New research widens continuum of risk associated with PVR in pulmonary hypertension - Healio

New research widens continuum of risk associated with PVR in pulmonary hypertension - Healio
Pulmonary-arterial-hypertension (PAH)-on-a-chip: fabrication, validation and application - DocWire News
CTEPH Severity Assessed by Dual Energy CT Parameters and Hemodynamics - Pulmonology Advisor

Posted: 05 Aug 2020 08:30 AM PDT

August 05, 2020

3 min read

Disclosures: Maron reports he receives personal fees from Actelion and is co-inventor of patents related to pulmonary hypertension. Please see the study for all other authors' relevant financial disclosures.

New data expand the range of pulmonary vascular resistance associated with mortality and heart failure in patients at risk for pulmonary hypertension undergoing right heart catheterization.

"Data from this study show that risk for adverse outcome associated with [pulmonary vascular resistance] in pulmonary hypertension emerges at around 2.2 Wood units, which is well below the [pulmonary vascular resistance] associated with the disease state in clinical practice. We identified patients with precapillary pulmonary hypertension at the time of right heart catheterization as particularly vulnerable," Bradley A. Maron, MD, cardiovascular medicine specialist at Brigham and Women's Hospital and assistant professor of Medicine at Harvard University, and colleagues wrote in The Lancet Respiratory Medicine.

Researchers conducted a retrospective cohort study of 40,082 patients (median age, 66.5 years; 96.7% male) undergoing right heart catheterization in the U.S. Veterans Affairs healthcare system from October 2007 through September 2016. Patients were included if they had complete right heart catheterization and were followed for at least 1 year. Fifty-eight percent of patients had a history of heart failure and 33.3% had a history of COPD. Eighty-one percent of patients were at risk for pulmonary hypertension based on an elevated mean pulmonary artery pressure (mPAP) of at least 19 mm Hg.

The primary outcome was time to all-cause mortality assessed by the Veteran Affairs vital status file. Results showed that the all-cause mortality hazard for pulmonary vascular resistance (PVR) was increased at 2.2 Wood units compared PVR of 1.0 Wood unit, when modeled as a continuous variable.

When the researchers compared PVR of 2.2 Wood units or more vs. less than 2.2 Wood units in patients with mPAP of at least 19 mm Hg and pulmonary artery wedge pressure of 15 mm Hg or less, the adjusted HR for mortality was 1.71 (95% CI, 1.59-1.84; P < .0001) and adjusted HR for heart failure hospitalization was 1.27 (95% CI, 1.13-1.43; P = .0001), according to the results.

Maron and colleagues also analyzed the relationship between PVR and clinical outcomes in a validation cohort of 3,699 patients (median age, 60.4 years; 50.3% male) that included 77.6% of patients with mPAP of at least 19 mm Hg. In this cohort, the researchers reported the adjusted HR for mortality was 1.81 (95% CI, 1.33-2.47; P = .0002) for the patients with mPAP of at least 19 mm Hg, PVR of 2.2 Wood units or more and pulmonary artery wedge pressure of 15 mm Hg or less.

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This study provides the first evidence-based determination of the appropriate vascular resistance levels used clinically to guide risk assessment in patients with pulmonary hypertension, Maron told Healio.

"These data clarify and widen the range of data from clinical tests that are used to identify and assess risk for patients with pulmonary hypertension. Findings from this study provide much-needed evidence to inform clinicians at point-of-care on who is at risk for major adverse events, including heart failure hospitalization and death," Maron told Healio. "This, in turn, provides an opportunity to capture a novel and substantial subpopulation of vulnerable patients that heretofore was considered normal."

Further, Maron noted that "adherence to risk factor modification and standard-of-care lung and cardiac therapy will become increasingly important in the patients identified in this study. Most importantly, these data provide a roadmap for identifying pulmonary hypertension early."

The researchers noted several limitations of the study, including a primarily male cohort, cohorts from a single country and exclusion of patients with incomplete records.

Maron and colleagues noted that further analyses are warranted.

"Additional research is needed that validates our findings in other pulmonary hypertension populations that are followed prospectively, and studies the effect of treatment on outcome in patients with pulmonary hypertension using the pulmonary artery pressure and pulmonary vascular levels used in our work," Maron told Healio.

For more information:

Bradley A. Maron, MD, can be reached at bmaron@bwh.harvard.edu.

Pulmonary-arterial-hypertension (PAH)-on-a-chip: fabrication, validation and application - DocWire News

Posted: 04 Aug 2020 11:00 PM PDT

This article was originally published here

Lab Chip. 2020 Aug 4. doi: 10.1039/d0lc00605j. Online ahead of print.

ABSTRACT

Currently used animal and cellular models for pulmonary arterial hypertension (PAH) only partially recapitulate its pathophysiology in humans and are thus inadequate in reproducing the hallmarks of the disease, inconsistent in portraying the sex-disparity, and unyielding to combinatorial study designs. Here we sought to deploy the ingenuity of microengineering in developing and validating a tissue chip model for human PAH. We designed and fabricated a microfluidic device to emulate the luminal, intimal, medial, adventitial, and perivascular layers of a pulmonary artery. By growing three types of pulmonary arterial cells (PACs)-endothelial, smooth muscle, and adventitial cells, we recreated the PAH pathophysiology on the device. Diseased (PAH) PACs, when grown on the chips, moved of out their designated layers and created phenomena similar to the major pathologies of human PAH: intimal thickening, muscularization, and arterial remodeling and show an endothelial to mesenchymal transition. Flow-induced stress caused control cells, grown on the chips, to undergo morphological changes and elicit arterial remodeling. Our data also suggest that the newly developed chips can be used to elucidate the sex disparity in PAH and to study the therapeutic efficacy of existing and investigational anti-PAH drugs. We believe this miniaturized device can be deployed for testing various prevailing and new hypotheses regarding the pathobiology and drug therapy in human PAH.

PMID:32749432 | DOI:10.1039/d0lc00605j

CTEPH Severity Assessed by Dual Energy CT Parameters and Hemodynamics - Pulmonology Advisor

Posted: 30 Jul 2020 08:30 AM PDT

In patients with chronic thromboembolic pulmonary hypertension (CTEPH), lung perfused blood volume (PBV) and mean pulmonary artery (PA) enhancement could be indicators of hemodynamics, according the results of a retrospective analysis published in the Journal of Computer Assisted Tomography.

Investigators sought to evaluate the link between dual-energy computed tomography (CT) quantitative parameters and hemodynamics in patients with CTEPH. Between April 2014 and July 2017, a total of 58 consecutive patients who had undergone dual-energy CT for a detailed examination or follow-up of their CTEPH received treatment at Nagoya University Hospital in Japan. A CTEPH diagnosis was confirmed with the use of ventilation/perfusion scintigraphy, right heart catheterization (RHC), and pulmonary arteriography.

Of the 58 consecutive patients, 6 were excluded from the study for a variety of reasons, leaving a total of 52 remaining patients to be assessed retrospectively. Of these 52 patients, 20 were men and 32 were women. The median participant age was 65.5 years. Dual-energy CT and RHC were performed within 6 months of each other. The participants' lung PBV and mean PA enhancement, which were measured at the pulmonary parenchymal phase, were compared with hemodynamics.

Correlations were demonstrated between dual-energy CT parameters and body weight with RHC hemodynamics. Mean lung PBV was significantly correlated with mean pulmonary arterial pressure (mPAP; Spearman rank correlation coefficient [r_s]=0.47; 95% CI, 0.23-0.66; P <.001), systolic ventricular pressure (r_s=0.44; 95% CI, 0.19-0.63; P =.001), right arterial pressure (r_s=0.32; 95% CI, 0.05-0.54; P =.022), and pulmonary vascular resistance (r_s=0.31; 95% CI, 0.04-0.53; P =.027)

In addition, whole lung PBV was significantly correlated with mPAP (P =.010); however the correlation coefficient was lower than that for lung PBV calculated when excluding the upper right zone. Furthermore, PA enhancement was significantly associated with cardiac index (P <.001) and with pulmonary vascular resistance (P <.001). The area under the curve (AUC) was 0.86 for lung PBV to predict mPAP >50 mm Hg. The AUC was also 0.86 for PA enhancement to predict pulmonary vascular resistance >1000 dyne·s/cm⁵.

The investigators concluded that the study findings showed the ability of the quantitative values of lung PBV and PA enhancement to identify patients with severe CTEPH. Thus, lung PBV and PA enhancement could be used as indicators of hemodynamics, with noninvasive quantitative dual-energy CT parameters helping to guide the management of patients with CTEPH.

Reference

Tsutsumi Y, Iwano S, Okumura N, et al. Assessment of severity in chronic thromboembolic pulmonary hypertension by quantitative parameters of dual-energy computed tomography. J Comput Assist Tomogr. 2020;44(4):578-585.

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