A Comparative Study of Systolic and Diastolic Mechanical Synchrony in Canine, Primate, and Healthy and Failing Human Hearts

Aim: Mechanical dyssynchrony (MD) is associated with heart failure (HF) and may be prognostically important in cardiac resynchronization therapy (CRT). Yet, little is known about its patterns in healthy or diseased hearts. We here investigate and compare systolic and diastolic MD in both right (RV) and left ventricles (LV) of canine, primate and healthy and failing human hearts.Methods and Results: RV and LV mechanical function were examined by pulse-wave Doppler in 15 beagle dogs, 59 rhesus monkeys, 100 healthy human subjects and 39 heart failure (HF) patients. This measured RV and LV pre-ejection periods (RVPEP and LVPEP) and diastolic opening times (Q-TVE and Q-MVE). The occurrence of right (RVMDs) and left ventricular systolic mechanical delay (LVMDs) was assessed by comparing RVPEP and LVPEP values. That of right (RVMDd) and left ventricular diastolic mechanical delay (LVMDd) was assessed from the corresponding diastolic opening times (Q-TVE and Q-MVE). These situations were quantified by values of interventricular systolic (IVMDs) and diastolic mechanical delays (IVMDd), represented as positive if the relevant RV mechanical events preceded those in the LV. Healthy hearts in all species examined showed greater LV than RV delay times and therefore positive IVMDs and IVMDd. In contrast a greater proportion of the HF patients showed both markedly increased IVMDs and negative IVMDd, with diastolic mechanical asynchrony negatively correlated with LVEF.Conclusion: The present IVMDs and IVMDd findings have potential clinical implications particularly for personalized setting of parameter values in CRT in individual patients to achieve effective treatment of HF.

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.

Sequential left ventricular electro-mechanical changes in presence of left bundle branch block

Introduction Recent cross-sectional studies suggest a relationship between persisting left bundle branch block (LBBB) and the extent of left ventricular (LV) electro-mechanical alterations over time. When patients are referred for cardiac resynchronization therapy (CRT), temporal data during the sub-clinical phase of disease is often missing. A longitudinal study using an animal model would provide a better understanding of the relationship between the onset of LBBB and the electro-mechanical changes. Purpose To investigate the sequential alterations in LV structure and function that develop over time in an animal model of LBBB. Methods Thirteen sheep were subjected to rapid DDD pacing (180 bpm; leads on right atrium and right ventricular free wall) in order to induce a LBBB-like conduction delay. All animals underwent an 8-week pacing protocol, whereas 4 of them were subjected to 16 weeks of pacing in total. Echocardiographic speckle tracking was used to assess circumferential strain of the septal and lateral wall. Septal and lateral wall thickness were measured at end-diastole. Cardiac magnetic resonance imaging was used to determine LV volumes and ejection fraction (LVEF). Examinations took place at baseline (before and after start of pacing), and after 8 and 16 weeks of pacing. All examinations were performed at a physiologic heart rate of 110 bpm. Results At baseline, DDD pacing induced an increase in QRS duration (+85%, p<0.0001) and LBBB-like mechanical dyssynchrony, with mild early-systolic notching and preserved systolic shortening of the septal wall. The lateral wall demonstrated early pre-stretch followed by increasing systolic shortening. No acute changes in LV end-diastolic volume, LVEF or septal or lateral wall thickness were observed (all p>0.05). After 8 weeks of DDD pacing, mechanical dyssynchrony worsened: septal notching increased, followed by reduced systolic shortening. After 16 weeks, the initial septal shortening was followed by profound stretching throughout systole. Lateral wall systolic shortening was reduced compared to baseline. QRS duration increased further by +12% (week 8) and +20% (week 16) (all p<0.001). End-diastolic volumes had increased by +39% (week 8) and +72% (week 16), whereas LVEF had decreased by −48% (week 8) and −56% (week 16) (all p<0.001). Septal wall thickness had reduced by −24% (week 8) and −33% (week 16), while lateral wall thickness had increased by +21% (week 8) and +30% (week 16) (all p<0.05). Conclusion A persisting LBBB-like conduction delay induces sequential changes in LV deformation patterns, and triggers morphological and electrical remodelling. These changes are similar to those observed in patients with LBBB and different degrees of LV dysfunction. Our data suggest a continuum due to the progression of LBBB-induced LV disease. In the clinic, patients with mild dysfunction should be closely monitored in order to treat dyssynchrony as soon as guideline indications are reached. FUNDunding Acknowledgement Type of funding sources: Other. Main funding source(s): This work was supported by a KU Leuven research grant