Pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a rare and debilitating disease characterized by abnormal proliferation and contraction of pulmonary vascular smooth muscle cells. The resulting increase in pressure and pulmonary vascular resistance results in progressive right heart failure, low cardiac output, and ultimately death if left untreated. PAH is defined by a persistent elevation in pulmonary artery pressure with normal left-sided pressures, differentiating it from left-sided heart disease. Symptoms progress from shortness of breath and decreasing exercise tolerance to right heart failure, with peripheral edema and marked functional limitation. Exercise-induced syncope, worsening symptoms at rest, and intractable right heart failure indicate critical disease. PAH may be idiopathic with no identifiable cause or associated with collagen vascular diseases, drugs, HIV, liver disease, and/or congenital heart disease. Familial or genetically mediated PAH accounts for a small percentage of cases. Advances in the understanding of pathobiological pathways that contribute to vascular proliferation and remodeling have resulted in new therapies that improve quality of life and survival. Emerging therapies focus on the nitric oxide, prostacyclin, and endothelin pathways. Nursing interventions are critical to ensure patients' success with these expensive and complex treatments and their optimal adjustment to living with PAH.     

Pulmonary arterial hypertension

Pulmonary arterial hypertension is a disease of the small pulmonary arteries characterized by vascular narrowing and increased pulmonary vascular resistance, which eventually leads to right ventricular failure. Vasoconstriction, vascular proliferation, remodeling of the pulmonary vessels, and thrombosis are all contributing factors to the increased vascular resistance seen in this disease. Pulmonary arterial hypertension develops as a sporadic disease (idiopathic), as an inherited disorder (familial), or in association with certain conditions (collagen vascular diseases, portal hypertension, human immunodeficiency virus infection, congenital systemic‐to‐pulmonary shunts, ingestion of drugs or dietary products, or persistent fetal circulation). The pathogenesis of pulmonary arterial hypertension is a complicated, multifactorial process. It seems doubtful that any one factor alone is sufficient to activate the necessary pathways leading to the development of this disease. Rather, clinically apparent pulmonary arterial hypertension most likely develops after a second insult occurs in an individual who is already susceptible owing to genetic factors, environmental exposures, or acquired disorders. Currently, there is no cure for pulmonary arterial hypertension but several novel therapeutic options are now available that can improve symptoms and increase survival.     

Pulmonary arterial hypertension

Pulmonary arterial hypertension is a disease of the small pulmonary arteries characterized by vascular narrowing and increased pulmonary vascular resistance, which eventually leads to right ventricular failure. Vasoconstriction, vascular proliferation, remodeling of the pulmonary vessels, and thrombosis are all contributing factors to the increased vascular resistance seen in this disease. Pulmonary arterial hypertension develops as a sporadic disease (idiopathic), as an inherited disorder (familial), or in association with certain conditions (collagen vascular diseases, portal hypertension, human immunodeficiency virus infection, congenital systemic-to-pulmonary shunts, ingestion of drugs or dietary products, or persistent fetal circulation). The pathogenesis of pulmonary arterial hypertension is a complicated, multifactorial process. It seems doubtful that any one factor alone is sufficient to activate the necessary pathways leading to the development of this disease. Rather, clinically apparent pulmonary arterial hypertension most likely develops after a second insult occurs in an individual who is already susceptible owing to genetic factors, environmental exposures, or acquired disorders. Currently, there is no cure for pulmonary arterial hypertension but several novel therapeutic options are now available that can improve symptoms and increase survival.     

Pulmonary arterial hypertension

PAH is a chronic disease requiring lifelong therapy, regardless of chosen treatment options. Nurses and other providers must allow for open, honest discussion on the risks and benefits of each therapy. Determining the best treatment option for patients requires consideration of the patient's overall function and social support. These patients benefit from comprehensive and collaborative support from facilities or centers trained in the management of the disease.     

Alcohol and arterial hypertension

The positive association between alcohol consumption and arterial pressure has been shown in several epidemiological surveys. This strong relationship has been demonstrated in many countries, independent of the known risk factors for hypertension; the dose-response appears to be linear in most studies. The lowering of blood pressure after stopping alcohol consumption and its rise after starting to take alcohol again are good evidence of a causal relationship. The pathophysiology of the hypertensive effect of alcohol is uncertain. Alcohol consumption seems to be a factor to be taken into account in the prevention and treatment of hypertension.     

Endothelin in arterial hypertension

A study was made of the concentration of endothelin (ET) in the plasma of patients suffering from arterial hypertension (AH), heart failure (HF) and in that of healthy volunteers. The concentration of ET in the normal subjects was within 4.0-8.6 pg/ml, in the patients with AH, it varied from 5.7 to 64.5 pg/ml, and in the patients suffering from HF, from 8.8 to 94.0 pg/ml. A subgroup of patients with essential hypertension, stage II B, showed a tendency towards a rise of the ET concentration in response to orthostatic load that was associated with an increase of the concentration of angiotensin-2.     

Understanding pulmonary arterial hypertension

New therapies improve the management of pulmonary arterial hypertension.     

Drug-associated pulmonary arterial hypertension

Introduction: While pulmonary arterial hypertension remains an uncommon diagnosis, various therapeutic agents are recognized as important associations. These agents are typically categorized into “definite”, “likely”, “possible”, or “unlikely” to cause pulmonary arterial hypertension, based on the strength of evidence.

Objective: This review will focus on those therapeutic agents where there is sufficient literature to adequately comment on the role of the agent in the pathogenesis of pulmonary arterial hypertension.

Methods: A systematic search was conducted using PubMed covering the period September 1970– 2017. The search term utilized was “drug induced pulmonary hypertension”. This resulted in the identification of 853 peer-reviewed articles including case reports. Each paper was then reviewed by the authors for its relevance. The majority of these papers (599) were excluded as they related to systemic hypertension, chronic obstructive pulmonary disease, human immunodeficiency virus, pulmonary fibrosis, alternate differential diagnosis, treatment, basic science, adverse effects of treatment, and pulmonary hypertension secondary to pulmonary embolism.

Agents affecting serotonin metabolism (and related anorexigens): Anorexigens, such as aminorex, fenfluramine, benfluorex, phenylpropanolamine, and dexfenfluramine were the first class of medications recognized to cause pulmonary arterial hypertension. Although most of these medications have now been withdrawn worldwide, they remain important not only from a historical perspective, but because their impact on serotonin metabolism remains relevant. Selective serotonin reuptake inhibitors, tryptophan, and lithium, which affect serotonin metabolism, have also been implicated in the development of pulmonary arterial hypertension.

Interferon and related medications: Interferon alfa and sofosbuvir have been linked to the development of pulmonary arterial hypertension in patients with other risk factors, such as human immunodeficiency virus co-infection.

Antiviral therapies: Sofosbuvir has been associated with two cases of pulmonary artery hypertension in patients with multiple risk factors for its development. Its role in pathogenesis remains unclear.

Small molecule tyrosine kinase inhibitors: Small molecule tyrosine kinase inhibitors represent a relatively new class of medications. Of these dasatinib has the strongest evidence in drug-induced pulmonary arterial hypertension, considered a recognized cause. Nilotinib, ponatinib, carfilzomib, and ruxolitinib are newer agents, which paradoxically have been linked to both cause and treatment for pulmonary arterial hypertension.

Monoclonal antibodies and immune regulating medications: Several case reports have linked some monoclonal antibodies and immune modulating therapies to pulmonary arterial hypertension. There are no large series documenting an increased prevalence of pulmonary arterial hypertension complicating these agents; nonetheless, trastuzumab emtansine, rituximab, bevacizumab, cyclosporine, and leflunomide have all been implicated in case reports.

Opioids and substances of abuse: Buprenorphine and cocaine have been identified as potential causes of pulmonary arterial hypertension. The mechanism by which this occurs is unclear. Tramadol has been demonstrated to cause severe, transient, and reversible pulmonary hypertension.

Chemotherapeutic agents: Alkylating and alkylating-like agents, such as bleomycin, cyclophosphamide, and mitomycin have increased the risk of pulmonary veno-occlusive disease, which may be clinically indistinct from pulmonary arterial hypertension. Thalidomide and paclitaxel have also been implicated as potential causes.

Miscellaneous medications: Protamine appears to be able to cause acute, reversible pulmonary hypertension when bound to heparin. Amiodarone is also capable of causing pulmonary hypertension by way of recognized side effects.

Conclusions: Pulmonary arterial hypertension remains a rare diagnosis, with drug-induced causes even more uncommon, accounting for only 10.5% of cases in large registry series. Despite several agents being implicated in the development of PAH, the supportive evidence is typically limited, based on case series and observational data. Furthermore, even in the drugs with relatively strong associations, factors that predispose an individual to PAH have yet to be elucidated.     

微小RNA与肺动脉高压

肺动脉高压(PAH)是一类以肺循环阻力增高为主要特征、最终导致右心功能不全、乃至死亡的慢性肺疾病,其病因复杂,预后差.微小RNA(miRNA)是一种内源性的非编码RNA,与PAiH的发生、发展密切相关,可能是潜在的药物治疗靶点.本文主要对miRNA在PAH慢性缺氧、骨形成蛋白Ⅱ型受体(BMPRR2)、apelin-APJ、以及右心功能不全等方面的研究进展进行综述,为探索PAH的发病机制、诊疗研究提供新的方向和思路.