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Education Posts

Group PH-LHD

Article Type: Pathobiology

Elucidating the Clinical Implications and Pathophysiology of Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction: A Call to Action: A Science Advisory From the American Heart Association

This is a comprehensive review of the published clinical studies related to pulmonary hypertension in heart failure with preserved ejection fraction (PH-HFpEF).  It includes clinical and hemodynamic definitions of the disease, epidemiology, pathophysiology, animal models and treatment approaches, and clinical trials. They importantly stress the urgent unmet need to make progress in this disease so as to reduce the high burden of the disease. This is a wonderful source document for finding the latest research and publications.

Citation
Brittain EL, Thenappan T, Huston JH, Agrawal V, Lai YC, Dixon D, Ryan JJ, Lewis EF, Redfield MM, Shah SJ, Maron BA; American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Lifestyle and Cardiometabolic Health; and Stroke Council. Elucidating the Clinical Implications and Pathophysiology of Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction: A Call to Action: A Science Advisory From the American Heart Association. Circulation. 2022 Jul 11:101161CIR0000000000001079
Source: https://pubmed.ncbi.nlm.nih.gov/35862198/

Understanding the Pathobiology of Pulmonary Hypertension Due to Left Heart Disease

This is an in depth authoritative review of the field of pulmonary hypertension due to left heart disease. Written by one of the most renown thought leaders, it covers all facets of basic and clinical science, with insights into potential effective therapies. A must read for anyone who is involved with translational of clinical investigations in this area.

Citation
Huston JH, Shah SJ. Understanding the Pathobiology of Pulmonary Hypertension Due to Left Heart Disease. Circ Res. 2022 Apr 29;130(9):1382-1403.
Source: https://pubmed.ncbi.nlm.nih.gov/35482841/

Targeting ATP-Sensitive K+ Channels to Treat Pulmonary Hypertension

This editorial offers an explanation of the recent science that implicates downregulation of K+ATP channels in various forms of pulmonary hypertension. Given the clinical safety of levosimendan as a K+ATP channel activator, it may hold great promise for many forms of pulmonary hypertension.

Citation
Breen E, Yuan JX. Targeting ATP-Sensitive K+ Channels to Treat Pulmonary Hypertension. Am J Respir Cell Mol Biol. 2022 May;66(5):476-478.
Source: https://pubmed.ncbi.nlm.nih.gov/35238728/

The Neurohormonal Basis of Pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction

This important review highlights the data showing a strong neurohormonal maladaptive basis underlying PH-HFpEF. These data provide a compelling argument for developing novel treatments that target these abnormalities to improve outcomes.

Citation
Obokata M, Kane GC, Reddy YNV, Melenovsky V, Olson TP, Jarolim P, Borlaug BA. The neurohormonal basis of pulmonary hypertension in heart failure with preserved ejection fraction. Eur Heart J. 2019 Dec 1;40(45):3707-3717.
Source: https://pubmed.ncbi.nlm.nih.gov/31513270/

Left Ventricular Dysfunction with Pulmonary Hypertension: Part 1: Epidemiology, Pathophysiology, And Definitions

This is the first part of an extraordinary 2-part review of the complexity of pulmonary hypertension in LV dysfunction. One particularly enlightening focus is on the difference between the reversible elevations in pulmonary pressure vs. irreversible elevations which explain why persistent pulmonary hypertension occurs in many of these patients.

Citation
Georgiopoulou VV, Kalogeropoulos AP, Borlaug BA, Gheorghiade M, Butler J. Left ventricular dysfunction with pulmonary hypertension: Part 1: epidemiology, pathophysiology, and definitions. Circ Heart Fail. 2013 Mar;6(2):344-54.
Source: https://pubmed.ncbi.nlm.nih.gov/23513049/

The Pathophysiology of Heart Failure with Preserved Ejection Fraction

Comprehensive review of the pathophysiology of HFpEF by a worldwide leader in the field. This paper explains why the term diastolic dysfunction does not adequately explain the very complex and diverse pathophysiology that underlies the abnormal compliance of the LV in HFpEF.

Citation
Borlaug BA. The pathophysiology of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2014 Sep;11(9):507-15.
Source: https://pubmed.ncbi.nlm.nih.gov/24958077/

The Role of ATP-sensitive Potassium Channels in Cellular Function and Protection in the Cardiovascular System

This review covers the role of K+ATP channels in cardiovascular disease and links cellular metabolism to clinical disease states. This suggests that the exploitation of K+ATP channel activators may prove useful as a treatment for many facets of cardiovascular disease.

Citation
Tinker A, Aziz Q, Thomas A. The role of ATP-sensitive potassium channels in cellular function and protection in the cardiovascular system. Br J Pharmacol. 2014 Jan;171(1):12-23.
Source: https://pubmed.ncbi.nlm.nih.gov/24102106/

Pulmonary Vascular Disease in the Setting of Heart Failure with Preserved Ejection Fraction

Current in-depth review of the clinical features and treatment approaches. A good reference source.

Citation
Levine AR, Simon MA, Gladwin MT. Pulmonary vascular disease in the setting of heart failure with preserved ejection fraction. Trends Cardiovasc Med. 2019 May;29(4):207-217
Source: https://pubmed.ncbi.nlm.nih.gov/30177249/

Splanchnic Nerve Block Mediated Changes in Stressed Blood Volume in Heart Failure

This important paper reviews 2 studies investigating the effects of splanchnic nerve block (SNB) on hemodynamics in patients with decompensated and ambulatory heart failure. They found that SNB reduced the estimated stressed blood volume in both studies at rest and throughout exercise. This provides strong validation of the role of stressed blood volume in PH-HFpEF.

Citation
Fudim M, Patel MR, Boortz-Marx R, Borlaug BA, DeVore AD, Ganesh A, Green CL, Lopes RD, Mentz RJ, Patel CB, Rogers JG, Felker GM, Hernandez AF, Sunagawa K, Burkhoff D. Splanchnic Nerve Block Mediated Changes in Stressed Blood Volume in Heart Failure. JACC Heart Fail. 2021 Apr;9(4):293-300.
Source: https://pubmed.ncbi.nlm.nih.gov/33714749/

Potassium (K +) Channels in the Pulmonary vasculature: Implications in Pulmonary Hypertension Physiological, Pathophysiological and Pharmacological Regulation

Very high-level review of the role of K+ channels regulating the pulmonary vasculature. They explain how K+ channel conductance plays a fundamental role in pulmonary arterial function by controlling pulmonary vascular tone, regulating the population of PASMC through controlling cell apoptosis, survival, and proliferation, and by regulating the release of endothelial vasodilator factors. Given the demonstrated role of altered K+ channels in the pathophysiology of PH, drugs targeting K+ channels, could be new promising therapeutic agents in PAH.

Citation
Mondéjar-Parreño G, Cogolludo A, Perez-Vizcaino F. Potassium (K+) channels in the pulmonary vasculature: Implications in pulmonary hypertension Physiological, pathophysiological and pharmacological regulation. Pharmacol Ther. 2021 Sep;225:107835.
Source: https://pubmed.ncbi.nlm.nih.gov/33744261/
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