The effect of renal transplantation on left ventricular function, electrocardiography, and mechanical synchrony by gated myocardial perfusion imaging.

BACKGROUND: Depressed left ventricular ejection fraction (LVEF), LV mechanical dyssynchrony (LVMD), and prolonged QTc interval predict poor outcomes in end-stage renal disease (ESRD). Renal transplantation improves mortality in ESRD patients but the effects of transplantation on these indices remain undefined. METHODS: We identified patients with myocardial perfusion imaging (MPI) before and after renal transplantation. A control group consisted of ESRD patients who underwent 2 MPIs but did not receive a transplant. Changes in LVEF, LVMD indices [phase standard deviation (SD) and bandwidth (BW)] by MPI, and electrocardiogram (ECG) indices were determined. RESULTS: The study population consisted of 32 ESRD patients (53% male, 50 ± 11 years, 59% African American, 65% diabetic). The second MPI was performed 31 months (13-59 months) after renal transplantation. LVEF (72 ± 10% vs. 67 ± 10%, P < 0.001) but not SD (22 ± 15° vs. 22 ± 11°, P = 0.9) or BW (58 ± 35° vs. 57 ± 29°, P = 0.9) improved after transplantation. There were no changes in these indices in the control group. QTc (425 ± 30 ms vs. 447 ± 32 ms, P = <0.001) but not QRS (90 ± 21 ms vs. 90 ± 21 ms, P = 0.9) improved significantly after renal transplantation. CONCLUSIONS: LVEF and QTc improved after renal transplantation but LVMD indices and QRS did not change, which suggests that LVMD and electrical dyssynchrony may be irreversible in ESRD.

Prognostic value of transient ischemic dilation with regadenoson myocardial perfusion imaging.

BACKGROUND: Transient ischemic dilation (TID) of the left ventricle seen on myocardial perfusion imaging (MPI) is sometimes used as a marker of severe coronary artery disease. The prognostic value of TID obtained using regadenoson, a selective adenosine A2A receptor agonist, as a stress agent for MPI has not been studied. METHODS: TID ratio was measured using an automated software program on consecutive patients with normal and abnormal perfusion pattern on regadenoson MPI at a single institution. An abnormal TID was defined as greater than 1.33. The primary outcome was a composite of cardiac death, non-fatal myocardial infarction (MI), and late coronary revascularization (CR, >90 days after MPI). RESULTS: The study population consisted of 887 patients (62 ± 12 years, 66% male, 48% diabetes, 46% prior CR, 75% with abnormal perfusion pattern, left ventricular ejection fraction-LVEF 55 ± 6%). An abnormal TID was present in 51 (6%) patients. Baseline characteristics were not different based on the presence or absence of TID. Early CR (≤90 days) was performed in 11 (22%) patients with vs 92 (11%) patients without TID (P = .04). During a mean follow-up of 29 ± 19 months, the primary outcome occurred in 271 (31%) patients (22% cardiac death, 6% MI, 9% late CR). TID was associated with increased risk of the primary outcome (log-rank P = .017), an association largely driven by late CR. In a Cox proportional model adjusted for multiple variables including perfusion defect size (PDS) and LVEF, the hazard ratio for TID was 1.92 (95% CI 1.20-3.08, P = .007). In the subset of patients with normal perfusion pattern, there was no association between TID and outcomes. CONCLUSIONS: TID on regadenoson MPI carries important prognostic information that is independent from PDS and LVEF, but this association is restricted to patients with abnormal perfusion on imaging.

The effect of bone marrow mononuclear stem cell therapy on left ventricular function and myocardial perfusion.

BACKGROUND: Bone marrow stem cell (BMC) transfer is an emerging therapy with potential to salvage cardiomyocytes during acute myocardial infarction and promote regeneration and endogenous repair of damaged myocardium in patients with left ventricular (LV) dysfunction. We performed a meta-analysis to examine the association between administration of BMC and LV functional recovery as assessed by imaging. METHODS AND RESULTS: Our meta-analysis included data from 32 trials comprising information on 1,300 patients in the treatment arm and 1,006 patients in the control arm. Overall, BMC therapy was associated with a significant increase in LV ejection fraction by 4.6% ± 0.7% (P < .001) (control-adjusted increase of 2.8% ± 0.9%, P = .001), and a significant decrease in perfusion defect size by 9.5% ± 1.4% (P < .001) (control-adjusted decrease of 3.8% ± 1.2%, P = .002). The effect of BMC therapy was similar whether the cells were administered via intra-coronary or intra-myocardial routes and was not influenced by baseline ejection fraction or perfusion defect size. CONCLUSIONS: BMC transfer appears to have a positive impact on LV recovery in patients with acute coronary syndrome and those with stable coronary disease with or without heart failure. Most studies were small and a minority used a core laboratory for image analysis.

Comparison of three commercially available softwares for measuring left ventricular perfusion and function by gated SPECT myocardial perfusion imaging.

BACKGROUND: The three softwares, Quantitative Perfusion SPECT (QPS), Emory Cardiac Toolbox, and 4 Dimension-Myocardial SPECT (4DM) are widely used with myocardial perfusion imaging (MPI) to determine perfusion defect size (PDS) and left ventricular (LV) function. There are limited data on the degree of agreement between these methods in quantifying the LV perfusion pattern and function. METHODS AND RESULTS: In 120 consecutive patients who had abnormal regadenoson SPECT MPI with a visually derived summed stress score ≥4, the correlation between the softwares for measurements of PDS, reversible, and fixed defects was poor to fair (Spearman's ρ = 0.18-0.72). Overall, estimation of defect size was smaller by QPS and larger by 4DM. There was discordance among the softwares in 62% of the cases in defining PDS as small/moderate/large. The correlation between the softwares was better for measuring LVEF, volumes and mass (ρ = 0.84-0.97), and discrepant results for defining normal/mild-moderate/severe LV systolic dysfunction were prevalent in 28% of the patients. CONCLUSION: There are significant differences between the softwares in measuring PDS as well as LV function, and more importantly in defining small, moderate, or large ischemic burden. These results suggest the necessity of using the same software when assessing interval changes by serial imaging.

The prognostic value of left ventricular mechanical dyssynchrony using gated myocardial perfusion imaging in patients with end-stage renal disease.

BACKGROUND: Prior studies show that left ventricular mechanical dyssynchrony (LVD), measured by gated SPECT myocardial perfusion imaging (MPI), identifies patients with end-stage renal disease (ESRD) at higher risk for all-cause mortality but these were in small number of patients. We sought to assess the interaction between LVD and LV perfusion pattern in risk-stratification of a large sample size of patients with ESRD. METHODS: From the renal transplantation database maintained at the University of Alabama at Birmingham, we identified consecutive patients with ESRD who had gated SPECT MPI between 2003 and 2007. MPIs were reprocessed to derive LV ejection fraction (EF), perfusion defect size, and LVD [phase bandwidth (BW) and phase standard deviation (SD)]. The primary end-point was all-cause mortality, which was prospectively collected and verified against the social security death index database. RESULTS: There were 828 patients aged 52.6 ± 0.36 years (45% were women and 60% had diabetes mellitus). The LVEF was 54.8 ± 0.4% and the perfusion pattern was abnormal in 334 patients (41%). During a follow-up period of 61 ± 0.9 months, 230 patients (28%) received renal transplants and 290 patients (35%) died. The phase BW (73.1 ± 2.6° vs 66.3 ± 1.8°, P = .02) and SD (25.2 ± 0.8° vs 23.4 ± 0.5°, P = .06) were greater in patients who died than those who survived indicating greater dyssynchrony. Patients with phase BW >56° or SD ≥21° (median values) had worse 5-year survival (64% vs 72%, and 66% vs 71%, log-rank P = .005 and P = .07, respectively). After adjusting for demographics, co-morbidities, LVEF, and perfusion pattern, phase BW was associated with worse outcome (hazard ratio 1.289 95% CI 1.010-1.644, P = .04). CONCLUSIONS: LVD by phase analysis of gated SPECT MPI provides prognostic value in ESRD beyond myocardial perfusion and EF.

The relationship of left ventricular mechanical dyssynchrony and cardiac sympathetic denervation to potential sudden cardiac death events in systolic heart failure.

BACKGROUND: Patients with heart failure (HF) are at increased risk for left ventricular (LV) dyssynchrony which is associated with sudden cardiac death (SCD). This study examined the association of LV mechanical dyssynchrony and cardiac sympathetic denervation with potential SCD events in symptomatic patients with HF and reduced ejection fraction (HFrEF). METHODS: Of the 917 HFrEF patients in ADMIRE-HF, 92 experienced adjudicated potential SCD events during a 17 months median follow-up. Propensity scores were used to assemble a matched cohort of 85 pairs of patients with and without potential SCD events. ADMIRE-HF subjects had rest gated SPECT Tc-99m and I-123 MIBG imaging. Perfusion images were processed using phase analysis software to derive phase standard deviation (SD), an index of mechanical dyssynchrony. RESULTS: Of the 92 patients who experienced adjudicated potential SCD events 23 had SCD, 5 fatal myocardial infarction, 7 resuscitated cardiac arrest, 46 had appropriate ICD therapy, and 11 had sustained ventricular tachycardia. Patients who experienced potential SCD events had significantly wider phase SD than matched control patients (62.3 ± 2.4º vs 55.5 ± 2.3º, P = .03) and were more likely to have a phase SD ≥ 60º (53 % vs 35 %, P = .03). Fewer patients with potential SCD events (6 % vs 15 % of the controls, P = .08) had an MIBG heart/mediastinum uptake-ratio ≥1.6. CONCLUSIONS: Among symptomatic HFrEF patients, LV mechanical dyssynchrony is independently associated with potential SCD events. Phase analysis may provide incremental prognostic information on top of current indicators of SCD risk in HFrEF.

Regadenoson: a focused update.

Since its approval by the Food and Drug Administration in 2008, regadenoson has become the most commonly used vasodilator in the United States. Previous reviews have summarized the pre-clinical and clinical data on the use of regadenoson for myocardial perfusion imaging (MPI). Since then, data have emerged on the safety of this agent in special groups of patients such as those with chronic kidney disease, airway disease (asthma and chronic obstructive pulmonary disease), and liver disease. There has also been recent interest in the use of regadenoson in hybrid protocols with exercise as a way to improve patient tolerance and image quality. Finally, although regadenoson was approved for clinical use based on the agreement rate of regadenoson MPI and adenosine MPI with regards to perfusion abnormalities, data are now available on the prognostic data derived from regadenoson MPI. We will briefly summarize these recent reports here in a focused update on the use of regadenoson for MPI.

Impact of left ventricular function and the extent of ischemia and scar by stress myocardial perfusion imaging on prognosis and therapeutic risk reduction in diabetic patients with coronary artery disease: results from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.

BACKGROUND: The Bypass Angioplasty Revascularization Investigation 2 Diabetes trial demonstrated similar long-term clinical effectiveness of revascularization (REV) and intensive medical (MED) therapy. Comparisons of post-intervention ischemic burden have not been explored but are relevant to treatment decisions. This study examined differences in 1-year stress myocardial perfusion SPECT (MPS) abnormalities by randomized treatment. METHODS: MPS was performed in 1,505 patients at 1-year following randomization. MPS images were analyzed (masked to treatment) by a Nuclear Core Laboratory using a quantitative percent (%) of total, ischemic, and scarred myocardium. Cox proportional hazards models were used to estimate the relationship between MPS variables and trial endpoints. RESULTS: At 1-year, nearly all REV patients underwent the assigned procedure; while 16% of those randomized to MED received coronary REV. Patients randomized to REV exhibited fewer stress perfusion abnormalities than MED patients (P < .001). CABG patients had more frequent ischemic and scarred myocardium encumbering ≥ 5% of the myocardium when compared to those receiving PCI. Patients randomized to MED had more extensive ischemia and the median % of the myocardium with perfusion abnormalities was lower following REV (3% vs 9%, P = .01). A total of 59% of REV patients had no inducible ischemia at 1-year compared to 49% of MED patients (P < .001). Within the CABG stratum, those randomized to MED had the greatest rate of ischemic (P = .032) and scarred (P = .017) perfusion abnormalities. At 1-year, more extensive and severe stress myocardial perfusion abnormalities were associated with higher 5-year rates of death and a combined endpoint of cardiac death or myocardial infarction (MI) rates (11.3%, 8.1%, 6.8%, for ≥ 10%, 5%-9.9%, and 1-4.9% abnormal myocardium at stress, respectively, P < .001). In adjusted models, selected MPS variables were significantly associated with an increased hazard of cardiac death or MI (hazard ratio = 1.11 per 5% increase in abnormal myocardium at stress, P = .004). CONCLUSIONS: Patient management strategies that focus on ischemia resolution can be useful to guide the efficacy of near-term therapeutic approaches. A 1-year post-therapeutic intervention myocardial perfusion scan provides important information regarding prognosis in stable CAD patients with diabetes.

The prognostic value of the heart rate response to adenosine in relation to diabetes mellitus and chronic kidney disease.

BACKGROUND: Myocardial perfusion imaging (MPI) is a useful method for risk assessment in patients with diabetes mellitus (DM) and chronic kidney disease (CKD), but these patients have a residual risk that is not accounted for by MPI. The objective of this study is to determine whether the heart rate response (HRR) to adenosine has an incremental prognostic value to MPI in high-risk patients. METHODS: The study group included 879 (age 61 ± 13 years, 48% women, 58% white, 40% DM, 49% CKD) consecutive patients who underwent adenosine MPI. Chronic kidney disease was defined as an estimated glomerular filtration rate <60 mL/min per 1.73 m(2) or dialysis replacement therapy. An HRR <10% (change from baseline) was considered blunted. The outcome of interest was overall mortality. RESULTS: During a follow-up period of 40 ± 14 months, 212 patients (24%) died. Patients with DM (23.4% ± 16.3% vs 29.4% ± 21.4%, P < .0001) and CKD (22.7% ± 17.6% vs 30.5% ± 20.4%, P < .0001) had lower HRR as compared with patients without DM and CKD, respectively. A blunted HRR was associated with increased mortality in the overall population and in those with DM and CKD and helped in risk stratification when added to traditional MPI findings. In a Cox regression model, a blunted HRR was the strongest predictor of mortality (hazard ratio 2.8, P < .0001) and provided additional prognostic data to MPI (hazard ratio 1.9, P < .0001) after controlling for age, gender, race, history of myocardial infarction, DM, CKD, ß-blocker use, and presence of chest pain. CONCLUSIONS: A blunted HRR to adenosine is an independent predictor of poor outcome, adds incremental value to MPI, and helps in better risk stratification in high-risk patient groups.

Impact of ischemia on left ventricular dyssynchrony by phase analysis of gated single photon emission computed tomography myocardial perfusion imaging.

BACKGROUND: There is increasing awareness of the value of phase analysis of gated tomographic myocardial perfusion imaging in assessing left ventricular (LV) dyssynchrony. A concern repeatedly raised in many studies is whether reversible defects in the stress images "ischemia" could affect the phase-derived standard deviation and bandwidth, the two commonly used dyssynchrony indices. We hypothesized that the stress and rest images should provide comparable information because the images are acquired 1 hour after the tracer injection. METHODS AND RESULTS: We studied two groups of patients with normal LV ejection fraction and no fixed perfusion defects. In group-1 (N = 20), the patients had reversible perfusion defects involving > 10% of the LV myocardium and in group-2 (N = 20), the patients had normal images. All patients underwent stress/rest-gated single photon emission computed tomography sestamibi imaging (the stress study was acquired with the lower dose) between January and March 2010. Patients with left bundle branch block or ventricular pacing were excluded. The patients in group-1 had a mean age of 61 ± 9 years, 65% were men, 75% Caucasians, and 70% had known prior coronary artery disease. The size of the reversible perfusion defect was 20 ± 13% (range 11%-50%) of the LV myocardium. The rest and stress phase-derived standard deviation (16 ± 6° vs 18 ± 8° and 16 ± 7° vs. 19 ± 6°) and the rest and stress bandwidth (42 ± 14° vs 46 ± 16° and 45 ± 17° vs 52 ± 12°), respectively, (P = NS for all) were similar in the two groups. The change (stress-rest) in standard deviation and bandwidth in groups 1 and 2 were not statistically significant (0.2 ± 3.1° vs 1.4 ± 4.7°, and 2 ± 13° vs 5 ± 13°, respectively, P = NS). There was no significant change from rest to stress in the standard deviation and the bandwidth in group-1 (P = .8 and .4, respectively) and group-2 (P = .2 and .08, respectively). There was no correlation between the size of the reversible perfusion defect and the change in phase standard deviation or bandwidth (r = 0.07 and 0.12, respectively, P = NS). CONCLUSIONS: The presence of even a large reversible perfusion defect does not alter the indices of mechanical dyssynchrony by phase analysis. Further, comparable information is obtained whether using a low dose or a high dose of the radiotracer.

The effect of ranolazine on the vasodilator-induced myocardial perfusion abnormality.

BACKGROUND: We previously reported that ranolazine improved myocardial ischemia during exercise myocardial perfusion imaging (MPI). Since the mechanism of reversible perfusion defects is different in exercise than vasodilator MPI, and based on the mechanism of action of ranolazine, we hypothesized that vasodilator stress MPI may fail to show improvement in myocardial perfusion pattern. METHODS: Patients (n = 18) with known coronary artery disease and with reversible perfusion defects on a clinically indicated vasodilator stress MPI were re-studied 4 weeks after ranolazine (500-1000 mg PO BID) was added to their conventional treatment in an open-label trial. Perfusion pattern was assessed using automated methods. RESULTS: The baseline left ventricular ejection fraction was 59% ± 14%. The total perfusion defect (measured by polar maps) was 22% ± 13% before and 21% ± 16% of LV myocardium after treatment (P = NS). The reversible defect size was 14% ± 10% before and 14% ± 11% of LV myocardium after treatment (P = NS). The automated-derived summed stress score was 12 ± 8 before and 12 ± 10 after treatment (P = NS) and the automated-derived summed difference score was 6 ± 5 before and 6 ± 5 after treatment (P = NS). Only 3 patients showed a decrease in reversible perfusion defect size with treatment. CONCLUSION: Vasodilator stress MPI failed to show improvement in perfusion pattern after ranolazine treatment in most patients with baseline reversible defects. This is consistent with the unique anti-ischemic mechanism of ranolazine, which acts on the late I Na channel.

Left ventricular dyssynchrony in patients with end-stage liver disease.

BACKGROUND: Limited published data suggested that patients with end-stage liver disease (ESLD) might have "cirrhotic cardiomyopathy," which could have an earlier stage manifested by mechanical dyssynchrony before left ventricular (LV) dysfunction. METHODS AND RESULTS: We studied consecutive patients with ESLD who had a stress-gated Tc-99m sestamibi myocardial perfusion imaging between 2008 and 2010 prior to liver transplant. Patients with LVEF < 50%, abnormal perfusion, or QRS ≥ 120 ms were excluded. Baseline demographics, co-morbidities, model for ESLD (MELD) score, LV volumes, mass, ejection fraction (EF), and dyssynchrony indices (standard deviation and bandwidth) were extracted. The phase indices were compared to a normal cohort. There were 179 patients with a mean age 53 ± 8 years, LVEF 72 ± 10%. Hepatitis C, non-alcoholic steatohepatitis, and alcohol abuse were the most common cause of liver cirrhosis (40%, 18%, and 14%, respectively). Patients with ESLD had similar standard deviation (14 ± 8° vs 15 ± 6°, P = NS) and bandwidth (41 ± 25° vs 42 ± 14°, P = NS) to the normal cohort. Only four patients (2%) had a standard deviation >27° (mean + 2 SD of the control group). The phase standard deviations and bandwidth similar in patients with MELD scores of ≤10, 11-18, 19-24, and ≥25 (P = NS for both). There was no correlation between the MELD score and standard deviation or bandwidth (r = -0.044 and -0.068, respectively, P = NS for both). Also, there was no correlation between the QTc and dyssynchrony indices. After 1-year follow-up, 22 patients died (12%). The dyssynchrony indices were similar among those who died and those who survived. CONCLUSION: Patients with ESLD and normal EF have no evidence for LV dyssynchrony.

Safety of regadenoson in patients with end-stage liver disease.

BACKGROUND: Regadenoson is a selective A(2A) receptor agonist that is used for vasodilator stress myocardial perfusion imaging (MPI). Since the drug is partially metabolized by the liver, its safety in patients with end-stage liver disease (ESLD) needs to be determined. METHODS AND RESULTS: We studied 168 consecutive patients with ESLD who had regadenoson stress gated single photon emission computed tomography MPI between January 2008 and March 2010 before planned orthotopic liver transplantation and compared the hemodynamic responses and safety profile to 168 control patients. There were 72 women (43%) in ESLD versus 87 (52%) in the control group (P = .1). The patients with ESLD were younger (58 ± 7 vs 62 ± 12 years, P = .0002), but more likely to be Caucasians (P = .002). The MPI images were normal in 161 patients (96%) in each group. The left ventricular ejection fraction was 72 ± 10% in ESLD and 66 ± 11% in the control patients (P = .0001). The heart rate increase in response to regadenoson was lower in patients with ESLD than in the control group (16 ± 11 vs 23 ± 16 bpm, P = .0001), but the changes in systolic and diastolic blood pressures were similar (-9 ± 12 vs -11 ± 14 mmHg and -6 ± 8 vs -7 ± 10 mmHg, respectively, P = NS). There were no deaths or medication-related adverse events that required hospitalization in either group within 30 days of the study. CONCLUSION: This is the first study to document the tolerability and safety profile of regadenoson in patients with ESLD.

A blunted heart rate response to regadenoson is an independent prognostic indicator in patients undergoing myocardial perfusion imaging.

BACKGROUND: Regadenoson myocardial perfusion imaging (MPI) is a useful method for risk assessment. We hypothesized that the heart rate response (HRR) to regadenoson carries incremental prognostic information to that derived from perfusion pattern and left ventricular (LV) ejection fraction (EF). METHODS AND RESULTS: The study population included 1,156 (60 ± 13 years, 46% women, 40% diabetes mellitus, 53% chronic kidney disease) patients. During a follow-up period of 22 ± 5 months, 103 patients died (9%). Independent determinants of the HRR included age, gender, race, diabetes mellitus, coronary revascularization, LVEF, use of insulin and aldosterone antagonists. Decreasing HRR was associated with stepwise increase in mortality (log-rank P < .0001). In a Cox proportional model for mortality that adjusted for age, gender, diabetes mellitus, renal disease, and MPI findings, HRR in the lowest quartile was independently associated with fivefold increase in mortality compared to the highest quartile [HR 5.2, 95% CI 2.3-12.0, P < .0001]. Patients with a normal HRR had a relatively low annualized total mortality despite the presence of risk factors. The addition of HRR to traditional MPI findings had a net reclassification improvement of 15%, P = .02. CONCLUSION: A blunted HRR to regadenoson is an independent predictor of poor outcome, adds incremental value to MPI, and helps in better risk stratification.

Impact of left ventricular dyssynchrony by phase analysis on cardiovascular outcomes in patients with end-stage renal disease.

BACKGROUND: Cardiovascular disease is the leading cause of mortality in patients with end-stage renal disease (ESRD). While left ventricular (LV) perfusion pattern and ejection fraction (EF) are important determinant of outcome, the prognostic importance of LV dyssynchrony, which can also be assessed by gated SPECT myocardial perfusion imaging (MPI), has not been well studied in this population. METHODS AND RESULTS: The indices of LV mechanical dyssynchrony were measured by automated analysis of gated SPECT MPI in patients with ESRD who were evaluated for transplantation at our institution (2001-2004) and who had coronary angiography within 6 months of the evaluation. All-cause mortality data were prospectively collected and verified against the social security death index database. The study population consisted of 144 ESRD patients aged 53 ± 9 years. 35% were women and 63% had diabetes mellitus. The LVEF was 48 ± 12%. They were followed-up for 41 ± 28 months during which time 55 (38%) died prior to renal transplantation. An abnormal QRS duration was not predictive of worse outcomes (log-rank P = .9). The median phase bandwidth (BW) was 62° (inter-quartile range 47-98°) and standard deviation (SD) was 23° (inter-quartile range 15-35°). Patients with a BW above the median had worse survival (log-rank P = .017) and there was a trend toward worse survival in those with a SD above the median (log-rank P = .096). A 2-year mortality was higher in those with BW ≥ 62° in the entire cohort, and in the subsets of patients with normal LVEF (log-rank P = .001), coronary artery disease by angiography, increased LV mass index, QRS <110 ms, and perfusion defect size <20% of the LV. CONCLUSIONS: LV mechanical dyssynchrony by phase analysis is a predictor of mortality in patients with ESRD. It may have a role in risk-stratifying patients and should be incorporated in future studies using gated MPI.

Relation of left-ventricular dyssynchrony by phase analysis of gated SPECT images and cardiovascular events in patients with implantable cardiac defibrillators.

BACKGROUND: Left-ventricular (LV) dyssynchrony could be measured by gated SPECT myocardial perfusion imaging (MPI). This study examined the relation between the degree of dyssynchrony and outcome in patients with implantable cardiac defibrillators (ICDs). METHODS AND RESULTS: We studied 70 patients with ICD and LV ejection fraction (EF) <.40 by gated MPI (performed within 6 weeks of the device implantation). The images were re-processed using phase analysis to derive phase standard deviation (SD) and histogram bandwidth. All-cause mortality and appropriate ICD shocks were identified as the primary endpoint. There were 87% men, aged 62 +/- 11 years. The EF was 26 +/- 8% (range 12%-39%). The phase SD was 51 degrees +/- 20 degrees (range 12 degrees -99 degrees ) and the histogram bandwidth was 157 degrees +/- 72 degrees (range 21 degrees -327 degrees ). The SD and bandwidth were significantly greater than corresponding values in patients with normal EF (15.8 +/- 11.8 degrees and 42.0 +/- 28.4 degrees , respectively, P < .0001, each). At 1 year, 8 patients (11%) died or had shocks. The patients with events had higher phase SD than those without events (60 +/- 5 degrees vs 50 +/- 21 degrees , P = .002). The histogram bandwidth was also higher in those with events (185 +/- 37 vs 154 +/- 75, P = .07). All patients with event had a phase SD >or= 50 degrees , while none of the patients with a phase SD < 50 degrees (N = 26) had an event (P = .02). CONCLUSIONS: The severity of LV dyssynchrony by phase analysis in patients with LV dysfunction, and ICD is associated with increased risk of death and appropriate ICD shock; a phase SD < 50 degrees was associated with no events at 1 year.

The impact of viability assessment using myocardial perfusion imaging on patient management and outcome.

BACKGROUND: Prior studies show that ischemic cardiomyopathy (ICM) patients with substantial viable myocardium have better survival with coronary revascularization (CR) than medical therapy (MT). When myocardial perfusion imaging (MPI) is used, the analysis is often based on visual scoring. We sought to determine the value of automated quantitative viability analysis in guiding management and predicting outcome. METHODS: We identified 246 consecutive ICM patients who had rest-redistribution gated SPECT thallium-201 MPI. Size and severity of perfusion defects were assessed by automated method. Regions with <50% activity vs normal were considered nonviable. Mortality was verified against the social security death index database. RESULTS: Of the 246 patients, 37% underwent CR within 3 months of MPI. The initial images showed a total perfusion defect size of 32 +/- 17%, redistribution of 3.5 +/- 4.6% and nonviable myocardium of 13 +/- 14%LV. Using multivariate logistic regression analysis, independent predictors of CR included chest pains (OR 2.74) and rest-delayed transient ischemic dilatation (OR 4.49), while a prior history of CR or ventricular arrhythmias favored MT. The cohort was followed-up for 41 +/- 30 m during which 111 patients (45%) died. Survival was better with CR than MT (P < .0001). For CR, survival was better for those with a smaller area of nonviable myocardium (risk of death increased by 5%/1% increase in size of nonviable myocardium, P = .009) but this was not seen in MT. CR had a mortality advantage over MT when the area of nonviable myocardium was

Differences in heart rate response to adenosine and regadenoson in patients with and without diabetes mellitus.

BACKGROUND: Adenosine and regadenoson increase heart rate (HR) when used as stress agents to produce coronary hyperemia due to direct sympathetic stimulation. We hypothesized that the HR response will be lower in patients with than in those without diabetes mellitus (DM). METHODS: We studied the HR response (percentage maximal increase) in 2,000 patients in The ADenoscan Versus regAdenosoN Comparative Evaluation for Myocardial Perfusion Imaging (ADVANCE MPI 1 and 2) Trials with known DM status. RESULTS: There were 643 patients with a history of DM (65.4 +/- 0.4 years, 32% women) and 1,357 patients with no DM (65.5 +/- 0.3 years, 29% women). Compared with non-DM, the DM group had higher HR at baseline (68.4 +/- 0.48 vs 65.2 +/- 0.31 beat/min, P < .001) and smaller HR response after adenosine or regadenoson administration (29.4% +/- 0.64% vs 36.1% +/- 0.54%, P < .001). Insulin therapy was associated with further blunting in the HR response (25.9% +/- 1.0% vs 31.2% +/- 0.8%, P < .001). After adjusting for beta-blocker intake, baseline HR, age, gender, renal function, systolic blood pressure, and left ventricular systolic function, DM independently accounted for a decrease in the HR response. CONCLUSIONS: The HR response to adenosine and regadenoson in patients with DM is blunted. If additional studies confer an agreement between traditional tests for determination of autonomic neuropathy and this measure, then examination of HR response to these agents during myocardial perfusion imaging might add prognostic power.

Serial evaluations of myocardial infarct size after alcohol septal ablation in hypertrophic cardiomyopathy and effects of the changes on clinical status and left ventricular outflow pressure gradients.

Alcohol septal ablation (ASA) as a treatment for obstructive hypertrophic cardiomyopathy produces septal infarction. There is a concern that such infarcts could be detrimental. Changes in the size of these infarcts by serial perfusion testing have not been studied. We performed resting serial-gated single-photon emission computed tomographic myocardial perfusion imaging in 30 patients (age 51+/-17 years, 57% were women) who had ASA between September 2003 and March 2007 before, 2+/-0.8 days (early), and 8.4+/-6.9 months (late) after ASA. Patients were also followed clinically and with serial 2-dimensional echocardiography. New York Heart Association class decreased from 3.50+/-0.51 before to 1.14+/-0.36 (p<0.0001) 3 months after ASA. The left ventricular (LV) outflow gradient (by Doppler echocardiography) decreased from 63+/-32 mm Hg before to 28+/-23 mm Hg after ASA (p<0.005). None of the patients had perfusion defects at rest before ASA. After ASA, perfusion defect size, involving the basal septum, decreased from 9.4+/-5.8% early to 5.2+/-4.2% of LV myocardium late after ASA (p<0.001). There were no changes in LV size and ejection fraction after ASA. In conclusion, ASA produces small basal ventricular septal infarcts (resting perfusion abnormality) involving<10% of the LV myocardium (including ventricular septum). There is a significant reduction in the perfusion abnormality late after ASA without an increase in LV outflow obstruction or recurrence of symptoms.