Case report
Efficacy of sildenafil in HIV-related pulmonary arterial hypertension Valeria Pergolaa, Cesare Carusoa, Roberto Gnarinib, Serafino Fazioc and Sergio Ferraroa Pulmonary arterial hypertension (PAH) is one of the longterm complications of HIV infection. The incidence of HIVPAH is estimated at 0.5% of HIV-infected individuals. The mechanism by which infection leads to full-blown PAH is unknown. We describe a 44-year-old female patient with HIV infection diagnosed in 2004. Pulmonary hypertension was diagnosed in 2006. Seven months after the first cardiovascular clinical signs had started, the patient was referred to hospital because she was in New York Heart Association functional class IV. She commenced treatment with sildenafil. After increasing the sildenafil dose to ensure therapeutic drug levels over 24 h, the PAH and physical performance of the patient improved significantly. Our experience confirms long-term benefits of sildenafil
Introduction Pulmonary arterial hypertension (PAH) is one of the long-term complications of HIV infection [1]. The increased prevalence of this disease in HIV-infected patients compared with the general population has been noted [2], demonstrating that HIV is clearly a risk factor for the development of PAH. The incidence of HIV-PAH is estimated at 0.5% of HIV-infected individuals [2,3]. Moreover, the effect of highly active anti-retroviral therapy (HAART) on the incidence of HIV-PAH has been controversial [2], but data on the long-term impact of HAART on the course of PAH have been lacking [4]. The pathogenesis of PAH is complex and probably results from the interaction of genetic and environmental factors [5,6]. However, the mechanism leading infection to full-blown PAH is unknown [5], and only few recent data are available on the treatment of HIV-PAH [7].
Case report We describe a 44-year-old female patient with HIV infection diagnosed in 2004. The patient was treated with lopinavir, tenofovir and lamivudin. She was a smoker and from 2005 hypertensive, in therapy with angiotensinconverting enzyme (ACE) inhibitors and diuretics. From 2006 she presented progressive shortness of breath, oedema of the legs, dry cough, fatigue and chest pain. Pulmonary hypertension was diagnosed. At the time PAH was diagnosed, her mean CD4 cell count was 234 cells/ml and the viral load was low. After accurate evaluation of the bleeding risk (the activated partial thromboplastin time and the prothrombin time were both 1558-2027 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
monotherapy in PAH-HIV adult patients with improvements in symptoms and echocardiographic findings.
J Cardiovasc Med 2015, 16 (suppl 2):S136–S137 Keywords: HIV, pulmonary arterial hypertension, sildenafil a
U.O.C. Cardiology, bServizio Ospedalizzazione Domiciliare, D. Cotugno Hospital, and cUniversity Federico II Medical School, Naples, Italy
Correspondence to Valeria Pergola, Cardiology Division, D. Cotugno Hospital, Naples Italy Tel: +00390815791803; e-mail: [email protected] Received 10 June 2009 Revised 30 January 2010 Accepted 7 February 2010
normal) she was treated with anticoagulant, vasodilatators and diuretic therapy. Seven months after the first cardiovascular clinical signs had started, there was a worsening of the disease. The patient was referred to our hospital because she had severe dyspnoea [New York Heart Association (NYHA) functional class IV]. Blood pressure (BP) was 115/80 mmHg, pulse was 95 beats/min, respiratory frequency was 35 breaths/min and basal arterial PO2 was 57 mmHg (fraction of inspired oxygen was 28%). We could not perform a 6-min walking test [8] because of her poor clinical condition. Chest radiography showed cardiomegaly and a prominent pulmonary artery. Electrocardiography showed right ventricular hypertrophy. Colour Doppler echocardiography demonstrated dilatation of the right heart chambers, pulmonary arterial systolic blood pressure (PAPs) was 140 mmHg, eccentricity index was 0.8 [9] and tricuspid annular plane systolic excursion (TAPSE) [10] was 15 mm. No signs of left heart disease or left-to-right shunt were detected at the echo study. A ventilation–perfusion lung scan excluded pulmonary embolism. Parenchymal or interstitial lung diseases were excluded by high-resolution computed tomography (CT) angiogram of the chest. Doppler ultrasound evaluation of the portal vein and liver did not show any signs of portal hypertension or chronic liver disease. Right heart catheterization confirmed PAH with very high pulmonary vascular resistance. The PAPs was 135 mmHg, mean pressure was 95 mmHg and diastolic BP was 78 mmHg. Pulmonary vascular resistance was 21 Wood index. Cardiac output was 3.6 l/min and wedge pressure was 16 mmHg. Vasoreactivity (inhaled nitric DOI:10.2459/JCM.0b013e3283388fb3
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
HIV-related pulmonary arterial hypertension Pergola et al. S137
oxide) was negative. After informed consent had been obtained the patient commenced treatment with sildenafil 12.5 mg three times a day. After increasing the sildenafil dose to 25 mg three times a day, the PAH and physical performance of the patient improved significantly. After 1 month PAPs was 125 mmHg, eccentricity index was 0.8 and TAPSE was 16 mm. NYHA class was II/III. After 2 months of therapy PAPs was 100 mmHg, eccentricity index was 0.8 and TAPSE was 18 mm. NYHA class was II/III. After 6 months of therapy PAPs was 80 mmHg, eccentricity index was 0.9, TAPSE was 22 mm and the symptoms clearly improved (functional NYHA class II). Arterial PO2 was 97 mmHg. Sixminute walking distance was 532 m.
new targets for therapy in this progressive and serious condition.
References 1 2
3
4
5 6
Discussion Two-thirds of HIV-PAH related mortalities are usually secondary to consequences of pulmonary hypertension, with the worst survival noted in NYHA class III–IV [2]. Our data demonstrated for the first time the long-term benefits of sildenafil monotherapy in an adult HIV-PAH patient, with improvements in symptoms and echocardiographic findings, and with favourable survival. Given recent improvements in the treatment of PAH, the early recognition of these individuals is essential [2,7,11]. Our case demonstrated that sildenafil offers the possibility of
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8
9
10
11
Sitbon O. HIV-related pulmonary arterial hypertension: clinical presentation and management. AIDS 2008; 22(3 Suppl):S55–S62. Opravil M, Sereni D. Natural history of HIV-associated pulmonary arterial hypertension: trends in the HAART era. AIDS 2008; 22(3 Suppl):S35– S40. Sitbon O, Lascoux-Combe C, Delfraissy JF, Teni PG, Raffi F, De Zuttere D, et al. Prevalence of HIV-related arterial hypertension in the current antiretroviral therapy era. Am J Respir Crit Care Med 2008; 177:108–113. Reinsch N, Buhr C, Krings P, Kaelsch H, Kahlert P, Konorza T, et al. Competence Network of Heart Failure. Effect of gender and highly active antiretroviral therapy on HIV-related pulmonary arterial hypertension: results of the HIV-HEART Study. HIV Med 2008; 9:550–556. Limsukon A, Saeed AI, Ramasamy V, Nalamati J, Dhuper S. HIV-related hypertension. Mt Sinai J Med 2006; 73:1037–1044. Voelkel NF, Cool CD, Flores S. From viral infection to pulmonary arterial hypertension: a role for viral proteins? AIDS 2008; 22(3 Suppl):S49– S53. Degano B, Yaı¨ci A, Le Pavec J, Savale L, Jaı¨s X, Camara B, et al. Long-term effects of bosentan in patients with HIV-associated pulmonary arterial hypertension. Eur Respir J 2009; 33:92–98. Gibbons WJ, Fruchter N, Sloan S, Levy RD. Reference values for a multiple repetition 6-min walk test in healthy adults older than 20 years. J Cardiopulm Rehabil 2001; 21:87–93. Ryan T, Petrovic O, Dillon JC, Feigenbaum H, Conley MJ, Armstrong WF. An echocardiographic index for separation of right ventricular volume and pressure overload. J Am Coll Cardiol 1985; 5:918–927. Kaul S, Tei C, Hopkins JM, Shah PM. Assessment of right ventricular function using two-dimensional echocardiography. Am Heart J 1984; 107:526–531. Palmieri EA, Affuso F, Fazio S, Lembo D. Tadalafil in primary pulmonary arterial hypertension. Ann Intern Med 2004; 141:743–744.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Efficacy of sildenafil in HIV-related pulmonary arterial hypertension Valeria Pergolaa, Cesare Carusoa, Roberto Gnarinib, Serafino Fazioc and Sergio Ferraroa Pulmonary arterial hypertension (PAH) is one of the longterm complications of HIV infection. The incidence of HIVPAH is estimated at 0.5% of HIV-infected individuals. The mechanism by which infection leads to full-blown PAH is unknown. We describe a 44-year-old female patient with HIV infection diagnosed in 2004. Pulmonary hypertension was diagnosed in 2006. Seven months after the first cardiovascular clinical signs had started, the patient was referred to hospital because she was in New York Heart Association functional class IV. She commenced treatment with sildenafil. After increasing the sildenafil dose to ensure therapeutic drug levels over 24 h, the PAH and physical performance of the patient improved significantly. Our experience confirms long-term benefits of sildenafil
Introduction Pulmonary arterial hypertension (PAH) is one of the long-term complications of HIV infection [1]. The increased prevalence of this disease in HIV-infected patients compared with the general population has been noted [2], demonstrating that HIV is clearly a risk factor for the development of PAH. The incidence of HIV-PAH is estimated at 0.5% of HIV-infected individuals [2,3]. Moreover, the effect of highly active anti-retroviral therapy (HAART) on the incidence of HIV-PAH has been controversial [2], but data on the long-term impact of HAART on the course of PAH have been lacking [4]. The pathogenesis of PAH is complex and probably results from the interaction of genetic and environmental factors [5,6]. However, the mechanism leading infection to full-blown PAH is unknown [5], and only few recent data are available on the treatment of HIV-PAH [7].
Case report We describe a 44-year-old female patient with HIV infection diagnosed in 2004. The patient was treated with lopinavir, tenofovir and lamivudin. She was a smoker and from 2005 hypertensive, in therapy with angiotensinconverting enzyme (ACE) inhibitors and diuretics. From 2006 she presented progressive shortness of breath, oedema of the legs, dry cough, fatigue and chest pain. Pulmonary hypertension was diagnosed. At the time PAH was diagnosed, her mean CD4 cell count was 234 cells/ml and the viral load was low. After accurate evaluation of the bleeding risk (the activated partial thromboplastin time and the prothrombin time were both 1558-2027 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
monotherapy in PAH-HIV adult patients with improvements in symptoms and echocardiographic findings.
J Cardiovasc Med 2015, 16 (suppl 2):S136–S137 Keywords: HIV, pulmonary arterial hypertension, sildenafil a
U.O.C. Cardiology, bServizio Ospedalizzazione Domiciliare, D. Cotugno Hospital, and cUniversity Federico II Medical School, Naples, Italy
Correspondence to Valeria Pergola, Cardiology Division, D. Cotugno Hospital, Naples Italy Tel: +00390815791803; e-mail: [email protected] Received 10 June 2009 Revised 30 January 2010 Accepted 7 February 2010
normal) she was treated with anticoagulant, vasodilatators and diuretic therapy. Seven months after the first cardiovascular clinical signs had started, there was a worsening of the disease. The patient was referred to our hospital because she had severe dyspnoea [New York Heart Association (NYHA) functional class IV]. Blood pressure (BP) was 115/80 mmHg, pulse was 95 beats/min, respiratory frequency was 35 breaths/min and basal arterial PO2 was 57 mmHg (fraction of inspired oxygen was 28%). We could not perform a 6-min walking test [8] because of her poor clinical condition. Chest radiography showed cardiomegaly and a prominent pulmonary artery. Electrocardiography showed right ventricular hypertrophy. Colour Doppler echocardiography demonstrated dilatation of the right heart chambers, pulmonary arterial systolic blood pressure (PAPs) was 140 mmHg, eccentricity index was 0.8 [9] and tricuspid annular plane systolic excursion (TAPSE) [10] was 15 mm. No signs of left heart disease or left-to-right shunt were detected at the echo study. A ventilation–perfusion lung scan excluded pulmonary embolism. Parenchymal or interstitial lung diseases were excluded by high-resolution computed tomography (CT) angiogram of the chest. Doppler ultrasound evaluation of the portal vein and liver did not show any signs of portal hypertension or chronic liver disease. Right heart catheterization confirmed PAH with very high pulmonary vascular resistance. The PAPs was 135 mmHg, mean pressure was 95 mmHg and diastolic BP was 78 mmHg. Pulmonary vascular resistance was 21 Wood index. Cardiac output was 3.6 l/min and wedge pressure was 16 mmHg. Vasoreactivity (inhaled nitric DOI:10.2459/JCM.0b013e3283388fb3
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
HIV-related pulmonary arterial hypertension Pergola et al. S137
oxide) was negative. After informed consent had been obtained the patient commenced treatment with sildenafil 12.5 mg three times a day. After increasing the sildenafil dose to 25 mg three times a day, the PAH and physical performance of the patient improved significantly. After 1 month PAPs was 125 mmHg, eccentricity index was 0.8 and TAPSE was 16 mm. NYHA class was II/III. After 2 months of therapy PAPs was 100 mmHg, eccentricity index was 0.8 and TAPSE was 18 mm. NYHA class was II/III. After 6 months of therapy PAPs was 80 mmHg, eccentricity index was 0.9, TAPSE was 22 mm and the symptoms clearly improved (functional NYHA class II). Arterial PO2 was 97 mmHg. Sixminute walking distance was 532 m.
new targets for therapy in this progressive and serious condition.
References 1 2
3
4
5 6
Discussion Two-thirds of HIV-PAH related mortalities are usually secondary to consequences of pulmonary hypertension, with the worst survival noted in NYHA class III–IV [2]. Our data demonstrated for the first time the long-term benefits of sildenafil monotherapy in an adult HIV-PAH patient, with improvements in symptoms and echocardiographic findings, and with favourable survival. Given recent improvements in the treatment of PAH, the early recognition of these individuals is essential [2,7,11]. Our case demonstrated that sildenafil offers the possibility of
7
8
9
10
11
Sitbon O. HIV-related pulmonary arterial hypertension: clinical presentation and management. AIDS 2008; 22(3 Suppl):S55–S62. Opravil M, Sereni D. Natural history of HIV-associated pulmonary arterial hypertension: trends in the HAART era. AIDS 2008; 22(3 Suppl):S35– S40. Sitbon O, Lascoux-Combe C, Delfraissy JF, Teni PG, Raffi F, De Zuttere D, et al. Prevalence of HIV-related arterial hypertension in the current antiretroviral therapy era. Am J Respir Crit Care Med 2008; 177:108–113. Reinsch N, Buhr C, Krings P, Kaelsch H, Kahlert P, Konorza T, et al. Competence Network of Heart Failure. Effect of gender and highly active antiretroviral therapy on HIV-related pulmonary arterial hypertension: results of the HIV-HEART Study. HIV Med 2008; 9:550–556. Limsukon A, Saeed AI, Ramasamy V, Nalamati J, Dhuper S. HIV-related hypertension. Mt Sinai J Med 2006; 73:1037–1044. Voelkel NF, Cool CD, Flores S. From viral infection to pulmonary arterial hypertension: a role for viral proteins? AIDS 2008; 22(3 Suppl):S49– S53. Degano B, Yaı¨ci A, Le Pavec J, Savale L, Jaı¨s X, Camara B, et al. Long-term effects of bosentan in patients with HIV-associated pulmonary arterial hypertension. Eur Respir J 2009; 33:92–98. Gibbons WJ, Fruchter N, Sloan S, Levy RD. Reference values for a multiple repetition 6-min walk test in healthy adults older than 20 years. J Cardiopulm Rehabil 2001; 21:87–93. Ryan T, Petrovic O, Dillon JC, Feigenbaum H, Conley MJ, Armstrong WF. An echocardiographic index for separation of right ventricular volume and pressure overload. J Am Coll Cardiol 1985; 5:918–927. Kaul S, Tei C, Hopkins JM, Shah PM. Assessment of right ventricular function using two-dimensional echocardiography. Am Heart J 1984; 107:526–531. Palmieri EA, Affuso F, Fazio S, Lembo D. Tadalafil in primary pulmonary arterial hypertension. Ann Intern Med 2004; 141:743–744.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
