Imaging predictors of response to cardiac resynchronization therapy: left ventricular work asymmetry by echocardiography and septal viability by cardiac magnetic resonance

Abstract

Aims: 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).

Methods and results: 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.

Conclusion: Assessment of myocardial work and septal viability identified CRT responders with high accuracy.

Keywords: Myocardial scar; Cardiac resynchronization therapy; Dyssynchrony; Heart failure; Left bundle branch block; Myocardial work.

Graphical Abstract

Figure 1

Left ventricular systolic function and work asymmetry. (A) Effect of cardiac resynchronization therapy on left ventricular volumes and function: Volumes and ejection fraction were similar in responders and non-responders before cardiac resynchronization therapy, but improved significantly only in responders. (B) Effects of cardiac resynchronization therapy on work: Before cardiac resynchronization therapy, responders have more work in the left ventricular lateral wall and less in the septum than non-responders (upper panels). This is reflected in a larger lateral-to-septal work difference (mid-panels). With cardiac resynchronization therapy, lateral wall work is reduced and septal work increased in both groups. Among responders, however, reduction in lateral wall work was far exceeded by increased septal work and explains why only responders showed improved global work (lower panels). One standard deviation indicated.

Take home figure

Left ventricular work asymmetry combined with septal viability identifies cardiac resynchronization therapy responders. (A–C  ) The panels are from the same patient and illustrate how the lateral-to-septal work difference is used in combination with viability by LGE-CMR to identify cardiac resynchronization therapy responders. Before cardiac resynchronization therapy (A) there is dominantly negative septal work, as indicated by the red-coloured pressure-strain loop area, but compensatory increase in left ventricular lateral wall work, which gives a large lateral-to-septal work difference. Viable septum (B) indicates potential for recovery of septal function. After 6 months with cardiac resynchronization therapy (C), there is fine recovery of septal function. The highly inefficient septal contractions before cardiac resynchronization therapy are converted to positive work throughout systole. The improvement in septal function was accompanied by reduced workload on the lateral wall. (D) ROC curve displaying combined assessment of work difference and septal viability for cardiac resynchronization therapy response prediction (n = 123). AUC, area under curve; AVC, aortic valve closure; CI, confidence interval; LGE-CMR, late gadolinium enhancement cardiac magnetic resonance; LVP, left ventricular pressure; ROC, receiver operating characteristic.

Figure 2

Septal scar identifies non-responder to cardiac resynchronization therapy. (A) Strain traces (left), pressure-strain loops (middle), and regional work (right) in a representative non-responder (with non-ischaemic cardiomyopathy) prior to cardiac resynchronization therapy. Similar to the patient in the Take home figure, there are highly inefficient septal contractions with predominantly negative work (red-coloured pressure-strain loop area), which leads to a large lateral-to-septal work difference. (B) LGE-CMR revealed extensive septal scar with limited potential for recovery of septal function with cardiac resynchronization therapy. (C) After 6 months with cardiac resynchronization therapy, there is only moderate recovery of septal function and, despite reduced workload on the left ventricular lateral wall, still significant lateral-to-septal work difference. AVC, aortic valve closure; LGE-CMR, late gadolinium enhancement cardiac magnetic resonance; LVP, left ventricular pressure.

Figure 3

Regional work and reverse remodelling. Lateral-to-septal work difference correlates with degree of reverse remodelling following cardiac resynchronization therapy. The black-dotted line represents 15% reduction in left ventricular end-systolic volume index, whereas the red-dotted line represents the proposed cut-off value for work difference of 860 mmHg·%. LW-S, lateral-to-septal.

Figure 4

Work asymmetry and septal viability as predictors of cardiac resynchronization therapy response. (A) Receiver operating characteristic curve displaying lateral-to-septal work difference as predictor of cardiac resynchronization therapy response in the entire study population (n = 195). (B) Receiver operating characteristic curve displaying the combined assessment of lateral-to-septal work difference and septal viability as predictor of cardiac resynchronization therapy response (n = 123). AUC, area under curve; CI, confidence interval.

Figure 5

Association of work asymmetry and septal viability with long-term survival. (A) Kaplan–Meier curve stratified according to the proposed cut-off value for lateral-to-septal work difference. (B) Kaplan–Meier curve stratified according to the proposed cut-off value for lateral-to-septal work difference combined with septal viability.