To the Editor
We thank Dr Jamous for his comments on our review of pulmonary hypertension (PH) due to left-sided heart disease (LHD).1 Dr Jamous brings up several important questions regarding the hemodynamic diagnosis of mixed PH in the setting of heart failure with preserved ejection fraction (HFpEF) and how to use vasodilators during right-sided heart catheterization. First, differentiating pulmonary arterial hypertension (PAH) from HFpEF can be very challenging, and differentiation should be based not solely on hemodynamics but also on clinical risk factors and other ancillary testing. There are published algorithms suggesting how right-sided heart catheterization can help distinguish between the two,2 but those guidelines are not evidence based, and further research in this area is needed.
At our center, we do a volume or exercise challenge in patients with clinical risk factors for HFpEF who have upper normal or slightly elevated left-sided heart filling pressure. A “disproportionate” increase in left-sided heart filling pressure is most consistent with HFpEF. There are no evidence-based protocols for how much volume to give or the level of exercise that should be achieved.
Once a patient has been found to have mixed PH, a systemic vasodilator (nitroprusside) can be given to assess reversibility. Reversibility would implicate a pulmonary vasoconstrictive response, whereas irreversibility would suggest the development of vascular remodeling. It is not known whether reversibility affects treatment response or prognosis. Hypothetically, patients with reversible (normalization of pulmonary artery pressure and pulmonary capillary wedge pressure) mixed PH may have a better response to medical management (systemic afterload reduction). Also hypothetically, patients with irreversible mixed PH may benefit from PH-specific therapies. Trials looking at PAH-specific therapies in PH due to LHD have, however, been largely disappointing. The question of whether a subgroup of patients with mixed fixed World Health Organization (WHO) group 2 PH may benefit from PH-specific therapies remains to be answered.
Last, pulmonary vasodilators (nitric oxide, epoprostenol, or adenosine) are indicated for vasoreactivity testing in WHO group 1 PAH and should not be used in evaluation of WHO group 2 PH due to LHD.
Footnotes
Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Hansdottir is the principal investigator and subinvestigator, respectively, at the University of Iowa for multicenter studies on pulmonary arterial hypertension sponsored by Actelion Pharmaceuticals US, Inc; Bayer AG; Gilead; INO Therapeutics LLC; and United Therapeutics Corporation. Dr Gehlbach has reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
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References
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