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

<div><p>Background</p><p>The effect of heart rate (HR) and body surface area (BSA) on pulmonary RC time and right ventricular (RV) load is unknown.</p><p>Methods</p><p>To 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.</p><p>Results</p><p>A 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.</p><p>Conclusion</p><p>Heart 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.</p></div

Multiple linear regression models for determinants of RC Time in Cohorts A-C.

<p>Multiple linear regression models for determinants of RC Time in Cohorts A-C.</p

RC curves for quintile 1 and quintile 5 of heart rate in cohorts A-C (p<0.0001 for comparison of curves after log-log transformation).

<p>RC curves for quintile 1 and quintile 5 of heart rate in cohorts A-C (p<0.0001 for comparison of curves after log-log transformation).</p

Hemodynamics at baseline and peak paced heart rate in Cohort D.

<p>Hemodynamics at baseline and peak paced heart rate in Cohort D.</p

RC curves for quintile 1 and quintile 5 of body-surface area in cohorts A-C (p<0.0001 for comparison of curves after log-log transformation).

<p>RC curves for quintile 1 and quintile 5 of body-surface area in cohorts A-C (p<0.0001 for comparison of curves after log-log transformation).</p

Baseline characteristics for Cohorts A-D.

<p>Baseline characteristics for Cohorts A-D.</p

Clinical phenotypes and survival of pre-capillary pulmonary hypertension in systemic sclerosis

<div><p>Pre-capillary pulmonary hypertension (PH) in systemic sclerosis (SSc) is a heterogeneous condition with an overall bad prognosis. The objective of this study was to identify and characterize homogeneous phenotypes by a cluster analysis in SSc patients with PH. Patients were identified from two prospective cohorts from the US and France. Clinical, pulmonary function, high-resolution chest tomography, hemodynamic and survival data were extracted. We performed cluster analysis using the k-means method and compared survival between clusters using Cox regression analysis. Cluster analysis of 200 patients identified four homogenous phenotypes. Cluster C1 included patients with mild to moderate risk pulmonary arterial hypertension (PAH) with limited or no interstitial lung disease (ILD) and low DLCO with a 3-year survival of 81.5% (95% CI: 71.4–88.2). C2 had pre-capillary PH due to extensive ILD and worse 3-year survival compared to C1 (adjusted hazard ratio [HR] 3.14; 95% CI 1.66–5.94; p = 0.0004). C3 had severe PAH and a trend towards worse survival (HR 2.53; 95% CI 0.99–6.49; p = 0.052). Cluster C4 and C1 were similar with no difference in survival (HR 0.65; 95% CI 0.19–2.27, p = 0.507) but with a higher DLCO in C4. PH in SSc can be characterized into distinct clusters that differ in prognosis.</p></div

Baseline characteristics.

<p>Baseline characteristics.</p

Distribution of patients with no, limited and extensive interstitial lung disease according to mean pulmonary artery pressure.

<p>Distribution of patients with no, limited and extensive interstitial lung disease according to mean pulmonary artery pressure.</p

Survival of the four clusters C1, C2, C3 and C4.

<p>The difference of survival between the 4 clusters was significant (p = 0.0002).</p