Does Chronic Atrial Fibrillation Affect Response Rates to Cardiac Resynchronization Therapy?
Presenter: Jessica A. Sutherland, MD, Loyola University Medical Center (Maywood, Illinois)
Background
As documented by several large randomized trials, cardiac resynchronization therapy (CRT), when employed in patients with wide QRS (≥ 130 ms) intervals and in New York Heart Association (NYHA) functional class III/IV heart failure, improves NYHA functional class and 6-minute hall walk distance, and reduces the rates of hospitalization and, possibly, mortality. Although the majority of patients benefit from the therapy, it is estimated that 10% to 30% of the patients do not respond to CRT.
Several parameters such as etiology (ischemic vs nonischemic), QRS duration, T-wave alternans, and echocardiographic tissue Doppler parameters have been studied to identify possible causes of nonresponse to CRT.
Chronic atrial fibrillation (CAF) is present in 10% to 30% of patients with congestive heart failure. There is only limited clinical data studying the effects of biventricular pacing in a population of patients with CAF, and the available data to date have been inconsistent.
Study Methods and Results
Investigators retrospectively analyzed the charts of 122 consecutive patients who underwent successful CRT pacemaker or implantable cardioverter defibrillator (ICD) implants to assess the impact of AF as a possible cause of nonresponse to CRT.
Patients with LV dysfunction (ejection fraction [EF] < 35%), NYHA Class III/IV heart failure, and QRS > 120 msec, with or without preexisting devices, were included in the study. Patients with failed device implant or with < 90% biventricular pacing were excluded from the analysis.
Patients were stratified into 2 groups:
Group I: CAF ≥ 6 months, failed ≥ 1 cardioversion (n = 31)
Group II: normal sinus rhythm (SR) or paroxysmal AF (PAF; n = 91).
Investigators assessed each individual chart to categorize the patient as either a responder or nonresponder to CRT. Responders were defined as those who experienced an improvement in ≥ 1 NYHA class; patients who did not improve in NYHA functional class were defined as nonresponders to therapy. Mean follow up was 9 ± 8 months.
Baseline characteristics were well balanced between the 2 groups with respect to age, proportion of patients in class III vs class IV, and mean EF (Table 1). There were also no significant differences in left ventricular (LV) lead positioning between the 2 groups. The majority of devices implanted were biventricular pacemakers with defibrillator capabilities (CRT + ICD).
Table 1. Baseline Characteristics
CAF = chronic atrial fibrillation; CRT = cardiac resynchronization therapy; EF = ejection fraction; ICD = implantable cardioverter defibrillator; LBBB = left bundle branch block; PAF = paroxysmal atrial fibrillation; SR = sinus rhythm
When stratifying patients according to functional class, the percentage of class III patients identified as responders to therapy did not significantly differ between patients with CAF (Group 1) and those with SR/PAF (Group II) (83% vs 87%, respectively; P = NS). However, it was noted that Group II patients in functional class IV heart failure were more likely to respond to therapy than Group I patients in class IV heart failure (73% vs 13%, respectively; P < .01) (Table 2).
Table 2. Responders to CRT by NYHA Functional Class: Group I vs Group II
CAF = chronic atrial fibrillation; PAF = paroxysmal atrial fibrillation; SR = sinus rhythm
EF was measured pre- and post-CRT. Whereas there were no significant improvements in EF from pre- to post-CRT in class IV patients regardless of group assignment, among class III patients, CRT was associated with a significant improvement in EF in group II patients and was associated with a trend toward significance in group I patients (Table 3).
Table 3. Change in EF From Pre- to Post-CRT by NYHA Functional Class:
Group I vs Group II
CRT = cardiac resynchronization therapy
A total of 15 deaths occurred in the entire study cohort, and the mortality rate did not differ between patients with CAF and those with SR/PAF (19% vs 10%, respectively; P = NS).
Univariate analysis identified CAF as the only statistically significant predictor of nonresponse in patients treated with CRT (P < .001).
Conclusions
CAF is common in patients with congestive heart failure. In class III patients, the response rates to CRT were similar among patients with CAF and those with SR/PAF. However, in class IV patients, those with CAF did not respond well to CRT. Further studies are required to determine whether CAF class IV patients constitute a group unlikely to respond to CRT.
Comments
AF in patients with congestive heart failure carries a higher mortality than among patients with normal SR. In this study, class IV patients with CAF did not respond well to CRT, as defined by improvement in NYHA class. Since NYHA class assessment is very subjective, it is not a reliable marker of response by itself. NYHA class, if combined with LVEF, LV end diastolic diameter, and/or mitral regurgitation, is a better marker of response rates.
In this study, patients who had significant improvement in LVEF were those in the SR/PAF group with class III heart failure. CAF patients in class IV had a deterioration in LVEF, however, and LVEF only trended toward significant improvement in CAF class III patients. Perhaps this finding would have been more significant had the trial assessed a larger population.
Nevertheless, this study is an interesting analysis that identifies a subset of patients who would not respond to CRT. A possible explanation for these findings could be the loss of atrial contribution to cardiac output in class IV patients as well as the irregularity in the ventricular rhythm. Poor ventricular rate control could prevent response to CRT due to tachycardia-mediated cardiomyopathy, but in this study, only those patients with > 90% biventricular paced rhythm were included; therefore, this represents good rate control.
The question then becomes: If these patients had their AV node ablated, would they respond better to CRT since the ventricular rhythm would be regularized?
A multivariate analysis in a larger group of patients, to include conventional risk factors of ischemic vs non ischemic cardiomyopathy, tissue Doppler, and QRS duration along with AF, would have added weight to the results.
References
As documented by several large randomized trials, cardiac resynchronization therapy (CRT), when employed in patients with wide QRS (≥ 130 ms) intervals and in New York Heart Association (NYHA) functional class III/IV heart failure, improves NYHA functional class and 6-minute hall walk distance, and reduces the rates of hospitalization and, possibly, mortality. Although the majority of patients benefit from the therapy, it is estimated that 10% to 30% of the patients do not respond to CRT.
Several parameters such as etiology (ischemic vs nonischemic), QRS duration, T-wave alternans, and echocardiographic tissue Doppler parameters have been studied to identify possible causes of nonresponse to CRT.
Chronic atrial fibrillation (CAF) is present in 10% to 30% of patients with congestive heart failure. There is only limited clinical data studying the effects of biventricular pacing in a population of patients with CAF, and the available data to date have been inconsistent.
Study Methods and Results
Investigators retrospectively analyzed the charts of 122 consecutive patients who underwent successful CRT pacemaker or implantable cardioverter defibrillator (ICD) implants to assess the impact of AF as a possible cause of nonresponse to CRT.
Patients with LV dysfunction (ejection fraction [EF] < 35%), NYHA Class III/IV heart failure, and QRS > 120 msec, with or without preexisting devices, were included in the study. Patients with failed device implant or with < 90% biventricular pacing were excluded from the analysis.
Patients were stratified into 2 groups:
Group I: CAF ≥ 6 months, failed ≥ 1 cardioversion (n = 31)
Group II: normal sinus rhythm (SR) or paroxysmal AF (PAF; n = 91).
Investigators assessed each individual chart to categorize the patient as either a responder or nonresponder to CRT. Responders were defined as those who experienced an improvement in ≥ 1 NYHA class; patients who did not improve in NYHA functional class were defined as nonresponders to therapy. Mean follow up was 9 ± 8 months.
Baseline characteristics were well balanced between the 2 groups with respect to age, proportion of patients in class III vs class IV, and mean EF (Table 1). There were also no significant differences in left ventricular (LV) lead positioning between the 2 groups. The majority of devices implanted were biventricular pacemakers with defibrillator capabilities (CRT + ICD).
Table 1. Baseline Characteristics
| Characteristics | Group I (CAF) (n = 31) |
Group II (SR/PAF) (n = 91) |
|---|---|---|
| Age (yrs) | 63.2 ± 7.5 | 65.6 ± 8.1 |
| Male (%) | 81 | 86 |
| Class III | 74 | 84 |
| Class IV | 26 | 16 |
| Mean EF (%) | 21.2 | 19.9 |
| IV inotrope (%) | 13 | 11 |
| QRS (ms) | 156 ± 22 | 149 ± 16 |
| LBBB (%) | 84 | 90 |
| Lead positioning/device | ||
| Lateral vein (%) | 64 | 76 |
| Posterolateral vein (%) | 23 | 16 |
| Anterolateral vein (%) | 13 | 8 |
| CRT + ICD (%) | 77 | 86 |
| CRT (%) | 23 | 14 |
When stratifying patients according to functional class, the percentage of class III patients identified as responders to therapy did not significantly differ between patients with CAF (Group 1) and those with SR/PAF (Group II) (83% vs 87%, respectively; P = NS). However, it was noted that Group II patients in functional class IV heart failure were more likely to respond to therapy than Group I patients in class IV heart failure (73% vs 13%, respectively; P < .01) (Table 2).
Table 2. Responders to CRT by NYHA Functional Class: Group I vs Group II
| Group I (CAF; n = 31) |
Group II (SR/PAF; n = 91) |
Group 1 Responders, n (%) | Group II Responders, n (%) | P | Odds Ratio | |
|---|---|---|---|---|---|---|
| Class III | 23 | 76 | 19/23 (83%) | 56/62 (87%) | NS | 0.72 |
| Class IV | 8 | 15 | 1/8 (13%) | 11/15 (73%) | < .01 | 0.06 |
EF was measured pre- and post-CRT. Whereas there were no significant improvements in EF from pre- to post-CRT in class IV patients regardless of group assignment, among class III patients, CRT was associated with a significant improvement in EF in group II patients and was associated with a trend toward significance in group I patients (Table 3).
Table 3. Change in EF From Pre- to Post-CRT by NYHA Functional Class:
Group I vs Group II
| Pre-CRT | Post-CRT | P | |
|---|---|---|---|
| Group I, class III | 21.4 | 26.9 | < .1 |
| Group II, class III | 19.9 | 28.2 | < .05 |
| Group I, class IV | 20.0 | 19.1 | NS |
| Group II, class IV | 19.6 | 22.5 | NS |
A total of 15 deaths occurred in the entire study cohort, and the mortality rate did not differ between patients with CAF and those with SR/PAF (19% vs 10%, respectively; P = NS).
Univariate analysis identified CAF as the only statistically significant predictor of nonresponse in patients treated with CRT (P < .001).
Conclusions
CAF is common in patients with congestive heart failure. In class III patients, the response rates to CRT were similar among patients with CAF and those with SR/PAF. However, in class IV patients, those with CAF did not respond well to CRT. Further studies are required to determine whether CAF class IV patients constitute a group unlikely to respond to CRT.
Comments
AF in patients with congestive heart failure carries a higher mortality than among patients with normal SR. In this study, class IV patients with CAF did not respond well to CRT, as defined by improvement in NYHA class. Since NYHA class assessment is very subjective, it is not a reliable marker of response by itself. NYHA class, if combined with LVEF, LV end diastolic diameter, and/or mitral regurgitation, is a better marker of response rates.
In this study, patients who had significant improvement in LVEF were those in the SR/PAF group with class III heart failure. CAF patients in class IV had a deterioration in LVEF, however, and LVEF only trended toward significant improvement in CAF class III patients. Perhaps this finding would have been more significant had the trial assessed a larger population.
Nevertheless, this study is an interesting analysis that identifies a subset of patients who would not respond to CRT. A possible explanation for these findings could be the loss of atrial contribution to cardiac output in class IV patients as well as the irregularity in the ventricular rhythm. Poor ventricular rate control could prevent response to CRT due to tachycardia-mediated cardiomyopathy, but in this study, only those patients with > 90% biventricular paced rhythm were included; therefore, this represents good rate control.
The question then becomes: If these patients had their AV node ablated, would they respond better to CRT since the ventricular rhythm would be regularized?
A multivariate analysis in a larger group of patients, to include conventional risk factors of ischemic vs non ischemic cardiomyopathy, tissue Doppler, and QRS duration along with AF, would have added weight to the results.
References
Oguz E, Dagdeviren B, Bilsel T, et al. Echocardiographic prediction of long-term response to biventricular pacemaker in severe heart failure. Eur J Heart Fail. 2002;4:83-90.
Molhoek SG, Bax JJ, van Erven L, et al. Comparison of benefits from cardiac resynchronization therapy in patients with ischemic cardiomyopathy versus Idiopathic Dilated cardiomyopathy. Am J Cardiol. 2004;93:860-863.
Exner DV, Cowan K, Wyse G, et al. Microvolt repolarization alternans identifies response to cardiac resynchronization therapy. Heart Rhythm. 2004;1(suppl):S25.
Singh SN, Fletcher RD, Fisher SG, et al. Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmias (CHF-STAT). N Engl J Med. 1995;333;77-82.
Leon AR, Greenberg JM, Kanuru N, et al. Cardiac resynchronization in patients with congestive heart failure and chronic atrial fibrillation. J Am Coll Cardiol. 2002;39:1258-1263.
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