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ESC Heart Failure Feb 2022Right ventricular (RV) dysfunction, pulmonary hypertension, and exercise intolerance have prognostic values, but their interrelation is not fully understood. We...
AIMS
Right ventricular (RV) dysfunction, pulmonary hypertension, and exercise intolerance have prognostic values, but their interrelation is not fully understood. We investigated how RV function alone and its coupling with pulmonary circulation (RV-PA) predict cardio-respiratory fitness in patients with heart failure and reduced ejection fraction (HFrEF).
METHODS AND RESULTS
The Evaluation of Resynchronization Therapy for Heart Failure (EARTH) study included 205 HFrEF patients with narrow (n = 85) and prolonged (n = 120) QRS duration undergoing implantable cardioverter defibrillator implantation. All patients underwent a comprehensive evaluation with exercise tolerance tests and echocardiography. We investigated the correlations at baseline between RV parameters {size, function [tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RV-FAC), and RV myocardial performance index (RV-MPI)], pulmonary artery systolic pressure (PASP), and tricuspid regurgitation}; left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVi), and left atrial volume index (LAVi); and cardiopulmonary exercise test (CPET) [peak VO , minute ventilation/carbon dioxide production (VE/VCO ), 6 min walk distance (6MWD), and submaximal exercise duration (SED)]. We also studied the relationship between RV-PA coupling (TAPSE/PASP ratio) and echocardiographic parameters in patients with both data available. Univariate and multivariate linear regression models were used. Patients enrolled in EARTH (overall population) were mostly male (73.2%), mean age 61.0 ± 9.8 years, New York Heart Association class II-III (87.8%), mean LVEF of 26.6 ± 7.7%, and reduced peak VO (15.1 ± 4.6 mL/kg/min). Of these, 100 had both TAPSE and PASP available (TAPSE/PASP population): they exhibited higher BNP, wider QRS duration, larger LVEDVi, with more having tricuspid regurgitation compared with the 105 patients for whom these values were not available (all P < 0.05). RV-FAC (β = 7.5), LAVi (β = -0.1), and sex (female, β = -1.9) predicted peak VO in the overall population (all P = 0.01). When available, TAPSE/PASP ratio was the only echocardiographic parameter associated with peak VO (β = 6.8; P < 0.01), a threshold ≤0.45 predicting a peak VO ≤ 14 mL/kg/min (0.39 for VO ≤ 12). RV-MPI was the only echocardiographic parameter associated with ventilatory inefficiency (VE/VCO ) and 6MWD (β = 21.9 and β = -69.3, respectively, both P ≤ 0.01) in the overall population. In presence of TAPSE/PASP, it became an important predictor for those two CPET (β = -18.0 and β = 72.4, respectively, both P < 0.01), together with RV-MPI (β = 18.5, P < 0.01) for VE/VCO . Tricuspid regurgitation predicted SED (β = -3.2, P = 0.03).
CONCLUSIONS
Right ventricular function assessed by echocardiography (RV-MPI and RV-FAC) is closely associated with exercise tolerance in patients with HFrEF. When the TAPSE/PASP ratio is available, this marker of RV-PA coupling becomes the stronger echocardiographic predictor of exercise capacity in this population, highlighting its potential role as a screening tool to identify patients with reduced exercise capacity and potentially triage them to formal peak VO and/or evaluation for advanced HF therapies.
Topics: Aged; Exercise Tolerance; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Pulmonary Circulation; Stroke Volume; Ventricular Function, Left; Ventricular Function, Right
PubMed: 34953062
DOI: 10.1002/ehf2.13726 -
Seminars in Cardiothoracic and Vascular... Mar 2020In heart transplantation, pulmonary hypertension and increased pulmonary vascular resistance followed by donor right ventricular dysfunction remain a major cause of... (Comparative Study)
Comparative Study Review
In heart transplantation, pulmonary hypertension and increased pulmonary vascular resistance followed by donor right ventricular dysfunction remain a major cause of perioperative morbidity and mortality. In lung transplantation, primary graft dysfunction remains a major obstacle because it can cause bronchiolitis obliterans and mortality. Pulmonary vasodilators have been used as an adjunct therapy for heart or lung transplantation, mainly to treat pulmonary hypertension, right ventricular failure, and associated refractory hypoxemia. Among pulmonary vasodilators, inhaled nitric oxide is unique in that it is selective in pulmonary circulation and causes fewer systemic complications such as hypotension, flushing, or coagulopathy. Nitric oxide is expected to prevent or attenuate primary graft dysfunction by decreasing ischemia-reperfusion injury in lung transplantation. However, when considering the long-term benefit of these medications, little evidence supports their use in heart or lung transplantation. Current guidelines endorse inhaled vasodilators for managing immediate postoperative right ventricular failure in lung or heart transplantation, but no guidance is offered regarding agent selection, dosing, or administration. This review presents the current evidence of inhaled nitric oxide in lung or heart transplantation as well as comparisons with other pulmonary vasodilators including cost differences in consideration of economic pressures to contain rising pharmacy costs.
Topics: Administration, Inhalation; Cost-Benefit Analysis; Heart Transplantation; Humans; Hypertension, Pulmonary; Lung Transplantation; Nitric Oxide; Primary Graft Dysfunction; Pulmonary Circulation; Vasodilator Agents; Ventricular Dysfunction, Right
PubMed: 31451092
DOI: 10.1177/1089253219870636 -
Seminars in Thoracic and Cardiovascular... 2022Optimal decision-making to determine the type and timing of surgical intervention for various congenital heart disease (CHD) requires adequate understanding and... (Review)
Review
Optimal decision-making to determine the type and timing of surgical intervention for various congenital heart disease (CHD) requires adequate understanding and interpretation of anatomic and physiologic data obtained from various imaging modalities. Cardiac magnetic resonance (CMR) has revolutionized the way we evaluate the anatomy and physiology of CHD. In addition to 2- and 3-dimensional anatomic data and volumetry, phase-contrast CMR allows quantitative measurements of cardiac output, pulmonary blood flow, pulmonary-to-systemic flow ratio, the amount of intracardiac shunt, valve regurgitation, and aortopulmonary collateral flows. This review article describes the utilization of CMR-derived flow data in surgical decision-making in three distinct subgroups: (1) patients with borderline left ventricle (LV) with emphasis on the ascending aortic flow and other physiologic parameters, (2) single ventricle patients who undergo bidirectional cavopulmonary shunt with emphasis on the impact of superior vena cava blood flow on postoperative physiology, and (3) patients with pulmonary atresia and major aortopulmonary collateral arteries with emphasis on the impact of total pulmonary blood flow and systemic-to-pulmonary flow ratio on clinical outcomes.
Topics: Clinical Decision-Making; Fontan Procedure; Heart Defects, Congenital; Humans; Pulmonary Artery; Pulmonary Circulation; Vena Cava, Superior
PubMed: 35835512
DOI: 10.1053/j.pcsu.2022.02.001 -
Respiratory Research Feb 2021Chronic obstructive pulmonary disease (COPD) is one of the most common chronic respiratory diseases with high morbidity and mortality. It has become the fifth most... (Review)
Review
Chronic obstructive pulmonary disease (COPD) is one of the most common chronic respiratory diseases with high morbidity and mortality. It has become the fifth most burdened and the third most deadly disease in the global economy and increases year by year. The prevention and treatment of COPD are urgent. Smoking is the main and most common risk factor for COPD. Cigarette smoke (CS) contains a large number of toxic substances, can cause a series of changes in the trachea, lung tissue, pulmonary blood vessels, and promotes the occurrence and development of COPD. In recent years, the development of epigenetics and molecular biology have provided new guidance for revealing the pathogenesis, diagnosis, and treatment of diseases. The latest research indicates that pulmonary vascular endothelial cell apoptosis initiates and participates in the pathogenesis of COPD. In this review, we summarize the current research on the epigenetic mechanisms and molecular biology of CS-induced pulmonary vascular endothelial cell apoptosis in COPD, providing a new research direction for pathogenesis of COPD and a new target for the diagnosis, treatment, and prevention of COPD.
Topics: Animals; Apoptosis; Cigarette Smoking; DNA Methylation; Endothelium, Vascular; Epigenesis, Genetic; Humans; Pulmonary Circulation; Pulmonary Disease, Chronic Obstructive; Tobacco Smoke Pollution
PubMed: 33546691
DOI: 10.1186/s12931-021-01630-1 -
International Journal of Molecular... Sep 2021Currently, no treatment can completely cure pulmonary hypertension (PH), which can lead to right ventricular failure and, consequently, death. Therefore, searching for... (Review)
Review
Currently, no treatment can completely cure pulmonary hypertension (PH), which can lead to right ventricular failure and, consequently, death. Therefore, searching for new therapies remains important. Increased resistance in pulmonary circulation is mainly caused by the excessive contraction and proliferation of small pulmonary arteries. Cannabinoids, a group of lipophilic compounds that all interact with cannabinoid receptors, exert a pulmonary vasodilatory effect through several different mechanisms, including mechanisms that depend on vascular endothelium and/or receptor-based mechanisms, and may also have anti-proliferative and anti-inflammatory properties. The vasodilatory effect is important in regulating pulmonary resistance, which can improve patients' quality of life. Moreover, experimental studies on the effects of cannabidiol (plant-derived, non-psychoactive cannabinoid) in animal PH models have shown that cannabidiol reduces right ventricular systolic pressure and excessive remodelling and decreases pulmonary vascular hypertrophy and pulmonary vascular resistance. Due to the potentially beneficial effects of cannabinoids on pulmonary circulation and PH, in this work, we review whether cannabinoids can be used as an adjunctive therapy for PH. However, clinical trials are still needed to recommend the use of cannabinoids in the treatment of PH.
Topics: Animals; Anti-Inflammatory Agents; Cannabidiol; Cannabinoids; Cell Proliferation; Disease Models, Animal; Endocannabinoids; Heart Ventricles; Humans; Hypertension, Pulmonary; In Vitro Techniques; Ligands; Lung; Nitric Oxide; Pulmonary Circulation; Receptors, Cannabinoid; Receptors, G-Protein-Coupled; Systole; Vasoconstriction; Vasodilation; Ventricular Dysfunction, Right
PubMed: 34576212
DOI: 10.3390/ijms221810048 -
JACC. Cardiovascular Imaging Aug 2023
Topics: Humans; Pulmonary Circulation; Predictive Value of Tests; Heart; Hypertension, Pulmonary; Pulmonary Artery; Heart Ventricles; Ventricular Function, Right
PubMed: 37115162
DOI: 10.1016/j.jcmg.2023.03.002 -
American Journal of Respiratory and... Jun 2021Data on the molecular mechanisms that regulate platelet-pulmonary endothelial adhesion under conditions of hypoxia are lacking, but may have important therapeutic...
Data on the molecular mechanisms that regulate platelet-pulmonary endothelial adhesion under conditions of hypoxia are lacking, but may have important therapeutic implications. To identify a hypoxia-sensitive, modifiable mediator of platelet-pulmonary artery endothelial cell adhesion and thrombotic remodeling. Network medicine was used to profile protein-protein interactions in hypoxia-treated human pulmonary artery endothelial cells. Data from liquid chromatography-mass spectrometry and microscale thermophoresis informed the development of a novel antibody (Ab) to inhibit platelet-endothelial adhesion, which was tested in cells from patients with chronic thromboembolic pulmonary hypertension (CTEPH) and three animal models . The protein NEDD9 was identified in the hypoxia thrombosome network . Compared with normoxia, hypoxia (0.2% O) for 24 hours increased HIF-1α (hypoxia-inducible factor-1α)-dependent NEDD9 upregulation . Increased NEDD9 was localized to the plasma-membrane surface of cells from control donors and patients with CTEPH. In endarterectomy specimens, NEDD9 colocalized with the platelet surface adhesion molecule P-selectin. Our custom-made anti-NEDD9 Ab targeted the NEDD9-P-selectin interaction and inhibited the adhesion of activated platelets to pulmonary artery endothelial cells from control donors and from patients with CTEPH . Compared with control mice, platelet-pulmonary endothelial aggregates and pulmonary hypertension induced by ADP were decreased in NEDD9 mice or wild-type mice treated with the anti-NEDD9 Ab, which also decreased chronic pulmonary thromboembolic remodeling . The NEDD9-P-selectin protein-protein interaction is a modifiable target with which to inhibit platelet-pulmonary endothelial adhesion and thromboembolic vascular remodeling, with potential therapeutic implications for patients with disorders of increased hypoxia signaling pathways, including CTEPH.
Topics: Adaptor Proteins, Signal Transducing; Animals; Blood Platelets; Cell Adhesion; Cells, Cultured; Endothelial Cells; Female; Humans; Hypoxia; Male; Mice; Middle Aged; Models, Animal; Pulmonary Circulation; Pulmonary Embolism; Signal Transduction
PubMed: 33523764
DOI: 10.1164/rccm.202003-0719OC -
Heart and Vessels Jul 2022There is a unique hyperbolic relationship between pulmonary vascular resistance (Rp) and compliance (Cp); however, the characteristics of this coupling curve in...
There is a unique hyperbolic relationship between pulmonary vascular resistance (Rp) and compliance (Cp); however, the characteristics of this coupling curve in pulmonary blood flow alterations remains unknown in children with congenital heart disease. We aimed to explore the Rp-Cp coupling and resistant-compliance (RC) time among them. We retrospectively reviewed catheterization data and calculated Rp and Cp in 217 subjects with ventricular septal defect. Median age and weight at catheterization were 2.8 (1.7-4.4) months and 4.3 (3.7-5.3) kg, respectively. Pulmonary hemodynamic parameters were as follows: mean pulmonary arterial pressure: 36 (28-43) mmHg; the amount of pulmonary blood flow (Qp): 14.2 (11.6-17.6) L/min/m; Rp: 1.95 (1.38-2.59) Wood unit m; Cp: 2.98 (2.42-3.88) mmHg/mL/m; and RC time: 0.35 (0.30-0.40) s. RC time remained unchanged according to alterations in Qp (P = 0.206); however, the relationship between logarithm transformations of Rp and Cp showed more steeper according to an increase in Qp. The pulmonary circulation depends upon Cp rather than Rp according to the degree of Qp despite the constancy in RC time. We should take both Rp and Cp into consideration when evaluating the pulmonary circulation among children with congenital heart disease.
Topics: Cardiac Catheterization; Child; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Pulmonary Artery; Pulmonary Circulation; Retrospective Studies; Vascular Resistance
PubMed: 35001144
DOI: 10.1007/s00380-021-02009-4 -
Current Opinion in Pulmonary Medicine Sep 2022Left heart disease is the most common cause of pulmonary hypertension. This review summarizes the current care of patients with pulmonary hypertension caused by left... (Review)
Review
PURPOSE OF REVIEW
Left heart disease is the most common cause of pulmonary hypertension. This review summarizes the current care of patients with pulmonary hypertension caused by left heart disease (PH-LHD) and discusses recent and active clinical trials in this patient population.
RECENT FINDINGS
The primary focus of interventions aimed at treating PH-LHD address the treatment of left heart disease. Significant advancements in the treatment of heart failure with preserved ejection fraction (HFpEF), a frequent cause of PH-LHD, are supported in the current literature. Patients with residual pulmonary hypertension despite optimal treatment of left heart disease have poor outcomes. Yet, interventions targeting the pulmonary vasculature in PH-LHD patients have not demonstrated significant benefits in studies to date. Current work focuses on differentiating isolated postcapillary pulmonary hypertension (IpcPH) from combined precapillary and postcapillary pulmonary hypertension (CpcPH) in a clinically consistent manner. It is hopeful that thorough phenotyping of PH-LHD patients will translate into effective treatment strategies addressing pulmonary vascular disease.
SUMMARY
Referral to centers of excellence, considerations for enrollment in clinical trials, and evaluation for transplant is recommended for patients with residual pulmonary hypertension despite optimal treatment of left heart disease, particularly those with CpcPH.
Topics: Heart Diseases; Heart Failure; Humans; Hypertension, Pulmonary; Pulmonary Circulation; Stroke Volume
PubMed: 35838362
DOI: 10.1097/MCP.0000000000000891 -
International Journal of Cardiology Jan 2024Right ventricular-pulmonary artery (RV-PA) coupling indicates efficiency of energy transfer from the right ventricle to the pulmonary circulation. The gold standard... (Review)
Review
Right ventricular-pulmonary artery (RV-PA) coupling indicates efficiency of energy transfer from the right ventricle to the pulmonary circulation. The gold standard measurement, end-systolic elastance/arterial elastance ratio (Ees/Ea), is derived from invasive pressure-volume loop, which is technically demanding, expensive and limited in clinical practice. Recent studies have proposed various non-invasive surrogates of Ees/Ea based on echocardiography assessment, of which TAPSE/PASP ratio is an easily-obtained and validated parameter in severe pulmonary hypertension and rapidly applicated in the diagnosis and risk evaluation of various diseases and cardiac intervention. In this review, we summarized principles and validations of echocardiographic surrogates, and their clinical utilities and also limitations. The goal is to systematically review the research advances of echocardiography assessment of RV-PA coupling and help to guide clinical practice.
Topics: Humans; Pulmonary Artery; Heart Ventricles; Echocardiography; Hypertension, Pulmonary; Pulmonary Circulation; Ventricular Dysfunction, Right; Ventricular Function, Right; Stroke Volume
PubMed: 37704177
DOI: 10.1016/j.ijcard.2023.131358