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Background: Implantable cardioverter-defibrillators (ICDs) improve outcomes in patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤35%. Less is known about whether outcomes varied between the 2 noninvasive imaging modalities used to estimate LVEF-2-dimensional echocardiography (2DE) and multigated acquisition radionuclide ventriculography (MUGA)-which use different principles (geometric vs count-based, respectively)., Objective: The purpose of this study was to examine whether the effect of ICD on mortality in patients with HF and LVEF ≤35% varied on the basis of LVEF measured by 2DE or MUGA., Methods: Of the 2521 patients with HF with LVEF ≤35% in the Sudden Cardiac Death in Heart Failure Trial, 1676 (66%) were randomized to either placebo or ICD, of whom 1386 (83%) had LVEF measured by 2DE (n = 971) or MUGA (n = 415). Hazard ratios (HRs) and 97.5% confidence intervals (CIs) for mortality associated with ICD were estimated overall, checking for interaction, and within the 2 imaging subgroups., Results: Of the 1386 patients in the present analysis, all-cause mortality occurred in 23.1% (160 of 692) and 29.7% (206 of 694) of patients randomized to ICD or placebo, respectively (HR 0.77; 97.5% CI 0.61-0.97), which is consistent with that in 1676 patients in the original report. HRs (97.5% CIs) for all-cause mortality in the 2DE and MUGA subgroups were 0.79 (0.60-1.04) and 0.72 (0.46-1.11), respectively (P = .693 for interaction). Similar associations were observed for cardiac and arrhythmic mortalities., Conclusion: We found no evidence that in patients with HF and LVEF ≤35%, the effect of ICD on mortality varied by the noninvasive imaging method used to measure LVEF., (Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

We have shown that silent myocardial infarction (SMI) on 12-lead ECG is associated with increased cardiovascular disease (CVD) risk in patients awaiting renal transplantation (RT). In this study, we evaluated the prevalence of SMI in patients undergoing RT and their prognostic value after RT. MI was determined by automated analysis of ECG. SMI was defined as ECG evidence of MI without a history of clinical MI (CMI). The primary outcome was a composite of CVD death, non-fatal MI and coronary revascularization after RT. Of the 1189 patients who underwent RT, a 12-lead ECG was available in >99%. Of the entire cohort 6% had a history of CMI while 7% had SMI by ECG. During a median follow-up of 4.6 years, 147 (12%) experienced the primary outcome (8% CVD death, 4% MI, 4% coronary revascularization) and 12% died. Both SMI and CMI were associated with an increased risk of CVD events and all-cause deaths. In a multivariable adjusted Cox-regression model, both SMI (adjusted hazard ratio 2.03 [1.25-3.30], p = .004) and CMI (2.15 [1.24-3.74], p = .007) were independently associated with the primary outcome. SMI detected by ECG prior to RT is associated with increased risk of CVD events after RT., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Background: Patients with advanced chronic kidney disease (CKD) have increased risk of myocardial infarction (MI). Silent MIs (SMIs) are common in CKD patients and carry increased mortality risk. The prevalence and prognostic value of SMI in advanced CKD has not been evaluated., Methods: We identified consecutive patients with advanced CKD who were evaluated for renal transplantation at the University of Alabama at Birmingham between June 2004 and January 2006. Clinical MI (CMI) was determined by review of medical records. SMI was defined as ECG evidence of MI without clinical history of MI. The primary end-point was a composite of death, MI, or coronary revascularization censored at time of renal transplantation., Results: The cohort included 1007 patients with advanced CKD aged 48±12years (58% men, 43% diabetes, 75% on dialysis). The prevalence of SMI and CMI was 10.7% and 6.7%, respectively. The only independent predictor of SMI was older age (odds ratio for age ≥50yrs. 2.32, p<0.001). During a median follow-up of 28months, 376 (37%) patients experienced the primary outcome (33% death, 2% MI, 5% coronary revascularization). In a multivariable adjusted Cox-regression model, both SMI (adjusted HR 1.58, [1.13-2.20], p=0.007) and CMI (adjusted HR 1.67 [1.15-2.43], p=0.007) were independently associated with the primary outcome. Further, both SMI (HR 2.37 [1.15-4.88], p=0.02) and CMI (HR 4.02 [1.80-8.98], p=0.001) were associated with increased risk after renal transplantation., Conclusions: SMI is more common than CMI in patients with advanced CKD. Both SMI and CMI are associated with increased risk of future cardiovascular events., (Published by Elsevier B.V.)

Objectives: This study sought to summarize the evidence on stress myocardial perfusion imaging (MPI) using cadmium-zinc-telluride (CZT) technology for the diagnosis of obstructive coronary artery disease (CAD). The CZT cameras are newly introduced, and comparative data with the conventional Anger technology (Anger-MPI) are lacking., Background: The diagnostic accuracy of Anger-MPI for detection of angiographically significant CAD is well established; however, less evidence is available on the diagnostic accuracy of CZT-MPI., Methods: Clinical studies comparing CZT-MPI and invasive coronary angiography were systematically searched and abstracted. Calculations of diagnostic accuracy, including sensitivity, specificity, likelihood ratios, and diagnostic odds ratio, were obtained with fixed and random effects, reporting point estimates and 95% confidence intervals., Results: Based on our search, a total of 16 studies (N = 2,092) were included. The sensitivity of CZT-MPI was 0.84 (95% confidence interval [CI]: 0.78 to 0.89), whereas the specificity of 0.69 (95% CI: 0.62 to 0.76) was significantly reduced. The positive likelihood ratio was 2.73 (95% CI: 2.21 to 3.39), the negative likelihood ratio was 0.24 (95% CI: 0.17 to 0.31), and the diagnostic odds ratio was 11.93 (95% CI: 7.84 to 17.42). At subgroup and meta-regression analyses, the diagnostic accuracy between D-SPECT and Discovery cameras was similar (p = 0.711) and not impacted upon by smaller sample size studies (p = 0.573)., Conclusions: CZT-MPI has satisfactory sensitivity for angiographically significant CAD, but its suboptimal specificity warrants further development and research., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The lack of standardized reporting of the magnitude of ischemia on noninvasive imaging contributes to variability in translating the severity of ischemia across stress imaging modalities. We identified the risk of coronary artery disease (CAD) death or myocardial infarction (MI) associated with ≥10% ischemic myocardium on stress nuclear imaging as the risk threshold for stress echocardiography and cardiac magnetic resonance. A narrative review revealed that ≥10% ischemic myocardium on stress nuclear imaging was associated with a median rate of CAD death or MI of 4.9%/year (interquartile range: 3.75% to 5.3%). For stress echocardiography, ≥3 newly dysfunctional segments portend a median rate of CAD death or MI of 4.5%/year (interquartile range: 3.8% to 5.9%). Although imprecisely delineated, moderate-severe ischemia on cardiac magnetic resonance may be indicated by ≥4 of 32 stress perfusion defects or ≥3 dobutamine-induced dysfunctional segments. Risk-based thresholds can define equivalent amounts of ischemia across the stress imaging modalities, which will help to translate a common understanding of patient risk on which to guide subsequent management decisions., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Myocardial perfusion imaging (MPI) with gated single-photon emission tomography provides important information on the extent and severity of myocardial perfusion abnormalities, including myocardial ischemia. The availability of software for automated quantitative assessment of myocardial perfusion in an objective and more reproducible manner than visual assessment has allowed MPI to be particularly effective in serial evaluation. Serial testing using MPI is widely used in guiding patient care despite the lack of well-defined appropriateness use criteria. This should not be surprising because ischemic heart disease is a life-long malady subject to dynamic changes throughout its natural course and particularly following man-made interventions that may improve or worsen the disease process, such as medical therapy and coronary revascularization. Serial MPI has filled an important clinical gap by providing crucial information for managing patients with changes in clinical presentations or in anticipation of such changes in patients with stable symptoms. In the research arena, serial MPI has been widely applied in randomized controlled trials to study the impact of various medical and interventional therapies on myocardial perfusion, as well as the relative merits of new imaging procedures (hardware and/or software), radiotracers, and stressor agents. Serial testing, however, unlike initial or 1-time testing, has more stringent requirements and is subject to variability because of technical, procedural, interpretational, and biological factors. The intrinsic variability of MPI becomes important in interpreting serial tests in order to define a true change in a given patient and to guide clinical decision making. The purpose of this first comprehensive review on this subject is to illustrate where serial MPI may be useful clinically and in research studies, and to highlight strategies for addressing the various issues that are unique to serial testing in order to derive more valid and robust data from the serial scans., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The Detection of Ischemia in Asymptomatic Diabetics (DIAD) study demonstrated a low 5-year hard cardiac event rate. We hypothesized that a blunted heart rate response (HRR, maximum percent change) to adenosine, a simple marker of cardiac autonomic neuropathy, will identify a cohort at higher cardiac risk., Methods: In DIAD, 518 participants were randomized to screening adenosine myocardial perfusion imaging (MPI) and had available data. HRR <20% was considered abnormal. The primary endpoint was a composite of nonfatal myocardial infarction and cardiac death., Results: During 4.7 ± 0.9 years of follow-up 15 (3%) participants experienced the primary outcome. Participants with lower HRR experienced more events than those with higher HRR (8%, 3%, 1%, for HRR <20% (n=79), 20-39% (n=182) and ≥ 40% (n=257), respectively, p=0.01). In a Cox proportional regression model that included MPI abnormalities and HRR, both were independently associated with cardiac events (p for model <0.001). HRR <20% was associated with 9-fold increased risk (p=0.007) and moderate/large abnormal MPI was associated with 6-fold increased risk (p=0.004). Participants with both abnormal MPI and HRR (n=8) were at highest risk for cardiac events (38%) whereas those with HRR ≥ 40%, irrespective of MPI abnormalities (n=234), were at extremely low risk (≤1%, log-rank p<0.001)., Conclusions: In DIAD, abnormal HRR to adenosine infusion is an independent predictor of cardiac events. This easily obtained marker of cardiac autonomic neuropathy identifies asymptomatic patients with type 2 diabetes mellitus at increased risk, particularly when associated with abnormal MPI, who may warrant further testing and more aggressive cardiovascular risk factor management., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Chronic kidney disease (CKD) is associated with worse survival in patients with implantable cardiac defibrillators (ICDs). This study examined the association of outcomes with CKD in patients receiving an ICD for primary versus secondary prevention., Methods: The study included 696 patients who underwent ICD placement for clinical reasons (59% primary, 41% secondary prevention) at the University of Alabama at Birmingham between January 2002 and September 2007. CKD was defined as an estimated glomerular filtration rate<60 ml/min/1.73 m(2) but not on dialysis. Outcomes of interest included overall mortality and first appropriate ICD therapy (shocks or anti-tachycardia pacing)., Results: After a follow-up of 50 ± 24 months, 213 patients died (31%) and 111 (16%) received appropriate ICD therapy. Patients with CKD had higher mortality than patients with no CKD in the primary (43% vs. 15%, p<0.001) and secondary prevention (37% vs. 23%, p = 0.003) groups. Patients with CKD were at higher risk of receiving an appropriate ICD therapy than patients without CKD in the primary (p<0.001) but not secondary prevention (p = 0.9) cohort. After adjusting for age, gender and multiple risk factors, CKD was independently associated with all-cause mortality and ICD therapy in the primary prevention group (HR 2.08 [1.34-3.23] and 3.53 [1.75-7.10], p = 0.001 and <0.0001, respectively) but not in the secondary prevention group (HR 1.27 [0.81-2.00], and 0.63 [0.35-1.13], p=0.3 and 0.2, respectively)., Conclusions: CKD is independently associated with increased mortality and appropriate ICD therapy in patients undergoing ICD implantation for primary but not secondary prevention., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Right ventricular ejection fraction (RVEF) < 20% is an independent predictor of poor outcomes in patients with advanced chronic systolic heart failure (HF). The aim of this study was to examine if the adverse effect of abnormally reduced RVEF varies by the receipt of beta-blockers., Methods: In the Beta-Blocker Evaluation of Survival Trial (BEST), 2708 patients with chronic advanced HF and left ventricular ejection fraction < 35%, receiving standard background therapy with renin-angiotensin inhibition, digoxin, and diuretics, were randomized to receive bucindolol or placebo. Of these 2008 had data on baseline RVEF, and 14% (146/1017) and 13% (125/991) of the patients receiving bucindolol and placebo respectively had RVEF < 20%., Results: Among patients in the placebo group, all-cause mortality occurred in 33% and 43% of patients with RVEF ≥ 20% and < 20% respectively (unadjusted hazard ratios {HR}, 1.33; 95% confidence intervals {CI}, 0.99-1.78; p = 0.055 and adjusted HR, 0.99; 95% CI, 0.71-1.37; p = 0.934). Among those receiving bucindolol, all-cause mortality occurred in 28% and 49% of patients with RVEF ≥ 20% and < 20% respectively (unadjusted HR, 2.15; 95% CI, 1.65-2.80; p < 0.001 and adjusted HR, 1.50; 95% CI, 1.08-2.07; p = 0.016). These differences were statistically significant (unadjusted and adjusted p for interaction, 0.016 and 0.053 respectively)., Conclusions: In ambulatory patients with chronic advanced systolic HF receiving renin-angiotensin inhibition, digoxin, and diuretics, RVEF < 20% had no intrinsic association with mortality. However, in those receiving additional therapy with bucindolol, RVEF < 20% had a significant independent association with increased risk of mortality., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The aim of this study was to test the hypothesis that patients with normal regadenoson myocardial perfusion imaging (MPI) have a low rate of cardiac events, similar to patients with normal adenosine MPI., Background: Regadenoson, a new selective adenosine A(2A) receptor agonist, is now a widely used stress agent for MPI. The low rate of cardiac events in patients with normal adenosine MPI is well-documented, but the prognostic implications of a normal regadenoson MPI have not been examined and compared with those with adenosine., Methods: Data on primary composite endpoint (cardiac death, myocardial infarction, and coronary revascularization) were collected for 2,000 patients (1,000 regadenoson, and 1,000 adenosine stress) with normal myocardial perfusion and left ventricular ejection fraction referred for vasodilator MPI. In addition, propensity scores were used to assemble a balanced cohort of 505 pairs of patients who were balanced on 36 baseline characteristics., Results: The primary endpoint occurred in 21 (2.1%; 1.1%/year) patients in the regadenoson group and 33 (3.3%; 1.7%/year) patients in the adenosine group (hazard ratio [HR] for regadenoson vs. adenosine: 0.62; 95% confidence interval [CI]: 0.36 to 1.08; p = 0.090). In the propensity-matched pairs, the primary endpoint occurred in 7 (1.4%; 0.7%/year) patients in the regadenoson group and 13 (2.6%; 1.3%/year) patients in the adenosine group (matched HR: 0.58; 95% CI: 0.23 to 1.48; p = 0.257). Cardiac deaths were infrequent in the entire sample and in the propensity-matched groups; the cardiac death rate was 0.9%/year and 1.15%/year in the regadenoson and adenosine groups (HR: 0.77; 95% CI: 0.42 to 1.43; p = 0.404) in the pre-match sample and 0.5%/year and 0.7%/year in the matched groups, respectively (HR: 0.83; 95% CI: 0.25 to 2.73; p = 0.763)., Conclusions: Major cardiac events are infrequent in patients with normal regadenoson MPI. These findings provide assurance that normal MPI using a simpler stress protocol with regadenoson provides prognostic data similar to normal adenosine MPI., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Reduced right ventricular ejection fraction (RVEF) is associated with poor outcomes in patients with chronic systolic heart failure (HF). Although most HF patients are older adults, little is known about the relationship between low RVEF and outcomes in older adults with systolic HF., Methods: Of the 2008 Beta-Blocker Evaluation of Survival Trial (BEST) participants with systolic HF (left ventricular ejection fraction ≤ 35%) 822 were ≥ 65 years and had data on baseline RVEF estimated by gated-equilibrium radionuclide ventriculography. Using RVEF ≥ 40% (n = 308) as reference, we examined association of RVEF 30-39% (n = 214), 20-29% (n = 206) and <20% (n = 94) with outcomes using Cox regression models., Results: All-cause mortality occurred in 36%, 40%, 39% and 56% of patients with RVEF ≥ 40%, 30-39%, 20-29% and <20% respectively. Compared with RVEF ≥ 40%, unadjusted hazard ratios (HR) and 95% confidence intervals (CI) for all-cause mortality associated with RVEF 30-39%, 20-29% and <20% were 1.19 (0.90-1.57; P = 0.220), 1.13 (0.84-1.51; P = 0.423) and 1.97 (1.43-2.73; P<0.001) respectively. Respective multivariable-adjusted HR's (95% CI's) for all-cause mortality were 1.19 (0.88-1.60; P = 0.261), 1.00 (0.73-1.39; P = 0.982) and 1.70 (1.14-2.53; P = 0.009). Adjusted HR's (95% CI's) associated with RVEF <20% (versus ≥ 40%) for cardiovascular mortality and HF mortality were 1.79 (1.17-2.76; P = 0.008) and 1.97 (1.02-3.83; P = 0.045) respectively. RVEF had no independent association with sudden cardiac death, all-cause or HF hospitalization., Conclusions: Abnormally low RVEF is a significant independent predictor of mortality, but not of HF hospitalization, in older adults with systolic HF., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objectives: This study examined the hypothesis that the improvement in myocardial blood flow (MBF) with ranolazine therapy could be detected by serial automated quantitative myocardial perfusion imaging (MPI) in patients with coronary artery disease (CAD) and myocardial ischemia., Background: Myocardial ischemia enhances late sodium current, which then causes cellular calcium overload leading to mechanical left ventricular dysfunction and arrhythmias. Ranolazine inhibits late sodium current and improves diastolic tension and MBF in the animal model., Methods: In this open-label, nonrandomized pilot study, we recruited 20 patients with known or a high probability of CAD and who had reversible perfusion defects on exercise treadmill gated single-photon emission computed tomography MPI while receiving conventional antianginal therapy. Ranolazine (up to 1,000 mg twice daily) was added to baseline therapy and a repeat treadmill MPI was obtained after 4 weeks. The extent and severity of total and reversible left ventricular perfusion abnormality (based on polar maps and a 17-segment model) were determined quantitatively using automated methods., Results: We screened 100 patients for 27 potential candidates; 5 declined and 2 did not complete the follow-up study. The mean age of the remaining 20 patients was 64 +/- 9 years; 30% were women and 50% had diabetes mellitus. The exercise time increased (425 +/- 105 s vs. 393 +/- 116 s, p = 0.017), and angina improved in 15 (75%) patients after ranolazine treatment. In the entire cohort, summed stress scores (10 +/- 7 vs. 13 +/- 8, p = 0.04) and summed difference scores (4.7 +/- 4 vs. 7.4 +/- 5, p = 0.0037) decreased at follow-up. An improvement in perfusion pattern and severity was noted in 14 (70%) patients. In these patients, the polar maps showed a decrease in total abnormality from 26 +/- 17% to 19 +/- 15% and a decrease in the reversible abnormality from 16 +/- 10% to 8 +/- 6% (all p values <0.05)., Conclusions: In this preliminary hypothesis-driven study, short-term ranolazine therapy was shown to improve myocardial perfusion and decrease the ischemic burden in patients with CAD.

Objectives: This study sought to determine whether regadenoson induces left ventricular perfusion defects of similar size and severity as seen with adenosine stress., Background: Total and ischemic left ventricular perfusion defect size predict patient outcome. Therefore, it is important to show that newer stressor agents induce similar perfusion abnormalities as observed with currently available ones., Methods: The ADVANCE MPI 2 (Adenosine versus Regadenoson Comparative Evaluation for Myocardial Perfusion Imaging) study was a prospective, double-blind, randomized trial comparing image results in patients undergoing standard gated adenosine single-photon emission computed tomography (SPECT) myocardial perfusion imaging who were then randomized in a 2:1 ratio to either regadenoson (N = 495) or a second adenosine SPECT (N = 260). Quantitative SPECT analysis was used to determine total left ventricular perfusion defect size and the extent of ischemia. Quantification was performed by a single observer who was blinded to randomization and image sequence., Results: Baseline gated perfusion results were similar in patients randomized to adenosine or regadenoson. No significant differences in total (11.5 +/- 15.7 vs. 11.4 +/- 15.8, p = 0.88) or ischemic (4.8 +/- 9.2 vs. 4.6 +/- 8.9, p = 0.43) perfusion defect sizes were observed between the regadenoson and adenosine groups, respectively. Linear regression showed a close correlation between adenosine and regadenoson for total (r = 0.97, p < 0.001) and ischemic (r = 0.95, p < 0.001) left ventricular perfusion defects. Serial differences in total (-0.03 +/- 3.89 vs. -0.13 +/- 4.16, p = 0.73) and ischemic (0.15 +/- 4.08 vs. 0.25 +/- 3.81, p = 0.74) perfusion defect size and left ventricular ejection fraction (0.12 +/- 0.32 vs. 0.15 +/- 0.35, p = 0.27) from study 1 to study 2 were virtually identical in patients randomized to regadenoson versus adenosine, respectively. The good correlation between serial adenosine and regadenoson studies regarding total (0.41 +/- 5.43 vs. 0.21 +/- 5.23, p = 0.76) and ischemic (0.17 +/- 5.31 vs. 0.23 +/- 6.08, p = 0.94) perfusion defects persisted in the subgroup of 308 patients with an abnormal baseline SPECT., Conclusions: Applying quantitative analysis, regadenoson induces virtually identical scintigraphic results as adenosine regarding the size and severity of left ventricular perfusion defects and the extent of scintigraphic ischemia.

Objectives: To compare the effects of age, gender, body mass index, and diabetes on the safety and efficacy of regadenoson stress myocardial perfusion imaging, and to assess the noninferiority of regadenoson to adenosine for the detection of reversible myocardial perfusion defects., Background: Previous reports have shown that a fixed unit bolus of regadenoson is safe and noninferior to adenosine for the detection of reversible perfusion defects by radionuclide imaging., Methods: Using a database of 2,015 patients, we evaluated the effects of age, gender, body mass index, and diabetes on the safety and efficacy of regadenoson compared to adenosine., Results: For detection of ischemia relative to adenosine, noninferiority was demonstrated for all patients (agreement rate difference 0%, 95% CI -6.2% to +6.8%). The average agreement rate between adenosine-adenosine and adenosine-regadenoson were 0.62 +/- 0.03 and 0.63 +/- 0.02. Detection of ischemia was also comparable in specific subgroups. Agreement was less for both agents in women versus men with moderate and large areas of ischemia. Compared to adenosine, regadenoson had a lower combined symptom score and less chest pain, flushing, and throat, neck, or jaw pain, but more headache and gastrointestinal discomfort. This was true in nearly all subgroups. Regadenoson patients reported feeling more comfortable (1.7 +/- .02 vs. 1.9 +/- 0.03, p < 0.001). Based on the overall tolerability score, women felt less comfortable than men with both stress agents. Image quality was rated good or excellent in 92% for both agents., Conclusions: Regadenoson can be safely administered as a fixed unit bolus and is as efficacious as adenosine in detecting ischemia regardless of age, gender, body mass index, and diabetes. Regadenoson is better tolerated overall and across various subgroups.