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Patients with idiopathic pulmonary arterial hypertension did not respond to treatment with an acute vasodilator challenge because they were unable to recruit functional capillary surface area to accommodate increased blood flow to the lungs, according to the results of a study published Jan. 19 in Annals of Internal Medicine.
Dr. David Langleben of McGill University, Montreal, and Dr. Stylianos E. Orfanos of Attikon Hospital, Athens, hypothesized that the increased pulmonary vascular resistance (PVR) noted in responders would be based on vascular tone rather than cellular obstruction, and therefore responders should be capable of recruiting functional capillary surface area (CSA) during a vasodilator challenge.
“Despite sharing the baseline hemodynamic profile of IPAH, responders and nonresponders [may] represent different vascular phenotypes and perhaps different diseases,” they wrote.
The investigators recruited 14 patients (12 female, 2 male) with IPAH, none of whom had previously received IPAH-specific therapy or had saline contrast evidence of intracardiac shunting on echocardiography. Each subject underwent a standardized right heart catheterization followed by insertion of a femoral artery sheath. After a 30-minute rest period, investigators measured baseline hemodynamics and pulmonary capillary, endothelium-bound, angiotensin-converting enzyme (PCEB-ACE) metabolic activity.
Subsequently, the researchers performed an acute vasodilator challenge on each patient using epoprostenol (Flolan, GlaxoSmithKline Canada), after which PCEB-ACE metabolic activity and hemodynamics were measured again at the peak epoprostenol dose – determined “individually by maximum hemodynamic response or adverse effects.”
Functional CSA was calculated and normalized to body surface area. Values among nonresponders before the vasodilator challenge and at the peak epoprostenol dose were compared using paired t-tests. Of the 14 subjects, 12 were found to be nonresponders to vasodilator challenge and 2 (1 female, 1 male) did respond to vasodilator challenge treatment. In nonresponders overall, mean pulmonary arterial pressure (mPAP) did not change significantly – 59.5 mm Hg to 58.1 mm Hg – but cardiac output increased and PVR decreased. In the two subjects who responded, cardiac output and PVR increased, but mPAP decreased 43.5 mm Hg to 31.5 mm Hg.
“These data show the inability of nonresponders with IPAH to open occluded arterioles and thus recruit more downstream capillaries to accommodate the observed increased lung blood volumes that should accompany vasodilator administration,” the researchers concluded.
Funding for this study was provided by the William and Ida Pencer Family Foundation, the Dimitrios Banousis Foundation, the Bank of Montreal Center for the Study of Heart Disease in Women, and the Jewish General Hospital Annual Walk for Pulmonary Hypertension, all at Jewish General Hospital. The authors disclosed no conflicts of interest.
Patients with idiopathic pulmonary arterial hypertension did not respond to treatment with an acute vasodilator challenge because they were unable to recruit functional capillary surface area to accommodate increased blood flow to the lungs, according to the results of a study published Jan. 19 in Annals of Internal Medicine.
Dr. David Langleben of McGill University, Montreal, and Dr. Stylianos E. Orfanos of Attikon Hospital, Athens, hypothesized that the increased pulmonary vascular resistance (PVR) noted in responders would be based on vascular tone rather than cellular obstruction, and therefore responders should be capable of recruiting functional capillary surface area (CSA) during a vasodilator challenge.
“Despite sharing the baseline hemodynamic profile of IPAH, responders and nonresponders [may] represent different vascular phenotypes and perhaps different diseases,” they wrote.
The investigators recruited 14 patients (12 female, 2 male) with IPAH, none of whom had previously received IPAH-specific therapy or had saline contrast evidence of intracardiac shunting on echocardiography. Each subject underwent a standardized right heart catheterization followed by insertion of a femoral artery sheath. After a 30-minute rest period, investigators measured baseline hemodynamics and pulmonary capillary, endothelium-bound, angiotensin-converting enzyme (PCEB-ACE) metabolic activity.
Subsequently, the researchers performed an acute vasodilator challenge on each patient using epoprostenol (Flolan, GlaxoSmithKline Canada), after which PCEB-ACE metabolic activity and hemodynamics were measured again at the peak epoprostenol dose – determined “individually by maximum hemodynamic response or adverse effects.”
Functional CSA was calculated and normalized to body surface area. Values among nonresponders before the vasodilator challenge and at the peak epoprostenol dose were compared using paired t-tests. Of the 14 subjects, 12 were found to be nonresponders to vasodilator challenge and 2 (1 female, 1 male) did respond to vasodilator challenge treatment. In nonresponders overall, mean pulmonary arterial pressure (mPAP) did not change significantly – 59.5 mm Hg to 58.1 mm Hg – but cardiac output increased and PVR decreased. In the two subjects who responded, cardiac output and PVR increased, but mPAP decreased 43.5 mm Hg to 31.5 mm Hg.
“These data show the inability of nonresponders with IPAH to open occluded arterioles and thus recruit more downstream capillaries to accommodate the observed increased lung blood volumes that should accompany vasodilator administration,” the researchers concluded.
Funding for this study was provided by the William and Ida Pencer Family Foundation, the Dimitrios Banousis Foundation, the Bank of Montreal Center for the Study of Heart Disease in Women, and the Jewish General Hospital Annual Walk for Pulmonary Hypertension, all at Jewish General Hospital. The authors disclosed no conflicts of interest.
Patients with idiopathic pulmonary arterial hypertension did not respond to treatment with an acute vasodilator challenge because they were unable to recruit functional capillary surface area to accommodate increased blood flow to the lungs, according to the results of a study published Jan. 19 in Annals of Internal Medicine.
Dr. David Langleben of McGill University, Montreal, and Dr. Stylianos E. Orfanos of Attikon Hospital, Athens, hypothesized that the increased pulmonary vascular resistance (PVR) noted in responders would be based on vascular tone rather than cellular obstruction, and therefore responders should be capable of recruiting functional capillary surface area (CSA) during a vasodilator challenge.
“Despite sharing the baseline hemodynamic profile of IPAH, responders and nonresponders [may] represent different vascular phenotypes and perhaps different diseases,” they wrote.
The investigators recruited 14 patients (12 female, 2 male) with IPAH, none of whom had previously received IPAH-specific therapy or had saline contrast evidence of intracardiac shunting on echocardiography. Each subject underwent a standardized right heart catheterization followed by insertion of a femoral artery sheath. After a 30-minute rest period, investigators measured baseline hemodynamics and pulmonary capillary, endothelium-bound, angiotensin-converting enzyme (PCEB-ACE) metabolic activity.
Subsequently, the researchers performed an acute vasodilator challenge on each patient using epoprostenol (Flolan, GlaxoSmithKline Canada), after which PCEB-ACE metabolic activity and hemodynamics were measured again at the peak epoprostenol dose – determined “individually by maximum hemodynamic response or adverse effects.”
Functional CSA was calculated and normalized to body surface area. Values among nonresponders before the vasodilator challenge and at the peak epoprostenol dose were compared using paired t-tests. Of the 14 subjects, 12 were found to be nonresponders to vasodilator challenge and 2 (1 female, 1 male) did respond to vasodilator challenge treatment. In nonresponders overall, mean pulmonary arterial pressure (mPAP) did not change significantly – 59.5 mm Hg to 58.1 mm Hg – but cardiac output increased and PVR decreased. In the two subjects who responded, cardiac output and PVR increased, but mPAP decreased 43.5 mm Hg to 31.5 mm Hg.
“These data show the inability of nonresponders with IPAH to open occluded arterioles and thus recruit more downstream capillaries to accommodate the observed increased lung blood volumes that should accompany vasodilator administration,” the researchers concluded.
Funding for this study was provided by the William and Ida Pencer Family Foundation, the Dimitrios Banousis Foundation, the Bank of Montreal Center for the Study of Heart Disease in Women, and the Jewish General Hospital Annual Walk for Pulmonary Hypertension, all at Jewish General Hospital. The authors disclosed no conflicts of interest.
FROM ANNALS OF INTERNAL MEDICINE
Key clinical point: Differential responses by patients with idiopathic pulmonary arterial hypertension (IPAH) to acute vasodilator challenge suggests that responders and nonresponders represent different vascular phenotypes and different diseases.
Major finding: In nonresponders to vasodilator challenge, mPAP increased and PVR decreased, while those who did respond saw both levels decrease; both cohorts experienced an increase in cardiac output.
Data source: Cohort study of 14 individuals with IPAH.
Disclosures: Funding provided by the William and Ida Pencer Family Foundation, the Dimitrios Banousis Foundation, the Bank of Montreal Center for the Study of Heart Disease in Women, and the Jewish General Hospital Annual Walk for Pulmonary Hypertension, all at Jewish General Hospital. The authors disclosed no conflicts of interest.
