Skip Navigation

European Journal of Heart Failure 2008 10(4):412-420; doi:10.1016/j.ejheart.2008.02.004
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (5)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Chattopadhyay, S.
Right arrow Articles by Cleland, J. G.F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chattopadhyay, S.
Right arrow Articles by Cleland, J. G.F.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2008 European Society of Cardiology

The effect of pharmacological stress on intraventricular dyssynchrony in left ventricular systolic dysfunction

Sudipta Chattopadhyaya,*, Mohammed F. Alamgira, Nikolay P. Nikitina, Alan G. Fraserb, Andrew L. Clarka and John G.F. Clelanda,1

a Department of Cardiology, University of Hull Kingston-upon-Hull, UK
b University Hospital of Wales Cardiff, UK

* Corresponding author. 36 St Stephens Mansions, Mount Stuart Square, Cardiff, CF10 5LQ, UK. Tel.: +44 2920 493543. E-mail address: diptochatt{at}yahoo.co.uk (S. Chattopadhyay).


   Abstract
Top
 Notes
 Abstract
1. Introduction
 2. Method
 3. Results
 4. Discussion
 5. Conclusion
 References
 
Background: Cardiac resynchronisation therapy (CRT) improves symptoms and exercise capacity in many patients with heart failure (HF) who have left ventricular systolic dysfunction (LVSD) and markers of dyssynchrony. LV dyssynchrony is conventionally measured at rest but the symptoms of heart failure occur predominantly on exercise. Induction or exacerbation of dyssynchrony during stress might identify additional patients who could benefit from CRT.

Methods and results: Seventy-seven patients (47 with QRSd<120 ms and 30 with QRSd>120 ms) with heart failure due to left ventricular systolic dysfunction and 22 normal subjects underwent dobutamine stress echocardiography using colour tissue Doppler imaging. Left intraventricular dyssynchrony was measured as the standard deviation of the time to peak velocity from the onset of the QRS (Ts-SD) and the difference between the maximum and minimum time to peak velocity (Tscor-diff) in the 12 non-apical segments at rest and during peak stress. Timings were corrected for heart rate. The mean values of these indices increased with stress in both groups of patients but not in control subjects (p < 0.001). The prevalence of conventionally-defined dyssynchrony also increased with stress.

Conclusion: In patients with heart failure, the severity and the prevalence of intraventricular dyssynchrony increase with stress. Whether stress-induced dyssynchrony will identify patients who might benefit from CRT awaits further research.

Key Words: Stress echocardiography • Dyssynchrony • Cardiac resynchronisation therapy • Tissue Doppler imaging

Received July 3, 2007; Revised December 3, 2007; Accepted February 4, 2008


   1. Introduction
Top
 Notes
 Abstract
 1. Introduction
2. Method
 3. Results
 4. Discussion
 5. Conclusion
 References
 
Left ventricular (LV) mechanical dyssynchrony is present in 30-50% of patients with heart failure and LV systolic dysfunction (LVSD) at rest, depending on the population studied and the definition of dyssynchrony applied [1-4]. The optimal method for assessing dyssynchrony is unclear. Prolonged QRS duration (QRSd), widely perceived as a marker of cardiac dyssynchrony, was a universal entry criterion for the randomised controlled trials demonstrating clinical and echocardiographic benefits of cardiac resynchronisation therapy (CRT) [5,6]. However, QRSd is a crude indicator of mechanical dyssynchrony [1,3] and QRSd prior to implantation and its reduction with CRT are poor predictors of therapeutic response [7]. Some non-randomised observations have suggested that direct measurement of mechanical systolic dyssynchrony before implantation may improve prediction of response to CRT either alone or in addition to QRSd but conclusive evidence is lacking [8-13]. These studies have considered dyssynchrony as a relatively stable phenomenon that neither changes during cardiovascular stress nor during prolonged follow-up [6]. The failure of current approaches to consistently identify therapeutic response, especially the long-term response, may reflect a failure to appreciate the potential for dyssynchrony to be a dynamic problem. We investigated the possibility that the prevalence and severity of LV dyssynchrony change when the ventricle is subjected to stress.


   2. Method
Top
 Notes
 Abstract
 1. Introduction
 2. Method
3. Results
 4. Discussion
 5. Conclusion
 References
 
2.1. Patients
Inclusion criteria were NYHA class II-IV symptoms despite the use of diuretics and, unless not tolerated or contraindicated, treatment with ACE inhibitors or angiotensin receptor antagonists and beta-blockers for at least 3 months, LV ejection fraction (LVEF)<40% and sinus rhythm. Exclusion criteria were an acute coronary syndrome in the previous 6 months, significant valvular abnormality or a technically inadequate echocardiogram. The study population was divided into two groups: WQRS group (QRSd≥120 ms) and NQRS group (QRSd<120 ms). The aetiology of heart failure was considered to be ischaemic if there was evidence of previous myocardial infarction or angiographic evidence of >50% stenosis in major coronary arteries. Subjects, referred for the investigation of cardiac function, with a low probability of ischaemic heart disease, without a history of myocardial infarction, diabetes, hypertension, with normal resting ECG and echocardiography and no inducible ischaemia on dobutamine stress echocardiography (DSE), acted as controls.

Following a clinical examination and ECG every subject underwent standard transthoracic echocardiography followed by DSE. All subjects gave written informed consent and the Medical Ethics Committee of the Hull and East Yorkshire NHS Trust approved the protocol.

2.2. Echocardiography
A standard set of images were recorded digitally at rest using GE Vingmed System V scanner (Horten, Norway) equipped with a 2.5 to 5-MHz phased-array transducer and analysed off-line. LV volumes and LVEF were assessed using the biplane modified Simpson's rule.

2.3. Stress echocardiography
2.3.1. Protocol
Beta-blockers were stopped 48 h before the study. All other drugs were continued. Dobutamine was infused intravenously for 3-minute stages at incremental doses of 5, 10, 20, 30 and 40 mcg/kg/min with 12-lead ECG and non-invasive blood pressure monitoring. The test was terminated if any of the following pre-specified end-points was reached: target heart rate reached [85%x(220-age in years)], new or worsening regional wall motion abnormality (decrease in visually assessed wall motion score by one grade in at least two segments with each stage of dobutamine), onset of atrial fibrillation, >3 consecutive ventricular ectopic beats, sudden lack of chronotropic response to dobutamine, any degree of atrioventricular block, persistent haemodynamic compromise (fall in the systolic blood pressure of ≥20 mm Hg for ≥3 min), ST depression or elevation of ≥2 mm in the chest leads and/or ≥1 mm in the limb leads or symptomatic with angina or severe breathlessness. In the absence of any other indications to terminate the test or contraindications, intravenous atropine (300 to 1000 µg) was administered if the target heart rate was not reached with 40 µg/kg/min of dobutamine.

2.3.2. Image acquisition and analysis
Conventional 2-D and colour tissue Doppler images (cTDI) were obtained at rest and the final 90 s of each infusion stage with breath-holding and excluding ventricular or atrial premature complexes. Images were optimised for pulse repetition frequency, colour saturation, sector size, and depth to allow high frame rates. The loops were stored on magneto-optical discs and analysed off-line using customised software (Echopac 6.3, GE Vingmed).

In the cTDI mode, a sample cursor was placed at the midpoint of each of the 12 non-apical segments of the lateral, septal, anterior, inferior, posterior and anteroseptal walls in the 3 apical views and myocardial velocity curves were reconstituted. The onset of the QRS to the peak of the T wave was taken as systole. The time to peak systolic velocity (Ts) was measured from the onset of the QRS complex to the peak of the myocardial systolic velocity during ejection in each of the 12 segments at rest and at peak stress [12,13]. Ts was corrected for heart rate (Tscor) using the Bazett's formula (Tscor=Ts/{surd}R-R) to allow comparison between the Ts of any segment at rest and at peak stress [14]. Any segment that developed the highest positive velocity after systole with low flat velocity profile during ejection phase was excluded from the analysis.

Intraventricular dyssynchrony was measured as the standard deviation of the Ts and Tscor of all 12 segments (Ts-SD and Tscor-SD) [2,12,13,15] and the maximum difference in the Ts (Ts-diff) and Tscor (Tscor-diff) between any two of the 12 segments [15]. A segment was labelled as "delayed" if the Ts or Tscor was >the mean+2SD of controls in that state (i.e. rest or stress). The prevalence of systolic dyssynchrony was defined as % of patients with Ts-SD, Tscor-SD, Ts-diff or Tscor-diff of >the mean+2SD of controls in that state. All timings were calculated as the average of 2 to 3 consecutive cardiac cycles. All images were analysed by a single investigator (SC) blinded to the clinical characteristics of the patient.

2.4. Statistical analysis
The data were analysed using SPSS version 12 for Windows (SPSS Inc, Chicago, Illinois, USA). The data was tested for normality. Continuous variables were described as means and standard deviations and categorical data as percentages. For comparison of continuous variables between the three groups one way ANOVA or Kruskal-Wallis one way ANOVA on ranks with appropriate post-hoc correction was used. The data at rest and peak stress were compared using Student's paired t test or the Wilcoxon signed rank test as appropriate. Proportions were compared using the Chi-square test. A two-tailed p value <0.05 was considered significant.

Intraobserver variability in the Ts measured at the 12 non-apical segments was calculated in a sample of 10 randomly selected patients at rest and at peak stress totalling 240 pairs of measurements. It was reported as mean±SD. Confidence limits (95%) of differences were computed and expressed as absolute values and percentages of the average values of paired velocity measurements.


   3. Results
Top
 Notes
 Abstract
 1. Introduction
 2. Method
 3. Results
4. Discussion
 5. Conclusion
 References
 
Between January 2002 and March 2003, 77 patients with heart failure (mean age 68±9 years, 60 (78%) males) were enrolled (47 (61%) in NQRS group and 30 (39%) in WQRS group) (Table 1). Patients were in New York Heart Association class II (n=42), III (n=26) and IV (n=9). The QRSd, LV volumes and wall motion score index (WMSI) at rest were higher in the WQRS group. Twenty-two controls (mean age 67±12 years, 14 (64%) males) were also enrolled. Controls and patients had similar characteristics apart from measures of LV dysfunction. All controls and 31 (40%) patients reached the target heart rate (THR), 33 (43%) reached >90%, 8 (10%) reached >80% and 5 (7%) reached >70% of the THR. There were no major adverse events or limiting side-effects during the study. Of those with heart failure, 32/77 (41.5%) complained of chest discomfort with or without minor ST-segment depression. The heart rate, systolic and diastolic blood pressure and the rate pressure product were higher at peak stress than at rest in all three groups (Table 2).


View this table:
[in this window]
[in a new window]

  		Table 1 Comparison of baseline clinical characteristics of the controls and study groups

 


View this table:
[in this window]
[in a new window]

  		Table 2 Comparison of response to stress in the controls and study groups

 
3.1. Segmental time to peak velocity (Ts) at rest and during stress
At rest, Ts could be measured in 261/264 (98.9%) segments in the control group compared to 896/924 (97.0%) segments in patients with heart failure (p=0.23). At peak stress, Ts could be measured in 260/264 (98.4%) segments in the control group and 906/924 (98.1%) in patients with heart failure (p=0.84). The overall intraobserver variability (Table 3) was low (range 1.2-5.9% at rest and 1.0-9.6% at peak stress). The variability was highest in the basal segment of the anteroseptal wall at rest and in the basal segment of the septum at peak stress.


View this table:
[in this window]
[in a new window]

  		Table 3 Intraobserver variability in the Ts measured in the 12 non-apical segments at rest and peak stress in a random sample of 10 patients

 
In patients with heart failure, the Ts was delayed in most myocardial segments at rest and in all myocardial segments at peak stress compared to controls (Fig. 1). Ts was shortened in most segments during stress except postero-basal, lateral-mid and postero-mid segments where Ts was similar to or delayed compared to resting values. Comparing patients with NQRS and WQRS, the mean Ts of each segment was similar at rest but at peak stress, the postero-basal, lateral-mid and postero-mid segments in the WQRS group were delayed compared to the NQRS (Fig. 1).


Figure 01
View larger version (34K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1 Segmental time to peak velocity (mean±SE), uncorrected (Ts) and corrected for heart rate (Tscor), at rest and stress across the groups. Unmarked values, p<0.05 NQRS and WQRS v controls; *p=ns, NQRS and WQRS v controls; {star}p<0.05 NQRS v WQRS. bulletControls {diamondsuit}NQRS {blacksquare}WQRS B = basal, M = mid, L = lateral, S = septal, I = inferior, A = anterior, P = posterior, AS = anteroseptal.

 
Correction for heart rate (Tscor) had little effect on the overall pattern (Fig. 1). The Tscor shortened in all segments with dobutamine stress in controls. It failed to shorten in any segment and increased in the mid-segments of the lateral and posterior walls in patients with and without wide QRS. At rest, Tscor was delayed in 6/264 (2.3%) segments in the control group compared to 73/564 (12.9%) in the NQRS (p<0.001) and 81/360 (22.5%) in the WQRS (p<0.001) (p<0.001 comparing patient QRS groups). At peak stress, delays were identified in 10/264 (3.8%) segments in the control group compared to 215/564 (39.4%) in the NQRS (p<0.001) and 163/360 (45.28%) in the WQRS (p<0.001) (p=0.08 comparing patient QRS groups). In response to stress, the Tscor lengthened in 44/264 (16.7%) segments in the control group compared to 262/564 (46.5%) in the NQRS (p<0.001) and 172/360 (47.8%) in the WQRS (p<0.001) (p=0.69 comparing patient QRS groups).

3.2. Standard deviation of the time to peak systolic velocity (Ts-SD)
Ts-SD uncorrected for heart rate was markedly greater in patients compared to control subjects but changed little with stress (Fig. 2). However, marked differences with stress were observed after correction for heart rate. In the controls, Ts-SD and Tscor-SD were 20.3±8.8 and 23.9±11.4 at rest and 22.3±6.7 and 28.4±7.3 at peak stress. At rest, a Tscor-SD>46.7 ms (mean+2SD of controls) was seen in one control subject and 46 (60%) patients with heart failure (p<0.001), 21(45%) in NQRS (p=0.004 v controls) and 25(83%) in WQRS (p<0.001 v controls) groups (p=0.003 for the difference between NQRS and WQRS groups). At peak stress, a Tscor-SD of >43.0 ms (mean+2SD of controls) was seen in none of the controls but 65 (83%) (p<0.0001) patients with heart failure, 36(77%) in NQRS (p<0.001 v controls) and 29(97%) in WQRS (p<0.001 v controls) groups (p=0.061 for the difference between patient QRS groups) (Fig. 3).


Figure 02
View larger version (66K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 2 Median, interquartile range, 95% confidence and outlying results for Ts-SD, Ts-diff, Tscor-SD and Tscor-diff at rest (R) and stress (S) in the NQRS, WQRS and control groups. *p<0.001 Figure 02p<0.05 {blacktriangleup}p=ns.

 


Figure 03
View larger version (42K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 3 Percentage of patients with Tscor-SD and Tscor-diff of >the mean+2SD of controls at rest and stress within and across the groups. *p=0.000 and ¶p=0.004 compared to controls.

 
3.3. Maximum difference between segmental peak velocities (Ts-diff)
Ts-diff uncorrected for heart rate was markedly greater in patients compared to control subjects and increased with stress especially in patients with WQRS (Fig. 2). After correction for heart rate, the effects of stress were even more marked in patients but not in control subjects. In the controls, Ts-diff and Tscor-diff were 62.7±24.4 and 73.6±30.5 at rest and 70.9±22.4 and 88.3±21.8 at peak stress. At rest, no (0%) control subject but 47 (61%) patients (p<0.001) had Tscor-diff>134.5 ms (mean+2SD of controls). Twenty-three (49%) patients in NQRS group (p<0.001 v controls) and 24(80%) in WQRS group (p<0.001 v controls) (p=0.024 for the difference between patient QRS groups) had Tscor-diff>134.5 ms. At peak stress, 38 (81%) patients in NQRS group (p<0.001 v controls), 30 (100%) patients in the WQRS group (p<0.001 v controls and p=0.038 comparing patient QRS groups) and none of the control subjects had Tscor-diff>131.8 ms (mean+2SD of controls) (Fig. 3).

Depending on the TD variable, 95-100% of controls were normal at rest and all remained that way at peak stress compared to 8-13% in the NQRS group and none in the WQRS group (Fig. 4). In 43% of NQRS patients, the TD variables were normal at rest and became abnormal at peak stress compared to 20% in the WQRS group and none of the controls. 80% of the WQRS patients were dyssynchronous at rest and continued to be abnormal at stress compared to 38-40% in the NQRS and none of the controls. Depending on the variable, 6-8% of patients in the NQRS group and none of the WQRS group improved with stress.


Figure 04
View larger version (32K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 4 Percentage of patients in whom the dyssynchrony indices either improved or worsened under stress grouped according to whether they were normal or abnormal at rest. *p<0.05, {blacktriangleup}p=ns. N-N, normal at rest and stress; N-A, normal at rest and abnormal at stress; A-N, abnormal at rest and normal at stress; A-A, abnormal at rest and stress.

 

   4. Discussion
Top
 Notes
 Abstract
 1. Introduction
 2. Method
 3. Results
 4. Discussion
5. Conclusion
 References
 
Cardiac dyssynchrony has rarely been studied during stress. This study corroborates the reported high prevalence of intraventricular dyssynchrony at rest in patients with LVSD irrespective of QRS duration [1-4]. However, during pharmacological stress both the prevalence and severity of dyssynchrony increase. Since the prevalence of dyssynchrony at rest is lower in patients with QRSd <120 ms the increase is most evident in this population. The prevalence of stress-induced dyssynchrony in these patients approached that observed in patients with QRSd>120 ms during pharmacological stress. Indeed, most patients with LVSD had dyssynchrony during stress regardless of QRS duration. Stress rarely improved dyssynchrony in this study.

Compared to control subjects, the time to peak systolic velocity was greater in most myocardial segments at rest and in all segments at peak stress in patients with LVSD regardless of QRS duration. Stress shortened the time to peak systolic velocity in all segments in healthy subjects and in most segments of patients with LSVD. Indeed, when corrected for heart rate, stress shortened the time to peak velocity in control subjects but not in patients with LSVD regardless of QRS duration. Additional delays in some segments were observed in the latter. The lateral and posterior wall segments were particularly prone to delay both at rest and during stress in patients regardless of QRSd, as previously reported in patients at rest [15,16]. The greater vulnerability of the LV free-wall to dyssynchrony presumably reflects an exaggeration of the usual pattern of ventricular activation in the presence of a dilated ventricle, greater myocardial mass, slowed intra-myocardial conduction and areas of fibrosis and scar [17].

Studies investigating the effects of pacing-induced tachycardia, exercise or pharmacological stress on ventricular dyssynchrony have yielded conflicting results [18-22]. Indices of dyssynchrony did not change in subjects without heart disease in these studies whether the stressor was exercise or dobutamine. Pacing induced tachycardia augmented LV mechanical dyssynchrony in one study of patients with non-ischaemic LVSD. In 65 patients with heart failure studied by Lafitte et al. [18], only 22 of whom had QRS<120 ms, the mean values of the dyssynchrony indices did not change with exercise stress. Dyssynchrony increased in 37% and diminished in 20%. The changes may partly have reflected measurement error given the technical difficulties of exercise echocardiography. Valzania et al. [21] reported a lack of increase in dyssynchrony indices, derived from timings not corrected for heart rate, with dobutamine stress in patients with QRSd≥130 ms undergoing CRT. This is consistent with our findings. Neither Hummel et al. [20] nor Da Costa et al. [22] reported the effects of stress on dyssynchrony in heart failure patients with wide QRS. Differences in the proportion of patients with QRSd<120 ms, the proportion with dyssynchrony at rest, the magnitude of change in heart rate, the stressor and the criteria by which dyssynchrony is judged to be present may account for some of the differences observed. Importantly, CRT appears to maintain its synchronising effect during exercise stress [23].

Pharmacological stress permitted us to investigate patients who were elderly with poor exercise capacity and mobility and those with severe heart failure; patients that are difficult or impossible to study using exercise stress [18]. Higher heart rates may be reached during exercise than with peak dose dobutamine but the rapid decline in heart rate after exercise and delays in acquisition are common [24] as are the difficulties in obtaining adequate images due to the increased rate and depth of breathing.

Dobutamine stress may be more likely to induce ischaemia than exercise [25] which may better unmask ischaemia-induced dyssynchrony. Patients with LVSD are prone to subendocardial ischaemia whether or not they have epicardial coronary disease [26,27] and treatments that decrease ischaemia may improve dyssynchrony [26,28,29]. Stress-induced dyssynchrony could reflect induction of ischaemia and we cannot discount this as a contributing factor. However, in the absence of substantial deterioration of WMSI and mitral annular velocity at peak stress, it is unlikely that clinically overt ischaemia played a significant role in inducing dyssynchrony in our patients. The chronotropic effect of dobutamine may at least partly be responsible. Pacing induced tachycardia augments LV mechanical dyssynchrony in patients with non-ischaemic LVSD [19].

4.1. Limitations of this study
We did not study the mechanism of stress-induced dyssynchrony nor its ability to predict the response to CRT. The absence of recent coronary angiograms or segmental strain data precludes exclusion of ischaemia as a mechanism. In the absence of data on the sequence of electrical activation through the LV at rest and stress, we are unable to say whether the stress induced worsening of dyssynchrony is due to alteration in the electrical activity as a result of changes in the conduction properties or impaired mechanical coupling. The dyssynchrony was assessed at heart rates that are unlikely to be reached in elderly patients with relatively sedentary life styles and optimally treated with beta-blockers. It is uncertain what effects would be produced by a lesser degree of stress. We did not explore the relationship of post-systolic motion induced by stress to dyssynchrony. Segments that developed extreme delay in attaining their highest positive velocity were excluded from analysis (36/924, 3.9%). These would have contributed even further to the severity of dyssynchrony on stress.

4.2. Clinical implications
It is far from clear how patients should be selected for CRT. QRS duration thresholds and echo dyssynchrony criteria were chosen rather arbitrarily as entry criteria for clinical trials based on pathophysiological concepts and observed associations in small series of patients. Widened QRS is a marker of more severe left ventricular dilatation and dysfunction [30] and may be a marker of dyssynchrony mainly because it indicates a sicker ventricle. There is remarkably little evidence that echo dyssynchrony is associated with a worse prognosis and indeed some evidence that inter-ventricular dyssynchrony is associated with a better outcome [6]. If QRS duration and dyssynchrony are being used as markers of risk rather than of dyssynchrony then NT-proBNP is better than either [31,32]. Now that we know that CRT works for some patients, it is important to find out whether current guidelines are appropriate or too restrictive.

Observational studies suggest that CRT may be effective in patients with narrower QRS [33,34] whether or not they have mechanical dyssynchrony at rest. Recent reports have failed to identify a strong-link between echo dyssynchrony at rest and outcome of CRT [35]. One of the many potential explanations for the lack of this relationship, may be that dyssynchrony is dynamic and changes with stress. If stress-dyssynchrony is an appropriate target for therapy stress-echocardiography might be considered necessary in order to select patients for CRT. However, if stress-dyssynchrony is as common as we suggest, then a strategy of CRT implantation in all patients who have persistent major LVSD could be considered a more pragmatic approach. These concepts need to be tested in randomised controlled trials. This data also suggests that measuring dyssynchrony only at rest underestimates its prevalence and fixed setting of the biventricular pacemakers may not be physiological in the presence of such dynamicity.


   5. Conclusion
Top
 Notes
 Abstract
 1. Introduction
 2. Method
 3. Results
 4. Discussion
 5. Conclusion
References
 
Dobutamine stress induces and exacerbates dyssynchrony in patients with LVSD. LV dyssynchrony, unmasked by stress in patients with narrow QRS, could be a target for therapy. If so, then most patients with LVSD, regardless of QRS duration or evidence of dyssynchrony at rest might benefit from CRT. This hypothesis remains to be tested.


   Notes
Top
 Notes
Abstract
 1. Introduction
 2. Method
 3. Results
 4. Discussion
 5. Conclusion
 References
 
1 Professor John GF Cleland was the Principal Investigator of the CARE-heart failure study and has received funding to attend meetings and honoraria for speaking on aspects of heart failure from Medtronic and Biotronik. No other conflicts of interest. Back


   References
Top
 Notes
 Abstract
 1. Introduction
 2. Method
 3. Results
 4. Discussion
 5. Conclusion
 References
 

  1. Fauchier L., Marie O., Casset-Senon D., Babuty D., Cosnay P., Fauchier J.P. Reliability of QRS duration and morphology on surface electrocardiogram to identify ventricular dyssynchrony in patients with idiopathic dilated cardiomyopathy. Am J Cardiol (2003) 92:341–344.[CrossRef][Web of Science][Medline]
  2. Yu C.M., Lin H., Zhang Q., Sanderson J.E. High prevalence of left ventricular systolic and diastolic asynchrony in patients with congestive heart failure and normal QRS duration. Heart (2003) 89:54–60.[Abstract/Free Full Text]
  3. Ghio S., Constantin C., Klersy C., et al. Interventricular and intraventricular dyssynchrony are common in heart failure patients, regardless of QRS duration. Eur Heart J (2004) 25:571–578.[Abstract/Free Full Text]
  4. Yu C.M., Yang H., Lau C.P., et al. Regional left ventricle mechanical asynchrony in patients with heart disease and normal QRS duration: implication for biventricular pacing therapy. Pacing Clin Electrophysiol (2003) 26:562–570.[CrossRef][Medline]
  5. Freemantle N., Tharmanathan P., Calvert M.J., Abraham W.T., Ghosh J., Cleland J.G. Cardiac resynchronisation for patients with heart failure due to left ventricular systolic dysfunction — a systematic review and meta-analysis. Eur J Heart Fail (2006) 8:433–440.[Abstract/Free Full Text]
  6. Cleland J.G., Nasir M., Tageldien A. Cardiac resynchronization therapy or atrio-biventricular pacing—what should it be called? Nat Clin Pract Cardiovasc Med (2007) 4:90–101.[CrossRef][Web of Science][Medline]
  7. Kashani A., Barold S.S. Significance of QRS complex duration in patients with heart failure. J Am Coll Cardiol (2005) 20(46):2183–2192.
  8. Breithardt O.A., Stellbrink C., Kramer A.P., et al. Echocardiographic quantification of left ventricular asynchrony predicts an acute hemodynamic benefit of cardiac resynchronization therapy. J Am Coll Cardiol (2002) 40:536–545.[Abstract/Free Full Text]
  9. Ansalone G., Giannantoni P., Ricci R., et al. Doppler myocardial imaging in patients with heart failure receiving biventricular pacing treatment. Am Heart J (2001) 142:881–896.[CrossRef][Web of Science][Medline]
  10. Sogaard P., Kim W.Y., Jensen H.K., et al. Impact of acute biventricular pacing on left ventricular performance and volumes in patients with severe heart failure. A tissue Doppler and three-dimensional echocardiographic study. Cardiology (2001) 95:173–182.[CrossRef][Web of Science][Medline]
  11. Nelson G.S., Curry C.W., Wyman B.T., et al. Predictors of systolic augmentation from left ventricular preexcitation in patients with dilated cardiomyopathy and intraventricular conduction delay. Circulation (2000) 101:2703–2709.[Abstract/Free Full Text]
  12. Yu C.M., Fung W.H., Lin H., Zhang Q., Sanderson J.E., Lau C.P. Predictors of left ventricular reverse remodeling after cardiac resynchronization therapy for heart failure secondary to idiopathic dilated or ischemic cardiomyopathy. Am J Cardiol (2003) 91:684–688.[CrossRef][Web of Science][Medline]
  13. Yu C.M., Chau E., Sanderson J.E., et al. Tissue Doppler echocardiographic evidence of reverse remodeling and improved synchronicity by simultaneously delaying regional contraction after biventricular pacing therapy in heart failure. Circulation (2002) 105:438–445.[Abstract/Free Full Text]
  14. Stoylen A., Wisloff U., Slordahl S. Left ventricular mechanics during exercise: a Doppler and tissue Doppler study. Eur J Echocardiogr (2003) 4:286–291.[Abstract/Free Full Text]
  15. Yu C.M., Fung J.W.-H., Zhang Q., et al. Tissue Doppler imaging is superior to strain rate imaging and postsystolic shortening on the prediction of reverse remodeling in both ischemic and nonischemic heart failure after cardiac resynchronization therapy. Circulation (2004) 110:66–73.[Abstract/Free Full Text]
  16. Zhang Y., Chan A.K., Yu C.M., et al. Left ventricular systolic asynchrony after acute myocardial infarction in patients with narrow QRS complexes. Am Heart J (2005) 149:497–503.[CrossRef][Web of Science][Medline]
  17. Akar F.G., Spragg D.D., Tunin R.S., Kass D.A., Tomaselli G.F. Mechanisms underlying conduction slowing and arrhythmogenesis in nonischemic dilated cardiomyopathy. Circ Res (2004) 95:717–725.[Abstract/Free Full Text]
  18. Lafitte S., Bordachar P., Lafitte M., et al. Dynamic ventricular dyssynchrony: an exercise-echocardiography study. J Am Coll Cardiol (2006) 47:2253–2259.[Abstract/Free Full Text]
  19. Kurita T., Onishi K., Dohi K., et al. Impact of heart rate on mechanical dyssynchrony and left ventricular contractility in patients with heart failure and normal QRS duration. Eur J Heart Fail (2007) 9:637–643.[Abstract/Free Full Text]
  20. Hummel J.P., Lindner J.R., Belcik J.T., et al. Extent of myocardial viability predicts response to biventricular pacing in ischemic cardiomyopathy. Heart Rhythm (2005) 2:1211–1217.[CrossRef][Web of Science][Medline]
  21. Valzania C., Gadler F., Eriksson M.J., Olsson A., Boriani G., Braunschweig F. Electromechanical effects of cardiac resynchronization therapy during rest and stress in patients with heart failure. Eur J Heart Fail (2007) 9:644–650.[Abstract/Free Full Text]
  22. Da Costa A., Thevenin J., Roche F., et al. Prospective validation of stress echocardiography as an identifier of cardiac resynchronization therapy responders. Heart Rhythm (2006) 3:406–413.[CrossRef][Web of Science][Medline]
  23. Bordachar P., Lafitte S., Reuter S., et al. Echocardiographic assessment during exercise of heart failure patients with cardiac resynchronization therapy. Am J Cardiol (2006) 97:1622–1625.[CrossRef][Web of Science][Medline]
  24. Pasquet A., Yamada E., Armstrong G., Beachler L., Marwick T.H. Influence of dobutamine or exercise stress on the results of pulsed-wave Doppler assessment of myocardial velocity. Am Heart J (1999) 138:753–758.[CrossRef][Web of Science][Medline]
  25. Cohen J.L., Ottenweller J.E., George A.K., Duvvuri S. Comparison of dobutamine and exercise echocardiography for detecting coronary artery disease. Am J Cardiol (1993) 72:1226–1231.[CrossRef][Web of Science][Medline]
  26. Cleland J.G., Pennell D.J., Ray S.G., et al. Myocardial viability as a determinant of the ejection fraction response to carvedilol in patients with heart failure (CHRISTMAS trial): randomised controlled trial. Lancet (2003) 362:14–21.[CrossRef][Web of Science][Medline]
  27. Skalidis E.I., Parthenakis F.I., Patrianakos A.P., Hamilos M.I., Vardas P.E. Regional coronary flow and contractile reserve in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol (2004) 44:2027–2032.[Abstract/Free Full Text]
  28. Dalle Mule J., Cleland J.G., Pennel D.J., et al. Beneficial effects of carvedilol in patients with ischemic cardiomyopathy and a "narrow" QRS: results of the CHRISTMAS study. Circulation (2003) 108. pIV-369.
  29. Duncan A., Francis D., Gibson D., Pepper J., Henein M. Electromechanical left ventricular resynchronisation by coronary artery bypass surgery. Eur J Cardiothorac Surg (2004) 26:711–719.[Abstract/Free Full Text]
  30. Khan N.K., Goode K.M., Cleland J.G., et al. Prevalence of ECG abnormalities in an international survey of patients with suspected or confirmed heart failure at death or discharge. Eur J Heart Fail (2007) 9:491–501.[Abstract/Free Full Text]
  31. Olsson L.G., Swedberg K., Cleland J.G., et al. Prognostic importance of plasma NT-pro BNP in chronic heart failure in patients treated with a beta-blocker: results from the Carvedilol Or Metoprolol European Trial (COMET) trial. Eur J Heart Fail (2007) 9:795–801.[Abstract/Free Full Text]
  32. Richardson M., Freemantle N., Calvert M.J., Cleland J.G., Tavazzi L. Predictors and treatment response with cardiac resynchronization therapy in patients with heart failure characterized by dyssynchrony: a pre-defined analysis from the CARE-HF trial. Eur Heart J (2007) 28:1827–1834.[Abstract/Free Full Text]
  33. Achilli A., Sassara M., Ficili S., et al. Long-term effectiveness of cardiac resynchronization therapy in patients with refractory heart failure and "narrow" QRS. J Am Coll Cardiol (2003) 42:2117–2124.[Abstract/Free Full Text]
  34. Gasparini M., Mantica M., Galimberti P., et al. Beneficial effects of biventricular pacing in patients with a "narrow" QRS. Pacing Clin Electrophysiol (2003) 26:169–174.[CrossRef][Medline]
  35. Cleland J.G., Abdellah A.T., Khaleva O., Coletta A.P., Clark A.L. Clinical trials update from the European Society of Cardiology Congress 2007: 3CPO, ALOFT, PROSPECT and statins for heart failure. Eur J Heart Fail (2007) 9:1070–1073.[Abstract/Free Full Text]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Eur J EchocardiogrHome page
P. Lancellotti, C. Szymanski, M. Moonen, C. Garweg, K. O'Connor, C. Tribouilloy, and L. A. Pierard
Dynamic left ventricular dyssynchrony: a potential cause of no contractile reserve in patients with low-gradient aortic stenosis
Eur J Echocardiogr, October 1, 2009; 10(7): 880 - 883.
[Abstract] [Full Text] [PDF]

Home page
 BMJHome page
R. M Cubbon and K. K A Witte
Cardiac resynchronisation therapy for chronic heart failure and conduction delay
BMJ, April 28, 2009; 338(apr28_2): b1265 - b1265.
[Full Text]

Home page
 J Am Coll CardiolHome page
J. G.F. Cleland, L. Tavazzi, J.-C. Daubert, A. Tageldien, and N. Freemantle
Cardiac resynchronization therapy are modern myths preventing appropriate use?
J. Am. Coll. Cardiol., February 17, 2009; 53(7): 608 - 611.
[Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
J. Cleland, N. Freemantle, S. Ghio, F. Fruhwald, A. Shankar, M. Marijanowski, Y. Verboven, and L. Tavazzi
Predicting the Long-Term Effects of Cardiac Resynchronization Therapy on Mortality From Baseline Variables and the Early Response: A Report From the CARE-HF (Cardiac Resynchronization in Heart Failure) Trial
J. Am. Coll. Cardiol., August 5, 2008; 52(6): 438 - 445.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (5)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Chattopadhyay, S.
Right arrow Articles by Cleland, J. G.F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chattopadhyay, S.
Right arrow Articles by Cleland, J. G.F.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?