Management and Outcomes of Kidney Transplant Candidates With Severe Pulmonary Hypertension: A Single-center Strategy and Experience.

Background: Severe pulmonary hypertension (PH) is associated with high mortality posttransplant and thus is considered a contraindication to kidney transplantation. In this study, we describe the pretransplant management and posttransplant outcomes in patients with severe PH using a multidisciplinary approach. Methods: Between 11 of 2013 and 8 of 2022, we identified all patients with severe PH on initial pretransplant workup who underwent ultrafiltration (UF) or medical therapy for PH before transplant. Posttransplant we evaluated the perioperative course, renal function, graft, and patient survival. We compared survival to those who remained waitlisted or were delisted. Results: Three-two patients (mean age = 55.03 ± 10.22 y) diagnosed with severe PH on pretransplant screening echocardiogram. Thirty patients (94%) were subjected to a median of 4 (range, 3-8) UF sessions with an average weight loss of 4.33 ± 2.6 kg. Repeat assessment of PH revealed a decline in mean pulmonary artery systolic pressure from 67 ± 12 mm Hg to 43 ± 13 mm Hg (P < 0.0001). Seventeen patients (53%) received a kidney transplant. The mean estimated Glomerular Filtration Rate at 3, 6, 9, and 12 mo was 72 ± 27, 72 ± 28, 75 ± 29, and 75 ± 29 mL/min/1.73 m2. Among, those who underwent transplantation both graft and patient survival was 100% at 1-y posttransplant. Overall, since the UF intervention, at a median follow-up of 88 ± 12 mo those transplanted had a patient survival of 88% while those who remained on dialysis had a survival of 53% (P = 0.0003). Conclusion: In this single-center study, we report postcapillary PH can be a significant contributor to elevations in pulmonary artery systolic pressure. Using a multidisciplinary approach, PH can improve with volume removal and phosphodiesterase 5 inhibitors therapy leading to a successful posttransplant outcome.

Protein-assisted scalable mechanochemical exfoliation of few-layer biocompatible graphene nanosheets.

A facile method to produce few-layer graphene (FLG) nanosheets is developed using protein-assisted mechanical exfoliation. The predominant shear forces that are generated in a planetary ball mill facilitate the exfoliation of graphene layers from graphite flakes. The process employs a commonly known protein, bovine serum albumin (BSA), which not only acts as an effective exfoliation agent but also provides stability by preventing restacking of the graphene layers. The latter is demonstrated by the excellent long-term dispersibility of exfoliated graphene in an aqueous BSA solution, which exemplifies a common biological medium. The development of such potentially scalable and toxin-free methods is critical for producing cost-effective biocompatible graphene, enabling numerous possible biomedical and biological applications. A methodical study was performed to identify the effect of time and varying concentrations of BSA towards graphene exfoliation. The fabricated product has been characterized using Raman spectroscopy, powder X-ray diffraction, transmission electron microscopy and scanning electron microscopy. The BSA-FLG dispersion was then placed in media containing Astrocyte cells to check for cytotoxicity. It was found that lower concentrations of BSA-FLG dispersion had only minute cytotoxic effects on the Astrocyte cells.

A Single Dose of Dietary Nitrate Increases Maximal Knee Extensor Angular Velocity and Power in Healthy Older Men and Women.

BACKGROUND: Aging results in reductions in maximal muscular strength, speed, and power, which often lead to functional limitations highly predictive of disability, institutionalization, and mortality in elderly adults. This may be partially due to reduced nitric oxide (NO) bioavailability. We, therefore, hypothesized that dietary nitrate (NO3-), a source of NO via the NO3- → nitrite (NO2-) → NO enterosalivary pathway, could increase muscle contractile function in older subjects. METHODS: Twelve healthy older (age 71 ± 5 years) men and women were studied using a randomized, double-blind, placebo-controlled, crossover design. After fasting overnight, subjects were tested 2 hours after ingesting beetroot juice containing or devoid of 13.4 ± 1.6 mmol NO3-. Plasma NO3- and NO2- and breath NO were measured periodically, and muscle function was determined using isokinetic dynamometry. RESULTS: N O 3 - ingestion increased (p < .001) plasma NO3-, plasma NO2-, and breath NO by 1,051% ± 433%, 138% ± 149%, and 111% ± 115%, respectively. Maximal velocity of knee extension increased (p < .01) by 10.9% ± 12.1%. Maximal knee extensor power increased (p < .05) by 4.4% ± 7.8%. CONCLUSIONS: Acute dietary NO3- intake improves maximal knee extensor angular velocity and power in older individuals. These findings may have important implications for this population, in whom diminished muscle function can lead to functional limitations, dependence, and even premature death.

TFM classification and staging of oral submucous fibrosis: A new proposal.

BACKGROUND: We have evaluated the rationale of existing grading and staging schemes of oral submucous fibrosis (OSMF) based on how they are categorized. A novel classification and staging scheme is proposed. METHODS: A total of 300 OSMF patients were evaluated for agreement between functional, clinical, and histopathological staging. Bilateral biopsies were assessed in 25 patients to evaluate for any differences in histopathological staging of OSMF in the same mouth. Extent of clinician agreement for categorized staging data was evaluated using Cohen's weighted kappa analysis. Cross-tabulation was performed on categorical grading data to understand the intercorrelation, and the unweighted kappa analysis was used to assess the bilateral grade agreement. Probabilities of less than 0.05 were considered significant. Data were analyzed using SPSS Statistics (version 25.0, IBM, USA). RESULTS: A low agreement was found between all the stages depicting the independent nature of trismus, clinical features, and histopathological components (K = 0.312, 0.167, 0.152) in OSMF. Following analysis, a three-component classification scheme (TFM classification) was developed that describes the severity of each independently, grouping them using a novel three-tier staging scheme as a guide to the treatment plan. CONCLUSION: The proposed classification and staging could be useful for effective communication, categorization, and for recording data and prognosis, and for guiding treatment plans. Furthermore, the classification considers OSMF malignant transformation in detail.

Dietary nitrate-induced increases in human muscle power: high versus low responders.

Maximal neuromuscular power is an important determinant of athletic performance and also quality of life, independence, and perhaps even mortality in patient populations. We have shown that dietary nitrate (NO3- ), a source of nitric oxide (NO), improves muscle power in some, but not all, subjects. The present investigation was designed to identify factors contributing to this interindividual variability. Healthy men (n = 13) and women (n = 7) 22-79 year of age and weighing 52.1-114.9 kg were studied using a randomized, double-blind, placebo-controlled, crossover design. Subjects were tested 2 h after ingesting beetroot juice (BRJ) either containing or devoid of 12.3 ± 0.8 mmol of NO3- . Plasma NO3- and nitrite (NO2- ) were measured as indicators of NO bioavailability and maximal knee extensor speed (Vmax ), power (Pmax ), and fatigability were determined via isokinetic dynamometry. On average, dietary NO3- increased (P < 0.05) Pmax by 4.4 ± 8.1%. Individual changes, however, ranged from -9.6 to +26.8%. This interindividual variability was not significantly correlated with age, body mass (inverse of NO3- dose per kg), body mass index (surrogate for body composition) or placebo trial Vmax or fatigue index (in vivo indicators of muscle fiber type distribution). In contrast, the relative increase in Pmax was significantly correlated (r = 0.60; P < 0.01) with the relative increase in plasma NO2- concentration. In multivariable analysis female sex also tended (P = 0.08) to be associated with a greater increase in Pmax. We conclude that the magnitude of the dietary NO3- -induced increase in muscle power is dependent upon the magnitude of the resulting increase in plasma NO2- and possibly female sex.

Dietary Nitrate Increases VO2peak and Performance but Does Not Alter Ventilation or Efficiency in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Patients with heart failure with reduced ejection fraction (HFrEF) exhibit lower efficiency, dyspnea, and diminished peak oxygen uptake (VO2peak) during exercise. Dietary nitrate (NO3-), a source of nitric oxide (NO), has improved these measures in some studies of other populations. We determined the effects of acute NO3- ingestion on exercise responses in 8 patients with HFrEF using a randomized, double-blind, placebo-controlled, crossover design. METHODS AND RESULTS: Plasma NO3-, nitrite (NO2-), and breath NO were measured at multiple time points and respiratory gas exchange was determined during exercise after ingestion of beetroot juice containing or devoid of 11.2 mmol of NO3-. NO3- intake increased (P < .05-0.001) plasma NO3- and NO2- and breath NO by 1469 ± 245%, 105 ± 34%, and 60 ± 18%, respectively. Efficiency and ventilation during exercise were unchanged. However, NO3- ingestion increased (P < .05) VO2peak by 8 ± 2% (ie, from 21.4 ± 2.1 to 23.0 ± 2.3 mL.min-1.kg-1). Time to fatigue improved (P < .05) by 7 ± 3 % (ie, from 582 ± 84 to 612 ± 81 seconds). CONCLUSIONS: Acute dietary NO3- intake increases VO2peak and performance in patients with HFrEF. These data, in conjunction with our recent data demonstrating that dietary NO3- also improves muscle contractile function, suggest that dietary NO3- supplementation may be a valuable means of enhancing exercise capacity in this population.

Microfibers as Physiologically Relevant Platforms for Creation of 3D Cell Cultures.

Microfibers have received much attention due to their promise for creating flexible and highly relevant tissue models for use in biomedical applications such as 3D cell culture, tissue modeling, and clinical treatments. A generated tissue or implanted material should mimic the natural microenvironment in terms of structural and mechanical properties as well as cell adhesion, differentiation, and growth rate. Therefore, the mechanical and biological properties of the fibers are of importance. This paper briefly introduces common fiber fabrication approaches, provides examples of polymers used in biomedical applications, and then reviews the methods applied to modify the mechanical and biological properties of fibers fabricated using different approaches for creating a highly controlled microenvironment for cell culturing. It is shown that microfibers are a highly tunable and versatile tool with great promise for creating 3D cell cultures with specific properties.

Acute Dietary Nitrate Intake Improves Muscle Contractile Function in Patients With Heart Failure: A Double-Blind, Placebo-Controlled, Randomized Trial.

BACKGROUND: Skeletal muscle strength, velocity, and power are markedly reduced in patients with heart failure, which contributes to their impaired exercise capacity and lower quality of life. This muscle dysfunction may be partially because of decreased nitric oxide (NO) bioavailability. We therefore sought to determine whether ingestion of inorganic nitrate (NO3 (-)) would increase NO production and improve muscle function in patients with heart failure because of systolic dysfunction. METHODS AND RESULTS: Using a double-blind, placebo-controlled, randomized crossover design, we determined the effects of dietary NO3 (-) in 9 patients with heart failure. After fasting overnight, subjects drank beetroot juice containing or devoid of 11.2 mmol of NO3 (-). Two hours later, muscle function was assessed using isokinetic dynamometry. Dietary NO3 (-) increased (P<0.05-0.001) breath NO by 35% to 50%. This was accompanied by 9% (P=0.07) and 11% (P<0.05) increases in peak knee extensor power at the 2 highest movement velocities tested (ie, 4.71 and 6.28 rad/s). Maximal power (calculated by fitting peak power data with a parabola) was therefore greater (ie, 4.74±0.41 versus 4.20±0.33 W/kg; P<0.05) after dietary NO3 (-) intake. Calculated maximal velocity of knee extension was also higher after NO3 (-) ingestion (ie, 12.48±0.95 versus 11.11±0.53 rad/s; P<0.05). Blood pressure was unchanged, and no adverse clinical events occurred. CONCLUSIONS: In this pilot study, acute dietary NO3 (-) intake was well tolerated and enhanced NO bioavailability and muscle power in patients with systolic heart failure. Larger-scale studies should be conducted to determine whether the latter translates into an improved quality of life in this population. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01682356.

Effect of acute dietary nitrate intake on maximal knee extensor speed and power in healthy men and women.

Nitric oxide (NO) has been demonstrated to enhance the maximal shortening velocity and maximal power of rodent muscle. Dietary nitrate (NO3(-)) intake has been demonstrated to increase NO bioavailability in humans. We therefore hypothesized that acute dietary NO3(-) intake (in the form of a concentrated beetroot juice (BRJ) supplement) would improve muscle speed and power in humans. To test this hypothesis, healthy men and women (n = 12; age = 22-50 y) were studied using a randomized, double-blind, placebo-controlled crossover design. After an overnight fast, subjects ingested 140 mL of BRJ either containing or devoid of 11.2 mmol of NO3(-). After 2 h, knee extensor contractile function was assessed using a Biodex 4 isokinetic dynamometer. Breath NO levels were also measured periodically using a Niox Mino analyzer as a biomarker of whole-body NO production. No significant changes in breath NO were observed in the placebo trial, whereas breath NO rose by 61% (P < 0.001; effect size = 1.19) after dietary NO3(-) intake. This was accompanied by a 4% (P < 0.01; effect size = 0.74) increase in peak knee extensor power at the highest angular velocity tested (i.e., 6.28 rad/s). Calculated maximal knee extensor power was therefore greater (i.e., 7.90 ± 0.59 vs. 7.44 ± 0.53 W/kg; P < 0.05; effect size = 0.63) after dietary NO3(-) intake, as was the calculated maximal velocity (i.e., 14.5 ± 0.9 vs. 13.1 ± 0.8 rad/s; P < 0.05; effect size = 0.67). No differences in muscle function were observed during 50 consecutive knee extensions performed at 3.14 rad/s. We conclude that acute dietary NO3(-) intake increases whole-body NO production and muscle speed and power in healthy men and women.

Spontaneous resolution of a branchial cleft cyst without intervention: a previously unreported outcome.

Branchial cleft cysts typically present as a persistent mass in the anterior triangle of the neck. Diagnosis is made by imaging and fine needle aspiration cytology and is confirmed histologically after excision. We report a branchial cleft cyst in a 27-year-old woman that resolved spontaneously over several weeks without surgical intervention. To the best of our knowledge this is the first report of such a case.

Reconstruction of a bilateral mandibular defect due to trauma using a single fibula free flap.

The reconstruction of noncontiguous bilateral mandibular defects using a single bony free flap is rarely performed because such defects are seldom encountered. This report describes the reconstruction of a bilateral body defect caused by shrapnel injury. A free vascularized osteomyocutaneous fibula flap was designed to replace 2 mandibular defects in the patient. The midportion of the fibula was resected without damage to the periosteum and vascular pedicle, and a skin paddle was used to monitor the flap. This would appear to be the first report of its use in the reconstruction of bilateral mandibular defects from trauma.

Patient outcome following 2 different stress imaging approaches: a prospective randomized comparison.

OBJECTIVES: The study sought to prospectively compare patient outcome after stress real-time myocardial contrast echocardiography (RTMCE) versus conventional stress echo (CSE), where contrast is used to optimize wall motion (WM) analysis. BACKGROUND: Myocardial perfusion imaging with RTMCE may improve the detection of coronary artery disease (CAD), and predict patient outcome. METHODS: Patients with intermediate to high pre-test probability referred for dobutamine or exercise stress echocardiography were prospectively randomized to either RTMCE or CSE. Definity contrast was used for CSE only when endocardial border delineation was inadequate (63% of studies). Studies were interpreted by either an experienced contrast reviewer (R1; n = 1257), or 4 Level 3 echocardiographers (R2) with basic contrast training (n = 806). Death, nonfatal myocardial infarction (MI), and revascularizations were recorded at follow-up. RESULTS: Follow-up was available in 2,014 patients (median 2.6 years). Mean age was 59 ± 13 years (53% women). An abnormal RTMCE was more frequently observed than an abnormal CSE (p < 0.001), and more frequently resulted in revascularization (p = 0.004). Resting WM abnormalities were also more frequently seen with RTMCE (p < 0.01), and were an independent predictor of death/nonfatal MI (p = 0.005) for RTMCE, but not CSE. The predictive value of a positive study, whether with CSE or RTMCE, was significant for both R1 and R2 reviewers in predicting the combined endpoint, but R1 was better than R2 at predicting patients at risk for death or nonfatal MI. CONCLUSIONS: Perfusion imaging with RTMCE improves the detection of CAD during stress echocardiography, and identifies those more likely to undergo revascularization following an abnormal study.

Value of reserve pulse pressure in improving the risk stratification of patients with normal myocardial perfusion imaging.

AIMS: To evaluate the incremental prognostic value of reserve-pulse pressure (reserve-PP: exercise-PP minus rest-PP) to standard risk factors among patients with suspected coronary artery disease (CAD) but normal exercise myocardial perfusion imaging (MPI). METHODS AND RESULTS: We studied 4269 consecutive symptomatic patients without known CAD who were referred for exercise MPI but had normal MPI results (mean age 58 ± 12 years, 56% females, 84% referred for evaluation of chest pain or dyspnoea, 95% with intermediate pretest likelihood of CAD). There were 202 deaths over 5.1 ± 1.4 years of follow-up. Reserve-PP was abnormal (<44 mmHg increase in PP from rest) in 1894 patients (44%). Patients with an abnormal reserve-PP had a higher risk of death compared with patients with normal reserve-PP [hazard ratio (HR): 2.47, 95% CI, 1.8-3.3]. In multivariable models adjusting for age, sex, ejection fraction, medications, heart rate recovery, Duke treadmill score (DTS), and rest-PP, each 10 mmHg lower reserve-PP was associated with a 20.6% increase in risk-adjusted mortality (adjusted HR 0.83, 95% CI 0.76-0.91). Models incorporating reserve-PP significantly reclassified risk compared with models without these parameters (net reclassification index 14.3%, P = 0.0007; integrated discrimination index 0.69, P = 0.01). CONCLUSION: In patients without a history of CAD and a normal MPI, an abnormal reserve-PP identified and reclassified those at higher risk of death independent of known risk factors and DTS.

Poor periodontal health: A cancer risk?

Evidence indicates that chronic infections and inflammation are associated with increased risk of cancer development. There has also been considerable evidence that proves the interrelationship between bacterial and viral infections and carcinogenesis. Periodontitis is a chronic oral infection thought to be caused by gram-negative anaerobic bacteria in the dental biofilm. Periodontal bacteria and viruses may act synergistically to cause periodontitis. Many studies have shown that periodontal pockets may act as reservoirs for human papilloma virus, cytomegalovirus, Epstein Barr virus, and suspected agents associated with oral cancer. Periodontitis, characterized by epithelial proliferation and migration, results in a chronic release of inflammatory cytokines, chemokines, growth factors, prostaglandins, and enzymes, all of which are associated with cancer development. This review article intends to shed light on the association between periodontal health and carcinogenesis.

Prospective randomized comparison of conventional stress echocardiography and real-time perfusion stress echocardiography in detecting significant coronary artery disease.

BACKGROUND: Although retrospective studies have suggested that myocardial perfusion and wall motion analysis with real-time myocardial contrast echocardiography (RTMCE) improves the detection of coronary artery disease (CAD) during dobutamine or exercise stress echocardiography, a prospective randomized comparison with conventional stress echocardiography that did not use RTMCE has not been performed. METHODS: A total of 1,776 patients with preserved resting left ventricular wall motion undergoing dobutamine or exercise stress echocardiography for suspicion of CAD were randomized to either non-RTMCE, for which contrast was used only for the approved indication of enhancing left ventricular opacification, or RTMCE, for which contrast infusion was used in all cases to examine both wall motion and myocardial perfusion. Comparisons in test positivity, and positive predictive value in those subsequently referred for quantitative coronary angiography, were performed. RESULTS: Patients randomized to RTMCE had significantly higher test positivity (22% for RTMCE vs 15% with non-RTMCE, P = .0002). The increased test positivity occurred without a difference in positive predictive value in predicting >50% diameter stenoses by quantitative coronary angiography (67% for non-RTMCE, 73% for RTMCE). The mechanism for increased detection of CAD with RTMCE was mostly due to the detection of subendocardial wall thickening abnormalities that would have gone undetected when examining transmural wall thickening. CONCLUSIONS: RTMCE improves the detection of CAD during dobutamine and exercise stress echocardiography, mainly by the detection of subendocardial ischemia.

Management of non-ST-segment elevation acute coronary syndrome: comparison of the updated guidelines from North America and Europe.

The American College of Cardiology/American Heart Association and the European Society of Cardiology published updated guidelines in 2011 for the management of patients with non-ST-segment elevation acute coronary syndrome. In this article, we highlight the most important new recommendations, review their supporting data, describe differences between the guidelines, and discuss new literature published since the latest guidelines were released. Key updates include detailed guidance regarding early risk stratification, use of coronary computed tomography angiography, selection of initial management strategy, novel antiplatelet agents, and new measures to enhance performance and quality. Major unique recommendations in the European Society of Cardiology guideline include endorsement of ticagrelor inhibitor or prasugrel (after delineation of coronary anatomy) as the first choice of P2Y12 inhibitors, establishment of protocols to identify patients for percutaneous coronary interventions vs. coronary artery bypass surgery, and use of the CRUSADE bleeding score. Meanwhile, unique recommendations in the American College of Cardiology/American Heart Association guideline include administration of prasugrel in selected patients before coronary angiography and consideration of continued dual antiplatelet therapy beyond 15 months after drug-eluting stent placement. Both guidelines include new recommendations endorsing platelet function and genetic testing in selected patients on clopidogrel, renal protection strategies, and less aggressive in patient's glycemic control. As these guidelines represent the most evidence-based approach, health care providers should become familiar with these updated recommendations to ensure optimal treatment of their patients with non-ST-segment elevation acute coronary syndrome.

Perspectives on the 2009 focused updates on the management of ST-segment elevation myocardial infarction and percutaneous intervention.

The American College of Cardiology, American Heart Association and Society of Angiography and Intervention recently published updated guidelines for management of patients with acute ST elevation myocardial infarction (STEMI) and percutaneous coronary intervention (PCI). In this article, we highlight the most important new recommendations and review the supporting data. Key aspects of these updates include guidance regarding the selection of antithrombotic therapy, caution in treating hyperglycemia with insulin, and opinion that insufficient data currently exist to recommend against concomitant administration of proton pump inhibitors and thienopyridines. New interventional recommendations include support for aspiration thrombectomy, drug eluting stents, PCI of unprotected left main disease, and use of fractional flow reserve to guide whether PCI is warranted in symptomatic patients with intermediate coronary stenoses. As these guidelines represent a synopsis of the most recently available data in the management of patients with STEMI, health care providers should familiarize themselves with these updated recommendations to ensure optimal treatment of their patients.

Day 1 care in patients with non-ST-segment elevation myocardial infarction.

In 2007, the American College of Cardiology/American Heart Association and the European Society of Cardiology updated their guidelines for the management of patients with non-ST-segment elevation myocardial infarction (NSTEMI). Based on evidence from recent clinical studies, both 2007 guidelines recommend early risk stratification, administration of appropriate pharmacologic therapy, and selective use of percutaneous coronary intervention in order to reduce morbidity and mortality in these patients. In this article, we focus on management of patients with NSTEMI during the first 24 h of presentation and present a clinical scenario to illustrate the current guidelines-based management strategy.

Management of ST-segment elevation myocardial infarction: Comparison of the updated guidelines from North America and Europe.

The American College of Cardiology/American Heart Association and the European Society of Cardiology each recently published updated guidelines for management of patients with acute ST elevation myocardial infarction. In this article, we highlight the most important new recommendations, review their supporting data, and describe differences between the guidelines. Key aspects of these updates include detailed guidance regarding the selection of a reperfusion strategy and the incorporation of newer adjunctive antithrombotic agents. Both new guidelines suggest caution in the administration of intravenous beta-blockers, avoidance of nonsteroidal anti-inflammatory agents, and support a more aggressive approach to secondary risk factor management. The 2 guidelines have some nuanced differences as well as some recommendations that are unique to each guideline. They present different levels of support for the 4 available adjunctive parenteral anticoagulants, vary in their endorsement of routine elective coronary angiography after fibrinolysis, and cite different targets for low density lipoprotein long-term. Major unique recommendations include the American College of Cardiology/American Heart Assocaition's emphasis of a stepped approach to analgesia in patients with musculoskeletal pain beginning with acetaminophen or aspirin and a lower target international normalized ratio in patients receiving warfarin, aspirin, and clopidogrel. Meanwhile, unique recommendations in the European Society of Cardiology guidelines include measures to prevent/treat microvascular obstruction and reperfusion injury associated with percutaneous coronary intervention and greater emphasis on maintaining eugylcemia. As these guidelines represent an evidence based approach, health care providers should become familiar with the new data and the resultant updated recommendations to ensure optimal treatment of their patients with ST-elevation myocardial infarction.

Incremental prognostic value of gated Rb-82 positron emission tomography myocardial perfusion imaging over clinical variables and rest LVEF.

OBJECTIVES: This investigation sought to study the incremental value of gated rubidium (Rb)-82 positron emission tomography (PET) myocardial perfusion imaging (MPI) over clinical variables for predicting survival and future cardiac events. BACKGROUND: The prognostic value of Rb-82 PET-MPI and left ventricular ejection fraction (LVEF) reserve (stress minus rest LVEF) is not well defined. METHODS: 1,432 consecutive patients undergoing gated rest/vasodilator stress rubidium-82 PET were followed up for at least 1 year. Of these, rest and peak stress LVEF and LVEF reserve were available in 985 patients. Cardiac events (CE) including cardiac death or nonfatal myocardial infarction and all-cause death were assessed. RESULTS: Over a mean follow-up of 1.7 +/- 0.7 years, 83 (5.8%) CE and 140 (9.7%) all-cause death were observed. There was an increase in risk for both end points with an increasing percentage of abnormal and ischemic myocardium. With normal, mild, moderate, or severely ischemic scans, the observed annualized rates of CE were 0.7%, 5.5%, 5%, and 11% and of all-cause death were 3.3%, 7.2%, 6.9%, and 12.5%, respectively. In 985 patients with peak stress gated data, the observed annualized rates of CE (2.1% vs. 5.3%, p < 0.001) and all-cause death (4.3% vs. 9.2%, p < 0.001) were higher in patients with an LVEF reserve <0% compared with those with an LVEF reserve >or=0%. On Cox proportional hazards analysis, after consideration of clinical, historical, and rest LVEF information, stress PET results and LVEF reserve yielded incremental prognostic value with respect to both CE and all-cause death. CONCLUSIONS: Vasodilator stress Rb-82 PET-MPI provides incremental prognostic value to historical/clinical variables and rest LVEF to predict survival free of CE and all-cause death. An increasing percentage of ischemia on PET-MPI is associated with an increase in the risk of CE and all-cause death. Left ventricular ejection fraction reserve provides significant independent and incremental value to Rb-82 MPI for predicting the risk of future adverse events.