Heart failure (HF) is highly prevalent and represents a considerable social and economic burden.

Cardiac resynchronization therapy (CRT) shows benefits in patients with end-stage HF, leading to improvements in left ventricular (LV) end-diastolic diameter and LV ejection fraction (LVEF) after 6 months of follow-up in randomized trials. CRT also has a beneficial impact on mortality, functional class and quality of life in all HF patients.1–4

The current guidelines recommend CRT (class I, level of evidence A) in patients in NYHA class III or IV on optimal medical therapy, LVEF ≤35% and QRS duration ≥120 ms.5

In spite of the evidence in favor of CRT, 20–40% of HF patients do not respond to the procedure. It has been suggested that one reason could be the criterion used to define dyssynchrony, the QRS width, which is not necessarily related to mechanical dyssynchrony.6,7 Observational studies have shown that the presence of left ventricular mechanical dyssynchrony is associated with a favorable response to CRT with LV reverse remodeling, decreased mitral regurgitation and consequent improvement in clinical outcome. By contrast, the absence of significant mechanical dyssynchrony appears to be associated with a high rate of non-response to CRT.8–11

The use of phase analysis of gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) for the evaluation of mechanical dyssynchrony has been described in previous studies.12–15 Standard gated SPECT short-axis imaging enables detection of three-dimensional regional maximal counts for each time frame. The variation in regional maximal counts is proportional to regional wall thickening through the cardiac cycle. Information on mechanical contraction of all regions (phase distribution) of the LV is obtained and displayed as either a histogram or a polar map. In a normal LV, regional contraction starts almost at the same time, resulting in a uniform polar map and a narrow and peaked phase histogram. The standard deviation of the left ventricular phases (phase SD) is a quantitative parameter that describes the dispersion of LV regional contraction and is used to assess mechanical dyssynchrony. Significant dyssynchrony is defined, according to previous studies, as a phase SD ≥43°.12,14–16

The aim of this study was to assess the prevalence and predictors of mechanical dyssynchrony in patients with impaired ventricular function. As a secondary objective we set out to evaluate the predictors of mechanical dyssynchrony in patients with normal or mildly abnormal rest perfusion images.

The study included 143 patients, 22 women (15.4%) and 121 men (84.6%), with a mean age of 62.8±11.7 years. Clinical, electrocardiographic and SPECT MPI characteristics are shown in Table 1.

The prevalence of known CAD in this group was 41.3% and among these patients there was also a significant prevalence of hypertension and diabetes.

On baseline ECG a QRS width ≥120 ms was observed in 43.7% of the patients and a pattern of bundle branch block (BBB) in 16.1%.

Almost all the exams were performed using pharmacological vasodilatation with adenosine (86%). A high number of abnormal perfusion images were seen (76.9%) and the prevalence of mechanical dyssynchrony was also high (53.1%). Figure 1 shows an example of a perfusion study with extensive defects and the related dyssynchrony analysis revealing mechanical dyssynchrony.

Figure 1.

Gated SPECT myocardial perfusion images (A) of a patient with an extensive fixed perfusion defect (fibrosis) and corresponding dyssynchrony analysis showing the polar map and phase histogram with a wide base and SD of 54.6° (B).

(0.34MB).

In Table 2 clinical, electrocardiographic and gated SPECT MPI characteristics are compared in patients with and without mechanical dyssynchrony according to SD.

The main differences between patients with and without mechanical dyssynchrony were the presence of diabetes and gated SPECT MPI variables. Patients with mechanical dyssynchrony had a higher prevalence of abnormal perfusion exams, with larger fixed defects, higher EDV and worse LVEF. In spite of the differences observed in the prevalence of QRS ≥120 ms, this was not statistically significant. Twenty-two patients had LVEF ≤35% and QRS ≥120 ms, and 17 of these patients had mechanical dyssynchrony.

Using logistic regression analysis, the univariate predictors of mechanical dyssynchrony were diabetes, the presence of abnormal perfusion, the extent of stress/rest perfusion defects, EDV and LVEF dysfunction. The presence of LVEF ≤35% and QRS ≥120 ms was also a predictor of mechanical dyssynchrony (Table 3).

Two multivariate models were built to identify variables that add incremental value over LVEF and QRS width, functioning as independent predictors of dyssynchrony.

In the clinical model (Table 4), diabetes was an independent predictor of mechanical dyssynchrony. The model incorporating MPI variables (SRS and EDV) added predictive value to the clinical one and in this model SRS and EDV were independent predictors of dyssynchrony (Table 5).

According to these results, perfusion abnormalities, particularly those present at rest, were strong predictors of mechanical dyssynchrony. To assess how the extent of SRS affects mechanical dyssynchrony, the same analysis was performed in the patient group with normal or mildly abnormal rest images, excluding those with SRS corresponding to LV involvement ≥10%.

In these patients QRS width, and in particular QRS ≥120 ms, were significantly more prevalent in patients with SD ≥43°, and as expected QRS ≥120 ms was the only predictor of mechanical dyssynchrony in this group (Tables 6 and 7).

This is a study of consecutive patients referred for gated SPECT MPI with impaired LVEF (≤50%). Our aim was to evaluate not only the prevalence of mechanical dyssynchrony in these patients but also its predictors among clinical, electrocardiographic and gated SPECT MPI variables. Mechanical dyssynchrony was defined, in accordance with previous studies, as a standard deviation, in phase analysis, of ≥43°.

The mean age of this group was 63 years, approximately 41% of the patients had a history of CAD (MI and/or myocardial revascularization) and there was also a significant prevalence of hypertension (62%) and diabetes (43%). Most of the patients thus had an intermediate to high risk of CAD.

In view of these findings, the high frequency of perfusion abnormalities found on gated SPECT MPI (77%) was not surprising. LVEF was ≤35% in 30.1% of the studied patients.

The precise prevalence of mechanical dyssynchrony in patients with impaired LVEF is still debated; although phase SD is a continuous variable it is used to dichotomize populations into normal vs. dyssynchronous using a cut-off value derived from data from a single center, with the inherent limitations. Even so, we used this value (43°) in our study, and a prevalence of 53% was found for mechanical dyssynchrony based on gated SPECT.17,18

The main differences between patients with and without mechanical dyssynchrony were the presence of diabetes and of an abnormal perfusion pattern (both higher in patients with mechanical dyssynchrony), LVEF (lower in patients with dyssynchrony), perfusion scores (with higher stress and rest scores and lower difference score in dyssynchrony patients) and EDV (higher in patients with mechanical dyssynchrony).

A wide QRS (≥120 ms) was more prevalent (although without statistical significance) in the dyssynchrony group (50%), but it should also be noted that among these patients, 50% had a narrow QRS. QRS duration was slightly greater in patients with dyssynchrony, but again without statistical significance. Several published studies have also found mechanical dyssynchrony in a considerable number of patients with a narrow QRS. The presence of ischemia and MI could be related to these findings.19 Whether these patients (with mechanical and without electrical dyssynchrony) benefit from CRT is still a matter of debate.20,21 Beshai et al. found no significant improvements with CRT in patients with narrow QRS.22,23

According to our results, there is a significant difference in LVEF (lower in patients with dyssynchrony) between the established groups. Dyssynchrony was identified in 72.1% of patients with LVEF ≤35% but also in 45.0% of those with LVEF between 35 and 50%. Similar findings have been described in previous studies.24 Atchey et al. found that 37% of patients with mild to moderate LVEF (35–50%) had significant degrees of mechanical dyssynchrony.25

The number of patients with LVEF and QRS criteria for CRT was also higher in the dyssynchrony group. Five of these patients (22.7%) did not demonstrate mechanical dyssynchrony. This result raises the issue of electrical without mechanical dyssynchrony; the existing evidence emphasizes the role of imaging techniques in the identification of the latter, and in the selection of patients who may benefit from CRT. It appears that CRT can correct mechanical dyssynchrony caused by electrical dyssynchrony.26–29

In univariate and multivariate logistic regression analysis, we found that in these patients the predictors of dyssynchrony were the presence of diabetes, the presence and extent of perfusion defects, especially rest score, EDV and LVEF. The simultaneous presence of wide QRS and low LVEF was also a predictor of mechanical dyssynchrony.

Diabetes is a powerful predictor of ischemic heart disease, so it was expected to find this relationship with mechanical dyssynchrony.30,31

Low LVEF and increased EDV are predictors of dyssynchrony. Low EF and an enlarged LV are accompanied by geometrical and morphological modifications and by conduction disturbances and changes in contraction patterns. These changes can potentially be reversed by CRT.32–34

We also found that the extent of perfusion defects, particularly of rest perfusion abnormalities, was also associated with increased dyssynchrony. This is not surprising considering that ischemic and infarcted segments exhibit significant degrees of motility changes (hypokinesia, akinesia or dyskinesia), resulting in abnormal contraction and dyssynchrony.35

Considering the presence of CRT criteria (QRS ≥120 ms and LVEF ≤35%), two models were built to identify independent predictors of mechanical dyssynchrony and the incremental values of adding these predictors to the conventional CRT criteria. In the model incorporating clinical and gated SPECT MPI variables, SRS and EDV were independent predictors of dyssynchrony and the incremental value of adding them to the CRT criteria was well demonstrated.

A study by Samad et al. had similar results but their study population had LVEF ≤35%. In these they found that QRS width was also an important predictor of mechanical dyssynchrony.36

In the study by Atchey et al. there was a weak correlation between QRS width and dyssynchrony in patients with LVEF between 35 and 50%.25 In our study, only 30.1% of patients had LVEF ≤35%, which could partly explain the lack of predictive value of QRS width in our population. It should also be borne in mind that these patients had a very high prevalence of perfusion abnormalities and known CAD, both of which lead to mechanical dyssynchrony. For this reason we also evaluated patients with a rest perfusion score under 10% of LV involvement. In these patients there was a clear relation between QRS width and the occurrence of mechanical dyssynchrony; in fact, QRS ≥120 ms was the only predictor of dyssynchrony. Rest perfusion abnormalities are associated with scar tissue, mechanical dyssynchrony and poor CRT response.37–40

Mechanical dyssynchrony has been evaluated by several methods in several contexts, and appears to be common not only in patients with impaired LVEF and wide QRS.18 According to the literature, mechanical dyssynchrony has additional value over QRS duration in predicting cardiac events in heart failure patients.41

This was an observational single-center cohort study with the limitations inherent to this kind of analysis. As symptoms of heart failure and functional class were not assessed, dyssynchrony could not be related to them, and this is an important constraint on further conclusions.

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  Far from questioning previous results and recommendations, this study corroborates the idea that mechanical dyssynchrony, according to established criteria, is highly prevalent in a population with impaired ventricular function and with a high prevalence of perfusion abnormalities.

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  Mechanical dyssynchrony is very common in patients with normal QRS width and mildly abnormal LVEF.

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  It was also found that clinical and MPI variables add value to the CRT criteria for predicting mechanical dyssynchrony.

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  In patients with normal or mildly abnormal rest images, QRS width was the only predictor of mechanical dyssynchrony.

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  In this context, gated SPECT myocardial perfusion imaging, which provides information on ischemia, fibrosis, ventricular function and dyssynchrony, is a valuable aid to therapeutic decision-making, including the use of cardiac resynchronization therapy.

The authors have no conflicts of interest to declare.