Saurabh Malhotra

Brief Myocardial Ischemia Produces Cardiac Troponin I Release and Focal Myocyte Apoptosis in the Absence of Pathological Infarction in Swine

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Clinical quantification of myocardial blood flow using PET: Joint position paper of the SNMMI cardiovascular council and the ASNC

Writing Group: Venkatesh L. Murthy (cochair)1, Timothy M. Bateman2, Rob S. Beanlands3, Daniel S. Berman4, Salvador Borges-Neto5, Panithaya Chareonthaitawee6, Manuel D. Cerqueira7, Robert A. deKemp3, E. Gordon DePuey8, Vasken Dilsizian9, Sharmila Dorbala10, Edward P. Ficaro11, Ernest V. Garcia12, Henry Gewirtz13, Gary V. Heller14, Howard C. Lewin15, Saurabh Malhotra16, April Mann17, Terrence D. Ruddy3, Thomas H. Schindler18, Ronald G. Schwartz19, Piotr J. Slomka4, Prem Soman20, and Marcelo F. Di Carli (cochair)10

Correction to: Clinical Quantification of Myocardial Blood Flow Using PET: Joint Position Paper of the SNMMI Cardiovascular Council and the ASNC

The above position statement originally published containing errors in the author metadata; specifically, the Expert Content Reviewers—Andrew Einstein, Raymond Russell and James R. Corbett—were tagged as full authors of the paper. The article metadata has now been corrected to remove Drs. Einstein, Russell and Corbett from the author line, and the PubMed record has been updated accordingly.

Life-Threatening Ventricular Arrhythmias: Current Role of Imaging in Diagnosis and Risk Assessment.

Sudden cardiac arrest continues to be a major cause of death from cardiovascular disease but our ability to predict patients at the highest risk of developing lethal ventricular arrhythmias remains limited. Left ventricular ejection fraction is inversely related to the risk of sudden death but has a low sensitivity and specificity for the population at risk. Nevertheless, it continues to be the main variable considered in identifying patients most likely to benefit from implantable defibrillators to prevent sudden death. Imaging myocardial sympathetic innervation with PET and SPECT as well as imaging characteristics of myocardial infarcts using gadolinium-enhanced cardiac magnetic resonance are emerging as imaging modalities that may further refine patient selection beyond ejection fraction. This review will primarily focus on employing advanced imaging approaches to identify patients with left ventricular dysfunction that are most likely to develop lethal arrhythmias and benefit from inserting a primary prevention implantable cardiac defibrillator. While not yet tested in prospective studies, we will review risk prediction models incorporating quantitative imaging and biomarkers that have been developed that appear promising to identify those at highest risk of sudden death.

Prognostic Significance of Imaging Myocardial Sympathetic Innervation.

There has been a longstanding interest in understanding whether the presence of inhomogeneity in myocardial sympathetic innervation can predict patients at risk of sudden cardiac arrest from lethal ventricular arrhythmias. The advent of radiolabeled norepinephrine analogs has allowed this to be imaged in patients with ischemic and non-ischemic cardiomyopathy using single, photon emission computed tomography (SPECT) and positron emission tomography (PET). Several observational studies have demonstrated that globally elevated myocardial sympathetic tone (as reflected by reduced myocardial norepinephrine analog uptake) can predict composite cardiac end-points including total cardiovascular mortality. More recent studies have indicated that quantifying the extent of regional denervation can predict the risk of lethal ventricular arrhythmias and sudden cardiac death. This review will summarize our current understanding of the prognostic significance of altered myocardial sympathetic innervation.

Radionuclide Assessment of Left Ventricular Dyssynchrony.

Phase analysis of gated myocardial perfusion single-photon emission computed tomography is a widely available and reproducible measure of left ventricular (LV) dyssynchrony, which also provides comprehensive assessment of LV function, global and regional scar burden, and patterns of LV mechanical activation. Preliminary studies indicate potential use in predicting cardiac resynchronization therapy response and elucidation of mechanisms. Because advances in technology may expand capabilities for precise LV lead placement in the future, identification of specific patterns of dyssynchrony may have a critical role in guiding cardiac resynchronization therapy.

Software-dependent processing variability in SPECT functional parameters: Clinical implications.

While gated myocardial perfusion SPECT (MPS) is primarily performed for the assessment of myocardial perfusion, its ability to assess left ventricular (LV) volumes and function is an extremely useful complement. More recently, parameters of LV mechanical dyssynchrony derived by phase analysis of MPS have been validated, adding yet another facet to the spectrum of functional information provided. A unique attribute of SPECT is that it is largely automated, and thus, has excellent precision (reproducibility and repeatability). However, several factors need to be controlled, to achieve optimum precision of SPECT functional data including the injected dose, timing of image acquisition after injection, background activity, and filter characteristics. Also known is the variability introduced by image reconstruction software. Hambye et al reported the variability in gated MPS LV volumes and ejection fraction (LVEF) processed by different software programs, and different versions of the same program. They obtained consecutive 64 9 64 and 128 9 128 matrix gated MPS acquisitions on 31 patients. Images were reconstructed using filtered backprojection, and LVEF and volumes computed by three different programs—quantitative gated SPECT (QGS), Emory Cardiac Toolbox (ECTb), and Stanford University algorithm (SU-Segami). Patients were divided into those with small (ESV \30 mL) and normal or large hearts. In patients with a small heart, varying any parameter including the matrix size resulted in significant differences in volumes and EF. In patients with ‘‘non-small’’ hearts, the authors reported a minimal influence of the matrix size on LVEF and volume measurements. In contrast, increasing the filter cut-off frequency (sharpening the image) significantly increased the measured volume. In patients with ‘non-small’’ hearts, there was good correlation among the volumes and EF derived, but significant absolute differences existed between programs and versions. Similarly, van der Veen et al compared LVEF and LV volumes obtained from gated MPS data on 148 patients using QGS and 4DM-SPECT. Again, despite excellent correlation, there were significant absolute differences between LVEF and volumes obtained by the two programs. On Bland–Altman analysis, 4DM-SPECT was found to have systematically higher volumes. However, there remained an excellent linear relationship between the measures obtained by the two software programs when a dynamic phantom was used as the reference standard. The mean difference in EF obtained by the two programs was 9.6 ± 4.6 EF units. Additionally, gender and body mass index (BMI) were found to significantly influence end-diastolic (EDV) and end-systolic volume (ESV). More recently, Ather et al compared parameters of perfusion and function obtained by QGS, ECTb, and 4DM-SPECT in 120 consecutive patients with an abnormal regadenoson MPS. Significant discrepancy was found in categorizing patients into small, moderate, and large defects. Categorization into normal, mild to moderately abnormal, and severely abnormal LV Reprint requests: Prem Soman, MD, PhD, FASNC, FRCP (UK), FACC, Division of Cardiology, Heart and Vascular Institute, University of Pittsburgh Medical Center, A-429 Scaife Hall, 200 Lothrop Street, Pittsburgh, PA 15213; somanp@upmc.edu J Nucl Cardiol 2017;24:622–4. 1071-3581/

Myocardial substrate after cardiac resynchronization therapy and the risk of ventricular arrhythmias

34.00 Copyright 2016 American Society of Nuclear Cardiology.

Vasodilator stress and left ventricular asynchrony

Myocardial remodeling is a central feature of failing hearts. It can take several forms, and the most easily recognizable ones are electrical remodeling (wide QRS complex with or without left bundle branch block) and mechanical remodeling (dilated and hypofunctioning left ventricle). This remodeling results in disorganized left ventricular (LV) contraction, which further promotes heart failure (HF) progression and has been shown to be an independent predictor of adverse cardiac events. Patients with myocardial remodeling and symptomatic HF that is refractory to medical therapy have been shown to derive symptomatic and mortality benefit from cardiac resynchronization therapy (CRT). This benefit has been largely thought to be secondary to reduced interventricular conduction delay, reduction in LV size, and consequently improved LV contractility. The Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure (COMPANION) trial tested the efficacy of CRT-pacemaker and CRT-defibrillator with medical therapy alone. The trial reported that both CRT-pacemaker and CRT-defibrillator provided significantly better survival and reduced hospitalizations when compared with medical therapy alone. Though not specifically studied, the logical advantage of a CRT-defibrillator would be arrhythmia prevention and CRT-pacemaker seemed to offer a similar level of survival, suggesting an anti-arrhythmic effect of CRT alone. Since then other studies have reported a potential anti-arrhythmic benefit from CRT. Ermis et al prospectively followed 18 patients undergoing an upgrade of a defibrillator to a CRT-defibrillator, for arrhythmic events. Prior to an upgrade to CRT-defibrillator, 72% of the patients experienced an arrhythmic outcome as opposed to only 11% following the upgrade, suggesting a role of CRT in ameliorating ventricular arrhythmias in patients with HF. In another study, 107 patient with CRT-defibrillator were prospectively followed for arrhythmic events after elective generator change. Occurrences of arrhythmic events before and after generator change were recorded and were studied in relation to CRT response and an ongoing need for a defibrillator (defined as a LV ejection fraction\40%). This study showed that, at the time of the generator change, 87% of the CRT responders were free of arrhythmic events compared to 70% of CRT non-responders. Following an elective generator change, only 5% of those without an ongoing need for a defibrillator experienced arrhythmic events, when compared to 72% with an ongoing need for a defibrillator. Although both these studies imply reverse remodeling after CRT to confer protection against ventricular arrhythmia, this was not specifically evaluated. A recent sub-analysis of the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADITCRT) trial specifically assessed the role of CRT-defibrillator in preventing arrhythmic outcomes. In this analysis, 1783 patients belonging to the MADIT-CRT study were stratified by LV ejection fraction of B or [30%, and the occurrence of fast ventricular arrhythmias was determined in both these groups. Patients with LV ejection fraction B30% had a higher rate of ventricular arrhythmia when compared to those with LV Reprint requests: Saurabh Malhotra, MD, MPH, FASNC, Division of Cardiovascular Medicine, Clinical and Translation Research Center, Jacob School of Medicine and Biomedical Sciences at the University at Buffalo, 875 Ellicott Street, Suite 7030, Buffalo, NY 14221; drsmalhotra@hotmail.com, smalhot@buffalo.edu J Nucl Cardiol 2017;24:1289–91. 1071-3581/

Quantitative Radionuclide Assessment of Cardiac Dyssynchrony: Breakthrough in Patient Selection for Cardiac Resynchronization Therapy for Refractory Heart Failure?

34.00 Copyright 2016 American Society of Nuclear Cardiology.