Novel Therapeutic Approaches to Preserve the Right Ventricle

Farha, Samar; Lundgrin, Erika L.; Erzurum, Serpil C.

doi:10.1007/s11897-012-0119-3

Cited by 16 publications

(13 citation statements)

References 49 publications

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“…The myocardial wall of the normally unstressed RV thickens in order to maintain cardiac output. This remodelling pattern eventually leads to an increased mismatch between myocardial blood supply and oxygen demand, resulting in myocardial ischaemia and downstream effects such as collagen formation and fibrosis . Oxidative stress triggers the production of reactive oxygen species, limits the availability of nitric oxide (NO) and significantly contributes to cell necrosis and apoptosis through release of inflammatory cytokines, such as tumour necrosis factor‐α, interleukin‐1, and interleukin‐6.…”

Section: Pathophysiologymentioning

confidence: 99%

Right heart dysfunction and failure in heart failure with preserved ejection fraction: mechanisms and management. Position statement on behalf of the Heart Failure Association of the European Society of Cardiology

Gorter

Veldhuisen

Bauersachs

et al. 2017

European J of Heart Fail

244

223

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There is an unmet need for effective treatment strategies to reduce morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Until recently, attention in patients with HFpEF was almost exclusively focused on the left side. However, it is now increasingly recognized that right heart dysfunction is common and contributes importantly to poor prognosis in HFpEF. More insights into the development of right heart dysfunction in HFpEF may aid to our knowledge about this complex disease and may eventually lead to better treatments to improve outcomes in these patients. In this position paper from the Heart Failure Association of the European Society of Cardiology, the Committee on Heart Failure with Preserved Ejection Fraction reviews the prevalence, diagnosis, and pathophysiology of right heart dysfunction and failure in patients with HFpEF. Finally, potential treatment strategies, important knowledge gaps and future directions regarding the right side in HFpEF are discussed.

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Section: Pathophysiologymentioning

confidence: 99%

Right heart dysfunction and failure in heart failure with preserved ejection fraction: mechanisms and management. Position statement on behalf of the Heart Failure Association of the European Society of Cardiology

Gorter

Veldhuisen

Bauersachs

et al. 2017

European J of Heart Fail

244

223

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“…Many therapies in development for PAH are focused on targeting the RV since heart failure is the ultimate cause of mortality in PAH. 4 PAH is predominant in females, with female ∶ male ratios of 1.4-4.1 ∶ 1. 5 Sexual dimorphism has also been observed in RV failure.…”

mentioning

confidence: 99%

Regulation and Function of miR‐214 in Pulmonary Arterial Hypertension

et al. 2016

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Dysregulation of microRNAs (miRNAs) can contribute to the etiology of diseases, including pulmonary arterial hypertension (PAH). Here we investigated a potential role for the miR-214 stem loop miRNA and the closely linked miR-199a miRNAs in PAH. All 4 miRNAs were upregulated in the lung and right ventricle (RV) in mice and rats exposed to the Sugen (SU) 5416 hypoxia model of PAH. Further, expression of the miRNAs was increased in pulmonary artery smooth muscle cells exposed to transforming growth factor β1 but not BMP4. We then examined miR-214 −/− mice exposed to the SU 5416 hypoxia model of PAH or normoxic conditions and littermate controls. There were no changes in RV systolic pressure or remodeling observed between the miR-214 −/− and wild-type hypoxic groups. However, we observed a significant increase in RV hypertrophy (RVH) in hypoxic miR-214 −/− male mice compared with controls. Further, we identified that the validated miR-214 target phosphatase and tensin homolog was upregulated in miR-214 −/− mice. Thus, miR-214 stem loop loss leads to elevated RVH and may contribute to the heart failure associated with PAH. Pulmonary arterial hypertension (PAH) is a disease characterized by narrowing of the small pulmonary arteries, leading to vascular remodeling, an elevation in pulmonary artery pressure, right ventricular hypertrophy (RVH), and heart failure. 1 Current therapies for PAH aim to reverse the endothelial dysfunction and vasoconstriction observed. 2 However, despite these therapies, PAH mortality rates remain high, and the 3-year survival of patients is only 54.9%. 3 Changes in the pulmonary vasculature are the primary cause of PAH; however, right ventricle (RV) function is a major determinant of the severity of symptoms and prognosis of pulmonary hypertension. Many therapies in development for PAH are focused on targeting the RV since heart failure is the ultimate cause of mortality in PAH. 4 PAH is predominant in females, with female ∶ male ratios of 1.4-4.1 ∶ 1. 5 Sexual dimorphism has also been observed in RV failure. Female PAH patients exhibit improved RV ejection fraction and survival compared with men. 6 This could be due at least in part to the protective effect of estrogen on RV function. 7,8 MicroRNAs (miRNAs) are involved in multiple cellular responses during normal development and disease; they act as posttranscriptional regulators to fine-tune protein synthesis. Evidence has emerged for a key role for miRNA in regulation of the cellular processes involved in PAH. We previously demonstrated that a range of miRNAs are dysregulated in rats exposed to models of PAH. 9 Later studies have shown that miR-21, the miR-143/145 cluster, miR-27a, the miR-17-92 cluster, miR-124, miR-150, miR-138, miR-190, miR-204, miR-206, miR-210, and miR-328 play a role in the development of PAH. 10 Multiple miRNAs could potentially be targeted in concert as therapeutics in PAH. 11 MicroRNA miR-214 is transcribed as a bicistronic primary transcript, which is processed to generate 4 separate mature miRNAs...

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“…Angiotensin convertase (ACE) inhibitor is considered as the cornerstone therapy to try to deter the progression of right ventricular hypertrophy related to pressure and volume overload. 21,22 However, ACE inhibitor administration was postponed in our patient, considering that she had a congenital solitary kidney as part of VACTERL association. Contrary to the belief that ACE inhibitors may lead to kidney damage, Simeoni M et al showed that anti-renin angiotensinaldosterone system drugs were renoprotective in patients with a solitary kidney.…”

Section: Discussionmentioning

confidence: 93%

Case report discussion of management of pink tetralogy of Fallot in VACTERL association

Putra

Hendrarto

2019

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Tetralogy of Fallot (TOF) and VACTERL are considered rare entities requiring medical attention with regards to diagnosis and management. When TOF is associated with VACTERL association, case management might differ from a simple case of TOF. Tetralogy of Fallot (TOF) is defined as a complex congenital cardiac abnormality characterized by ventricular septal defect, right outflow tract obstruction, right ventricular hypertrophy, and overriding aorta.1 The term was coined in 1888 by Fallot of Marseilles, even though the defect had been described in 1673 by Steno of Denmark. The entity was then studied extensively to deliver better care management through medical and surgical approaches.2

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Novel Therapeutic Approaches to Preserve the Right Ventricle

Cited by 16 publications

References 49 publications

Right heart dysfunction and failure in heart failure with preserved ejection fraction: mechanisms and management. Position statement on behalf of the Heart Failure Association of the European Society of Cardiology

Right heart dysfunction and failure in heart failure with preserved ejection fraction: mechanisms and management. Position statement on behalf of the Heart Failure Association of the European Society of Cardiology

Regulation and Function of miR‐214 in Pulmonary Arterial Hypertension

Case report discussion of management of pink tetralogy of Fallot in VACTERL association

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