Catheterization and Cardiovascular Interventions 83:796–802 (2014)
Safety of Percutaneous Left Atrial Appendage Closure with the Amplatzer Cardiac Plug in Patients with Atrial Fibrillation and Contraindications to Anticoagulation Jens Wiebe, MD, Stefan Bertog, MD, Jennifer Franke, MD, Olga Wettstein, MD, Katharina Lehn, MD, Ilona Hofmann, MD, Laura Vaskelyte, MD, and Horst Sievert,* MD Objective: To evaluate the safety of percutaneous left atrial appendage (LAA) closure with the Amplatzer Cardiac Plug (ACP) in patients with nonvalvular atrial fibrillation (AF) who are not eligible for oral anticoagulation with warfarin. Background: Anticoagulation is the treatment of choice for prevention of strokes in patients with AF, but some patients have contraindications to anticoagulation. Methods: A total of 60 patients with a CHA2DS2-VASc score of at least 1 and contraindications to warfarin who underwent percutaneous LAA closure with the ACP were included. Stroke risk assessment was performed with the CHADS2 and CHA2DS2-VASc score and the bleeding risk was calculated with the HAS-BLED-score. Follow-up included office visits, telephone inquiries, and mail contact. Results: Mean CHADS2-, CHA2DS2-VASc-, and HAS-BLED scores were 2.6 (6 1.4), 4.3 (6 1.7), and 3.3 (6 1.0), respectively. Twenty-five percent had a history of previous bleeding without oral anticoagulation and 63.3% while receiving oral anticoagulation. In 36.7% other contraindications to warfarin were present. Procedural success was achieved in 95%. Mean follow-up time was 1.8 (1.0–2.8) years. The estimated annual stroke risk based on the CHADS2-score was 5.8%. The estimated annual bleeding risk on warfarin based on the HAS-BLED score was 3.7%. During follow-up, the annual incidence of stroke was 0%. Major bleeding complications occurred in 1.9% annually. Conclusions: Percutaneous LAA closure with the ACP in patients with contraindications to oral anticoagulation is safe. The stroke and bleeding risk after percutaneous LAA closure is lower than predicted by conventional risk scores. VC 2013 Wiley Periodicals, Inc. Key words: left atrial appendage closure; coagulation; embolization
INTRODUCTION
Atrial fibrillation (AF) is the most common arrhythmia [1–3] with an age-dependent increase in prevalence [1–3]. It is accompanied with a high stroke risk [4] and oral anticoagulation with Vitamin K antagonists (VKA) has been shown to reduce this risk substantially [5]. Therefore,
CardioVascular Center Frankfurt, Germany Conflict of interest: Nothing to report. Disclosures: The CardioVascular Center received study honoraria, consulting fees and travel expenses from ev3, Abbott, Access Closure, AGA, Angiomed, Aptus, Arstasis, Atritech, Atrium, Avinger, Bard, Boston Scientific, Bridgepoint, Cardiac Dimensions, CardioKinetix, CardioMEMS, Coherex, Contego, CSI, CVRx, EndoCross, EndoTex, Epitek, ev3, FlowCardia, Gore, Guidant, Guided Delivery Systems, Inc., InSeal Medical, Lumen Biomedical, HLT, Kensey Nash, Kyoto Medical, Lifetech, Lutonix, Maya Medical, Medinol, Medtronic, NDC, NMT, OAS, Occlutech, Osprey, Ovalis, Pathway, PendraCare, Percardia, pfm Medical, Recor, ResMed, Rox Medical, C 2013 Wiley Periodicals, Inc. V
according to current guidelines, oral anticoagulation with VKA is the treatment of choice for prevention of strokes and other thromboembolic events [6,7]. Next to VKA, recently, dabigatran, a direct thrombin inhibitor, and rivaroxaban, a factor Xa inhibitor, have been shown to have at least equivalent efficacy compared with
Sadra, Sorin, Spectranetics, SquareOne, Trireme, Trivascular, Velocimed, Veryan, Vessix. The CardioVascular Center holds stock options from: Cardiokinetix, Access Closure, Lumen Biomedical, Coherex, SMT. *Correspondence to: Prof. Dr. med. Horst Sievert, CardioVascular Center Frankfurt, Seckbacher Landstrasse 65, 60389 Frankfurt, Germany. E-mail: [email protected] Received 23 April 2013; Revision accepted 28 November 2013 DOI: 10.1002/ccd.25329 Published online 11 December 2013 in Wiley Online Library (wileyonlinelibrary.com)
Safety of Percutaneous LAA Closure
VKA [8,9]. Nonetheless, similar to VKA, they are associated with a significant bleeding risk [8,9]. In addition, percutaneous left atrial appendage (LAA) occlusion has been demonstrated to be at least noninferior to conventional anticoagulation with VKA for stroke prevention [10]. Importantly, in the only randomized trial available comparing percutaneous LAA closure to anticoagulation, patients with contraindications to VKA were excluded and VKA were routinely administered for 45 days after implantation [10]. Many patients, however, are at prohibitive risk for even temporary anticoagulation. Data regarding the safety of LAA occlusion in the absence of even temporary anticoagulation are limited. The aim of this study was to determine the safety of percutaneous LAA occlusion with the Amplatzer Cardiac Plug (ACP, St. Jude Medical, Minneapolis, MN) followed by antiplatelet therapy only (without anticoagulation). METHODS
797
anticoagulant and antiplatelet therapy), determination of risk scores (CHADS2 [13], CHA2DS2-VASc [14], HAS-BLED [15]), physical examination, and EKG. Echocardiographic assessment was performed via transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) to determine technical suitability. Patients with pericardial effusion, intracardiac thrombus or with LAA sizes and anatomy that did not allow safe device implantation were excluded. TTE and EKG were repeated prior to discharge. Physical examination, EKG and TEE evaluation were repeated at 1-, 6-, and 12-month follow-up by the implantation site or referring cardiologist. The TEE focus was the detection of device- or procedure-related adverse events (AE, e.g. remaining atrial septal defects after transseptal puncture or pericardial effusion), device position and residual flow around the device. A peri-device leak of 5 mm was considered relevant because in the only published randomized controlled trial to date, at this leak magnitude, anticoagulation with warfarin was continued. Subsequently, clinical follow-up was performed according to the patients’ wishes, by the implanting site, the referring cardiologist or by telephone and/ or mail.
Study Design Between January 2009 and December 2012, all consecutive patients with nonvalvular AF and a CHA2DS2VASc-score of at least 1 who were not eligible for oral anticoagulation with VKA and underwent ACP implantation were analyzed retrospectively and included in this study. This includes patients with contraindications as defined in the warfarin product label, a history of severe bleeding while receiving anticoagulant therapy as well as a history of bleeding tendencies in the absence of anticoagulation or blood dyscrasia. Patients who were unable to maintain a stable INR and those with a known hypersensitivity to warfarin or a high-risk of falling were also included. Patients who requested elective LAA closure despite an absence of contraindications to anticoagulation were not enrolled in this study.
Major AE We differentiated five categories of AE: procedurerelated, cardiovascular, noncardiovascular, bleeding, and cerebral ischemia [stroke/Transient ischemic attack (TIA)]. Major AE included events that were fatal, lifethreatening, needed hospitalization, or prolongation of current hospitalization or led to considerable disability. Of note, bleeding complications were considered major if transfusion and/or hospitalization were required or if an ongoing hospitalization was prolonged.
Device Descriptions and Procedure
Statistical Analysis
The ACP (AGA Medical, Minneapolis, MN), a catheter-based self-expanding device, was implanted in all patients. The device itself and the implantation procedure have previously been described in detail [11,12].
Categorical variables were presented in counts and percentages, whereas continuous variables were presented as the mean with standard deviation (SD) and interquartile range. To compare categorical variables the Chi-Square or the Fisher’s exact test was used, whereas for continuous variables the Mann-WhitneyWilcoxon U test was applied. A P-value < 0.05 was considered as statistically significant.
Medical Treatment During implantation, heparin was administered with a goal activated clotting time of at least 200 sec. After the procedure, patients were instructed to take life-long daily acetyl salicylic acid (100 mg) in addition to 3 months of clopidogrel (75 mg). Baseline and Follow-Up Assessments Baseline evaluation included assessment of patients’ medical history and current medication (focusing on
Ethics The study was performed in adherence with the guidelines of the Declaration of Helsinki. Risks, benefits, and alternatives were discussed in detail with the patient and written consent was obtained prior to the procedure.
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
798
Wiebe et al.
TABLE I. Baseline Characteristics N Age (mean years 6 SD) CHADS2 (mean score 6 SD) CHA2DS2-VASc (mean score 6 SD) Congestive heart failure (%, n/N) Hypertension (%, n/N) Age 65–74 years (%, n/N) Age 75 years (%, n/N) Diabetes (%, n/N) History of stroke/ TIAa (%, n/N) Vascular disease (%, n/N) Female gender (%, n/N) HAS-BLED (mean score 6 SD) Abnormal renal function (%, n/N) Abnormal liver function (%, n/N) History of bleeding (%, n/N) Labile INRb (%, n/N) Age 65 years (%, n/N) Antiplatelet therapy (%, n/N) Alcohol abuse (%, n/N) a
TABLE II.
Contraindications
60
31.7 95.0 48.3 38.3 26.7 33.3 49.2 38.3 16.7 10.0 81.7 5.0 86.7 15.0 3.3
72.9 6 8.1 2.6 6 1.4 4.3 6 1.7 (19/60) (57/60) (29/60) (23/60) (16/60) (20/60) (29/60) (23/60) 3.3 6 1.0 (10/60) (6/60) (49/60) (3/60) (52/60) (9/60) (2/60)
TIA: transient ischemic attack. INR: international normalized ratio.
b
RESULTS
A total of 60 patients were included in this study. Mean age at the time of enrollment was 72.9 years (6 8.1), 38.3% were female. All patients suffered from non-valvular AF (23.3% paroxysmal, 22.8% persistent, and 34.7% permanent). Mean CHADS2-, CHA2DS2VASc-, and HAS-BLED-scores were 2.6 (6 1.4), 4.3 (6 1.7), and 3.3 (6 1.0), respectively. The frequencies of individual risk factors are listed in Table I. Eightyfive percent of patients had one, 13.3% two and 1.7% three contraindications to warfarin. A significant bleeding history in the absence of, or while taking oral anticoagulation, was reported in 25.0 and 63.3%, respectively. Gastrointestinal and intracranial hemorrhages were the most common bleeding locations. A total of 14.3% of all patients who experienced a bleeding complication had required transfusions. In 36.7% other contraindications to Warfarin were present (Table II). The implantation was successful in 95.0 % (Table III). In three cases, implantation was not possible due to unsuitable LAA anatomy. Two of these patients remained on Warfarin and 1 patient continued dual antiplatelet therapy. There was no evidence of a significant residual flow 5 mm at implantation or followup. A residual leak
Safety of Percutaneous Left Atrial Appendage Closure with the Amplatzer Cardiac Plug in Patients with Atrial Fibrillation and Contraindications to Anticoagulation Jens Wiebe, MD, Stefan Bertog, MD, Jennifer Franke, MD, Olga Wettstein, MD, Katharina Lehn, MD, Ilona Hofmann, MD, Laura Vaskelyte, MD, and Horst Sievert,* MD Objective: To evaluate the safety of percutaneous left atrial appendage (LAA) closure with the Amplatzer Cardiac Plug (ACP) in patients with nonvalvular atrial fibrillation (AF) who are not eligible for oral anticoagulation with warfarin. Background: Anticoagulation is the treatment of choice for prevention of strokes in patients with AF, but some patients have contraindications to anticoagulation. Methods: A total of 60 patients with a CHA2DS2-VASc score of at least 1 and contraindications to warfarin who underwent percutaneous LAA closure with the ACP were included. Stroke risk assessment was performed with the CHADS2 and CHA2DS2-VASc score and the bleeding risk was calculated with the HAS-BLED-score. Follow-up included office visits, telephone inquiries, and mail contact. Results: Mean CHADS2-, CHA2DS2-VASc-, and HAS-BLED scores were 2.6 (6 1.4), 4.3 (6 1.7), and 3.3 (6 1.0), respectively. Twenty-five percent had a history of previous bleeding without oral anticoagulation and 63.3% while receiving oral anticoagulation. In 36.7% other contraindications to warfarin were present. Procedural success was achieved in 95%. Mean follow-up time was 1.8 (1.0–2.8) years. The estimated annual stroke risk based on the CHADS2-score was 5.8%. The estimated annual bleeding risk on warfarin based on the HAS-BLED score was 3.7%. During follow-up, the annual incidence of stroke was 0%. Major bleeding complications occurred in 1.9% annually. Conclusions: Percutaneous LAA closure with the ACP in patients with contraindications to oral anticoagulation is safe. The stroke and bleeding risk after percutaneous LAA closure is lower than predicted by conventional risk scores. VC 2013 Wiley Periodicals, Inc. Key words: left atrial appendage closure; coagulation; embolization
INTRODUCTION
Atrial fibrillation (AF) is the most common arrhythmia [1–3] with an age-dependent increase in prevalence [1–3]. It is accompanied with a high stroke risk [4] and oral anticoagulation with Vitamin K antagonists (VKA) has been shown to reduce this risk substantially [5]. Therefore,
CardioVascular Center Frankfurt, Germany Conflict of interest: Nothing to report. Disclosures: The CardioVascular Center received study honoraria, consulting fees and travel expenses from ev3, Abbott, Access Closure, AGA, Angiomed, Aptus, Arstasis, Atritech, Atrium, Avinger, Bard, Boston Scientific, Bridgepoint, Cardiac Dimensions, CardioKinetix, CardioMEMS, Coherex, Contego, CSI, CVRx, EndoCross, EndoTex, Epitek, ev3, FlowCardia, Gore, Guidant, Guided Delivery Systems, Inc., InSeal Medical, Lumen Biomedical, HLT, Kensey Nash, Kyoto Medical, Lifetech, Lutonix, Maya Medical, Medinol, Medtronic, NDC, NMT, OAS, Occlutech, Osprey, Ovalis, Pathway, PendraCare, Percardia, pfm Medical, Recor, ResMed, Rox Medical, C 2013 Wiley Periodicals, Inc. V
according to current guidelines, oral anticoagulation with VKA is the treatment of choice for prevention of strokes and other thromboembolic events [6,7]. Next to VKA, recently, dabigatran, a direct thrombin inhibitor, and rivaroxaban, a factor Xa inhibitor, have been shown to have at least equivalent efficacy compared with
Sadra, Sorin, Spectranetics, SquareOne, Trireme, Trivascular, Velocimed, Veryan, Vessix. The CardioVascular Center holds stock options from: Cardiokinetix, Access Closure, Lumen Biomedical, Coherex, SMT. *Correspondence to: Prof. Dr. med. Horst Sievert, CardioVascular Center Frankfurt, Seckbacher Landstrasse 65, 60389 Frankfurt, Germany. E-mail: [email protected] Received 23 April 2013; Revision accepted 28 November 2013 DOI: 10.1002/ccd.25329 Published online 11 December 2013 in Wiley Online Library (wileyonlinelibrary.com)
Safety of Percutaneous LAA Closure
VKA [8,9]. Nonetheless, similar to VKA, they are associated with a significant bleeding risk [8,9]. In addition, percutaneous left atrial appendage (LAA) occlusion has been demonstrated to be at least noninferior to conventional anticoagulation with VKA for stroke prevention [10]. Importantly, in the only randomized trial available comparing percutaneous LAA closure to anticoagulation, patients with contraindications to VKA were excluded and VKA were routinely administered for 45 days after implantation [10]. Many patients, however, are at prohibitive risk for even temporary anticoagulation. Data regarding the safety of LAA occlusion in the absence of even temporary anticoagulation are limited. The aim of this study was to determine the safety of percutaneous LAA occlusion with the Amplatzer Cardiac Plug (ACP, St. Jude Medical, Minneapolis, MN) followed by antiplatelet therapy only (without anticoagulation). METHODS
797
anticoagulant and antiplatelet therapy), determination of risk scores (CHADS2 [13], CHA2DS2-VASc [14], HAS-BLED [15]), physical examination, and EKG. Echocardiographic assessment was performed via transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) to determine technical suitability. Patients with pericardial effusion, intracardiac thrombus or with LAA sizes and anatomy that did not allow safe device implantation were excluded. TTE and EKG were repeated prior to discharge. Physical examination, EKG and TEE evaluation were repeated at 1-, 6-, and 12-month follow-up by the implantation site or referring cardiologist. The TEE focus was the detection of device- or procedure-related adverse events (AE, e.g. remaining atrial septal defects after transseptal puncture or pericardial effusion), device position and residual flow around the device. A peri-device leak of 5 mm was considered relevant because in the only published randomized controlled trial to date, at this leak magnitude, anticoagulation with warfarin was continued. Subsequently, clinical follow-up was performed according to the patients’ wishes, by the implanting site, the referring cardiologist or by telephone and/ or mail.
Study Design Between January 2009 and December 2012, all consecutive patients with nonvalvular AF and a CHA2DS2VASc-score of at least 1 who were not eligible for oral anticoagulation with VKA and underwent ACP implantation were analyzed retrospectively and included in this study. This includes patients with contraindications as defined in the warfarin product label, a history of severe bleeding while receiving anticoagulant therapy as well as a history of bleeding tendencies in the absence of anticoagulation or blood dyscrasia. Patients who were unable to maintain a stable INR and those with a known hypersensitivity to warfarin or a high-risk of falling were also included. Patients who requested elective LAA closure despite an absence of contraindications to anticoagulation were not enrolled in this study.
Major AE We differentiated five categories of AE: procedurerelated, cardiovascular, noncardiovascular, bleeding, and cerebral ischemia [stroke/Transient ischemic attack (TIA)]. Major AE included events that were fatal, lifethreatening, needed hospitalization, or prolongation of current hospitalization or led to considerable disability. Of note, bleeding complications were considered major if transfusion and/or hospitalization were required or if an ongoing hospitalization was prolonged.
Device Descriptions and Procedure
Statistical Analysis
The ACP (AGA Medical, Minneapolis, MN), a catheter-based self-expanding device, was implanted in all patients. The device itself and the implantation procedure have previously been described in detail [11,12].
Categorical variables were presented in counts and percentages, whereas continuous variables were presented as the mean with standard deviation (SD) and interquartile range. To compare categorical variables the Chi-Square or the Fisher’s exact test was used, whereas for continuous variables the Mann-WhitneyWilcoxon U test was applied. A P-value < 0.05 was considered as statistically significant.
Medical Treatment During implantation, heparin was administered with a goal activated clotting time of at least 200 sec. After the procedure, patients were instructed to take life-long daily acetyl salicylic acid (100 mg) in addition to 3 months of clopidogrel (75 mg). Baseline and Follow-Up Assessments Baseline evaluation included assessment of patients’ medical history and current medication (focusing on
Ethics The study was performed in adherence with the guidelines of the Declaration of Helsinki. Risks, benefits, and alternatives were discussed in detail with the patient and written consent was obtained prior to the procedure.
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
798
Wiebe et al.
TABLE I. Baseline Characteristics N Age (mean years 6 SD) CHADS2 (mean score 6 SD) CHA2DS2-VASc (mean score 6 SD) Congestive heart failure (%, n/N) Hypertension (%, n/N) Age 65–74 years (%, n/N) Age 75 years (%, n/N) Diabetes (%, n/N) History of stroke/ TIAa (%, n/N) Vascular disease (%, n/N) Female gender (%, n/N) HAS-BLED (mean score 6 SD) Abnormal renal function (%, n/N) Abnormal liver function (%, n/N) History of bleeding (%, n/N) Labile INRb (%, n/N) Age 65 years (%, n/N) Antiplatelet therapy (%, n/N) Alcohol abuse (%, n/N) a
TABLE II.
Contraindications
60
31.7 95.0 48.3 38.3 26.7 33.3 49.2 38.3 16.7 10.0 81.7 5.0 86.7 15.0 3.3
72.9 6 8.1 2.6 6 1.4 4.3 6 1.7 (19/60) (57/60) (29/60) (23/60) (16/60) (20/60) (29/60) (23/60) 3.3 6 1.0 (10/60) (6/60) (49/60) (3/60) (52/60) (9/60) (2/60)
TIA: transient ischemic attack. INR: international normalized ratio.
b
RESULTS
A total of 60 patients were included in this study. Mean age at the time of enrollment was 72.9 years (6 8.1), 38.3% were female. All patients suffered from non-valvular AF (23.3% paroxysmal, 22.8% persistent, and 34.7% permanent). Mean CHADS2-, CHA2DS2VASc-, and HAS-BLED-scores were 2.6 (6 1.4), 4.3 (6 1.7), and 3.3 (6 1.0), respectively. The frequencies of individual risk factors are listed in Table I. Eightyfive percent of patients had one, 13.3% two and 1.7% three contraindications to warfarin. A significant bleeding history in the absence of, or while taking oral anticoagulation, was reported in 25.0 and 63.3%, respectively. Gastrointestinal and intracranial hemorrhages were the most common bleeding locations. A total of 14.3% of all patients who experienced a bleeding complication had required transfusions. In 36.7% other contraindications to Warfarin were present (Table II). The implantation was successful in 95.0 % (Table III). In three cases, implantation was not possible due to unsuitable LAA anatomy. Two of these patients remained on Warfarin and 1 patient continued dual antiplatelet therapy. There was no evidence of a significant residual flow 5 mm at implantation or followup. A residual leak
