A machine learning method integrating ECG and gated SPECT for cardiac resynchronization therapy decision support.

PURPOSE: Cardiac resynchronization therapy (CRT) has been established as an important therapy for heart failure. Mechanical dyssynchrony has the potential to predict responders to CRT. The aim of this study was to report the development and the validation of machine learning models which integrate ECG, gated SPECT MPI (GMPS), and clinical variables to predict patients' response to CRT. METHODS: This analysis included 153 patients who met criteria for CRT from a prospective cohort study. The variables were used to model predictive methods for CRT. Patients were classified as "responders" for an increase of LVEF ≥ 5% at follow-up. In a second analysis, patients were classified as "super-responders" for an increase of LVEF ≥ 15%. For ML, variable selection was applied, and Prediction Analysis of Microarrays (PAM) approach was used to model response while Naïve Bayes (NB) was used to model super-response. These ML models were compared to models obtained with guideline variables. RESULTS: PAM had AUC of 0.80 against 0.72 of partial least squares-discriminant analysis with guideline variables (p = 0.52). The sensitivity (0.86) and specificity (0.75) were better than for guideline alone, sensitivity (0.75) and specificity (0.24). Neural network with guideline variables was better than NB (AUC = 0.93 vs. 0.87) however without statistical significance (p = 0.48). Its sensitivity and specificity (1.0 and 0.75, respectively) were better than guideline alone (0.78 and 0.25, respectively). CONCLUSIONS: Compared to guideline criteria, ML methods trended toward improved CRT response and super-response prediction. GMPS was central in the acquisition of most parameters. Further studies are needed to validate the models.

Ischemia-guided vs routine non-culprit vessel angioplasty for patients with ST segment elevation myocardial infarction and multi-vessel disease: the IAEA SPECT STEMI trial.

BACKGROUND: In patients with multi-vessel disease presenting with ST elevation myocardial infarction (STEMI), the efficacy and safety of ischemia-guided, vs routine non-culprit vessel angioplasty has not been adequately studied. METHODS: We conducted an international, randomized, non-inferiority trial comparing ischemia-guided non-culprit vessel angioplasty to routine non-culprit vessel angioplasty, following primary PCI for STEMI. The primary outcome was the between-group difference in percent ischemic myocardium at follow-up stress MPI. All MPI images were processed and analyzed at a central core lab, blinded to treatment allocation. RESULTS: In all, 109 patients were enrolled from nine countries. In the ischemia-guided arm, 25/48 (47%) patients underwent non-culprit vessel PCI following stress MPI. In the routine non-culprit PCI arm, 43/56 (77%) patients underwent angioplasty (86% within 6 weeks of randomization). The median percentage of ischemic myocardium on follow-up imaging (mean 16.5 months) was low, and identical (2.9%) in both arms (difference 0.13%, 95%CI - 1.3%-1.6%, P < .0001; non-inferiority margin 5%). CONCLUSION: A strategy of ischemia-guided non-culprit PCI resulted in low ischemia burden, and was non-inferior to a strategy of routine non-culprit vessel PCI in reducing ischemia burden. Selective non-culprit PCI following STEMI offers the potential for cost-savings, and may be particularly relevant to low-resource settings. (CTRI/2018/08/015384).

Reproducibility of global LV function and dyssynchrony parameters derived from phase analysis of gated myocardial perfusion SPECT: A multicenter comparison with core laboratory setting.

BACKGROUND: Gated myocardial perfusion scintigraphy (GMPS) phase analysis is an important tool to investigate the physiology of left ventricular (LV) dyssynchrony. We aimed to test the performance of GMPS LV function and phase analysis in different clinical settings and on a diverse population. METHODS: This is a post hoc analysis of a prospective, non-randomized, multinational, multicenter cohort study. Clinical evaluation and GMPS prior to cardiac resynchronization therapy (CRT)(baseline) and 6-month post CRT (follow-up) were done. LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), LV ejection fraction (LVEF), LV phase standard deviation (LVPSD), and percentage of left ventricle non-viable (PLVNV) were obtained by 10 centers and compared to the core lab. RESULTS: 276 GMPS studies had all data available from individual sites and from core lab. There were no statistically significant differences between all variables except for LVPSD. When subjects with no mechanical dyssynchrony were excluded, LVPSD difference became non-significant. LVESV, LVEF, LVPSD and PLVNV had strong correlation in site against core lab comparison. Bland-Altman plots demonstrated good agreement. CONCLUSIONS: The presented correlation and agreement of LV function and dyssynchrony analysis over different sites with a diverse sample corroborate the strength of GMPS in the management of heart failure in clinical practice.

Clinical and gated SPECT MPI parameters associated with super-response to cardiac resynchronization therapy.

PURPOSE: We sought to evaluate the behavior of cardiac mechanical synchrony as measured by phase SD (PSD) derived from gated MPI SPECT (gSPECT) in patients with super-response after CRT and to evaluate the clinical and imaging characteristics associated with super-response. METHODS: 158 subjects were evaluated with gSPECT before and 6 months after CRT. Patients with an improvement of LVEF > 15% and NYHA class I/II or reduction in LV end-systolic volume > 30% and NYHA class I/II were labeled as super-responders (SR). RESULTS: 34 patients were classified as super-responders (22%) and had lower PSD (32° ± 17°) at 6 months after CRT compared to responders (45° ± 24°) and non-responders 46° ± 28° (P = .02 for both comparisons). Regression analysis identified predictors independently associated with super-response to CRT: absence of previous history of CAD (odds ratio 18.7; P = .002), absence of diabetes mellitus (odds ratio 13; P = .03), and history of hypertension (odds ratio .2; P = .01). CONCLUSION: LV dyssynchrony after CRT implantation, but not at baseline, was significantly better among super-responders compared to non-super-responders. The absence of diabetes, absence of CAD, and history of hypertension were independently associated with super-response after CRT.

Nuclear Cardiology in Women and Underrepresented Minority Populations.

PURPOSE OF REVIEW: To outline sex-specific features of coronary artery disease (CAD) that should be considered in the assessment of women, including those from ethnic minority populations with suspected stable ischemic heart disease (IHD). Second, to determine the latest nuclear imaging tools available to assess microvascular CAD. RECENT FINDINGS: Latest studies indicate that women are more likely to have ischemia with no obstructive coronary arteries (INOCA) and paradoxically have worse outcomes. Therefore, the evaluation of women with suspected IHD should include assessing microvascular and epicardial coronary circulation. The prevalence of CAD is increasing in younger women due to the increased cardiovascular disease (CVD) risk burden. CAD is often underrecognized in these patients. There is increasing recognition that INOCA is not benign and should be accurately diagnosed and managed. Nuclear imaging assesses the full spectrum of CAD from microvascular CAD to multivessel obstructive epicardial CAD. Further research on myocardial blood flow (MBF) assessment with PET MPI is needed.

Choosing between anatomy and function is not always evident for the heart of end-stage renal disease patients. How low can we go?

Patients with chronic kidney disease (CKD) are at a very high risk of adverse cardiovascular events. In CKD patients, vascular calcification is more prevalent, appears at an earlier age, and is more severe than in the general population. CKD physiology rather than the effects of dialysis is the primary driver of microvascular disease in these patients. Considering the significant morbidity and mortality attributable to cardiovascular disease in the CKD population, risk stratification remains an important challenge. Topics such as function vs anatomy to properly risk stratify these patients, as well as future perspectives on non-invasive techniques, will be addressed.

Left ventricular mechanical dyssynchrony in patients with chest pain and normal epicardial coronary arteries.

BACKGROUND: To detect ischemia in patients with angina and normal coronaries frequently represents a complex diagnosis. METHODS: To investigate whether left ventricular mechanical dyssynchrony by phase analysis contributes in the evaluation of patients with chest pain and normal coronaries, gated-SPECT myocardial perfusion imaging (MPI) at rest and 30 minutes post-stress was performed in 218 patients with normal epicardial coronaries, who were divided into two groups: those with summed difference score (SDS) ≥ 4 (54 patients, Group 1), and those with SDS < 4 (164 patients, Group 2). Intraventricular synchronism-phase standard deviation (PSD) and histogram bandwidth (HBW)-was evaluated by phase analysis. RESULTS: Women were significantly more frequent in Group 2 (those without ischemia in SPECT MPI): 113 (69%) vs 25 (46%), P = .00001. In males, left ventricular ejection fraction (LVEF) and ventricular volumes were not significantly different between patients with or without ischemia. However, ischemic females showed significantly higher ventricular volumes, minor post-stress LVEF and more negative delta LVEF (- 3.9 vs 0.34, P = .0008) than the non-ischemic ones. There was a significant post-stress increase of PSD and HBW among males, although not among females. According to SSS (≥ 4, with ischemia/necrosis; < 4, without ischemia/necrosis), post-stress PSD and HBW significantly increase both in male and female, and PSD and HBW were significantly higher in females with SSS ≥ 4 compared to those with SSS < 4 (PSD rest: 19.04° vs 11.72°, P < .0001; HBW rest: 58.85° vs 38.21°, P < .0001). PSD and HBW were also higher among males with SSS ≥ 4 compared to those with SSS < 4, although not significantly. CONCLUSION: Higher ventricular volumes in females and dyssynchrony are associated with inducible ischemia in MPI in patients with chest pain and normal coronaries. Stress-induced ischemia increases degree of dyssynchrony.

Value of intraventricular dyssynchrony assessment by gated-SPECT myocardial perfusion imaging in the management of heart failure patients undergoing cardiac resynchronization therapy (VISION-CRT).

BACKGROUND: Placing the left ventricular (LV) lead in a viable segment with the latest mechanical activation (vSOLA) may be associated with optimal cardiac resynchronization therapy (CRT) response. We assessed the role of gated SPECT myocardial perfusion imaging (gSPECT MPI) in predicting clinical outcomes at 6 months in patients submitted to CRT. METHODS: Ten centers from 8 countries enrolled 195 consecutive patients. All underwent gSPECT MPI before and 6 months after CRT. The procedure was performed as per current guidelines, the operators being unaware of gSPECT MPI results. Regional LV dyssynchrony (Phase SD) and vSOLA were automatically determined using a 17 segment model. The lead was considered on-target if placed in vSOLA. The primary outcome was improvement in ≥1 of the following: ≥1 NYHA class, left ventricular ejection fraction (LVEF) by ≥5%, reduction in end-systolic volume by ≥15%, and ≥5 points in Minnesota Living With Heart Failure Questionnaire (MLHFQ). RESULTS: Sixteen patients died before the follow-up gSPECT MPI. The primary outcome occurred in 152 out of 179 (84.9%) cases. Mean change in LV phase standard deviation (PSD) at 6 months was 10.5°. Baseline dyssynchrony was not associated with the primary outcome. However, change in LV PSD from baseline was associated with the primary outcome (OR 1.04, 95% CI 1.01-1.07, P = .007). Change in LV PSD had an AUC of 0.78 (0.66-0.90) for the primary outcome. Improvement in LV PSD of 4° resulted in the highest positive likelihood ratio of 7.4 for a favorable outcome. In 23% of the patients, the CRT lead was placed in the vSOLA, and in 42% in either this segment or in a segment within 10° of it. On-target lead placement was not significantly associated with the primary outcome (OR 1.53, 95% CI 0.71-3.28). CONCLUSION: LV dyssynchrony improvement by gSPECT MPI, but not on-target lead placement, predicts clinical outcomes in patients undergoing CRT.

Diastolic dyssynchrony assessment by gated myocardial perfusion-SPECT in subjects who underwent cardiac resynchronization therapy.

BACKGROUND: Left ventricular diastolic dyssynchrony (LVDD) can be assessed by gated myocardial perfusion single-photon emission computed tomography (GMP-SPECT). LVDD is an area of interest in subjects who underwent cardiac resynchronization therapy (CRT). The aim of this post hoc analysis was to assess the role of LVDD in subjects with CRT who were followed up at 6-month period. MATERIAL & METHODS: Left ventricular diastolic dyssynchrony was assessed by GMP-SPECT at baseline and after CRT procedure in 160 subjects from 10 different cardiological centers. CRT procedure was performed as per current guidelines. Outcomes were defined as improvement in ≥1 New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF) by 5%, and reduction in end-systolic volume (ESV) by 15% and 5% points in Minnesota Living with Heart Failure Questionnaire. LVDD was defined as diastolic phase standard deviation ≥40 ± 14°. RESULTS: Improvement in NYHA functional class occurred in 105 (65.6%), LVEF in 74 (46.3%), decrease in ESV in 86 (53.8%), and Minnesota score in 85 (53.1%) cases. Baseline LV diastolic standard deviation was 53.53° ± 20.85 and at follow-up 40.44° ± 26.1283; (P < 0.001). LVDD was not associated with improvement in clinical outcomes at follow-up. CONCLUSION: CRT improves both systolic and diastolic dyssynchrony values at 6-month follow-up. LVDD at baseline is correlated with cardiac functionality at follow-up, but not with overall favorable clinical outcomes.

Could myocardial viability be related to left ventricular dyssynchrony? Simultaneous evaluation by gated SPECT-MPI.

BACKGROUND: Left ventricular contraction dyssynchrony (LVCD) has been related to induced ischemia and transmural scar but the interplay of myocardial viability and dyssynchrony is unknown. The aim of the present study was to establish the role of dyssynchrony in the context of a viability study performed with nitrate augmentation gated single photon emission computed tomography (GSPECT) myocardial perfusion imaging (MPI). METHODS: Fifty-four consecutive patients with ischemic dilated cardiomyopathy (IDC) and depressed left ventricular ejection fraction (LVEF) were included. They underwent a two-day rest/nitroglycerine (NTG) study GSPECT MPI to determine the myocardial viability. Patients with a nitrate-induced uptake increase of > 10% vs baseline, in at least, two consecutive dysfunctional segments were considered viable as well as those who showed no improvement in the uptake but the uptake was > 50% on post NTG study. Patients with no nitrate-induced uptake increase of > 10% and the uptake of < 50% were considered non-viable. Perfusion, function and LVCD were compared in 25 viable patients vs 29 non-viable patients at baseline and after NTG administration. RESULTS: After NTG administration, in the viable group, the LVEF increased (36.44 ± 6.64% vs 39.84 ± 6.39%) and the end-systolic volume decreased significantly (119.28 ± 31.77 mL vs 109.08 ± 33.17 mL) (P < 0.01). These patients also experienced a significant reduction in the LVCD variables: phase standard deviation was reduced in the post NTG study (57.77° ± 19.47° vs 52.02° ± 17.09°) as well as the phase histogram bandwidth (190.20° ± 78.83° vs 178.0° ± 76.14°) (P < 0.05). Functional and LVCD variables remained similar in the non-viable patients (P > 0.05). CONCLUSION: In patients with IDC and depressed LVEF, the myocardial viability detected by rest/ NTG GSPECT MPI, might determine LVCD improvement.

Ischemic heart disease in Latin American women current perspective and call to action.

Cardiovascular diseases (CVDs) constitute the main cause of death in Latin America (LA), with ischemic heart disease (IHD) as the principal cause in most countries. Women are particularly at risk of premature death by CVDs. Nevertheless, in LA, as in other parts of the world, there is a misconception at public level of the importance of CVDs in women; thus, CVDs do not get as much coverage as breast cancer campaigns. Women frequently have atypical symptoms and nonobstructive coronary artery disease as well as inequity in medical and interventional treatments; therefore, care should be built upon these differences. We show the epidemiological situation of IHD in LA women and present a strategy to face the problem, considering the control of risk factors, the optimized utilization of available resources, and the role of research. The role of the International Atomic Energy Agency is highlighted. To adequately face the problem of CVD in LA women, a coordinated approach is necessary, involving medical professionals, governments, scientific societies, and international organizations, as well as the population concerned. In low- and middle-income countries, where the best use of available financial and technological resources is mandatory, a clinical management combining prevention, guidelines, and clinical judgment is required.

Association between non-perfusion parameters and presence of ischemia in gated-SPECT myocardial perfusion imaging studies.

BACKGROUND: Combined assessment of perfusion and function improves diagnostic and prognostic power of gated-SPECT in patients with coronary artery disease. The aim of this study was to investigate whether the presence of stress-induced ischemia is associated with abnormal resting left ventricular (LV) function and intraventricular dyssynchrony. METHODS AND RESULTS: Gated-SPECT myocardial perfusion imaging (MPI) at rest and 15 min post-stress was performed in 101 patients, who were divided into three groups: those with stress-induced ischemia (Group 1, n = 58), those with normal scans (Group 2, n = 28), and those with scar but no ischemia (Group 3, n = 15). More extensive perfusion defects were found in patients of Groups 1 and 3 [Summed stress score (SSS): 13 ± 8 and 21 ± 9, respectively]. In Group 2, the mean SSS was 1.5. The mean change in LV ejection fraction (LVEF at stress - LVEF at rest) was higher in Group 1 v. Group 2 patients: -5.54% ± 6.24% vs -2.46% ± 5.56%, p = 0.02. Group 3 patients also had higher values, similar to Group 1: -6.47% ± 8.82%. Patients with ischemia had almost 50% higher end-diastolic volumes than patients with normal MPI. Similarly, end-systolic volumes were almost twice as high in this group (p < 0.0001). In addition, the histogram bandwidth, a measure of intraventricular dyssynchrony, was greater in Group 1. CONCLUSIONS: Baseline differences in left ventricular volumes and degree of dyssynchrony are associated with inducible ischemia on stress testing in a gated-SPECT MPI. Stress-induced ischemia increases the degree of intraventricular dyssynchrony.

Value of gated-SPECT MPI for ischemia-guided PCI of non-culprit vessels in STEMI patients with multivessel disease after primary PCI.

There remains a clinical question of which patients benefit from revascularization of non-culprit coronary artery stenosis in the setting of acute ST-segment elevation myocardial infraction (STEMI). This is a large population of patients with prior studies showing 40 to 70% of patients with STEMI having non-culprit stenosis. This article reviews the current state of the literature evaluating outcomes of those previously randomized to revascularization of non-culprit stenosis around the time of the STEMI. We propose a new study design to utilize gated-SPECT in the decision process by using an ischemic burden of > 5% as a cut-off for revascularization vs. complete revascularization without ischemia assessment.

Functional versus anatomical approach in stable coronary artery disease patients: Perspective of low- and middle-income countries.

Coronary artery disease (CAD) is the primary cause of death worldwide. Nevertheless, while mortality rates have decreased over the last decades in high-income countries, in many low- and middle-income countries, the situation is just the opposite. Thus, the utilization of the more rational approach to diagnose, risk-stratify, and guide cost-effective management in these patients is of utmost importance in a setting of limited financial resources. Topics such as function versus anatomy with the focus on prognosis in stable CAD patients, as well as future perspectives on noninvasive techniques, will be addressed.

Current status of nuclear cardiology practice in Latin America and the Caribbean.

The burden of cardiovascular diseases (CVDs) in the world is ever growing. They represent the first cause of death worldwide and in Latin America. Nuclear cardiology has a well-established role in the management of patient with CVDs and is being increasingly integrated into the healthcare systems in the region. However, there remains variability as to the infrastructure available across the countries, in terms of existing technology, radiopharmaceuticals, and human resources. The approximate number of gamma (γ) cameras in the region is 1348, with an average of 2.25 per million population; Argentina and Brazil having the largest number. Nearly 80% of the existing cameras are single-photon emission tomography (SPECT), of which 8% are hybrid SPECT-CT systems. Positron emission tomography technology is steadily increasing, and currently, there is an average of 0.25 scanners per million inhabitants, indicating that there is a potential to expand the capacities in order to cover the needs. Four countries have nuclear reactors for research purposes, which allow the production of technetium-99 m (Argentina, Chile, Mexico and Peru), while four (Argentina, Brazil, Cuba, and Mexico) assemble 99Mo-99mTc generators. As for the nuclear cardiology studies, about 80% of studies performed are gated SPECT myocardial perfusion imaging; less than 10% are multi-gated acquisition (mainly for evaluation of cardiac toxicity in cancer patients), and the other 10% correspond to other types of studies, such as viability detection, and adrenergic innervation studies with 123I-MIBG. Physical stress is preferred, when possible, based on the clinical condition of the patient. Regarding human resources, there is an average of 1.1 physicians and 1.3 technologists per γ camera, with 0.1 medical physicists and 0.1 radiopharmacists per center in the region. The future of nuclear cardiology in Latin America and the Caribbean is encouraging, with great potential and possibilities for growth. National, regional, and international cooperation including support from scientific societies and organizations such as International Atomic Energy Agency, American Society of Nuclear Cardiology, and Latin American Association of Biology and Nuclear Medicine Societies, as well as governmental commitment are key factors for the development of the specialty. A multimodality approach in cardiac imaging will contribute to a better management of patients with CVDs.

Detection of post-exercise stunning by early gated SPECT myocardial perfusion imaging: results from the IAEA multi-center study.

BACKGROUND: Transient post-ischemic LV dysfunction due to myocardial stunning in patients with coronary artery disease can be missed by conventional gated SPECT (GSPECT) acquisitions. The aim of this IAEA-sponsored multi-center study was to determine whether early post-exercise imaging is more likely to detect stunning than conventional without adversely affecting image quality or perfusion information. METHODS AND RESULTS: Patients undergoing exercise/rest GSPECT were enrolled in this international multicenter study. Post-exercise studies were acquired at 15 ± 5 minutes after radiotracer injection (Stress-1) and repeated at 60 ± 15 minutes (Stress-2). Rest studies (R) were acquired at 60 minutes post injection. A core laboratory quantitatively assessed perfusion pattern and LV blinded to the acquisition time. Ischemia was defined as summed stress score (SDS) ≥4, and stunning was defined as the difference between rest and post-stress LVEF (Δ-LVEF). In the 229 patients enrolled into the study, both image quality and perfusion information were similar between Stress-1 and Stress-2. Post-stress LVEF was associated with both ischemia and time of acquisition, with a significant correlation between SDS and Δ-LVEF, which was stronger at Stress-1 than Stress-2 in the ischemic compared to the non-ischemic population (r = 0.23 vs 0.08, P = 0.10). CONCLUSIONS: Early post-exercise imaging is feasible, and can potentially improve the detection of post-ischemic stunning without compromising image quality and perfusion data.

A new method of modeling the multi-stage decision-making process of CRT using machine learning with uncertainty quantification.

Aims: Current machine learning-based (ML) models usually attempt to utilize all available patient data to predict patient outcomes while ignoring the associated cost and time for data acquisition. The purpose of this study is to create a multi-stage machine learning model to predict cardiac resynchronization therapy (CRT) response for heart failure (HF) patients. This model exploits uncertainty quantification to recommend additional collection of single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) variables if baseline clinical variables and features from electrocardiogram (ECG) are not sufficient. Methods: 218 patients who underwent rest-gated SPECT MPI were enrolled in this study. CRT response was defined as an increase in left ventricular ejection fraction (LVEF) > 5% at a 6±1 month follow-up. A multi-stage ML model was created by combining two ensemble models: Ensemble 1 was trained with clinical variables and ECG; Ensemble 2 included Ensemble 1 plus SPECT MPI features. Uncertainty quantification from Ensemble 1 allowed for multi-stage decision-making to determine if the acquisition of SPECT data for a patient is necessary. The performance of the multi-stage model was compared with that of Ensemble models 1 and 2. Results: The response rate for CRT was 55.5% (n = 121) with overall male gender 61.0% (n = 133), an average age of 62.0±11.8, and LVEF of 27.7±11.0. The multi-stage model performed similarly to Ensemble 2 (which utilized the additional SPECT data) with AUC of 0.75 vs. 0.77, accuracy of 0.71 vs. 0.69, sensitivity of 0.70 vs. 0.72, and specificity 0.72 vs. 0.65, respectively. However, the multi-stage model only required SPECT MPI data for 52.7% of the patients across all folds. Conclusions: By using rule-based logic stemming from uncertainty quantification, the multi-stage model was able to reduce the need for additional SPECT MPI data acquisition without sacrificing performance.