New trends in ICD implantation offer additional options as well as potential challenges for ICD implanters. In this article, the author discusses the benefits of these new technologies, including improved patient outcomes and the potential for simpler and safer procedures.
BackgroundIn February 2010, a 62-year-old female patient complained to her doctor of shortness of breath with routine activities. BNP was elevated at 736 and an echocardiogram demonstrated systolic dysfunction with an ejection fraction (EF) of ~25%. Nuclear scan showed no ischemia or infarction and confirmed the depressed EF. ECG showed left bundle branch block (LBBB) with a QRS duration of 142 msec, and Holter monitoring showed infrequent PVCs with a heart rate from 49 to 133. Three months after appropriate therapy with an ACE inhibitor, beta blocker, and diuretic, the patient was improved but still had symptoms with moderate exertion consistent with NYHA Class II status. Echocardiogram showed persistently depressed EF now estimated at 30%. Based on the failure of improvement in left ventricular (LV) systolic function, the patient was then referred for consideration of an ICD based on indications from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT).1 Device options for this patient in June 2010 were for a single or dual chamber intravenous device, as cardiac resynchronization therapy (CRT) was approved only for patients with class III or IV heart failure despite optimal medical therapy. While in the NCDR® ICD Registry™ only about 20% of devices are single chamber,2 in the absence of an indication for pacing or recurrent atrial arrhythmias, a single chamber ICD was implanted. In September 2010, based on the results of the MADIT-CRT study,3 the FDA expanded indications for CRT devices to include selected class I and II congestive heart failure (CHF) patients, such as the patient described. Additionally, a new device that is entirely subcutaneous and includes no intracardiac hardware is under investigation at multiple centers in the United States. Had these two new options been available, they might have changed the surgical approach in this patient. The implication of these expanded ICD options merits review and understanding.
Expanded Indications for CRTThe COMPANION Trial4 in 2004 demonstrated the benefits of CRT pacing in patients with an EF 120 msec, and symptomatic class III or IV CHF. Subsequent FDA approval of this therapy adhered to these pre-implant parameters, and thus, CRT therapy was limited to patients with highly symptomatic CHF. The MADIT-CRT was a multicenter randomized study enrolling patients from the US, Canada and Europe to explore the potential benefits of CRT in optimally medically managed, but less symptomatic patients earlier in the course of CHF, who otherwise met criteria for an ICD. Sponsored by Boston Scientific, the study enrolled a total of 1,820 adults >21 years of age with class I or II CHF due to either an ischemic or non-ischemic etiology (Table 1). The class I and II ischemic cardiomyopathy patients qualified for an ICD based on MADIT II criteria (previous MI >40 days, revascularization >3 months, and EF 5 Patients with non-ischemic cardiomyopathy and class II CHF qualifying for an ICD based on the SCD-HeFT trial criteria were also enrolled,1 except consistent with the ischemic patients, the enrollment EF criteria was lowered from 35% to 30%. The QRS duration was also increased to 130 msec from the 120 msec used in the COMPANION trial. Patients were randomized in a 3:2 fashion to a CRT device or a conventional ICD and followed to a combined endpoint of reduction in mortality or occurrence of a non-fatal heart failure event, whichever came first. The data was monitored continuously by an independent data and safety monitoring board that stopped the study in July 2009 after the results crossed the boundary for superiority of CRT therapy. After an average follow up of 2.4 years, the endpoint occurred about one-third less frequently in the CRT patients than in those with a conventional ICD (17.2% vs. 25.3%: p = 0.001).3 The difference in endpoint was caused exclusively by a 41% reduction in heart failure events as the mortality in each group (~3%) was similar. There was no difference in the benefit of CRT therapy based on etiology of heart failure, age, ejection fraction, or ventricular volumes. Both genders responded favorably to CRT, but females seemed to have a greater benefit than males. QRS duration of 150 msec also divided responders from nonresponders with benefit seen only in the longer QRS duration group. After a further 6 months of analysis, there was a 57% decrease in the combined endpoint amongst the subgroup of patients with LBBB who received CRT.6 There was a 35% relative risk reduction in all-cause mortality and a 63% risk reduction in first heart failure events in this subpopulation. The ejection fraction was increased by 12% vs. 3% for the non-CRT group, and end-diastolic and systolic volumes decreased by 57 and 62% vs. 15 and 19%. Based on this data, the FDA expanded indications for the use of ICDs with CRT pacing to patients with ischemic class I or II CHF, and non-ischemic class II CHF who have an ejection fraction 130 msec. The benefit of CRT therapy, however, comes at a cost, both economic and otherwise. The CRT patients had about a 50% higher complication rate including infection, pneumothorax, and hematoma requiring evacuation in the first 30 days compared to the conventional ICD patients (6.1% vs. 4.1%). Additionally, coronary venous dissection with pericardial effusion (5 patients) and coronary sinus lead dislodgement resulting in repositioning (44 patients) occurred in an additional 4.5%. This increase in adverse events was also seen in the recently published RAFT study.7 While the decrease in heart failure events will be cost saving, they will be partially offset by the increased cost of these adverse events and the CRT system itself. Additionally, CRT systems have shortened longevity due to the near 100% pacing with earlier need for replacement. Therefore, the exciting benefits offered by the utilization of this technology will have to be assessed against the real world cost. Studies like MADIT-CRT are conducted with clearly defined inclusion and exclusion criteria using rigorous monitoring and are typically performed at high volume implant centers with significant clinical expertise. Questions of how the results of these trials translate to the real world formed the basis for CMS mandating a national ICD registry when it expanded coverage to include the MADIT II and SCD-HeFT indications. Going forward, Boston Scientific is working with the ACC National Cardiovascular Data Registry (ACC-NCDR™) to develop a protocol to leverage the expertise and the rich data set of the ICD Registry to track the outcome of MADIT-CRT type patients implanted with Boston Scientific devices. This will extend the evaluation of CRT in mild heart failure to a broader population of patients and centers over a longer follow-up duration.
Subcutaneous ICDsIn contrast to this extension of existing but complex technology into a broader patient population, a new and potentially simpler technology is being investigated as another alternative for these patients. Implantable ICD systems use intravascular leads to deliver the energy for pacing and defibrillation and sense signals of cardiac origin to trigger therapy. Placement issues, stability, survivability, and the electrical demands make leads structurally complex and challenging to manufacture. Unfortunately, placement can be complicated by pneumothorax, vascular occlusion, cardiac perforation or mechanical arrhythmias. Leads can also fail over time, resulting in loss of appropriate device function. Non-infected but failed intravascular hardware can be abandoned with little upfront risk. However, the presence of preexisting leads may compromise vascular access and limit options if additional leads are required for upgrades or new lead failures. Old leads can be removed, but there are real and potentially mortal risks of vascular or cardiac injury, especially as the longevity of the failed hardware increases. For these reasons, leads are often viewed as the weak link in these systems.8 As a potential solution to these issues, an entirely subcutaneous defibrillator system (S-ICD® System, Cameron Health, Inc., San Clemente, CA) with no intravascular hardware has been developed and tested. Initial temporary testing demonstrated a parasternal subcutaneous lead coupled to a lateral thoracic ICD pulse generator had the best defibrillation energy and acceptable sensing (Figure 1). Compared to a standard system, the defibrillation threshold is substantially higher with the S-ICD (32 vs. 11 joules) but within the safety margin of the 80-joule device.9 Initial permanent human implants in New Zealand confirmed acceptable arrhythmia detection and effective defibrillation with adequate safety margin (Figure 2). Further investigation in a larger population in New Zealand and Europe confirmed these initial findings8 and led to CE certification. Successful conversion of induced VF was accomplished in 98%, and after 10 months of follow up, all 12 spontaneous arrhythmias were detected and successfully terminated. Complications included infection in 2 and lead revision in 4. A larger, non-randomized open-label trial is ongoing in the US, New Zealand and Europe with the intent to enroll 330 patients and follow them for up to 5 years. Goals of the study are achievement of 180-day complication-free survival of >79% and >88% efficacy in terminating induced VF. The system consists of a tripolar electrode with sensing ring electrodes proximal and distal to an 8 cm length shocking coil. The lead is tunneled subcutaneously about 1 cm left lateral to the sternum stretching roughly from the manubrium to the inferior margin of the sixth rib and connected to an 80-joule, 69.9 cc ICD positioned at approximately the anterior axillary line. Implantation success requires appropriate sensing of induced VF and successful defibrillation twice with 65 joules. This simplified system eliminates intravascular hardware and the potential for lung, vascular, or cardiac injury. Future vascular or cardiac risks related to subsequent lead removal, if mandated by infection, lead failure or disease progression, are also avoided and vascular access is preserved if needed for CRT placement later. Because placement of the subcutaneous lead is done anatomically, fluoroscopic imaging is unnecessary, facilitating the procedure and enhancing its safety. Sensing is achieved over 1 of 3 available vectors between the electrodes and S-ICD, but due to the lack of intracardiac hardware, long-term pacing is not feasible. Brief, high-energy, post-shock pacing is available. This restricts implants to patients who do not require bradycardia pacing support. Patients with ventricular tachycardia that is easily and reproducibly terminated with painless anti-tachycardia pacing are also excluded from the current trial. The potential impact of this type of technology on the ICD market is not clear. In the NCDR® ICD Registry™, about 40% of ICDs presently implanted are CRT devices. The impact of MADIT-CRT discussed here will likely increase this percentage. Thus, perhaps 50% of patients in the future may be candidates for CRT devices. Of the remainder, if implant percentages remain roughly the same, about 15–20% will be single chamber implants. Some of these may require pacing for AF with a slow rate, and some of the dual chamber implants may not really need pacing rate support. Therefore, a potential market share in the 10–20% range seems plausible. If a totally subcutaneous device favorably alters patient and physician acceptance of this treatment option, the total volume of ICD implants might also grow.
ConclusionIn summary, the evolution of ICD implantation as evidenced by these two trends will offer additional options and potential challenges for ICD implanters. However, the benefits of improved patient outcome with CRT and the potential for simpler and safer procedures with the S-ICD suggest a growing role for these technologies in the future.
1. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005;352:225-237. 2. Hammill SC, Kremers MS, Stevenson LW, et al. Review of the registry’s fourth year, incorporating lead data and pediatric ICD procedures and use as a national performance measure. Heart Rhythm 2010;9:1340-1345. 3. Moss AJ, Hall WJ, Cannom DS, et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med 2009;361:1329-1338. 4. Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004;350:2140-2150. 5. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877-883. 6. The Multicenter Automatic Defibrillator Implantation Trial – Cardiac Resynchronization Therapy (MADIT-CRT). Accessed November 9, 2010. http://www.bostonscientific.com/cardiac-rhythm-resources/clinical/madit-crt-trial.html. 7. Tang AS, Wells GA, Talajic M, et al. Cardiac-resynchronization therapy for mild-to-moderate heart failure. N Engl J Med 2010 Nov 14. 8. Maisel WH. Transvenous implantable cardioverter-defibrillator leads: The weakest link. Circulation 2007;115:1461-1463. 9. Bardy GH, Smith WM, Hood MA, et al. An entirely subcutaneous implantable cardioverter-defibrillator. N Engl J Med 2010;363:36-44.