Dharmavaram, Naga

Abstract Deep phenotyping of pulmonary hypertension (PH) with multimodal diagnostic exercise interventions can lead to early focused therapeutic interventions. Herein, we report methods to simultaneously assess pulmonary impedance, differential biventricular myocardial strain, and right ventricular:pulmonary arterial (RV:PA) uncoupling during exercise, which we pilot in subjects with suspected PH. As proof-of-concept, we show that four subjects with different diagnoses [pulmonary arterial hypertension (PAH); chronic thromboembolic disease (CTEPH); PH due to heart failure with preserved ejection fraction (PH-HFpEF); and noncardiac dyspnea (NCD)] have distinct patterns of response to exercise. RV:PA coupling assessment with exercise was highest-to-lowest in this order: PAH > CTEPH > PH-HFpEF > NCD. Input impedance (Z0) with exercise was highest in precapillary PH (PAH, CTEPH), followed by PH-HFpEF and NCD. Characteristic impedance (ZC) tended to decline with exercise, except for the PH-HFpEF subject (initial Zc increase at moderate workload with subsequent decrease at higher workload with augmentation in cardiac output). Differential myocardial strain was normal in PAH, CTEPH, and NCD subjects and lower in the PH-HFpEF subject in the interventricular septum. The combination of these metrics allowed novel insights into mechanisms of RV:PA uncoupling. For example, while the PH-HFpEF subject had hemodynamics comparable to the NCD subject at rest, with exercise coupling dropped precipitously, which can be attributed (by decreased myocardial strain of interventricular septum) to poor support from the left ventricle (LV). We conclude that this deep phenotyping approach may distinguish afterload sensitive vs. LV-dependent mechanisms of RV:PA uncoupling in PH, which may lead to novel therapeutically relevant insights.

Abstract PurposeOur study aimed to use chest CT-angiogram (CTA) to assess if right ventricular (RV) dilation, quantified as an increased RV:LV (left ventricle) ratio, is associated with adverse outcomes in the novel coronavirus (COVID-19) infection.MethodsWe reviewed clinical, laboratory, and chest CTA findings in COVID-19 patients (n=100), and two control groups: normal subjects (n=10) and subjects with organizing pneumonia (n=10). On a chest CTA, we measured basal dimensions of the RV and LV in a focused 4-chamber view; and dimensions of pulmonary artery (PA) and aorta (AO) at the PA bifurcation level. ResultsAmong the COVID-19 cohort, the mean age (±SD) was 55.1±14.9 years and 55% were female. A higher RV:LV ratio was correlated with adverse outcomes, defined as ICU admission, intubation, or death. In patients with adverse outcomes, the RV:LV ratio was 1.06±0.10, vs 0.95±0.15 in patients without adverse outcomes. Among the adverse outcomes group, compared to the control subjects with organizing pneumonia, the lung parenchymal damage was lower (22.6±9.0 vs 32.7±6.6), yet the RV:LV ratio was higher (1.06±0.14 vs 0.89±0.07). In ROC analysis, RV:LV ratio had an AUC= 0.707 with an optimal cut-off of RV:LV 1.1 as a predictor of adverse outcomes. In a validation cohort (n=25), an RV:LV ≥1.1 as a cut-off predicted adverse outcomes with an odds ratio of 76:1.ConclusionIn COVID-19 patients, RV:LV ratio ≥1.1 on CTA-chest is correlated with adverse outcomes. RV dilation in COVID-19 is out of proportion to parenchymal lung damage, pointing towards a vascular and/or thrombotic injury in the lungs.