PAVE: The Left Ventricular-Based Cardiac Stimulation Post AV Nodal Ablation Evaluation Study
PAVE: The Left Ventricular-Based Cardiac Stimulation Post AV Nodal Ablation Evaluation Study
Presenter: Rahul N. Doshi, MD, Sunrise Hospital and Medical Center (Las Vegas, Nevada)
Atrioventricular (AV) nodal ablation with pacing is an alternative therapeutic option in patients with atrial fibrillation (AF) and difficult-to-control ventricular rates that are unresponsive to medical therapy or who cannot be adequately treated with pharmacologic agents alone. The ablation procedure entails the targeted destruction of the AV node, which is the heart tissue that conducts the electrical impulse from the atria to the ventricles. Thus, AV nodal ablation followed by right ventricular (RV) pacing provides correction of tachycardia-induced cardiomyopathy.
Although RV pacing is the traditional pacing approach, it alters the natural sequence of ventricular activation and contraction and may be associated with poorer outcomes, particularly in patients with some degree of heart failure. Conversely, biventricular pacing can correct the mechanical dyssynchrony found in patients with heart failure and intrinsic conduction system disease. Whether the use of biventricular pacing following AV nodal ablation for AF results in better outcomes compared with RV pacing was not known prior to this trial.
Study Design and Methods
The Left Ventricular-Based Cardiac Stimulation Post AV Nodal Ablation Evaluation (PAVE) study was a prospective, randomized study that evaluated biventricular pacing after AV nodal ablation in patients with AF, regardless of the left ventricular systolic function or New York Heart Association (NYHA) functional class.
Primary Endpoint: Exercise capacity as measured by the distance walked during the 6-minute walk test.
Secondary Endpoints
Inclusion Criteria:
Exclusion Criteria:
Patients were randomized in a 2:1 fashion to either ablation plus RV pacing or ablation plus biventricular pacing. Patients randomized to biventricular pacing were implanted with the Frontier Model 5508 and the Aescula Left Heart Lead model 1055 (St. Jude Medical, St. Paul, Minnesota) (both for investigational use only in the United States). Patients randomized to RV pacing were implanted with approved single-chamber devices, also from St. Jude Medical, the study's sponsor. Patients were followed at 6 weeks, 3 months, 6 months, and every 6 months thereafter.
Results
Device implantation was attempted in a total of 252 patients; biventricular pacing in 146 patients and RV pacing in 106 patients. Unsuccessful biventricular device implantation occurred in 21 patients, vs 0 unsuccessful RV pacing implants. Compared with biventricular pacing, more deaths occurred in patients randomized to RV pacing (6 vs 10, respectively). The final population of patients eligible for analysis included 102 RV pacing patients and 82 biventricular pacing patients. There was no significant difference in baseline clinical characteristics between the 2 groups (Table).
Table. PAVE: Baseline Clinical Characteristics
ACE, angiotensin converting enzyme; NYHA, New York Heart Association
The 6-minute walk test results are shown in Figure 1 (distance in meters shown as rounded). Although both groups initially had an improvement in walking distance, only patients in the biventricular arm of the study continued to improve at 6-month follow-up (P = .03) (Figure 2).
Figure 1. PAVE: 6-minute walk test results.
Figure 2. PAVE: Improvement in 6-minute walk distance.
There was also an improvement in peak VO2 from 6 weeks to 6 months (secondary endpoint) in the biventricular pacing arm (difference of 1.02 mL/kg/min; P < .01). In addition, exercise duration during cardiopulmonary exercise testing significantly improved at 6-month follow-up in the biventricular pacing group (change, 41.5 seconds from 6 weeks to 6 months; P < .01). There were no significant changes in peak VO2 or in exercise performance, however, in the RV pacing group.
Although not a predefined endpoint, it was noted that left ventricular ejection fraction deteriorated in patients who had been assigned to RV pacing, whereas it remained the same in those patients assigned to biventricular pacing (p < 0.03; Figure 3). Kaplan-Meier survival curves were similar in both groups. With respect to quality of life from baseline to 6-month follow-up, biventricular pacing patients fared better compared with RV pacing patients (P = .03).
Figure 3. PAVE: Left ventricular ejection fraction.
Conclusions
The investigators reached the following conclusions:
Patients with chronic AF either refractory to medical treatment or unable to tolerate pharmacologic treatment represent the candidates for AV nodal ablation with permanent pacemaker implantation. According to the present study, the use of biventricular pacing not only prevents the deterioration of long-term function of the heart, but also can improve the exercise capacity of these patients. Obviously, deployment of the pacing leads during biventricular pacemaker implantation is more complex, as was demonstrated by the failure rate in the current study. I believe that the long-term follow-up of these patients will be crucial for our understanding of the long-term effects of biventricular pacing in this patient population.
Atrioventricular (AV) nodal ablation with pacing is an alternative therapeutic option in patients with atrial fibrillation (AF) and difficult-to-control ventricular rates that are unresponsive to medical therapy or who cannot be adequately treated with pharmacologic agents alone. The ablation procedure entails the targeted destruction of the AV node, which is the heart tissue that conducts the electrical impulse from the atria to the ventricles. Thus, AV nodal ablation followed by right ventricular (RV) pacing provides correction of tachycardia-induced cardiomyopathy.
Although RV pacing is the traditional pacing approach, it alters the natural sequence of ventricular activation and contraction and may be associated with poorer outcomes, particularly in patients with some degree of heart failure. Conversely, biventricular pacing can correct the mechanical dyssynchrony found in patients with heart failure and intrinsic conduction system disease. Whether the use of biventricular pacing following AV nodal ablation for AF results in better outcomes compared with RV pacing was not known prior to this trial.
Study Design and Methods
The Left Ventricular-Based Cardiac Stimulation Post AV Nodal Ablation Evaluation (PAVE) study was a prospective, randomized study that evaluated biventricular pacing after AV nodal ablation in patients with AF, regardless of the left ventricular systolic function or New York Heart Association (NYHA) functional class.
Primary Endpoint: Exercise capacity as measured by the distance walked during the 6-minute walk test.
Secondary Endpoints
Functional capacity as measured by peak VO2 during cardiopulmonary exercise testing
Health-related quality of life measured by score of Short Form (SF)-36 questionnaire
Inclusion Criteria:
Chronic AF for at least 1 month
Elective AV nodal ablation and permanent pacemaker implantation
NYHA class I/II/III heart failure
Ability to walk < 450 meters during 6-minute walk test
Stable cardiovascular medication regimen for 5 drug half-lives prior to enrollment
Exclusion Criteria:
NYHA class IV heart failure
Ability to walk > 450 meters during 6-minute test
Patients with an implantable cardioverter defibrillator (ICD), considered for an ICD, or considered for cardiac surgery
Prosthetic valve replacements
Severe musculoskeletal disorders
Patients were randomized in a 2:1 fashion to either ablation plus RV pacing or ablation plus biventricular pacing. Patients randomized to biventricular pacing were implanted with the Frontier Model 5508 and the Aescula Left Heart Lead model 1055 (St. Jude Medical, St. Paul, Minnesota) (both for investigational use only in the United States). Patients randomized to RV pacing were implanted with approved single-chamber devices, also from St. Jude Medical, the study's sponsor. Patients were followed at 6 weeks, 3 months, 6 months, and every 6 months thereafter.
Results
Device implantation was attempted in a total of 252 patients; biventricular pacing in 146 patients and RV pacing in 106 patients. Unsuccessful biventricular device implantation occurred in 21 patients, vs 0 unsuccessful RV pacing implants. Compared with biventricular pacing, more deaths occurred in patients randomized to RV pacing (6 vs 10, respectively). The final population of patients eligible for analysis included 102 RV pacing patients and 82 biventricular pacing patients. There was no significant difference in baseline clinical characteristics between the 2 groups (Table).
Table. PAVE: Baseline Clinical Characteristics
| Characteristic | Right Ventricular Pacing (n = 106) |
Biventricular Pacing (n = 146) |
|---|---|---|
| Age (yrs) | 67 | 70 |
| Male (%) | 68 | 62 |
| NYHA class I/II/III (%) | 21/40/39 | 12/54/34 |
| Ejection fraction (%) | 46 ± 15 | 47 ± 17 |
| QRS duration (msec) | 100 ± 21.5 | 104.3 ± 27.7 |
| Hypertension (%) | 52 | 63 |
| Coronary artery disease (%) | 30 | 37 |
| Valvular heart disease (%) | 16 | 16 |
| Nonischemic cardiomyopathy (%) | 21 | 16 |
| Medical Therapy | ||
| ACE inhibitors (%) | 44.3 | 50.7 |
| Beta blockers (%) | 53.8 | 55.5 |
The 6-minute walk test results are shown in Figure 1 (distance in meters shown as rounded). Although both groups initially had an improvement in walking distance, only patients in the biventricular arm of the study continued to improve at 6-month follow-up (P = .03) (Figure 2).
There was also an improvement in peak VO2 from 6 weeks to 6 months (secondary endpoint) in the biventricular pacing arm (difference of 1.02 mL/kg/min; P < .01). In addition, exercise duration during cardiopulmonary exercise testing significantly improved at 6-month follow-up in the biventricular pacing group (change, 41.5 seconds from 6 weeks to 6 months; P < .01). There were no significant changes in peak VO2 or in exercise performance, however, in the RV pacing group.
Although not a predefined endpoint, it was noted that left ventricular ejection fraction deteriorated in patients who had been assigned to RV pacing, whereas it remained the same in those patients assigned to biventricular pacing (p < 0.03; Figure 3). Kaplan-Meier survival curves were similar in both groups. With respect to quality of life from baseline to 6-month follow-up, biventricular pacing patients fared better compared with RV pacing patients (P = .03).
The investigators reached the following conclusions:
In patients with chronic AF treated with AV nodal ablation, biventricular pacing produces a statistically significant improvement in functional capacity, when compared with RV pacing, as measured by the 6-minute walking test, peak VO2, and exercise duration.
This improvement reflects a sustained benefit in the biventricular group rather than deterioration in the RV pacing group.
Therefore, the results of the PAVE study suggest that biventricular pacing should be the preferred mode of therapy in patients undergoing AV nodal ablation for the control of chronic AF.
Patients with chronic AF either refractory to medical treatment or unable to tolerate pharmacologic treatment represent the candidates for AV nodal ablation with permanent pacemaker implantation. According to the present study, the use of biventricular pacing not only prevents the deterioration of long-term function of the heart, but also can improve the exercise capacity of these patients. Obviously, deployment of the pacing leads during biventricular pacemaker implantation is more complex, as was demonstrated by the failure rate in the current study. I believe that the long-term follow-up of these patients will be crucial for our understanding of the long-term effects of biventricular pacing in this patient population.
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