Richard A. Krasuski

Long-Term Healthcare and Cost Outcomes of Disease Management in a Large, Randomized, Community-Based Population With Heart Failure

Background—Because of the prevalence and expense of congestive heart failure (CHF), significant efforts have been made to develop disease management (DM) programs that will improve clinical and financial outcomes. The effectiveness of such programs in a large, heterogeneous population of CHF patients remains unknown. Methods and Results—We randomized 1069 patients (aged 70.9±10.3 years) with systolic (ejection fraction 35±9%) or echocardiographically confirmed diastolic heart failure (HF) to assess telephonic DM over an 18-month period. Data were collected at baseline and at 6-month intervals. Survival analysis was performed by Kaplan-Meier and Cox regression methods. Healthcare utilization was defined after extensive record review, with an attempt to account for all inpatient and outpatient visits, medications, and diagnostic tests. We obtained data on 92% of the patients, from nearly 53 000 health-related encounters. Total cost per patient was defined by adding estimated costs for the observed encounters, excluding the cost of the DM. Kaplan-Meier analysis showed that DM patients had a reduced mortality rate (P=0.037), with DM patients surviving an average of 76 days longer than controls. Subgroup analysis showed that DM had beneficial outcomes in patients with systolic HF (hazard ratio 0.62; P=0.040), which was more pronounced in NYHA classes III and IV. Although improvements in NYHA class were more likely with DM (P<0.001), 6-minute walk data from 217 patients in whom data were available at each visit showed no significant benefit from DM (P=0.08). Total and CHF-related healthcare utilization, including medications, office or emergency department visits, procedures, or hospitalizations, was not decreased by DM. Repeated-measures ANOVA for cost by group showed no significant differences, even in the higher NYHA class groups. Conclusions—Participation in DM resulted in a significant survival benefit, most notably in symptomatic systolic HF patients. Although DM was associated with improved NYHA class, 6-minute walk test results did not improve. Healthcare utilization was not reduced by DM, and it conferred no cost savings. DM in HF results in improved life expectancy but does not improve objective measures of functional capacity and does not reduce cost.

A Randomized Trial of a Strategy for Increasing High-Density Lipoprotein Cholesterol Levels: Effects on Progression of Coronary Heart Disease and Clinical Events

Context Most trials that address lipid management focus on reducing low-density lipoprotein (LDL) cholesterol levels rather than increasing high-density lipoprotein (HDL) cholesterol levels. Contribution In this double-blind trial, 143 military retirees with low HDL cholesterol levels and coronary artery disease were randomly assigned to placebo or aggressive HDL cholesterolincreasing therapy with gemfibrozil, niacin, and cholestyramine for 30 months. All participants received diet and exercise counseling. Compared with the placebo group, the treated group had a 20% decrease in total cholesterol level; a 36% increase in HDL cholesterol level; less focal coronary stenosis; fewer total cardiovascular events; and more flushing, skin rashes, and abdominal symptoms. Cautions The small trial had limited ability to assess clinical outcomes. The Editors Large epidemiologic studies have repeatedly demonstrated that cardiovascular risk increases proportionally with increasing total cholesterol and low-density lipoprotein (LDL) cholesterol levels and decreasing high-density lipoprotein (HDL) cholesterol levels (1, 2). Although many studies have documented that statins, drugs that primarily reduce LDL cholesterol levels, significantly reduce the risk for cardiovascular events (3-7), prospective studies that examine the clinical effects of increasing HDL cholesterol levels have been more limited. The Coronary Drug Project first reported evidence of a mortality benefit in patients treated with niacin; however, the difference was seen long after withdrawal of the study drug, making the mechanism of benefit less clear (8). The Helsinki Heart Study (9) examined the use of gemfibrozil in primary prevention. Coronary events were reduced by 34%, but the increase in HDL cholesterol level was modest (only 11%). The Bezafibrate Infarction Prevention Trial failed to show a reduction in cardiovascular events in the composite population, although a recent reanalysis of the data suggests an improved outcome in patients experiencing a greater increase in HDL cholesterol level (10). The Veterans Affairs HDL Intervention Trial (VA-HIT) (11) demonstrated a modest reduction in coronary events when gemfibrozil was used in patients with normal levels of LDL cholesterol and low levels of HDL cholesterol. The authors ascribed most of the reduction in clinical events to the improvement in HDL cholesterol, although the overall improvement was only approximately 6% with drug therapy. More recently, a combination of a statin (simvastatin) with niacin was found to favorably modify both HDL cholesterol and LDL cholesterol levels and reduce cardiovascular events compared with both placebo therapy and underlying treatment with antioxidants in a cohort of 160 patients with coronary disease (12). Despite a significant increase in mean HDL cholesterol levels, the overwhelming treatment effect in this study was the reduction in LDL cholesterol level (42% in the treatment group). The most suggestive evidence of benefit from an increase in HDL cholesterol level has come from trials assessing the effect on coronary stenosis. Trials of quantitative angiography after monotherapy with fibrates (13), as well as combinations of medications that both reduce LDL cholesterol levels and increase HDL cholesterol levels (14-18), have shown an attenuation in angiographic progression. Nissen and colleagues (19) recently took this theory a step further by demonstrating that an infusion of a recombinant form of HDL, apolipoprotein A-I Milano, can lead to regression of angiographic stenosis as assessed by intravascular ultrasonography. We undertook the Armed Forces Regression Study (AFREGS) in 1993 to determine whether coronary atherosclerosis, assessed by quantitative coronary angiography and clinical coronary events, would improve when combination drug therapy focused on increasing HDL cholesterol levels in a sample of patients with fairly normal LDL cholesterol levels and low HDL cholesterol levels. A pilot study by Whitney and colleagues (20) showed the feasibility of this trial design, and the safety of using these drugs in combination has been previously established (21). Methods Patients Participants living within a 150-mile radius of Wilford Hall Medical Center in San Antonio, Texas, who could provide written informed consent were eligible for enrollment. We recruited men and women younger than 76 years of age who had established or suspected coronary artery disease (positive results on an exercise treadmill test or classic angina) and did not have unstable symptoms. We allowed LDL cholesterol levels up to 4.1 mmol/L (160 mg/dL) with HDL cholesterol levels less than 1.0 mmol/L (40 mg/dL) after adherence to the American Heart Association (AHA) step II diet for at least 6 months. We set no lower limit to either HDL cholesterol or LDL cholesterol level. Each patient was required to have measurable stenosis between 30% and 80% of the luminal diameter within the coronary tree by caliper inspection. Patients with stenosis greater than 80% were eligible if they had a favorable prognosis based on functional testing (ability to exercise for >9 minutes on a full Bruce protocol exercise treadmill test). Exclusions included a major vascular event (myocardial infarction, cerebrovascular accident, coronary artery bypass grafting, or other coronary catheterbased intervention) within 6 months, a history of congestive heart failure (other than in the setting of myocardial infarction), or a left ventricular ejection fraction less than 0.4 on ventriculography. Other exclusion criteria included alcohol or substance abuse within the past year, uncontrolled arrhythmias, resistant hypertension, diabetes, uncontrolled gout, uncontrolled thyroid disease, liver or gall bladder disease, renal dysfunction (creatinine concentration > 176.8 mol/L [>2.0 mg/dL] or proteinuria greater than 2+ by dipstick or 500 mg/24 h), uncontrolled peptic ulcer disease, or pancreatic disorders. In addition, we excluded patients taking any lipid-modifying medications within 4 weeks of randomization, heparin or coumarin-type anticoagulants, long-term oral corticosteroid therapy, or other immunosuppressive agents. We also excluded patients if they had hypersensitivity to or history of intolerance that required cessation of therapy for any component of gemfibrozil, nicotinic acid, cholestyramine, aspirin, or nitrates. Other exclusion criteria were the potential for childbearing, technically inadequate coronary arteriography for stenosis quantification, or any serious condition that we thought would compromise participation in the study or preclude survival for the duration of the study. We thoroughly informed participants of the details of the study. Each patient voluntarily enrolled and signed an informed consent statement that the Wilford Hall Medical Center Institutional Review Board reviewed and approved. From screening laboratory records, we identified 1290 participant candidates and invited them to participate (Figure 1). Of the 847 patients who attended the introductory briefing, 671 met LDL cholesterol and HDL cholesterol entry criteria on fasting lipid analysis. Of the 269 participants who eventually provided informed consent, 55 subsequently withdrew for personal reasons, most commonly citing a fear of cardiac catheterization, and an additional 27 met an exclusion criterion. Of the 187 participants who completed the 6-month lifestyle modification phase and underwent coronary angiography, 44 were excluded after initial coronary arteriography; 27 had extensive coronary disease necessitating revascularization (percutaneous coronary intervention in 3 patients and coronary artery bypass grafting in 24 patients), and 17 had insignificant coronary disease on angiography. Thus, we eventually randomly assigned 143 patients (11% of those initially contacted) to either pharmacologic therapy or placebo. Figure 1. Flow of patients through the study. Protocol After inclusion and exclusion criteria were met, a 6- to 8-month run-in period was performed to ensure that patients could adhere to the prescribed diet. During this phase, all patients received diet counseling from a study dietitian, exercise guidance from an exercise specialist, and smoking cessation advice. All study participants committed to attending a bimonthly food show for training in the AHA step II diet, with reinforcing presentations from the dietitian, exercise specialist, and cardiologist that discussed cardiac risk factor modification. We randomly assigned each participant by using a computer-generated randomization schedule. The central pharmacy held the code, and the information was not shared with physicians or patients until the completion of the protocol. Patients were randomly assigned to 1 of 2 treatment groups: pharmacologic therapy with gemfibrozil, niacin, and cholestyramine or conventional therapy. The goal of therapy was to increase HDL cholesterol level by at least 25%. The study was double-blind and placebo-controlled. The pharmaceutical company prepared all medications and placebos, and the central pharmacy dispensed them at 30-day intervals. The pharmacologic therapy group began receiving gemfibrozil, 600 mg twice per day. Short-acting niacin was added in the third month at a dosage of 250 mg/d and was titrated to 3000 mg/d as tolerated. Cholestyramine was added in the sixth month, and the dosage was titrated to 16 g/d as tolerated. The conventional therapy group was maintained on the AHA step II diet and applicable matching placebos for the duration of the investigation. If LDL cholesterol levels exceeded 4.14 mmol/L (160 mg/dL) during the trial, cholestyramine was administered in an open-label fashion. Participants visited 1 clinic on a monthly basis for the duration of the study. At each monthly visit, clinicians measured vital signs and weight, counted unused study drugs, reviewed changes in medications or medical status, provided ne

Long-term outcome and impact of surgery on adults with coronary arteries originating from the opposite coronary cusp.

Background— An anomalous coronary artery from the opposite sinus of Valsalva may increase sudden death risk in children and young adults, and surgical intervention is often recommended. The impact of this lesion when recognized in the adult and its management are ill defined. Methods and Results— We reviewed 210 700 cardiac catheterizations performed over a 35-year period at a single institution and identified 301 adults with an anomalous coronary artery from the opposite sinus of Valsalva, either anomalous right coronary artery from the left cusp or anomalous left main coronary artery from the right cusp. Patients were stratified by the pathway of the anomalous artery and the chosen treatment. Among the 301 patients with anomalous coronary artery from the opposite sinus of Valsalva (0.14% of the cohort), 79% had anomalous right coronary artery from the left cusp, and 18% had an interarterial course (IAC). Patients with IAC were younger (52±13 versus 59±13 years; P=0.001) and more likely to undergo surgical intervention (52% versus 27%; P<0.001), but mortality was not increased with IAC. Among the 54 patients with IAC, 28 underwent surgical repair with no perioperative deaths. Patients evaluated since 2000 were significantly more likely to be referred for surgery (P=0.004). Surgical patients were more likely to have abnormal stress tests (90% versus 43%; P=0.01) and had more extensive atherosclerosis but less diabetes mellitus (0% versus 23%; P=0.01). Long-term survival at 10 years appeared similar in both groups. Conclusions— In this single-center cohort study of patients with an anomalous coronary artery from the opposite sinus of Valsalva, surgical management appears to have been favored recently. Despite no perioperative mortality, a positive impact on long-term survival was not observed. The impact of surgery in older adults with anomalous coronary arteries arising from the opposite coronary sinus with IAC deserves further study.

Inhaled Nitric Oxide Selectively Dilates Pulmonary Vasculature in Adult Patients With Pulmonary Hypertension, Irrespective of Etiology

OBJECTIVES We sought to compare the responses of patients with pulmonary hypertension from primary and secondary causes (PPH and SPH, respectively) to inhaled nitric oxide (iNO) in the cardiac catheterization laboratory. BACKGROUND Pulmonary hypertension can lead to right ventricular pressure overload and failure. Although vasodilators are effective as therapy in patients with PPH, less is known about their role in adults with SPH. Inhaled nitric oxide can accurately predict the response to other vasodilators in PPH and could be similarly utilized in SPH. METHODS Forty-two patients (26 to 77 years old) with pulmonary hypertension during cardiac catheterization received iNO. Demographic and hemodynamic data were collected. Their response to iNO was defined by a decrease of > or =20% in mean pulmonary artery (PA) pressure or pulmonary vascular resistance (PVR). RESULTS Mean PA pressures and PVR were lower during nitric oxide (NO) inhalation in all patients with pulmonary hypertension. Seventy-eight percent of patients with PPH and 83% of patients with SPH were responders to iNO. A trend was seen toward a greater response with larger doses of NO in patients with SPH. Nitric oxide was a more sensitive predictor of response (79%), compared with inhaled oxygen (64%), and was well tolerated, with no evidence of systemic effects. Elevation in right ventricular end-diastolic pressure appeared to predict poor vasodilatory response to iNO. CONCLUSIONS Nitric oxide is a safe and effective screening agent for pulmonary vasoreactivity. Regardless of etiology of pulmonary hypertension, pulmonary vasoreactivity is frequently demonstrated with the use of NO. Right ventricular diastolic dysfunction may predict a poor vasodilator response.

Prevalence and repair of intraoperatively diagnosed patent foramen ovale and association with perioperative outcomes and long-term survival

CONTEXT A recent survey suggested that cardiothoracic surgeons may alter planned procedures to repair incidentally discovered patent foramen ovale (PFO). How frequently this occurs and the impact on outcomes remain unknown. OBJECTIVE To measure the frequency of incidentally discovered PFO closure during cardiothoracic surgery and determine its perioperative and long-term impact. DESIGN, SETTING, AND PATIENTS We reviewed the intraoperative transesophageal echocardiograms of 13,092 patients without prior diagnosis of PFO or atrial septal defect undergoing surgery at the Cleveland Clinic, Cleveland, Ohio, from 1995 through 2006. Postoperative outcomes were prospectively collected until discharge. MAIN OUTCOME MEASURES All-cause hospital mortality and stroke were predetermined primary outcomes; length of hospital stay, length of intensive care unit stay, and time on cardiopulmonary bypass were secondary outcomes. RESULTS Intraoperative PFO was diagnosed in 2277 patients in the study population (17%), and risk factors for stroke were similar in patients with and without PFO. After propensity matching was performed with the comparator groups, patients with PFO demonstrated similar rates of in-hospital death (3.4% vs 2.6%, P = .11) and postoperative stroke (2.3% vs 2.3%, P = .84). Surgical closure was performed in 639 PFO patients (28%), and surgeons were more likely to close defects in patients who were younger (mean [SD] age, 61.1 [14] vs 64.4 [13] years; P < .001), were undergoing mitral or tricuspid valve surgery (51% vs 32%, P < .001), or had history of transient ischemic attack or stroke (16% vs 10%, P < .001). Patients with repaired PFO demonstrated a 2.47-times greater odds (95% confidence interval, 1.02-6.00) of having a postoperative stroke compared with those with unrepaired PFO (2.8% vs 1.2%, P = .04). Long-term analysis demonstrated that PFO repair was associated with no survival difference (P = .12). CONCLUSIONS Incidental PFO is common in patients undergoing cardiothoracic surgery but is not associated with increased perioperative morbidity or mortality. Surgical closure appears unrelated to long-term survival and may increase postoperative stroke risk.

Serial echocardiographic evaluation of restenosis after successful percutaneous mitral commissurotomy

OBJECTIVES This study was designed to determine predictors of restenosis after successful percutaneous mitral commissurotomy (PMC) and its relationship to late clinical outcome. BACKGROUND The restenosis rate after PMC and its relationship to late clinical outcome is poorly defined. METHODS Serial echocardiography was performed in 310 patients who underwent PMC. Restenosis, defined as mitral valve area (MVA) <1.5 cm(2) and > or = 50% loss of initial MVA increase, was determined by both two-dimensional (2D) and Doppler echocardiography. Clinical, echocardiographic and cardiac catheterization variables were evaluated to determine predictors of restenosis. The relationship between restenosis and major adverse clinical events (death, repeat PMC or mitral valve replacement) and functional status was assessed. RESULTS Acute procedural success occurred in 206 patients (66%), who were then followed for restenosis. The cumulative restenosis rate was approximately 40% at six years after successful PMC (44% by 2D and 40% by Doppler MVA). The only independent predictor of restenosis was echocardiographic score (restenosis at five years was 20% for score <8 vs. 61% for score > or = 8, p < 0.001). The decline in MVA and occurrence of restenosis was gradual and progressive during the follow-up period. Procedural results and baseline factors predicted event-free survival. Restenosis by 2D MVA was related to adverse events or New York Heart Association functional class 3 to 4 symptoms, but restenosis was not an independent predictor of clinical outcome by multivariate analysis. CONCLUSIONS Restenosis is a common, gradual and progressive occurrence after successful PMC and is predicted by higher echocardiographic score. Restenosis is related to late adverse clinical outcome, though clinical outcome remains best predicted by the acute procedural results of PMC.

Effects of Combination Lipid Therapy on Coronary Stenosis Progression and Clinical Cardiovascular Events in Coronary Disease Patients with Metabolic Syndrome: A Combined Analysis of the Familial Atherosclerosis Treatment Study (FATS), the HDL-Atherosclerosis Treatment Study (HATS), and the Armed Forces Regression Study (AFREGS)

We examined the impact of metabolic syndrome (MS) on coronary stenosis progression and major cardiovascular (CV) events and investigated the mitigating effects of low-density lipoprotein (LDL) cholesterol lowering and LDL cholesterol lowering plus high-density lipoprotein (HDL) cholesterol increasing. This analysis combined individual patient data from 445 subjects who participated in 3 double-blinded, randomized, placebo-controlled trials (FATS, HATS, and AFREGS) comparing intensive lipid therapy to placebos on coronary stenosis progression by quantitative coronary angiography and on major CV events. The primary end points were change in mean proximal coronary diameter stenosis (Delta%S(prox)) over 3 years and the frequency of the predefined composite of coronary artery disease death, nonfatal myocardial infarction, stroke, and revascularization due to worsening ischemia. Patients with MS had 50% more rapid coronary stenosis progression and 64% increased CV event frequency compared to those without. More rapid coronary stenosis progression was significantly and independently associated with a 3.5-fold increased event risk (p <0.001). Combination lipid therapy significantly decreased stenosis progression by 83% (Delta%S(prox) 0.5 vs 2.9, p <0.001) in patients with MS and induced a small net regression in those without (Delta%S(prox) -0.3 vs 2.0, p <0.001). Combination therapy decreased the event rate by 54% (13% vs 28%, p = 0.03) in those with MS and by 82% (3% vs 17%, p = 0.002) without. On average, each 10% decrease in LDL cholesterol or 10% increase in HDL cholesterol was significantly associated with a 0.3 Delta%S(prox) decrease. Each 10% decrease in LDL cholesterol or 10% increase in HDL cholesterol was associated with 11% (p = 0.02) or 22% (p <0.001) event risk decrease. In conclusion, patients with MS have significantly more rapid coronary stenosis progression and a higher frequency of CV events. Greater stenosis progression rate is associated with a higher event rate. LDL cholesterol-lowering and HDL cholesterol-increasing therapies independently and significantly decrease coronary stenosis progression and decrease CV events.

Pulmonary Vein Isolation for the Treatment of Drug-Refractory Atrial Fibrillation in Adults with Congenital Heart Disease

BACKGROUND Atrial fibrillation (AF) is a common arrhythmia in adults with congenital heart disease (CHD). Long-term antiarrhythmic therapy (AAT) in these patients has significant shortcomings. The safety and efficacy of pulmonary vein antrum isolation (PVAI) for the treatment of AF in CHD is presently unknown. HYPOTHESIS We hypothesized that PVAI for AF in patients with CHD is effective and safe. METHODS We reviewed a prospective cohort of 4315 patients (age ≥ 18) undergoing PVAI for drug refractory AF at a single institution and identified 36 consecutive patients with CHD (single ventricle physiology, tetralogy of Fallot, coarctation of the aorta, ventricular septal defects, atrial septal defects (ASD) and cardiomyopathy resulting from anomalous origin of the left main coronary from the pulmonary artery). A second cohort of 355 consecutive patients with noncongenital structural heart disease (NSHD) (coronary artery disease, valvular heart disease, ejection fraction <50%, or prior noncongenital cardiac surgery) undergoing PVAI during the same time period was used as a control. Success was defined as freedom from AF starting two months after PVAI in the absence AAT until the end of follow-up. Partial success was defined as freedom from AF in the presence of AAT until the end of follow-up. Combined success was defined as the sum of success and partial success. We compared the outcomes with the use of propensity-score matching in the overall cohort. RESULTS Patients with NSHD were older and had higher prevalence of hypertension (P < .01), diabetes (P < .01) and hyperlipidemia (P < .01). The most common CHD lesion was ASD (61%) and the most common NSHD lesion was valvular heart disease (57%). After one PVAI, success was achieved in 42% and 53% at 300 days in the CHD and NSHD groups respectively. Four-year success was achieved in 27% and 36% in the CHD and NSHD groups, respectively. There were no significant differences in the success rates between patients groups (P= .46), nor were there any differences in left atrial size or changes in ejection fraction after one or two PVAI in the respective groups. Complication rates between the CHD and NSHD groups were similar (15% vs. 11%, P= .42) except for a higher risk of vascular site complications in patients with CHD (8% vs. 1%, P < .05). CONCLUSION PVAI is an attractive treatment modality in drug refractory AF in CHD, with combined success rates in excess of 60%. The maintenance of sinus rhythm after PVAI in CHD appears similar to that of NSHD and warrants prospective validation.

Conversion to Atorvastatin in Patients Intolerant or Refractory to Simvastatin Therapy: The CAPISH Study

OBJECTIVE To examine the safety and efficacy of switching from simvastatin to atorvastatin in patients who had either an inadequate lipid-lowering response with, or an adverse reaction to, simvastatin. PATIENTS AND METHODS The Conversion to Atorvastatin in Patients Intolerant or Refractory to Simvastatin Therapy (CAPISH) study was designed in 2 parts: a retrospective cohort study of patients (group A), identified from a large pharmacy database, who converted from simvastatin to atorvastatin at a single academic military medical center (between April 1998 and March 2002) and a prospective cohort study of patients (group B) monitored in a lipid clinic at the same institution (between April 2002 and March 2003). Group A was identified by 2 or more simvastatin prescription fills and at least 1 atorvastatin prescription fill. Group B was identified by a physician-perceived need to switch from simvastatin to atorvastatin. Clinical, pharmaceutical, and laboratory records of both cohorts were reviewed. RESULTS Approximately 1 in 4 simvastatin-treated patients discontinued therapy during a 4-year period. The most common reason for switching to atorvastatin was inadequate low-density lipoprotein (LDL) cholesterol control, although asymptomatic creatine kinase (CK) elevation and myalgias were also common. In most cases of myositis and in nearly all cases of rhabdomyolysis, patients were taking 80 mg of simvastatin. Achievement of National Cholesterol Education Program LDL cholesterol goals increased from 25% to 63% in group A and from 13% to 78% in group B, both P<.001. Significant reductions in CK also were seen in both groups. Adherence to atorvastatin was greater than 80% in both groups after 28.1+/-13.2 months (group A, 841 patients) and 8.1+/-3.8 months (group B, 104 patients). Among patients not taking atorvastatin at follow-up, 58% were no longer taking statins. CONCLUSION Atorvastatin was well tolerated in patients who previously were taking simvastatin. Serum lipid panels were improved substantially and CK levels were decreased without compromise to patient safety.

Association of anemia and long-term survival in patients with pulmonary hypertension

BACKGROUND Anemia is a marker of worsened clinical outcome in patients with heart failure from left ventricular dysfunction. Pulmonary hypertension often results in right ventricular dysfunction. Accordingly we sought to examine the association of hemoglobin levels and long-term all-cause mortality in a cohort of patients with pulmonary hypertension. METHODS Baseline demographic information, clinical characteristics and fasting blood work were obtained in a cohort of 145 patients with pulmonary hypertension referred for pulmonary vasodilator testing. Data was retrospectively analyzed with Cox-proportional hazards analysis. RESULTS Baseline characteristics of the cohort included age (mean±SD) 55.8±14.6 years, 75% women, 50% with idiopathic pulmonary hypertension, mean pulmonary artery pressure 46.1±14.2 mm Hg and arterial O(2) saturation 91±6 %. The most commonly utilized pulmonary hypertension specific therapeutic agents in descending order of frequency were epoprostenol (27%), sildenafil (21%), bosentan (17%), and treprostinil (6%). Over a median follow-up of 2.1 years, there were 39 deaths (26.9%). Patients who died had significantly lower hemoglobin levels than those survived (12.2±2.3 vs. 13.7±2.0, p<0.001). After adjustment for known predictors of death and pulmonary hypertension etiology, anemic patients were 3.3 times more likely to die than non-anemic patients (95% CI [1.43-7.51], p=0.005). CONCLUSIONS Hemoglobin levels closely parallel survival in pulmonary hypertension. Modification of anemia in this disorder could alter the clinical course and calls for further research in this area.