Right heart in pulmonary hypertension: from adaptation to failure

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.

Autologous skeletal myoblast patch implantation prevents the deterioration of myocardial ischemia and right heart dysfunction in a pressure-overloaded right heart porcine model

“…However, the prolonged pressure overload advances the metabolic remodeling of cardiomyocytes, owing to persistent mechanical stress on the myocardium and severe ischemic conditions [8,12,13,19,20]. Eventually, the right heart failure progresses to a decompensated stage with impaired RV function due to the reduction in cardiac reserve [13,[60][61][62]. Considering the results of the 11 C-acetate PET, the angiogenic effect of patch implantation suppresses the metabolic remodeling of cardiomyocytes and maintains the cardiac reserve of the RV, by avoiding chronic ischemic conditions.…”

Resveratrol Prevents Right Ventricle Remodeling and Dysfunction in Monocrotaline-Induced Pulmonary Arterial Hypertension with a Limited Improvement in the Lung Vasculature

“…Currently, approved therapies target three main pathways important in endothelial function: the prostacyclin and nitric oxide pathways, which are underexpressed, and the endothelin pathway, which is overexpressed in PAH patients [3]. PAH triggers a series of events on RV function, including activation of several signaling pathways that regulate cell growth, metabolism, extracellular matrix remodeling, and energy production [4,5]. Right heart failure syndrome emerges in the setting of 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 microRNA expression [4].…”

“…PAH triggers a series of events on RV function, including activation of several signaling pathways that regulate cell growth, metabolism, extracellular matrix remodeling, and energy production [4,5]. Right heart failure syndrome emerges in the setting of 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 microRNA expression [4]. Current therapeutic schemes have not been able to regulate these mechanisms in the long term; therefore, there is a need for more successful strategies to manage right ventricular heart failure in the future [4].…”

Right heart catheterization for pulmonary hypertension during the coronavirus disease 2019 pandemic

“…Expert recommendations from the sixth World Symposium on pulmonary hypertension (PH) characterize PH by a mean pulmonary artery pressure (mPAP) >20 mmHg that can be caused by a variety of conditions and is associated with worse outcomes. 8 Pulmonary arterial hypertension is a form a pre-capillary PH that tends to progress to right heart failure (RHF), 9 with a five-year survival of 61.2-65.4%, despite the availability of many specific therapies. 10 In spite of continuous progress in non-invasive diagnostic modalities, right heart catheterization (RHC) remains the gold standard for diagnosis.…”