Ablation of Atrial Flutter in Severe Pulmonary Hypertension
Ablation of Atrial Flutter in Severe Pulmonary Hypertension
Typical atrial flutter is a commonly encountered supraventricular arrhythmia resulting from reentry in a counter-clockwise circuit in the right atrium. The anatomic and electrophysiologic substrate for typical atrial flutter involves a region of slowed conduction in the cavotricuspid annulus with conduction block in the Eustachian ridge and the crista terminalis. As a macroreentrant rhythm, it is responsive to entrainment and amenable to radiofrequency catheter ablation of the cavotricuspid isthmus. Technological advances and the definition of an endpoint of bidirectional isthmus block have contributed to the success of the procedure. In a recent meta-analysis, acute success rates from 153 studies including 10,719 patients was 94% with complications reported in 2.6% of patients. In this analysis, atrial flutter recurrence rates significantly reduced by use of 8- to 10-mm tip or irrigated radiofrequency catheters (6.7% vs 13.8%, P < 0.05) and by use of bidirectional cavotricuspid isthmus block as a procedural endpoint (9.3% vs 23.6%, P < 0.05). A minority of patients in this analysis (46%) had evidence of any structural heart disease. However, excellent clinical outcomes of isthmus-dependent flutter ablation as first line therapy have been demonstrated in patients with ischemic, nonischemic, and hypertrophic cardiomyopathy, valvular and congenital disease.
Among the many factors that can contribute to substrate for typical atrial flutter is pressure load of the right ventricle (RV) resulting from severe pulmonary arterial hypertension (PAH). This results in right atrial enlargement and hypertrophy providing the anatomic and electrophysiologic substrate for typical atrial flutter. PAH, a vasculopathy with progressive intimal proliferation with increasing pulmonary vascular resistance, results in an increase in right ventricular afterload thereby predisposing to atrial flutter. Survival in the era of treatment with prostacyclin derivatives and a phosphodiesterase type-5 inhibitor are 83%, 67%, and 58% at 1, 2, and 3 years, respectively. Clinical evidence of right ventricular failure, 6-minute walk test (6 MWT), B-type natriuretic peptide (BNP), right atrial pressure, and functional class are correlated with outcomes. Right heart failure is the main cause of death in this disease.
The annual incidence of a supraventricular tachycardia is 2.8% in patients with severe PAH with typical atrial flutter being the most common arrhythmia. Patients with severe PAH tolerate loss of normal sinus rhythm poorly with loss of coordinated atial contraction resulting in lowered cardiac output. In this respect, reestablishing and maintaining normal sinus rhythm assume particular clinical significance in this patient population. Development of an atrial arrhythmia such as atrial flutter impacts negatively on the prognosis. Antiarrhythmic therapy is limited by lack of efficacy and adverse effects particularly the negative inotropy in the setting of right ventricular dysfunction. In this respect, a potentially curative approach such as ablation might be a reasonable strategy depending on the proven risks and benefits.
An aggressive approach to the restoration and maintenance of sinus rhythm has been taken in some patients with PAH and atrial arrhythmias including atrial flutter. Restoration of sinus rhythm in patients with PAH has been shown to contribute to an improvement in the 6 MWT and functional class. The mean distance of a 6 MWT prior to a supraventricular arrhythmia was 423.7 m whereas following the arrhythmia it decreased to a mean of 251 meters. Although only 17.8% (N = 5) of patients in this series had atrial flutter, those patients had the most notable decrease. All patients had evidence of clinical improvement with restoration of sinus rhythm with an average increase in the 6 MWT by 196 meters (8). Twenty-six percent of patients (N = 5) died during follow-up. Further observations are available in a cohort of 22 patients with severe PAH (mean function class III) and typical atrial flutter who underwent radiofrequency ablation. An improvement in functional class by two in 1 patient and by 1 in 8 patients at 3 months. Of note, 2 patients were deceased at the time of follow-up as a result of non-procedural related deaths reflecting the inherent progressive nature of severe PAH.
In this issue of JCE, Bradfield and colleagues extend the limited observations on atrial flutter ablation in patients with severe PAH. These investigators evaluated a cohort of 12 patients, undergoing 14 procedures, who had severe PAH reflected by baseline systolic pulmonary artery pressure (SPAP) of 99 ± 35 mmHg and NYHA Class III heart failure symptoms. Reported outcomes included a decrease in SPAP, a trend toward improved 6 MWT, and decreased BNP levels. These observations are even more remarkable, as noted by the authors, due to the high overall mortality of the PAH cohort. Six out of 12 of the PAH patients were deceased at 54 months follow-up compared with no mortality in a control group of 30 patients undergoing flutter ablation without PAH. The authors note that development of atrial arrhythmias such as atrial flutter may be reflection of longstanding elevated atrial pressures resulting in remodeling and suggestive of more severe disease. Recurrence of atrial arrhythmias other than isthmus-dependent atrial flutter is not surprising given the degree of abnormal atrial remodeling in patients with severe PAH.
Several procedural considerations were noted in this series including challenging venous access with one case of bilateral low extremity venous occlusion and another case of atrial dilatation preventing coronary sinus cannulation from either internal jugular or femoral approach. Given the underlying disease process of PAH, potentially resulting from chronic thromboembolism, occlusion of an access site is not unexpected. In 29% of PAH cases, the physicians chose to tailor peri-procedural administration of medications by using nitric oxide to decrease right heart pressure. Inclusion of a control group of 30 patients undergoing atria flutter ablation without PAH provides a useful comparison for this study. In the control patients acute success was 100% and there were no complications. Longer term observations in the control group are severely limited by no data on 15 of 30 (50%) patients at 3 months. However, 14/15 (93%) were free of atrial flutter and 13 of 15 (86%) were completely free of any arrhythmia at 3 months. The authors do contribute novel observations, including the fact that the surface ECG is not a reliable predictor of cavotricuspid isthmus dependence. In addition, the cycle lengths of the atrial flutter are longer that typically observed. Thus, the ECG is of limited clinical utility in determining the origin of the atrial flutter in PAH.
In considering ablation of atrial flutter in the setting of severe PAH in the report of this issue of Journal of Cardiovascular Electrophysiology, it is appropriate to invoke the term "pushing the outside of the envelope." This term was first used in mathematics and subsequently applied to aviation and popularized by Tom Wolfe's 1979 book, The Right Stuff. The phrase was developed to refer to the limits aviation parameters that define safe and successful flight. In the same manner, in interventional electrophysiology, physicians assess a wide range of complex clinical and technical factors to ensure that procedures are within the envelope of safety and success. In this report, the investigators "push the outside of the envelope," by performing cavotricuspid isthmus ablation in an inherently higher risk patient population. While patient selection and refinement of technical aspect of the procedure have made ablation of atrial flutter a safe and successful procedure for most patients, it is evident that for those with severe PAH, the risks are considerable and the outcomes less favorable. While the acute success was noted in 8 of 10 (80%) patients, only 5 of 10 (50%) were completely arrhythmia free at 3 months with 3 of 10 having recurrent atrial arrhythmias different than their initial atrial flutter. Complications were noted in 14% of patients including one hospitalization for right heart failure and one death within 24 hours of the procedure. Five patients died within one year of the procedure. The proposed multicenter prospective trial of atrial flutter ablation in these high risk patients with PAH is laudable. However, given the high mortality in this patient population and unfavorable outcomes with atrial flutter, this trial would present many challenges. In the final analysis, the report by Bradford and prior observations provide a cautionary note that atrial flutter ablation in patients with severe PAH may be "pushing the outside of the envelope" given the considerable complication rates and marginal outcomes reported to date.
Editorial Comment
Typical atrial flutter is a commonly encountered supraventricular arrhythmia resulting from reentry in a counter-clockwise circuit in the right atrium. The anatomic and electrophysiologic substrate for typical atrial flutter involves a region of slowed conduction in the cavotricuspid annulus with conduction block in the Eustachian ridge and the crista terminalis. As a macroreentrant rhythm, it is responsive to entrainment and amenable to radiofrequency catheter ablation of the cavotricuspid isthmus. Technological advances and the definition of an endpoint of bidirectional isthmus block have contributed to the success of the procedure. In a recent meta-analysis, acute success rates from 153 studies including 10,719 patients was 94% with complications reported in 2.6% of patients. In this analysis, atrial flutter recurrence rates significantly reduced by use of 8- to 10-mm tip or irrigated radiofrequency catheters (6.7% vs 13.8%, P < 0.05) and by use of bidirectional cavotricuspid isthmus block as a procedural endpoint (9.3% vs 23.6%, P < 0.05). A minority of patients in this analysis (46%) had evidence of any structural heart disease. However, excellent clinical outcomes of isthmus-dependent flutter ablation as first line therapy have been demonstrated in patients with ischemic, nonischemic, and hypertrophic cardiomyopathy, valvular and congenital disease.
Among the many factors that can contribute to substrate for typical atrial flutter is pressure load of the right ventricle (RV) resulting from severe pulmonary arterial hypertension (PAH). This results in right atrial enlargement and hypertrophy providing the anatomic and electrophysiologic substrate for typical atrial flutter. PAH, a vasculopathy with progressive intimal proliferation with increasing pulmonary vascular resistance, results in an increase in right ventricular afterload thereby predisposing to atrial flutter. Survival in the era of treatment with prostacyclin derivatives and a phosphodiesterase type-5 inhibitor are 83%, 67%, and 58% at 1, 2, and 3 years, respectively. Clinical evidence of right ventricular failure, 6-minute walk test (6 MWT), B-type natriuretic peptide (BNP), right atrial pressure, and functional class are correlated with outcomes. Right heart failure is the main cause of death in this disease.
The annual incidence of a supraventricular tachycardia is 2.8% in patients with severe PAH with typical atrial flutter being the most common arrhythmia. Patients with severe PAH tolerate loss of normal sinus rhythm poorly with loss of coordinated atial contraction resulting in lowered cardiac output. In this respect, reestablishing and maintaining normal sinus rhythm assume particular clinical significance in this patient population. Development of an atrial arrhythmia such as atrial flutter impacts negatively on the prognosis. Antiarrhythmic therapy is limited by lack of efficacy and adverse effects particularly the negative inotropy in the setting of right ventricular dysfunction. In this respect, a potentially curative approach such as ablation might be a reasonable strategy depending on the proven risks and benefits.
An aggressive approach to the restoration and maintenance of sinus rhythm has been taken in some patients with PAH and atrial arrhythmias including atrial flutter. Restoration of sinus rhythm in patients with PAH has been shown to contribute to an improvement in the 6 MWT and functional class. The mean distance of a 6 MWT prior to a supraventricular arrhythmia was 423.7 m whereas following the arrhythmia it decreased to a mean of 251 meters. Although only 17.8% (N = 5) of patients in this series had atrial flutter, those patients had the most notable decrease. All patients had evidence of clinical improvement with restoration of sinus rhythm with an average increase in the 6 MWT by 196 meters (8). Twenty-six percent of patients (N = 5) died during follow-up. Further observations are available in a cohort of 22 patients with severe PAH (mean function class III) and typical atrial flutter who underwent radiofrequency ablation. An improvement in functional class by two in 1 patient and by 1 in 8 patients at 3 months. Of note, 2 patients were deceased at the time of follow-up as a result of non-procedural related deaths reflecting the inherent progressive nature of severe PAH.
In this issue of JCE, Bradfield and colleagues extend the limited observations on atrial flutter ablation in patients with severe PAH. These investigators evaluated a cohort of 12 patients, undergoing 14 procedures, who had severe PAH reflected by baseline systolic pulmonary artery pressure (SPAP) of 99 ± 35 mmHg and NYHA Class III heart failure symptoms. Reported outcomes included a decrease in SPAP, a trend toward improved 6 MWT, and decreased BNP levels. These observations are even more remarkable, as noted by the authors, due to the high overall mortality of the PAH cohort. Six out of 12 of the PAH patients were deceased at 54 months follow-up compared with no mortality in a control group of 30 patients undergoing flutter ablation without PAH. The authors note that development of atrial arrhythmias such as atrial flutter may be reflection of longstanding elevated atrial pressures resulting in remodeling and suggestive of more severe disease. Recurrence of atrial arrhythmias other than isthmus-dependent atrial flutter is not surprising given the degree of abnormal atrial remodeling in patients with severe PAH.
Several procedural considerations were noted in this series including challenging venous access with one case of bilateral low extremity venous occlusion and another case of atrial dilatation preventing coronary sinus cannulation from either internal jugular or femoral approach. Given the underlying disease process of PAH, potentially resulting from chronic thromboembolism, occlusion of an access site is not unexpected. In 29% of PAH cases, the physicians chose to tailor peri-procedural administration of medications by using nitric oxide to decrease right heart pressure. Inclusion of a control group of 30 patients undergoing atria flutter ablation without PAH provides a useful comparison for this study. In the control patients acute success was 100% and there were no complications. Longer term observations in the control group are severely limited by no data on 15 of 30 (50%) patients at 3 months. However, 14/15 (93%) were free of atrial flutter and 13 of 15 (86%) were completely free of any arrhythmia at 3 months. The authors do contribute novel observations, including the fact that the surface ECG is not a reliable predictor of cavotricuspid isthmus dependence. In addition, the cycle lengths of the atrial flutter are longer that typically observed. Thus, the ECG is of limited clinical utility in determining the origin of the atrial flutter in PAH.
In considering ablation of atrial flutter in the setting of severe PAH in the report of this issue of Journal of Cardiovascular Electrophysiology, it is appropriate to invoke the term "pushing the outside of the envelope." This term was first used in mathematics and subsequently applied to aviation and popularized by Tom Wolfe's 1979 book, The Right Stuff. The phrase was developed to refer to the limits aviation parameters that define safe and successful flight. In the same manner, in interventional electrophysiology, physicians assess a wide range of complex clinical and technical factors to ensure that procedures are within the envelope of safety and success. In this report, the investigators "push the outside of the envelope," by performing cavotricuspid isthmus ablation in an inherently higher risk patient population. While patient selection and refinement of technical aspect of the procedure have made ablation of atrial flutter a safe and successful procedure for most patients, it is evident that for those with severe PAH, the risks are considerable and the outcomes less favorable. While the acute success was noted in 8 of 10 (80%) patients, only 5 of 10 (50%) were completely arrhythmia free at 3 months with 3 of 10 having recurrent atrial arrhythmias different than their initial atrial flutter. Complications were noted in 14% of patients including one hospitalization for right heart failure and one death within 24 hours of the procedure. Five patients died within one year of the procedure. The proposed multicenter prospective trial of atrial flutter ablation in these high risk patients with PAH is laudable. However, given the high mortality in this patient population and unfavorable outcomes with atrial flutter, this trial would present many challenges. In the final analysis, the report by Bradford and prior observations provide a cautionary note that atrial flutter ablation in patients with severe PAH may be "pushing the outside of the envelope" given the considerable complication rates and marginal outcomes reported to date.