ASAIO Journal 2016
Adult Circulatory Support
Arrhythmias in Patients with Cardiac Implantable Electrical Devices after Implantation of a Left Ventricular Assist Device Andrew N. Rosenbaum,* Walter K. Kremers,† Sue Duval,‡ Scott Sakaguchi,§ Ranjit John,¶ and Peter M. Eckman║
Utilization of continuous-flow left ventricular assist devices (CF-LVADs) for advanced heart failure is increasing, and the role of cardiac implantable electrical devices (CIED) is unclear. Prior studies of the incidence of arrhythmias and shocks are frequently limited by ascertainment. One hundred and seventy-eight patients were examined with a previous CIED who were implanted with a CF-LVAD. Medical history, medications, and CIED data from device interrogations were gathered. A cardiac surgery control group (n = 38) was obtained to control for surgical factors. Several clinically significant events increased after LVAD implantation: treatedzone ventricular arrhythmias (VA; p < 0.01), monitored-zone VA (p < 0.01), antitachycardia pacing (ATP)-terminated episodes (p < 0.01), and shocks (p = 0.01), although administered shocks later decreased (p < 0.01). Presence of a preimplant VA was associated with postoperative VA (odds ratio [OR]: 4.31; confidence interval [CI]: 1.5–12.3, p < 0.01). Relative to cardiac surgery, LVAD patients experienced more perioperative events (i.e., monitored VAs and shocks, p < 0.01 and p = 0.04). Neither implantable cardioverter defibrillator (ICD) shocks before implant nor early or late postimplant arrhythmias or shocks predicted survival (p = 0.07, p = 0.55, and p = 0.55). Our experience demonstrates time-dependent effects on clinically significant arrhythmias after LVAD implantation, including evidence that early LVAD-related arrhythmias may be caused by the unique arrhythmogenic effects of VAD implant. ASAIO Journal 2016; 62:274–280.
patients undergoing implantation of a CF-LVAD have a cardiac implantable electrical device (CIED: pacemaker, implantable cardioverter defibrillator [ICD] or cardiac resynchronization therapy device with or without defibrillation [CRT-D or CRTP, respectively]) before implant, often performed as primary or secondary prophylaxis for life-threatening arrhythmia as a result of pivotal studies.2–4 However, once implantation of an LVAD proceeds, the incidence of ventricular arrhythmias (VAs) is typically higher than baseline rates or remains elevated.5–8 Evidence of increased incidence of arrhythmias has prompted consideration of prophylactic implantation of an ICD in this population,9,10 although other studies suggest that ICDs may not impart a survival advantage.11 Despite the high prevalence of this dual device therapy, concerns about negative interactions between the two devices persist. Electrical interference was considered a theoretical risk;12 however, utilization of a CIED in LVAD patients has not revealed a significant effect.13 There are changes in lead parameters, such as changes in lead sensing and capture,14 lead impedance, and amplitude12 after LVAD implantation that may affect performance of the CIED device.14 The long-term incidence of clinically significant arrhythmias has not been fully investigated. Studies have rarely used CIED data to comprehensively analyze arrhythmia events. Furthermore, the trends in these arrhythmias over time have not been investigated with device-level data in conjunction with longterm changes in electrical parameters and medication usage, which could serve to increase the cumulative understanding of electrical changes in the myocardium, prompting changes in medical management and questions of prophylactic ICD placement. Our purpose was to thoroughly investigate the changes in electrical parameters and arrhythmias over time after implantation of a LVAD in patients with CIED, specifically ICD or CRTD, using device-level data. We also sought to compare early arrhythmias to a control set of cardiac surgery patients to determine unique LVAD implantation-related factors, such as ventriculotomy, may be related to arrhythmic events.
Key words: LVAD, CIED, Ventricular arrhythmias, Mortality.
There
has been increasing use of continuous-flow left ventricular assist devices (CF-LVAD) as data have shown improved survival compared with earlier devices.1 Many From the *Department of Medicine, †Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota; ‡Lillehei Clinical Research Unit, Cardiovascular Division, University of Minnesota Medical School, Minneapolis, Minnesota; §Cardiovascular Division, Department of Medicine, ¶Division of Cardiothoracic Surgery, Department of Surgery, University of Minnesota, Minneapolis, Minnesota; and ║Minneapolis Heart Institute, Minneapolis, Minnesota. Submitted for consideration October 2015; accepted for publication in revised form January 2016. P.M.E. has received prior grant support (Thoratec, Heartware), consulting and honoraria (Thoratec and Heartware). Disclosure: P.M.E. has received honoraria and research funding from St. Jude Medical (Thoratec) and from HeartWare. All other authors have no conflicts of interest to report. Correspondence: Andrew N. Rosenbaum, Mayo Clinic Rochester, 200 1st St. SW, Rochester, MN 55905. Email: Rosenbaum.Andrew@ mayo.edu.PI: Peter M. Eckman. Email: [email protected]. Copyright © 2016 by the American Society for Artificial Internal Organs
Methods We conducted a retrospective review of 178 consecutive patients who had a previous CIED (Boston Scientific/Guidant [Boston Scientific Corporation, Marlborough, MA]; Medtronic [Medtronic plc, Dublin, Ireland]; or St. Jude [St. Jude Medical, Inc., St. Paul, MN]) in place and were implanted with a continuous-flow LVAD (Heartmate II [Thoratec Corp, Pleasanton, CA]; Ventrassist [Ventracor Ltd., Sydney, Australia]; or HeartWare [HeartWare International, Inc., Framingham, MA]) from November 2005 to April of 2010 at a single institution. All CIEDs in this study were ICD or CRT-D. A list of all mechanical circulatory support patients is kept for administrative purposes and all patients in the database have consented to utilization
DOI: 10.1097/MAT.0000000000000349
274
Copyright © American Society of Artificial Internal Organs. Unauthorized reproduction of this article is prohibited.
275
ARRHYTHMIAS FOLLOWING LVAD IMPLANT
of their medical data for research purposes. The Institutional Review Board at the University of Minnesota approved the current study. Data Collection Data were gathered from the electronic and paper medical records and primary CIED interrogation records. Baseline characteristics were obtained, including device type, etiology of heart failure and pertinent electrophysiological, clinical data, such as history of atrial fibrillation, ablations, and ventricular ablations. Preoperative medication data were obtained, including standard heart failure medications, inotropes, and antiarrhythmic medications. CIED device data included indication for implant; history of ICD shocks; brand and model of CIED (all CRT devices were CRT-D); lead impedance, amplitude, pulse width and sensitivity; mode; and episodes or events. Atrial events were derived from device-level data, including supraventricular tachycardia episodes and time in atrial fibrillation. Two types of VAs were identified: monitored VA episodes, defined as slow ventricular tachycardia and nonsustained ventricular tachycardia within the “monitor” zone (without programmed therapies based on device-level programming), and treated VA episodes, defined as ventricular fibrillation or ventricular tachycardia within the “treat” zone, which received therapies. Therapies for treated episodes included multiple options for ATP or shocks, with some devices including an option for ATP during initial capacitor charge. All decisions regarding programming thresholds were left to the discretion of individual clinicians. Baseline rates of arrhythmias were derived from interrogations within 1 year before LVAD implant. Preimplant and postimplant 12 lead EKG interval data were obtained. Postimplant medications at discharge, CIED lead data, including impedance, programmed amplitude and pulse width, and sensitivity were obtained. Postimplant medications were medications given at the time of discharge from the implantation hospitalization. All LVADs were functioning properly at the time of discharge as well. Monitored and treated episodes in the first 30 days postimplant were extracted from CIED-level data and episodes over the subsequent 150 days were compared (days 30–180 postimplant). Control Subjects A cohort of 38 patients with a CIED in place who underwent any cardiac surgery via sternotomy were obtained for comparison to the LVAD cohort. These patients were gathered to control for surgical factors related to cardiac surgery as they relate to arrhythmias in the postoperative setting. Surgeries included any combination of valve replacement (mitral: 34%, aortic: 34%), coronary artery bypass grafting (34%), MAZE (8%), and pericardiectomy/pericardial window (5%), and none of the control surgeries included ventriculotomy. All the baseline data and postsurgical data were obtained in a similar fashion to the LVAD patients. Data Analysis Characteristics between groups were compared using the t test or Fisher’s exact test as appropriate. Matched data were
compared with a matched pair t test for continuous data or McNemar’s test for binomial data as appropriate. Postsurgical quantitative variables, e.g., monthly-adjusted arrhythmias, were compared between the surgical groups using analysis of covariance (ANCOVA) including the baseline value as a covariate. For treated ventricular episode and event data, values used in the analysis were capped at 10, i.e., values greater than 10 were replaced by 10, to reduce the influence of outliers. Odds ratios (ORs) were used to assess risk factors for VAs. Survival analysis was conducted using log-rank tests between Kaplan–Meier curves. For survival analysis involving postsurgery assessments, landmark analysis was conducted to avoid immortality bias.15 Distribution of survival times were assessed and landmark time was determined to be 28 days or 6 months, depending on the predictor. All data were analyzed using JMP 10 Pro (SAS Institute Inc., Cary, NC). Results Baseline characteristics are described in Table 1. Baseline characteristics for LVAD patients (n = 178) include a mean (± SD) age of 57 ± 14 years, 81% male, 58% with an ischemic etiology of heart failure. Thirty-seven percent of LVAD patients had a history of atrial fibrillation. Six percent of the LVAD patients had a history of ventricular tachycardia ablation. The distribution of CIED devices was 44% ICD and 56% CRT. Left ventricular assist device patients were followed for a median of 14.4 months (IQR: 6.5, 26.8). 8.5% of patients were lost to follow-up during the study period. There were no major LVAD malfunctions during the follow-up period (pump thrombosis or need for exchange). Medications Medications before and after LVAD implant are also presented in Table 1. Beta-blocker usage decreased from 76% preimplant to 27% at discharge on LVAD therapy (p < 0.01). ACE inhibitor or angiotensin receptor blocker (ACEi/ARB) usage decreased as well from 69% preimplant to 26% at discharge on LVAD therapy (p < 0.01). Aldosterone antagonist usage decreased from 33% to 6% (p < 0.01). Oral potassium supplementation increased after LVAD placement with 63% discharged with oral potassium replacement compared with 34% preimplant (p < 0.01). Amiodarone use increased significantly after implant from 30% to 47% (p < 0.01), while decreasing in the control group (p < 0.01). Milrinone and dobutamine were typically stopped. Sotalol use decreased from 4% to 2% (p = 0.25), whereas dofetilide was rarely used and mexiletine use did not change (4% to 5%, p = 0.71). Electrocardiographic and CIED Data Trends in electrocardiographic data are shown in Table 2. At a median follow-up time of 30 days postimplant (IQR: 14, 110), QRS duration decreased significantly (149 to 128 ms, p < 0.01). QT interval decreased significantly (449 to 412 ms, p < 0.01) and heart rate increased from 83 to 98 bpm (p < 0.01) such that QTc did not change significantly (520 to 522, p = 0.85). QTc changes were independent of amiodarone use (p = 0.15). Cardiac implantable electrical device parameters were notable for decreases in most mean lead impedances: RA (491 to 463 Ω, p = 0.01), RV (460 to 451 Ω, p = 0.27), LV (551 to 505 Ω, p < 0.01), and HV (42 to 38 Ω, p < 0.01). In comparison, no significant changes in lead
Copyright © American Society of Artificial Internal Organs. Unauthorized reproduction of this article is prohibited.
276 ROSENBAUM et al. Table 1. Baseline Characteristics for LVAD and Cardiac Surgery Patients
Baseline Characteristic Age (mean ± SD) Sex (male) HF etiology (ischemic) Medical history AF AF ablation VT ablation Medications BB ACEi/ARB Furosemide-equivalent diuretic dose (mg) Aldosterone antagonist Oral potassium Milrinone Dobutamine Amiodarone/codarone Sotalol Dofetilide Mexiletine ICD CRT
Cardiac Surgery control subjects p Value for (n = 38) Change Preop
Cardiac Surgery p Value control subjects (LVAD vs. (n = 38) p Value for control subjects, Postop Change Preop)
LVAD Patients (n = 178) Preimplant
LVAD Patients (n = 167) Postimplant
57 ± 14 81% 58%
-
-
60 ± 13 66% N/A
-
-
0.18 0.08 N/A
37% 12% 6%
-
-
53% 21% 8%
-
-
0.08 0.11 0.57
76% 69% 99 ± 101
27% 26% 60 ± 90
Adult Circulatory Support
Arrhythmias in Patients with Cardiac Implantable Electrical Devices after Implantation of a Left Ventricular Assist Device Andrew N. Rosenbaum,* Walter K. Kremers,† Sue Duval,‡ Scott Sakaguchi,§ Ranjit John,¶ and Peter M. Eckman║
Utilization of continuous-flow left ventricular assist devices (CF-LVADs) for advanced heart failure is increasing, and the role of cardiac implantable electrical devices (CIED) is unclear. Prior studies of the incidence of arrhythmias and shocks are frequently limited by ascertainment. One hundred and seventy-eight patients were examined with a previous CIED who were implanted with a CF-LVAD. Medical history, medications, and CIED data from device interrogations were gathered. A cardiac surgery control group (n = 38) was obtained to control for surgical factors. Several clinically significant events increased after LVAD implantation: treatedzone ventricular arrhythmias (VA; p < 0.01), monitored-zone VA (p < 0.01), antitachycardia pacing (ATP)-terminated episodes (p < 0.01), and shocks (p = 0.01), although administered shocks later decreased (p < 0.01). Presence of a preimplant VA was associated with postoperative VA (odds ratio [OR]: 4.31; confidence interval [CI]: 1.5–12.3, p < 0.01). Relative to cardiac surgery, LVAD patients experienced more perioperative events (i.e., monitored VAs and shocks, p < 0.01 and p = 0.04). Neither implantable cardioverter defibrillator (ICD) shocks before implant nor early or late postimplant arrhythmias or shocks predicted survival (p = 0.07, p = 0.55, and p = 0.55). Our experience demonstrates time-dependent effects on clinically significant arrhythmias after LVAD implantation, including evidence that early LVAD-related arrhythmias may be caused by the unique arrhythmogenic effects of VAD implant. ASAIO Journal 2016; 62:274–280.
patients undergoing implantation of a CF-LVAD have a cardiac implantable electrical device (CIED: pacemaker, implantable cardioverter defibrillator [ICD] or cardiac resynchronization therapy device with or without defibrillation [CRT-D or CRTP, respectively]) before implant, often performed as primary or secondary prophylaxis for life-threatening arrhythmia as a result of pivotal studies.2–4 However, once implantation of an LVAD proceeds, the incidence of ventricular arrhythmias (VAs) is typically higher than baseline rates or remains elevated.5–8 Evidence of increased incidence of arrhythmias has prompted consideration of prophylactic implantation of an ICD in this population,9,10 although other studies suggest that ICDs may not impart a survival advantage.11 Despite the high prevalence of this dual device therapy, concerns about negative interactions between the two devices persist. Electrical interference was considered a theoretical risk;12 however, utilization of a CIED in LVAD patients has not revealed a significant effect.13 There are changes in lead parameters, such as changes in lead sensing and capture,14 lead impedance, and amplitude12 after LVAD implantation that may affect performance of the CIED device.14 The long-term incidence of clinically significant arrhythmias has not been fully investigated. Studies have rarely used CIED data to comprehensively analyze arrhythmia events. Furthermore, the trends in these arrhythmias over time have not been investigated with device-level data in conjunction with longterm changes in electrical parameters and medication usage, which could serve to increase the cumulative understanding of electrical changes in the myocardium, prompting changes in medical management and questions of prophylactic ICD placement. Our purpose was to thoroughly investigate the changes in electrical parameters and arrhythmias over time after implantation of a LVAD in patients with CIED, specifically ICD or CRTD, using device-level data. We also sought to compare early arrhythmias to a control set of cardiac surgery patients to determine unique LVAD implantation-related factors, such as ventriculotomy, may be related to arrhythmic events.
Key words: LVAD, CIED, Ventricular arrhythmias, Mortality.
There
has been increasing use of continuous-flow left ventricular assist devices (CF-LVAD) as data have shown improved survival compared with earlier devices.1 Many From the *Department of Medicine, †Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota; ‡Lillehei Clinical Research Unit, Cardiovascular Division, University of Minnesota Medical School, Minneapolis, Minnesota; §Cardiovascular Division, Department of Medicine, ¶Division of Cardiothoracic Surgery, Department of Surgery, University of Minnesota, Minneapolis, Minnesota; and ║Minneapolis Heart Institute, Minneapolis, Minnesota. Submitted for consideration October 2015; accepted for publication in revised form January 2016. P.M.E. has received prior grant support (Thoratec, Heartware), consulting and honoraria (Thoratec and Heartware). Disclosure: P.M.E. has received honoraria and research funding from St. Jude Medical (Thoratec) and from HeartWare. All other authors have no conflicts of interest to report. Correspondence: Andrew N. Rosenbaum, Mayo Clinic Rochester, 200 1st St. SW, Rochester, MN 55905. Email: Rosenbaum.Andrew@ mayo.edu.PI: Peter M. Eckman. Email: [email protected]. Copyright © 2016 by the American Society for Artificial Internal Organs
Methods We conducted a retrospective review of 178 consecutive patients who had a previous CIED (Boston Scientific/Guidant [Boston Scientific Corporation, Marlborough, MA]; Medtronic [Medtronic plc, Dublin, Ireland]; or St. Jude [St. Jude Medical, Inc., St. Paul, MN]) in place and were implanted with a continuous-flow LVAD (Heartmate II [Thoratec Corp, Pleasanton, CA]; Ventrassist [Ventracor Ltd., Sydney, Australia]; or HeartWare [HeartWare International, Inc., Framingham, MA]) from November 2005 to April of 2010 at a single institution. All CIEDs in this study were ICD or CRT-D. A list of all mechanical circulatory support patients is kept for administrative purposes and all patients in the database have consented to utilization
DOI: 10.1097/MAT.0000000000000349
274
Copyright © American Society of Artificial Internal Organs. Unauthorized reproduction of this article is prohibited.
275
ARRHYTHMIAS FOLLOWING LVAD IMPLANT
of their medical data for research purposes. The Institutional Review Board at the University of Minnesota approved the current study. Data Collection Data were gathered from the electronic and paper medical records and primary CIED interrogation records. Baseline characteristics were obtained, including device type, etiology of heart failure and pertinent electrophysiological, clinical data, such as history of atrial fibrillation, ablations, and ventricular ablations. Preoperative medication data were obtained, including standard heart failure medications, inotropes, and antiarrhythmic medications. CIED device data included indication for implant; history of ICD shocks; brand and model of CIED (all CRT devices were CRT-D); lead impedance, amplitude, pulse width and sensitivity; mode; and episodes or events. Atrial events were derived from device-level data, including supraventricular tachycardia episodes and time in atrial fibrillation. Two types of VAs were identified: monitored VA episodes, defined as slow ventricular tachycardia and nonsustained ventricular tachycardia within the “monitor” zone (without programmed therapies based on device-level programming), and treated VA episodes, defined as ventricular fibrillation or ventricular tachycardia within the “treat” zone, which received therapies. Therapies for treated episodes included multiple options for ATP or shocks, with some devices including an option for ATP during initial capacitor charge. All decisions regarding programming thresholds were left to the discretion of individual clinicians. Baseline rates of arrhythmias were derived from interrogations within 1 year before LVAD implant. Preimplant and postimplant 12 lead EKG interval data were obtained. Postimplant medications at discharge, CIED lead data, including impedance, programmed amplitude and pulse width, and sensitivity were obtained. Postimplant medications were medications given at the time of discharge from the implantation hospitalization. All LVADs were functioning properly at the time of discharge as well. Monitored and treated episodes in the first 30 days postimplant were extracted from CIED-level data and episodes over the subsequent 150 days were compared (days 30–180 postimplant). Control Subjects A cohort of 38 patients with a CIED in place who underwent any cardiac surgery via sternotomy were obtained for comparison to the LVAD cohort. These patients were gathered to control for surgical factors related to cardiac surgery as they relate to arrhythmias in the postoperative setting. Surgeries included any combination of valve replacement (mitral: 34%, aortic: 34%), coronary artery bypass grafting (34%), MAZE (8%), and pericardiectomy/pericardial window (5%), and none of the control surgeries included ventriculotomy. All the baseline data and postsurgical data were obtained in a similar fashion to the LVAD patients. Data Analysis Characteristics between groups were compared using the t test or Fisher’s exact test as appropriate. Matched data were
compared with a matched pair t test for continuous data or McNemar’s test for binomial data as appropriate. Postsurgical quantitative variables, e.g., monthly-adjusted arrhythmias, were compared between the surgical groups using analysis of covariance (ANCOVA) including the baseline value as a covariate. For treated ventricular episode and event data, values used in the analysis were capped at 10, i.e., values greater than 10 were replaced by 10, to reduce the influence of outliers. Odds ratios (ORs) were used to assess risk factors for VAs. Survival analysis was conducted using log-rank tests between Kaplan–Meier curves. For survival analysis involving postsurgery assessments, landmark analysis was conducted to avoid immortality bias.15 Distribution of survival times were assessed and landmark time was determined to be 28 days or 6 months, depending on the predictor. All data were analyzed using JMP 10 Pro (SAS Institute Inc., Cary, NC). Results Baseline characteristics are described in Table 1. Baseline characteristics for LVAD patients (n = 178) include a mean (± SD) age of 57 ± 14 years, 81% male, 58% with an ischemic etiology of heart failure. Thirty-seven percent of LVAD patients had a history of atrial fibrillation. Six percent of the LVAD patients had a history of ventricular tachycardia ablation. The distribution of CIED devices was 44% ICD and 56% CRT. Left ventricular assist device patients were followed for a median of 14.4 months (IQR: 6.5, 26.8). 8.5% of patients were lost to follow-up during the study period. There were no major LVAD malfunctions during the follow-up period (pump thrombosis or need for exchange). Medications Medications before and after LVAD implant are also presented in Table 1. Beta-blocker usage decreased from 76% preimplant to 27% at discharge on LVAD therapy (p < 0.01). ACE inhibitor or angiotensin receptor blocker (ACEi/ARB) usage decreased as well from 69% preimplant to 26% at discharge on LVAD therapy (p < 0.01). Aldosterone antagonist usage decreased from 33% to 6% (p < 0.01). Oral potassium supplementation increased after LVAD placement with 63% discharged with oral potassium replacement compared with 34% preimplant (p < 0.01). Amiodarone use increased significantly after implant from 30% to 47% (p < 0.01), while decreasing in the control group (p < 0.01). Milrinone and dobutamine were typically stopped. Sotalol use decreased from 4% to 2% (p = 0.25), whereas dofetilide was rarely used and mexiletine use did not change (4% to 5%, p = 0.71). Electrocardiographic and CIED Data Trends in electrocardiographic data are shown in Table 2. At a median follow-up time of 30 days postimplant (IQR: 14, 110), QRS duration decreased significantly (149 to 128 ms, p < 0.01). QT interval decreased significantly (449 to 412 ms, p < 0.01) and heart rate increased from 83 to 98 bpm (p < 0.01) such that QTc did not change significantly (520 to 522, p = 0.85). QTc changes were independent of amiodarone use (p = 0.15). Cardiac implantable electrical device parameters were notable for decreases in most mean lead impedances: RA (491 to 463 Ω, p = 0.01), RV (460 to 451 Ω, p = 0.27), LV (551 to 505 Ω, p < 0.01), and HV (42 to 38 Ω, p < 0.01). In comparison, no significant changes in lead
Copyright © American Society of Artificial Internal Organs. Unauthorized reproduction of this article is prohibited.
276 ROSENBAUM et al. Table 1. Baseline Characteristics for LVAD and Cardiac Surgery Patients
Baseline Characteristic Age (mean ± SD) Sex (male) HF etiology (ischemic) Medical history AF AF ablation VT ablation Medications BB ACEi/ARB Furosemide-equivalent diuretic dose (mg) Aldosterone antagonist Oral potassium Milrinone Dobutamine Amiodarone/codarone Sotalol Dofetilide Mexiletine ICD CRT
Cardiac Surgery control subjects p Value for (n = 38) Change Preop
Cardiac Surgery p Value control subjects (LVAD vs. (n = 38) p Value for control subjects, Postop Change Preop)
LVAD Patients (n = 178) Preimplant
LVAD Patients (n = 167) Postimplant
57 ± 14 81% 58%
-
-
60 ± 13 66% N/A
-
-
0.18 0.08 N/A
37% 12% 6%
-
-
53% 21% 8%
-
-
0.08 0.11 0.57
76% 69% 99 ± 101
27% 26% 60 ± 90
