Left ventricular (LV) failure in left bundle branch block is caused by loss of septal function and compensatory hyperfunction of the LV lateral wall (LW) which stimulates adverse remodelling. This study investigates if septal and LW function measured as myocardial work, alone and combined with assessment of septal viability, identifies responders to cardiac resynchronization therapy (CRT). In a prospective multicentre study of 200 CRT recipients, myocardial work was measured by pressure-strain analysis and viability by cardiac magnetic resonance (CMR) imaging (n = 125). CRT response was defined as ≥15% reduction in LV end-systolic volume after 6 months. Before CRT, septal work was markedly lower than LW work (P < 0.0001), and the difference was largest in CRT responders (P < 0.001). Work difference between septum and LW predicted CRT response with area under the curve (AUC) 0.77 (95% CI: 0.70–0.84) and was feasible in 98% of patients. In patients undergoing CMR, combining work difference and septal viability significantly increased AUC to 0.88 (95% CI: 0.81–0.95). This was superior to the predictive power of QRS morphology, QRS duration and the echocardiographic parameters septal flash, apical rocking, and systolic stretch index. Accuracy was similar for the subgroup of patients with QRS 120–150 ms as for the entire study group. Both work difference alone and work difference combined with septal viability predicted long-term survival without heart transplantation with hazard ratio 0.36 (95% CI: 0.18–0.74) and 0.21 (95% CI: 0.072–0.61), respectively. Assessment of myocardial work and septal viability identified CRT responders with high accuracy.

Regional myocardial work may be assessed by pressure–strain analysis using a non-invasive estimate of left ventricular pressure (LVP). Strain by speckle tracking echocardiography (STE) is not always accessible due to poor image quality. This study investigated the estimation of regional myocardial work from strain by feature tracking (FT) cardiac magnetic resonance (CMR) and non-invasive LVP. Thirty-seven heart failure patients with reduced ejection fraction, left bundle branch block (LBBB), and no myocardial scar were compared to nine controls without LBBB. Circumferential strain was measured by FT-CMR in a mid-ventricular short-axis cine view, and longitudinal strain by STE. Segmental work was calculated by pressure–strain analysis. Twenty-five patients underwent ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography. Segmental values were reported as percentages of the segment with maximum myocardial FDG uptake. In LBBB patients, net CMR-derived work was 51 ± 537 (mean ± standard deviation) in septum vs. 1978 ± 1084 mmHg·% in the left ventricular (LV) lateral wall (P < 0.001). In controls, however, there was homogeneous work distribution with similar values in septum and the LV lateral wall (non-significant). Reproducibility was good. Segmental CMR-derived work correlated with segmental STE-derived work and with segmental FDG uptake (average r = 0.71 and 0.80, respectively). FT-CMR in combination with non-invasive LVP demonstrated markedly reduced work in septum compared to the LV lateral wall in patients with LBBB. Work distribution correlated with STE-derived work and energy demand as reflected in FDG uptake. These results suggest that FT-CMR in combination with non-invasive LVP is a relevant clinical tool to measure regional myocardial work.

Background and aim: The presence of mechanical dyssynchrony on echocardiography is associated with reverse remodelling and decreased mortality after cardiac resynchronization therapy (CRT). Contrarily, myocardial scar reduces the effect of CRT. This study investigated how well a combined assessment of different markers of mechanical dyssynchrony and scarring identifies CRT responders. Methods: In a prospective multicentre study of 170 CRT recipients, septal flash (SF), apical rocking (ApRock), systolic stretch index (SSI), and lateral-to-septal (LW-S) work differences were assessed using echocardiography. Myocardial scarring was quantified using cardiac magnetic resonance imaging (CMR) or excluded based on a coronary angiogram and clinical history. The primary endpoint was a CRT response, defined as a ≥15% reduction in LV end-systolic volume 12 months after implantation. The secondary endpoint was time-to-death. Results: The combined assessment of mechanical dyssynchrony and septal scarring showed AUCs ranging between 0.81 (95%CI: 0.74–0.88) and 0.86 (95%CI: 0.79–0.91) for predicting a CRT response, without significant differences between the markers, but significantly higher than mechanical dyssynchrony alone. QRS morphology, QRS duration, and LV ejection fraction were not superior in their prediction. Predictive power was similar in the subgroups of patients with ischemic cardiomyopathy. The combined assessments significantly predicted all-cause mortality at 44 ± 13 months after CRT with a hazard ratio ranging from 0.28 (95%CI: 0.12–0.67) to 0.20 (95%CI: 0.08–0.49). Conclusions: The combined assessment of mechanical dyssynchrony and septal scarring identified CRT responders with high predictive power. Both visual and quantitative markers were highly feasible and demonstrated similar results. This work demonstrates the value of imaging LV mechanics and scarring in CRT candidates, which can already be achieved in a clinical routine.

Background: The response to cardiac resynchronization therapy (CRT) depends on septal viability and correction of abnormal septal motion. This study investigates if cardiac magnetic resonance (CMR) as a single modality can identify CRT responders with combined imaging of pathological septal motion (septal flash) and septal scar. Methods: In a prospective, multicenter, observational study of 136 CRT recipients, septal scar was assessed using late gadolinium enhancement (LGE) (n = 127) and septal flash visually from cine CMR sequences. The primary endpoint was CRT response, defined as ≥15% reduction in LV end-systolic volume with echocardiography after 6 months. The secondary endpoint was heart transplantation or death of any cause assessed after 39 ± 13 months. Results: Septal scar and septal flash were independent predictors of CRT response in multivariable analysis (both p < 0.001), while QRS duration and morphology were not. The combined approach of septal scar and septal flash predicted CRT response with an area under the curve of 0.86 (95% confidence interval (CI): 0.78–0.94) and was a strong predictor of long-term survival without heart transplantation (hazard ratio 0.27, 95% CI: 0.10–0.79). The accuracy of the approach was similar in the subgroup with intermediate (130–150 ms) QRS duration. The combined approach was superior to septal scar and septal flash alone (p < 0.01). Conclusions: The combined assessment of septal scar and septal flash using CMR as a single-image modality identifies CRT responders with high accuracy and predicts long-term survival.

Response to cardiac resynchronization therapy (CRT) is reduced in patients with high left ventricular (LV) scar burden, in particular when scar is located in the LV lateral wall or septum. Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) can identity scar, but is not feasible in all patients. This study investigates if myocardial metabolism by ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) and contractile function by echocardiographic strain are alternatives to LGE-CMR. In a prospective multicenter study, 132 CRT candidates (91% with left bundle branch block) were studied by speckle tracking strain echocardiography, and 53 of these by FDG-PET. Regional myocardial FDG metabolism and peak systolic strain were compared to LGE-CMR as reference method. Reduced FDG metabolism (10% could rule out transmural scar with high sensitivity (80%) and high negative predictive value (96%). Neither FDG-PET nor strain identified septal scars (for both, AUC < 0.80). In CRT candidates, FDG-PET is an excellent alternative to LGE-CMR to identify scar in the LV lateral wall. Furthermore, preserved strain in the LV lateral wall has good accuracy to rule out transmural scar. None of the modalities can identify septal scar. The present study is part of the clinical study "Contractile Reserve in Dyssynchrony: A Novel Principle to Identify Candidates for Cardiac Resynchronization Therapy (CRID-CRT)", which was registered at clinicaltrials.gov (identifier NCT02525185).