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Jan 14, 2015

Mechanical Dispersion by Strain Echocardiography


 

Patients with mutations in the lamin A/C gene (LMNA) constitute a small but important part (5% to 8%) of those with familial dilated cardiomyopathy. The cardiac phenotype is malignant and characterized by atrioventricular block, as well as supraventricular and ventricular arrhythmias, which often precede cardiac dilation. It is therefore important  to screen high-risk individuals in order to prevent sudden cardiac death.

Mechanical Dispersion by Strain Echocardiography: A Predictor of Ventricular Arrhythmias in Subjects With Lamin A/C Mutations has been published in JACC Cardiovascular Imaging. Authored by Center Director of Cardiology Research Kristina Haugaa, PhD student Nina Hasselberg and Center Director Thor Edvardsen.

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Sudden death is the first symptom of heart disease in many patients. Prevention of sudden death must therefore be achieved by screening groups of high-risk individuals and offering an implantable cardioverter-defibrillator (ICD) as the primary prevention therapy in selected individuals. Selecting patients for primary ICD therapy remains challenging. Patients with mutations in the lamin A/C gene (LMNA) constitute a small but important part (5% to 8%) of those with familial dilated cardiomyopathy. The cardiac phenotype is malignant and characterized by atrioventricular block, as well as supraventricular and ventricular arrhythmias, which often precede cardiac dilation (1). General ICD guidelines for dilated cardiomyopathy patients, recommending primary prevention ICD at ejection fraction (EF) <30% to 35%, are not appropriate in patients with LMNA mutations, and we have recently reported on risk predictors in this population (1). Dispersed myocardial contraction by strain echocardiography, mechanical dispersion, is an excellent marker of ventricular arrhythmias and is independent of EF 2 and 3. We hypothesized that mechanical dispersion by strain echocardiography may be a marker of ventricular arrhythmias beyond EF in patients with LMNA mutations and therefore serve as a risk marker of ventricular arrhythmias before EF decrease.

We included 33 LMNA mutation-positive subjects (35 ± 16 years), of which 13 (39%) were probands and 20 (61%) were mutation-positive family members. At presentation, 9 (27%) fulfilled criteria of dilated cardiomyopathy whereas 24 (73%) had normal or mildly dilated cardiac dimensions. Ventricular arrhythmias were defined as nonsustained (ns) ventricular tachycardia (VT) if ≥3 consecutive ventricular beats ≥120 beats/min lasting <30 s (n = 6). Sustained VT was defined as VT lasting >30 s, VT with hemodynamic deterioration or ventricular fibrillation (VF) (n = 5). No VT were detected in 22 subjects. All subjects gave written informed consent in this institutional review board–approved study.

By speckle tracking echocardiography, peak longitudinal negative strain was assessed in 16 left ventricular segments and averaged to global longitudinal strain (GLS). Time intervals from start Q/R on electrocardiogram to peak negative strain during the cardiac cycle were assessed. Mechanical dispersion was defined as the standard deviation of this time interval from 16 left ventricular segments, reflecting myocardial contraction heterogeneity 4 and 5.

Mean EF was 51 ± 11%, GLS –20.4 ± 3.8%, and mechanical dispersion 42 ± 12 ms. As expected, subjects with sustained VT/VF had reduced cardiac function by EF and GLS when compared with patients without sustained VT/VF (p = 0.001 and p = 0.01, respectively) and mechanical dispersion was pronounced (p = 0.001) (Figure 1). Only mechanical dispersion was increased in those with any arrhythmic events (nsVT + sustained VT, n = 11) versus patients free of arrhythmic events (n = 22) (49 ± 14 ms vs. 38 ± 10 ms, p = 0.02), whereas EF and GLS were not different (EF: 47 ± 15% vs. 53 ± 7%, p = 0.14; GLS: –19.2 ± 5.3% vs. –21.0 ± 2.9%, p = 0.22). There was a significant linear trend toward an increase of mechanical dispersion by severity of arrhythmias (p = 0.001) (Figure 1). By receiver-operating characteristic analyses, mechanical dispersion showed good discrimination of those with nsVT + sustained VT (area under the curve [AUC]mec disp: 0.74, 95% confidence interval [CI]: 0.55 to 0.93; AUCEF: 0.64, 95% CI: 0.41 to 0.86, and AUCGLS: 0.54, 95% CI: 0.30 to 0.78).

Figure 1
Mechanical Dispersion in Lamin A/C Mutation Positive Subjects

(Top) Strain curves from apical 4-chamber view in a lamin A/C mutation-positive subject without (left) and with (right)ventricular tachycardia (VT). Arrows are indicating time from start Q/R on electrocardiogram to peak longitudinal strain. Mechanical dispersion is pronounced in the subject with VT (right). (Bottom left) Bar charts of relation between echocardiographic parameters and severity of VT. Patients with sustained VT/ventricular fibrillation (VF) (pink bars) had significantly higher values of mechanical dispersion and lower left ventricular ejection fraction (LVEF) and absolute global longitudinal strain (GLS) than did those with no VT (green bars). Mechanical dispersion showed a positive linear trend along with severity of VT (p = 0.001). (Bottom right) Receiver-operating characteristic (ROC) curves in 33 lamin A/C mutation positive subjects for the ability of mechanical dispersion, LVEF and GLS to discriminate between those without (n = 22) and with nonsustained VT/sustained VT/VF (n = 11).

Figure options

Mechanical dispersion may be an additive marker of ventricular arrhythmias in patients with relatively preserved ventricular function early in LMNA disease. This finding is in line with our previous results demonstrating mechanical dispersion as a predictor of ventricular arrhythmias in patients with EF >35%. Mechanical dispersion may overcome the limitation of EF, which predicts poor outcome only in those with obviously reduced ventricular function.

References

1 N.E. Hasselberg, T. Edvardsen, H. Petri, et al.
Risk prediction of ventricular arrhythmias and myocardial function in lamin A/C mutation positive subjects
Europace, 16 (2014), pp. 563–571
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2 K.H. Haugaa, B.L. Grenne, C.H. Eek, et al.
Strain echocardiography improves risk prediction of ventricular arrhythmias after myocardial infarction
J Am Coll Cardiol Img, 6 (2013), pp. 841–850
Article
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3 K.H. Haugaa, B. Goebel, T. Dahlslett, et al.
Risk assessment of ventricular arrhythmias in patients with nonischemic dilated cardiomyopathy by strain echocardiography
J Am Soc Echocardiogr, 25 (2012), pp. 667–673 
Article
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4 K.H. Haugaa, M.K. Smedsrud, T. Steen, et al.
Mechanical dispersion assessed by myocardial strain in patients after myocardial infarction for risk prediction of ventricular arrhythmia
J Am Coll Cardiol Img, 3 (2010), pp. 247–256 
Article
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5 K.H. Haugaa, J.P. Amlie, K.E. Berge, T.P. Leren, O.A. Smiseth, T. Edvardsen
Transmural differences in myocardial contraction in long-QT syndrome: mechanical consequences of ion channel dysfunction
Circulation, 122 (2010), pp. 1355–1363 
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