History
A 62-year-old woman was seen at the cardiology outpatient clinic. Her medical history was significant for the onset of mild heart failure symptoms 2 years previously. She had a past left ventricular ejection fraction (LVEF) of 32% and a diagnosis of nonischemic cardiomyopathy because no significant coronary artery disease was seen on coronary angiography. She was treated medically for heart failure and had undergone implantable cardioverter-defibrillator (ICD) placement. Because she did not have a left bundle branch block (LBBB), she was not considered for cardiac resynchronization therapy (CRT) at the time, with New York Heart Association (NYHA) class II heart failure symptoms. She remained active, working full time, but recently had 6 months of progressive dyspnea on mild exertion, consistent with NYHA class III heart failure symptoms. She was treated with loop diuretics, an angiotensin-converting enzyme inhibitor, and carvidilol. Her medical history is significant for hysterectomy, oophorectomy, appendectomy, tonsillectomy, and mild hypothyroidism. She previously smoked one pack of cigarettes per day but quit smoking 11 years ago.
Comments
This patient has nonischemic cardiomyopathy with an ICD implanted as a primary prevention indication. She experienced 6 months of progressive dyspnea on exertion.
Current Medications
The patient was taking furosemide 40 mg daily, enalapril 10 mg twice daily, carvedilol 12.5 mg twice daily, atorvastatin 10 mg daily, levothyroxine 25 mcg daily, and aspirin 325 mg daily.
Comments
This patient was on appropriate pharmacologic therapy for systolic heart failure.
Current Symptoms
The patient was experiencing progressive dyspnea that occurred with everyday activity and occasional ankle swelling. She denied chest pain, paroxysmal nocturnal dyspnea, palpitations, lightheadedness, or syncope.
Comments
These symptoms are consistent with heart failure, in NYHA class III. She was referred for echocardiography and consideration for CRT.
Physical Examination
FIGURE 36-1 Electrocardiogram before implant.
Comments
Mild ankle edema supports the diagnosis of heart failure. Systolic murmur at the left sternal border is consistent with known mild tricuspid regurgitation.
Laboratory Data
Comments
No laboratory abnormalities were present that would account for worsening heart failure.
Electrocardiogram
Findings
The electrocardiogram (ECG) revealed normal sinus rhythm, occasional premature ventricular complexes, nonspecific intraventricular conduction delay with a QRS width of 140 ms, and nonspecific T-wave changes (Figure 36-1)
Comments
The patient has a widened QRS complex with a duration greater than 120 ms. However, the morphology of the QRS complex is not a typical LBBB and the QRS duration is intermediately widened (range 120-149 ms).
FIGURE 36-2 Chest radiograph.
Chest Radiograph
Findings
The chest radiograph showed cardiomegaly with past ICD implantation and evidence of pulmonary vascular congestion (Figure 36-2).
Comments
Evidence of mild congestive heart failure was confirmed on radiography.
Echocardiogram
Findings
The echocardiogram demonstrated global hypokinesia of the left ventricle (Figure 36-3). The LVEF was 28%. Mild mitral regurgitation, mild left atrial enlargement, and evidence of an ICD lead in situ also were seen.
Comments
The echocardiogram is consistent with nonischemic cardiomyopathy and depressed ejection fraction that is slightly less than at the previous visit.
Findings
The six time-strain curves plot the wall thickening toward the center of the left ventricular cavity as segmental radial strain. Evidence of significant dyssynchrony with an anteroseptal to posterior wall delay of 312 ms (≥ 130 ms) was present.2
FIGURE 36-3 Apical four-chamber view. See expertconsult.com for video. 
FIGURE 36-4 Speckle tracking radial strain from midventricular short-axis view.
Comments
The presence of a typical radial strain pattern of dyssynchrony usually seen in patients with LBBB was noted on echocardiography. Early thickening in the inferoseptal, anteroseptal, and anterior segments was visible (Figure 36-4, red, yellow, and cyan curves), with later activation in posterior, lateral, and inferior wall (see Figure 36-4, violet, green, and dark blue curves). This patient has intraventricular mechanical dyssynchrony with a QRS duration of 140 ms and a non-LBBB pattern. Another useful measure of dyssynchrony is 12-site standard deviation by tissue Doppler longitudinal velocities, but this was not performed in this patient.
Findings
The interventricular mechanical delay (IVMD), defined as the difference between left and right ventricle preejection delay, is 52 ms (left ventricular delay compared with that of the right ventricle) (Figure 36-5). Typically, an IVMD of 40 ms or greater is considered significant interventricular dyssynchrony.2
FIGURE 36-5 Pulsed Doppler interventricular mechanical delay (IVMD). LVOT, Left ventricular outflow tract; RVOT, right ventricular outflow tract.
Comments
The IVMD, assessed by this relatively simple pulsed Doppler technique, also demonstrated significant interventricular dyssynchrony.
Focused Clinical Questions and Discussion Points
Question
Does an indication for CRT implantation exist in this patient based on guidelines in the current literature?
Discussion
Although previous CRT guidelines used a QRS width greater than 120 ms regardless of QRS morphology as a criterion, 2012 updated guidelines have changed.5 CRT is not considered the strongest benefit for patients with an LVEF of 35% or less and NYHA class II, III, or IV symptoms, with a class I indication (strongest level of evidence) only for patients with QRS duration of 150 ms or greater and LBBB morphology. Patients with a QRS of 120 to 149 with LBBB morphology or a QRS of 150 ms or greater and non-LBBB morphology have a class IIA indication, and patients with a QRS of 120 to 149 and non-LBBB morphology have class IIB. These guidelines were based on clinical trial data that did not consider echocardiographic dyssynchrony. This represents a general shift of opinion to focus more on the ECG, with patients with less prolonged QRS durations and atypical QRS morphologies now being viewed as a group with heterogeneous response to CRT. Selection criteria using the ECG result in identifying approximately 30% of patients who are considered nonresponders to CRT. These more limiting guidelines may improve the responder rate, but unfortunately may limit the use of CRT to patients who may benefit. This imposes a significant challenge on clinicians considering implanting CRT devices, because the goal is to help as many patients with heart failure as possible who may benefit from treatment, including device therapy.
Question
What additional information can echocardiographic dyssynchrony provide in the setting of patients with moderately prolonged QRS durations (QRS 120-149 ms)?
Discussion
Evidence from single-center studies1,3 indicates that echocardiographic dyssynchrony parameters can predict response and long-term prognosis in patients who receive CRT. In particular, patients who lack mechanical dyssynchrony at baseline do not appear to benefit from CRT. In patients with a QRS of 120 to 149 ms, those with significant radial dyssynchrony appeared to have outcomes similar to those of patients with a QRS of 150 ms or greater, whereas patients with a QRS of 120 to 149 ms but without radial dyssynchrony had a significantly lower survival rate (log rank p = 0.002). These data support the importance of radial strain dyssynchrony as an adjunct to provide prognostic information in patients with intermediate QRS width (120-149 ms).
Question
What is the role of dyssynchrony in patients with non-LBBB morphology?
Discussion
The greatest level of evidence for CRT response is in patients with LBBB. However, patients with non-LBBB, which includes interventricular conduction delay (IVCD), as in this case, or right bundle branch block (RBBB), have variable response to CRT. Mechanical dyssynchrony has been shown4 to be less frequently observed in patients with shorter QRS duration and non-LBBB (i.e., radial dyssynchrony 85% in LBBB, 59% in IVCD, and 40% in RBBB). However, in patients with non-LBBB morphology, absence of dyssynchrony is a strong negative prognostic marker (radial dyssynchrony: hazard ratio [HR] 2.6, 95% confidence interval [CI] 1.47-4.53, p <0.001; IVMD: HR 4.9, 95% CI 2.60-9.16, p <0.001). Specifically, this study showed that patients with non-LBBB morphology and mechanical dyssynchrony by speckle tracking radial strain or IVMD had significant improvement in LVEF after CRT (23 ± 6 to 31 ± 10, p = 0.001), whereas non-LBBB patients who lacked baseline dyssynchrony had no significant improvement in LVEF (25 ± 6 to 27 ± 8, p = not significant) or end systolic volume.
Question
Which dyssynchrony indices should be used in evaluation of patients with a QRS duration less than 150 ms or non-LBBB morphology?
Discussion
Currently, no consensus has been reached as to which dyssynchrony index is best. Although tissue Doppler imaging longitudinal velocity measures, such as 12-site standard deviation or the Yu Index, have been described as useful measures associated with patient outcome,3 speckle tracking–derived radial strain anteroseptal to posterior wall delay was examined most closely in our study of patients without LBBB. The pulse Doppler–derived IVMD is also important because it reflects a large degree of dyssynchrony and is simple to perform. Dyssynchrony indices associated with patient outcome when examining patients with non-LBBB morphologies and a QRS duration of 120 to 149 ms were speckle tracking radial strain anteroseptal to posterior wall delay and intraventricular mechanical delay.
Final Diagnosis
This patient has nonischemic cardiomyopathy and depressed ejection fraction with a history of ICD placement. Because her heart failure symptoms progressed on optimal medical therapy, upgrade to CRT-D was contemplated. The patient has a class IIB indication according to the 2012 guidelines for CRT therapy, which means a less strong indication based purely on the ECG. The speckle tracking and pulsed Doppler dyssynchrony study supports mechanical dyssynchrony being present to a significant degree. This has been associated with improved patient outcomes after CRT.
Plan of Action
Intervention
A CRT implantation was performed with successful left ventricular lead positioning in a lateral location. The pulse generator was exchanged for a CRT-D device. No complications occurred during the procedure.
Outcome
The postoperative period was uneventful. The symptoms of the patient improved within 2 weeks after CRT to her previous NYHA class II status. At 6 months a follow-up echocardiogram was obtained that showed improvement in overall left ventricular ejection fraction from 28% to 42% (Figure 36-6). No hospitalizations for heart failure occurred in the year of observation after CRT implantation, and the patient enjoyed a more active lifestyle. 
Findings
Evidence indicated an increase in ejection fraction to 42%.
Comments
In this setting, upgrade to a CRT device resulted in improvement of symptomatology in left ventricular function. Dyssynchrony echocardiography as an adjunct to the ECG helped the physician select this patient for CRT implantation, and she received significant benefit from this therapy.
Selected References
1. Delgado V., van Bommel R.J., Bertini M. et al. Relative merits of left ventricular dyssynchrony, left ventricular lead position, and myocardial scar to predict long-term survival of ischemic heart failure patients undergoing cardiac resynchronization therapy. Circulation. 2011;123:70–78.
2. Gorcsan 3rd. J., Abraham T., Agler D.A. et al. Echocardiography for cardiac resynchronization therapy: recommendations for performance and reporting—a report from the American Society of Echocardiography Dyssynchrony Writing Group endorsed by the Heart Rhythm Society. J Am Soc Echocardiogr. 2008;21:191–213.
3. Gorcsan 3rd. J., Oyenuga O., Habib P.J. et al. Relationship of echocardiographic dyssynchrony to long-term survival after cardiac resynchronization therapy. Circulation. 2010;122:1910–1918.
4. Hara H., Oyenuga O.A., Tanaka H. et al. The relationship of QRS morphology and mechanical dyssynchrony to long-term outcome following cardiac resynchronization therapy. Eur Heart J. 2012;33:2680–2691.
5. Tracy C.M., Epstein A.E., Darbar D. et al. 2012 ACC/AHA/HRS focused update of the 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines. Circulation. 2012;126:1784–1800.
