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BACKGROUND: The yield of myocardial perfusion imaging is low in contemporary patients with suspected coronary artery disease (CAD) selected based on American College of Cardiology Foundation/American Heart Association pretest probability estimate. We compared traditional pretest estimates of CAD probability with the prevalence of abnormal myocardial perfusion single-photon emission computed tomography (MPS). METHODS: This was a cohort study from a single academic center. Consecutive stable patients without known CAD referred for stress MPS for suspected CAD between 2004 and 2011 were identified (n=15 777). Angina typicality was determined using standard criteria. Abnormal MPS perfusion was defined as a summed stress score ≥4, ischemia as summed stress score ≥4 and summed difference score ≥2, and extensive ischemia as summed difference score ≥8 using a standard, 17-segment model of the left ventricle. The pretest probability of CAD was determined using the American College of Cardiology Foundation/American Heart Association criteria. RESULTS: Overall, 14% (n=2177) of patients had abnormal MPS of whom 11% (n=1698) had ischemia and 4% (n=684) extensive ischemia. In patients with chest pain who underwent treadmill MPS (n=4764), only 27% reported angina on the treadmill. Typical angina was associated with the highest prevalence for positive MPS (33% in men and 14% in women), ischemia (30% in men and 12% in women), and extensive ischemia (22% in men and 4% in women) when compared with other symptom categories. Prevalence of MPS abnormality was substantially lower than expected based on pretest probability estimates across most sex and age groups. In multivariable analysis, the pretest probability estimate was not an independent predictor of abnormal MPS. CONCLUSIONS: Traditional estimates of pretest probability of CAD are not predictive of MPS perfusion abnormality and overestimate its prevalence in stable patients. [ABSTRACT FROM AUTHOR]

Cardiac resynchronization therapy improves mortality and morbidity in patients with heart failure (HF) with wide QRS complex and diminished left ventricular (LV) function, but response is variable.The Speckle Tracking Assisted Resynchronization Therapy for Electrode Region (STARTER) was a prospective, double-blind, randomized controlled trial testing the hypothesis that an incremental benefit to cardiac resynchronization therapy would be gained by echo-guided (EG) transvenous LV lead placement versus a routine fluoroscopic approach. EG LV lead placement was attempted at the site of latest time to peak radial strain by speckle tracking echocardiography. The prespecified primary end point was first HF hospitalization or death. Of 187 New York Heart Association class II to IV patients with HF (62% ischemic; ejection fraction 26±6%; QRS 159±27 ms), 110 were randomized to EG and 77 to routine strategies. Primary events included 30 deaths and 37 HF hospitalizations over 1.8 years. Using intention-to-treat, patients randomized to an EG strategy had a significantly more favorable event-free survival (hazard ratio, 0.48; 95% confidence interval, 0.28-0.82; P=0.006). Exact or adjacent concordance of LV lead with latest site could be achieved in 85% of the EG group and occurred fortuitously in 66% of controls (P=0.010) and was associated with an improvement in event-free survival (hazard ratio, 0.40; 95% confidence interval, 0.22-0.71; P=0.002).A strategy of EG LV lead placement for cardiac resynchronization therapy improved patient outcomes by reducing the combined risk of death or HF hospitalizations and has implications for delivery of cardiac resynchronization therapy.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00156390. [ABSTRACT FROM AUTHOR]

The article discusses the paper "A Prospective Pilot Study to Evaluate the Relationship Between Acute Change in Left Ventricular Synchrony After Cardiac Resynchronization Therapy and Patient Outcome Using a Single-Injection Gated SPECT Protocol by Mati Friehling and others. It states that researchers sought to find a relationship between major changes in left ventricular synchrony (LV) after cardiac resynchronization therapy (CRT) and patient outcomes. The methods and conclusions are presented.

Background: Single photon emission computed tomography (SPECT) has limited ability to identify multivessel and microvascular coronary artery disease. Gamma cameras with cadmium zinc telluride detectors allow the quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR). However, evidence of its accuracy is limited, and of its reproducibility is lacking. We aimed to validate 99mTc-sestamibi SPECT MBF and MFR using standard and spline-fitted reconstruction algorithms compared with 13N-ammonia positron emission tomography in a cohort of patients with known or suspected coronary artery disease and to evaluate the reproducibility of this technique. Methods: Accuracy was assessed in 34 participants who underwent dynamic 99mTc-sestamibi SPECT and 13N-ammonia positron emission tomography and reproducibility in 14 participants who underwent 2 99mTc-sestamibi SPECT studies, all within 2 weeks. A rest/pharmacological stress single-day SPECT protocol was performed. SPECT images were reconstructed using a standard ordered subset expectation maximization (OSEM) algorithm with (N=21) and without (N=30) application of spline fitting. SPECT MBF was quantified using a net retention kinetic model‚ and MFR was derived as the stress/rest MBF ratio. Results: SPECT global MBF with splines showed good correlation with 13N-ammonia positron emission tomography (r=0.81, P <0.001) and MFR estimates (r=0.74, P <0.001). Correlations were substantially weaker for standard reconstruction without splines (r=0.61, P <0.001 and r=0.34, P =0.07, for MBF and MFR, respectively). Reproducibility of global MBF estimates with splines in paired SPECT scans was good (r=0.77, P <0.001), while ordered subset expectation maximization without splines led to decreased MBF (r=0.68, P <0.001) and MFR correlations (r=0.33, P =0.3). There were no significant differences in MBF or MFR between the 2 reproducibility scans independently of the reconstruction algorithm (P >0.05 for all). Conclusions: MBF and MFR quantification using 99mTc-sestamibi cadmium zinc telluride SPECT with spatiotemporal spline fitting improved the correlation with 13N-ammonia positron emission tomography flow estimates and test/retest reproducibility. The use of splines may represent an important step toward the standardization of SPECT flow estimation. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. [ABSTRACT FROM AUTHOR]

Background: Technetium-99 m pyrophosphate protocols for transthyretin cardiac amyloidosis diagnosis have variably used 1- and 3-hour imaging time points. We investigated whether imaging at 1 hour with superior efficiency had comparable diagnostic accuracy as 3-hour imaging. Methods: This is a registry analysis of patients with suspected transthyretin cardiac amyloidosis referred for technetium-99 m pyrophosphate at a single tertiary center from June 2015 through January 2019. Patients underwent planar and single-photon emission computed tomography (SPECT) imaging at 1 and 3 hours. A positive Tc-99m pyrophosphate study was defined by the presence of diffuse myocardial tracer uptake on SPECT. For planar imaging, visual semiquantitative (grades 0-3, ≥2 considered positive) and quantitative heart to contralateral ratios (≥1.5 considered positive) were used. Results: Two hundred thirty-three patients (69% men; median age, 77 [69–83] years) underwent the study protocol. There were 60 (25.8%) patients with diffuse myocardial uptake, 1 (0.4%) with regional uptake, and 172 (73.8%) with no myocardial uptake. Results of SPECT were identical at 1 and 3 hours. Planar imaging at 1 hour had 98% sensitivity and 96% specificity. Planar grade 0 uptake or heart to contralateral ratio ≤1.2 and planar grade 3 uptake or heart to contralateral ratio ≥2.0 were always associated with negative and positive SPECT, respectively. For planar grades 1 and 2 uptake and heart to contralateral ratio 1.3 to 1.9, SPECT was needed to make a diagnosis. No patient with light-chain cardiac amyloidosis had positive SPECT. Conclusions: An efficient 1-hour technetium-99 m pyrophosphate protocol had comparable diagnostic performance to a 3-hour protocol. [ABSTRACT FROM AUTHOR]

Background: In the phase 3 randomized controlled study ATTRibute-CM (Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy), acoramidis, a transthyretin stabilizer, demonstrated significant efficacy on the primary end point. Participants with transthyretin amyloid cardiomyopathy who completed ATTRibute-CM were invited to enroll in an open-label extension study (OLE). We report the efficacy and safety data of acoramidis in participants who completed ATTRibute-CM and enrolled in the ongoing OLE., Methods: Participants who previously received acoramidis through month 30 in ATTRibute-CM continued to receive it (continuous acoramidis), and those who received placebo through month 30 were switched to acoramidis (placebo to acoramidis). Participants who received concomitant tafamidis in ATTRibute-CM were required to discontinue it to be eligible to enroll in the OLE. Clinical efficacy outcomes analyzed through month 42 included time to event for all-cause mortality (ACM) or first cardiovascular-related hospitalization (CVH), ACM alone, first CVH alone, ACM or recurrent CVH, change from baseline in NT-proBNP (N-terminal pro-B-type natriuretic peptide), 6-minute walk distance, serum transthyretin, and Kansas City Cardiomyopathy Questionnaire Overall Summary score. Safety outcomes were analyzed through month 42., Results: Overall, 438 of 632 participants in ATTRibute-CM completed treatment, and 389 enrolled in the ongoing OLE (263 continuous acoramidis and 126 placebo to acoramidis). The hazard ratio for ACM or first CVH was 0.57 (95% CI, 0.46-0.72) at month 42 based on a stratified Cox proportional hazards model ( P <0.0001) favoring continuous acoramidis. Similar analyses were performed on ACM alone and first CVH alone, with hazard ratios of 0.64 (95% CI, 0.47-0.88) and 0.53 (95% CI, 0.41-0.69), respectively, at month 42. Treatment effects for NT-proBNP and 6-minute walk distance also favored continuous acoramidis. On initiation of open-label acoramidis in the placebo-to-acoramidis arm, there was a prompt increase in serum transthyretin. Quality of life assessed by Kansas City Cardiomyopathy Questionnaire Overall Summary score was well preserved in continuous-acoramidis participants compared with the placebo-to-acoramidis participants. No new clinically important safety issues were identified in this long-term evaluation., Conclusions: Early initiation and continuous use of acoramidis in the ATTRibute-CM study through month 42 of the ongoing OLE study were associated with sustained clinical benefits in a contemporary transthyretin amyloid cardiomyopathy cohort, with no clinically important safety issues newly identified., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04988386., Competing Interests: Dr Judge has received consultancy fees from Alexion Pharmaceuticals, Alleviant Medical, Alnylam Pharmaceuticals, Attralus, BridgeBio Pharma, Cytokinetics, Lexeo Therapeutics, Novo Nordisk, Pfizer, Rocket Pharmaceuticals, Renovacor, and Tenaya Therapeutics; his institution received clinical trial funding from Array Biopharma, BridgeBio Pharma (formerly Eidos Therapeutics), MyoKardia, and Pfizer. Dr Gillmore has acted as a consultant, advisor, or speaker for Alnylam Pharmaceuticals, AstraZeneca, Attralus, BridgeBio Pharma, Intellia Therapeutics, Ionis Pharmaceuticals, Lycia Therapeutics, and Pfizer. Dr Alexander has acted as a consultant, advisor, or speaker for Arbor Biotechnologies, Attralus, Intellia Therapeutics, and Prothena Biosciences. Dr Ambardekar reports no conflicts. Dr Cappelli has acted as a consultant, advisor, or speaker for Alnylam Pharmaceuticals, Amicus Therapeutics, AstraZeneca, BridgeBio Pharma (formerly Eidos Therapeutics), Novo Nordisk, Bayer, and Pfizer. Dr Fontana has acted as a consultant, advisor, or speaker for Alnylam, Alexion, AstraZeneca, Attralus, Bayer, BridgeBio Pharma (formerly Eidos Therapeutics), Caelum Biosciences, Cardior, Intellia Therapeutics, Ionis Pharmaceuticals, Janssen Pharmaceuticals, Lexeo Therapeutics, Novo Nordisk, Pfizer, and Prothena Biosciences; owns stock or stock options of Lexeo Therapeutics and Myocardium; has received research grants from Alnylam, AstraZeneca, BridgeBio Pharma, and Pfizer; and has received a salary from British Heart Foundation intermediate fellowship. Dr García-Pavía has acted as a consultant, advisor, or speaker for Alexion Pharmaceuticals, Alnylam Pharmaceuticals, AstraZeneca, Attralus, Bayer, BridgeBio Pharma (formerly Eidos Therapeutics), Intellia Therapeutics, Ionis Pharmaceuticals, Neuroimmune, Novo Nordisk, and Pfizer; his institution received research or educational funding from Alnylam Pharmaceuticals, AstraZeneca, BridgeBio Pharma (formerly Eidos Therapeutics), Intellia Therapeutics, Novo Nordisk, and Pfizer. Dr Grodin has acted as a researcher for the Texas Health Resources clinical scholarship, BridgeBio Pharma (formerly Eidos Therapeutics), Pfizer, and National Heart, Lung, and Blood Institute (R01HL160892) and as a consultant, advisor, or speaker for Alexion, Alnylam, AstraZeneca, BridgeBio Pharma, Intellia, Lumanity, Novo Nordisk, Pfizer, Tenax Therapeutics, and Ultromics. Dr Grogan has acted as a researcher for Alnylam Pharmaceuticals, BridgeBio Pharma (formerly Eidos Therapeutics), Intellia Therapeutics, Janssen Pharmaceuticals, Novo Nordisk, and Pfizer and as a consultant, advisor, or speaker for Alnylam, BridgeBio Pharma, Janssen Pharmaceuticals, Novo Nordisk, and Pfizer. Dr Hanna has acted as a consultant, advisor, or speaker for Alexion Pharmaceuticals, Alnylam Pharmaceuticals, Attralus, BridgeBio Pharma (formerly Eidos Therapeutics), Ionis Pharmaceuticals, and Pfizer. Dr Masri has acted as a researcher for Attralus, Cytokinetics, Ionis Pharmaceuticals, and Pfizer and as a consultant, advisor, or speaker for Akros Pharma, Alexion Pharmaceuticals, Alnylam Pharmaceuticals, AstraZeneca, Attralus, BioMarin Pharmaceutical, BridgeBio Pharma (formerly Eidos Therapeutics), Bristol Myers Squibb, Cytokinetics, Haya Therapeutics, Ionis Pharmaceuticals, Lexicon Pharmaceuticals, Pfizer, Prothena Biosciences, and Tenaya Therapeutics. Dr Nativi-Nicolau has acted as a researcher for Alnylam Pharmaceuticals, AstraZeneca, BridgeBio Pharma (formerly Eidos Therapeutics), and Pfizer. Dr Obici has acted as a consultant, advisor, or speaker for Alnylam Pharmaceuticals, AstraZeneca, BridgeBio Pharma (formerly Eidos Therapeutics), Ionis Pharmaceuticals, Novo Nordisk, Pfizer, and Sobi–Swedish Orphan Biovitrum. Dr Hvitfeldt Poulsen has received consulting fees from Bayer A/S, BridgeBio Pharma (formerly Eidos Therapeutics), and Pfizer A/S and research support from Novo Nordisk A/S. Dr Sarswat has acted as a researcher for Pfizer and as a consultant, advisor, or speaker for Alnylam, AstraZeneca, BridgeBio Pharma (formerly Eidos Therapeutics), Novo Nordisk, and Pfizer. Dr Shah has acted as a consultant, advisor, or speaker for Pfizer. Dr Soman has acted as a researcher for Pfizer and as a consultant, advisor, or speaker for Alnylam Pharmaceuticals, BridgeBio Pharma (formerly Eidos Therapeutics), and Pfizer. Drs Lystig, Cao, Wang, Pecoraro, Tamby, Katz, Sinha, and Fox are employees and stockholders of BridgeBio Pharma. Dr Maurer has acted as a researcher for the National Institutes of Health (R01HL139671 and R01AG081582-01), Alnylam Pharmaceuticals, Attralus, BridgeBio Pharma (formerly Eidos Therapeutics), Intellia Therapeutics, Ionis Pharmaceuticals, and Pfizer and as a consultant or advisor for Akcea Therapeutics, Alnylam Pharmaceuticals, AstraZeneca, Attralus, BridgeBio Pharma (formerly Eidos Therapeutics), Intellia Therapeutics, Ionis Pharmaceuticals, Novo Nordisk, and Pfizer.

Purpose: Iodine-123 meta-iodobenzylguanidine (I-mIBG) imaging has prognostic value in patients with heart failure (HF). Renal dysfunction is prevalent in HF patients. I-mIBG is excreted by the kidneys, and the effect of renal dysfunction on its myocardial uptake and established prognostic value in HF patients is unknown., Materials and Methods: The data analysed are from patients with New York Heart Association (NYHA) class II or III HF enrolled in the AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) study. Myocardial uptake and retention of I-mIBG were assessed by the early and late heart-to-mediastinal (HM) ratio. Effect of renal dysfunction on the prognostic value of I-mIBG was determined by multivariable-predicted survival analysis stratified by glomerular filtration rate (GFR) and late HM ratio. Cox proportional hazard models were used to determine the predictors of cardiac events (CEs, defined as death, HF progression or life-threatening arrhythmia)., Results: Complete data were available on 867 patients. The GFR range was 19-140 ml/min, and 344 (40%) patients had renal dysfunction (GFR<60 ml/min). A total of 523 (60%) and 689 (80%) patients had early and late HM ratios below the previously established prognostic cutoff of 1.6. There was no relationship between early or late HM ratios and GFR after controlling for HF severity (NYHA class and norepinephrine levels), indicating a lack of effect of renal dysfunction on the HM ratio. Significant independent predictors of CE were (hazard ratio, P), b-type natriuretic peptide level (1.4, <0.001), left ventricular ejection fraction (0.95, <0.001), BMI (1.04, 0.002), cardiac glycoside use (1.42, 0.019) and late HM ratio (7.04, 0.008). Neither GFR nor its interaction with late HM ratio was a significant predictor of CE., Conclusion: Renal dysfunction does not affect the HM ratios or the prognostic value of I-mIBG imaging in HF patients.

Objective: Left ventricular (LV) function and dyssynchrony parameters measured from serial gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) using blinded processing had a poorer repeatability than when manual side-by-side processing was used. The objective of this study was to validate whether an automatic alignment tool can reduce the variability of LV function and dyssynchrony parameters in serial gated SPECT MPI., Methods: Thirty patients who had undergone serial gated SPECT MPI were prospectively enrolled in this study. Thirty minutes after the first acquisition, each patient was repositioned and a gated SPECT MPI image was reacquired. The two data sets were first processed blinded from each other by the same technologist in different weeks. These processed data were then realigned by the automatic tool, and manual side-by-side processing was carried out. All processing methods used standard iterative reconstruction and Butterworth filtering. The Emory Cardiac Toolbox was used to measure the LV function and dyssynchrony parameters., Results: The automatic tool failed in one patient, who had a large, severe scar in the inferobasal wall. In the remaining 29 patients, the repeatability of the LV function and dyssynchrony parameters after automatic alignment was significantly improved from blinded processing and was comparable to manual side-by-side processing., Conclusion: The automatic alignment tool can be an alternative method to manual side-by-side processing to improve the repeatability of LV function and dyssynchrony measurements by serial gated SPECT MPI.

Coronary artery disease is currently the largest killer in the western world, and is estimated to become the leading cause of death worldwide by the year 2020. The question therefore is whether magnetic resonance imaging currently has a place in the already extremely well equipped armamentarium of cardiac testing. Although it is promising, its clinical use is somewhat limited by high cost and low availability of equipment and trained personnel. The absence of portable systems for cardiac application make cardiac magnetic resonance imaging in the emergency room, at the patient's bedside or in the doctor's office impossible. The comparison of the cardiac magnetic resonance imaging with proven and cost-effective techniques like echocardiography and nuclear imaging will be decisive in terms of the choice of imaging modalities in cardiology.