Joseph Dell'Orfano, MD

 This 72-year-old patient presented in 2004 with near syncope and chest discomfort. Coronary angiography revealed significant left anterior descending artery stenosis which was stented. She had acute restenosis with acute myocardial infarction, which prompted repeat intervention 3 days later. Her maximum creatine kinase was 4494 and her troponin was greater than 50. Her course was complicated by atrial fibrillation, which was treated with amiodarone. Left ventricular ejection fraction (LVEF) 1 week later was 25%. Nonsustained ventricular tachycardia was seen. Planning for a prophylactic implantable cardioverter defibrillator (ICD) following her recuperation began, but the patient unfortunately suffered an in-hospital cardiac arrest, which prompted implant of a single chamber ICD. 

 She was again hospitalized 1 month later with congestive heart failure (CHF) and rapid atrial fibrillation that triggered her ICD. She continued to deteriorate with respect to her congestive heart failure symptoms and eventually became New York Heart Association (NYHA) class IV requiring intermittent outpatient dobutamine therapy. She was hospitalized once again earlier this year. At that time electrocardiogram showed sinus rhythm with a QRS duration of 100 ms. Her congestive heart failure was aggressively treated and she was discharged from the hospital. She was referred for an outpatient evaluation for cardiac resynchronization. 

Cardiac resynchronization therapy (CRT) has been shown to be effective in patients with QRS prolongation. Current guidelines suggest a minimal QRS duration of 130 msec, although the COMPANION study enrolled patients with QRS duration of 120 msec or longer. Unfortunately, not all patients with QRS prolongation benefit from CRT. Moreover, some patients with a narrow QRS are demonstrated to have dyssynchrony on echocardiography despite a narrow QRS complex. In the present case, the patient indeed had a narrow QRS. She was therefore referred for echocardiography in order to evaluate for left ventricular (LV) dyssynchrony. She was noted to have an LVEF of 25%. Tissue Doppler images are seen in 

. These measurements are taken at the anterior, posterior, lateral and septal mitral valve annulus. In this case, the time from the onset of the QRS to the peak of the first positive Doppler deflection (S wave) is measured. This measurement is 179 msec at the septal position (panel A) and 275 msec at the lateral position (panel B) which is consistent with a septolateral delay of 96 ms and presence of significant mechanical dyssynchrony. These measurements may now be automated on newer echo machines. 

Based upon these measurements, it was concluded that this patient did indeed have left ventricular mechanical dyssynchrony and would derive benefit from cardiac resynchronization treatment. The patient was referred for upgrade of her existing ICD to a biventricular ICD. In this case, the old ICD was removed. A new atrial pacing lead was implanted and a new coronary sinus lead was placed in the mid lateral branch of her coronary sinus. She was discharged later that same day in stable condition. 

The patient tolerated the procedure well and was next seen in the office 2 weeks later for a postsurgical wound check. At that time she reported a marked improvement in her symptoms. A chest radiograph is shown in 

. This shows appropriate positions of the ICD lead in the right ventricle (RV), the atrial lead in the right atrium (A) and the tranvenous LV lead in the mid-lateral epicardial vein (LV). She has remained on her preoperative medical regimen including carvedilol, furosemide, lisinopril, and amiodarone. At her last visit she had NYHA class II symptoms of CHF. She has not been readmitted to the hospital in the 6 months since her upgrade. 

Cardiac resynchronization is a proven therapy for patients with class III and IV congestive heart failure in the setting of severe LV systolic dysfunction and widened QRS duration. Several echocardiographic markers for LV dyssynchrony have been recognized. Patients with LV dyssynchrony and a narrow QRS may benefit from biventricular pacing as well. Randomized trials are currently underway to evaluate this new indication. Patients with narrow QRS and heart failure comprise 2/3rd of all patients with heart failure. Physicians should evaluate such patients for presence of mechanical dyssynchrony, the presence of which should prompt treatment with cardiac resynchronization. 

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Cardiac resynchronization treatment (CRT) has moved into the mainstream of patient care after several randomized studies have demonstrated improved quality of life, reversed remodeling, and decreased heart failure hospitalizations. More recently, 2 large studies have demonstrated a mortality benefit of CRT independent of implantable cardioverter defibrillator

Cardiac resynchronization in a patient with Class IV heart failure and narrow QRS-the role of mechanical dyssynchrony

 of the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial, which examined the role of prophylactic implantable cardioverter defibrillator (ICD) implantation in patients with nonischemic cardiomyopathy. This trial, which assigned 458 patients with nonischemic cardiomyopathy (left ventricular ejection fraction [LVEF] < 36%) to randomly receive standard medical therapy versus medical therapy plus single chamber ICD, showed no significant difference in mortality. There are several possible reasons for this, as proposed by the authors of the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). Probably most significant is that 22% of patients enrolled had New York Heart Association (NYHA) I symptoms of heart failure whereas patients randomized in SCD-HeFT were required to have at least NYHA II symptoms.

 In this post-hoc analysis of the DEFINITE data, the authors      found that patients with 

 diagnosed cardiomyopathy who received an ICD had significantly improved survival compared with those with standard therapy. By contrast there was no significant difference between treatment groups among patients with a remote diagnosis of cardiomyopathy. 

 Indications for ICDs have recently been expanded based on the results of several landmark trials including the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) and SCD-HeFT trials. The MADIT II trial enrolled patients with a prior myocardial infarction (MI) and LVEF < 30%. This trial demonstrated a significant reduction in mortality among those patients who received an ICD. The SCD-HeFT trial by contrast, did not require the presence a previous MI. Rather, this trial enrolled 2521 patients with NYHA II and III congestive heart failure (CHF). There was a fairly even mix between ischemic and nonischemic cardiomyopathy. The Comparison of Medical Therapy, Pacing and Defibrillation in Chronic Heart Failure (COMPANION) trial supports these trials and also found a significant benefit in patients with CHF who underwent ICD implantation.

 Based on this data regarding primary prevention of sudden death in CHF, the American College of Cardiology/ American Heart Asssociation clinical guidelines for the treatment of patients with CHF (published in 2005) list implantation of a prophylactic ICD as a class I indication in those patients who have LVEF < 30% and who have class II or III CHF (patients with LVEF 31%-35% are listed as class II a). Centers for Medicare and Medicaid Services guidelines were updated in 2005 to reflect these expanded indications. However, patients with nonischemic cardiomyopathy must have CHF diagnosed > 9 months before implantation. The current study suggests that this is not the correct approach, however, and that patients with recent diagnoses should be considered for ICD implantation. 

 One major issue to contend with is the appropriate medical treatment of CHF. In these trials, all patients were on optimal medical therapy. It may be argued that the 3- to 9-month waiting period is appropriate to: (1) ensure that medical therapy has been initiated and is working: (2) ensure that the cardiomyopathy and CHF is not reversible; and (3) ensure that acute CHF is appropriately treated and the patient is stable enough to undergo ICD implantation. In fact, the Defibrillator in Acute MI Trial (DINAMIT) study showed that ICD implantation early after an acute MI may be deleterious.

 There may be similar danger in patients in the early      stages of their CHF treatment.  

 This is an important study because it points out that a waiting period before prophylactic ICD implantation may not be appropriate in patients with nonischemic cardiomyopathy. However, there are some important reasons why it may not be appropriate to treat patients in the early phase of their diagnosis. Further study is needed to fully answer this question. After all, timing is everything. 

This review presents a substudy analysis of the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial, which examined the role of prophylactic implantable cardioverter defibrillator (ICD) implantation in patients with nonischemic cardiomyopathy.

Joseph Dell'Orfano, MD

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