The 6-min walk test (6MW) as an efficacy endpoint in pulmonary arterial hypertension clinical trials: demonstration of a ceiling effect.

BACKGROUND: PAH trials traditionally use 6MW as the primary endpoint. Concerns regarding a "ceiling effect" masking efficacy have led to exclusion of patients with milder disease from most trials (BL 6MW>450 m). STRIDE I evaluated the selective endothelin A receptor antagonist, sitaxsentan (SITAX), in a 12-week randomized, double-blind, trial (178 patients) employing placebo (PBO), 100 mg or 300 mg SITAX orally once daily in PAH and included patients with NYHA class II, congenital heart disease and a BL 6MW>450 m, groups often excluded from previous trials. METHODS: We analyzed 6MW effects For All Pts (intention-to treat) and those meeting Traditional enrollment criteria, defined as patients with NYHA class III or IV and 6MW< or =450 m at BL with idiopathic PAH or PAH related to connective tissue disease. The 100 mg and 300 mg SITAX arms are pooled based on similar treatment effects on 6MW. CONCLUSION: Existence of a "ceiling effect" is supported by these data. The magnitude of the treatment effect and statistical power when using 6MW as the endpoint. Comparisons between PAH trials that do not adjust for the effects of differing enrollment criteria require caution.

Secondary pulmonary hypertension--diagnosis and management.

Secondary pulmonary hypertension (SPHtn) is generally attributable to abnormalities in structure or function of the heart or lung parenchyma. While often defined as a physiologic parameter, pulmonary hypertension (PHtn) can be a major contributor to death and disability in cardiopulmonary diseases. Both detection and management are a challenge. We will review the pathophysiology, diagnostic tools, and treatment strategies in SPHtn with an emphasis on cor pulmonale associated with chronic obstructive pulmonary disease (COPD), pulmonary vasculopathies, and pulmonary embolus. The pathophysiology and common etiologies of SPHtn can be divided into three major categories: (1) elevated pulmonary venous pressure (LV failure and mitral valve disease), (2) pulmonary vascular occlusive disease with or without pulmonary parenchymal disease (pulmonary emboli, COPD, connective tissue diseases), and (3) hypoxemia (sleep apnea). The echo-Doppler is a simple cost-effective tool for detecting PHtn, evaluating right ventricular function, and distinguishing common etiologies such as abnormal systolic and diastolic left ventricular function and mitral valve disease. The ventilation-perfusion radionuclide scan can be used to exclude thromboembolic PHtn, but a helical computer tomography with contrast or pulmonary angiography are necessary to distinguish patients that may benefit from a pulmonary thromboendarterectomy. The six minute walk oxygen saturation test is useful as a quantitative measure of functional capacity, prognosis, response to therapy, and oxygen requirement. Treatment strategies in cor pulmonale are tailored to the specific diagnosis, but generally include proper nutrition, exercise, oxygen supplementation, medications such as digoxin, diuretics, anti-coagulation, and pulmonary vasodilator therapy in selected patients.

Lung and heart-lung transplant practice patterns in pulmonary hypertension centers.

BACKGROUND: Transplant practice patterns for pulmonary hypertension in the epoprostenol era are unknown. METHODS: Thirty-five centers in North America, Europe, and Israel were surveyed regarding practice patterns for lung and heart-lung transplant. RESULTS: New York Heart Association class and distance on a 6-minute walk were considered most useful for deciding who to refer for listing. Patients with New York Heart Association class I to II were referred for listing in 26% of centers, while 57% were classified as New York Heart Association class III or greater after epoprostenol failure. Twenty-nine of the 35 centers had transplant programs that performed approximately 75% of the International Registry volume annually. A double lung transplant was preferred by 83% of centers and heart-lung transplant in the remaining centers. The wait time for lung transplant averaged 16.8 months (range 4-36) and for heart-lung transplant averaged 21.3 months (range 6-36) and was significantly longer in the United States. The mean maximum age for heart-lung transplant was 51.4 years (range 35-65), double lung transplant 58.3 years (range 45-65), and single lung transplant 63.1 years (range 50-70). Fifty-three percent of centers transplant New York Heart Association class III or IV patients, 26% class IIIb-IV, and 21% only class IV. Eighty percent of centers use a transplant hold status. Major unqualified exclusions were hepatitis in 38%, 1 or more hepatic (90%) or renal (100%) criteria, smoking 97%, and obesity in 93%. CONCLUSIONS: Physicians and patients should be aware of the considerable variability in practice patterns for transplantation in pulmonary hypertension, despite published guidelines.

Usefulness of visceral obesity (waist/hip ratio) in predicting vascular endothelial function in healthy overweight adults.

Vascular endothelial dysfunction (VED) is associated with obesity; however, its etiology remains controversial. By determining the predictors of fasting and postprandial endothelial function in overweight adults without other cardiovascular risk factors, we were able to investigate novel mechanisms directly linking obesity to VED. Thirty-two healthy adults (body mass index [BMI] > or =27 kg/m(2)) underwent determination of fasting low-density lipoprotein (LDL) particle size, high sensitivity C-reactive protein levels, anthropometric measurements, and endothelial function by flow-mediated dilation (FMD) of the brachial artery. Postprandial lipemia and FMD were measured 4 hours after ingestion of a high-fat meal. Blood pressures and fasting levels of lipoproteins, glucose, insulin, and fatty acids were within normal limits in all subjects. An abdominal fat pattern, as determined by an increased waist/hip ratio (WHR), was the sole significant predictor of FMD (r = -0.58, p = 0.001), despite no significant correlation between whole body obesity (BMI) and FMD. At comparable levels of BMI, obese subjects with a WHR > or =0.85 had a significantly blunted FMD compared with those with a WHR <0.85 (3.93 +/- 2.85% vs 8.34 +/- 5.47%, p = 0.016). Traditional coronary risk factors, C-reactive protein, postprandial lipemia, and LDL particle size did not predict FMD. We found no appreciable alteration in the postprandial state from fasting FMD (6.31 +/- 4.62% vs 6.25 +/- 5.47%, p = 0.95). The same results were found when women were analyzed alone. Increased abdominal adiposity determined by a simple WHR is a strong independent predictor of VED even in healthy overweight adults; this is a finding unexplained by alterations in conventional risk factors, systemic inflammation, or the atherogenic lipoprotein pattern.

Association between self-reported physical activity and vascular reactivity in postmenopausal women.

Short-term exercise training has been associated with improved endothelial-dependent vasodilation, but the impact of long-term habitual physical activity on vascular reactivity is not established. We studied the correlation between self-reported, habitual physical activity and vasoreactivity in non-smoking, non-diabetic, postmenopausal women (n=34, mean age 65.6+/-7.4 years). Vasoreactivity was evaluated by the percentage and absolute change in brachial artery diameter in response to reactive hyperemia induced by occlusion-release, and in response to cold pressor testing (CPT). Habitual physical activity was assessed by a standardized questionnaire based on participant recall. Our results indicate that 64.7% of the women were exercising-to-sweat > or =1x/week, 4.8 flights of stairs were climbed/day, 5.0 city blocks were walked/day and 29.4% participated in moderately physically demanding daily activity. There was a significant association between the number of city blocks walked daily and exercising-to-sweat > or =1x/week with brachial artery percentage and absolute change to CPT (P<0.05). Women who reported a moderately physically demanding daily activity had a significantly greater brachial reactivity percentage change in response to CPT compared with those performing less demanding daily activity (2.0+/-3.6 versus 1.4+/-7.0%, P<0.05). The response to reactive hyperemia was also greater in those women reporting moderately physically demanding daily activity compared to less active women (6.5+/-5.4 versus 5.8+/-5.9%, P=n.s.), but this did not reach statistical significance. Stepwise, multivariate analysis adjusting for body mass index and HDL-cholesterol eliminated the association between physical activity and brachial reactivity in response to CPT, suggesting that physical activity may affect vasoreactivity via these mechanisms. This study suggests that moderate levels of self-reported physical activity are associated with a greater brachial reactivity in response to CPT and supports the recommendation that moderate intensity physical activity may be cardioprotective in postmenopausal women.

Unexplained exertional limitation: characterization of patients with a mitochondrial myopathy.

Exercise intolerance is a common complaint, the cause of which often remains elusive after a comprehensive evaluation. In this report, we describe 28 patients with unexplained dyspnea or exertional limitation secondary to biopsy-proven mitochondrial myopathies. Patients were prospectively identified from a multidisciplinary dyspnea clinic at a tertiary referral center. All patients were without underlying pulmonary, cardiac, or other neuromuscular disorders. Patients underwent history, physical examination, complete pulmonary function testing, respiratory muscle testing, cardiopulmonary exercise testing, and muscle biopsy. Results were compared with a group of normal control subjects. The estimated period prevalence was 8.5% (28 of 331). Spirometry, lung volumes, and gas exchange were normal in patients and control subjects. Compared with control subjects, the patient group demonstrated decreased exercise capacity (maximum achieved V O(2) 67 versus 104% predicted; p < 0.0001) and respiratory muscle weakness (PI(max) 77 versus 115% predicted; p = 0.001). These patients have a characteristic exercise response that was hyperventilatory (peak VE/V CO(2); 55 versus 42) and hypercirculatory (maximum heart rate - baseline heart rate/V O(2)max - baseline V O(2)max; 91 versus 41) compared to control subjects. Patients stopping exercise due to dyspnea (n = 16) (as compared with muscle fatigue, n = 11) displayed weaker respiratory muscles (Pdi(max) 61 versus 115 cm H(2)O; p = 0.01) and were more likely to reach mechanical ventilatory limitation (V Emax/ MVV 0.81 versus 0.58; p = 0.02). The sensation of dyspnea was related to indices of respiratory muscle function including respiratory rate and inspiratory flow. We conclude that mitochondrial myopathies are more prevalent than previously reported. The characteristic physiological profile may be useful in the diagnostic evaluation of mitochondrial myopathy.

Abnormal brachial artery flow-mediated vasodilation in young adults with major depression.

Depressive illness in patients without traditional risk factors for coronary artery disease is associated with striking abnormalities of endothelial function and elevation of circulating markers of atherosclerosis propensity. Further studies are needed to define the mechanisms that underlie these observations.

Oxygen desaturation on the six-minute walk test and mortality in untreated primary pulmonary hypertension.

There are no reliable predictors of mortality in primary pulmonary hypertension (PPH). This study assessed whether exercise oxygen desaturation and distance achieved during a six-minute walk are associated with mortality in moderately symptomatic patients with PPH. Thirty-four patients with PPH underwent a pretreatment six-minute walk test, and an invasive haemodynamic assessment of pulmonary vasodilator reserve, to select the best treatment option (epoprostenol in 27 and nifedipine in 7). Median follow-up was 26 months (12 months for the nonsurvivors was 26%), and median survival, >46 months by Kaplan-Maier estimate. The mean+/-SD distance walked was 275+/-155 m and reduction in arterial oxygen saturation (Sa,O2) at maximal distance (deltaSa,O2) was 8.4+/-4.5%). A distance < or =300 m increased mortality risk by 2.4, and a deltaSa,O2 of > or = 10% increased mortality risk by 2.9. Only Sa,O2 at peak distance, deltaSa,O2 and pulmonary vascular resistance (PVR) were related to mortality. After adjusting for PVR, there remained a 27% increase in risk of death for each per cent decrease in Sa,O2. The six-minute walk distance and exercise oxygen saturation may be helpful in selecting patients with primary pulmonary hypertension for whom transplant listing is appropriate.

Balloon atrial septostomy in end-stage pulmonary hypertension guided by a novel intracardiac echocardiographic transducer.

Blade and balloon atrial septostomy has been used to reduce cardiopulmonary symptoms and as a bridge to lung or heart lung transplant in primary pulmonary hypertension. Due to severe right atrial dilatation and resultant loss of anatomical landmarks, the procedure is technically difficult, and the reported postprocedure mortality rate varies between 5% and 50%. Among others, marked systemic desaturation and systemic hypotension presumably secondary to an excessively large atrial septal defect have been reported as causes of postprocedure death. We report a case where a novel intracardiac catheter-based phased-array 5.5--10 MHz transducer with spectral and color-flow Doppler capabilities was used to assist a balloon atrial septostomy and to obtain hemodynamic data in a patient with end-stage pulmonary hypertension.

Electron-beam computed tomography in the diagnosis of coronary artery disease: a meta-analysis.

BACKGROUND: Electron-beam computed tomography (EBCT) is a new, noninvasive method of detecting coronary artery calcification that is being increasingly advocated as a diagnostic test for coronary artery disease (CAD). Before its clinical use is justified, however, the overall accuracy of EBCT must be better defined. OBJECTIVE: To estimate the accuracy of EBCT in diagnosing obstructive CAD. DATA SOURCES: English-language studies from January 1, 1979, through February 29, 2000, were retrieved using MEDLINE and Current Contents databases, bibliographies, and expert consultation. STUDY SELECTION: We included a study if it (1) used EBCT as a diagnostic test; (2) reported cases in absolute numbers of true-positive, false-positive, true-negative, and false-negative results; and (3) used coronary angiography as the reference standard for diagnosing obstructive CAD (defined as > or = 50% diameter stenosis). DATA EXTRACTION: Data were extracted from the included articles by 2 independent reviewers. DATA SYNTHESIS: Weighted pooled analysis and summary receiver operating characteristic (ROC) curve analysis were used to determine sensitivity and specificity rates. Results from 9 studies with 1662 subjects were included. Pooled sensitivity for EBCT was 92.3% (95% confidence interval [CI], 90.7%-94.0%) and pooled specificity was 51.2% (95% CI, 47.5%-54.9%). Maximum joint sensitivity and specificity for EBCT from its summary ROC curve was 75%. As the threshold for defining an abnormal test varied, sensitivity and specificity changed. For a threshold that resulted in a sensitivity of 90%, specificity was 54%; when sensitivity was 80%, specificity rose to 71%. CONCLUSION: The performance of EBCT as a diagnostic test for obstructive CAD is reasonable based on sensitivity and specificity rates from its summary ROC curve.

Carotid artery vasoreactivity in response to sympathetic stress correlates with coronary disease risk and is independent of wall thickness.

OBJECTIVES: We designed a study to determine the carotid artery (CA) response to sympathetic activity and to determine whether the response correlates with coronary risk and is independent of wall thickness (IMT). BACKGROUND: Brachial artery reactivity in response to wall stress correlates with coronary risk and coronary disease (CAD). The reactivity of the CA, which is susceptible to atherosclerosis, has not been evaluated. METHODS: The change in diameter of the CA (deltaCAdiam) during a cold pressor test and after nitroglycerin and IMT were measured with ultrasound in 93 men and women at average risk, high risk and with CAD. RESULTS: At 90 s during a cold pressor test average-risk subjects increased CAdiam by 7.9+/-3.3%, which was significantly less in the high-risk group (1.5+/-1.8%), and vasoconstriction occurred in the group of subjects with CAD (-6.9+/-2.7%) (p < 0.01 for comparisons). There were no differences in response to nitroglycerin. Coronary risk was an independent predictor of the %deltaCAdiam (p < 0.0001). Wall thickness, age, systolic pressure and triglycerides each correlated negatively, and high-density lipoprotein cholesterol correlated positively with %deltaCAdiam. The major variable associated with the %deltaCAdiam, was group (p = 0.0001). After adjusting for smoking, age and high-density lipoprotein cholesterol, there was no association between the %deltaCAdiam, and IMT and %deltaCAdiam, but not IMT, was predictive of groups. CONCLUSIONS: The CA response to a sympathetic stimulus is altered in the presence of coronary risk factors and CAD and appears to reflect endothelial function independent of IMT. Carotid artery reactivity may be a valuable adjunctive noninvasive method to assess coronary risk.

Potential clinical and economic effects of homocyst(e)ine lowering.

BACKGROUND: Elevated total homocyst(e)ine levels (>/=11 micromol/L) have been identified as a potential risk factor for coronary heart disease. However, the benefits expected from lowering homocyst(e)ine levels with folic acid and vitamin B(12) supplementation have yet to be demonstrated in clinical trials. SUBJECTS AND METHODS: We constructed a decision analytic model to estimate the clinical benefits and economic costs of 2 homocyst(e)ine-lowering strategies: (1) "treat all"-no screening, daily supplementation with folic acid (400 microg) and vitamin B(12) (cyanocobalamin; 500 microg) for all; (2) "screen and treat"-screening, followed by daily supplementation with folic acid and vitamin B(12) for individuals with elevated homocyst(e)ine levels. Simulated cohorts of 40-year-old men and 50-year-old women in the general population were evaluated. In the base-case analysis, we assumed that lowering elevated levels would reduce excess coronary heart disease risk by 40%; however, this assumption and others were evaluated across a broad range of potential values using sensitivity analysis. Primary outcomes were discounted costs per life-year saved. RESULTS: Although the treat-all strategy was slightly more effective overall, the screen and treat strategy resulted in a much lower cost per life-year saved ($13,600 in men and $27,500 in women) when compared with no intervention. Incremental cost-effectiveness ratios for the treat-all strategy compared with the screen and treat strategy were more than $500,000 per life-year saved in both cohorts. Sensitivity analysis showed that cost-effectiveness ratios for the screen and treat strategy remained less than $50,000 per life-year saved under several unfavorable scenarios, such as when effective homocyst(e)ine lowering was assumed to reduce the relative risk of coronary heart disease-related death by only 11% in men or 23% in women. CONCLUSIONS: Homocyst(e)ine lowering with folic acid and vitamin B(12) supplementation could result in substantial clinical benefits at reasonable costs. If homocyst-(e)ine lowering is considered, a screen and treat strategy is likely to be more cost-effective than universal supplementation. Arch Intern Med. 2000;160:3406-3412.

Usefulness of brachial artery reactivity to isometric handgrip exercise in identifying patients at risk and with coronary artery disease.

The change in brachial artery (BA) diameter after release of an occluding cuff has been used as a measure of endothelial function, to characterize atherosclerotic risk factors, and as a surrogate marker for coronary artery disease (CAD). We compared the change in BA diameter to isometric handgrip (IHG) with the occlusion release method to determine if a physiologic stress could be used to distinguish patients at risk and with CAD. BA diameter was measured by ultrasound during and after IHG, and after occlusion release in 93 subjects. At 120 seconds after release of IHG, BA diameter increased by 9.99 +/- 8.3% (p <0.001) in 26 average-risk patients, increased 1.84 +/- 5.7% in 37 high-risk patients, and decreased 3.9 +/- 5.6% in 30 patients with CAD (p = 0.0001 for trend and p < 0.01 between groups). There was a good correlation between change in BA diameter to IHG and occlusion release (r = 0.763 and p = 0.0001). The capacity for IHG and BA occlusion to characterize subjects by group was comparable with the exception of high-risk patients versus patients with CAD (80.5% for IHG vs 71.6% for occlusion and release, p = 0.086). BA response to IHG may be useful for identifying risk factors, patients at risk and with preclinical CAD, and the assessment of treatment strategies.

Reversible pulmonary hypertension in POEMS syndrome--another etiology of triggered pulmonary vasculopathy?

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome, a plasma cell dyscrasia associated with pulmonary hypertension, has been treated in the past with anticytokine strategies with a poor outcome. A patient is described who had POEMS syndrome with precapillary pulmonary hypertension and Raynaud's phenomenon, and who responded well to a short course of corticosteroids and long term nifedipine. POEMS syndrome, like anorexigens, cocaine, portal hypertension and human immunodeficiency virus infection, may be another trigger for the pulmonary vascular occlusive process found in primary pulmonary hypertension.

Analysis of CYP21 coding polymorphisms in three ethnic populations: further evidence of nonamplifying CYP21 alleles among whites.

BACKGROUND: Adrenal steroid 21-hydroxylase is essential for the synthesis of both mineralocorticoids and glucocorticoids. The gene for this enzyme, CYP21, contains several frequent coding polymorphisms. Because of its essential function in steroid synthesis, polymorphisms in this enzyme might influence a variety of disease processes. However, before disease-association studies are performed, it is important to understand the frequency of these polymorphisms among normal individuals. METHODS: Using polymerase chain reaction (PCR) with restriction enzyme digestion or size length polymorphism analysis, we measured the frequencies of the +Leu(10), Arg102Lys, and Ser268Thr polymorphisms in CYP21 in healthy whites, blacks, and Indian Americans. The subjects were all young female college students participating in a study of relative risks for cardiovascular disease in these populations. RESULTS: The frequency of each polymorphism among whites, blacks, and Indian Americans were as follows: +Leu(10), 0.55, 0.96, 0.75; Arg102, 0.63, 0.97, 0.82; and Ser268, 0.92, 0.68, 0.79, respectively. With the exception of the frequencies of the Ser268Thr polymorphism among blacks and Indian Americans, there were significantly different frequencies of each polymorphism among all groups (P<.05). Among whites, the distribution of genotypes for the +Leu(10) and Arg102Lys polymorphisms deviated significantly from expected Hardy-Weinberg values because of an excess of homozygotes. CONCLUSIONS: Among the ethnic groups, there are statistically significant differences in the frequencies of these common coding polymorphisms in CYP21 that need to be considered in disease-association studies. Deviation from Hardy-Weinberg distributions might be explained by allelic dropout during PCR, a phenomenon previously reported at this locus.

Diagnostic value of resting tricuspid regurgitation velocity and right ventricular ejection flow parameters for the detection of exercise induced pulmonary arterial hypertension.

UNLABELLED: Our objectives were to evaluate resting tricuspid regurgitation velocity (TRV) and right ventricular outflow tract velocity curve (RVOTvc) profiles as markers for development of exercise induced pulmonary arterial hypertension (ExPHT). ExPHT is an elusive cause of dyspnea and fatigue. When present, Doppler echocardiography can detect and quantify elevated pulmonary pressure. However, the characteristics and diagnostic value of resting TRV and RVOTvc indices in patients with ExPHT have not been fully addressed. The study population consisted of 52 subjects (mean age 40.5 +/- 10.9, range 22-68 years) and was divided into three subsets as follows: 1. Patients (n = 22) with overt pulmonary hypertension (PHT), 2. Patients (n = 8) with ExPHT, 3. Healthy, asymptomatic volunteers (n = 22). RVOTvc indices included: Mean and peak velocity, systolic velocity time integral (VTI); velocity time integral at peak velocity (VTImax), acceleration time; ejection time. TRV was used as an index of pulmonary artery systolic pressure. There were significant differences between normals and ExPHT for TRV, acceleration time, VTI(Vmax). TRV and VTImax were predictive of EXPHT in a logistic regression model. CONCLUSION: (1) Patients with ExPHT have distinct Doppler velocity patterns suggesting the presence of a compromised pulmonary vascular bed even with normal pulmonary pressure at rest. (2) TRV and RVOTvc indices have potential diagnostic value in the early detection of ExPHT.

Echocardiographic predictors of an adverse response to a nifedipine trial in primary pulmonary hypertension: diminished left ventricular size and leftward ventricular septal bowing.

BACKGROUND: The clinical course in primary pulmonary hypertension (PPH) is improved by calcium channel blocker therapy in those with a favorable hemodynamic response during a trial of high-dose oral nifedipine. Although trials of nifedipine are performed only in patients who demonstrate pulmonary vasodilator reserve to short-acting agents, this response does not predict the safety of nifedipine treatment, which can result in severe first-dose hypotension and death. STUDY OBJECTIVES: To identify echocardiographic parameters that predict first-dose nifedipine-induced hypotension in patients with PPH. METHODS: The pretrial echocardiograms of 23 consecutive PPH patients (mean age, 42.3 +/- 13 years; 77% female) undergoing evaluation of pulmonary vasodilator reserve with nifedipine were analyzed. Patients were classified as those who suffered first-dose nifedipine hypotension (group 1) and those who did not (group 2). Echocardiographic measures of chamber size and septal geometry in the two groups were compared. RESULTS: Five measures reflecting diminished left ventricular (LV) size and leftward ventricular septal bowing were found to be associated with nifedipine hypotension: LV transverse diameter in systole (LVDs; p = 0.007), LV transverse diameter in diastole (LVDd; p = 0.05), LV area in systole (LVAs; p = 0.009), LV area in diastole (LVAd; p = 0.03), the ratio of RV to LVAs (p = 0. 02), and leftward ventricular septal bowing (p = 0.01). The LV dimensions found to best predict nifedipine-induced hypotension were LVDs < 2.7 cm, LVDd < 4.0 cm, LVAs < 15.5 cm(2), and LVAd < 20.0 cm(2). CONCLUSIONS: Readily available echocardiographic parameters in patients with PPH are predictive of nifedipine-induced hypotension, and can be used to select patients in whom a trial of nifedipine should be avoided.

Echocardiographic features of primary pulmonary hypertension.

Primary pulmonary hypertension (PPH) is essentially a diagnosis of exclusion and usually is made late because of the nonspecific nature of the early signs and symptoms. Echocardiography is a key screening test in the diagnostic algorithm of patients with suspected PPH. The purpose of this study was to define the echocardiographic Doppler features in patients with PPH at the time of diagnosis. From 1992 to 1997, 51 patients were diagnosed with PPH at our institution. All underwent a standardized transthoracic echocardiographic examination, including a contrast study and transthoracic echocardiographic examination if indicated. Pulmonary artery systolic pressure was calculated from the tricuspid regurgitation jet. The majority of patients had pulmonary artery systolic pressure greater than 60 mm Hg (96%) associated with systolic flattening of the interventricular septum (90%), enlarged right atrium (92%) and ventricle (98%), and reduced right ventricular systolic function (76%). There was an increase in the interventricular septal thickness (>1.2 cm) in 21 (43%) of 49 patients, accompanied by a septal/posterior wall ratio greater than 1.3 in 11 (22%) of 49. Although a reduction in both left ventricular systolic and diastolic volumes was noted, global left ventricular systolic function was preserved in all patients. Mitral E/A ratio was less than 0.7 in 7 (22%) patients studied. Color Doppler revealed moderate to severe tricuspid regurgitation and pulmonic insufficiency in 41 (80%) of 51 and 16 (31%) of 51 of cases, respectively. Pericardial effusion (7 small and 1 moderate) and patent foramen ovale (n = 12) were also frequently detected. At the time of initial diagnosis, PPH is associated with secondary cardiac abnormalities in the majority of patients.