Drug-Induced Pulmonary Arterial Hypertension: A More Complicated Prognosis - Pulmonology Advisor

Posted: 22 Apr 2019 02:00 AM PDT

While methamphetamine use had been implicated in myocardial infarction, cardiac arrhythmias, and ischemic cardiomyopathy, recent reports have indicated that intravenous (IV) methamphetamine also attacks the lung tissue.¹ Data compiled at a Stanford University pulmonology clinic in California reported that 85% of drug-induced pulmonary arterial hypertension (D-PAH) stemmed from methamphetamine use.¹ The prognosis for these patients was substantially worse than for patients with idiopathic PAH; the median 5-year survival for patients with D-PAH was 35%.¹

In patients with a history of IV drug use, HIV and hepatitis C virus (HCV) coinfection can complicate the course of PAH.² Individuals with HIV who have a higher risk for PAH include women, IV drug users, and have HCV coinfection.² Inquiring about interferon therapy in patients with a history of HCV and IV drug use is essential because interferon alpha and beta have been linked to left ventricular systolic dysfunction.²

Other Drugs Linked to PAH

Although methamphetamine-associated D-PAH is a recent phenomenon, other drugs have been implicated in PAH for longer than 50 years.¹ Around that time, amphetamine diet pills that led to PAH were taken off the market.¹ Today experts recognize that PAH complications arise from both US Food and Drug Administration (FDA)-approved and illicit drugs.¹

Documented drugs implicated in PAH include:

Aminorex
Fenfluramine
Dexfenfluramine
Toxic rapeseed oil
Benfluorex
Selective serotonin reuptake inhibitors (SSRIs)¹

Illicit drugs likely to cause PAH include:

Amphetamines
Dasatinib
L-tryptophan
Methamphetamine¹

Although the course of D-PAH may be indistinguishable from idiopathic PAH, the former has a more unpredictable prognosis.¹ Both types of PAH lead to right heart failure and often occlusive arterial disease.¹

Another Look at Idiopathic PAH

When Kelly M. Chin, MD, associate professor of pulmonology from University of Texas Southwestern Medical Center in Dallas, and colleagues, examined potential causes of idiopathic PAH in 2006, they found that almost one-third of 340 cases were attributed to methamphetamine use.³

The retrospective study also found that patients with idiopathic PAH were 10.14 times more likely to have used stimulants than patients with known causes of PAH and 7.63 times more likely to have used stimulants than patients with chronic thromboembolic pulmonary hypertension (CTEPH).³ When the study was conducted, an estimated 5.2% of the American population had reported ever having used methamphetamines.³ Younger patients (mean age, 47.1 years) were more likely to be diagnosed with idiopathic PAH, whereas older patients were likelier to have a known cause for PAH and CTEPH (mean age, 49.1 years and mean age, 53 years; respectively).³

"We found a significant association between the use of stimulants, particularly methamphetamine, and unexplained PAH," said Dr Chin. "Subsequent studies have found a similar association, including among non-IV drug users (inhaled, oral). Our hope is that clinicians will be particularly thorough in their drug and substance use histories in PAH patients."

"Demographic features are often surprising — stimulants are used by some [patients] recreationally, but in other cases patients are using or abusing them to stay awake or to try and treat fatigue or other medical issues," Dr Chin continued. "I have found some patients taking 'just a little' each morning just to get themselves going who were seemingly quite functional and did not fit typical methamphetamine stereotypes."

Although the study was conducted before the peak of the opioid epidemic, recent data on drug-induced PAH have not linked it to opioid abuse. "Opioids are not thought to contribute to PAH, though a few case reports involving recurrent embolization of talc and other substances from injecting crushed pills have been reported," Dr Chin noted.

Foreign-Body Embolization

When a drug meant to be taken orally is injected, the fragments of the tablet can lodge in the arteries, causing a pulmonary embolism.⁴ Because tablets are typically manufactured with a thickening agent, they are often not water soluble, and as a result can obscure vasculature.⁴ The most common sites for embolisms include the lungs, any organ system, the liver, the kidneys, and the heart.⁴

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Pulmonary Hypertension

Widening the Definition and Use of Palliative Care in PAH - The Cardiology Advisor

Posted: 05 Apr 2019 12:00 AM PDT

While the prognosis for patients with pulmonary arterial hypertension (PAH) has improved since the introduction of PAH-specific therapies, mortality and morbidity associated with the disease remain high. The 7-year survival rate for PAH is 50%, according to findings from a 2012 study of 2635 individuals, and many patients have numerous intolerable symptoms despite treatment.^1,2

In addition to physical limitations due to symptoms such as fatigue and shortness of breath, mental health disorders commonly affect patients with PAH. According to one study, there was a 35% prevalence of psychological disorders in patients with PAH, and other studies have shown elevated rates of depression, anxiety, and panic attacks in this population.^2,3 The caregivers of these patients are also vulnerable to stress, exhaustion, depression, and social impairment.

In many of individuals with PAH, this range of factors often contribute to a poor health-related quality of life (HRQoL), which is influenced by indicators such as functional status and physical, social, and emotional well-being. Various studies have observed that HRQoL in patients with PAH may be similar to that in patients with other chronic illnesses including cancer, spinal cord injury, and interstitial lung disease.

Although palliative care can improve HRQoL in PAH, such interventions are underused in this group because of misconceptions about its role. For example, a study published in 2014 found that many physicians view palliative care as an approach to be implemented in the context of end-of-life care.⁴ However, palliative care is "focused on providing relief from symptoms and stress caused by any chronic illness… [and] improving the HRQoL of the patient and family," according to a paper published in December 2018 in European Respiratory Review.² "It is appropriate at any age or stage of disease and importantly, it must be provided in concert with curative treatment." [Read about one cardiologist's shift in perspective on this topic.]

The most recent CHEST guidelines on PAH treatment contain a consensus statement supporting the integration of palliative care into PAH management, noting significant improvements in outcomes observed in other pulmonary diseases, including lung cancer.⁵ Although the expert panel did not identify any studies that examined the effects of palliative interventions combined with standard PAH care, this "lack of evidence… does not negate the potential benefits palliative care offers to all patients and families for assisting in management of disease burden, pain, and symptoms of chronic or acute needs," they stated. "The addition of palliative care interventions to assist in management of disease burden and symptoms can often be beneficial to improving patient quality of life."

The 2018 review described invasive palliative interventions including atrial septostomy, pulmonary artery denervation (PADN), and right ventricular assist devices, as well as noninvasive interventions including treatment for depression and anxiety, pain control, patient education and support groups, management of symptoms such as nausea and dyspnea, financial assistance, and pastoral counseling. Although research regarding palliative care in PAH is scant, studies have reported improvements in 6-minute walking distance, World Health Organization functional status, and mean pulmonary artery pressure in patients with PAH who underwent atrial septostomy or PADN.^6,7 Further research is needed to explore the effect of various invasive and noninvasive palliative approaches.

"It is important that physicians come to understand that palliative care is not the same as end-of-life care, and that palliative care is best when offered alongside life-prolonging therapies," the review authors concluded. "As there is a better understanding of what palliative care can offer, patients should know that a referral to palliative care is not 'giving up' but instead is an effort to thoroughly investigate all possible avenues for making quality of life the best it can be."

Pulmonology Advisor spoke with the following experts to learn more about palliative care in PAH: Lauren Goodman, MD, a pulmonary, critical care, and palliative medicine physician at the Ohio State University Wexner Medical Center in Columbus; and Roham Zamanian, MD, FCCP, associate professor of pulmonary and critical care medicine at the Stanford University Medical Center and director of the Stanford Adult Pulmonary Hypertension Program in California.

Pulmonology Advisor: What are some potential benefits of palliative care in patients with PAH and what are your thoughts on why it is underutilized in this population?

Dr Goodman:Although some PAH symptoms can be alleviated by treating the condition, others tend to persist even with maximal treatment. These symptoms often include at least dyspnea, fatigue, and anorexia. There can also be significant side effects and complications of PAH treatments, some of which require creativity and patience to manage.

Patients with PAH often think of their PAH physicians as their lifesavers. They may feel that if they mention ongoing symptoms, they will sound unappreciative, ungrateful, or perhaps even unworthy of the care and sometimes aggressive treatments they are receiving. Patients may also worry that continued symptoms or complaints would reduce their chances of being listed for or receiving a transplant, if transplant is an option.

While physicians both need and want to know about their patients' symptoms, time available to explore the severity and effect of symptoms can be limited. Palliative care physicians are often allotted more time for visits and fully expect to explore symptoms in depth with patients and with their families, if the patient desires.

This article originally appeared on Pulmonology Advisor

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Pulmonary Arterial Hypertension Pulmonary Hypertension

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