1. What was learned from this study regarding the value of Pulmonary Vascular Resistance (PVR) measured non-invasively in prognosis of patients with pulmonary hypertension?

In this study we assessed for echocardiographic parameters that are significantly associated with mortality in a cohort of patients with at least moderately elevated pulmonary artery systolic pressures (> 60 mm Hg). We found that tricuspid plane systolic excursion (TAPSE) distance and right ventricular (RV) free wall thickness were the only two parameters that are significantly associated with survival. Cardiopulmonary comorbidities were common in this cohort. About 68% of patients had elevated LAP, 41.5% had an LVEF < 55%. We estimated pulmonary vascular resistance using the guideline-directed equation (PVR = ratio of peak tricuspid regurgitant velocity to the right ventricular outflow tract time-velocity integral (TRV/TVIRVOT) x 10 + 0.16)¹. Slightly over half the patients had an elevated PVR (>3 WU) and mean PVR was significantly elevated in the deceased patients. Others have demonstrated the prognostic value of invasively estimated PVR in pulmonary hypertension². Yet, age-adjusted, echo-derived PVR did not significantly increase the hazards of mortality in our study. This discrepancy highlights some of the methodological limitations in assessment of PVR by echo as acknowledged by Abbas et. al.¹. The lack of estimates of wedge pressure, right atrial pressure and heart rate in the equation, coupled with lack of precision of echocardiographically-derived pulmonary artery systolic pressure^3,4 may contribute to errors in calculations. Hence, larger studies evaluating and comparing alternative methodologies to estimate PVR non-invasively are needed for use in a heterogeneous population with PH.

2. The mean age in the study cohort was 78 years. How do data from this study influence strategies for diagnosis and management of older populations with pulmonary hypertension?

Pulmonary artery pressure (PAP) and the prevalence of pulmonary hypertension increases with increasing age^5,6, and with cardiopulmonary co-morbidities⁶ that are common in the aging population. Also, elevated pulmonary artery pressure relates with poor survival and heart failure admissions independent of co-morbid conditions and age. In this study, we show that RV dysfunction in the presence of elevated PAP further aids in risk stratification in this population. This study builds on prior literature demonstrating the poor prognosis associated with RV dysfunction, in predominantly elderly patients with PH and high prevalence of cardio-pulmonary comorbidities. Despite the evidence of elevated risk associated with both high PAP and RV dysfunction, these observations remain under recognized in vulnerable populations^7,8. Recognition of these at risk patients and work up for reversible causes (such as hypoxia and CTEPH) in appropriate patients is urgently needed. The management algorithms for PAH are being carefully evaluated and tested⁹. In contrast, studies are needed to evaluate whether PAP is a modifiable risk factor in settings of non-PAH pulmonary hypertension, and testing therapeutic strategies (pharmacological and non-pharmacological) may result in lowering PAP and improving RV function in at-risk populations to reduce morbidity and mortality.

References

1. Abbas AE, Fortuin FD, Schiller NB, Appleton CP, Moreno CA, Lester SJ. A simple method for noninvasive estimation of pulmonary vascular resistance. Journal of the American College of Cardiology. 2003;41(6):1021-7.
2. Tampakakis E, Leary PJ, Selby VN, De Marco T, Cappola TP, Felker GM, et al. The diastolic pulmonary gradient does not predict survival in patients with pulmonary hypertension due to left heart disease. JACC Heart failure. 2015;3(1):9-16.
3. Fisher MR, Forfia PR, Chamera E, Housten-Harris T, Champion HC, Girgis RE, et al. Accuracy of Doppler echocardiography in the hemodynamic assessment of pulmonary hypertension. Am J Respir Crit Care Med. 2009;179(7):615-21.
4. Rich JD, Shah SJ, Swamy RS, Kamp A, Rich S. Inaccuracy of Doppler echocardiographic estimates of pulmonary artery pressures in patients with pulmonary hypertension: implications for clinical practice. Chest. 2011;139(5):988-93.
5. Lam CS, Borlaug BA, Kane GC, Enders FT, Rodeheffer RJ, Redfield MM. Age-associated increases in pulmonary artery systolic pressure in the general population. Circulation. 2009;119(20):2663-70.
6. Choudhary G, Jankowich M, Wu WC. Prevalence and clinical characteristics associated with pulmonary hypertension in African-Americans. PloS one. 2013;8(12):e84264.
7. Maron BA, Choudhary G, Khan UA, Jankowich MD, McChesney H, Ferrazzani SJ, et al. The Clinical Profile and Under-Diagnosis of Pulmonary Hypertension in U.S. Veteran Patients. Circulation Heart failure. 2013.
8. Kingrey JF, Panos RJ, Ying J, Meganathan K, Vandivier R, Elwing JM. Provider recognition and response to echocardiographic findings indicating pulmonary hypertension in the Veterans affairs medical center population. Pulm Circ. 2013;3(2):389-95.
9. Galie N, Corris PA, Frost A, Girgis RE, Granton J, Jing ZC, et al. Updated treatment algorithm of pulmonary arterial hypertension. Journal of the American College of Cardiology. 2013;62(25 Suppl):D60-72.

Keywords: Aged, Algorithms, Atrial Pressure, Blood Pressure, Cohort Studies, Comorbidity, Echocardiography, Heart Failure, Heart Rate, Hypertension, Pulmonary, Prevalence, Prognosis, Pulmonary Artery, Pulmonary Wedge Pressure, Risk Factors, Vascular Resistance, Ventricular Dysfunction, Right, Ventricular Function, Right, Vulnerable Populations

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