Rafi Sakhi

Currently, ICMs are used for continuous monitoring of the heart rhythm. Considering the remote monitoring capabilities, the diagnostic capabilities may expand to other fields. The most promising field is to remotely monitor patients with heart failure in order to detect early signs of worsening heart failure. The CHAMPION study has demonstrated that patients with NYHA III heart failure who are managed with remote monitoring using a wireless implantable hemodynamic monitoring system (CardioMEMS™, Abbott) have a reduction in heart-failure-related hospitalizations 32. The CardioMEMS™ system monitors the pulmonary artery pressure using a small pressure sensor which is permanently implanted in the distal pulmonary artery. It is also possible to use physiological trends for detecting early signs of worsening heart failure. The MultiSENSE study demonstrated that the HeartLogic™ diagnostic (Boston Scientific) can predict future heart failure events 33. HeartLogic™ uses multiple sensors in an ICD to track changes in heart sounds, intrathoracic impedance, respiration, heart rate and patient activity metrics. When the composite index crosses a certain threshold, the clinician is proactively alerted via remote monitoring. It is likely that heart failure diagnostics can be incorporated in an ICM providing the possibility to remotely monitor patients with heart failure who do not have an ICD. For example, the purpose of the currently ongoing LINQ HF study (Medtronic) is to assess the relationship between changes in LINQ derived data and other physiologic parameters with subsequent acute decompensated heart failure events (NCTO27S8PON). No results have been published yet. In conclusion, we expect that the availability of heart failure diagnostics will be an important milestone in the evolution of ICMs.

Part II –

In part II of this thesis we evaluated the suitability of different patient categories for a subcutaneous ICD (S-ICD). The current guidelines give a class IIa recommendation for an S-ICD as an alternative to a transvenous ICD if there is no need for pacing therapy, cardiac resynchronization therapy (CRT) or antitachycardia pacing (ATP). Furthermore, to prevent inappropriate shocks due to T-wave oversensing it is recommended that every candidate undergo vector screening to check if they qualify for an S-ICD. In Chapter 8 we evaluated the potential candidacy for an S-ICD at the time of first replacement in a cohort of patients with a transvenous single chamber ICD who did not need pacing at the time of implantation. At the time of first ICD replacement, 69% of patients was potentially suitable for an S-ICD. Thus, 31% needed either ATP, CRT and/or bradypacing during the first battery-lifetime. For individual end points, annual incidence rates were 4.9% appropriate ATP, 1.8% for CRT, and 0.3% for pacing-dependency. No baseline variables could predict which patient would potentially be suitable for an S-ICD.

If a patient is considered a candidate for an S-ICD (no need for pacing, ATP or CRT), then vector screening is performed to check if the patient has a suitable QRS-T morphology. Usually this was done manually using a manual ECG-screening tool and a vector electrocardiogram. Recently, an Automated Screening Tool (AST) became available, fully automating this process of vector screening. In Chapter 9 we prospectively evaluated the eligibility for a S-ICD using the two screening tools (manual vector screening versus AST) in different patient categories including patients with cardiomyopathy, congenital heart disease and inherited primary arrhythmia syndrome. There was a high vector eligibility using either method (93% versus 92%, P = 0.45). Furthermore, agreement between the two screening methods was 94%. Patients with hypertrophic cardiomyopathy more often had a failed screening test in comparison to other patients.

Previous studies have demonstrated that several standard 12-lead ECG characteristics are associated with the eligibility for a S-ICD based on manual vector screening 34-36. In Chapter 10, we investigated which 12-lead ECG characteristics were associated with eligibility for an S-ICD based on AST in a heterogenous population. We found that QRS ≤ 130 ms, absence of QRS/T discordance in lead II and R/T-ratio ≥3.5 in lead II were independently associated with S-ICD eligibility based on AST. Patients who fulfilled all three criteria (n=83, 33%) had a passing rate of 100%. Therefore, our results suggest that patients who fulfill the three 12-lead ECG criteria do not need additional vector screening for S-ICD eligibility.

Part II - Discussion

There are several advantages of an S-ICD in comparison to a transvenous ICD. These include the reduced risk of lead dysfunction, elimination of risk of endocarditis, lower procedural risk and relative ease of extraction. Disadvantages of an S-ICD are the inability to provide pacing (including ATP and CRT), larger pulse generator size, shorter battery longevity and requirement of a pre-implant ECG screening. Although the current guidelines recommend that an S-ICD should be considered as an alternative to a transvenous ICD 37, there is only a modest implementation of this technology in clinical practice. A physician may have the opinion that a patient without immediate need for pacing therapy or ATP may potentially require these therapies in the future, thereby opting for a transvenous ICD to be on the safe side.

We demonstrated that the majority (69%) of patients who have a transvenous single chamber ICD would have qualified for an S-ICD at the time of first replacement. The most important reason not to qualify for an S-ICD was the occurrence of ATP (4.9% per year). Interestingly, the risk of pacing dependency was low in this population (0.3% per year). Thus, based on our data we can conclude that the potential need for future pacing therapy is low in a standard ICD population who do not have a need for pacing therapy at implantation. With regard to the development of the need of CRT, it is important to realize that a de novo CRT-implantation is easier than an upgrade to CRT in a patient who have a transvenous ICD 38, 39.

If a patient is a potential candidate for a S-ICD, then a pre-implant vector screening is recommended by the manufacturer to avoid the risk of QRS/T-wave oversensing. Previously, this was done using a ruler and printed vector electrocardiogram. To automate this process, the manufacturer has developed the Automated Screening Tool (AST). We demonstrated that AST has a good agreement with the previous manual vector screening for identifying suitable patients for an S-ICD. Furthermore, we demonstrated that the single-vector passing rate was high (92%) in a heterogenous patient population including patients with congenital heart disease and inheritable primary arrhythmia syndromes. The only exception were patients with hypertrophic cardiomyopathy, who had a lower passing rate (83%) based on AST. Importantly, previous studies have demonstrated that the passing rate may further decline when testing was done during exercise 40-42. Furthermore, we demonstrated that a pre-implant vector screening can potentially be omitted if the patient fulfills specific criteria on a standard 12-lead ECG (i.e., QRS duration of ≤130ms, R/T-ratio ≥3.5 in lead II and absence of T-wave discordance in lead II). Although we tested our model in a validation cohort, external validation in a larger population is necessary. Furthermore, we don’t know the risk of inappropriate shocks when patients with an S-ICD are screened based on our 12-lead ECG model.

Finally, the risk of inappropriate shocks due to cardiac oversensing has been reduced by the recent introduction of SMART Pass technology. The SMART Pass feature activates an additional high-pass filter thereby reducing the amplitude of lower frequency signals (e.g., T-waves). This feature has resulted in reduction of first inappropriate shock by 50% 43. Considering this technological improvement, some physicians have chosen not to perform pre-implant vector screening.

Future perspectives

Although the S-ICD has several theoretical advantages in comparison to the traditional transvenous ICD, the ongoing PRAETORIAN trial will provide more insight in the advantages and disadvantages of the S-ICD 44. The primary endpoint is a composite of inappropriate shocks and ICD-related complications. An interesting concept that is being explored is the modular S-ICD system, consisting of a combined system including a leadless cardiac pacemaker (LCP) and S-ICD system 45, 46. This combined system will be able to provide ATP, which is currently one of the major disadvantages of the current S-ICD system. Reliable device-device communication between the EMPOWER™ LCP and EMBLEM™ S-ICD, through the use of galvanic coupling, has been confirmed in animal studies 45, 46. Furthermore, firmware upgrade of the S-ICD to enable the ability to communicate with the LCP can be performed in existing S-ICD without replacement or explantation of the device. The advantage of the modular S-ICD system is that an S-ICD can be implanted in eligible patients and an EMPOWER™ LCP be implanted later when patients develop the need for ATP. Human clinical studies are expected soon.