Pulmonary Hypertension, Right Ventricular Failure, and Kidney: Different from Left Ventricular Failure?

End-stage left ventricular failure or chronic heart failure (CHF) causes severe lung inflammation, vascular remodeling, WHO type-2 pulmonary hypertension, and right ventricular hypertrophy. However, the molecular mechanism of CHF-induced lung inflammation and remodeling is largely unknown. CD44 is a member of the hyaluronate receptor family of cell adhesion molecules, which has been shown to play a selective role in controlling macrophage and lymphocyte migration. Here we demonstrated that end-stage CHF causes a dramatic increase of CD44 expression in heart and lung in human and mice. Histological staining shows that CD44 is predominantly expressed in leukocytes such as macrophages. Flow cytometry analysis further demonstrates that CD44 is predominantly expressed in F4/80 positive macrophages, CD4+, and CD8+ T cells. CD44 expression is dramatically increased in activated T cell subsets. To further determine the physiological role of CD44 in CHF-induced lung remodeling and type-2 pulmonary hypertension, we studied the effect of CD44 blockade on type-2 pulmonary hypertension development in a group of mice with existing moderate left ventricular failure without apparent lung remodeling. Interestingly, we found that blockade CD44 with blocking antibodies (Abs) significantly attenuate the development of lung vascular and interstitial leukocyte infiltration, lung vascular remodeling, fibrosis, and increase of right ventricular hypertrophy. Blockade CD44 signaling also significantly attenuated further decline of left ventricular ejection fraction in mice with existing LV failure. In addition, we demonstrated that induction of T regulatory cells with IL-2 and IL-2 Abs complex significantly attenuated the infiltration of CD44 positive leukocytes in lung tissue, lung vascular remodeling, lung fibrosis, and right ventricular hypertrophy in mice with existing moderate left ventricular failure. Together, these data indicate an important role of CD44 in left ventricular failure-induced lung inflammation, and type-2 pulmonary hypertension, suggesting that inhibition of CD44 may attenuate heart failure progression and type-2 pulmonary hypertension.

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Left atrio‐ventricular valve degeneration, left ventricular dilation and right ventricular failure: A possible association with pulmonary hypertension and aetiology of ascites in broiler chickens

Avian Pathology ◽

10.1080/03079459808419274 ◽

1998 ◽

Vol 27 (1) ◽

pp. 51-59 ◽

Cited By ~ 26

Author(s):

A. A. Olkowski ◽

H. L. Classen ◽

L. Kumor

Keyword(s):

Pulmonary Hypertension ◽

Right Ventricular ◽

Broiler Chickens ◽

Left Ventricular ◽

Right Ventricular Failure ◽

Ventricular Failure ◽

Ventricular Dilation ◽

Left Ventricular Dilation

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Pulmonary Hypertension Related to Left-Sided Cardiac Pathology

Pulmonary Medicine ◽

10.1155/2011/381787 ◽

2011 ◽

Vol 2011 ◽

pp. 1-11 ◽

Cited By ~ 25

Author(s):

Todd L. Kiefer ◽

Thomas M. Bashore

Keyword(s):

Pulmonary Hypertension ◽

Right Ventricular ◽

Pressure Overload ◽

Therapeutic Strategies ◽

Left Ventricular ◽

Right Ventricular Failure ◽

Valve Disease ◽

Ventricular Failure ◽

Cardiac Pathology ◽

Pathologic Processes

Pulmonary hypertension (PH) is the end result of a variety of diverse pathologic processes. The chronic elevation in pulmonary artery pressure often leads to right ventricular pressure overload and subsequent right ventricular failure. In patients with left-sided cardiac disease, PH is quite common and associated with increased morbidity and mortality. This article will review the literature as it pertains to the epidemiology, pathogenesis, and diagnosis of PH related to aortic valve disease, mitral valve disease, left ventricular systolic and diastolic dysfunction, and pulmonary veno-occlusive disease. Moreover, therapeutic strategies, which focus on treating the underlying cardiac pathology will be discussed.

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Pulmonary hypertension and right ventricular failure in left ventricular systolic dysfunction

Current Opinion in Cardiology ◽

10.1097/hco.0b013e3283522098 ◽

2012 ◽

pp. 1 ◽

Cited By ~ 2

Author(s):

Thomas G. Di Salvo

Keyword(s):

Pulmonary Hypertension ◽

Right Ventricular ◽

Left Ventricular Systolic Dysfunction ◽

Systolic Dysfunction ◽

Left Ventricular ◽

Right Ventricular Failure ◽

Ventricular Systolic Dysfunction ◽

Ventricular Failure

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Pulmonary hypertension with or without right ventricular failure as short-term prognostic predictors in patients with AHF

European Heart Journal Acute Cardiovascular Care ◽

10.1093/ehjacc/zuab020.037 ◽

2021 ◽

Vol 10 (Supplement_1) ◽

Author(s):

M Quintana Da Silva ◽

JE Gimenez ◽

J Martinez ◽

J Ojeda ◽

D Gomes

Keyword(s):

Pulmonary Hypertension ◽

Logistic Regression ◽

Multivariate Analysis ◽

Right Ventricular ◽

Left Ventricular ◽

Right Ventricular Failure ◽

Left Ventricular Ejection ◽

Ventricular Failure ◽

Ventricular Ejection Fraction ◽

Prognostic Predictors

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Different registries have reported Right Ventricular Failure (RVF) as a predictor of IH mortality in patients with AHF. However, the association of different degrees of Pulmonary Hypertension (PH) associated with or without RVF as prognostic predictors of IH mortality and Rehospitalization (RH) at 60 days is not well stablished. Methods We included 394 consecutive patients from January 2012 to August 2020 with the primary diagnosis of AHF and different degrees of PH with or without RVF. IH mortality and RH after 60 days of patients with AHF and the presence of RVF with or without PH were evaluated and stratified by severity into mild, moderate and severe PH and forms of presentation of AHF. Univariate, bivariate and multivariate analysis was performed by logistic regression of the independent variables. The qualitative variables were analyzed by the chi square test and the quantitative variables by T Test. P was considered significant at values <0.05. Results The mean age was 74 years, 40% female, HBP 49%, dyslipidemia 52%, obesity 52%, type 2 DM 42%, smoking 28% and COPD 26%. 16% were de novo AHF and 84% with exacerbated CHF. Global RVF 6%. PH was present in 60%, being 24% mild, 25% moderate, 10% severe. The Left ventricular Ejection fraction (LVEF) mean was 52% (SD ± 15.1); Preserved 60%, Intermediate Range 18% and Reduced 22%. The IH mortality was 6.6% and the RH rate at 60 days was 21%. In the bivariate analysis for IH mortality, RVF was identified as an independent predictor of mortality (p = 0.001) nor for RH (p = 0.857). The different levels of PH were not identified as predictors of IH Mortality as well as RH. LVEF ranges did not show significant differences, nor in the forms of AHF presentation. The combined analysis of RVF or Left with different degrees of PHT did not show significant differences in IH mortality and RH.In the multivariate analysis by logistic regression for IH mortality, the presence of RVF maintained independence as a predictor variable (p = 0.004). Conclusion In our population of patients with AHF, the presence of RVF is a predictor of IH mortality regardless of the presence of PH, the PH and LVEF ranges. The presence of RVF was not associated with a higher rate of RH at 60 days.

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