scholarly journals Management of Pulmonary Hypertension in Left Heart Disease

2021 ◽  
Vol 17 (2) ◽  
pp. 115-123
Author(s):  
Francesca Macera ◽  
Jean-Luc Vachiéry
Keyword(s):  
Pulmonary Hypertension ◽  
Ejection Fraction ◽  
Current Knowledge ◽  
Heart Diseases ◽  
Endothelin Receptor ◽  
Left Heart ◽  
Reduced Ejection Fraction ◽  
Pulmonary Arterial ◽  
Approved Drugs ◽  
Prevalent Form

Pulmonary hypertension due to left heart diseases (PH-LHD) is the most prevalent form of pulmonary hypertension. It frequently complicates heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF) and negatively impacts prognosis, particularly when a precapillary component is present. PH-LHD is distinctive from pulmonary arterial hypertension (PAH) even though both conditions may share some common characteristics. In addition, the mechanisms involved in the development of a precapillary component are yet to be fully clarified, in particular in PH due to HFpEF. Several studies have been exploring PAH pathways as potential therapies for PH-LHD, but no PAH-approved drug has demonstrated efficacy in PH-LHD. Rather, some classes of drugs, such as endothelin-receptor antagonists or prostacycline-analogues, have been found to be harmful in patients with HF. Therefore, at present, the only established treatments for PH-LHD are those that target the heart as recommended in the international guidelines for HF. Based on current knowledge, off-label prescription of PAH-approved drugs in PH-LHD patients must be strongly discouraged.

scholarly journals Pulmonary vascular mechanical consequences of ischemic heart failure and implications for right ventricular function

2019 ◽  
Vol 316 (5) ◽  
pp. H1167-H1177 ◽  
Author(s):  
Jennifer L. Philip ◽  
Thomas M. Murphy ◽  
David A. Schreier ◽  
Sydney Stevens ◽  
Diana M. Tabima ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Pulmonary Fibrosis ◽  
Ejection Fraction ◽  
Right Ventricle ◽  
Pulmonary Vasculature ◽  
Left Heart ◽  
Left Heart Failure ◽  
Reduced Ejection Fraction ◽  
Pathologic Features

Left heart failure (LHF) is the most common cause of pulmonary hypertension, which confers an increase in morbidity and mortality in this context. Pulmonary vascular resistance has prognostic value in LHF, but otherwise the mechanical consequences of LHF for the pulmonary vasculature and right ventricle (RV) remain unknown. We sought to investigate mechanical mechanisms of pulmonary vascular and RV dysfunction in a rodent model of LHF to address the knowledge gaps in understanding disease pathophysiology. LHF was created using a left anterior descending artery ligation to cause myocardial infarction (MI) in mice. Sham animals underwent thoracotomy alone. Echocardiography demonstrated increased left ventricle (LV) volumes and decreased ejection fraction at 4 wk post-MI that did not normalize by 12 wk post-MI. Elevation of LV diastolic pressure and RV systolic pressure at 12 wk post-MI demonstrated pulmonary hypertension (PH) due to LHF. There was increased pulmonary arterial elastance and pulmonary vascular resistance associated with perivascular fibrosis without other remodeling. There was also RV contractile dysfunction with a 35% decrease in RV end-systolic elastance and 66% decrease in ventricular-vascular coupling. In this model of PH due to LHF with reduced ejection fraction, pulmonary fibrosis contributes to increased RV afterload, and loss of RV contractility contributes to RV dysfunction. These are key pathologic features of human PH secondary to LHF. In the future, novel therapeutic strategies aimed at preventing pulmonary vascular mechanical changes and RV dysfunction in the context of LHF can be tested using this model. NEW & NOTEWORTHY In this study, we investigate the mechanical consequences of left heart failure with reduced ejection fraction for the pulmonary vasculature and right ventricle. Using comprehensive functional analyses of the cardiopulmonary system in vivo and ex vivo, we demonstrate that pulmonary fibrosis contributes to increased RV afterload and loss of RV contractility contributes to RV dysfunction. Thus this model recapitulates key pathologic features of human pulmonary hypertension-left heart failure and offers a robust platform for future investigations.

scholarly journals Pulmonary hypertension due to left heart diseases

ESC CardioMed ◽  
2018 ◽  
pp. 2543-2547
Author(s):  
Jean-Luc Vachiery
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Heart Disease ◽  
Negative Impact ◽  
Heart Diseases ◽  
Exercise Intolerance ◽  
Left Heart ◽  
Common Complication ◽  
Reduced Ejection Fraction ◽  
Left Heart Disease

Pulmonary hypertension is a common complication of left heart diseases. Although it may be encountered in all disorders, pulmonary hypertension in left heart disease is most common in heart failure with preserved or reduced ejection fraction. When present, pulmonary hypertension in left heart disease has been associated with more symptoms, exercise intolerance, and a negative impact on outcome.

scholarly journals Under pressure: pulmonary hypertension associated with left heart disease

2015 ◽  
Vol 24 (138) ◽  
pp. 665-673 ◽  
Author(s):  
Harrison W. Farber ◽  
Simon Gibbs
Keyword(s):  
Pulmonary Hypertension ◽  
Heart Disease ◽  
Survival Rates ◽  
Left Ventricular ◽  
Left Heart ◽  
Mean Pulmonary Arterial Pressure ◽  
Left Heart Disease ◽  
Right Heart Catheterisation ◽  
Pulmonary Capillary ◽  
Pulmonary Arterial

Pulmonary hypertension (PH) associated with left heart disease (PH-LHD) is the most common type of PH, but its natural history is not well understood. PH-LHD is diagnosed by right heart catheterisation with a mean pulmonary arterial pressure ≥25 mmHg and a pulmonary capillary wedge pressure >15 mmHg. The primary causes of PH-LHD are left ventricular dysfunction of systolic and diastolic origin, and valvular disease. Prognosis is poor and survival rates are low. Limited progress has been made towards specific therapies for PH-LHD, and management focuses on addressing the underlying cause of the disease with supportive therapies, surgery and pharmacological treatments. Clinical trials of therapies for pulmonary arterial hypertension in patients with PH-LHD have thus far been limited and have provided disappointing or conflicting results. Robust, long-term clinical studies in appropriate target populations have the potential to improve the outlook for patients with PH-LHD. Herein, we discuss the knowledge gaps in our understanding of PH-LHD, and describe the current unmet needs and challenges that are faced by clinicians when identifying and managing patients with this disease.

scholarly journals Chamber-enriched gene expression profiles in failing human hearts with reduced ejection fraction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xin Luo ◽  
Jun Yin ◽  
Denise Dwyer ◽  
Tracy Yamawaki ◽  
Hong Zhou ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Human Genetics ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Left Heart ◽  
Reduced Ejection Fraction ◽  
Cell Type Composition ◽  
Type Composition ◽  
Underlying Mechanisms

AbstractHeart failure with reduced ejection fraction (HFrEF) constitutes 50% of HF hospitalizations and is characterized by high rates of mortality. To explore the underlying mechanisms of HFrEF etiology and progression, we studied the molecular and cellular differences in four chambers of non-failing (NF, n = 10) and HFrEF (n = 12) human hearts. We identified 333 genes enriched within NF heart subregions and often associated with cardiovascular disease GWAS variants. Expression analysis of HFrEF tissues revealed extensive disease-associated transcriptional and signaling alterations in left atrium (LA) and left ventricle (LV). Common left heart HFrEF pathologies included mitochondrial dysfunction, cardiac hypertrophy and fibrosis. Oxidative stress and cardiac necrosis pathways were prominent within LV, whereas TGF-beta signaling was evident within LA. Cell type composition was estimated by deconvolution and revealed that HFrEF samples had smaller percentage of cardiomyocytes within the left heart, higher representation of fibroblasts within LA and perivascular cells within the left heart relative to NF samples. We identified essential modules associated with HFrEF pathology and linked transcriptome discoveries with human genetics findings. This study contributes to a growing body of knowledge describing chamber-specific transcriptomics and revealed genes and pathways that are associated with heart failure pathophysiology, which may aid in therapeutic target discovery.

scholarly journals Targeting Endothelial Function to Treat Heart Failure with Preserved Ejection Fraction: The Promise of Exercise Training

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Andreas B. Gevaert ◽  
Katrien Lemmens ◽  
Christiaan J. Vrints ◽  
Emeline M. Van Craenenbroeck
Keyword(s):  
Heart Failure ◽  
Endothelial Dysfunction ◽  
Exercise Training ◽  
Ejection Fraction ◽  
Current Knowledge ◽  
Beta Blockers ◽  
Preserved Ejection Fraction ◽  
Cellular Mechanisms ◽  
Converting Enzyme Inhibitors ◽  
Reduced Ejection Fraction

Although the burden of heart failure with preserved ejection fraction (HFpEF) is increasing, there is no therapy available that improves prognosis. Clinical trials using beta blockers and angiotensin converting enzyme inhibitors, cardiac-targeting drugs that reduce mortality in heart failure with reduced ejection fraction (HFrEF), have had disappointing results in HFpEF patients. A new “whole-systems” approach has been proposed for designing future HFpEF therapies, moving focus from the cardiomyocyte to the endothelium. Indeed, dysfunction of endothelial cells throughout the entire cardiovascular system is suggested as a central mechanism in HFpEF pathophysiology. The objective of this review is to provide an overview of current knowledge regarding endothelial dysfunction in HFpEF. We discuss the molecular and cellular mechanisms leading to endothelial dysfunction and the extent, presence, and prognostic importance of clinical endothelial dysfunction in different vascular beds. We also consider implications towards exercise training, a promising therapy targeting system-wide endothelial dysfunction in HFpEF.

Abstract 19944: Targeted Therapy of Pulmonary Hypertension in Patients With Heart Failure and Preserved Ejection Fraction: Safety and Efficacy in Comparison to IPAH in Compera

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Stephan Rosenkranz ◽  
Marius M Hoeper ◽  
Doerte Huscher ◽  
David Pittrow ◽  
Christian F Opitz
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Ejection Fraction ◽  
Preserved Ejection Fraction ◽  
Evidence Based Treatment ◽  
Patients With Heart Failure ◽  
Venous Oxygen Saturation ◽  
Initial Ph ◽  
Pulmonary Arterial

Background: While targeted therapies are available for idiopathic pulmonary arterial hypertension (IPAH), evidence based treatment recommendations for pulmonary hypertension (PH) associated with heart failure and preserved ejection fraction (HFpEF) are lacking. Methods and Results: Out of 5,935 patients in the prospective COMPERA registry, we analyzed patients with “typical” IPAH (n=421, ≤2 of the following risk factors: BMI >30 kg/m2, hypertension, CAD, diabetes and atrial fibrillation at the time of diagnosis), “atypical” IPAH (n=139, >2 risk factors) or PH-HFpEF (n=226) who received targeted PH therapies. Patients with PH-HFpEF, when compared to “typical” and “atypical” IPAH were older (73±8 vs. 62±17 and 71±9 years), had a higher BMI (30 vs. 26 and 32 kg/m2), and more comorbidities (98% vs. 73% and 100%, all p<0.001), respectively. However, mean PAP (46±9 vs. 47±13 and 44±11 mmHg), cardiac index (2.2±0.7 vs. 2,3±0,8 and 2,2±0,8 l/min), and mixed venous oxygen saturation (62±7 vs. 62±10 and 63±9%, all ns) were almost identical. As compared to “typical” and “atypical” IPAH, PH-HFpEF patients had a higher PAWP (20±4 vs. 9±3 and 10±4 mmHg), resulting in a lower calculated PVR (559±270 vs. 861±477 and 784±844 dyn.s.cm-5). Survival at 1, 2 and 3 years post diagnosis was not different between groups. PDE-5 inhibitors were the most common form of initial PH treatment in PH-HFpEF (94%), and combination therapy was less common compared to “typical” or “atypical” IPAH at 1 year (7% vs. 44% and 26%). All 3 groups responded to targeted PH therapies at 12 months, while treatment effects were less pronounced in PH-HFpEF: Compared to baseline, the median increase of the 6MWD at 1 year was 29, 50, and 60 m, respectively. Treatment discontinuations occurred more frequently in patients with PH-HFpEF than in IPAH, either because of side effects or lack of improvement. Conclusions: Despite almost identical alterations of pulmonary artery pressure and cardiac output, patients with PH-HFpEF differed with respect to age, comorbidities and certain hemodynamic features when compared to “typical” or “atypical” IPAH. All groups responded to targeted PH therapy, however tolerability and efficacy of PH drugs were reduced in patients with PH-HFpEF while survival was not different.

Pulmonary hypertension: definition

ESC CardioMed ◽  
2018 ◽  
pp. 2482-2484
Author(s):  
Stephan Rosenkranz
Keyword(s):  
Pulmonary Hypertension ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Left Heart ◽  
Chronic Lung Diseases ◽  
Common Causes ◽  
Thromboembolic Pulmonary Hypertension ◽  
Underlying Causes ◽  
Pulmonary Arterial ◽  
Clinical Phenotyping ◽  
Global Population

Pulmonary hypertension (PH) in general is characterized by an elevation of pulmonary artery pressure which may result from various underlying causes. PH is a common disorder affecting approximately 1% of the global population, and up to 10% of patients older than 65 years of age. The most common causes are diseases of the left heart and chronic lung diseases, whereas disorders primarily originating from the pulmonary vessels including pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension remain relatively rare conditions. PH is primarily defined by haemodynamic variables, and subdivided into pre- and post-capillary PH. Further information obtained from imaging, pathology, genetics, and clinical phenotyping may be required for accurate subclassification of PH.

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