Imaging cardiac resynchronisation therapy (CRT)

Background

Cardiac imaging provides a multiparametric approach to various diseases. In particular, in patients with heart failure, these techniques provide a high volume of information on blood flow distribution, metabolism and regional/global function.
Among interventions able to improve quality of life and outcome, CRT has been proposed in patients with drug-refractory heart failure and left bundle branch block (LBBB), and imaging and optimisation of CRT has been based mostly on echocardiography.

LBBB

This conduction abnormality is very complex and results associated to major changes in regional wall motion, perfusion and metabolism. Patients with LBBB commonly have abnormal ventricular septal motion with a decrease in regional kinesis, an abnormal pressure gradient between the left and the right ventricles and an increase in left ventricular end diastolic diameter (1). Moreover, LBBB reduces global left ventricular function and may induce regional metabolic and perfusion abnormalities. These effects may be negligible in patients with preserved global ventricular function but in patients with heart failure they may contribute to a further decrease in clinical conditions and functional class.

The multiple effects of CRT

The physiological effects of CRT are to correct the non uniformity of ventricular activation, contraction and relaxation sequences, reducing the LBBB-induced mechanical interventricular dyssynchrony between the right and the left ventricle and the intraventricular dyssynchrony within the left ventricle. CRT increases left ventricular filling time, decreases septal dyskinesis, reduces mitral regurgitation, thus improving haemodynamics.
These acute multiple effects of CRT can be accompanied by more complex perfusion or metabolic adaptations that may lead to long-term benefits even in patients who do not show any increase in left ventricular ejection fraction. Probably, CRT works on a wide spectrum and these “mismatch” observations simply reflect patients in whom the clinical improvement is not obtained by a volumetric resynchronisation. These observations demonstrate that wall motion data cannot explain all the effects of CRT.

CRT and echocardiography

In responders, CRT improves a broad range of measures of cardiac function and most of these measurements can be obtained and monitored by echocardiography. In fact, the mechanical effect of reducing the degree of ventricular dyssyncrony is accompanied by both an increase in the EF, a decrease in the left ventricular end-diastolic dimension and in the magnitude of mitral regurgitation. However, the percentage of CRT non responders has been described to be as high as 30% to 50% of heart failure patients showing LBBB, thus revealing that echocardiography alone is far from providing optimal selection of candidates to CRT at its higher level of application (intra and inter vetricular asynchrony).
Recently, an individual assessment as well as a pathophysiologic characterisation of the LBBB type has been suggested before implantation. The site of the left ventricular delay should be assessed in each patient with the rationale of biventricular pacing being to pace the most delayed left ventricular wall (2). This could represent one of the several factors responsible for the relatively high prevalence of patients with an unchanged or worsening condition after CRT. Magnetic Resonance Imaging and fast Computed Tomography have not provided yet any finding able to assist in the identification of nonresponders. Theoretically, a 3D, quantitative mapping of asynchrony and wall thickness/thickening should be able to provide a better characterisation, especially in patients with severe volume overload in whom echocardiography may suffer from artifacts or result technically difficult for patients’ characteristics.

CRT and metabolism

Regional metabolic changes induced by CRT have been demonstrated in a significant group of patients with LBBB and heart failure.
These studies demonstrated that after CRT, septal glucose uptake improves (3), and this metabolic normalisation could be explained by a flexible regulation of cardiomyocyte gene expression for the insulin-sensitive glucose transporter GLUT-4 that may induce septal insulin resistance in patients with heart failure and LBBB.
However, a reduced septal glucose uptake has no power in identifying responders, and this metabolic restoration contributes more to expanding the pathophisiology of CRT effect rather than to assist in the selection of patients to be treated.

CRT and myocardial perfusion

Perfusion assessed by gated SPECT offers the advantage of providing combined information on bood flow distribution and regional wall motion. Published papers focused on myocardial perfusion concluded that CRT may induce septal reperfusion. One of the possible explanations of this septal reperfusion is the haemodynamic effect of LBBB. In fact, experimental evidence suggests that early septal contraction against a relaxed left ventricular free wall reduces septal workload because pressure is still low and no ejection occurs. On the other hand, in patients with LBBB late activation of the left ventricular lateral wall occurs at higher stress, because the earlier activated septum has already developed tension.
Another recent observation with gated SPECT is that patients with severe resting perfusion defects do not show significant improvement in left ventricular ejection fraction or reduction in cardiac volumes when compared to patients with less severe perfusion abnormalities (4).
Thus, the contribution of Gated SPECT includes both diagnostic and pathophysiological information, providing an additional parameter, perfusion, to be associated with the standard echocardiographic approach.

Reducing the rate of CRT nonresponders by increasing the application of 3D imaging techniques. The discrepancy among study populations characterised by echocardiography or by 3D techniques, the multiple effects of CRT on wall motion, perfusion and metabolism, the evidence that severe perfusion defects limit the benefit of CRT, and the advantages obtained by 3D imaging techniques in identifying responders to different treatments suggest that investigations on blood flow distribution or metabolism may contribute to improve the identification of patients who may benefit from this treatment. In particular, these perfusion and metabolic data should be obtained simultaneously with volume measurements, since a severe volume overload represents a “no return” point for the majority of treatments in heart failure (5). This is probably the case of pharmacological therapy with beta-blockers, revascularisation of viable dysfunctioning myocardium and aneurismectomy.
Today, gated SPECT seems to offer the perfusion/volume evaluation match at the lowest cost and offers the best quantitative output.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.