Left ventricular mechanical dyssynchrony by phase

Authors: Fadi G Hage

Publish Date: 2013/11/22

Volume: 21, Issue: 1, Pages: 67-70

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Abstract

Heart failure HF is a major public health problem Recent estimates indicate that more than 5 million patients have clinically manifest HF in the United States and more than 650000 new cases are diagnosed annually1 Overall prognosis in this population remains poor A recent study using a national registry in Sweden of more than 1 million hospital admissions between 1988 and 2004 compared the impact of HF vs the most common forms of cancer lung colorectal prostate and bladder cancer for men and lung colorectal bladder breast and ovarian cancer for women2 Annual incidence of firstever hospitalization for HF and cancer per 100000 were 484 and 373 for men and 470 and 350 for women older than 20 years HF was associated with unadjusted casefatality rate of 59 within 5 years compared to 58 for patients with cancer The total cost of HF in the United States for 2013 is estimated at 32 billion which is projected to increase to 70 billion by 20303 These mortality and economic figures highlight the public health care burden of HFOver the last few decades devicebased therapies have revolutionized the treatment of HF Implantable cardioverter defibrillators ICDs are used for the primary and secondary prevention of sudden cardiac death in patients at high risk4 In addition cardiac resynchronization therapy CRT or biventricular pacing has been shown to reverse ventricular remodeling ameliorate mitral regurgitation improve left ventricular ejection fraction LVEF and decrease HF hospitalization and allcause mortality4 Initial studies were performed in patients with New York Heart Association NYHA class III or ambulatory class IV HF symptoms LVEF ≤ 35 and QRS duration ≥ 120 ms The bulk of the data was in patients with class III symptoms left bundle branch block LBBB pattern and QRS  150 ms5 Recent evidence extended the benefit of CRT to patients with milder HF A metaanalysis of five randomized clinical trials that included 4317 patients with NYHA class I or II HF LVEF ≤ 40 and QRS ≥ 120 ms demonstrated a 19 reduction in overall mortality 95 CI 135 and a 32 reduction in HF events or hospitalization 95 CI 2141 in patients receiving CRT + ICD vs ICD alone6 In this analysis 29 patients needed to be treated to prevent 1 death and 15 needed to be treated to prevent 1 HF hospitalization In asymptomatic patients NYHA class I the reduction in HF hospitalization remained statistically significant while the reduction in mortality was not This analysis was limited by a small number of events analyzed for asymptomatic patients The recently updated guidelines state that CRT can be useful in patients with NYHA class II HF class I indication for patients with LVEF ≤ 35 sinus rhythm LBBB QRS ≥ 150 ms and class IIa indication for similar patients with QRS 120149 ms or with atrial fibrillation and class IIb for patients with nonLBBB and QRS ≥ 150 ms and may be considered in patients with NYHA class I HF class IIb indication for patients with LVEF ≤ 30 ischemic etiology sinus rhythm LBBB QRS ≥ 150 ms CRT is not indicated for patients with NYHA class I or II HF nonLBBB and QRS  150 ms class III14It is widely recognized that as much as a third of patients that receive CRT based on current indications do not derive clinical benefit7 Furthermore a subset of patients that do not have prolonged QRS may benefit from CRT due to the presence of mechanical but not electrical dyssynchrony This created a need for identifying LV mechanical dyssynchrony using imaging Traditionally this has been performed with echocardiography which provides several parameters that assess mechanical dyssynchrony ranging from septal wall to posterior wall delay and tissue Doppler imaging to speckle tracking and threedimensional echocardiography8 These echocardiographic parameters showed modest sensitivity and specificity for predicting response to CRT in a multicenter study with large intraobserver and interobserver variations with poor agreement between these different parameters910 A recent multicenter trial randomized 809 patients with NYHA class III or IV HF LVEF ≤ 35 QRS  130 ms and evidence of LV mechanical dyssynchrony by echocardiography that underwent CRT implantation to CRT capability turned on or off11 CRT did not reduce the rate of death or hospitalization for HF and there was a signal for increased mortality in the group that had CRT turned on HR 18 95 CI 1129 This highlights the risk of CRT implantation in patients that will not benefit from resynchronization beyond the wasted resources Indeed in a recent article in the Journal Friehling et al12 demonstrated that right ventricular pacing may worsen LV synchrony in patients with LBBBGated SPECT myocardial perfusion imaging allows for the assessment of LV mechanical dyssynchrony using phase analysis1314 This technique measures the onset of mechanical contraction across the LV which can be shown as a “phase polar map” similar to the perfusion polar maps or as a phase histogram The standard deviation phase standard deviation PSD and the width encompassing 95 of the samples of the phase histogram phase bandwidth PBW have been validated as indices of LV synchrony The advantages of this technique have been reviewed at length and they include automaticity reproducibility and availability with current myocardial perfusion imaging without the requirement for additional imaging1314 Values for phase analysis indices in control subjects and in patients with abnormal LV systolic function LBBB right bundles branch block and paced rhythm have been published15 Interestingly LV mechanical dyssynchrony by phase analysis is at best moderately correlated with electrical dyssynchrony r = 05 for PSD and QRS r = 04 for PBW and QRS16 Preliminary studies performed on a small number of patients showed that phase analysis indices may be helpful in predicting CRT response17 Furthermore LV mechanical dyssynchrony by phase analysis was associated with poor prognosis in patients with ischemic cardiomyopathy and LVEF ≤ 3518 in patients with LVEF ≤ 40 who have an ICD19 and in those with endstage renal disease20In this issue of the Journal Goldberg et al21 retrospectively studied the prognostic value of LV mechanical dyssynchrony by phase analysis in patients with nonischemic cardiomyopathy normal perfusion on stress and rest images with no prior history of CAD or coronary revascularization with LVEF 3550 and QRS  150 ms who underwent myocardial perfusion imaging for clinical indications LV mechanical dyssynchrony indices were determined by phase analysis of the stress images using the Corridor 4DM software which expresses PSD and PBW in rather than degrees The study population included 324 patients age 62 ± 13 years 62 male 36 diabetes LVEF 44 ± 5 87 with QRS ≤ 120 ms who were followedup for 47 ± 23 years during which 86 patients 26 died There was no significant correlation between QRS and PSD or PBW stressing the dissociation of electric and mechanical dyssynchrony in patients with mildmoderate LV systolic dysfunction A previous study also reported very poor correlation between the two in a similar population of patients with LVEF 355022 When the population was divided into tertiles of PSD 36 3652 52 there was a nonstatistically significant trend toward higher annualized mortality with increasing PSD 47 56 and 70 P = 2 In a multivariate Cox proportional hazard model that adjusted for baseline demographics comorbidities medication use QRS and LVEF the highest tertile of PSD was associated with a twofold increased risk of death compared to the lowest tertile HR 197 95 CI 106366 P = 033 Similar findings were reported for PSD included in the model as continuous variable and for PBW Importantly PSD continued to be an independent predictor of death when analyzed in patients with QRS ≤ 120 msIn order to fully understand the implications of these findings we have to appreciate the limitations of this study First the study population is relatively small with only 86 deaths over a mean study period of almost 5 years Since the outcome of patients with HF is generally poor as discussed above the interest is in prognostication over a shorter time frame The KaplanMeier survival curves Figure 4 in21 appear to separate at 1 year of followup but this is unlikely to be statistically significant given the small number of events Second the findings are of borderline statistical significance and are only significant in the multivariate model Third the distribution of PSD in this population is very narrow The upper tertile of PSD 52 in this population lies within the normal distribution15 In contrast Atchley et al22 reported that as many as 29 of patients with LVEF 3550 and QRS  120 ms had a PSD ≥ 43° or 12 Unlike the current study the majority of patients studied by Atchley et al22 had known CAD and perfusion abnormalities on imaging ~90 It is not clear whether this is the reason for the discrepancy in prevalence of LV mechanical dyssynchrony between the two studies but the applicability of the prognostic findings to clinical care is problematic if the prevalence of dyssynchrony in this population is low Fourth as the authors point out the presence and severity of HF symptoms ie NYHA class which is a validated prognostic indicator is not accounted for Finally the cause of death is not available In another study published in this issue of the Journal we show that in patients with HF and LVEF ≤ 35 LV mechanical dyssynchrony is independently associated with potential sudden cardiac death events sudden cardiac death fatal myocardial infarction spontaneous sustained 30 seconds ventricular tachyarrhythmia resuscitated cardiac arrest or appropriate ICD discharge23 In this population of 917 HF patients from the AdreView Myocardial Imaging for Risk Evaluation in Heart Failure ADMIREHF study patients who experienced potential sudden cardiac death events had significantly wider PSD than matched control patients 623° ± 24° vs 555° ± 23° P = 03 and were more likely to have a PSD ≥ 60º 53 vs 35 P = 03 Similar to the study by Goldberg et al21 the number of events was relatively low 92 subjects experienced potential sudden cardiac death events and the findings were of borderline statistical significanceThe importance of the study by Goldberg et al21 is the finding that LV mechanical dyssynchrony may carry prognostic data independent of electric dyssynchrony and LVEF in a HF population with only mildmoderate LV systolic dysfunction that does not qualify for CRT or ICD under the current guidelines If these findings are verified in a larger population from a multicenter study preferably with prospective prespecified design that includes adjudicated endpoints they will add to our current risk stratification tools a novel prognostic indicator in this overall highrisk population and open the door for interventional studies that select patients with higher likelihood to benefit from device therapy

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