Prognostic utility of splenic response ratio in dipyridamole PET myocardial perfusion imaging.

BACKGROUND: Cardiac magnetic resonance perfusion studies with adenosine stress have shown that splenic response can identify patients with inadequate pharmacologic stress. We investigate the incremental prognostic impact of splenic response ratio (SRR) in patients with normal Rubidium (Rb)-82 PET myocardial perfusion imaging (MPI). METHODS: Consecutive patients undergoing dipyridamole Rb-82 PET MPI for the evaluation of coronary artery disease were screened. Spleen and liver Rb-82 activity was measured and the SRR was calculated: SRR = (Spleen stress/Liver stress)/(Spleen rest/Liver rest). Major adverse cardiac events (MACE) were determined at 1 year of follow-up in patients with normal summed stress score and normal summed difference score. RESULTS: Of the 839 patients screened, the spleen was visualized in 703 (84%) of scans. There was significantly higher MACE observed in splenic non-responders vs splenic responders in both the normal SSS (7.8% vs 2.9%, P = .027) and the normal SDS groups (7.4% vs 2.2%, P = .014). In multivariate analysis in patients with normal SDS, splenic response was a significant, independent predictor of MACE (HR 2.97, 95% CI 1.10 to 8.04, P = .033). CONCLUSIONS: SRR is a novel imaging metric to identify patients with sub-maximal vasodilator stress and an incremental prognostic marker in patients with normal SDS and SSS (Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01128023).

Long-Term Follow-Up of Outcomes With F-18-Fluorodeoxyglucose Positron Emission Tomography Imaging-Assisted Management of Patients With Severe Left Ventricular Dysfunction Secondary to Coronary Disease.

BACKGROUND: Whether viability imaging can impact long-term patient outcomes is uncertain. The PARR-2 study (Positron Emission Tomography and Recovery Following Revascularization) showed a nonsignificant trend toward improved outcomes at 1 year using an F-18-fluorodeoxyglucose positron emission tomography (PET)-assisted strategy in patients with suspected ischemic cardiomyopathy. When patients adhered to F-18-fluorodeoxyglucose PET recommendations, outcome benefit was observed. Long-term outcomes of viability imaging-assisted management have not previously been evaluated in a randomized controlled trial. METHODS AND RESULTS: PARR-2 randomized patients with severe left ventricular dysfunction and suspected CAD being considered for revascularization or transplantation to standard care (n= 195) versus PET-assisted management (n=197) at sites participating in long-term follow-up. The predefined primary outcome was time to composite event (cardiac death, myocardial infarction, or cardiac hospitalization). After 5 years, 105 (53%) patients in the PET arm and 111 (57%) in the standard care arm experienced the composite event (hazard ratio for time to composite event =0.82 [95% confidence interval 0.62-1.07]; P=0.15). When only patients who adhered to PET recommendations were included, the hazard ratio for the time to primary outcome was 0.73 (95% confidence interval 0.54-0.99; P=0.042). CONCLUSIONS: After a 5-year follow-up in patients with left ventricular dysfunction and suspected CAD, overall, PET-assisted management did not significantly reduce cardiac events compared with standard care. However, significant benefits were observed when there was adherence to PET recommendations. PET viability imaging may be best applied when there is likely to be adherence to imaging-based recommendations. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00385242.

Reduced Myocardial Flow in Heart Failure Patients With Preserved Ejection Fraction.

BACKGROUND: There remains limited insight into the pathophysiology and therapeutic advances directed at improving prognosis for patients with heart failure with preserved ejection fraction (HFpEF). Recent studies have suggested a role for coronary microvascular dysfunction in HFpEF. Rb-82 cardiac positron emission tomography imaging is a noninvasive, quantitative approach to measuring myocardial flow reserve (MFR), a surrogate marker for coronary vascular health. The aim of this study was to determine whether abnormalities exist in MFR in patients with HFpEF without epicardial coronary artery disease. METHODS AND RESULTS: A total of 376 patients with ejection fraction ≥50%, no known history of obstructive coronary artery disease, and a confirmed diagnosis of heart failure (n=78) were compared with patients with no evidence of heart failure (n=298), further stratified into those with (n=186) and without (n=112) hypertension. Global and regional left ventricular MFR was calculated as stress/rest myocardial blood flow using Rb-82 positron emission tomography. Patients with HFpEF were more likely to be older, female, and have comorbid hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, anemia, and renal dysfunction. HFpEF was associated with a significant reduction in global MFR (2.16±0.69 in HFpEF versus 2.54±0.80 in hypertensive controls; P<0.02 and 2.89±0.70 in normotensive controls; P<0.001). A diagnosis of HFpEF was associated with 2.62 times greater unadjusted odds of having low global MFR (defined as <2.0) and remained a significant predictor of reduced global MFR after adjusting for comorbidities. CONCLUSIONS: HFpEF, in the absence of known history for obstructive epicardial coronary artery disease, is associated with reduced MFR independent of other risk factors.

Prognostic value of rubidium-82 positron emission tomography in patients after heart transplant.

BACKGROUND: Cardiac allograft vasculopathy is a key prognostic determinant after heart transplant. Detection and risk stratification of patients with cardiac allograft vasculopathy are problematic. Positron emission tomography using rubidium-82 allows quantification of absolute myocardial blood flow and may have utility for risk stratification in this population. METHODS AND RESULTS: Patients with a history of heart transplant undergoing dipyridamole rubidium-82 positron emission tomography were prospectively enrolled. Myocardial perfusion and left ventricular ejection fraction were recorded. Absolute flow quantification at rest and after dipyridamole stress as well as the ratio of mean global flow at stress and at rest, termed myocardial flow reserve, were calculated. Patients were followed for all-cause death, acute coronary syndrome, and heart failure hospitalization. A total of 140 patients (81% men; median age, 62 years; median follow-up, 18.2 months) were included. There were 14 events during follow-up (9 deaths, 1 acute coronary syndrome, and 4 heart failure admissions). In addition to baseline clinical variables (estimated glomerular filtration rate, previously documented cardiac allograft vasculopathy), relative perfusion defects, mean myocardial flow reserve, and mean stress myocardial blood flow were significant predictors of adverse outcome. CONCLUSIONS: Abnormalities on rubidium-82 positron emission tomography were predictors of adverse events in heart transplant patients. Larger prospective studies are required to confirm these findings.

Effects of short-term continuous positive airway pressure on myocardial sympathetic nerve function and energetics in patients with heart failure and obstructive sleep apnea: a randomized study.

BACKGROUND: Heart failure with reduced ejection fraction and obstructive sleep apnea (OSA), 2 states of increased metabolic demand and sympathetic nervous system activation, often coexist. Continuous positive airway pressure (CPAP), which alleviates OSA, can improve ventricular function. It is unknown whether this is due to altered oxidative metabolism or presynaptic sympathetic nerve function. We hypothesized that short-term (6-8 weeks) CPAP in patients with OSA and heart failure with reduced ejection fraction would improve myocardial sympathetic nerve function and energetics. METHODS AND RESULTS: Forty-five patients with OSA and heart failure with reduced ejection fraction (left ventricular ejection fraction 35.8±9.7% [mean±SD]) were evaluated with the use of echocardiography and 11C-acetate and 11C-hydroxyephedrine positron emission tomography before and ≈6 to 8 weeks after randomization to receive short-term CPAP (n=22) or no CPAP (n=23). Work metabolic index, an estimate of myocardial efficiency, was calculated as follows: (stroke volume index×heart rate×systolic blood pressure÷Kmono), where Kmono is the monoexponential function fit to the myocardial 11C-acetate time-activity data, reflecting oxidative metabolism. Presynaptic sympathetic nerve function was measured with the use of the 11C-hydroxyephedrine retention index. CPAP significantly increased hydroxyephedrine retention versus no CPAP (Δretention: +0.012 [0.002, 0.021] versus -0.006 [-0.013, 0.005] min(-1); P=0.003). There was no significant change in work metabolic index between groups. However, in those with more severe OSA (apnea-hypopnea index>20 events per hour), CPAP significantly increased both work metabolic index and systolic blood pressure (P<0.05). CONCLUSIONS: In patients with heart failure with reduced ejection fraction and OSA, short-term CPAP increased hydroxyephedrine retention, indicating improved myocardial sympathetic nerve function, but overall did not affect energetics. In those with more severe OSA, CPAP may improve cardiac efficiency. Further outcome-based investigation of the consequences of CPAP is warranted. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00756366.

Identification of inflamed aortic plaque in conventional fluorodeoxyglucose-positron emission tomography myocardial viability studies.

BACKGROUND: It has been shown that (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is useful in identifying inflamed plaque in major arteries. This study evaluated the feasibility of inflamed plaque detection with routinely acquired cardiac FDG-PET viability studies in patients with severe coronary artery disease and left ventricular dysfunction. METHODS: Clinically indicated myocardial viability scans using FDG and PET combined with computed tomography from 103 patients were retrospectively analyzed for FDG uptake in the proximal, ascending, and descending thoracic aorta. Aortic uptake was graded on the basis of peak and mean target-to-background ratio (TBR): grade 0, < 1; grade 1, 1.01-1.49; grade 2, 1.5-1.99; and grade 3, > 2. RESULTS: Of the 103 patients, 71 (68.9%) had a history of myocardial infarction, 88 (85.4%) were on statins, and 70 (68%) were on angiotensin-converting enzyme (ACE) inhibitors. Increased FDG uptake (mean TBR grade 1-3) was seen in 79 of 103 patients (77%), and grade 3 aortic uptake based on peak TBR was found in 12 of 103 patients (12%). CONCLUSIONS: Detection of inflamed atherosclerotic plaque in the aorta with conventional FDG viability scans is feasible. The rate of very positive uptake in this population of ischemic heart disease patients is low, possibly reflecting aggressive secondary risk factor modification including statin and ACE inhibitor use.

Does quantification of myocardial flow reserve using rubidium-82 positron emission tomography facilitate detection of multivessel coronary artery disease?

BACKGROUND: Relative myocardial perfusion imaging (MPI) is the standard imaging approach for the diagnosis and prognostic work-up of coronary artery disease (CAD). However, this technique may underestimate the extent of disease in patients with 3-vessel CAD. Positron emission tomography (PET) is also able to quantify myocardial blood flow. Rubidium-82 ((82)Rb) is a valid PET tracer alternative in centers that lack a cyclotron. The aim of this study was to assess whether assessment of myocardial flow reserve (MFR) measured with (82)Rb PET is an independent predictor of severe obstructive 3-vessel CAD. METHODS: We enrolled a cohort of 120 consecutive patients referred to a dipyridamole (82)Rb PET MPI for evaluation of ischemia neither with prior coronary artery bypass graft nor with recent percutaneous coronary intervention that also underwent coronary angiogram within 6 months of the PET study. Patients with and without 3-vessel CAD were compared. RESULTS: Among patients with severe 3-vessel CAD, MFR was globally reduced (<2) in 88% (22/25). On the adjusted logistic Cox model, MFR was an independent predictor of 3-vessel CAD [.5 unit decrease, HR: 2.1, 95% CI (1.2-3.8); P = .015]. The incremental value of (82)Rb MFR over the SSS was also shown by comparing the adjusted SSS models with and without (82)Rb MFR (P = .005). CONCLUSION: (82)Rb MFR is an independent predictor of 3-vessel CAD and provided added value to relative MPI. Clinical integration of this approach should be considered to enhance detection and risk assessment of patients with known or suspected CAD.

Reduced septal glucose metabolism predicts response to cardiac resynchronization therapy.

BACKGROUND: Up to 50% of patients do not respond to Cardiac Resynchronization Therapy (CRT). Recent work has focused on quantifying mechanical dyssynchrony and left ventricular scar. Septal reverse-mismatch (R-MM) (reduced FDG uptake vs perfusion) has been observed in patients with cardiomyopathy and prolonged QRS duration. We hypothesized that a greater quantity of septal R-MM would indicate a greater potential for reversibility of the cardiomyopathy, when the dyssynchrony is improved with CRT. Therefore, this study's objective was to assess whether greater septal R-MM pattern predicts response to CRT. METHODS AND RESULTS: Forty-nine patients had pre-implant Rubidium-82 and Fluorine-18-fluorodeoxyglucose PET scanning. Total and regional left ventricular scar size and extent of R-MM were calculated. Response to CRT was defined as ≥10% improvement in left ventricular end-systolic volume or ≥5% absolute ejection fraction improvement. In the non-ischemic cardiomyopathy subset non-responders had significantly less septal R-MM than responders (13.1% compared to 27.1%, P = .012). There were correlations between the extent of septal R-MM and the increase in ejection fraction (r = 0.692, P = .0004) and reduction in left ventricular end-systolic volume (r = -0.579, P = .004). For each 5% absolute increase in extent of septal R-MM the odds ratio of being a responder was 2.17 (95% CI 1.15, 4.11, P = .017). Extent of septal R-MM displayed high sensitivity and specificity (area under curve = 0.855, P = .017) to predict response. CONCLUSIONS: In patients with non-ischemic cardiomyopathy, greater extent of septal glucose metabolic R-MM pattern, predicted response to CRT. This parameter may be useful for identifying patients who benefit from CRT.

Does FDG PET-assisted management of patients with left ventricular dysfunction improve quality of life? A substudy of the PARR-2 trial.

BACKGROUND: Patients with left ventricular dysfunction whose management is directed by F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging may have a quality of life (QOL) benefit over standard care. METHODS: Among 430 patients randomized in the PET and Recovery Following Revascularization (PARR)-2 trial to FDG PET-assisted management vs standard, QOL scores were obtained using the European Quality of Life-5 Dimensions (EQ-5D) in 427 patients at baseline (FDG PET n = 216; standard n = 211) and 355 patients at 12-month follow-up (FDG PET n = 184; standard n = 171). EQ-5D scores between FDG PET and standard arms were compared using mixed model repeated measures (MMRM). Subgroup analysis compared EQ-5D scores between patients in FDG PET who adhered to PET recommendations (Adherence) vs standard using MMRM. Interaction of revascularization with management was assessed using a general linear model. RESULTS: A trend toward higher EQ-5D scores in FDG PET was observed (P = 0.056). Subgroup analysis showed a significant difference favouring adherence (P = 0.04). Higher QOL at 6 months for FDG PET (P = 0.02) and Adherence (P = 0.02) were observed. For revascularization, an interaction with management (FDG PET vs standard) for QOL was observed (6 months: P = 0.01; 12 months: P = 0.1); Adherence (6 months: P = 0.01; 12 months: P = 0.1). CONCLUSIONS: FDG PET-directed management improves QOL, at least in the short-term and with adherence to recommendations. This may relate to revascularization, and may indicate better treatment selection using FDG PET.

Impaired myocardial flow reserve on rubidium-82 positron emission tomography imaging predicts adverse outcomes in patients assessed for myocardial ischemia.

OBJECTIVES: We evaluated the prognostic value of myocardial flow reserve (MFR) using rubidium-82 ((82)Rb) positron emission tomography (PET) in patients assessed for ischemia. BACKGROUND: The clinical value of MFR quantification using (82)Rb PET beyond relative myocardial perfusion imaging remains uncertain. METHODS: We prospectively enrolled 704 consecutive patients; 677 (96%) completed follow-up (median 387 days [interquartile range: 375 to 416 days]). Patients were divided into 4 groups: I, normal summed stress score (SSS) (<4) and normal myocardial flow reserve (MFR) (>2); II, normal SSS and MFR <2; III, SSS ≥4 and MFR ≥2; IV, SSS ≥4 and MFR <2. RESULTS: For patients with a normal SSS and those with an abnormal SSS, there were significant differences in outcomes for hard events (cardiac death and myocardial infarction) between patients with MFR ≥2 and those with MFR <2 (I: 1.3% vs. II: 2% [p = 0.029]; III: 1.1% vs. IV: 11.4% [p = 0.05]) and for major adverse cardiac events (MACE) (p = 0.003 and p < 0.001, respectively). In the adjusted Cox model, MFR was an independent predictor of hard events (hazard ratio: 3.3; 95% confidence interval: 1.1 to 9.5; p = 0.029) and MACE (hazard ratio: 2.4, 95% confidence interval: 1.4 to 4.4, p = 0.003). The incremental prognostic value of the MFR over the SSS was demonstrated by comparing the adjusted SSS model with and without the MFR for hard events (p = 0.0197) and MACE (p = 0.002). CONCLUSIONS: MFR quantified using (82)Rb PET predicts hard cardiac events and MACE independent of the SSS and other parameters. Routine assessment of (82)Rb PET-quantified MFR could improve risk stratification for patients being investigated for ischemia.

Altered myocardial glucose utilization and the reverse mismatch pattern on rubidium-82 perfusion/F-18-FDG PET during the sub-acute phase following reperfusion of acute anterior myocardial infarction.

BACKGROUND: Reperfused myocardium post-acute myocardial infarction (AMI) may have altered metabolism with implications for therapy response and function recovery. We explored glucose utilization and the "reverse mismatch" (RMM) pattern (decreased F-18-fluorodeoxyglucose (FDG) uptake relative to perfusion) in patients who underwent mechanical reperfusion with percutaneous coronary intervention (PCI) for AMI. METHODS AND RESULTS: Thirty-one patients with anterior wall AMI treated with acute reperfusion, with left ventricular ejection fraction ≤45%, underwent rest rubidium-82 (Rb-82) and FDG PET 2-10 days post-AMI. Resting echocardiograms were used to assess wall motion abnormalities. Significant RMM occurred in 15 (48%) patients and was associated with a shorter time to PCI of 2.9 hours (2.2, 13.3 hours) compared to patients without significant RMM: 11.4 hours (3.9, 22.4 hours) (P = .03). Within the peri-infarct regions, segments with significant RMM were more likely to have wall motion abnormalities (OR = 2.3 (1.1, 4.7), P = .02) compared to segments without significant RMM. CONCLUSIONS: RMM is a common pattern on perfusion/FDG PET during the sub-acute phase following reperfusion of AMI and is associated with shorter times to PCI. Within the peri-infarct region, RMM occurs frequently and is more often associated with wall motion abnormalities than segments without RMM. Whether this represents a myocardial metabolic shift during the sub-acute phase of recovery warrants further study.

Relation between right ventricular function and increased right ventricular [18F]fluorodeoxyglucose accumulation in patients with heart failure.

BACKGROUND: Left heart failure is characterized by alterations in metabolic substrate utilization, and metabolic modulation may be a future strategy in the management of heart failure. Little is known about cardiac metabolism in the right ventricle and how it relates to other measures of right ventricular (RV) function. This study was designed to measure glucose metabolism in the right ventricle, as estimated by [(18)F]fluorodeoxyglucose (FDG) positron emission tomography imaging and to determine the relation between RV function and FDG uptake in patients with heart failure. METHODS AND RESULTS: A total of 68 patients underwent cardiac [(18)F]FDG positron emission tomography scanning with measurement of RV FDG uptake as a standardized uptake value. Perfusion imaging was acquired at rest with rubidium-82 or [(13)N]ammonia. RV function was determined by equilibrium radionuclide ventriculography. Relative RV FDG uptake was determined as the ratio of RV to LV standardized uptake value. Fifty-five percent of these patients had ischemic cardiomyopathy. The mean LV and RV ejection fractions were 21±7% and 35±10%, respectively. There was a correlation between RV ejection fraction and the ratio of RV to LV FDG uptake whether the entire LV myocardium (r=-0.40, P<0.001) or LV free wall (r=-0.43, P<0.001) was used. This relation persisted in the subgroup with nonischemic cardiomyopathy (r=-0.37, P=0.04). RV FDG uptake was weakly related to increased RV systolic pressure but not related to LV size, function, or FDG uptake. The correlation between RV ejection fraction and RV/LV FDG was maintained after partial-volume correction (r=-0.68, P<0.001). CONCLUSIONS: RV dysfunction is associated with an increase in RV FDG uptake, the magnitude of which may be correlated with severity.

18F-FDG PET imaging of myocardial viability in an experienced center with access to 18F-FDG and integration with clinical management teams: the Ottawa-FIVE substudy of the PARR 2 trial.

UNLABELLED: (18)F-FDG PET may assist decision making in ischemic cardiomyopathy. The PET and Recovery Following Revascularization (PARR 2) trial demonstrated a trend toward beneficial outcomes with PET-assisted management. The substudy of PARR 2 that we call Ottawa-FIVE, described here, was a post hoc analysis to determine the benefit of PET in a center with experience, ready access to (18)F-FDG, and integration with clinical teams. METHODS: Included were patients with left ventricular dysfunction and suspected coronary artery disease being considered for revascularization. The patients had been randomized in PARR 2 to PET-assisted management (group 1) or standard care (group 2) and had been enrolled in Ottawa after August 1, 2002 (the date that on-site (18)F-FDG was initiated) (n = 111). The primary outcome was the composite endpoint of cardiac death, myocardial infarction, or cardiac rehospitalization within 1 y. Data were compared with the rest of PARR 2 (PET-assisted management [group 3] or standard care [group 4]). RESULTS: In the Ottawa-FIVE subgroup of PARR 2, the cumulative proportion of patients experiencing the composite event was 19% (group 1), versus 41% (group 2). Multivariable Cox proportional hazards regression showed a benefit for the PET-assisted strategy (hazard ratio, 0.34; 95% confidence interval, 0.16-0.72; P = 0.005). Compared with other patients in PARR 2, Ottawa-FIVE patients had a lower ejection fraction (25% +/- 7% vs. 27% +/- 8%, P = 0.04), were more often female (24% vs. 13%, P = 0.006), tended to be older (64 +/- 10 y vs. 62 +/- 10 y, P = 0.07), and had less previous coronary artery bypass grafting (13% vs. 21%, P = 0.07). For patients in the rest of PARR 2, there was no significant difference in events between groups 3 and 4. The observed effect of (18)F-FDG PET-assisted management in the 4 groups in the context of adjusted survival curves demonstrated a significant interaction (P = 0.016). Comparisons of the 2 arms in Ottawa-FIVE to the 2 arms in the rest of PARR 2 demonstrated a trend toward significance (standard care, P = 0.145; PET-assisted management, P = 0.057). CONCLUSION: In this post hoc group analysis, a significant reduction in cardiac events was observed in patients with (18)F-FDG PET-assisted management, compared with patients who received standard care. The results suggest that outcome may be benefited using (18)F-FDG PET in an experienced center with ready access to (18)F-FDG and integration with imaging, heart failure, and revascularization teams.

Effect of lateral wall scar on reverse remodeling with cardiac resynchronization therapy.

BACKGROUND: Up to 50% of patients do not respond to cardiac resynchronization therapy (CRT). Recent work has focused on quantifying left ventricular (LV) scar, with conflicting results. Some studies have shown that the global extent of LV scar is important, whereas others found the size of the septal or lateral wall scar to be key. OBJECTIVE: This study sought to examine the relative importance of the size and distribution of LV scar in determining reverse remodeling to CRT. METHODS: Forty-nine patients had pre-implantation rubidium-82 and fluorine-18-fluorodeoxyglucose positron emission tomography scanning. Total and regional LV scar size were calculated. Response to CRT was pre-specified as > or =10% improvement in LV end-systolic volume and/or > or =5% absolute ejection fraction improvement. RESULTS: Responders (n = 31) had significantly less lateral wall scar than responders (5.6% compared with 24.5%, P = .008) but a similar extent of global and septal scar. In the ischemic group, responders' median lateral wall scar size was 11.2% (IQR 0.0 to 31.2), compared with 47.8% (IQR 21.2 to 73.4) P = .052. In the ischemic group, for each 5% absolute decrease in lateral scar size, the odds ratio of being a responder was 1.87 (95% CI: 1.11 to 3.15, P = .018). In the nonischemic group, median lateral wall scar size of responders was 3.4% (IQR 0.0 to 10.3) compared with the nonresponders, 14.4% (IQR 9.0 to 27.8), P = .046. CONCLUSION: Responders had significantly less lateral wall scar than nonresponders, but a similar extent of global and septal scar. This held true in both ischemic and nonischemic cardiomyopathy patients.

Increasing benefit from revascularization is associated with increasing amounts of myocardial hibernation: a substudy of the PARR-2 trial.

OBJECTIVES: We sought to determine: 1) whether F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) parameters identify high-risk patients who gain benefit from revascularization; 2) whether there is a cut point for such benefit; and 3) predictors of outcome in patients with severe left ventricular (LV) dysfunction due to coronary artery disease. BACKGROUND: Patients with ischemic LV dysfunction might benefit from revascularization but not without risk. The FDG PET imaging can detect viable myocardium that recovers after revascularization. In the PARR-2 (PET and Recovery Following Revascularization-2) trial, FDG PET imaging showed a nonsignificant trend for improved outcome compared with standard care. Understanding the predictors of outcome from this prospective trial should help better identify patients at risk and which patients most benefit from revascularization. METHODS: This post hoc analysis included 182 patients with left ventricular ejection fraction (LVEF) <35% and coronary artery disease, being considered for revascularization work-up, and randomized to the PET arm of PARR-2. The primary outcome was a composite of cardiac death, myocardial infarction, or cardiac repeat hospital stay at 1 year. RESULTS: There is an interaction between PET mismatch and protocol revascularization such that higher mismatch, when combined with revascularization, yields fewer primary outcome events (p = 0.02). On the basis of adjusted Cox modeling, with reduced mismatch (<7%), the risk is not significantly different with or without revascularization. As mismatch increases above this mark, risk is reduced with revascularization. Increasing creatinine (for a 10-mumol/l increase: hazard ratio: 1.03, 95% confidence interval: 1.01 to 1.06, p = 0.010) is also associated with increased risk, whereas decreasing LVEF (for a 2% decrease: hazard ratio: 1.08, 95% confidence interval: 0.99 to 1.18, p = 0.087) trends toward an association with increased risk. CONCLUSIONS: In this post hoc analysis, patients with ischemic cardiomyopathy with larger amounts of mismatch have improved outcome with revascularization. Renal function was also an independent predictor of outcome. The FDG PET seems to define high-risk patients that gain benefit from revascularization. (PET and Recovery Following Revascularization [PARR 2]; NCT00385242).

F-18-fluorodeoxyglucose positron emission tomography imaging-assisted management of patients with severe left ventricular dysfunction and suspected coronary disease: a randomized, controlled trial (PARR-2).

OBJECTIVES: We conducted a randomized trial to assess the effectiveness of F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)-assisted management in patients with severe ventricular dysfunction and suspected coronary disease. BACKGROUND: Such patients may benefit from revascularization, but have significant perioperative morbidity and mortality. F-18-fluorodeoxyglucose PET can detect viable myocardium that might recover after revascularization. METHODS: Included were patients with severe left ventricular (LV) dysfunction and suspected coronary disease being considered for revascularization, heart failure, or transplantation work-ups or in whom PET was considered potentially useful. Patients were stratified according to recent angiography or not, then randomized to management assisted by FDG PET (n = 218) or standard care (n = 212). The primary outcome was the composite of cardiac death, myocardial infarction, or recurrent hospital stay for cardiac cause, within 1 year. RESULTS: At 1 year, the cumulative proportion of patients who had experienced the composite event was 30% (PET arm) versus 36% (standard arm) (relative risk 0.82, 95% confidence interval [CI] 0.59 to 1.14; p = 0.16). The hazard ratio (HR) for the composite outcome, PET versus standard care, was 0.78 (95% CI 0.58 to 1.1; p = 0.15); for patients that adhered to PET recommendations for revascularization, revascularization work-up, or neither, HR = 0.62 (95% CI 0.42 to 0.93; p = 0.019); in those without recent angiography, for cardiac death, HR = 0.4 (95% CI 0.17 to 0.96; p = 0.035). CONCLUSIONS: This study did not demonstrate a significant reduction in cardiac events in patients with LV dysfunction and suspected coronary disease for FDG PET-assisted management versus standard care. In those who adhered to PET recommendations and in patients without recent angiography, significant benefits were observed. The utility of FDG PET is best realized in this subpopulation and when adherence to recommendations can be achieved.

Reasons for escalating pacemaker implants.

Surveys of pacing practice have shown a steady increase in pacemaker implantation rates in the past 15 years, despite no major changes in United States guidelines for permanent pacing. There are no data to explain why this is occurring. In this study, records were extracted from the National Hospital Discharge Survey to investigate this. There were 3 major findings. First, age-adjusted implantation rates increased progressively over the study period from 370 per million in 1990 to 612 per million in 2002. Second, it was found that the escalating implantation rate is attributable to increasing implantation for isolated sinus node dysfunction (SND). Implantation for SND increased significantly over the study period (by 102%), whereas implantation for all other indications did not. The increasing implantation for SND is due primarily to the increasing prevalence of SND, with a lesser increase in implantation rate relative to prevalence rate. The third major finding of this study is that there has been a progressive relative and absolute increase in the dual-chamber implantation rate. In 2002, 82.8% of all initial pacemaker implantations were dual-chamber devices. Furthermore, the National Hospital Discharge Survey data indicate that the major randomized pacing trials seem to have had no impact on pacing practice in the United States. In conclusion, age-adjusted implantation rates increased progressively over the study period. This escalating implantation rate is primarily attributable to increasing implantation for SND.