Biomedical subjects

R J Barst

Publications and source records attributed to R J Barst.

At least 55 records · Page 3Linked to original sources

PubMed1997

Mapping of familial primary pulmonary hypertension locus (PPH1) to chromosome 2q31-q32.

BACKGROUND: The pathogenesis of primary pulmonary hypertension (PPH) is unknown, although in some instances families with multiple affected members suggest a genetic etiology. METHODS AND RESULTS: We used microsatellite markers and linkage analysis in a large family with PPH to determine the chromosomal location of their disease gene. We tested a second, ethnically distinct, family for cosegregation of disease with markers from the linked region. We mapped the disease locus PPH1; GDB/HUGO designation (GDB:1381541; July 1996), approved when this work was accepted for publication in abstract form (Circulation. 1996;94[suppl I]:1-49.), in these families to a 27-cM region on chromosome 2q31-q32, with a maximum lod score of 3.87 associated with markers D2S350 and D2S364. CONCLUSIONS: Cosegregation of this region with disease in different ethnic groups suggests that we mapped an important locus in familial PPH. Careful study of additional families and sporadic cases will be required to confirm this localization of PPH1 and characterize its overall role.

Adolescent↗

PubMed1997

Effects of long-term infusion of prostacyclin (epoprostenol) on echocardiographic measures of right ventricular structure and function in primary pulmonary hypertension. Primary Pulmonary Hypertension Study Group.

BACKGROUND: Right heart failure is an important cause of morbidity and mortality in primary pulmonary hypertension. In a recent prospective, randomized study of severely symptomatic patients, treatment with prostacyclin (epoprostenol) produced improvements in hemodynamics, quality of life, and survival. This article describes the echocardiographic characteristics of participants in this trial; the relationship of echocardiographic variables to hemodynamic parameters, exercise capacity, and quality of life; and the echocardiographic changes associated with prostacyclin therapy. METHODS AND RESULTS: The 81 patients enrolled in this multicenter trial were randomized to treatment with a long-term infusion of prostacyclin in addition to conventional therapy (n = 41) or conventional therapy alone (n = 40) for 12 weeks. Echocardiograms and assessments of hemodynamics, exercise capacity, and quality of life were performed before and after the treatment phase. On baseline evaluation, patients had marked right ventricular dilatation and dysfunction, abnormal septal curvature, and significant tricuspid regurgitation with a high regurgitant velocity. Pericardial effusions were common. More pronounced abnormalities in right heart structure and function were associated with higher pulmonary arterial and mean right atrial pressures, lower cardiac index, and impaired exercise capacity but had no predictable relationship to quality-of-life indicators. The 12-week infusion of prostacyclin had beneficial effects on right ventricular size, curvature of the interventricular septum, and maximal tricuspid regurgitant jet velocity. CONCLUSIONS: The echocardiographic manifestations of severe primary pulmonary hypertension reflect abnormalities in hemodynamics and exercise capacity. Prostacyclin has beneficial effects on right heart structure and function that may contribute to the clinical improvement and prolonged survival observed with this drug.

Adult↗

PubMed1997

Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin.

Our ultimate goal in treating patients is to improve their quality of life and to increase survival. The optimal treatment for primary pulmonary hypertension will continue to change as our understanding of its causes improves and as progress is made in lung transplantation. There is no one best treatment for all patients. Optimal medical and surgical treatment must be tailored to the individual with changes in therapeutic regimens based on serial evaluations. Quality of life and survival have improved with current treatments and the future should offer additional therapies-inhaled nitric oxide, endothelin receptor blockers, and other modulators of the pulmonary vascular bed-to improve further the treatment of this disease. In conclusion, although primary pulmonary hypertension, if untreated, is most often a rapidly progressive and fatal disease, recent advances in the treatment have significantly improved the outcome for patients. Although transplantation is often considered the only definitive treatment for patients with primary pulmonary hypertension, medical treatment seems to be an effective long term palliation to successful transplantation as well as a possible alternative treatment to transplantation in selected children and adults. Quality of life and cost analyses, as well as longer follow up studies are needed to determine the best treatment for patients with primary pulmonary hypertension.

Anticoagulants↗

PubMed1997

Primary pulmonary hypertension, tissue plasminogen activator antibodies, and HLA-DQ7.

Antibodies to fibrin-bound tissue plasminogen activator (tPA) have been found in autoimmune diseases with vascular injury, such as systemic lupus erythematosus and scleroderma. The purpose of this study was to determine whether patients with primary pulmonary hypertension (PPH) have an immunogenetically determined response to fibrin-bound tPA. Antibodies to fibrin-bound tPA were determined in three patient groups: 45 adults with PPH, 41 children with PPH, and 40 children with anatomically large congenital pulmonary to systemic communications (PHT+shunt). The frequencies of the HLA class II (DRB1,3,4,5, and -DQB1) alleles in these three patient groups were compared with those of 51 healthy Caucasian control subjects. Fibrin-bound tPA antibodies were found in four of 45 (9%) adults with PPH, four of 41 (10%) children with PPH, and one of 40 (2.5%) children with PHT-shunt. HLA class II typing, which was available for seven of nine Caucasians with fibrin-bound tPA antibodies, revealed that six of seven (86%) patients typed HLA-DQ7 (DQB1*0301) and one typed HLA-DQ6. The 86% frequency of HLA-DQ7 in the antibody positive patients was significant compared with the 29% frequency in the healthy control subjects (p = 0.007, p corrected [pc] = 0.05, OR = 14.4). Of interest, these antibody-positive patients, although lacking antiphospholipid antibodies, shared an amino acid epitope, common to HLA-DQB1*06,07 and 08 subtypes, which was previously reported to be associated with the lupus anticoagulant. In conclusion, antibodies to fibrin-bound tPA and HLA-DQ7, and possibly the same epitope associated with the lupus anticoagulant, defined a small subset of children and adults with PPH.

Adolescent↗

PubMed1996

A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension.

BACKGROUND: Primary pulmonary hypertension is a progressive disease for which no treatment has been shown in a prospective, randomized trial to improve survival. METHODS: We conducted a 12-week prospective, randomized, multicenter open trial comparing the effects of the continuous intravenous infusion of epoprostenol (formerly called prostacyclin) plus conventional therapy with those of conventional therapy alone in 81 patients with severe primary pulmonary hypertension (New York Heart Association functional class III or IV). RESULTS: Exercise capacity was improved in the 41 patients treated with epoprostenol (median distance walked in six minutes, 362 m at 12 weeks vs. 315 m at base line), but it decreased in the 40 patients treated with conventional therapy alone (204 m at 12 weeks vs. 270 m at base line; P < 0.002 for the comparison of the treatment groups). Indexes of the quality of life were improved only in the epoprostenol group (P < 0.01). Hemodynamics improved at 12 weeks in the epoprostenol-treated patients. The changes in mean pulmonary-artery pressure for the epoprostenol and control groups were -8 percent and +3 percent, respectively (difference in mean change, -6.7 mm Hg; 95 percent confidence interval, -10.7 to -2.6 mm Hg; P < 0.002), and the mean changes in pulmonary vascular resistance for the epoprostenol and control groups were -21 percent and +9 percent, respectively (difference in mean change, -4.9 mm Hg/liter/min; 95 percent confidence interval, -7.6 to -2.3 mm Hg/liter/min; P < 0.001). Eight patients died during the study, all of whom had been randomly assigned to conventional therapy (P = 0.003). Serious complications included four episodes of catheter-related sepsis and one thrombotic event. CONCLUSIONS: As compared with conventional therapy, the continuous intravenous infusion of epoprostenol produced symptomatic and hemodynamic improvement, as well as improved survival in patients with severe primary pulmonary hypertension.

Adult↗

PubMed1996

Primary pulmonary hypertension: immunogenetic response to high-mobility group (HMG) proteins and histone.

HLA class II alleles (DNA typing) and antibodies to HMG-1,2,14,17 proteins and H1 histone were determined in three predominantly Caucasian groups of patients with pulmonary hypertension (PHT). Forty-four adults had primary pulmonary hypertension (PPH), 42 children had PPH, and 41 children had PHT associated with anatomically large congenital pulmonary to systemic shunts (PHT + shunt). The HLA class II alleles in the Caucasian patients were compared with those of 51 healthy Caucasian controls. Eight (18%) of 44 sera from adults with PPH bound HMG-14 and 23 (52%) bound H1. None of 42 sera from children with PPH bound either HMG-14/17 or HMG-1/2, whereas four (10%) bound H1. In the PHT + shunt group of 41 children, two (5%) bound HMG-14, one (3%) bound HMG-17, four (10%) bound HMG-1 and/or HMG-2, and six (15%) bound H1. Among the 12 HMG antibody-positive patients, HLA-DQ6 was present in nine of 10 HLA typed patients (six PPH adults and three PHT + shunt children), seven of whom had antibodies to HMG-14 and one to HMG-17. The 100% frequency of HLA-DQ6 in seven Caucasian patients with antibodies to HMG-14/17 was statistically significant when compared with the 41% frequency of -DQ6 present in 51 healthy Caucasian controls (pc = 0.027, pc = Bonferroni correction, OR = 21.3). In contrast, when compared with controls, 25 patients with PPH and anti-H1 antibodies (21 adults and four children) had increased frequencies of HLA-DQ7 and -DR5 (60% versus 29%, P = 0.010, OR = 3.6 and 48% versus 22%, P = 0.018, OR = 3.4), which were not significant after correction. In essence, antibodies to HMG-14 and to H1 proteins were present predominantly in adults with PPH, suggesting that the pattern of response to HMG-14/17 was similar to that previously reported in systemic lupus erythematosus (SLE) and drug-induced autoimmunity. This is the first report of an association between autoantibodies directed against HMG and H1 with immunogenetic markers. These data suggest that a subset of patients with PPH may have an autoimmune disease.

Adolescent↗

PubMed1996

Diagnosis and treatment of pulmonary artery hypertension.

It is intellectually unsatisfying for physicians to admit that a group of patients remain for whom no cure is available in modern medicine. Despite our inability to cure pulmonary artery hypertension, therapeutic medical and surgical advances over the past decade have resulted in significant improvements in the outcome for children with various forms of pulmonary hypertension. This review discusses the work-up and evaluation of a child who presents with pulmonary artery hypertension and discusses recent therapeutic advances. The roles of anticoagulation, vasodilator therapy (including inhaled nitric oxide and chronic intravenous prostacyclin), and transplantation are discussed. These therapeutic modalities have improved quality of life, exercise capacity, and pulmonary hemodynamics as well as long-term survival for children with pulmonary hypertension.

Child↗

PubMed1996

Quantitative three dimensional echocardiography in patients with pulmonary hypertension and compressed left ventricles: comparison with cross sectional echocardiography and magnetic resonance imaging.

OBJECTIVE: To evaluate the accuracy of quantitative three dimensional echocardiography in patients with deformed left ventricles. DESIGN: Three dimensional and cross sectional echocardiographic estimates of left ventricular volume and ejection fraction were prospectively compared to those obtained from magnetic resonance imaging. SETTING: Echocardiography laboratory of a university hospital. PATIENTS: 26 patients (9 months to 42 years, median age 11 years) with pulmonary hypertension and fixed reversal of normal interventricular septal curvature. MAIN OUTCOME MEASURES: Left ventricular end diastolic and end systolic volumes and ejection fraction. RESULTS: Three dimensional echocardiographic comparison to magnetic resonance imaging (MRI) yielded r values of 0.94 and 0.87 with a bias of -6.9 (SD 6.9) ml and -16 (11.2) ml for systolic and diastolic volumes respectively. Inter-observer variability was minimal (8.3% and 7.6% respectively). Cross sectional echocardiography gave correlation coefficients of 0.62 and 0.80 and bias of 3.1 (14.1) ml and 16.3 (18.3) ml for systolic and diastolic volumes respectively. Ejection fraction by three dimensional echocardiography also had closer agreement with MRI (bias = 1.1 (7.7)%) than cross sectional echocardiography (bias = 4.4 (13.9)%). CONCLUSIONS: Three dimensional echocardiography provides reliable estimates of left ventricular volumes and ejection fraction, comparable to magnetic resonance imaging in pulmonary hypertension patients with compressed ventricular geometry. Because it eliminates the need for geometric assumptions it shows closer agreement with magnetic resonance imaging in that setting than cross sectional echocardiography.

Adolescent↗

PubMed1996

Primary pulmonary hypertension in HIV infection: an outcome determined by particular HLA class II alleles.

Primary pulmonary hypertension (PPH) may have an autoimmune basis that is influenced by host immunogenetics. The pathogenesis of primary pulmonary hypertension in human immunodeficiency virus (HIV) infection is unclear. The objective of this study was to determine whether patients with PPH and HIV infection have distinctive immunogenetic profiles. Ten racially mixed HIV-infected patients with PPH were typed for human leukocyte antigen (HLA) class II (DRB1, 3, 4, 5 and DQB1) by DNA-PCR sequence-specific oligonucleotide probes. Results were compared with two control groups: 128 HIV-negative Caucasians and a previously reported group of 97 HIV-positive, racially mixed control subjects. In those with PPH, there was a significantly increased frequency of HLA-DR6 (-DRB1*1301/2 subtypes) and of HLA-DR52 (DRB3*0301 subtype). These findings suggest that HIV-associated PPH reflects a host response to HIV-1 determined by one or more HLA-DR alleles located within the major histocompatibility complex. The same HLA-DR6 subtype found at increased frequency in our patients has previously been associated with the development of a CD8 lymphocytic host response to HIV-1, termed diffuse infiltrative lymphocytosis syndrome (DILS), which resembles autoimmune Sjogren's disease and is associated with prolonged survival. Together, these findings suggest that HIV-positive PPH may represent a clinical outcome that has similarities with that resulting from the immunogenetically determined host response present in DILS.

Adult↗

PubMed1995

Blade balloon atrial septostomy in patients with severe primary pulmonary hypertension.

BACKGROUND: Patients with severe primary pulmonary hypertension have a poor prognosis, but those with a patent foramen ovale may survive longer. A few reports of clinical improvement after blade balloon atrial septostomy in patients with severe pulmonary vascular disease have appeared. The purpose of this study was to systematically evaluate the effects of blade balloon atrial septostomy on clinical signs and symptoms, hemodynamics, and survival in patients with severe primary pulmonary hypertension. METHODS AND RESULTS: Blade balloon atrial septostomy was performed on 15 children and young adults with severe primary pulmonary hypertension. Despite maximal medical therapy, prior to septostomy all patients had recurrent syncope and 8 had severe right heart failure. Thirteen patients survived the procedure. After blade balloon atrial septostomy, no patient experienced further syncope, and signs and symptoms of right heart failure improved in all New York Heart Association Class IV patients. Within 24 hours after the procedure and at follow-up catheterization 7 to 27 months after septostomy, there was a significant increase in cardiac index, resulting in an increase in systemic oxygen transport. There was improved long-term survival in the 13 patients who survived blade balloon atrial septostomy compared with similar groups of primary pulmonary hypertension patients who received standard therapy (P < .05). CONCLUSIONS: Blade balloon atrial septostomy resulted in clinical and hemodynamic improvement and improved survival in selected patients with severe primary pulmonary hypertension.

Adult↗

PubMed1994

Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin.

OBJECTIVE: To evaluate the effects of long-term-intravenous infusion of prostacyclin on exercise capacity, hemodynamics, and survival in patients with primary pulmonary hypertension. DESIGN: Open, multicenter, uncontrolled trial. SETTING: Four referral centers. PATIENTS: 18 patients with primary pulmonary hypertension: 1 New York Heart Association (NYHA) class II patient, 13 NYHA class III patients, and 4 NYHA class IV patients. INTERVENTIONS: Continuous intravenous prostacyclin administered by portable infusion pumps. All patients were treated with anticoagulant agents. MEASUREMENTS AND MAIN RESULTS: With the 6-minute walk used to evaluate exercise capacity, patients could walk on average more than 100 meters farther after prostacyclin therapy was initiated (distance at 6 months, 370 +/- 119 meters compared with 264 +/- 160 meters at baseline; P < 0.001; distance at 18 months, 408 +/- 138 meters; P = 0.02 compared with baseline). Hemodynamics were improved at 6 months: The cardiac index increased 18% (95% CI, 0.1% to 36.7%; P = 0.02), and mean pulmonary artery pressure and total pulmonary resistance decreased 9% (CI, 1.4% to 15.7%; P = 0.03) and 26% (CI, 6.1% to 46.3%; P = 0.02), respectively, compared with baseline. The improvements in cardiac index and total pulmonary resistance were maintained at 12 months (27% increase [CI, 1.3% to 51.9%; P = 0.05] and 32% decrease [CI, 9.7% to 53.6%; P = 0.02] compared with baseline, respectively). Survival was improved in NYHA class III and IV patients who received continuous prostacyclin (n = 17; follow-up, 37 to 69 months) when compared with historical controls who received standard therapy (National Institutes of Health Primary Pulmonary Hypertension Registry, n = 31, P = 0.045). Kaplan-Meier estimates of 1-, 2-, and 3-year survival rates for the patients treated with prostacyclin were 86.9%, 72.4%, and 63.3%, respectively, compared with 77.4%, 51.6%, and 40.6% for the historical control group (hazard ratio, 2.9 [CI, 1.0 to 8.0; P = 0.045]). Serious complications attributable to the drug and delivery system included two deaths and seven episodes of nonfatal sepsis in three patients. CONCLUSIONS: Continuous intravenous prostacyclin resulted in sustained clinical and hemodynamic improvement and probably in improved survival in patients with severe primary pulmonary hypertension. Despite potentially serious complications, long-term prostacyclin may be especially helpful in seriously ill patients awaiting transplantation.

Adult↗

PubMed1994

Estimation of pulmonary artery pressure in patients with primary pulmonary hypertension by quantitative analysis of magnetic resonance images.

The use of magnetic resonance (MR) images for estimating mean pulmonary artery pressure (PAP) was tested by comparing main pulmonary artery (MPA) and middescending thoracic aorta (AO) caliber in 12 patients with primary pulmonary hypertension (PPH) with measurements made in eight other patients who were observed for diseases other than heart disease (controls). The ratio MPA/AO and the ratios of vessel caliber normalized to body surface area (MPAI and AOI, respectively) were computed. The PAP was obtained in all PPH patients and compared with caliber measurements. The PPH MPA (3.6 +/- 0.8 cm) was significantly larger than the control MPA (2.9 +/- 0.3 cm, p = 0.02); the PPH MPAI (2.8 +/- 0.7 cm/M2) was significantly greater than the control MPA (1.7 +/- 0.2 cm/M2, p < 0.0001). Control AO (2.2 +/- 0.3 cm) was significantly greater than PPH AO (1.6 +/- 0.4 cm, p < 0.0001); there was no significant difference between control AOI (1.3 +/- 0.2 cm/M2) and PPH AOI (1.2 +/- 0.2 cm/M2, p = 0.25). The PPH MPA/AO (2.3 +/- 0.6) was significantly greater than the control MPA/AO (1.3 +/- 0.1, p < 0.0001); overlap between MPA in the two groups was eliminated by indexing values to AO caliber (MPA/AO). Among PPH patients there was strong correlation between PAP and MPA/AO (PAP = 24 x MPA/AO + 3.7, r = 0.7, p < 0.01). Increased MPA/AO denotes the presence of pulmonary hypertension and may be used to estimate PAP.

Adult↗

PubMed1993

Estimation of right ventricular mass in normal subjects and in patients with primary pulmonary hypertension by nuclear magnetic resonance imaging.

OBJECTIVES: This study was designed to test the accuracy of nuclear magnetic resonance (NMR) imaging as a noninvasive technique for estimating right ventricular mass in normal subjects and in patients with primary pulmonary hypertension. BACKGROUND: An accurate means of noninvasively estimating right ventricular mass may allow better characterization of the degree of right-sided pressure or volume overload caused by underlying cardiac or pulmonary diseases. METHODS: End-diastolic short-axis electrocardiogram (ECG)-gated spin echo NMR images of the heart were obtained in vivo in 13 patients with primary pulmonary hypertension and 10 normal adult volunteers. Both right and left ventricular mass were computed by summing the myocardial slice volumes over all slices spanning the myocardium and multiplying by myocardial density. This technique of myocardial mass determination was verified by imaging 10 calf hearts and comparing the NMR-determined right and left myocardial mass with the actual mass determined by weighing the right and left ventricles. RESULTS: In the calf heart study, an excellent correlation was obtained between the directly measured ventricular mass and the NMR-calculated mass, for both the right and the left ventricle. Patients with primary pulmonary hypertension had an elevated right ventricular mass index compared with that of normal subjects (62.69 +/- 8.72 g/m2 vs. 23.32 +/- 1.36 g/m2, p < 0.0005). There was no significant difference in left ventricular mass index between the two groups. Both mean intraobserver and inter-observer variability in myocardial mass determination were low. Linear regression analysis between right ventricular mass index and mean pulmonary artery pressure was significant (r = 0.75, p < 0.003). CONCLUSIONS: Electrocardiogram-gated spin echo NMR imaging of the heart may be used for quantitating right ventricular mass in normal subjects and in patients with primary pulmonary hypertension, in whom it may also provide an alternative noninvasive technique for estimating mean pulmonary artery pressure.

Adolescent↗

PubMed1992

Direct quantitation of right and left ventricular volumes with nuclear magnetic resonance imaging in patients with primary pulmonary hypertension.

To test the utility of electrocardiographically gated spin echo nuclear magnetic resonance (NMR) imaging in quantitating right and left ventricular volumes and function in patients with primary pulmonary hypertension, right and left ventricular end-diastolic and end-systolic volumes, stroke volumes and ejection fractions were determined in 11 patients with primary pulmonary hypertension and in 10 subjects with normal echocardiographic findings. Ventricular chamber volumes were computed by summing the ventricular chamber volumes of each NMR slice at end-diastole and end-systole. This technique was verified by comparison of results obtained by this method and with the water displacement volumes of eight water-filled latex balloons and ventricular casts of eight excised bovine hearts. In the patients with primary pulmonary hypertension, right ventricular volume indexes were 121 +/- 45 ml/m2 at end-diastole and 70.1 +/- 41.6 ml/m2 at end-systole; both values were significantly greater than values in the normal subjects (67.9 +/- 13.4 and 27.9 +/- 7.5 ml/m2, respectively). Left ventricular end-diastolic volume index was significantly less in the patients (44.9 +/- 9.7 ml/m2) than in the normal subjects (68.9 +/- 13.1 ml/m2). There was no significant difference in left ventricular end-systolic volume between the two groups (24.4 +/- 8.6 and 27.1 +/- 7.8 ml/m2, respectively). Right and left ventricular ejection fractions in the patients with primary pulmonary hypertension (0.43 +/- 0.21 and 0.46 +/- 0.15, respectively) were significantly less than values in normal subjects (0.59 +/- 0.09 and 0.6 +/- 0.11, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Evidence for the association of unexplained pulmonary hypertension in children with the major histocompatibility complex.

BACKGROUND: A link between primary pulmonary hypertension (PPH) and autoimmune disorders has been postulated. To investigate this relation, we performed immunofluorescent antinuclear antibody tests (ANA) and serological human leukocyte antigen (HLA)-A, B, C, DR, and DQ typing on two groups of Caucasian children with unexplained pulmonary hypertension (PHT) and their parents. METHODS AND RESULTS: Group 1 consisted of 17 children with PPH including two patients with familial PPH and three patients with trivial congenital pulmonary to systemic communications. Group 2 consisted of 13 children with advanced PHT and anatomically large congenital pulmonary to systemic communications (PHT + shunt). Both groups had comparably severe pulmonary vascular disease documented by cardiac catheterization. The following statistically significant data (p less than 0.05) were obtained when the study groups were compared with those published for normal controls. Although positive ANAs and varying titers of autoantibodies were found in both groups of children and mothers (not fathers), +ANAs were only significant for the maternal groups. The PPH (group 1) children had increased frequencies of HLA-DR3, DRw52, and DQw2 and decreased DR5, whereas the group 2 (PHT + shunt) children (also their parents) had no statistically significant alterations in any of the DR or DQ alleles. The PPH mothers had decreased DQw3, an allele in linkage disequilibrium with DR5. CONCLUSIONS: These immunogenetic data suggest that childhood PPH appears to be associated with the major histocompatibility complex alleles HLA-DR3, DRw52, and DQw2. This newly found correlation of juvenile PPH with these alleles adds this disease to the DR3+ group of autoimmune diseases. Further studies are needed to determine whether there is also an immunological or autoimmune component in some children with PHT + shunt lesions because this group lacked an HLA association.

Adult↗

PubMed1992

Familial pulmonary hypertension: immunogenetic findings in four Caucasian kindreds.

A postulated association between primary pulmonary hypertension (PPH) and autoimmune diseases prompted this study. To see if autoantibodies and an association with the major histocompatibility locus (MHC) accompany the familial form of pulmonary hypertension (PHT), we determined human leukocyte antigen (HLA)-class I (A,B,C) and HLA-class II (DR,DQ) typing serologically, serum immunoglobulin (Ig) isotypes, and antinuclear (ANA)-autoantibodies in three families in which more than one member had PPH (FPPH) and in a fourth family with PPH and PHT associated with congenital heart disease. The three FPPH families had 15 PPH + members, eight (in whom the alleles were determined or could be inferred) typed for HLA-DRw52 and seven for HLA-DR3,DRw52,DQw2. These three families each had one PPH+,DR3+ member, with an immunoglobulin isotype deficiency, one with IgA and two with mild IgG. The fourth family differed in that both the patient and asymptomatic relatives had varying autoantibodies and different HLA associations. This family had an anti-centromere+ child with PHT and a congenital heart lesion, a mother who died of PPH, and asymptomatic ANA+ relatives (father anti-Sm+/anti-RNP+; autoantibodies unknown in fraternal twin sister and in maternal grandmother). HLA typing showed that the proband and her fraternal twin sister received DR5,DRw52,DQw3 from their father whereas the proband received DR4,DRw53,DQw3 from the mother and her sister received DR2,DQw1. In summary, three FPPH families had multiple PPH+ members who lacked autoantibodies and typed for HLA-DR3,DRw52,DQw2, whereas a fourth family with familial PHT had PHT+ and PHT- members with autoantibodies and different HLA associations.

Adolescent↗

PubMed1991

Survival in patients with primary pulmonary hypertension. Results from a national prospective registry.

OBJECTIVE: To characterize mortality in persons diagnosed with primary pulmonary hypertension and to investigate factors associated with survival. DESIGN: Registry with prospective follow-up. SETTING: Thirty-two clinical centers in the United States participating in the Patient Registry for the Characterization of Primary Pulmonary Hypertension supported by the National Heart, Lung, and Blood Institute. PATIENTS: Patients (194) diagnosed at clinical centers between 1 July 1981 and 31 December 1985 and followed through 8 August 1988. MEASUREMENTS: At diagnosis, measurements of hemodynamic variables, pulmonary function, and gas exchange variables were taken in addition to information on demographic variables, medical history, and life-style. Patients were followed for survival at 6-month intervals. MAIN RESULTS: The estimated median survival of these patients was 2.8 years (95% Cl, 1.9 to 3.7 years). Estimated single-year survival rates were as follows: at 1 year, 68% (Cl, 61% to 75%); at 3 years, 48% (Cl, 41% to 55%); and at 5 years, 34% (Cl, 24% to 44%). Variables associated with poor survival included a New York Heart Association (NYHA) functional class of III or IV, presence of Raynaud phenomenon, elevated mean right atrial pressure, elevated mean pulmonary artery pressure, decreased cardiac index, and decreased diffusing capacity for carbon monoxide (DLCO). Drug therapy at entry or discharge was not associated with survival duration. CONCLUSIONS: Mortality was most closely associated with right ventricular hemodynamic function and can be characterized by means of an equation using three variables: mean pulmonary artery pressure, mean right atrial pressure, and cardiac index. Such an equation, once validated prospectively, could be used as an adjunct in planning treatment strategies and allocating medical resources.

Adult↗

PubMed1991

Hemodynamic correlates of exercise function in patients with primary pulmonary hypertension.

The purpose of this investigation was to study the hemodynamic correlates of exercise function in patients with primary pulmonary hypertension and to further define the role of exercise testing in the evaluation of these individuals. Data from the progressive exercise tests and subsequent cardiac catheterization in 16 consecutive patients, aged 16.9 +/- 10.4 years (range 6 to 35), with primary pulmonary hypertension were prospectively collected and analyzed. Exercise capacity averaged 40 +/- 36% (range 0 to 117%) of that predicted for age, height and gender. Statistically significant correlations existed between exercise capacity and 10 invasively measured hemodynamic variables. Mean right atrial pressure, a variable previously noted to be one of the best predictors of survival in patients with primary pulmonary hypertension, correlated best with exercise capacity (r = -0.83, p less than 0.0001). Exercise capacity greater than 75% of the predicted value identified the two patients who had a positive response to acute pulmonary vasodilator drug testing. Poor exercise capacity (less than 10% of the predicted value) identified the three patients who died during or soon after cardiac catheterization. The ability of exercise testing to identify patients at high risk for cardiac catheterization was superior to that of other noninvasive variables. Results of exercise testing may help guide decisions regarding the optimal timing of heart-lung or single lung transplantation.

Adolescent↗