 Although the monogenetic defect of sickle cell anemia, resulting in substitution of valine for glutamic acid in the codon for b-globin synthesis, is certainly the origin of the anemia that drives much of the multiorgan pathology known to characterize the disease, the degree of proximity with which that anemia affects ventricular remodeling or function on either side of the heart remains unclear.…”

Right ventriculo–arterial uncoupling and impaired contractile reserve in obese patients with unexplained exercise intolerance

“…This makes a significant drug contribution of beta blockade in the Obese+ePVH group unlikely. Recent evidence suggests that reduction in tachycardia, observed in the Obese+ePVH group on exercise, may act to reduce RV pulsatile loading and thus total afterload (Metkus et al 2016 ). We cannot therefore discount the possibility of both detrimental and beneficial effects of beta blockade on RV and pulmonary vascular exercise responses in our Obese+ePVH cohort.…”

Pathophysiology of the right ventricle and of the pulmonary circulation in pulmonary hypertension: an update

“…A series of studies showed recently that PVR and PAC are inversely related, and RC-time is constant over a wide range of severities, aetiologies and treatments of PH (figure 3) [41, 45, 46]. It is noteworthy that RC-time is decreased when PAWP increases in patients with heart failure [47, 48]. The fact that PVR takes the wedge pressure into account, whereas compliance, calculated as SV/PP, does not, gives rise to an altered RC-time in post-capillary PH.…”