Biomedical subjects

Srinivas Murali

Publications and source records attributed to Srinivas Murali.

At least 19 recordsLinked to original sources

PubMed2006

Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension.

RATIONALE: Small, open-label studies suggest that combinations of existing therapies may be effective for pulmonary arterial hypertension (PAH). OBJECTIVE: To evaluate the safety and efficacy of adding inhaled iloprost, a prostacyclin analog, to the endothelin receptor antagonist bosentan in patients with PAH. METHODS: In a randomized, multicenter, double-blind trial, inhaled iloprost (5 mug) or placebo was added to stable monotherapy with bosentan for 12 wk. Efficacy endpoints included change from baseline in 6-min-walk distance (6-MWD), modified New York Heart Association (NYHA) functional class, hemodynamic parameters, and time to clinical worsening. MEASUREMENTS AND MAIN RESULTS: A total of 67 patients with PAH (55% idiopathic PAH, 45% associated PAH, 94% NYHA class III, and mean baseline 6-MWD of 335 m) were randomized. At Week 12, patients receiving iloprost had a mean increase in 6-MWD of 30 m (p = 0.001); placebo patients had a mean 6-MWD increase of 4 m (p = 0.69), with a placebo-adjusted difference of +26 m (p = 0.051). NYHA status improved by one class in 34% of iloprost versus 6% of placebo patients (p = 0.002). Iloprost delayed the time to clinical worsening (p = 0.0219). Improvements were noted in postinhalation placebo-adjusted change in mean pulmonary artery pressure (-8 mm Hg; p < 0.001) and pulmonary vascular resistance (-254 dyn x s x cm(-5); p < 0.001). Combination therapy was well tolerated. CONCLUSIONS: Within the limitations of a relatively small sample size, results of this study demonstrate that the addition of inhaled iloprost in patients with PAH with reduced exercise capacity on bosentan monotherapy is safe and efficacious.

Adolescent↗

PubMed2006

Temporal trends and drug exposures in pulmonary hypertension: an American experience.

BACKGROUND: Reports have linked anorexigen intake to an increased risk of pulmonary arterial hypertension (PAH). With the rise in anorexigen use in the latter half of the last decade, we established a surveillance network within the United States to monitor temporal trends in the number of reported cases of PAH. We also studied whether use of anorexigens and other drugs differed among patients with pulmonary hypertension of different etiologies. METHODS: Newly diagnosed subjects (N = 1335) at 13 tertiary pulmonary hypertension centers were enrolled between January 1998 and June 2001. Patient-reported medication use was obtained by a telephone interview. Patients were classified as to the type of pulmonary hypertension. Poisson regression models were fitted to monthly case counts, and logistic regression methods were used to assess the association between type of pulmonary hypertension and medication use. RESULTS: The average monthly number of reported cases of PAH and other categories of pulmonary hypertension did not change over the study period. Fenfluramine or dexfenfluramine use during the 5 years before the time of the interview was preferentially associated with PAH. Fenfluramine/dexfenfluramine use was particularly common in cases referred but found not to have pulmonary hypertension. CONCLUSIONS: No epidemic of anorexigen-related PAH was evident during the study period. As persons who had taken fenfluramine or dexfenfluramine were particularly likely to be referred for evaluation of pulmonary hypertension, it is unlikely that the failure to detect an anorexigen-induced rise in primary pulmonary hypertension was because of underascertainment. The association between fenfluramine derivatives and PAH is consistent with the risk elevations previously reported.

Adolescent↗

PubMed2006

Right ventricular dyssynchrony in heart failure: a tissue Doppler imaging study.

BACKGROUND: The development of right ventricular dysfunction is a poor prognostic sign in patients with heart failure (HF). Although left ventricular dyssynchrony has been well described, it is not known whether right ventricular dyssynchrony coexists in HF. We used tissue Doppler imaging to determine whether right ventricular dyssynchrony is also present in HF patients. METHODS AND RESULTS: In 34 HF patients (mean age 56 +/- 13 years), we measured longitudinal strain at the right ventricular free wall, interventricular septum, and left ventricular lateral wall. Right ventricular and left ventricular dyssynchrony were defined as the difference in time to peak strain between the right ventricular free wall and the septum and between the left ventricular lateral wall and septum, respectively. Mean right ventricular dyssynchrony was 59 +/- 45 ms and the mean left ventricular dyssynchrony was 80 +/- 62 ms. We found a strong correlation between right ventricular dyssynchrony and pulmonary artery systolic pressure (r = 0.73; P < .001) and a negative correlation between right ventricular dyssynchrony and right ventricular fractional area change (r = -0.43; P < .02). CONCLUSION: HF patients exhibit right ventricular dyssynchrony by strain imaging which correlates with pulmonary hypertension and right ventricular dysfunction.

Adult↗

PubMed2006

Pulmonary arterial hypertension.

PURPOSE OF REVIEW: The prevalence of pulmonary arterial hypertension is rising worldwide. Significant progress in our understanding of the pathobiology of pulmonary arterial hypertension has resulted in a shift from vasodilator therapy to the development of specific drugs targeting seminal molecular derangements of this disorder. This review highlights the recent advances in treatment and provides directions for the future care. RECENT FINDINGS: Induction of endothelin-1 and decreased transcription of nitric oxide and prostacyclin leads to pulmonary vasoconstriction that triggers several downstream molecular events which result in pulmonary vascular remodeling. Treatment with endothelin receptor antagonists, prostanoids and phosphodiesterase-5 inhibitors that prevent breakdown of cGMP have all demonstrated benefits in prospective, randomized, controlled trials of pulmonary arterial hypertension patients. Future strategies will combine these therapies to explore whether targeting more than one pathway provides synergistic long-term benefit. SUMMARY: Treatment guidelines developed by the American College of Chest Physicians aim to ensure that evidence-based approaches are practiced. Because of genetic heterogeneity in treatment effects and outcomes among patients, pharmacogenetics which will study polymorphisms that modulate the response to treatment will enable physicians to deliver cost-effective, tailored treatments for all pulmonary arterial hypertension patients in the future.

Antihypertensive Agents↗

PubMed2005

Myocardial recovery using ventricular assist devices: prevalence, clinical characteristics, and outcomes.

BACKGROUND: Ventricular assist devices (VADs) are important bridges to cardiac transplantation. VAD support may also function as a bridge to ventricular recovery (BTR); however, clinical predictors of recovery and long-term outcomes remain uncertain. We examined the prevalence, characteristics, and outcomes of BTR subjects in a large single center series. METHODS AND RESULTS: We implanted VADs in 154 adults at the University of Pittsburgh from 1996 through 2003. Of these implants, 10 were BTR. This included 2/80 (2.5%) ischemic patients (supported 42 and 61 days, respectively). Both subjects had surgical revascularization, required perioperative left VAD support, and were alive and transplant-free at follow up (232 and 1319 days, respectively). A larger percentage of nonischemic patients underwent BTR (8/74, 11%; age 30+/-14; 88% female; left ventricular ejection fraction 18+/-6%; supported 112+/-76 days). Three had myocarditis, 4 had post-partum cardiomyopathy (PPCM), and 1 had idiopathic cardiomyopathy. Five received biventricular support. After explantation, ventricular function declined in 2 PPCM patients who then required transplantation. Ventricular recovery in the 6 nonischemic patients surviving transplant-free was maintained (left ventricular ejection fraction 54+/-5%; follow-up 1.5+/-0.9 years). Overall, 8 of 10 BTR patients are alive and free of transplant (follow-up 1.6+/-1.1 years). CONCLUSIONS: In a large single center series, BTR was evident in 11% of nonischemic patients, and the need for biventricular support did not preclude recovery. For most BTR subjects presenting with acute inflammatory cardiomyopathy, ventricular recovery was maintained long-term. VAD support as BTR should be considered in the care of acute myocarditis and PPCM.

Acute Disease↗

PubMed2005

Biventricular assist device utilization for patients with morbid congestive heart failure: a justifiable strategy.

BACKGROUND: The rationale for the use of a biventricular assist device (BiVAD) for morbid congestive heart failure (MCHF) has been questioned because of historically unacceptable rates of postimplant and post-transplant mortality as well as perceived barriers to their outpatient management. METHODS AND RESULTS: All patients who received a Thoratec BiVAD from January 1990 to December 2003 at the University of Pittsburgh were studied retrospectively. There were a total of 73 patients (32% ischemic, 21% idiopathic, and 47% other) who had a BiVAD implanted. Before implantation, 100% were on > or =1 inotropic agent, and 77% had an intra-aortic balloon pump. Overall survival was 69%; 42 patients (84%) received cardiac transplantation, 5 patients (10%) were weaned, and 3 (6%) remained supported on BiVAD. If the 14 patients with postcardiotomy failure and acute myocardial infarction with shock are excluded, the overall survival improves to 75%. Five-year actuarial survival after heart transplantation was 58%. Of the 29 patients implanted before 2000, the 4-month actuarial freedom from driveline infections, bloodstream infections, and neurological events was 10%, 54%, and 48%, respectively, whereas the rates of these events for the 44 patients implanted after 2000 improved to 70%, 79%, and 80%, respectively. Since 2000, 21 (48%) patients were discharged from the hospital, of whom 38% went to an outpatient residence, 33% to a skilled nursing facility, and 29% to home. Once discharged, > or =1 readmission occurred in 45% and > or =2 readmissions in 48%. CONCLUSIONS: BiVAD support for MCHF has an acceptable overall mortality and survival to transplantation. Morbidity has been significantly reduced in the past 4 years, and management as an outpatient is achievable.

Adult↗

PubMed2005

Right ventricular dyssynchrony in patients with pulmonary hypertension is associated with disease severity and functional class.

BACKGROUND: Abnormalities in right ventricular function are known to occur in patients with pulmonary arterial hypertension. OBJECTIVE: Test the hypothesis that chronic elevation in pulmonary artery systolic pressure delays mechanical activation of the right ventricle, termed dyssynchrony, and is associated with both symptoms and right ventricular dysfunction. METHODS: Fifty-two patients (mean age 46 +/- 15 years, 24 patients with chronic pulmonary hypertension) were prospectively evaluated using several echocardiographic parameters to assess right ventricular size and function. In addition, tissue Doppler imaging was also obtained to assess longitudinal strain of the right ventricular wall, interventricular septum, and lateral wall of the left ventricle and examined with regards to right ventricular size and function as well as clinical variables. RESULTS: In this study, patients with chronic pulmonary hypertension had statistically different right ventricular fractional area change (35 +/- 13 percent), right ventricular end-systolic area (21 +/- 10 cm2), right ventricular Myocardial Performance Index (0.72 +/- 0.34), and Eccentricity Index (1.34 +/- 0.37) than individuals without pulmonary hypertension (51 +/- 5 percent, 9 +/- 2 cm2, 0.27 +/- 0.09, and 0.97 +/- 0.06, p < 0.005, respectively). Furthermore, peak longitudinal right ventricular wall strain in chronic pulmonary hypertension was also different -20.8 +/- 9.0 percent versus -28.0 +/- 4.1 percent, p < 0.01). Right ventricular dyssynchrony correlated very well with right ventricular end-systolic area (r = 0.79, p < 0.001) and Eccentricity Index (r = 0.83, p < 0.001). Furthermore, right ventricular dyssynchrony correlates with pulmonary hypertension severity index (p < 0.0001), World Health Organization class (p < 0.0001), and number of hospitalizations (p < 0.0001). CONCLUSION: Lower peak longitudinal right ventricular wall strain and significantly delayed time-to-peak strain values, consistent with right ventricular dyssynchrony, were found in a small heterogeneous group of patients with chronic pulmonary hypertension when compared to individuals without pulmonary hypertension. Furthermore, right ventricular dyssynchrony was associated with disease severity and compromised functional class.

Echocardiography↗

PubMed2005

Benefit of cardiac resynchronization therapy to a patient with a narrow QRS complex and ventricular dyssynchrony identified by tissue synchronization imaging.

This report described an 81-year-old woman with severe symptomatic heart failure, reduced ejection fraction, mitral regurgitation, and an electrocardiographic QRS width of 118 ms who had ventricular dyssynchrony identified by echocardiographic tissue synchronization imaging. Because of her severe heart failure symptoms on maximal medical therapy, referral to implant a defibrillator, and mechanical dyssynchrony, she underwent cardiac resynchronization-defibrillator therapy with lateral left ventricular lead placement. This resulted in an immediate 30% increase in stroke volume and 35% decrease in mitral regurgitation. Echocardiographic tissue synchronization imaging may play a role in identifying mechanical dyssynchrony in patients with narrow QRS duration who may potentially benefit from cardiac resynchronization therapy.

Aged, 80 and over↗

PubMed2005

Differential exercise performance on ventricular assist device support.

BACKGROUND: Ventricular assist devices (VADs) are approved for destination therapy because they improve survival in end-stage heart failure (HF). VADs are powered pneumatically or electrically. Pneumatic and electric left ventricular assist devices (LVADs) and biventricular assist devices (BiVADs) provide excellent hemodynamic support at rest, but differences in their effects on exercise tolerance are unclear. We sought to evaluate the effect of devices with varying operating parameters on exercise capacity. METHODS: Exercise physiology data obtained during maximal exercise with on-line gas-exchange analysis were collected for 38 consecutive VAD-implanted HF patients referred for exercise testing. RESULTS: Electric LVADs were implanted in 18 patients, and pneumatic LVADs in 10 patients. Percent of predicted peak exercise oxygen consumption (VO2%) was significantly greater in pneumatic LVAD patients (52.1 +/- 11.1% vs 38.2 +/- 11.3%, p < 0.05). The 10 patients implanted with a pneumatically powered LVAD were compared to 10 patients implanted with a pneumatically powered BiVAD. LVAD-supported patients had a higher VO2% (52.1 +/- 11.1% vs 36.5 +/- 17.7%, p < 0.05). CONCLUSIONS: HF patients supported with a pneumatic LVAD appear to have better exercise tolerance than those receiving an electric LVAD. Patients on LVAD support have better exercise tolerance than BiVAD-supported patients. This highlights the importance of right ventricular function to exercise tolerance in HF patients, and may have implications for future VAD design.

Adult↗

PubMed2005

Peripartum cardiomyopathy.

OBJECTIVE: To provide a review of the cardiac and obstetrical literature regarding the development of peripartum cardiomyopathy and, in particular, to examine risk factors, incidence, diagnosis, prognosis, and evidence-based treatment modalities. DESIGN: An extensive review of the current literature. RESULTS: Peripartum cardiomyopathy is a cardiomyopathy of unknown cause that occurs in pregnant females, most commonly in the early postpartum period. It shares many clinical characteristics with idiopathic dilated cardiomyopathy but occurs at a younger age and is associated with a better prognosis. Diagnosis is based upon the clinical presentation of congestive heart failure and objective evidence of left ventricular systolic dysfunction. Conventional pharmacologic therapy for congestive heart failure, such as diuretics, digoxin, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and beta-adrenergic blockers, are routinely used and are quite effective. For those patients who remain refractory to conventional pharmacologic therapy, cardiac transplantation and mechanical circulatory support are viable options. CONCLUSION: Mortality rates in peripartum cardiomyopathy have decreased, and this is most likely related to advances over the past 5 yrs in medical therapy for heart failure. Aggressive use of implantable defibrillators has significantly reduced the risk of sudden death in these patients. For >50% of peripartum cardiomyopathy patients, left ventricular function normalizes with pharmacologic therapy. However, subsequent pregnancies almost always are associated with recurrence of left ventricular systolic dysfunction.

Cardiomyopathies↗

PubMed2004

Pharmacogenetic interactions between angiotensin-converting enzyme inhibitor therapy and the angiotensin-converting enzyme deletion polymorphism in patients with congestive heart failure.

OBJECTIVES: We evaluated the interaction of angiotensin-converting enzyme (ACE) inhibitor therapy with the effect of the ACE D/I polymorphism on heart failure survival. BACKGROUND: The ACE deletion allele, ACE-D, is associated with increased ACE activity. The utilization of ACE genotyping to predict the impact of ACE inhibitor dose has not been previously evaluated. METHODS: We prospectively studied 479 subjects with systolic dysfunction (left ventricular ejection fraction 0.25 +/- 0.08). Subjects were divided on the basis of ACE inhibitor therapy into low dose ( 50%, n = 201), or those receiving angiotensin receptor antagonists (n = 51). Patients were genotyped for the ACE D/I polymorphism, followed to the end point of death or cardiac transplantation, and transplant-free survival compared by genotype. RESULTS: The ACE-D allele was associated with an increased risk of events (p = 0.026). In analysis by ACE inhibitor dose, this effect was primarily in the low-dose group (1-year percent event-free survival: II/ID/DD = 86/77/71,2-year = 79/66/59, p = 0.032). In the standard-dose group, the impact was markedly diminished (1-year: II/ID/DD = 91/81/80, 2-year: 77/70/71, p = 0.64). The impact of beta-blockers and high dose ACE inhibitors was greatest in subjects with the ACE DD genotype (p = 0.001) and was less apparent with the II and ID genotypes (p = 0.38). CONCLUSIONS: Higher doses of ACE inhibitors diminished the impact of the ACE-D allele, and the benefits of beta-blockers and high-dose ACE inhibitors appeared maximal for DD patients. Determination of ACE genotype may help target therapy for patients with heart failure.

Adrenergic beta-Antagonists↗

PubMed2004

Intermittent outpatient ultrafiltration for the treatment of severe refractory congestive heart failure.

BACKGROUND: Patients with severe congestive heart failure (CHF) become refractory to conventional medical therapy, leading to recurrent rehospitalizations. We examined the impact of intermittent outpatient ultrafiltration (UF), using either peritoneal dialysis or hemofiltration, on long-term clinical outcomes in patients with refractory CHF. METHODS AND RESULTS: We analyzed clinical and hemodynamic data in 19 consecutive patients with refractory CHF who received intermittent outpatient UF for at least 1 year between July 1998 and November 2002. The mean left ventricular ejection fraction of all 19 patients was 30.2 +/- 19.0%. All patients (100.0%) were New York Heart Association (NYHA) class IV. Only 5 patients (26.3%) received peritoneal dialysis; the remaining 14 (73.7%) received hemofiltration. There were 6 patients with a normal left ventricular ejection fraction (45%). After UF was started, the number of patients that were considered inotrope-dependent was reduced from 86.4% to 36.8% (P < .005). Compared with the year before UF was initiated, the number of CHF hospitalizations during follow-up was reduced from 2.6 to 0.3 (P < .005), and the NYHA class was improved from 4 to 3.1 (P < .005). Among all patients, 2 deaths were related to complications of UF, and cumulative 1-year survival was 63.2%. CONCLUSION: Our study suggests that UF is a safe, feasible therapy, but it needs further evaluation in carefully designed, prospective, randomized clinical trials. UF has the potential for offering another important therapeutic option for patients with severe and refractory CHF.

Adult↗

PubMed2004

Effect of the TNF-alpha-promoter polymorphism on cardiac allograft rejection.

BACKGROUND: A polymorphism exists in the tumor necrosis factor alpha (TNF-alpha) promoter (position -308, G/A = TNFA1/TNFA2). The TNFA2 allele is associated with increased TNF-alpha production in vitro and has been reported to increase the risk of allograft rejection in pediatric recipients of cardiac transplantation. We examined the effect of the TNFA2 allele on the risk of allograft rejection in adult cardiac transplant recipients. METHODS: We prospectively analyzed 57 subjects (aged 54 +/- 11 years, 84% men, 49% ischemic) who underwent cardiac transplantation between October 1996 and July 2001. Patients were observed after transplantation (mean, 910 +/- 605 days) and the frequency of allograft rejection (biopsy Grade > or =2) in patients with the TNFA2 allele (Group A, n = 15) was compared with TNFA1 homozygotes (Group B, n = 42). Overall survival and time to rejection episodes also were compared between groups. RESULTS: The frequency of allograft rejection was similar between groups (Group A, 8/15 [56%]; Group B, 22/42 [52%]; p = 0.77). Time to rejection also was comparable (Group A, 17 +/- 11 days; Group B, 20 +/- 20 days, p = 0.74). Overall post-transplant survival was similar between groups (1- and 2-year percentage survival: Group A, 87% and 78%, Group B, 88% and 82%, p = 0.35). CONCLUSION: The TNFA2 allele was not associated with increased risk of rejection in adult cardiac transplant recipients. The impact of this polymorphism on overall post-transplant outcomes will require investigation in larger multicenter studies.

Adult↗

PubMed2004

Serial dobutamine stress echocardiography with Doppler assessment of the left internal thoracic artery graft after minimally invasive bypass for a patient with an orthotopic heart transplant.

Select patients who have undergone orthotopic heart transplantation with proximal left anterior disease may be candidates for minimally invasive direct coronary artery bypass surgery. Combining left internal thoracic artery transthoracic Doppler flow assessment with wall motion assessment during dobutamine stress echocardiography adds to the utility of this test by focusing attention on the graft's status as well as detecting ischemia due to cardiac allograft vasculopathy.

Aged↗

PubMed2004

Interaction of implantable defibrillator therapy with angiotensin-converting enzyme deletion/insertion polymorphism.

INTRODUCTION: The angiotensin-converting enzyme deletion allele (ACE D) decreases survival in patients with advanced heart failure. Whether the adverse impact on survival reflects an increased risk of pump failure or arrhythmic sudden death remains uncertain. If the ACE D genotype increases the risk of sudden death, implantable cardioverter defibrillator (ICD) therapy should diminish its negative impact. We sought to evaluate the effect of ICD therapy on ACE D genetic risk. METHODS AND RESULTS: The Genetic Risk Assessment of Cardiac Events (GRACE) study enrolled 479 patients at the University of Pittsburgh between 1996 and 2001. Blood was genotyped for the ACE D/I (deletion/insertion) polymorphism. Of the 479 patients, 82 (77% male, 84% Caucasian, age 56 +/- 11 years, 60% ischemic, left ventricular ejection fraction 0.23 +/- 0.08) received an ICD and were selected for outcomes analysis (mean follow-up 871 +/- 538 days). Transplant-free survival and survival alone were compared in ACE DD patients (n = 24, 29%) versus ACE DI/II patients (n = 58, 71%). Survival was significantly improved in ACE DI/II patients compared to those without an ICD (1 year: 93% vs 87%; 2 year: 89% vs 77%; P = 0.02) but not in ACE DD patients. Transplant-free survival among patients with an ICD was significantly worse in ACE DD versus ACE DI/II (1 year: 67% vs 88%, 2 year: 55% vs 80%, P = 0.03). Analysis of survival as a single endpoint revealed a similar result (1 year = 78% vs 94%; 2 year: 72% vs 88%; P = 0.05). ICD telemetry data showed a nonsignificant trend toward fewer individuals with arrhythmias in the ACE-DD group (46% vs 65%, P = 0.22) CONCLUSION: ICDs do not diminish the adverse influence of the ACE DD genotype on survival. This finding suggests that mortality in this high-risk genetic subset of patients is due to progression of heart failure rather than arrhythmic sudden death.

Alleles↗

PubMed2004

Use of a wearable defibrillator in terminating tachyarrhythmias in patients at high risk for sudden death: results of the WEARIT/BIROAD.

The automatic ICD improves survival in patients with a history of sudden cardiac arrest. However, some patients do not meet the guidelines for ICD implantation or are unable to receive an implantable device. This study tested the hypothesis that these patients could benefit from a wearable cardioverter defibrillator. Patients with symptomatic heart failure and an ejection fraction of <0.30 (WEARIT Study) or patients having complications associated with high risk for sudden death after a myocardial infarction or bypass surgery not receiving an ICD for up to 4 months (BIROAD Study) were enrolled into two studies. After a total of 289 patients had been enrolled in the trial (177 in WEARIT and 112 in BIROAD), prespecified safety and effectiveness guidelines had been met. Six (75%) of eight defibrillation attempts were successful. Six inappropriate shock episodes occurred during 901 months of patient use (0.67% unnecessary shocks per month of use). Twelve deaths occurred during the study 6 sudden deaths: 5 not wearing and 1 incorrectly wearing the device). Most patients tolerated the device although 68 patients quit due to comfort issues or adverse reactions. The results of the present study suggest that a wearable defibrillator is beneficial in detecting and effectively treating ventricular tachyarrhythmias in patients at high risk for sudden death who are not clear candidates for an ICD and may be useful as a bridge to transplantation or ICD in some patients.

Death, Sudden, Cardiac↗

PubMed2003

Effect of the Asp298 variant of endothelial nitric oxide synthase on survival for patients with congestive heart failure.

BACKGROUND: Significant variation exists within the endothelial nitric oxide synthase (NOS3) gene that may influence cardiovascular risk. The Asp298 variant of NOS3 has a shorter half-life in endothelial cells. Given the importance of nitric oxide in the heart failure syndrome, we evaluated the effect of this variant on event-free survival in a population with systolic dysfunction. METHODS AND RESULTS: Four hundred sixty-nine patients (72% male, 49% ischemic; mean age, 56+/-12 years) with systolic dysfunction (left ventricular ejection fraction < or =0.45) were enrolled in a study of Genetic Risk Assessment of Cardiac Events (GRACE). The polymorphism in exon 7 of NOS3, a G-T transition at position 894 that results in a Glu to Asp amino acid substitution for codon 298, was genotyped and subjects were followed prospectively to the end point of death or heart transplantation. Event-free survival was compared on the basis of the presence (group 1, n=266) or absence (group 2, n=203) of the Asp298 variant. Event-free survival was significantly poorer in patients with the Asp298 variant (percent event-free survival group 1 at 1/2/3 years=78/65/54; group 2=82/72/64, P=0.03). In subset analysis, the adverse impact of the Asp298 variant was primarily in patients with nonischemic cardiomyopathy (group 1=82/73/63; group 2=87/79/71, P=0.03) and was not apparent among patients with ischemic heart disease (group 1=75/59/47; group 2=74/62/54, P=0.71). CONCLUSIONS: For patients with heart failure caused by systolic function, the Asp298 variant of NOS3 is associated with poorer event-free survival, particularly in patients with nonischemic cardiomyopathy.

Adult↗

PubMed2003

Impact of beta-blocker therapy on functional capacity criteria for heart transplant listing.

BACKGROUND: Peak exercise oxygen consumption is a widely used parameter to determine the need for transplant listing in patients with severe heart failure. Currently, beta-blocker therapy is known to benefit patients with severe heart failure, although it has minimal or no effects on peak exercise oxygen consumption. This raises the hypothesis that peak exercise oxygen consumption transplant-listing criteria are not valid for patients with heart failure who receive beta-blocker therapy. METHODS: We compared outcomes in patients with chronic heart failure who underwent heart transplant evaluation with peak exercise oxygen consumption </= 14.0 ml/kg/min and who were treated with beta-blockers (n = 48) or who were not treated with beta-blockers (n = 55). RESULTS: Outcomes were significantly better for patients treated with beta-blockers (combined end-points of death, transplantation as United Network for Organ Sharing [UNOS] Status 1 or 2, and ventricular assist device placement, p = 0.0001). The 1-year survival was 92% and 3-year survival was 71% in the patients treated with beta-blockers, and 69% and 48% in the patients not treated with beta-blockers (compared with UNOS transplant survival data of 92% 1-year and 77% 3-year survival rates). CONCLUSIONS: Patients with chronic heart failure and severe functional impairment who were treated with beta-blockers have significantly better outcomes compared with similarly functionally impaired patients who were not treated with beta-blockers, and these patients would not be expected to derive a survival benefit from transplantation. Thus, in patients treated with beta-blockers, the use of peak exercise oxygen consumption as a criterion to list for heart transplantation may no longer be valid. Alternatively, non-usage of beta-blockers may be a criterion to list for transplantation.

Adrenergic beta-Antagonists↗