Risk Factor Reduction for AF and Implications for Ablation
Risk Factor Reduction for AF and Implications for Ablation
The study comprised consecutive patients with a body mass index (BMI) ≥27 kg/m and ≥1 risk factor (hypertension, glucose intolerance/DM, hyperlipidemia, OSA, smoking, or alcohol excess) undergoing initial catheter ablation for symptomatic AF despite the use of antiarrhythmic medication.
All patients provided written informed consent for the ablation procedure and collection of their clinical data. The Human Research Ethics Committee of the Royal Adelaide Hospital and University of Adelaide approved the study protocol.
All suitable patients were offered risk factor management (RFM) in a dedicated physician-directed clinic at the time of initial assessment. Patients who accepted this strategy formed the intervention group (RFM group), and those who declined formed the control group. Only patients with ongoing significant symptoms, despite the use of antiarrhythmic medications and RFM, underwent AF ablation. Exclusion criteria were: history of myocardial infarction or cardiac surgery in the previous 12 months; previous AF ablation; active malignancy; autoimmune or systemic inflammatory disease; severe renal or hepatic failure; and <12 months' follow-up after their procedure.
Patients participating in RFM attended a physician-directed RFM clinic (in addition to their arrhythmia follow-up) every 3 months and were managed according to American College of Cardiology/American Heart Association guidelines.
Blood pressure (BP) was measured thrice daily by using a home-based automated monitor and an appropriate-sized cuff. In addition, exercise stress testing was performed to determine the presence of exercise-induced hypertension, with BP >200/100 mm Hg considered as evidence to optimize therapy. Lifestyle advice constituted dietary salt restriction. Pharmacotherapy was initiated by using renin-angiotensin-aldosterone system antagonists, with other agents used when necessary to achieve a target BP of <130/80 mm Hg at least 80% of the time. These were corroborated by in-office and 24-h ambulatory BP measurements, as required. Echocardiography was monitored to ensure resolution of left ventricular (LV) hypertrophy.
A structured motivational and goal-directed program using face-to-face counseling was used for weight reduction. Patients were encouraged to utilize support counseling and schedule more frequent reviews, as required. Initial weight reduction was attempted by using a meal plan and behavior modification. Participants were required to maintain a diet and physical activity diary. Meals consisted of high-protein and low glycemic index, calorie-controlled foods. If patients lost <3% of weight after 3 months, they were then prescribed very low calorie meal replacement sachets (Prima Health Solutions, Sydney, Australia, or Nestlé Health Science, Sydney, Australia) for 1 to 2 meals per day. The initial goal was to reduce body weight by 10%. After patients achieved the initial goal, meal replacement was substituted with high-protein and low glycemic index, calorie-controlled foods to achieve a target BMI of ≤25 kg/m. Low-intensity exercise was prescribed initially for 20 min thrice weekly, increasing to at least 200 min of moderate-intensity activity per week.
Lipids were initially managed with lifestyle measures; if patients were unable to achieve low-density lipoprotein cholesterol levels <100 mg/dl after 3 months, use of a hydroxymethylglutaryl coenzyme A reductase inhibitor was then initiated. Fibrates were used for isolated hypertriglyceridemia (triglycerides >500 mg/dl) or added to statin therapy if triglyceride levels were >200 mg/dl and non–high-density lipoprotein cholesterol levels were >130 mg/dl.
A glucose tolerance test was performed if fasting glucose levels were 100 to 125 mg/dl. Impaired glucose tolerance or DM was initially managed with lifestyle measures. If patients were unable to maintain glycosylated hemoglobin (HbA1c) levels ≤6.5% after 3 months, metformin was started. Patients in both groups with suboptimal glycemic control (HbA1c >7%) were referred to a specialized diabetes clinic.
In-laboratory overnight polysomnography was scored by qualified sleep technicians and reviewed with follow-up by a sleep physician. The scoring was according to the American Academy of Sleep Medicine alternate polysomnography scoring criteria. Patients were offered therapy if the apnea–hypopnea index (AHI) was ≥30/h or if it was >20/h with resistant hypertension or problematic daytime sleepiness. Treatment included positional therapy and continuous positive airway pressure (CPAP).
The "5As" (ask, advise, assess, assist, and arrange follow-up) structured smoking cessation framework was adopted. Smokers were offered behavioral support through a multidisciplinary clinic with the aim of smoking cessation.
Written and verbal counseling was provided with regular supportive follow-up for alcohol reduction to ≤30 g/week.
The control group was given information on management of risk factors. However, they continued RFM under the direction of their treating physician.
The ablation procedure was performed with the operator blinded to the patient's study group. The ablation technique used at our institution has been described previously and included wide-encircling pulmonary vein ablation with an endpoint of electrical isolation (pulmonary vein isolation) in all patients. Further substrate modification was performed for patients with AF episodes ≥48 h or if the largest left atrial (LA) dimension exceeded 57 mm. This included linear ablation (roofline and/or mitral isthmus) with an endpoint of bidirectional block and/or electrogram-guided ablation of fractionated sites.
If patients developed recurrent arrhythmia after the blanking period (3 months), repeat ablation was offered. Individual operators decided on the extent of additional ablation undertaken beyond reisolation of the pulmonary veins.
Physicians blinded to the patient's study group assessed patients for arrhythmia recurrence. Reviews were every 3 months for the first year and then every 6 months thereafter. At each review, AF recurrence was ascertained from patients' symptoms, electrocardiograms, and ambulatory 7-day monitoring. Two independent observers blinded to patient group analyzed the ambulatory recordings. In the absence of any arrhythmia, antiarrhythmic drugs were stopped at 4 to 6 weeks. No patient continued on amiodarone after ablation. All patients underwent anticoagulation by using warfarin for ≥3 months after ablation.
Procedural success was determined as the absence of any atrial arrhythmia ≥30 s after a 3-month blanking period.
AF symptom burden and severity were quantified by using the validated Atrial Fibrillation Severity Scale (AFSS, University of Toronto, Toronto, Ontario, Canada). The AFSS is used to quantify 3 domains of AF-related symptoms: frequency, duration, and severity. A symptom subscale was also determined. The AFSS questionnaire was administered at baseline and at follow-up after ablation.
Transthoracic echocardiography was performed at baseline and yearly by using a 3.5-MHz probe. Measurements were performed according to American Society of Echocardiography guidelines by an operator blinded to the study group.
Categorical variables are represented by frequencies and percentages, and continuous variables are summarized by mean ± SD. Repeated measure analysis of variance was used to assess the interaction between the groups over time. The significance of the interaction in the analysis of variance was used to assess these changes. Comparisons of variables for both the control and RFM groups were performed by using paired samples Student t tests. For nominal variables, such as diabetes and sleep apnea (AHI >30), changes were only assessed for patients who were positive at baseline. The change in the status at final follow-up was compared between the 2 groups by using chi-square tests. The Kaplan-Meier product-limit method was used to estimate the time to recurrence and event-free survival curves after the last ablation procedure. Requirement for a repeat procedure was considered an endpoint. Predictors of recurrent AF were assessed in Cox regression models after verifying proportionality assumptions. Candidate variables with p < 0.1 in univariate analyses were considered in multivariate stepwise regression models. Two-tailed p values <0.05 were considered statistically significant. Statistical analysis was performed by using SPSS version 21.0 (IBM SPSS Statistics, IBM Corporation, Armonk, New York).
Methods
Study Population
The study comprised consecutive patients with a body mass index (BMI) ≥27 kg/m and ≥1 risk factor (hypertension, glucose intolerance/DM, hyperlipidemia, OSA, smoking, or alcohol excess) undergoing initial catheter ablation for symptomatic AF despite the use of antiarrhythmic medication.
All patients provided written informed consent for the ablation procedure and collection of their clinical data. The Human Research Ethics Committee of the Royal Adelaide Hospital and University of Adelaide approved the study protocol.
Study Protocol
All suitable patients were offered risk factor management (RFM) in a dedicated physician-directed clinic at the time of initial assessment. Patients who accepted this strategy formed the intervention group (RFM group), and those who declined formed the control group. Only patients with ongoing significant symptoms, despite the use of antiarrhythmic medications and RFM, underwent AF ablation. Exclusion criteria were: history of myocardial infarction or cardiac surgery in the previous 12 months; previous AF ablation; active malignancy; autoimmune or systemic inflammatory disease; severe renal or hepatic failure; and <12 months' follow-up after their procedure.
RFM Group
Patients participating in RFM attended a physician-directed RFM clinic (in addition to their arrhythmia follow-up) every 3 months and were managed according to American College of Cardiology/American Heart Association guidelines.
Blood Pressure Control
Blood pressure (BP) was measured thrice daily by using a home-based automated monitor and an appropriate-sized cuff. In addition, exercise stress testing was performed to determine the presence of exercise-induced hypertension, with BP >200/100 mm Hg considered as evidence to optimize therapy. Lifestyle advice constituted dietary salt restriction. Pharmacotherapy was initiated by using renin-angiotensin-aldosterone system antagonists, with other agents used when necessary to achieve a target BP of <130/80 mm Hg at least 80% of the time. These were corroborated by in-office and 24-h ambulatory BP measurements, as required. Echocardiography was monitored to ensure resolution of left ventricular (LV) hypertrophy.
Weight Management
A structured motivational and goal-directed program using face-to-face counseling was used for weight reduction. Patients were encouraged to utilize support counseling and schedule more frequent reviews, as required. Initial weight reduction was attempted by using a meal plan and behavior modification. Participants were required to maintain a diet and physical activity diary. Meals consisted of high-protein and low glycemic index, calorie-controlled foods. If patients lost <3% of weight after 3 months, they were then prescribed very low calorie meal replacement sachets (Prima Health Solutions, Sydney, Australia, or Nestlé Health Science, Sydney, Australia) for 1 to 2 meals per day. The initial goal was to reduce body weight by 10%. After patients achieved the initial goal, meal replacement was substituted with high-protein and low glycemic index, calorie-controlled foods to achieve a target BMI of ≤25 kg/m. Low-intensity exercise was prescribed initially for 20 min thrice weekly, increasing to at least 200 min of moderate-intensity activity per week.
Lipid Management
Lipids were initially managed with lifestyle measures; if patients were unable to achieve low-density lipoprotein cholesterol levels <100 mg/dl after 3 months, use of a hydroxymethylglutaryl coenzyme A reductase inhibitor was then initiated. Fibrates were used for isolated hypertriglyceridemia (triglycerides >500 mg/dl) or added to statin therapy if triglyceride levels were >200 mg/dl and non–high-density lipoprotein cholesterol levels were >130 mg/dl.
Glycemic Control
A glucose tolerance test was performed if fasting glucose levels were 100 to 125 mg/dl. Impaired glucose tolerance or DM was initially managed with lifestyle measures. If patients were unable to maintain glycosylated hemoglobin (HbA1c) levels ≤6.5% after 3 months, metformin was started. Patients in both groups with suboptimal glycemic control (HbA1c >7%) were referred to a specialized diabetes clinic.
Sleep-disordered Breathing Management
In-laboratory overnight polysomnography was scored by qualified sleep technicians and reviewed with follow-up by a sleep physician. The scoring was according to the American Academy of Sleep Medicine alternate polysomnography scoring criteria. Patients were offered therapy if the apnea–hypopnea index (AHI) was ≥30/h or if it was >20/h with resistant hypertension or problematic daytime sleepiness. Treatment included positional therapy and continuous positive airway pressure (CPAP).
Smoking and Alcohol
The "5As" (ask, advise, assess, assist, and arrange follow-up) structured smoking cessation framework was adopted. Smokers were offered behavioral support through a multidisciplinary clinic with the aim of smoking cessation.
Written and verbal counseling was provided with regular supportive follow-up for alcohol reduction to ≤30 g/week.
Control Group
The control group was given information on management of risk factors. However, they continued RFM under the direction of their treating physician.
Catheter Ablation
The ablation procedure was performed with the operator blinded to the patient's study group. The ablation technique used at our institution has been described previously and included wide-encircling pulmonary vein ablation with an endpoint of electrical isolation (pulmonary vein isolation) in all patients. Further substrate modification was performed for patients with AF episodes ≥48 h or if the largest left atrial (LA) dimension exceeded 57 mm. This included linear ablation (roofline and/or mitral isthmus) with an endpoint of bidirectional block and/or electrogram-guided ablation of fractionated sites.
If patients developed recurrent arrhythmia after the blanking period (3 months), repeat ablation was offered. Individual operators decided on the extent of additional ablation undertaken beyond reisolation of the pulmonary veins.
Follow-up
Physicians blinded to the patient's study group assessed patients for arrhythmia recurrence. Reviews were every 3 months for the first year and then every 6 months thereafter. At each review, AF recurrence was ascertained from patients' symptoms, electrocardiograms, and ambulatory 7-day monitoring. Two independent observers blinded to patient group analyzed the ambulatory recordings. In the absence of any arrhythmia, antiarrhythmic drugs were stopped at 4 to 6 weeks. No patient continued on amiodarone after ablation. All patients underwent anticoagulation by using warfarin for ≥3 months after ablation.
Procedural success was determined as the absence of any atrial arrhythmia ≥30 s after a 3-month blanking period.
AF Symptom Burden
AF symptom burden and severity were quantified by using the validated Atrial Fibrillation Severity Scale (AFSS, University of Toronto, Toronto, Ontario, Canada). The AFSS is used to quantify 3 domains of AF-related symptoms: frequency, duration, and severity. A symptom subscale was also determined. The AFSS questionnaire was administered at baseline and at follow-up after ablation.
Cardiac Structure
Transthoracic echocardiography was performed at baseline and yearly by using a 3.5-MHz probe. Measurements were performed according to American Society of Echocardiography guidelines by an operator blinded to the study group.
Statistical Analysis
Categorical variables are represented by frequencies and percentages, and continuous variables are summarized by mean ± SD. Repeated measure analysis of variance was used to assess the interaction between the groups over time. The significance of the interaction in the analysis of variance was used to assess these changes. Comparisons of variables for both the control and RFM groups were performed by using paired samples Student t tests. For nominal variables, such as diabetes and sleep apnea (AHI >30), changes were only assessed for patients who were positive at baseline. The change in the status at final follow-up was compared between the 2 groups by using chi-square tests. The Kaplan-Meier product-limit method was used to estimate the time to recurrence and event-free survival curves after the last ablation procedure. Requirement for a repeat procedure was considered an endpoint. Predictors of recurrent AF were assessed in Cox regression models after verifying proportionality assumptions. Candidate variables with p < 0.1 in univariate analyses were considered in multivariate stepwise regression models. Two-tailed p values <0.05 were considered statistically significant. Statistical analysis was performed by using SPSS version 21.0 (IBM SPSS Statistics, IBM Corporation, Armonk, New York).
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