Right heart in pulmonary hypertension: from adaptation to failure

Research output: Contribution to journalReview article

Abstract

Right ventricular (RV) failure (RVF) has garnered significant attention in recent years because of its negative impact on clinical outcomes in patients with pulmonary hypertension (PH). PH triggers a series of events, including activation of several signaling pathways that regulate cell growth, metabolism, extracellular matrix remodeling, and energy production. These processes render the RV adaptive to PH. However, RVF develops when PH persists, accompanied by RV ischemia, alterations in substrate and mitochondrial energy metabolism, increased free oxygen radicals, increased cell loss, downregulation of adrenergic receptors, increased inflammation and fibrosis, and pathologic microRNAs. Diastolic dysfunction is also an integral part of RVF. Emerging non-invasive technologies such as molecular or metallic imaging, cardiac MRI, and ultrafast Doppler coronary flow mapping will be valuable tools to monitor RVF, especially the transition to RVF. Most PH therapies cannot treat RVF once it has occurred. A variety of therapies are available to treat acute and chronic RVF, but they are mainly supportive, and no effective therapy directly targets the failing RV. Therapies that target cell growth, cellular metabolism, oxidative stress, and myocyte regeneration are being tested preclinically. Future research should include establishing novel RVF models based on existing models, increasing use of human samples, creating human stem cell-based in vitro models, and characterizing alterations in cardiac excitation–contraction coupling during transition from adaptive RV to RVF. More successful strategies to manage RVF will likely be developed as we learn more about the transition from adaptive remodeling to maladaptive RVF in the future.

Original languageEnglish (US)
JournalPulmonary Circulation
Volume9
Issue number3
DOIs
StatePublished - Jul 1 2019

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Pulmonary Hypertension
Growth
Cell- and Tissue-Based Therapy
MicroRNAs
Adrenergic Receptors
Muscle Cells
Energy Metabolism
Free Radicals
Extracellular Matrix
Regeneration
Reactive Oxygen Species
Oxidative Stress
Fibrosis
Stem Cells
Therapeutics
Down-Regulation
Ischemia
Inflammation
Technology

Keywords

  • cardiac hypertrophy
  • pulmonary hypertension
  • right ventricular failure

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Right heart in pulmonary hypertension : from adaptation to failure. / Ren, Xianfeng; Johns, Roger A.; Gao, Wei Dong.

In: Pulmonary Circulation, Vol. 9, No. 3, 01.07.2019.

Research output: Contribution to journalReview article

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N2 - Right ventricular (RV) failure (RVF) has garnered significant attention in recent years because of its negative impact on clinical outcomes in patients with pulmonary hypertension (PH). PH triggers a series of events, including activation of several signaling pathways that regulate cell growth, metabolism, extracellular matrix remodeling, and energy production. These processes render the RV adaptive to PH. However, RVF develops when PH persists, accompanied by RV ischemia, alterations in substrate and mitochondrial energy metabolism, increased free oxygen radicals, increased cell loss, downregulation of adrenergic receptors, increased inflammation and fibrosis, and pathologic microRNAs. Diastolic dysfunction is also an integral part of RVF. Emerging non-invasive technologies such as molecular or metallic imaging, cardiac MRI, and ultrafast Doppler coronary flow mapping will be valuable tools to monitor RVF, especially the transition to RVF. Most PH therapies cannot treat RVF once it has occurred. A variety of therapies are available to treat acute and chronic RVF, but they are mainly supportive, and no effective therapy directly targets the failing RV. Therapies that target cell growth, cellular metabolism, oxidative stress, and myocyte regeneration are being tested preclinically. Future research should include establishing novel RVF models based on existing models, increasing use of human samples, creating human stem cell-based in vitro models, and characterizing alterations in cardiac excitation–contraction coupling during transition from adaptive RV to RVF. More successful strategies to manage RVF will likely be developed as we learn more about the transition from adaptive remodeling to maladaptive RVF in the future.

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