Recalibrating pulmonary vascular resistance to predict heart failure

29 Oct 2020

In patients with pulmonary hypertension, an elevated pulmonary vascular resistance (PVR) of 3.0 Wood units (WU) or more has been known to be associated with poor clinical prognosis.1 In a recent study published in The Lancet Respiratory Medicine, a PVR of 2.2 WU appeared to be capable of independently predicting major clinical events of mortality and heart failure (HF) hospitalization.1 With a lower PVR value limit now found to be likely abnormal and clinically meaningful, the hemodynamic parameters that are currently used to define pulmonary hypertension clinically in patients with cardiopulmonary disease may require reconsideration.1

HF is the most common cause of death in patients who suffer from pulmonary arterial hypertension (PAH).2 Where patients with a mean pulmonary artery pressure (mPAP) 25mmHg, pulmonary arterial wedge pressure (PAWP) ≤15mmHg, or PVR >3 WU are likely to have PAH, the spectrum of PVR risk in pulmonary hypertension (PH) is not known.1,3

To evaluate the relationship between PVR and adverse clinical outcomes in PH, a retrospective cohort study has recruited 40,082 veterans from the Veterans Affairs Clinical Assessment, Reporting, and Tracking (VA-CART) Program who had right-heart catheterization (RHC) in the VA system from October 1, 2007 to September 30, 2016.4 The primary cohort consisted of 96.7% male with a median age of 66.5 years.1 The median follow-up was 1,153 days which included patients with a history of HF (23,201 [57.9%]), chronic obstructive pulmonary disease (13,348 [33.3%]), and those who were at risk of pulmonary hypertension based on a mPAP ­19mmHg (32,725 [81.6%]).1

When modeled as a continuous variable, the all-cause mortality hazard for PVR was found to increase at around 2.2 WU compared with PVR of 1.0 WU.1 Among patients with an mPAP 19mmHg and pulmonary artery wedge pressure ≤15mmHg, the adjusted hazard ratio (HR) for mortality and HF hospitalization were 1.71 (95% CI: 1.59-1.84; p<0.0001) and 1.27 (95% CI: 1.13- 1.43; p=0.0001), respectively, when comparing patients with PVR ­2.2 WU to <2.2 WU. For the validation cohort of 2,870 patients (49.4% male) with mPAP ­19mmHg, the adjusted HR for mortality of patients with mPAP ­19mmHg, PVR ­2.2 WU, and pulmonary artery wedge pressure ≤15mmHg (1,221 [42.5%] of 2,870) was 1.81 (95% CI: 1.33–2.47; p=0.0002).1

Based on the study results, the greatest increase in all-cause mortality HR emerged at around 2.2 WU.1 From a clinical perspective, while an elevated PVR of ­3.0 WU has been conventionally used as a prognostic marker for death and HF in pulmonary hypertension subgroups, the PVR threshold of ­3.0 WU in patients with an mPAP of around 20-25mmHg has excluded a sizeable group of vulnerable patients.1,4 By clarifying a lower limit of PVR that is prognostic, patients with mildly elevated mPAP can be included in the early detection of pulmonary hypertension.1 In addition to higher diagnostic specificity, this PVR threshold of 2.2 WU also seems to emphasize the detection of severe or late pulmonary hypertension.1 Moreover, the findings from this study suggest that early engagement of multidisciplinary care plans such as close monitoring, functional assessments and behavior modifications could be considered without pharmacotherapy in patients having mPAP 19mmHg, PVR ­2.2 WU, and non pulmonary arterial hypertension with PVR ­3.0 WU.1 By determining the minimal mPAP and PVR associated with adverse outcomes, an evidence-based entry point into preventive medicine for pulmonary hypertension can be realized.1

By widening the continuum of clinical risk for mortality and HF in patients with elevated pulmonary artery pressure referred for RHC to include those with PVR ­2.2 WU, clinicians may be able to adopt early detection strategies to capture and assist this large and vulnerable population.1 While further studies would be required to confirm the generalizability of these findings in at-risk populations with fewer cardiopulmonary comorbidities, the results of this study have nonetheless supported the reconsideration of hemodynamic variables to identify patients with pulmonary hypertension.1

  1. Maron B A et al. Pulmonary vascular resistance and clinical outcomes in patients with pulmonary hypertension: a retrospective cohort study. Lancet Respir Med. 2020; 8: 873-884.
  2. Pulmonary Hypertension News. Pulmonary Hypertension and Heart Failure. Accessed September 25, 2020.
  3. Rosenkranz S et al. Right heart catheterisation: best practice and pitfalls in pulmonary hypertension. Eur Respir Rev. 2015; 24: 642–652.
  4. Kirkner R M et al. PVR reassessed as predictor of heart failure. CHEST Physician. 2020; 1-4.
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