Echocardiographic Findings and Follow-Up in Two HIVAssociated Pulmonary Arterial Hypertension Cases

Mircea Bajdechi^1*, Adriana Gurghean², Georgiana-Elena Stoian², Dragos-Cosmin Zaharia², Tudor Constantinescu², Cristina-Elena Micu¹, Roxana Cernat¹, Irina Magdanela Dumitru¹ and Sorin Rugina^1
*Correspondence: Mircea Bajdechi, Faculty of Medicine-“Ovidius”, University of Constanta, Romania, Spain, Tel: +40720569706, Email:

Keywords

Pulmonary arterial hypertension • HIV • Cardiovascular • Echocardiography • Global longitudinal strain • Sildenafil

Abbreviations

HIV: Human Immunodeficiency Virus • NYHA: New York Heart Association • 6MWD: 6-Minute Walk Distance • sPAP: Systolic Pulmonary Arterial Pressure • RV GLS: Right Ventricle Global Longitudinal Strain

Introduction

Pulmonary Arterial Hypertension (PAH) associated with HIV infection is a separate entity and represents a special subgroup in the classification of pulmonary hypertension, developed by the European Society of Cardiology. Most of the studies reported a prevalence of 0.5%, confirmed by cardiac catheterization [1,2]. Echocardiographic studies showed higher PAH prevalence on these patients, between 6-14%, most of them being completely asymptomatic [3,4]. The occurrence of antiretroviral therapy did not change this prevalence.

The diagnosis should be suspected when signs and symptoms appear. Echocardiography can suggest the diagnostic and it is indicated in symptomatic patients or as a result of electrocardiographic abnormalities. The gold standard method of diagnosing pulmonary arterial hypertension is right heart catheterization. The treatment principles of HIV-associated pulmonary hypertension are similar to those of primary pulmonary hypertension, but there are some special considerations such as avoiding calcium channel blockers or avoiding co-administration of sildenafil with protease inhibitors [5].

PAH has a negative impact on the quality of life and it represents an independent mortality risk for these patients. Despite specific treatment, PAH was directly involved in 72% of deaths among the patients [6].

We present these two patients living with HIV, who are included in the Romanian National Program of Pulmonary Arterial Hypertension. For patients, the possible thromboembolism or left heart dysfunction were excluded. Each case has its own particularities, but both of them responded to treatment.

Case Report

Case I

A 31-year-old female from Bucharest, came to our cardiology department for evaluation. She was infected with HIV-1 by iatrogenic procedures and she is part of „The Romanian HIV cohort”, which includes over 5000 patients that were infected during childhood between 1987-1989. In 2002 she was diagnosed with HIV infection and by then, the CD4 number was <200/μL. She refused specific therapy at that time. Since 2008, she has accepted the antiretroviral treatment and she has been treated with abacavir, lamivudine, lopinavir and ritonavir. Using this medication, the infection was controlled, with undetectable viremia and increasing CD4 cells number (Table 1).

In 2018 she was diagnosed with pulmonary arterial hypertension. At the diagnosis, she presented with shortness of breath, orthopnea associated with lower limb edema. The echocardiographic evaluation suggested high pulmonary arterial pressure and right cardiac catheterization confirmed precapillary pulmonary arterial hypertension. Since then, specific pulmonary arterial hypertension therapy with sildenafil combined with diuretic therapy including furosemide and spironolactone has been started. Also, the antiretroviral therapy has been changed and now she is on tenofovir, lamivudine and raltegravir and on this medication an improvement in clinical and paraclinical status was observed.

On this evaluation, the electrocardiogram showed sinus rhythm, 60 bpm, and right ventricular strain pattern. Echocardiography (Figure 1) revealed dilated right chambers, right ventricular dysfunction and high pulmonary arterial pressure with a normal left ventricle ejection fraction and normal mitral function.

Now she has an improved life quality, she is active at work and considers that she has a normal life.

Case II

A 46-year-old male from Bucharest came to our cardiology department for evaluation. In 2014, he was diagnosed with HIV-1 as a result of searching for the etiology of pulmonary arterial hypertension. He acquired the infection by sexual contact. At pulmonary arterial hypertension diagnosis time, his symptoms were fatigue and dyspnea at medium effort. The echocardiography revealed high pulmonary arterial pressure. Right cardiac catheterization confirmed pre-capillary pulmonary arterial hypertension. Since then, specific PAH therapy with sildenafil combined with diuretic therapy including furosemide and spironolactone and antiretrovirals like lamivudine, zidovudine and raltegravir has been started. The patient has intermittent adherence on antiretroviral therapy and discontinued the treatment for several months between 2016 and 2017.

Echocardiography (Figure 2) showed dilated right chambers, right ventricular dysfunction and pulmonary hypertension with a normal left ventricle function and normal mitral function.

Therapeutic compliance in the last three years has improved the clinical and paraclinical status, without requiring hospitalization (Table 2).

Discussion

These two patients are included in the Romanian National Program of Pulmonary Arterial Hypertension. In both patient, the possible thromboembolism or left heart dysfunction were excluded. Each case has its own particularities, but both of them responded to treatment. Although, the occurrence of antiretroviral therapy has not changed the prevalence of PAH in persons living with HIV, it appears that interruption of antiretroviral therapy in patients who have already developed the disease may exacerbate the symptoms.

Pulmonary arterial hypertension has multiple and incompletely elucidated mechanisms, but inflammation plays the central role. One particular element is that dendritic cells from the pulmonary artery maintain on their surface the virus, releasing cytokines (IL-1 beta, IL-6, TNF alpha, platelet growth factor) leading to local tissue injury. Systemic cytokine release has procoagulant effect, increases the expression of endothelial adhesion molecules and accumulation of inflammatory cells in the pulmonary artery. For sure, not only the release of cytokines is responsible for the development of PH in these patients, because their values are high in most of them and only a small part develop PH. Recent studies showed that even in the absence of pulmonary arterial hypertension, a degree of remodelling of the right heart has been described in a proportion of HIV-infected patients [7].

The prevalence of Pulmonary Arterial Hypertension (PAH) in HIV-infected patients is up to one thousand times higher than in general population. Predictive factors for the development of pulmonary hypertension are feminine gender, hepatitis C infection, cocaine use and HIV viral load [8]. Among the users of intravenous drugs, the prevalence of pulmonary hypertension can reach 59% [6].

Despite the high prevalence of pulmonary hypertension in these patients compared to the general population, the guideline does not recommend echocardiographic screening in these patients (IIIC). Cardiac ultrasonography should be performed as a result of electrocardiographic changes or in symptomatic patients. However, the recommendations of the Sixth World Symposium on Pulmonary Hypertension propose echocardiographic evaluation in symptomatic patients or who have several risk factors (female sex, HCV infection, Nef or Tat mutations, Afro-americans). Paraclinical changes of right overload may appear early, so evaluation of these patients by new paraclinical techniques (speckle tracking) should be done [9].

The treatment principles of HIV-associated pulmonary hypertension are similar to those of primary pulmonary hypertension, but there are some special considerations such as avoiding calcium channel blockers [5].

The patients with WHO functional class I do not require specific PH treatment and they should be monitored every three to six months. WHO functional class II-IV should be referred to a specialized PAH center. In these two cases, sildenafil improves clinical and paraclinical parameters. Sildenafil should be avoided in those receiving a pharmacologic boosting agent such as ritonavir or cobicistat and it can significantly decreases protease inhibitor levels [10]. In the literature, other phosphodiesterase inhibitors (tadalafil or vardenafil) have not been adequately studied in these patients.

Conclusion

Pulmonary Arterial Hypertension (PAH) associated with HIV infection is a separate entity. The mechanisms are multifactorial and incompletely elucidated. The prevalence is up to one thousand times higher than in general population. Sildenafil is the treatment of choice, but interaction with certain antiretroviral drugs should be considered. Mortality is high, usually due to right heart failure and PAH is considered an independent predictor of death in HIVinfected patients.

Conflict of Interests

The authors declare no conflict of interest.

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