The right kind of rarefaction: Coronary microvascular remodeling in right ventricle failure

JHLT Open Pub Date : 2026-02-01 Epub Date: 2025-12-02 DOI:10.1016/j.jhlto.2025.100459

Cyrus Vahdatpour MD, MS , Katharine Clapham MD , Steven M. Kawut MD, MS , Kirk Jones Jr DO , John J. Ryan MD , Danielle Petty MD , Shannon Talbot MD , Kimberly Dumoff MD , Ellen C. Keeley MD, MS , Priti Lal MD , Andrew J. Bryant MD , Alex M. Parker MD , Jeremy A. Mazurek MD , Leonid Mirson MD , Andrew Murphy MD , Andrew Baird MD , Megan Schwietert MD , Alissa Schurr DO , Andrew Stein MD, PHD , Scott M. Hansen , Dylan Miller MD

{"title":"The right kind of rarefaction: Coronary microvascular remodeling in right ventricle failure","authors":"Cyrus Vahdatpour MD, MS , Katharine Clapham MD , Steven M. Kawut MD, MS , Kirk Jones Jr DO , John J. Ryan MD , Danielle Petty MD , Shannon Talbot MD , Kimberly Dumoff MD , Ellen C. Keeley MD, MS , Priti Lal MD , Andrew J. Bryant MD , Alex M. Parker MD , Jeremy A. Mazurek MD , Leonid Mirson MD , Andrew Murphy MD , Andrew Baird MD , Megan Schwietert MD , Alissa Schurr DO , Andrew Stein MD, PHD , Scott M. Hansen , Dylan Miller MD","doi":"10.1016/j.jhlto.2025.100459","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Right ventricular failure (RVF) is the primary determinant of outcomes in pulmonary hypertension (PH). Coronary microvascular dysfunction (CMD), defined by capillary rarefaction and endothelial dysfunction, may contribute to RVF but remains poorly characterized. CMD, defined by capillary rarefaction and endothelial dysfunction, may contribute to RVF through impaired myocardial oxygen delivery and fibrotic remodeling.</div></div><div><h3>Objectives</h3><div>To characterize right ventricle (RV) CMD and myocardial fibrosis in explanted human hearts and examine associations with echocardiographic and hemodynamic indices of RVF across PH subtypes.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 57 adult patients who underwent orthotopic heart transplantation at 3 institutions (2023-2024). Explanted hearts were classified by PH subtype: combined pre-/post-capillary PH (CpcPH, <em>n</em> = 24), isolated post-capillary PH (IpcPH, <em>n</em> = 22), and no PH (<em>n</em> = 11). Digital pathology quantified RV and left ventricle (LV) capillary density and interstitial fibrosis across epicardial, mid-wall, and endocardial regions. Associations with echocardiographic measures and hemodynamic parameters were assessed.</div></div><div><h3>Results</h3><div>A total of 57 hearts (70% male, median age 52 years) were analyzed. Median time from listing to transplantation was 1.6 months (IQR: 0.7-6.1). Mean RV capillary density was 653 ± 204 microvessels/mm<sup>2</sup> and correlated significantly with TAPSE (ρ<sub>s</sub> = 0.49, <em>p</em> < 0.001) and tricuspid annular plane systolic excursion to systolic pulmonary artery pressure (TAPSE/sPAP) ratio (ρ<sub>s</sub> = 0.33, <em>p</em> = 0.037). Compared to patients without PH, patterns of reduced mid-wall capillary density in PH subtypes were observed (CpcPH: β = −228 microvessels/mm<sup>2</sup>, <em>p</em> = 0.031; IpcPH: β = −238 microvessels/mm<sup>2</sup>, <em>p</em> = 0.043). Diabetes mellitus was associated with reduced LV sub-endocardial capillary density (β = −207, <em>p</em> = 0.006). Unadjusted analysis showed higher RV fibrosis in patients without PH (<em>p</em> = 0.024); however, after adjusting for clinical confounders, including heart failure etiology, this difference was not significant, highlighting the heterogenous nature of fibrosis in end-stage heart failure.</div></div><div><h3>Conclusions</h3><div>Capillary rarefaction is a measurable histopathologic feature in explanted RV tissue that correlates with functional indices of RV performance. Our proof-of-concept findings suggest CMD may contribute to RV systolic dysfunction independent of PH subtype.</div></div>","PeriodicalId":100741,"journal":{"name":"JHLT Open","volume":"11 ","pages":"Article 100459"},"PeriodicalIF":0.0000,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JHLT Open","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2950133425002587","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/12/2 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Right ventricular failure (RVF) is the primary determinant of outcomes in pulmonary hypertension (PH). Coronary microvascular dysfunction (CMD), defined by capillary rarefaction and endothelial dysfunction, may contribute to RVF but remains poorly characterized. CMD, defined by capillary rarefaction and endothelial dysfunction, may contribute to RVF through impaired myocardial oxygen delivery and fibrotic remodeling.

Objectives

To characterize right ventricle (RV) CMD and myocardial fibrosis in explanted human hearts and examine associations with echocardiographic and hemodynamic indices of RVF across PH subtypes.

Methods

We retrospectively analyzed 57 adult patients who underwent orthotopic heart transplantation at 3 institutions (2023-2024). Explanted hearts were classified by PH subtype: combined pre-/post-capillary PH (CpcPH, n = 24), isolated post-capillary PH (IpcPH, n = 22), and no PH (n = 11). Digital pathology quantified RV and left ventricle (LV) capillary density and interstitial fibrosis across epicardial, mid-wall, and endocardial regions. Associations with echocardiographic measures and hemodynamic parameters were assessed.

Results

A total of 57 hearts (70% male, median age 52 years) were analyzed. Median time from listing to transplantation was 1.6 months (IQR: 0.7-6.1). Mean RV capillary density was 653 ± 204 microvessels/mm² and correlated significantly with TAPSE (ρ_s = 0.49, p < 0.001) and tricuspid annular plane systolic excursion to systolic pulmonary artery pressure (TAPSE/sPAP) ratio (ρ_s = 0.33, p = 0.037). Compared to patients without PH, patterns of reduced mid-wall capillary density in PH subtypes were observed (CpcPH: β = −228 microvessels/mm², p = 0.031; IpcPH: β = −238 microvessels/mm², p = 0.043). Diabetes mellitus was associated with reduced LV sub-endocardial capillary density (β = −207, p = 0.006). Unadjusted analysis showed higher RV fibrosis in patients without PH (p = 0.024); however, after adjusting for clinical confounders, including heart failure etiology, this difference was not significant, highlighting the heterogenous nature of fibrosis in end-stage heart failure.

Conclusions

Capillary rarefaction is a measurable histopathologic feature in explanted RV tissue that correlates with functional indices of RV performance. Our proof-of-concept findings suggest CMD may contribute to RV systolic dysfunction independent of PH subtype.

查看原文本刊更多论文

正确的稀疏类型：右心室衰竭时冠状动脉微血管重构

背景：右心室衰竭（RVF）是肺动脉高压（PH）预后的主要决定因素。冠状动脉微血管功能障碍（CMD），由毛细血管稀疏和内皮功能障碍定义，可能导致裂谷热，但仍缺乏明确的特征。由毛细血管稀疏和内皮功能障碍定义的CMD可能通过心肌氧输送受损和纤维化重塑导致裂谷热。目的探讨人离体心脏右心室CMD与心肌纤维化的关系，探讨不同PH亚型RVF与超声心动图和血流动力学指标的关系。方法回顾性分析2023-2024年在3家医院接受原位心脏移植的57例成人患者。将离体心脏按PH亚型分为：合并毛细前/毛细后PH （CpcPH, n = 24）、分离毛细后PH （IpcPH, n = 22）和无PH （n = 11）。数字病理学量化右心室和左心室（LV）毛细血管密度和间质纤维化跨越心外膜、中壁和心内膜区域。评估超声心动图测量和血流动力学参数的相关性。结果共分析57例心脏，其中男性占70%，中位年龄52岁。从上市到移植的中位时间为1.6个月（IQR: 0.7-6.1）。右心室平均毛细血管密度为653±204微血管/mm2，与三尖瓣环面收缩偏移与肺动脉收缩压之比（ρs = 0.49, p < 0.001）、三尖瓣环面收缩偏移与肺动脉收缩压之比（ρs = 0.33, p = 0.037）显著相关。与非PH患者相比，PH亚型中壁毛细血管密度降低（CpcPH: β = - 228微血管/mm2， p = 0.031; IpcPH: β = - 238微血管/mm2， p = 0.043）。糖尿病与左室心内膜下毛细血管密度降低相关（β = - 207, p = 0.006）。未经校正分析显示，没有PH的患者右心室纤维化较高（p = 0.024）；然而，在调整了包括心力衰竭病因在内的临床混杂因素后，这种差异并不显著，这突出了终末期心力衰竭中纤维化的异质性。结论左心室组织的毛细血管稀疏是一个可测量的组织病理学特征，与右心室功能指标相关。我们的概念验证结果表明，CMD可能导致心室收缩功能障碍，与PH亚型无关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

JHLT Open

自引率

0.00%

发文量