Original Article
Evaluation of baseline contractile reserve vs dyssynchrony as a predictor of functional improvement and long term outcome after resynchronization pacing therapy: A radionuclide stress study

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Aim

To assess the predictive value of baseline ventricular dyssynchrony and myocardial contractile reserve (mCR) in identifying responders to cardiac resynchronization therapy (CRT).

Methods

We prospectively studied 57 patients selected for CRT according to current recommendations. Regional dyssynchrony was evaluated by parametric phase imaging of ecg-gated equilibrium radionuclide angiography (ERNA). The mean inter-ventricular phase delay and the standard deviation to mean left ventricular (LV) phase angle were used as a measure of inter- and intra-ventricular dyssynchrony, respectively. Change in LV ejection fraction (LVEF) during low-dose dobutamine (LDD) was measured to assess mCR. ERNA was repeated at 6 months to evaluate changes in LVEF after CRT. Combined end-points of re-hospitalization for heart failure, heart transplantation, and cardiac death were assessed over a period of 76 months (mean 43 ± 31).

Results

Baseline dyssynchrony was present in most patients (85%). After CRT only one half of patients showed a reduction in intra-ventricular dyssynchrony and 33% an increase in LVEF by >5%. Improvement of LVEF was not predicted by baseline LVEF, clinical presentation, dyssynchrony parameters or QRS duration. There was a significant relationship between changes in LVEF during LDD testing and after CRT (r = 0.65; P < .0001). Logistic regression analysis identified mCR as independent predictor of improvement in LVEF (P = .039; OR = 3.84; CI 95% = 1.06-13.9), resynchronization (P = .046; OR = 4.20; CI 95% = 1.03-17.2), and event-free survival (P = .002; OR = 0.10; CI 95% = 0.02-0.43).

Conclusions

In patients with left ventricular dysfunction and baseline dyssynchrony as assessed by ERNA, evaluation of mCR during LDD may help predicting functional improvement and selecting potential responders to CRT.

Introduction

Cardiac resynchronization therapy (CRT) has emerged as an adjunctive treatment option in patients with drug-refractory heart failure. Current guidelines indicate as candidates to CRT the patients with low left ventricular ejection fraction (LVEF ≤35%), advanced heart failure (NYHA functional class III or IV) and prolonged QRS duration (>130 ms).1,2 However, with the use of these criteria, approximately 30% of patients fail to improve clinical symptoms and 40%-50% show no improvement in LV function.3., 4., 5., 6., 7., 8., 9.

Therefore, considering the potential for a greatly expanded patient population with heart failure undergoing CRT and the cost of the treatment, interest has been shifted toward more accurate criteria of selection and identification of potential responders to therapy before pacemaker implantation.10 It has been recognized that the effect of CRT is likely modulated by multiple factors including baseline left ventricular function and extent of ventricular dyssynchrony, correct lead positioning and pacing, but also the extent of myocardial fibrosis and tissue viability as estimated by measurement of myocardial contractile reserve (mCR).11., 12., 13., 14., 15.

Several cardiac imaging modalities have been proposed to evaluate ventricular function and dyssynchrony of contraction including M-Mode, bi-dimensional, and tissue Doppler imaging of trans-thoracic echocardiography16., 17., 18. and nuclear imaging techniques with phase analysis of either ecg-gated equilibrium radionuclide angiography (ERNA)19., 20., 21., 22. or SPECT myocardial perfusion imaging.23

Among several methods to unmask viable and recruitable myocardium in the failing heart, low-dose dobutamine (LDD) stress testing in association with either cardiac echocardiographic or radionuclide imaging has gained recognition as an important and accurate modality to predict functional improvement after interventions.24., 25., 26.

The aim of this study was to prospectively evaluate whether simultaneous assessment of baseline ventricular dyssynchrony, wall motion abnormalities and mCR by ERNA and LDD stress testing may help identifying responders to treatment.

Section snippets

Patients and Study Design

We studied 57 patients (47 male and 10 female; age 73.5 ± 7.5 years) with drug-refractory heart failure, fulfilling current indication criteria for CRT. Patients with permanent atrial fibrillation were excluded. Twenty-one patients with sustained or non-sustained ventricular tachyarrhythmias requiring cardiac resynchronization-defibrillator device were included. The clinical characteristics of patients groups are shown in Table 1.

All patients underwent baseline ERNA with parametric phase

Effect of CRT on Dyssynchrony and Left Ventricular Function

At baseline, most candidates for CRT (85%) had evidence of intra-ventricular dyssynchrony (Table 1) but there was a weak correlation between intra-ventricular dyssynchrony and LVEF (r = 0.38) (Figure 2). No correlation was found between inter-ventricular dyssynchrony and LVEF (r = 0.17) or baseline QRS duration (r = 0.18).

The effect of CRT was examined in 53 patients who completed the pre-implant and post-CRT evaluation. Four patients were excluded from further analysis after attempted

Discussion

Several large clinical trials have been conducted to assess the functional changes and clinical outcome after CRT. These studies have shown improvement in functional status, quality of life, exercise capacity, and left ventricular function in CRT patients as compared to controls.3., 4., 5., 6., 7., 8., 9. However, placebo effect in CRT patients has been described in about 40% of pacing-off CRT patients in Miracle trial.5 Only two studies have reported a decrease in the risk of death and

Acknowledgments

We are indebted to Luca Ceriani MD (Lugano, Switzerland) for its strong and skilled work in the evaluation of the first nuclear studies. We are also grateful to Rocco Lucianini (Varese, Italy) for its help in data processing and image analysis, to Laura Gaiara MD for data collection and to Claudio Marcassa, MD (Veruno, Italy) and Roberto De Ponti, MD (Varese, Italy) for their friendly help in reviewing the manuscript.

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