Pulmonary Hypertension in HIV Infected Persons

9/24/01 (Shang)

RE: A 30 year old African American male with worsening cough.

Question: Is pulmonary hypertension a recognized phenomenon in HIV infection?

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Unique Identifier: 21333387 / PubMed Identifier: 11440333

Authors: Seoane L. Shellito J. Welsh D. de Boisblanc BP.

Institution: Section of Pulmonary/Critical Care Medicine, Louisiana State University Health Sciences Center, New Orleans, USA.

Abstract: Pulmonary hypertension occurs with increased frequency among patients with human immunodeficiency virus (HIV) infection. Although the pathogenesis of HIV-associated pulmonary hypertension remains unknown, it appears to occur independently of other risk factors associated with pulmonary vasculopathy, such as chronic hepatitis C infection and intravenous drug use. Signs and symptoms are typical of those immunocompetent patients with primary pulmonary hypertension, but because many HIV-infected patients are receiving intensive medical supervision, the diagnosis of pulmonary hypertension is often made at an earlier stage. Acute responses to epoprostenol are similar to those among non-HIV-infected individuals, but the benefits of long-term, intravenous treatment with epoprostenol in HIV-infected patients is unknown. Future investigations should define the true incidence of pulmonary hypertension and the long-term effects of epoprostenol on survival among HIV-infected individuals. Physicians should be alert to possible pulmonary hypertension in persons infected with HIV. [References: 49]

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Unique Identifier: 21073527 / PubMed Identifier: 11205929

Authors: Pellicelli AM. Barbaro G. Palmieri F. Girardi E. D'Ambrosio C. Rianda A. Barbarini G. Frigiotti D. Borgia MC. Petrosillo N.

Institution: Second Division of Infectious Diseases, IRCCS Lazzaro Spallanzani Hospital, Rome, Italy. adriapel@tin.it

Abstract: The relationship between grade of pulmonary hypertension and factors associated with human immunodeficiency virus among patients with HIV infection is poorly documented. This report documents the most extensive attempt made thus far to determine whether a relationship exists between degree of pulmonary hypertension and the following conditions: HIV risk factor, degree of immunosuppression, presence or absence of AIDS, and presence or absence of liver cirrhosis. A retrospective study involving a search of the published literature on primary pulmonary hypertension among HIV cases from 1987 to 1998, using the Medline and Aidsline databases was conducted. Patients for whom secondary causes of pulmonary hypertension could be excluded were selected, and the following information for each was recorded: age, gender, risk factors for HIV infection, HIV disease stage according to the Centers for Disease Control, previous opportunistic and neoplastic diseases, CD4+ cell count (cells/L), presence or absence of liver cirrhosis, pulmonary systolic artery pressure level, and lung pathology specimens. Information about the patient's survival time was also recorded. Seventy-six patients were judged to have primary pulmonary hypertension and were included in the study. While no correlation was found between pulmonary systolic artery pressure level and CD4+ cell counts, a statistically significant difference was found between HIV-positive patients with and without AIDS as determined by the Centers for Disease Control criteria with regard to the degree of pulmonary hypertension, expressed as pulmonary systolic artery pressure level (85.4 +/- 17 mm Hg vs 71.8 +/- 15 mm Hg, p < 0.013). Although a higher PAPS was present in HIV cirrhotic patients, a statistically significant difference was not found between degree of pulmonary hypertension and evidence of hepatic cirrhosis (85 +/- 21 mm Hg vs 73.1 +/- 15 mm Hg, p < 0.062). Patients with AIDS and primary pulmonary hypertension present a higher degree of pulmonary hypertension than non-AIDS patients. Pulmonary hypertension associated with HIV seems to be related to a cytokine-related stimulation and proliferation of endothelium. High levels of cytokines present in AIDS patients can favor pulmonary hypertension, but the role of a host response to HIV--determined by one or more HLA subtypes--is suspected to enhance high cytokine production levels. [References: 64]

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Unique Identifier: 20524241 / PubMed Identifier: 11069824

Authors: Aguilar RV. Farber HW.

Institution: The Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.

Abstract: Although HIV-associated pulmonary hypertension and primary pulmonary hypertension (PPH) are clinically and histologically similar, treatment options for the former are limited. Treatment with calcium channel blockers (CCB), proven to be beneficial in a subset of patients with PPH, has been disappointing in HIV-associated pulmonary hypertension and there are no data examining the effects of long-term epoprostenol in this entity. Six patients with severe HIV-associated pulmonary hypertension were treated with continuous intravenous epoprostenol infusions. Acute infusion of epoprostenol resulted in a significant (p < 0.05) decrease in mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) of 16. 4 and 32.7%, respectively, and a significant (p < 0.05) increase in mean cardiac output (CO) of 36.9%. At 1 yr, mean PAP and PVR had decreased by 21.7 and 54.9% (p < 0.05), respectively, and mean CO had increased by 51.4% (p < 0.05) when compared with baseline values. Repeat catheterizations of three patients at 2 yr and one patient at 40 mo demonstrated further improvement or maintenance of hemodynamics. In addition, NYHA functional class improved in all patients. We conclude that epoprostenol infusion is effective in improving hemodynamic and functional status in this cohort of six patients with HIV-associated pulmonary hypertension acutely and long-term.

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[Link Directly to Fulltext Article in OVID]

Unique Identifier: 20490288 / PubMed Identifier: 11035689

Authors: Mehta NJ. Khan IA. Mehta RN. Sepkowitz DA.

Institution: Department of Medicine, Long Island College Hospital, Brooklyn, NY, USA.

Abstract: OBJECTIVE: To report two new cases of HIV-related pulmonary hypertension and to review and analyze the existing reports on the subject. METHOD: Two new cases of HIV-related pulmonary hypertension are described, and the cases, case series, and related articles on the subject in all languages were identified through a comprehensive MEDLINE search. RESULTS: Among the 131 reviewed cases, 54% were male, and the age range was 2 to 56 years (mean, 33 years). The interval between the diagnosis of HIV disease and the diagnosis of pulmonary hypertension was 33 months. In 82% of cases, pulmonary hypertension was related solely to HIV infection. Presenting symptoms were progressive shortness of breath (85%), pedal edema (30%), nonproductive cough (19%), fatigue (13%), syncope or near-syncope (12%), and chest pain (7%). The mean (+/- SD) pulmonary arterial systolic BP was 67 +/- 18 mm Hg (n = 116), and diastolic BP was 40+/-11 mm Hg (n = 39). Pulmonary vascular resistance was 983+/-420 dyne. s. cm(-5) (n = 29). Chest radiographs demonstrated cardiomegaly (72%) and pulmonary artery prominence (71%). Right ventricular hypertrophy was the most common electrocardiographic finding (67%). Dilatation of the right heart chambers was the most common echocardiographic finding (98%). Plexogenic pulmonary arteriopathy was the most common histopathology (78%). Pulmonary function tests demonstrated mild restrictive patterns with variably reduced diffusing capacities. The responses to vasodilator agents and antiretroviral therapy was variable. Sixty-six patients died during a median follow-up period of 8 months. The median length of time from diagnosis to death was 6 months. CONCLUSION: HIV infection is an independent risk factor for the development of pulmonary hypertension. The appearance of unexplained cardiopulmonary symptoms in HIV-infected individuals should suggest pulmonary hypertension. [References: 55]

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Unique Identifier: 99071017 / PubMed Identifier: 9855375

Authors: Pellicelli AM. Palmieri F. D'Ambrosio C. Rianda A. Boumis E. Girardi E. Antonucci G. D'Amato C. Borgia MC.

Institution: II Department of Infectious Disease, IRCCS Lazzaro Spallanzani Hospital, Rome, Italy.

Abstract: Previous cases of pulmonary hypertension (PH) in human immunodeficiency virus (HIV) infection have been reported in the literature. The role of HIV in PH is still debatable. The purpose of this report was to analyze whether HIV plays a direct or indirect role in PH pathogenesis. Between February and November 1997, 56 HIV-infected patients with cardiac symptoms and signs were studied by serial color Doppler echocardiography. In four patients (7.1%), PH not related to other well-known associated conditions, was disclosed. In spite of a low serum HIV RNA viral load and a high-efficacy antiretroviral therapy, including a protease inhibitor in two patients, PH developed and worsened. It could be hypothesized that in some patients with an individual immunogenetic predisposition, a high secretion of cytokines and endothelin-1 stimulated by an unidentified pathogen different from HIV could lead to PH. Antiretroviral therapy seems not to prevent or reduce right ventricle pressure gradient in PH.

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Unique Identifier: 99016292 / PubMed Identifier: 9799910

Authors: Golpe R. Fernandez-Infante B. Fernandez-Rozas S.

Institution: Respiratory Section, University Hospital Marques de Valdecilla, Santander, Spain.

Abstract: Several cardiorespiratory diseases can complicate human immunodeficiency virus infection. Primary pulmonary hypertension is a rare clinical disorder which carries a bad prognosis. More than 90 cases of HIV-associated primary pulmonary hypertension have been reported to date. Although its pathogenesis remains unknown, some evidence suggests a possible role for the virus itself in its development. Genetic susceptibility may also be implicated. The clinical and histopathologic features of this entity do not differ from those of classic primary pulmonary hypertension. The diagnosis requires a high degree of clinical suspicion and a careful evaluation to rule out causes of secondary pulmonary hypertension. In addition to supportive measures, anticoagulation and vasodilators have been used to treat this disorder, although sufficient data regarding long-term results with these therapies are lacking. [References: 47]

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[Link Directly to Fulltext Article in OVID]

Unique Identifier: 98337251 / PubMed Identifier: 9674494

Authors: Smith FB. Arias JH. Elmquist TH. Mazzara JT.

Institution: Department of Pathology, St. Vincent's Hospital and Medical Center of New York, New York 10011, USA.

Abstract: Postmortem examination of the lungs of a patient with advanced AIDS who had developed pulmonary arterial hypertension late in the course of the illness demonstrated extensive cytomegalovirus (CMV) infection in endothelial cells of the lung microvasculature. Enlarged CMV-infected endothelial cells were present in virtually all histologic sections of the lungs, protruded into and compromised the lumens of the small vessels they lined, and were estimated by image cytometry of immunohistochemically stained sections to comprise 0.8% of the total lung tissue volume. Comparison with experimental microvascular embolization studies suggests that this amount of compromise of the microvascular luminal area of the lung is sufficient to elevate pulmonary arterial pressure significantly. Pathologic features in this case differed from both the plexogenic arteriopathy seen in previously reported cases of AIDS-associated primary pulmonary hypertension and the usual form of CMV pneumonitis in AIDS in which alveolar epithelial cells are the predominant site of infection.

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Unique Identifier: 98234582 / PubMed Identifier: 9573500

Authors: Silva-Cardoso J. Moura B. Ferreira A. Martins L. Bravo-Faria D. Mota-Miranda A. Rocha-Goncalves F. Lecour H. Cerqueira-Gomes M.

Institution: Porto Cardiovascular Research, Porto Medical School, Hospital de S. Joao, Portugal.

Abstract: BACKGROUND: Some of the most frequent manifestations of heart involvement in human immunodeficiency virus (HIV) infection include right and left ventricular dysfunction. The pathogenesis remains obscure. METHODS AND RESULTS: This prospective clinical and echocardiographic study involved 181 patients at all stages of HIV infection. We tested a set of clinical variables using a backward logistic regression model to assess their ability to independently predict the presence of ventricular dysfunction. The presence of pulmonary infections (all etiologies mixed) was the only variable independently associated with isolated right ventricular dysfunction (odds ratio = 4.08; P = .02). Signs suggestive of pulmonary arterial hypertension were present in 71% of the patients with right ventricular dilation. History of previous opportunistic infections (all etiologies mixed) (odds ratio = 10.9; P = .0026) and time since the diagnosis of acquired immunodeficiency syndrome more than 12 months (odds ratio = 6.6; P = .03) were the only two independent predictors of left ventricular dysfunction. CONCLUSIONS: Isolated right ventricular dysfunction may be secondary to pulmonary hypertension caused by repetitive pulmonary infections and not to primary myocardial disease. The aggressive treatment of opportunistic infections may become an important element of heart failure prophylaxis in HIV infection because they may be associated with left ventricular dysfunction.

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[Link Directly to Fulltext Article in OVID]

Unique Identifier: 98103913 / PubMed Identifier: 9443676

Authors: Mesa RA. Edell ES. Dunn WF. Edwards WD.

Institution: Department of Internal Medicine, Mayo Clinic Rochester, Minnesota 55905, USA.

Abstract: In this article, we describe pulmonary hypertension in two men (31 and 43 years of age) with human immunodeficiency virus (HIV) infection who were examined at Mayo Clinic Rochester. Among 88 reported cases (including the two current ones) of HIV- or acquired immunodeficiency syndrome (AIDS)-associated pulmonary hypertension, 61% were male; the age range was 2 to 56 years (mean, 32). Dyspnea was the usual initial symptom. Of the 74 patients in whom pulmonary artery pressure was recorded or calculated by echocardiography, systolic pressures ranged from 49 to 118 mm Hg (mean, 68). Of the 33 cases in which lung tissue was evaluated microscopically, 28 (85%) were of the plexogenic variant of pulmonary arterial hypertension. Of the other five cases examined histologically, three consisted of thrombotic pulmonary arteriopathy (one was due to recurrent thromboembolism, and the other two were due to in situ thrombosis), and two were of pulmonary venoocclusive disease. No correlation existed between either CD4 counts or a history of pulmonary infections and the development of pulmonary hypertension. In 15 of the 88 patients (17%), confounding factors for hypertensive pulmonary vascular disease were present, including coexisting liver disease in 13 and coagulation abnormalities in 2. In 83% of the patients, the development of pulmonary hypertension seems to have been related primarily to the chronic HIV infection. Pulmonary hypertension was more rapidly progressive in patients with HIV or AIDS than in those with primary pulmonary hypertension; the reported time intervals between onset of symptoms and diagnosis were 6 months and 30 months, respectively. The 1-year survival rate for patients with HIV and pulmonary hypertension was 51%, based on the follow-up data compiled from the 63 patients in whom it was described; this compares with a 1-year survival rate of 68% for patients with primary pulmonary hypertension. Death was considered a direct consequence of pulmonary hypertension in 29 (76%) of the 38 fatal cases. [References: 61]

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Unique Identifier: 97235906 / PubMed Identifier: 9117037

Authors: Opravil M. Pechere M. Speich R. Joller-Jemelka HI. Jenni R. Russi EW. Hirschel B. Luthy R.

Institution: Department of Medicine, University Hospitals of Zurich, Switzerland.

Abstract: To assess the clinical and echocardiographic time course, prognosis, and possible etiology of HIV-associated primary pulmonary hypertension (PPH), we prospectively followed all 19 patients in whom PPH was diagnosed in our centers. Women (12 cases) and injecting drug use (16 cases) predominated; the median CD4 lymphocytes count was 83/microliter (range, 1 to 740). Matched control subjects without PPH were identified within the Swiss HIV Cohort Study. Frozen serum samples of both groups were then reanalyzed for autoimmune parameters, neopterin, beta-2-microglobulin, and thyroid-stimulating hormone. The median follow up of the patients was 1.3 yr. Follow-up Doppler echocardiography was available in 13 patients. The RVSP-RAP pressure gradient decreased by 3.2 mm Hg for those six patients who received antiretroviral treatment but increased by 19.0 mm Hg for untreated patients (p = 0.026). PPH was the cause of eight of 17 deaths. The probability of surviving was significantly decreased in patients with PPH in comparison with the control subjects; the median survival was 1.3 versus 2.6 yr (p < 0.05). Patients with PPH had significantly higher anticardiolipin IgM, anti SS-B, and neopterin, but all other laboratory values did not differ between cases and control subjects. In conclusion, HIV-associated PPH contributed significantly to mortality. Antiretroviral treatment may exert a beneficial effect on the pressure gradient. A possible role of an autoimmune phenomenon in the pathogenesis could not be substantiated.

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[Link Directly to Fulltext Article in OVID]

Unique Identifier: 96074222 / PubMed Identifier: 7487262

Authors: Weiss JR. Pietra GG. Scharf SM.

Institution: Pulmonary and Critical Care Division, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, NY, USA.

Abstract: We report two cases of human immunodeficiency virus (HIV) seropositivity and pulmonary hypertension seen at our institution and present a comprehensive literature review and available histopathologic findings of the association between HIV seropositivity and pulmonary hypertension. Studies and reviews pertaining to HIV seropositivity and pulmonary hypertension were identified through a MEDLINE search and reference citations. All studies and series found in the MEDLINE search were reviewed and are discussed in this article. Where data were available, comparisons and analyses were made between groups of reported cases of HIV seropositivity and pulmonary hypertension with regard to the following parameters: sex distribution, mode of acquiring HIV infection, presence or absence of the acquired immunodeficiency syndrome, CD4 cell counts, PO2 or oxygen saturation by pulse oximetry, concurrent lower respiratory tract infection, and histopathologic features. We conclude that there is strong evidence for pulmonary hypertension associated with HIV infection that is histologically indistinguishable from primary pulmonary hypertension. Consequently, HIV-seropositive patients with unexplained dyspnea should be evaluated for primary pulmonary hypertension. Prospective studies in HIV-positive patients are indicated. [References: 26]