Ventricular dyssynchrony significantly impairs cardiac performance. However, the independent role of interventricular dyssynchrony (interVD) and intraventricular dyssynchrony (intraVD) in the development of abnormalities of systolic and diastolic performance is unclear. Cardiac magnetic resonance imaging was performed in 39 patients with left bundle branch block and 13 healthy patients. Structural and functional parameters of the left ventricle and degrees of interVD and intraVD were measured. We found that interVD was inversely correlated with left ventricular (LV) ejection fraction (r = −0.8, p <0.0001) and positively correlated with LV end-diastolic volume (r = 0.4, p <0.01), LV end-systolic volume (r = 0.6, p <0.0001), and LV mass (r = 0.4, p <0.01), thus indicating that interVD significantly affects systolic function and favors ventricular remodeling. Multivariate analysis further confirmed that interVD was an independent predictor of systolic dysfunction. Interestingly, we found that interVD was not associated with abnormalities of diastolic performance. Conversely, we found that intraVD significantly impaired diastolic function, whereas it had no effect on systolic function. IntraVD was inversely correlated with peak filling rate (r = −0.7, p <0.0001) and 1/2 filling fraction (r = 0.4, p = 0.04) and positively correlated with time to peak filling rate (r = 0.6, p <0.0001), validated parameters of diastolic function. Multivariate analysis confirmed that intraVD was an independent predictor of diastolic dysfunction. In conclusion, our study suggests that the 2 components of ventricular dyssynchrony differently affect cardiac performance. If confirmed in prospective studies, our results may help to predict the prognosis of patients with left bundle branch block and different degrees of interVD and intraVD, particularly those subjects undergoing cardiac resynchronization therapy.
The objective of this study was to investigate the independent effects of interventricular dyssynchrony (interVD) and intraventricular dyssynchrony (intraVD) on cardiac remodeling and functional changes that occur in patients with isolated left bundle branch block (LBBB). Cardiac magnetic resonance (CMR) imaging was the technique of choice for this study because it is considered the gold standard in the quantification of left ventricular (LV) size and function and has been previously shown to be an accurate tool in the assessment of interVD and intraVD.
Methods
We retrospectively analyzed all patients with LBBB referred for a CMR evaluation from 2006 through 2011. The study was approved by the institutional review board of St. Luke’s and Roosevelt Hospitals. LBBB was diagnosed according to standard electrocardiographic criteria: QRS duration ≥120 ms and absence of initial R wave followed by a wide deep S wave in the right precordial leads on 12-lead electrocardiogram.
We included only patients with isolated LBBB without evidence of cardiomyopathy from secondary cardiovascular diseases. We excluded patients with a history or evidence of familial cardiomyopathy, supraventricular or ventricular arrhythmias, presence of significant valve disease, pulmonary hypertension, and significant pericardial or pleural effusion. We excluded patients displaying cardiac late enhancement after contrast CMR (intramyocardial scar) and presenting with CMR evidence of acute myocarditis, chronic myocardial inflammatory disease, and infiltrative cardiomyopathy. Remarkably, we did not include patients with a history or evidence of coronary artery disease. Coronary artery disease was defined by the presence of a stress perfusion abnormality or CMR evidence of transmural or subendocardial infarct. Coronary artery disease was also defined by the presence of an obstructive coronary lesion detected by coronary computed tomographic analysis performed on the same day. Cause of LBBB in the included patients was considered a primary conduction abnormality. Thirteen healthy volunteers with no abnormal findings during physical examination, no conduction abnormalities on electrocardiogram, and normal LV function were evaluated for comparison.
Patients were imaged with a 1.5-T scanner using an 8-element phased-array coil (Signa EXCITE, GE Medical Systems, Milwaukee, Wisconsin). Images were acquired with electrocardiographic gating and breath holding. After scout image acquisition, short- and long-axis cine images were acquired using a steady-state free precession pulse sequence with the following parameters: repetition time 3.3 ms, echo time 1.4 ms, 20 views per segment, field of view 35 × 35 cm, acquisition matrix 192 × 160, slice thickness 8 mm, slice gap 0 mm, flip angle 45°, receive bandwidth 125 kHz, and 20 to 30 phases depending on heart rate. IntraVD was determined from short-axis steady-state free precession sequences. It was defined as the time difference between peak contraction of the septum and the most delayed wall. This is a similar method used by M-mode echocardiography but CMR overcomes several of its limitations by providing better visualization of the LV endocardium because of its superior contrast and spatial resolution. Phase-contrast images were acquired perpendicular to the proximal pulmonary artery and perpendicular to the proximal aorta to quantify interVD. InterVD was determined from the velocity-encoded phase-contrast sequences. It was defined as the temporal difference between the onset of aortic and pulmonary flow. Images were reviewed and analyzed using ReportCard 4.0 (GE Medical Systems, Milwaukee, Wisconsin) for volumetric and flow analysis. LV and right ventricular volumes were determined by manual endocardial border tracing in the short axis, from base to apex in end-diastolic and end-systolic phases. Diastolic function was evaluated using custom software (Suite Heart 1.0; GE Medical Systems, Milwaukee, Wisconsin). Semiautomatic segmentation was performed for basal and midventricular short-axis slices across all temporal phases to assess the time course of global volumetric filling. A volume–time curve was generated from all frames of all cines. Three diastolic parameters were evaluated: peak filling rate, time to filling rate, and 1/2 filling fraction. The 1/2 filling fraction was defined as percent diastolic filling occurring during the first 1/2 of diastole. These parameters are derived by LV volume filling analysis and represent validated indexes for assessment of diastolic function, which are well correlated with echocardiograph indexes of diastolic function. Because CMR represents the gold standard for measurement of cardiac volumes, these parameters have some advantages with respect to transvalvular mitral inflow velocities, which are measured using phase-contrast sequencing. In fact, phase-contrast sequencing is often technically difficult perform and it is significantly influenced by flow turbulences. Absolute duration of systole was defined as the interval from onset of the R wave to the time to reach end-systolic volume. Duration of LV diastole was defined as the interval from end-systolic volume to end-diastolic volume. These measurements were expressed as percent complete cardiac cycle. Three independent measurements of interVD were performed in each patient by 2 different blinded observers.
All analyses were carried out using a standard statistical package (SPSS 16.0, SPSS, Inc., Chicago, Illinois). Continuous variables were expressed as mean ± SD. Categorical variables were expressed as frequency and percentage. We performed univariate analyses of continuous variables using Student’s t test and chi-square test for categorical variables. All tests were 2-tailed and statistical significance was accepted at a p value <0.05. Correlation between interVD and intraVD and ventricular parameters were calculated using the Pearson correlation coefficient. Inter- and intraobserver variabilities were measured using Bland–Altman analysis and intraclass correlation coefficient analysis. Univariate and multivariate regression analyses were performed to assess for predictors of LV systolic and diastolic dysfunction.
Results
We evaluated 39 consecutive patients with isolated LBBB (19 men) and 13 healthy patients (7 men). Baseline characteristics of the 2 groups are presented in Table 1 . As expected, patients with LBBB had larger end-diastolic and end-systolic LV volumes, larger LV mass, and increased interVD and intraVD. LV systolic time was longer and LV filling time was shorter in patients with LBBB compared to healthy patients, without any significant difference in the entire cardiac cycle duration. No significant differences in right ventricular dimension or performance were observed.
| Variable | LBBB (n = 39, 80%) | Control Group (n = 10, 20%) | p Value |
|---|---|---|---|
| Age (years) | 59.5 ± 11.2 | 53.2 ± 13.6 | NS |
| Body surface area (kg/m 2 ) | 1.8 ± 0.2 | 1.8 ± 0.3 | NS |
| Heart rate (beats/min) | 66.8 ± 9.4 | 62.75 ± 9.6 | NS |
| QRS duration (ms) | 143 ± 14 | 98.2 ± 7.3 | <0.0001 |
| Left ventricular ejection fraction (%) | 48.9 ± 6.6 | 63.1 ± 5.3 | <0.0001 |
| Left ventricular end-diastolic volume index (ml/m 2 ) | 90.6 ± 19.9 | 74.6 ± 11.1 | <0.01 |
| Left ventricular end-systolic index (ml/m 2 ) | 46.9 ± 15 | 27.5 ± 6.3 | <0.0001 |
| Stroke volume (ml) | 78.6 ± 18.5 | 84.4 ± 18 | NS |
| Stroke volume index (ml/m 2 ) | 44.4 ± 6.7 | 47 ± 7.9 | NS |
| Mass (g/m 2 ) | 62.7 ± 16.1 | 52.8 ± 12.4 | 0.04 |
| Left ventricular systolic time (percent cardiac cycle) | 44.1 ± 7.4 | 34.6 ± 5.6 | <0.001 |
| Left ventricular filling time (percent cardiac cycle) | 55.9 ± 7.4 | 65.4 ± 5.6 | <0.0001 |
| Duration of cardiac cycle (ms) | 889.6 ± 126.6 | 945.8 ± 174.6 | NS |
| Peak filling rate (ml/s) | 324 ± 59.7 | 395.9 ± 31.4 | 0.0001 |
| Time to peak filling rate (ms) | 270.1 ± 128 | 160.7 ± 19.6 | <0.01 |
| 1/2 filling rate | 0.6 ± 0.1 | 0.7 ± 0.2 | <0.01 |
| Right ventricular ejection fraction (%) | 60 ± 5.8 | 58.6 ± 6.9 | NS |
| Right ventricular end-diastolic volume index (ml/m 2 ) | 72.3 ± 12.7 | 77.8 ± 11.9 | NS |
| Right ventricular end-systolic volume index (ml/m 2 ) | 28.3 ± 7.9 | 32.6 ± 9.7 | NS |
| Left atrium (ml) | 57.5 ± 16.6 | 56.2 ± 9.2 | NS |
| Interventricular dyssynchrony (ms) | 64.6 ± 25.8 | 0 | <0.0001 |
| Intraventricular dyssynchrony (ms) | 111.7 ± 25.8 | 0 | <0.0001 |
We investigated how interVD and intraVD selectively affect systolic and diastolic parameters. Surprisingly, we found that interVD and intraVD differently affected systolic and diastolic performances. Coefficients of correlation between cardiac parameters and mechanical dyssynchrony are presented in Table 2 and Figure 1 . InterVD was found to be significantly associated with systolic dysfunction. InterVD was inversely correlated with LV ejection fraction, whereas it was positively correlated with LV end-diastolic volume index, LV end-systolic volume index, and LV mass. Multivariate analysis demonstrated that interVD was an independent predictor of LV systolic dysfunction and increased LV end-systolic volume index when adjusted for age, gender, and intraVD. Of note, for every 10-ms increase in interVD delay, there was a 2% decrease in ejection fraction and a 4-ml/m 2 increase in LV end-systolic volume index. Surprisingly, interVD was not associated with derangements of diastolic function.
| Parameters LBBB | InterVD | IntraVD | ||||
|---|---|---|---|---|---|---|
| r 2 | r | p Value | r 2 | r | p Value | |
| Interventricular dyssinchrony | 0.01 | 0.1 | NS | |||
| QRS duration (ms) | 0.01 | 0.1 | NS | 0.01 | 0.1 | NS |
| Left ventricular ejection fraction (%) | 0.6 | −0.8 | <0.0001 | 0.05 | −0.2 | NS |
| Left ventricular end-diastolic volume index (ml/m 2 ) | 0.2 | 0.4 | <0.01 | 0.04 | 0.2 | NS |
| Left ventricular end-systolic index (ml/m 2 ) | 0.4 | 0.6 | <0.0001 | 0.06 | 0.2 | NS |
| Stroke volume (ml/m 2 ) | 0.01 | 0.1 | NS | 0.01 | 0.1 | NS |
| Mass (g/m 2 ) | 0.2 | 0.4 | <0.01 | 0.01 | 0.1 | NS |
| Right ventricular ejection fraction (%) | 0.01 | −0.1 | NS | 0.01 | 0.1 | NS |
| Right ventricular end-diastolic volume index (ml/m 2 ) | 0.01 | 0.1 | NS | 0.01 | −0.1 | NS |
| Right ventricular end-systolic volume index (ml/m 2 ) | 0.01 | 0.1 | NS | 0.01 | −0.1 | NS |
| Peak filling rate (ml/s) | 0.01 | 0.1 | NS | 0.5 | −0.7 | <0.0001 |
| Time to peak filling rate (ms) | 0.02 | 0.1 | NS | 0.4 | 0.6 | <0.0001 |
| 1/2 filling fraction | 0.03 | 0.2 | NS | 0.2 | −0.4 | 0.04 |
| Left atrium (ml) | 0.01 | 0.1 | NS | 0.03 | 0.2 | NS |
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