Incremental Value of Left Ventricular Mechanical Dyssynchrony Assessment by Nitrogen-13 Ammonia ECG-Gated PET in Patients With Coronary Artery Disease

Background: Phase analysis is a technique used to assess left ventricular mechanical dyssynchrony (LVMD) in nuclear myocardial imaging. Previous studies have found an association between LVMD and myocardial ischemia. We aim to assess the potential diagnostic value of LVMD in terms of myocardial viability, and ability to predict major adverse cardiac events (MACE), using Nitrogen-13 ammonia ECG-gated positron emission tomography (gPET).Methods: Patients with coronary artery disease (CAD) who underwent Nitrogen-13 ammonia and Fluorine-18 FDG myocardial gPET were enrolled, and their gPET imaging data were retrospectively analyzed. Patients were followed up and major adverse cardiac events (MACE) were recorded. The Kruskal-Wallis test and Mann-Whitney U test were performed to compare LVMD parameters among the groups. Binary logistic regression analysis, receiver operating characteristic (ROC) curve analysis, and multiple stepwise analysis curves were applied to identify the relationship between LVMD parameters and myocardial viability. Kaplan–Meier survival curves and the log-rank test were used to look for differences in the incidence of MACE.Results: In total, 79 patients were enrolled and divided into three groups: Group 1 (patients with only viable myocardium, n = 7), Group 2 (patients with more viable myocardium than scar, n = 33), and Group 3 (patients with less viable myocardium than scar, n = 39). All LVMD parameters were significantly different among groups. The median values of systolic phase standard deviation (PSD), systolic phase histogram bandwidth (PHB), diastolic PSD, and diastolic PHB between Group 1 and Group 3, and Group 2 and Group 3 were significantly different. A diastolic PHB of 204.5° was the best cut-off value to predict the presence of myocardial scar. In multiple stepwise analysis models, diastolic PSD, ischemic extent, and New York Heart Association (NYHA) classification were independent predictive factors of viable myocardium and myocardial scar. The incidence of MACE in patients with diastolic PHB > 204.5° was 25.0%, higher than patients with diastolic PHB <204.5° (11.8%), but the difference was not significant.Conclusions: LVMD generated from Nitrogen-13 ammonia ECG-gated myocardial perfusion imaging had added diagnostic value for myocardial viability assessment in CAD patients. LVMD did not show a definite prognostic value.

Design and Clinical Evaluation of Pharmacologic Stress-Test with Dalargin for SPECT Detection of Viable Myocardium in Patients after Myocardial Infarction

Purpose: To develop a functional stress-test with Dalargin used as a pharmacological stress agent and to study its diagnostic capabilities for quantifying the general and segmental systolic function of the left ventricle in patients with IHD using SPECT and echo methods. Material and methods: The study comprised 29 male patients with CHD-angina of 2-3 functional classes, studied on 15–25 days (on average 20 ± 2.8 days) after a large-focal myocardial infarction. A fractional step-wise injection of Dalargin was performed with step doses as 0.1 mg / kg (1 ml up to a total of 8 ml, with intervals of 90 seconds, for a total of 12 minutes), in a supine position. After each dose of Dalargin, blood pressure, heart rate, ECG were recorded, and an echocardiographic assessment of hemodynamic parameters and local contractility was carried out. At the peak of the effect of dalargin, 99mTc-Tetrofosmin was administered intravenously (370 – 540 MBq), followed by chest SPECT. Results: The optimal dose of dalargin for assessing the contractility of the LV was 0.3 mg/kg. From the data of myocardial perfusion SPECT, at dalargin test, the number of segments with normal regional blood supply increased statistically significantly from 56,0 % to 64,7 %, the number of hypoperfused segments decreased from 41.0% to 33.7% as compared to rest, and the number of non-perfused ones – from 3.0 % to 1.6 %. Spearman’s correlation coefficient between segmental contractility and local perfusion at the top dalargin inotropic effect was high and significant (R=0.67, p<0.01). The sensitivity and specificity of the pharmacological test with intravenous administration of dalargin for prediction of postoperative improvement of perfusion and contractility of the viable myocardium were: sensitivity 78.8 %, specificity 76.4 %, diagnostic accuracy 77.6 %. Conclusion. The use of the agonist of the μ - and δ-opioid receptors dalargin as a pharmacological stress-agent at perfusion SPECT and Stress Echocardiography to assess the contractile reserve of a dysfunctional viable myocardium is informative and appropriate. In patients with IHD who have suffered a myocardial infarction and are referred to myocardial revascularization, dalargin can be employed as an effective stress-agent for assessing the reserve of perfusion and contractility of dysfunctional left ventricular myocardium using perfusion SPECT and echocardiography.

Assessment of stunned and viable myocardium using manganese-enhanced MRI

ObjectiveIn a proof-of-concept study, to quantify myocardial viability in patients with acute myocardial infarction using manganese-enhanced MRI (MEMRI), a measure of intracellular calcium handling.MethodsHealthy volunteers (n=20) and patients with ST-elevation myocardial infarction (n=20) underwent late gadolinium enhancement (LGE) using gadobutrol and MEMRI using manganese dipyridoxyl diphosphate. Patients were scanned ≤7 days after reperfusion and rescanned after 3 months. Differential manganese uptake was described using a two-compartment model.ResultsAfter manganese administration, healthy control and remote non-infarcted myocardium showed a sustained 25% reduction in T1 values (mean reductions, 288±34 and 281±12 ms). Infarcted myocardium demonstrated less T1 shortening than healthy control or remote myocardium (1157±74 vs 859±36 and 835±28 ms; both p<0.0001) with intermediate T1 values (1007±31 ms) in peri-infarct regions. Compared with LGE, MEMRI was more sensitive in detecting dysfunctional myocardium (dysfunctional fraction 40.5±11.9 vs 34.9%±13.9%; p=0.02) and tracked more closely with abnormal wall motion (r2=0.72 vs 0.55; p<0.0001). Kinetic modelling showed reduced myocardial manganese influx between remote, peri-infarct and infarct regions, enabling absolute discrimination of infarcted myocardium. After 3 months, manganese uptake increased in peri-infarct regions (16.5±3.5 vs 22.8±3.5 mL/100 g/min, p<0.0001), but not the remote (23.3±2.8 vs 23.0±3.2 mL/100 g/min, p=0.8) or infarcted (11.5±3.7 vs 14.0±1.2 mL/100 g/min, p>0.1) myocardium.ConclusionsThrough visualisation of intracellular calcium handling, MEMRI accurately differentiates infarcted, stunned and viable myocardium, and correlates with myocardial dysfunction better than LGE. MEMRI holds major promise in directly assessing myocardial viability, function and calcium handling across a range of cardiac diseases.Trial registration numbersNCT03607669; EudraCT number 2016-003782-25.

Volume-weighted unipolar endocardial voltage: An excellent, novel parameter for predicting cardiac mortality in patients with dilated cardiomyopathy and ventricular arrhythmias

Funding Acknowledgements Type of funding sources: None. Background Patients with dilated cardiomyopathy (DCM) and ventricular tachyarrhythmias (VT) are at risk for heart failure (HF) death. Global left ventricular endocardial voltage may reflect the amount of excitable viable myocardium and identify patients at risk for rapid progression to end-stage HF. Aim To determine if volume-weighted endocardial voltage, as a surrogate for the total excitable viable myocardium, predicts mortality in patients with DCM and VT. Methods Consecutive patients with DCM, who underwent high-density endocardial voltage mapping for VT or PVC ablation (2012-2018), were included. Mapping data were transferred from CARTO to ParaView after excluding valve areas. The volume-weighted UV and BV (vwUV, vwBW) were calculated by mathematically integrating the UV and BV over the whole LV (thereby correcting for mapping density heterogeneity) divided by the endocardial LV surface area and corrected for LV wall thickness determined by echocardiography. The prognostic values of vwUV and vwBV for cardiac function and cardiac death were evaluated. Results One hundred three patients (VT, n = 83 and PVC, n = 20; age, 57 ± 14yrs; LVEF, 39 ± 13%; [likely] pathogenic genetic variants 33 [32%]; amiodarone use 36 [35%]) were included. VwUV and vwBV were 9.94 ± 3.42 and 4.70 ± 1.46. During a median follow-up of 24 months, cardiac mortality was 18% (end-stage HF 16/19, the median time to death 5.7 months). Patients who died had a significantly lower vwUV and vwBV (vwUV 5.62 ± 0.93 vs. 10.91 ± 3.10, P &lt; 0.001; vwBV 2.99 ± 0.70 vs. 5.04 ± 1.28, P &lt; 0.001). The optimal cutoff of vwUV for predicting HF-related death was 6.64 (AUC, 0.98; Sensitivity, 94%; Specificity, 95%), superior to LVEF or vwBV (AUC, 0.77, 0.92, respectively, Figure A). In multivariable analysis, vwUV remained the only significant predictor for cardiac death (for one decrease, HR 2.66, CI 1.41-5.00, P = 0.002), independently of LVEF, NT-proBNP, vwBV, genetic variants, and amiodarone use. In a subanalysis, the correlations between vwUV and changes of LVEF over time after voltage mapping were analyzed in patients with mid-range (HFmrEF, EF40-49%, n = 27) and reduced (HFrEF, EF &lt; 40%, n = 53) LVEF, respectively. In patients with HFmrEF, a significant LVEF deterioration (defined as an EF decrease &gt;5% and transition to HFrEF) occurred in 22% and was strongly related with a low vwUV (6.65 ± 1.15 vs. 10.08 ± 2.92, P = 0.02, Figure B left). Furthermore, in patients with HFrEF, a significant LVEF improvement (defined as an EF increase &gt;5% and transition to HFmrEF) was noted in 32% and was correlated with a high vwUV (11.68 ± 2.70 vs. 8.62 ± 2.69, P = 0.002, Figure B right). Conclusion VwUV is a newly proposed surrogate for the amount of LV viable myocardium, available from routine endocardial mapping and an excellent parameter to identify patients with DCM at high risk for rapid progression to HF-related death. Abstract Figure. vwUV and outcomes

Can the 12-Lead Electrocardiogram Predict Myocardial Viability?

Introduction: In patients with coronary artery disease and left ventricular dysfunction, the assessment of myocardial viability, prior to revascularisation has been shown to be of significant benefit. Most methods to assess myocardial viability such as Positron Emission Tomography (PET) and Cardiac MRI (CMR) are not readily available in resource constrained settings. The present study sought to determine if an easily available and inexpensive tool, such as the 12-lead surface Electrocardiogram (ECG) can be used as a screening tool to assess for myocardial viability. It is hypothesised that the R wave height as a marker of electrical activity would correlate with viability. Aim: To determine if the surface ECG can be used to predict myocardial viability. Materials and Methods: This retrospective study was conducted at the Christian Medical College and Hospital, Vellore, Tamil Nadu, India. Among all patients who had undergone CMR viability assessment as part of their routine care between February 2008 and October 2017, and analysis and preliminary write up was done between November 2017 and Decemeber 2018, 119 patients with previous anterior wall myocardial infarctions were identified. The 12-Lead ECGs of these patients were assessed for the height of R wave in lead V3 and sum of R wave heights in all precordial leads. Myocardial viability was assessed based on the extent of Late Gadolinium Enhancement (LGE) on CMR. Measures of diagnostic accuracy including sensitivity, specificity, predictive values and likelihood ratios were calculated. Results: It was found that a R wave height of less than 3 mm in lead V3 was 90.3% sensitive for the detection of non viable myocardium. Similarly, when the sum of the R wave heights in all precordial leads was less than 28.5 mm, it was 93.2% sensitive for the detection of non viable myocardium. Conclusion: In patients with previous anterior wall myocardial infarctions when the R wave height was less than 3 mm in lead V3, it was 90.3 % sensitive to identify those with non viable Left Anterior Descending artery (LAD) territory. The 12-Lead ECG is therefore a sensitive, inexpensive and easily available screening test to assess for LAD territory non viability.

The myocardial infarction size measuring using modern methods

An accurate quantitative assessment of myocardium necrosis area and the viable zone (stunned and hibernating) in patients with myocardial infarction is crucial for the preoperative patient selection and predicting the cardiac surgery effectiveness. Currently, researchers and clinicians are most interested in the problem of determining the viable myocardium zone. However, only the necrosis zone area directly correlates with the patients prognosis and determines the heart pathological remodeling processes. In the distant period, the data obtained can be used to predict the post-infarction period course or for analysis the relationship of the necrosis zone with arrhythmogenesis, and a number of other indicators. Thus, the necrosis zone and the viable myocardium zone are two parameters that need to be monitored in dynamics in all patients after myocardial infarction. The most accurate and reproducible method for determining the necrosis area is contrast magnetic resonance imaging of the heart, however, this technique is still inaccessible in most hospitals. In this regard, it remains relevant to estimate the necrotic myocardium area by ubiquitous non-invasive methods such as electrocardiography and echocardiography.

Revascularization in Ischemic Heart Failure: A Review

Ischemic heart disease as a cause of heart failure is common in India, ranging from 48% to 71%. The pathoanatomic basis of LV dysfunction is not only due to infarcted myocardium, but also due to viable but dysfunctional myocardium (hibernating/stunned myocardium) and structural abnormalities (mitral regurgitation/ventricular septal defect aneurysm) consequent to obstructive coronary artery disease. Evaluation of dysfunctional but viable myocardium is a key determinant of recovery of LV function, and magnitude of recovery is proportional to the amount of dysfunctional viable myocardium which if more than 25% LV (4 segments out of 17 segments model) results in improvement in function and size (reverse remodeling). Most of the data regarding therapy come from observational, registry data showing better outcomes with coronary artery bypass graft than percutaneous coronary intervention and medical therapy. The need for more multicentric, randomized controlled trials regarding recovery of LV function by various therapies is more than ever now.