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Objectives This study was designed to identify the incidence of late complete heart block (CHB) first identified at least 48 hours post alcohol septal ablation (ASA). Background Septal reduction with ASA is a therapeutic option for patients with symptomatic hypertrophic obstructive cardiomyopathy (HCM). CHB, resulting from the septal infarct, is a known complication with a reported incidence of 9–22%. The incidence of CHB more than 48 hours post-procedure is unknown. Methods Consecutive patients who underwent ASA were analyzed and clinical characteristics associated with late CHB were assessed. Late CHB was defined as first identification of CHB more than 48 hours after ASA. Results From 2002–2013, 145 subjects underwent 168 ASA procedures and were followed for a mean of 3.2 +/− 2.3 years. The incidence of late CHB was 8.9% (15/168 ASA procedures). Heart block occurred from 48 hours to 3-years post-procedure. In a multivariable model, patients with any CHB were more likely to have had multiple ASA procedures (OR 4.14; 95% CI: 1.24, 13.9; P

Because alcohol septal ablation (ASA) for the treatment of symptomatic hypertrophic cardiomyopathy (HC) with left ventricular (LV) outflow tract (LVOT) obstruction results in a myocardial infarct of up to 10% of ventricular mass, LV systolic function could decline over time. We evaluated LV function during longitudinal follow-up in a cohort of patients who underwent ASA. We studied 145 consecutive patients with HC that underwent 167 ASA procedures from 2002 to 2011. Echocardiographic follow-up was available in 139 patients (96%). Echocardiographic indexes included LV ejection fraction (LVEF), mitral regurgitation severity, systolic anterior motion of the anterior mitral leaflet, and resting and provoked LVOT gradients. All patients had a baseline LVEF of55%. LVEF was preserved in 97.1% of patients over a mean follow-up time of 3.1±2.3 years (maximum 9.7). Mild LV systolic dysfunction was observed (LVEF range 44% to 54%) in only 4 patients. Mitral regurgitation severity improved in 67% (n=112 of 138 with complete data). Resting LVOT gradient declined from a mean of 75 to 19 mm Hg (p0.001), and provoked gradient declined from a mean of 101 to 33 mm Hg (p0.001). New York Heart Association class improved from a mean of 2.9±0.4 to 1.3±0.5 (p0.001). In conclusion, LV systolic function is only mildly reduced in a minority of patients after ASA for symptomatic HC; other echocardiographic and functional measures were significantly improved.

Objectives: The purpose of the study is to identify the predictors of clinical outcome (mortality and survival without repeat septal reduction procedures) of alcohol septal ablation for the treatme...

Objective: To evaluate the clinical utility of images acquired from rotational coronary angiographic (RA) acquisitions compared to standard “fixed” coronary angiography (SA). Background: RA is a novel angiographic modality that has been enabled by new gantry systems that allow calibrated automatic angiographic rotations and has been shown to reduce radiation and contrast exposure compared to SA. RA provides a dynamic multiple-angle perspective of the coronaries during a single contrast injection. Methods: The screening adequacy, lesion assessment, and a quantitative coronary analysis (QCA) of both SA and RA were compared by independent blinded review in 100 patients with coronary artery disease (CAD). Results: SA and RA recognize a similar total number of lesions (P = 0.61). The qualitative assessment of lesion characteristics and severity between modalities was comparable and lead to similar clinical decisions. Visualization of several vessel segments (diagonal, distal RCA, postero-lateral branches and posterior-descending) was superior with RA when compared to SA (P < 0.05). A QCA comparison (MLD, MLA, LL, % DS) revealed no difference between SA and RA. The volume of contrast (23.5 ± 3.1 mL vs. 39.4 ± 4.1; P = 0.0001), total radiation exposure (27.1 ± 4 vs. 32.1 ± 3.8 Gycm2; P = 0.002) and image acquisition time (54.3 ± 36.8 vs. 77.67 ± 49.64 sec; P = 0.003) all favored RA. Conclusion: Coronary lesion assessment, coronary screening adequacy, and QCA evaluations are comparable in SA and RA acquisition modalities in the diagnosis of CAD however RA decreases contrast volume, image acquisition time, and radiation exposure. © 2009 Wiley-Liss, Inc.

Current expert-recommended views for coronary angiography are based on heuristic experience and have not been scientifically studied. We sought to identify optimal viewing regions for first and second order vessel segments of the coronary arteries that provide optimal diagnostic value in terms of minimizing vessel foreshortening and overlap. Using orthogonal 2D images of the coronary tree, 3D models were created from which patient-specific optimal view maps (OVM) allowing quantitative assessment of vessel foreshortening and overlap were generated. Using a novel methodology that averages 3D-based optimal projection geometries, a universal OVM was created for each individual coronary vessel segment that minimized both vessel foreshortening and overlap. A universal OVM model for each coronary segment was generated based on data from 137 patients undergoing coronary angiography. We identified viewing regions for each vessel segment achieving a mean vessel foreshortening value of 5.8 +/- 3.9% for the left coronary artery (LCA) and 5.6 +/- 3.6% for the right coronary artery (RCA). The overall mean overlap values achieved were 8.7 +/- 7.9% for the LCA and 4.6 +/- 3.2% for the RCA. This scientifically-based OVM evaluation of coronary vessel segments provides the means to facilitate acquisitions during coronary angiography and interventions that minimize imaging inaccuracies related to foreshortening and overlap, improving the accuracy, efficiency, and safety of diagnostic and interventional coronary procedures.

The amount of O(2) available to tissues is essentially the product of cardiac output, [Hb], and O(2) saturation. Saturation depends on P(O2) and the O(2)Hb dissociation curve. With altitude, increased [2,3-DPG] shifts the dissociation curve rightward, but hypocapnia and alkalosis move it leftward. We determined both standard and in vivo P(50) in 5 fit subjects decompressed over 42 days in an altitude chamber to the equivalent of the Mt. Everest summit (Operation Everest II). Arterial and venous blood was sampled at five "altitudes " (P(B) = 760, 429, 347, 282, 253 mmHg), and P(O2), P(CO2), pH, O(2) saturation, [Hb] and [2,3-DPG] were measured. As reported previously, 2,3-DPG levels increased from 1.7 (P(B) = 760) to 3.8 mmol/L (P(B) = 282). Standard P(50) also increased (from 28.2 mmHg at sea level to 33.1 on the summit, p

This study was designed to identify the incidence of late complete heart block (CHB) first identified at least 48 hours post alcohol septal ablation (ASA).Septal reduction with ASA is a therapeutic option for patients with symptomatic hypertrophic obstructive cardiomyopathy (HCM). CHB, resulting from the septal infarct, is a known complication with a reported incidence of 9-22%. The incidence of CHB more than 48 hours post-procedure is unknown.Consecutive patients who underwent ASA were analyzed and clinical characteristics associated with late CHB were assessed. Late CHB was defined as first identification of CHB more than 48 hours after ASA.From 2002-2013, 145 subjects underwent 168 ASA procedures and were followed for a mean of 3.2 +/- 2.3 years. The incidence of late CHB was 8.9% (15/168 ASA procedures). Heart block occurred from 48 hours to 3-years post-procedure. In a multivariable model, patients with any CHB were more likely to have had multiple ASA procedures (OR 4.14; 95% CI: 1.24, 13.9; P 0.05) and high resting and provoked left ventricular outflow tract (LVOT) gradient assessed by catheterization (OR per 10 mmHg gradient 1.14; 95% CI: 1.0, 1.20; P 0.05). After multivariable adjustment, only a high provokable LVOT gradient remained an independent predictor of late CHB (OR per 10 mmHg gradient 1.14 [95% CI 1.02-1.29]).Late CHB is a common complication of ASA for treatment of symptomatic HCM. Post-discharge electrocardiographic surveillance for atrioventricular conduction disease should be considered after ASA, especially for those with a high provokable LVOT gradient.

The goal of this study was to determine the severity of vessel foreshortening in standard angiographic views used during percutaneous coronary intervention (PCI). Coronary angiography is limited by its two-dimensional (2D) representation of three-dimensional (3D) structures. Vessel foreshortening in angiographic images may cause errors in the assessment of lesions or the selection and placement of stents. To date, no technique has existed to quantify these 2D limitations or the performance of physicians in selecting angiographic views. Stent deployment was performed in 156 vessel segments in 149 patients. Using 3D reconstruction models of each patient's coronary tree, vessel foreshortening was measured in the actual working view used for stent deployment. A computer-generated optimal view was then identified for each vessel segment and compared to the working view. Vessel foreshortening ranged from 0 to 50% in the 156 working views used for stent deployment and varied by coronary artery and by vessel segment within each artery. In general, views of the mid circumflex artery were the most foreshortened and views of the right coronary artery were the least foreshortened. Expert-recommended views frequently resulted in more foreshortening than computer-generated optimal views, which had only 0.5% ± 1.2% foreshortening with < 2% overlap for the same 156 segments. Optimal views differed from the operator-selected working views by ≥ 10° in over 90% of vessels and frequently occurred in entirely different imaging quadrants. Vessel foreshortening occurs frequently in standard angiographic projections during stent deployment. If unrecognized by the operator, vessel foreshortening may result in suboptimal clinical results. Modifications to expert-recommended views using 3D reconstruction may improve visualization and the accuracy of stent deployment. These results highlight the limitations of 2D angiography and support the development of real-time 3D techniques to improve visualization during PCI. Catheter Cardiovasc Interv 2005;64:451–459. © 2005 Wiley-Liss, Inc.

Stent implantation results in important three-dimensional (3D) changes in arterial geometry which may be associated with adverse events. Previous attempts to quantify these 3D changes have been limited by two-dimensional techniques. Using a 3D reconstruction technique, vessel curvatures at end-diastole (ED) and end-systole (ES) were measured before and after stent placement of 100 stents (3 stent cell designs, 6 stent types). After stenting, the mean curvature at ED and ES decreased by 22 and 21%, respectively, and represents a straightening effect on the treated vessel. This effect was proportional to the amount of baseline curvature as high vessel curvature predicted more profound vessel straightening. When analyzed by stent cell design, closed-cell stents resulted in more vessel straightening than other designs (open cell or modified slotted tubes). Stent implantation resulted in the transmission of shape changes to stent ends and generated hinge points or buckling. Stent implantation creates 3D changes in arterial geometry which can be quantified using a 3D reconstruction technique.

Traditional angiography of the vasculature is limited by its 2-dimensional projection of complex 3-dimensional structures and the consequent imaging artifacts that interfere with visualization. During the last 10 years, technologies capable of minimizing the shortcomings of traditional angiography have been developed and are now in clinical use. Rotational angiography and 3-dimensional imaging are 2 of these powerful tools and, together, represent a major advance in the angiographic diagnosis and treatment of patients with coronary, cerebral, and peripheral vascular disease.

This study evaluates the safety and clinical utility of rotational angiography in the diagnosis of coronary artery disease. High-speed rotational angiography is a newly available angiographic modality that gives a dynamic multiple-angle perspective of the coronary tree during a single contrast injection. We prospectively randomized 56 patients referred for diagnostic coronary angiography to either standard or rotational angiography. Contrast and radiation utilization were compared between the two groups. The number of additional cine acquisitions needed was used to determine adequacy of the diagnostic study protocol. Rotational angiography was successfully completed in all subjects. There was a 33% reduction in contrast utilization in the rotational group as compared to the standard group (35.6 ± 12.6 vs. 52.8 ± 10.7 ml, respectively; P < 0.0001). Additionally, there was a 28% reduction in total radiation exposure in the rotational group as compared to the standard group (39.0 ± 18.5 vs. 53.9 ± 23.4 Gycm2, respectively; P = 0.01). Total whole-body radiation exposure to the primary operator was 144 mrem with rotational angiography and 170 mrem with standard angiography. Procedure time tended to be shorter for rotational angiography (353.9 ± 146.7 vs. 396.8 ± 165.8 s; P = 0.3). Rotational coronary angiography can be rapidly performed in any patient and provides a significant reduction in contrast and radiation utilization while at the same time providing adequate angiographic data to complement or replace standard coronary angiography in the evaluation of coronary artery disease. Catheter Cardiovasc Interv 2004;62:167–174. © 2004 Wiley-Liss, Inc.

Very little is known about any interaction between patent foramen ovale (PFO) and various hypercoagulable disorders that have been associated with cryptogenic stroke. Percutaneous PFO closure for secondary prevention of paradoxical thromboembolization is receiving increasing attention. Hypercoagulability may affect the potential risks and expected benefits of percutaneous PFO closure. Consecutive patients undergoing percutaneous PFO closure at a single center were screened for the presence of antiphospholipid antibodies, elevated lipoprotein(a), hyperhomocysteinemia, and dysfibrinogenemia. Sixteen of 34 patients (47%) with complete arterial hypercoagulability screening had laboratory evidence of arterial hypercoagulability. Thirteen of these patients (38%) had antiphospholipid antibodies. Antiphospholipid antibodies appear to be common in patients referred for percutaneous PFO closure for secondary prevention of systemic thromboembolic events. Thorough testing based on established recommendations is warranted. Further studies are needed regarding the interaction between PFO and various hypercoagulable disorders that have been associated with cryptogenic stroke.

Third-generation intracoronary stents allow deployment at higher pressures, possibly obviating the need for high-pressure postdilations and also possibly reducing restenosis. This study evaluated the ability of the Tristar Coronary Stent System to produce optimal stent deployment as measured by intravascular ultrasound (IVUS) and quantitative coronary angiography in 46 patients. Optimal stent deployment was defined as minimal luminal area > 80% of the average of the proximal and distal reference luminal areas. After initial deployment, 74.5% of stents met criteria for optimal stent deployment by IVUS, with an average stent expansion ratio of 89.6%. Ten stents (18.2%) were postdilated. Four patients (8.7%) had a major adverse cardiac event, one patient died, one patient had a myocardial infarction, and two patients had target vessel revascularization at 6 months. The Tristar stent system produces optimal deployment without the need for routine postdilation and results in optimal clinical outcomes.

Left ventricular pressure-volume relationships expressed as pV loops could yield important hemodynamic information in the cardiac catheterization laboratory. Many clinical situations might benefit from a quantitative assessment of left ventricular function. Potential applications of pV loops include the assessment of vasoactive and inotropic drugs, balloon valvuloplasty, coronary angioplasty, and surgical treatment of valvular heart disease. For many years the clinical use of pV loops has been hindered by logistical difficulties. The ability to merge on-line concurrent digital imaging data for computation of left ventricular volume and digital left ventricular pressure wave forms obtained from high fidelity tip-transducer angiocatheters has allowed us to develop a technique which can generate pV loops during cardiac catheterization procedures. The method offers an automated measurement of left ventricular volume independent of edge detection or an interactive technique for tracing endocardial borders by a trained operator. Illustrative case studies are included to demonstrate the potential of the method during ventricular angiographic procedures. Implementation and computational time requirements of the method are discussed. The concept and the value of pV loop generation to study left ventricular performance has been known for many years. Combining digital imaging and digital physiologic data obtained with disposable tip-transducer angiocatheters with modern networking technology, the technique can more easily be applied to catheterization procedures and could enhance invasive hemodynamic assessment of left ventricular function.

Background: Current coronary angiographic techniques display complex three-dimensional (3D) coronary structures in two dimensions (2D). We have developed a 3D reconstruction (3DR) algorithm using standard single-plane angiographic images that allows for 3D display of coronary structures. The purpose of this study was to validate our 3DR algorithm and quantify anatomic characteristics of the right coronary artery (RCA) in vivo. Methods: Accuracy and reproducibility studies were performed using 3DRs of a coronary phantom and in vivo following 3DRs in 40 patients. The anatomic features of the RCA were then quantified in 100 patients. Results: Comparison of length and bifurcation angles (BA) from the phantom to the 3DRs revealed good accuracy and correlation for both (r = 0.95 and 0.93 respectively), with diameter error of

Background —Primary pulmonary hypertension results from progressive narrowing of the precapillary pulmonary vasculature. A variety of endothelial abnormalities have been identified, including a net reduction in pulmonary clearance of the vasoconstrictor and smooth muscle mitogen endothelin-1. In many patients, net pulmonary release of endothelin-1 is observed. Chronic infusions of epoprostenol (prostacyclin) improve functional capacity, survival, and hemodynamics in patients with advanced primary pulmonary hypertension. We hypothesized that the epoprostenol infusions, as compared with conventional therapy, might alter the abnormal pulmonary endothelin-1 homeostasis. Methods and Results —Using a subset of patients from a larger randomized study comparing epoprostenol plus conventional therapy (n=11 in the present study) with conventional therapy alone (n=7 in the present study), we determined the ratio of plasma endothelin-1 levels in systemic arterial blood leaving the lung to levels in mixed venous blood entering the lung both before randomization and after 88 days of continuous therapy. There were no differences between the 2 groups before therapy, but by day 88, the epoprostenol-treated group had a greater proportion of patients (82%) with an arterial/venous ratio P Conclusions —These results suggest that continuous epoprostenol therapy may have a beneficial effect on the balance between endothelin-1 clearance and release in many patients with primary pulmonary hypertension and may provide one explanation for the salutary effect of epoprostenol in this disease.

Using quantitative RT-PCR in RNA from right ventricular (RV) endomyocardial biopsies from intact nonfailing hearts, and subjects with moderate RV failure from primary pulmonary hypertension (PPH) or idiopathic dilated cardiomyopathy (IDC), we measured expression of genes involved in regulation of contractility or hypertrophy. Gene expression was also assessed in LV (left ventricular) and RV free wall and RV endomyocardium of hearts from end-stage IDC subjects undergoing heart transplantation or from nonfailing donors. In intact failing hearts, downregulation of b 1 -receptor mRNA and protein, upregulation of atrial natriuretic peptide mRNA expression, and increased myocyte diameter indicated similar degrees of failure and hypertrophy in the IDC and PPH phenotypes. The only molecular phenotypic difference between PPH and IDC RVs was upregulation of b 2 -receptor gene expression in PPH but not IDC. The major new findings were that ( a ) both nonfailing intact and explanted human ventricular myocardium expressed substantial amounts of a -myosin heavy chain mRNA ( a -MHC, 23‐34% of total), and ( b ) in heart failure a -MHC was downregulated (by 67‐84%) and b -MHC gene expression was upregulated. We conclude that at the mRNA level nonfailing human heart expresses substantial a -MHC. In myocardial failure this alteration in gene expression of MHC isoforms, if translated into protein expression, would decrease myosin ATPase enzyme velocity and slow speed of contraction. ( J. Clin. Invest. 1997. 100:2315‐2324.) Key words: a -myosin

Pyrogenic reactions are potentially life-threatening complications caused by bacterial endotoxin. After two cardiac catheterization patients developed rigors the same day, the procedures were halted and a case control study was conducted. To identify case patients (persons with rigors 10(4) colony forming units/mL) and endotoxin (434 endotoxin units [EU]/mL]); the reprocessed cups had no live bacteria but had elevated endotoxin levels (median 2,250 EU). Exposure to contaminated glass medicine cups probably resulted in pyrogenic reactions and contributed to death in two critically ill patients.

Previous studies have indicated that native Tibetans have a larger lung capacity and better maintain arterial O2 saturation during exercise than Han ("Chinese") acclimatized lowlanders. To test if differences in ventilation or alveolar-arterial O2 gradient (A-aDO2) were responsible, we compared 10 lifelong Tibetan and 9 Han acclimatized newcomer residents of Lhasa (3658 m) at rest and during progressive exercise. Resting blood gas tensions and arterial O2 saturation in the two groups were similar. During exercise the Tibetans had lower total ventilation and higher arterial CO2 tensions than the Han (both P < 0.01) and markedly lower A-aDO2 (7 +/- 1 vs. 11 +/- 1, 13 +/- 1 vs. 18 +/- 1, and 14 +/- 1 vs. 20 +/- 1 mmHg at light, medium, and heavy workloads respectively, all P < 0.01). The Tibetans' narrower A-aDO2 compensated for their lower exercise ventilation such that arterial O2 tension and saturation were raised above acclimatized newcomer values and better maintained during exercise. We concluded that the Tibetans exhibited more efficient pulmonary gas exchange which compensated for reduced ventilation and lessened respiratory effort.

Angiotensin II causes pulmonary vasoconstriction in man and in animals, and angiotensin-converting enzyme (ACE) inhibitors have prevented the development of chronic pulmonary hypertension in animals models. Angiotensin II may contribute to lung vascular remodeling in pulmonary hypertensive disease, since cilazapril, an inhibitor of ACE, reduces pulmonary vascular medical thickening in chronically hypoxic rats with established pulmonary hypertension. Furthermore, the ACE DD genotype, which has been associated with increased circulating and tissue ACE activity, has been associated with left ventricular hypertrophy in human hypertensive disorders. The ACE DD genotype may also 'permit' a greater hypertrophic adaptation of the pressure-over-loaded right ventricle. In fact, we have shown that pulmonary hypertension patients with maintained cardiac output and less right-heart failure fall into the group with the DD genotype and that patients with a low cardiac output and more severe right-heart failure fall into the group with the non-DD genotype, supporting the hypothesis. We assessed cardiopulmonary hemodynamics in patients with primary (unexplained) pulmonary hypertension and segregated the patients based on their ACE genotype. For similar mean pulmonary artery pressures in the DD and non-DD groups, the cardiac output was substantially lower in the patients with the non-DD genotype, whereas the values for mean right atrial pressure and pulmonary vascular resistance were double when compared with the DD group. Our data show that the ACE DD genotype is prevalent in patients with severe pulmonary hypertension and is a marker of maintained right ventricular function.

The purpose of the study is to identify the predictors of clinical outcome (mortality and survival without repeat septal reduction procedures) of alcohol septal ablation for the treatment of patients with hypertrophic obstructive cardiomyopathy.Alcohol septal ablation is used for treatment of medically refractory hypertrophic obstructive cardiomyopathy patients with severe outflow tract obstruction. The existing literature is limited to single-center results, and predictors of clinical outcome after ablation have not been determined. Registry results can add important data.Hypertrophic obstructive cardiomyopathy patients (N = 874) who underwent alcohol septal ablation were enrolled. The majority (64%) had severe obstruction at rest, and the remaining had provocable obstruction. Before ablation, patients had severe dyspnea (New York Heart Association [NYHA] functional class III or IV: 78%) and/or severe angina (Canadian Cardiovascular Society angina class III or IV: 43%).Significant improvement (p0.01) occurred after ablation (~5% in NYHA functional classes III and IV, and 8 patients in Canadian Cardiovascular Society angina class III). There were 81 deaths, and survival estimates at 1, 5, and 9 years were 97%, 86%, and 74%, respectively. Left anterior descending artery dissections occurred in 8 patients and arrhythmias in 133 patients. A lower ejection fraction at baseline, a smaller number of septal arteries injected with ethanol, a larger number of ablation procedures per patient, a higher septal thickness post-ablation, and the use beta-blockers post-ablation predicted mortality.Variables that predict mortality after ablation, include baseline ejection fraction and NYHA functional class, the number of septal arteries injected with ethanol, post-ablation septal thickness, beta-blocker use, and the number of ablation procedures.

To test the hypothesis that native high-altitude residents have less beta-sympathetic and more parasympathetic tone than newcomers, we compared the effects of beta-sympathetic and parasympathetic blockade in 10 Tibetan and 9 Han acclimatized male residents of Lhasa, Tibet Autonomous Region, China (elevation 3,658 m). Each subject was studied during cycle ergometer exercise at 70, 132, and 191 W after placebo (normal saline), beta-sympathetic (propranolol, 0.2 mg/kg iv), or parasympathetic (atropine, 0.04 mg/kg iv) blockade in random order on different days. At rest, the fall in resting heart rate with propranolol and the rise with atropine were equal in Tibetan and Han subjects. During exercise, the fall in heart rate with propranolol relative to placebo values was greater in the Han than in the Tibetan group, whereas the rise in heart rate with atropine was greater in the Tibetans. Propranolol or atropine administration did not change minute ventilation per unit O2 consumption in either group. At the highest level of exercise on the placebo day, the Tibetans achieved a higher work load and level of O2 consumption than the Han subjects. Propranolol or atropine reduced O2 consumption and work load similarly in the two groups at the highest exercise level. The results supported our hypothesis that native Tibetan residents of high altitude exhibit more para-sympathetic and less beta-sympathetic tone during exercise. Neither relatively greater parasympathetic nor less sympathetic activation appeared implicated in the greater exercise capacity of Tibetans compared with that of acclimatized newcomer residents of high altitude.

Background The safety and efficacy of percutaneous closure of atrial septal defects (ASDs) is determined by several variables, including defect size, presence of adequate rim tissue, relationship to other cardiac structures, and associated congenital anomalies. Objective We sought to determine the accuracy of computed tomographic angiography (CTA) in predicting a defect’s size compared with pre-procedural transesophageal echocardiography (TEE) and to the current “gold standard” balloon sizing by intracardiac echocardiography (ICE). Methods Thirty-five consecutive patients referred for possible percutaneous closure of suspected secundum ASD were evaluated with gated multislice CTA after initial TEE screening. Axial and sagittal image planes of the ASD from the CTA multiplanar reformation (MPR) images were used to measure the defect size and surface area. Results Of the 35 patients with secundum-type ASDs, 5 subjects had disqualifying anatomy by CTA and 2 had an unsuccessful closure, resulting in a procedural success rate of 93%. Measurement of defect area by gated MPR images provided the strongest correlate to ICE balloon size. In large ASDs, TEE was less well correlated to the maximum defect size and identification of the inferior/inferoposterior rims than CTA. Conclusions Cardiac CTA is an accurate and useful technique for pre-procedural assessment of ASDs and may be superior to conventional TEE in large defects that have deficient inferior rims.

Constriction of small pulmonary arteries and arterioles and focal vascular injury are features of pulmonary hypertension. Because thromboxane A2 is both a vasoconstrictor and a potent stimulus for platelet aggregation, it may be an important mediator of pulmonary hypertension. Its effects are antagonized by prostacyclin, which is released by vascular endothelial cells. We tested the hypothesis that there may be an imbalance between the release of thromboxane A2 and prostacyclin in pulmonary hypertension, reflecting platelet activation and an abnormal response of the pulmonary vascular endothelium.We used radioimmunoassays to measure the 24-hour urinary excretion of two stable metabolites of thromboxane A2 and a metabolite of prostacyclin in 20 patients with primary pulmonary hypertension, 14 with secondary pulmonary hypertension, 9 with severe chronic obstructive pulmonary disease (COPD) but no clinical evidence of pulmonary hypertension, and 23 normal controls.The 24-hour excretion of 11-dehydro-thromboxane B2 (a stable metabolite of thromboxane A2) was increased in patients with primary pulmonary hypertension and patients with secondary pulmonary hypertension, as compared with normal controls (3224 +/- 482, 5392 +/- 1640, and 1145 +/- 221 pg per milligram of creatinine, respectively; P less than 0.05), whereas the 24-hour excretion of 2,3-dinor-6-keto-prostaglandin F1 alpha (a stable metabolite of prostacyclin) was decreased (369 +/- 106, 304 +/- 76, and 644 +/- 124 pg per milligram of creatinine, respectively; P less than 0.05). The rate of excretion of all metabolites in the patients with COPD but no clinical evidence of pulmonary hypertension was similar to that in the normal controls.An increase in the release of the vasoconstrictor thromboxane A2, suggesting the activation of platelets, occurs in both the primary and secondary forms of pulmonary hypertension. By contrast, the release of prostacyclin is depressed in these patients. Whether the imbalance in the release of these mediators is a cause or a result of pulmonary hypertension is unknown, but it may play a part in the development and maintenance of both forms of the disorder.

Type 2 diabetes mellitus (T2DM) has been associated with reduced peak exercise capacity (VO(2peak)). The causes of this impairment are not clearly established, but evidence suggests that abnormalities in cardiac function play a significant role. We hypothesized that exercise would be associated with impaired cardiac function and hemodynamics in recently diagnosed T2DM, even in the absence of clinically evident cardiovascular complications.After baseline normal echocardiography screening, 10 premenopausal women with uncomplicated T2DM (average duration of diagnosed T2DM, 3.6 yr) and 10 healthy nondiabetic women of similar age, weight, and activity levels performed a peak cardiopulmonary exercise test while instrumented with an indwelling pulmonary artery catheter for assessing cardiac function. On separate days, technetium-99m sestamibi (cardolite) imaging was performed to assess myocardial perfusion at rest and peak exercise in seven T2DM and seven control patients.Resting measures of cardiac hemodynamics were similar in T2DM and control subjects. Absolute VO(2peak) (mL x min(-1)) and peak cardiac output (L x min(-1)) tended to be lower in T2DM than in control subjects but did not reach statistical significance. However, pulmonary capillary wedge pressure (PCWP) rose significantly more during exercise in T2DM than in controls (148% vs 109% increase at peak exercise, P0.01). Normalized myocardial perfusion index was lower in persons with diabetes than in controls (11.0 +/- 3.5 x e(-9) vs 17.5 +/- 8.1 x e(-9), respectively, P0.05) and inversely related to peak exercise PCWP (R = -0.56, P0.05).Cardiac hemodynamics during graded exercise are altered in women with recently diagnosed T2DM as demonstrated by the disproportionate increase in PCWP at peak exercise compared with controls subjects. Cardiac abnormalities observed are potentially early signs of subclinical cardiac dysfunction associated with T2DM, which may precede the more greatly impaired cardiac function at rest and with exercise observed in longer established T2DM.

We hypothesized that the increased exercise arterial lactate concentration on arrival at high altitude and the subsequent decrease with acclimatization were caused by changes in blood lactate flux. Seven healthy men [age 23 +/- 2 (SE) yr, wt 72.2 +/- 1.6 kg] on a controlled diet were studied in the postabsorptive condition at sea level, on acute exposure to 4,300 m, and after 3 wk of acclimatization to 4,300 m. Subjects received a primed-continuous infusion of [6,6–2D]glucose (Brooks et al. J. Appl. Physiol. 70:919–927, 1991) and [3–13C]lactate and rested for a minimum of 90 min followed immediately by 45 min of exercise at 101 +/- 3 W, which elicited 51.1 +/- 1% of the sea level peak O2 consumption (VO2peak; 65 +/- 2% of both acute altitude and acclimatization). During rest at sea level, lactate appearance rate (Ra) was 0.52 +/- 0.03 mg.kg-1.min-1; this increased sixfold during exercise to 3.24 +/- 0.19 mg.kg-1.min-1. On acute exposure, resting lactate Ra rose from sea level values to 2.2 +/- 0.2 mg.kg-1.min-1. During exercise on acute exposure, lactate Ra rose to 18.6 +/- 2.9 mg.kg-1.min-1. Resting lactate Ra after acclimatization (1.77 +/- 0.25 mg.kg-1.min-1) was intermediate between sea level and acute exposure values. During exercise after acclimatization, lactate Ra (9.2 +/- 0.7 mg.kg-1.min-1) rose from resting values but was intermediate between sea level and acute exposure values. The increased exercise arterial lactate concentration response on arrival at high altitude and subsequent decrease with acclimatization are due to changes in blood lactate appearance.(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate the hypothesis that altitude exposure and acclimatization result in increased dependency on blood glucose as a fuel, seven healthy males (23 +/- 2 yr, 72.2 +/- 1.6 kg, mean +/- SE) on a controlled diet were studied in the postabsorptive condition at sea level (SL), on acute altitude exposure to 4,300 m (AA), and after 3 wk of chronic altitude exposure to 4,300 m (CA). Subjects received a primed continuous infusion of [6,6-2D]glucose and rested for a minimum of 90 min, followed immediately by 45 min of exercise at 101 +/- 3 W, which elicited 51.1 +/- 1% of the SL maximal O2 consumption (VO2 max; 65 +/- 2% of altitude VO2 max). At SL, resting arterial glucose concentration was 82.4 +/- 3.2 mg/dl and rose significantly to 91.2 +/- 3.2 mg/dl during exercise. Resting glucose appearance rate (Ra) was 1.79 +/- 0.02 mg.kg-1.min-1; this increased significantly during exercise at SL to 3.71 +/- 0.08 mg.kg-1.min-1. On AA, resting arterial glucose concentration (85.8 +/- 4.1 mg/dl) was not different from sea level, but Ra (2.11 +/- 0.14 mg.kg-1.min-1) rose significantly. During exercise on AA, glucose concentration rose to levels seen at SL (91.4 +/- 3.0 mg/dl), but Ra increased more than at SL (to 4.85 +/- 0.15 mg.kg-1.min-1; P less than 0.05). Resting arterial glucose was significantly depressed with CA (70.8 +/- 3.8 mg/dl), but resting Ra increased to 3.59 +/- 0.08 mg.kg-1.min-1, significantly exceeding SL and AA values.(ABSTRACT TRUNCATED AT 250 WORDS)

Redundant or accessory mitral valve tissue (AMVT) is a rare clinical condition. It is an even rarer cause of left ventricular outflow tract obstruction. We report a case of an adult male with medically unresponsive hypertrophic obstructive cardiomyopathy in whom real-time three-dimensional transesophageal echocardiography was used to both diagnose the presence of coexistent asymmetric septal hypertrophy and AMVT as well as confirm the safety and efficacy of treatment with alcohol septal ablation.

A method is proposed that allows for a fully automated computation of a series of high-resolution volumetric reconstructions of a patient's coronary arteries based on a single rotational acquisition. During the 7.2 second acquisition the coronary arteries are injected with contrast material while the imaging system rotates around the patient to obtain a series of X-ray projection images over an angular range of 180 degrees. Based on the simultaneously recorded ECG-signal the projection images corresponding to the same cardiac cycle can be utilized to reconstruct three-dimensional (3D) high-spatial-resolution angiograms of the coronary arteries in multiple (3D+t) cardiac phases within the cardiac cycle. The proposed acquisition protocol has been applied to 22 patients and the tomograpic reconstructions depicted the main arteries as well as the main bifurcations in multiple cardiac phases in all enrolled patients. For the first time, this feasibility study shows that a three-dimensional description of the coronary arteries can be obtained intraprocedurally in a conventional interventional suite by means of tomographic reconstruction from projection images without any user interaction.

RV dysfunction in idiopathic (primary) pulmonary hypertension (IPAH) is often characterized by chamber dilation, ventricular hypertrophy, and impaired systolic function. In this study we characterize right ventricular (RV) chamber size, end-diastolic thickness, myocardial mass, and ejection fraction in patients with right ventricular heart failure from IPAH, n = 16 and compare these characteristics to a control population of cardiac transplant patients (TX, n = 4) and a group of normal subjects (N, n = 5). Subjects underwent both gated cardiac magnetic resonance imaging (MRI) of the right ventricle and right heart catheterization (RHC). Using parameters from both the MRI and RHC, an estimate of RV end-systolic relative wall stress (RWS) was calculated. RV RWS was 34.7 +/- 8.4 and 17.3 +/- 3.8 Kdynes/cm2 in the cardiac transplant and control subjects respectively and was significantly elevated 104.1 Kdynes/cm2 in IPAH patients (IPAH vs N and TX; p = 0.004 and 0.008 ). RV ejection fraction RVEF was lower in IPAH patients 0.36 +/- .10 than in N and TX 0.57 +/- .04 and 0.55 +/- .08 respectively, (p = 0.0006 N and 0.0007 TX). An inverse linear correlation was demonstrated between RWS and RVEF (y = 215- 332x; R = .80, por = .0001). Right ventricular RWS is significantly elevated in IPAH and may provide a useful quantitative monitoring tool in patients with IPAH to assess the benefit of different therapeutic interventions and provide prognostic information.

This article discusses percutaneous patent foramen ovale closure.

Hypothesis/introduction A polymorphic marker within the angiotensin-converting enzyme (ACE) gene has been associated with circulating and tissue ACE activity and with a variety of forms of cardiovascular disease. Since angiotensin II (Ang II) causes pulmonary vasoconstriction and vascular and myocardial remodelling, we postulated a role for the renin-angiotensin system and the ACE DD genotype in the pathophysiology of primary pulmonary hypertension (PPH) and in the right ventricular response to pressure overload in these patients. Methods and results The incidence of the ACE DD genotype was evaluated in 60 patients with severe PPH compared with two normal control populations, a group of healthy population-based controls (n=158) and subjects found suitable for cardiac organ donation (n=79). Genomic DNA extracted from peripheral leukocytes was amplified using the polymerase chain reaction to detect polymorphic markers. Haemodynamics were determined by right heart catheterisation in a subset of the PPH patients. The frequency of the ACE DD genotype was 45% in the patients with PPH, compared with 24% in the organ donors, and 28% in populationbased healthy controls (p=0.01 for chi-square test). Of the 32 PPH patients with baseline haemodynamics, 12 exhibited the ACE DD genotype and 20 were non-DD. While the mean pulmonary artery pressure and the duration of symptoms attributable to pulmonary hypertension was not different between the DD and non-DD groups, cardiac output was significantly lower (3.29±0.27 vs. 5.07±0.37 L/minute, p=0.002) and the trouvemean right atrial pressure tended to be higher (8.85±1.29 vs. 4.92±1.27 mmHg, p=0.08) in the non-DD group. The reduction in cardiac output seen in the non-DD group was not due to a difference in heart rate, but to a significant reduction in stroke volume, consistent with a decreased contractile state. In addition, non-DD patients exhibited a significantly worse functional capacity (NYHA Class 3.14±0.12 vs. 2.40±0.28, p=0.02). Conclusions 1) The ACE DD genotype is significantly increased in patients with severe PPH compared with normal controls, suggesting that certain individuals may be genetically predisposed to developing pulmonary hypertension. 2) The ACE DD genotype is associated with preserved right ventricular function in PPH patients, supporting a compensatory myocardial or inotropic role for Ang II in the pressure overloaded right ventricle.

The objective of this study was to derive a method for quantifying the dynamic geometry of coronary arteries. Coronary artery geometry plays an important role in atherosclerosis. Coronary artery geometry also influences the performance of coronary interventions. Conversely, implantation of stents may alter coronary artery geometry. Clinical tools to define vessel shape have not been readily available. Using a Frenet-Serret curvature analysis applied to 3D reconstruction data derived from standard coronary angiograms, 21 coronary arteries were analyzed at end-diastole (ED) and end-systole (ES). Vessels were divided anatomically: type 1 consisted of vessels lying in the AV groove (left circumflex, right coronary) and type 2 consisted of vessels overlying actively contracting myocardium (left anterior descending, diagonal, obtuse marginal, right ventricular marginal, posterior descending, posterolateral). Vessel segments were analyzed by assessing the changes in curvature, torsion, and discrete flexion points (FPs), areas of systolic bending in the arterial contour. The curvature from ED to ES of type 1 vessels was unchanged (-0.02 +/- 0.03 cm(-1)), while the curvature change of type 2 vessels showed a 38% increase (0.33 +/- 0.04 cm(-1); P < 0.001). Type 1 vessels had fewer FPs per vessel than type 2 vessels (0.38 +/- 0.18 and 2.40 +/- 0.23 FP/vessel, respectively; P < 0.001). FPs were more common in distal segments and branch vessels. A method to quantify cyclic changes in coronary artery shape was applied to 3D data sets derived from standard coronary angiograms. Coronary arteries undergo a cyclic change in shape resulting in changes in overall curvature as well as formation of discrete flexion points. These changes in vessel shape are asymmetrically distributed in coronary arteries.

Evidence is reviewed from our recent (1987-1991) investigations which demonstrate better high-altitude adaptation among Tibetans than in acclimatized newcomers or other lifelong high-altitude residents. Characteristics of oxygen transport contributing to the Tibetans' remarkable exercise performance are described.

Background . In this study we explored different risk model options to provide clinicians with predictions for resource utilization. The hypotheses were that predictors of mortality are not predictive of resource consumption, and that there is a correlation between cost estimates derived using a cost-to-charge ratio or a product-line costing approach. Methods . From March 1992 to June 1995, 2,481 University of Colorado Hospital patients admitted for ischemic heart disease were classified by diagnosis-related group code as having undergone or experienced coronary bypass procedures (CBP), percutaneous cardiovascular procedures (PCVP), acute myocardial infarction (AMI), and other cardiac-related discharges (Other). For each diagnosis-related group, Cox proportional hazards models were developed to determine predictors of cost, charges, and length of stay. Results . The diagnosis groups differed in the clinical factors that predicted resource use. As the two costing methods were highly correlated, either approach may be used to assess relative resource consumption provided costs are reconciled to audited financial statements. Conclusions . To develop valid prediction models for costs of care, the clinical risk factors that are traditionally used to predict risk-adjusted mortality may need to be expanded.

Pulmonary hypertension is a progressive and often fatal complication of the scleroderma spectrum of disease for which no treatment has been proven effective in a randomized trial.To determine the effect of epoprostenol on pulmonary hypertension secondary to the scleroderma spectrum of disease.Randomized, open-label, controlled trial.17 pulmonary hypertension referral centers.111 patients with moderate to severe pulmonary hypertension.Epoprostenol plus conventional therapy or conventional therapy alone.The primary outcome measure was exercise capacity. Other measures were cardiopulmonary hemodynamics, signs and symptoms of pulmonary hypertension and scleroderma, and survival.Exercise capacity improved with epoprostenol (median distance walked in 6 minutes, 316 m at 12 weeks compared with 270 m at baseline) but decreased with conventional therapy (192 m at 12 weeks compared with 240 m at baseline). The difference between treatment groups in the median distance walked at week 12 was 108 m (95% CI, 55.2 m to 180.0 m) (P0.001). Hemodynamics improved at 12 weeks with epoprostenol. The changes in mean pulmonary artery pressure for the epoprostenol and conventional therapy groups were -5.0 and 0.9 mm Hg, respectively (difference, -6.0 mm Hg [CI, -9.0 to -3.0 mm Hg), and the mean changes in pulmonary vascular resistance were -4.6 and 0.9 mm Hg/L per minute, respectively (difference, -5.5 mm Hg/L per minute [CI, -7.3 to -3.7 mm Hg/L per minute). Twenty-one patients treated with epoprostenol and no patients receiving conventional therapy showed improved New York Heart Association functional class. Borg Dyspnea Scores and Dyspnea-Fatigue Ratings improved in the epoprostenol group. Trends toward greater improvement in severity of the Raynaud phenomenon and fewer new digital ulcers were seen in the epoprostenol group. Four patients in the epoprostenol group and five in the conventional therapy group died (P value not significant). Side effects of epoprostenol therapy included jaw pain, nausea, and anorexia. Adverse events related to the epoprostenol delivery system included sepsis, cellulitis, hemorrhage, and pneumothorax (4% incidence for each condition).Continuous epoprostenol therapy improves exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary hypertension due to the scleroderma spectrum of disease.

Hyperuricemia occurs frequently in patients with myeloproliferative and lymphoproliferative disorders and in patients with congenital heart disease associated with polycythemia. Whether hyperuricemia is common in patients with severe pulmonary hypertension is not known.In the Pulmonary Hypertension Center at the University of Colorado Health Sciences Center between September 1991 and August 1997, 442 consecutive patients were evaluated with right heart catheterization; 191 patients also had a measurement of the serum uric acid (UA) in close temporal proximity to the hemodynamic evaluation.Of the 191 patients with a complete data set, 99 patients had primary pulmonary hypertension (PPH) and 92 had secondary pulmonary hypertension. For the entire cohort with severe pulmonary hypertension (n = 191), there was a positive correlation between the natural logarithm of the serum UA (lnUA) and the mean right atrial pressure (RAP; r = 0.47; p0.001). When analyzed separately, the correlation between lnUA and RAP was stronger in the patients with PPH (r = 0.642; p0.001). This correlation cannot be explained by diuretic use or impaired hepatocellular function. Neither mean pulmonary artery pressure nor cardiac output was as well correlated with the RAP when compared with the lnUA. Some patients with PPH had serum UA measurements repeated during treatment with chronic IV prostacyclin infusion. Eleven of these 18 patients (61%) demonstrated a decrease in serum UA during prostacyclin treatment.There is a positive correlation between the RAP elevation and the serum UA levels in patients with PPH. Serum UA levels drop in some, but not all PPH patients during chronic prostacyclin infusion therapy.

Pulmonary hypertension develops in approximately 2% of patients with portal hypertension. Diagnosis is often difficult and requires a high degree of clinical suspicion. Treatment of patients with portal and pulmonary hypertension is limited, and mean survival following diagnosis is approximately 15 months. The effect of liver transplantation on the natural history of disease is discussed.

Automated computation of left ventricular (LV) global and regional function using contrast angiography has not yet become a routine procedure with the advent of digital cardiac imaging systems. We describe a new technique to compute LV volume curves which does not require the use of manual or semi-automated detection of endocardial borders and provides on-line implementation of volumetric curves and computation of pressure volume loops during catheterization. The approach uses the concepts of variable entropy (or information) of left ventricular images throughout the cardiac cycle. LV volume curves are computed with an interpolation scheme using those LV volume curves of a patient data base which are associated with the closest variation in entropy in the RAO projection to the analyzed patient data according to a simple metric. Computed LV volume curves were correlated with those obtained with manual tracing. Left ventricular ejection fraction (LVEF), time to end systole (TES) and angiographic cardiac output (CO) were compared to those obtained with the manual method. Results using a data base of 365 patients revealed excellent correlation (r = 0.97) between manually derived volume curves and volume curves computed with the automated technique within a large range of LVEFs. In 87% of all cases the computed LVEF values were found within +/- 10% of the value obtained with the gold standard method. The systolic phase of the volume curves showed that 81% of all cases had the same accuracy. The TES showed much more variation due to undersampling of the cardiac cycle in time (r = 0.71).

It has been proposed that the contribution of myocardial tissue angiotensin converting enzyme (ACE) to angiotensin II (Ang II) formation in the human heart is low compared with non-ACE pathways. However, little is known about the actual in vivo contribution of these pathways to Ang II formation in the human heart. To examine angiotensin II formation in the intact human heart, we administered intracoronary 123I-labeled angiotensin I (Ang I) with and without intracoronary enalaprilat to orthotopic heart transplant recipients. The fractional conversion of Ang I to Ang II, calculated after separation of angiotensin peptides by HPLC, was 0.415 +/- 0.104 (n = 5, mean +/- SD). Enalaprilat reduced fractional conversion by 89%, to a value of 0.044 +/- 0.053 (n = 4, P = 0.002). In a separate study of explanted hearts, a newly developed in vitro Ang II-forming assay was used to examine cardiac tissue ACE activity independent of circulating components. ACE activity in solubilized left ventricular membrane preparations from failing hearts was 49.6 +/- 5.3 fmol 125I-Ang II formed per minute per milligram of protein (n = 8, +/- SE), and 35.9 +/- 4.8 fmol/min/mg from nonfailing human hearts (n = 7, P = 0.08). In the presence of 1 microM enalaprilat, ACE activity was reduced by 85%, to 7.3 +/- 1.4 fmol/min/mg in the failing group and to 4.6 +/- 1.3 fmol/min/mg in the nonfailing group (P < 0.001). We conclude that the predominant pathway for angiotensin II formation in the human heart is through ACE.

A new technique has been developed to compute left ventricular (LV) time activity curves from gated blood pool (GBP) studies without the use of manual, semiautomated or fully automated edge detection algorithms. The method utilizes the correlation of entropy calculated from the counts of a fixed region of interest covering the left ventricle during a cardiac cycle to compute the LV volume curve for a new patient. The new LV volume curve is obtained through interpolation of those volume curves of a data base which are associated with the closest variations in normalized entropy to the new one. The computed LV time activity curves agree with those obtained from manual or fully automated outlines of the left ventricle within 9 percent for the selected set of 67 patients demonstrating the potential of the method. The accuracy of calculated LV volume curves can be improved theoretically to any degree by increasing the number of cases in the data base of known statistical feature vectors associated with the LV images and LV volume curves. The new method for computation of LV curves is very efficient and robust when compared to traditional techniques.

There are few data concerning the complications and technical difficulties encountered when cardiac catheterization is performed using peripheral bypass grafts for vascular access. All cardiac catheterizations performed at our institution from January 1, 1984 to April 1, 1991 were retrospectively reviewed to assess the in-hospital clinical outcomes in patients who had arterial access for catheterization achieved via prosthetic graft puncture. Seventeen procedures had percutaneous puncture of a vascular graft from a total of 2,929 arterial catheterizations performed. The interval from graft placement to catheterization was 7.5 +/- 1.1 years. Arterial sheaths were employed in all cases and corresponded to the catheter size, with 5F systems used in 53% and 7F or larger systems used in the remaining patients. No intraprocedural or postprocedural complications were recognized. Technical difficulties were limited to the inability to selectively cannulate a nondominant right coronary artery in 1 patient. We conclude that percutaneous introduction of an arterial sheath and left heart catheterization via remotely implanted vascular bypass grafts is not associated with an increased risk of procedural complications or technical difficulties.

Elevated pulmonary arterial pressure in high-altitude residents may be a maladaptive response to chronic hypoxia. If so, well-adapted populations would be expected to have pulmonary arterial pressures that are similar to sea-level values. Five normal male 22-yr-old lifelong residents of > or = 3,600 m who were of Tibetan descent were studied in Lhasa (3,658 m) at rest and during near-maximal upright ergometer exercise. We found that resting mean pulmonary arterial pressure [15 +/- 1 (SE) mmHg] and pulmonary vascular resistance (1.8 +/- 0.2 Wood units) were within sea-level norms and were little changed while subjects breathed a hypoxic gas mixture [arterial O2 pressure (PaO2) = 36 +/- 2 Torr]. Near-maximal exercise [87 +/- 13% maximal O2 uptake (VO2max)] increased cardiac output more than threefold to values of 18.3 +/- 1.2 l/min but did not elevate pulmonary vascular resistance. Breathing 100% O2 during near-maximal exercise did not reduce pulmonary arterial pressure or vascular resistance. We concluded that this small sample of healthy Tibetans with lifelong residence > or = 3,658 m had resting pulmonary arterial pressures that were normal by sea-level standards and exhibited minimal hypoxic pulmonary vasoconstriction, both at rest and during exercise. These findings are consistent with remarkable cardiac performance and high-altitude adaptation.

Unexplained, or primary, pulmonary hypertension, is usually a rapidly fatal disease, in which the use of vasodilator therapy is controversial (14, 22, 25). While some authors have proposed that there may be a significant vasoconstrictive component to the increased pulmonary arterial pressure and resistance (2, 7, 11, 19), others have indicated that such a component is usually small and/or unimportant (13). This controversy has likely arisen because the disease is relatively uncommon, its pathogenesis is not understood, it is usually diagnosed late in the natural history, and the rate of progression is variable between patients. Yet investigation into the problem is important because persons afflicted are often young and otherwise healthy. Needed was a prospective, longitudinal study in a relatively large group of patients, where the magnitude of the vasoconstrictive component could be measured acutely and compared to results of long term treatment.

Operation Everest II was designed to examine the physiological responses to gradual decompression simulating an ascent of Mt Everest (8,848 m) to an inspired PO2 of 43 mmHg. The principal studies conducted were cardiovascular, respiratory, muscular-skeletal and metabolic responses to exercise. Eight healthy males aged 21-31 years began the "ascent" and six successfully reached the "summit", where their resting arterial blood gases were PO2 = 30 mmHg and PCO2 = 11 mmHg, pH = 7.56. Their maximal oxygen uptake decreased from 3.98 +/- 0.2 L/min at sea level to 1.17 +/- 0.08 L/min at PIO2 43 mmHg. The principal factors responsible for oxygen transport from the atmosphere to tissues were (1) Alveolar ventilation--a four fold increase. (2) Diffusion from the alveolus to end capillary blood--unchanged. (3) Cardiac function (assessed by hemodynamics, echocardiography and electrocardiography)--normal--although maximum cardiac output and heart rate were reduced. (4) Oxygen extraction--maximal with PvO2 14.8 +/- 1 mmHg. With increasing altitude maximal blood and muscle lactate progressively declined although at any submaximal intensity blood and muscle lactate was higher at higher altitudes.