Editor's Note: Expert analysis based on the article Mazimba S, Mejia-Lopez E, Black G, et al. Diastolic pulmonary gradient predicts outcomes in group 1 pulmonary hypertension (analysis of the NIH primary pulmonary hypertension registry). Respir Med 2016;119:81-6.

Diastolic pulmonary gradient (DPG) is a novel hemodynamic marker that is calculated as the difference between pulmonary artery diastolic pressure (PADP), and mean pulmonary capillary wedge pressure (PCWP). A DPG value ≥ 7 mm Hg signals the presence of pulmonary vascular remodeling in patients with combined pre- and post-capillary pulmonary hypertension (CPCPH).¹ Diastolic pulmonary gradient has the appeal of being less sensitive to changes in loading conditions, thereby serving as a robust marker for pre-capillary pulmonary vascular remodeling in patients with pulmonary hypertension- left heart disease (PH-LHD).² In these patients, an elevated DPG ≥ 7 mm Hg is associated with increased mortality. Therefore, we evaluated the prognostic utility of DPG in patients with "primary pulmonary hypertension", now referred to as group 1 PH, using the National Institute of Health Primary Pulmonary Hypertension (NIH-PPH) database. Interestingly, we found that there was an independent association between DPG and 5 year mortality.³

Relationship Between Diastolic Pulmonary Gradient and Mortality in Patients with "Primary Pulmonary Hypertension" Now Group 1 PH

Our analysis of the NIH-PPH database demonstrated two key findings. First, we found that DPG has a wider distribution in group 1 PH (mean DPG was 31.6 mm Hg ± 13.8 mm Hg) than in CPCPH patients. With this greater bandwidth in group 1 PH, the magnitude of the numerical values of DPG offset the potential measurement errors and technical limitations of DPG that are encountered in PH-LHD. Some of the factors responsible for the technical limitations include low absolute values of DPG in PH-LHD, errors in the measurements of PADP or PCWP, phasic variations of PADP (especially with fluid catheters), and the contribution of large V waves to the mean PCWP.^4,5

The second key finding was that increasing DPG was significantly associated with increased mortality during the 5 years of the study, even after adjustment for the pulmonary hypertension connection (PHC) equation. The PHC risk equation was derived in the contemporary era of pulmonary vasodilator therapies, uses component variables of mean right atrial pressure, mean pulmonary artery pressure, and cardiac index.⁶ The association of DPG with mortality remained valid even when DPG was analyzed as either a continuous or a categorical variable. When analyzed as a continuous variable, DPG had a hazard ratio (HR) of 1.29/10 mm Hg (95% C.I. 1.13-1.48) for mortality during the 5 years of the study.

When DPG was grouped in quartiles (≤ 23 mm Hg, 24-30 mm Hg, 31-40 mm Hg, and > 40 mm Hg), there was indeed a clear separation of survival rates in these quartiles, with worse survival noted in higher quartiles (log-rank P=0.003). Increasing DPG was also significantly associated with worsening indices of right ventricular function (right atrial pressure, pulmonary vascular resistance, cardiac index and pulmonary artery capacitance). When DPG was dichotomized using a binary cut off of 40 mm Hg (based on sensitivity analysis), the HR for DPG > 40 mm Hg for 5-year mortality was 2.03 (p=0.01).

Potential Clinical Application of DPG in Group 1 PH

From a clinical utility standpoint, DPG is an easily measured index from two invasively derived hemodynamic parameters (PADP and mean PCWP). Furthermore, for group 1 PH patients, DPG has a greater signal-to-noise ratio with respect to mortality than in PH-LHD and may be an important hemodynamic tool in risk stratification. A DPG > 30-40 mm Hg is associated with the worst prognosis and may warrant an aggressive treatment approach.

References

1. Gerges C, Gerges M, Lang MB, et al. Diastolic pulmonary vascular pressure gradient: a predictor of prognosis in "out-of-proportion" pulmonary hypertension. Chest 2013;143:758-66.
2. Naeije R, Vachiery JL, Yerly P, Vanderpool R. The transpulmonary pressure gradient for the diagnosis of pulmonary vascular disease. Eur Respir J 2013;41:217-23.
3. Mazimba S, Mejia-Lopez E, Black G, et al. Diastolic pulmonary gradient predicts outcomes in group 1 pulmonary hypertension (analysis of the NIH primary pulmonary hypertension registry). Respir Med 2016;119:81-6.
4. Tampakakis E, Leary PJ, Selby VN, et al. The diastolic pulmonary gradient does not predict survival in patients with pulmonary hypertension due to left heart disease. JACC Heart Fail 2015;3:9-16.
5. Gerges C, Gerges M, Lang IM. Characterization of pulmonary hypertension in heart failure using the diastolic pressure gradient: the conundrum of high and low diastolic pulmonary gradient. JACC Heart Fail 2015;3:424-5.
6. Thenappan T, Shah SJ, Rich S, Tian L, Archer SL, Gomberg-Maitland M. Survival in pulmonary arterial hypertension: a reappraisal of the NIH risk stratification equation. Eur Respir J 2010;35:1079-87.

Keywords: Atrial Pressure, Blood Pressure, Diastole, Hypertension, Pulmonary, Pulmonary Artery, Pulmonary Wedge Pressure, Pulmonary Heart Disease, Survival Rate, Vascular Resistance, Vasodilator Agents, Ventricular Function, Right

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