News:Cardiac Resynchronization Therapy and Single Center Experience Links Survival

October 1, 2007 By Grendel Burrell [mailto:grendel.burrell@gmail.com]

CRT improved symptoms, left ventricular (LV) structure, function, and survival in clinical trials (1, 2). However, in clinical practice, physicians and patients report a highly variable clinical response to CRT and questions have remained about whether survival benefit is limited to only those patients who experience improvement in clinical status or cardiac structure and function.

In this study, all patients were on optimized pharmacologic therapies for the management of HF, and indications for CRT were ejection fraction (EF) < 35%, and QRS >120 ms. Lateral or posterolateral LV lead placement was preferred. Standard device settings included atrioventricular (AV) delay of 100 ms (sensed) and 130 ms (paced), interventricular delay of 0 ms with DDD or DDDR mode and standard lower (50–60 beats/min) and upper (120–130 beats/min) pacing rates. 84% of patients in the study received CRT-D devices.

The average patient age was 68 ± 11 years, and 83% were male. 61% of patients had an ischemic etiology for their heart failure. Pre-implant, 20% were NYHA Class II, 60% NYHA Class II, and 18% NYHA Class IV at baseline. QRS duration was 167+/-34 msec. 23% of patients had atrial fibrillation. 35% of patients had moderate, and 22% experienced severe, mitral regurgitation.

There were no significant differences in age, gender, etiology of HF, NYHA class, QRS duration, EF, LV diastolic function, MR severity, RV enlargement, plasma creatinine, or hemoglobin between patients who did or did not return for follow-up. The patients who returned for follow-up had larger LVEDV (242 +/-72 vs. 221+/-71 mL, P = 0.04) and higher PASP (48 +/- 15 vs. 41 +/- 15, P = 0.002) and tended to have larger LVESV (190 +/- 65 mL vs. 173 +/- 65 mL, P = 0.053), compared with those who did not return. With an interquartile range of 8.0–25.5 months, the median follow-up interval for the survival analysis was 16.7 months. The authors found no difference in survival between those who did or did not return for follow-up and no difference in unadjusted survival between those who received CRT with or without a defibrillator (P = 0.53).

Timing and follow up were at the discretion of the physician who referred the patient for CRT. 174 patients returned to Mayo for follow-up (the remainders were followed locally) and 127 had repeat echocardiography at a mean of 5.4+/-5.1 months after implant. Of the174 patients with clinical follow-up, 70% were on digoxin, 88% were taking an angiotensin converting enzyme inhibitor or receptor blocker, 83% were on beta-blocker therapy, and 39% on an aldosterone antagonist. 71% had repeat echocardiography during follow-up evaluation, and in those patients, EF, LV systolic and diastolic volumes, diastolic dysfunction, MR severity grade, and PASP improved at follow up. However, RV enlargement and dysfunction, creatinine, and hemoglobin did not show improvement. Diastolic dysfunction grade improved after CRT (mean change, 0.3 +/- 0.1, P = 0.03), but this was assessed in only 44 patients before and after device implantation.

75% of patients had ≥0.5 improvement in NYHA class and/or a ≥5% improvement in LVEF. 19% of patients had improved NYHA class ≥0.5 with an increase in LVEF <5%. There was a significant correlation between change in NYHA functional class and change in EF (r = −0.46). Correlations between change in NYHA functional class and change in PASP or MR severity grade were statistically significant but weaker (r values < 0.25 and P < 0.05 for both), while there was no correlation between change in NYHA functional class and changes in systolic or diastolic LV volumes (P > 0.05 for both).

Baseline clinical characteristics and survival were similar among those who did or did not return for follow-up. In paired analyses, NYHA class (－0.56 ± 0.07, p < 0.0001), ejection fraction (EF, 6.3 ± 0.7%, P < 0.0001), LV dimension (－2.7 ± 0.6 mm, P < 0.0001), pulmonary artery systolic pressure (PASP, －4.6 ± 1.3 mm Hg, P = 0.0007), and MR severity grade (－0.20 ± 0.05, P = 0.0002) improved after CRT. Survival after CRT was associated with decrease in NYHA class (risk ratio [RR]=0.43, P = 0.0004), increase in EF (RR = 0.94, P = 0.02), and decrease in PASP (RR = 0.96, P = 0.03). Changes in EF and NYHA class were correlated (r =－0.46, P < 0.0001) and, after adjusting for this covariance, the change in NYHA (P = 0.04) but not EF (P = 0.12) was associated with improved survival.

In the Mayo experience, clinical follow-up of patients post CRT revealed variable but significant improvements in symptoms, LV systolic and diastolic volume, EF, and MR severity. The authors describe the association between improvement in LV diastolic dysfunction or pulmonary hypertension and outcomes after CRT. They postulate that enhanced LV systolic and diastolic functions, as well as decreased severity of MR, contribute to the reduction of pulmonary hypertension. Symptomatic improvement correlated with positive changes in EF, MR severity, and PASP, but these correlations were not strong. The clinical response rate to CRT in this study is approximately 70%. A similar rate of response has been reported in clinical trials (3, 4) According to lead author Yong-Mei Cha, MD, only those patients who were nonresponders were underwent AV and VV optimization.

This study provides some evidence that patients who have a favorable symptomatic response to CRT may experience survival benefit with or without the effect of CRT on echocardiographic parameters. The authors wonder whether symptomatic “nonresponse” or echocardiographic “nonresponse” should prompt consideration of changes in device or lead parameters and the efficacy of any such changes in regard to improvement in symptoms, echocardiographic parameters or survival remains to be defined.

At Mayo, according to Dr. Cha, “Nonresponders are characterized by improvement in NYHA < 0.5 (clinical) and/or LVEF <5% or LVESV reduction <10% (structural).”  At the Mayo Clinic, Rochester, CRT devices are not routinely optimized prior to discharge. However, according to Dr. Cha, their practice may change based an ongoing CRT registry that will continue to generate important data on their CRT experience, outside of clinical trials.

References:

 
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