Effect of COVID-19 in Pulmonary Hypertension

To the Editor:

Montani and colleagues should be commended for their excellent effort in comprehensively analyzing the effect of coronavirus disease (COVID-19) in patients with pulmonary hypertension (PH) (1). However, I noticed a few issues related to the interpretation of the findings of this study. First of all, the hemodynamic and phenotypic characterization of PH is unclear. The authors stressed that all patients had precapillary PH without providing data related to pulmonary arterial wedge pressure (PAWP). In this study, all patients were older (>60 yr of age) and had one or multiple risk factors for coronary artery disease and heart failure. The risk factors for systolic and diastolic left ventricular dysfunction included systemic hypertension, obesity, diabetes, chronic renal failure, immunosuppression and other cardiac diseases (2). Patients exposed to these risk factors are likely to develop heart failure with preserved or reduced ejection fraction. The cardiac index data (median, 2.8 L/m/m²; range, 2.2–3.5 L/m/m²) in the survivor and nonsurvivor groups indicated a heterogeneous population of patients composed of groups with heart failure with preserved and reduced ejection fraction. In this scenario, hemodynamic characterization on the basis of PAWP becomes necessary to exclude isolated postcapillary PH (IpcPH) and combined post- and precapillary PH (CpcPH). Heart failure with preserved or reduced ejection fraction nearly always leads to CpcPH or IpcPH (3). In this heterogeneous population, the primary pathologies must have originated in the left ventricle in most patients, and PH seemed a secondary manifestation of heart failure. A normal right atrial pressure (6–9 mm Hg) in the presence of high brain natriuretic peptide or N-terminal pro–brain natriuretic peptide in nearly 50% of patients also indicated left ventricular failure with normal right ventricular function.

It is indeed surprising that all these diverse etiologies manifest only in precapillary PH. Unarguably, mortality due to COVID-19 in this population cannot be attributed entirely to precapillary PH. Nevertheless, a few risk factors (smoking, chronic respiratory disease) could have manifested entirely in precapillary PH. Therefore, readers would be curious to know the hemodynamic characterization of PH on the basis of PAWP and stratification of clinical outcomes after COVID-19. Furthermore, a comparison of clinical outcomes in isolated precapillary PH, heart failure with preserved ejection fraction, and heart failure with reduced ejection fraction would have been meaningful. The authors may conclude that patients with heart failure or precapillary hypertension who contracted COVID-19 had high rates of hospitalization and in-hospital mortality.

The considerably lower values of Dl_CO in the nonsurvivors are noteworthy. Lung parenchymal lesions appeared more extensive in nonsurvivors, and the severity of precapillary PH grades cannot entirely explain lower Dl_CO. Therefore, it is conceivable to conclude that structural lung lesions, not precapillary PH, contributed to mortality.

The majority of patients in this study received pulmonary vasodilator therapy. Considering the patient population in this study, many patients could have PH due to left heart disease (4). The authors refuted this hypothesis and contended that pulmonary arterial hypertension (PAH)–specific medications may not be protective during COVID-19. Pulmonary vasodilator therapy has not been shown to improve outcomes in PH due to left heart disease. Therefore, it may not be logical to refute the hypothesis, as the beneficial effects of PAH-specific medications could have been counteracted by possible harmful effects in PH due to left heart disease. Moreover, the nonsurvivors had poor Dl_CO, and patients with poor Dl_CO have a different kind of vasculopathy and are less responsive to PAH therapy (5). Furthermore, the investigators should have also aimed to provide echocardiographic data and medications used to treat comorbidities.

In conclusion, symptomatology and cardiac catheterization data of PH and heart failure are often indistinguishable in older populations with multiple comorbidities. Isolated precapillary PH should be clearly differentiated from IpcPH and CpcPH, as PAH-directed therapy may not be appropriate for all three phenotypes of PH. The impact of PAH-directed therapy in a mixed population of individuals with PH and COVID-19 may not be assessed distinctly.