Implantable cardioverter defibrillators – driven by MR compatibility, subcutaneous devices

In spite of a relatively short history, the use of implantable cardioverter defibrillators (ICDs) has been growing by leaps and bounds. For clinicians, an ICD offers a direct means to avoid sudden cardiac death. Other reasons for the popularity of ICDs include advances in technology, above all miniaturization. More recently, new implantation methodologies such as subcutaneous ICD promise a further boost to their use. The working of ICDs are also easy to explain to patients. There is, nevertheless, one major challenge which ICDs have to still address: limitations to battery life.

Primary and secondary prevention
The principle behind an ICD is relatively straightforward, and covers two broad types of prevention: primary and secondary.
Primary prevention, which accounts for the bulk of ICD implants, refers to patients who have not yet suffered life-threatening arrhythmia.
Secondary prevention concerns survivors of cardiac arrest secondary to ventricular fibrillation or sustained tachycardia (together known as a tachyarrhythmia). Although the user group is smaller, secondary prevention makes the strongest case for an ICD.

Differentiating ventricular tachycardia and ventricular fibrillation
After implantation, the ICD continuously monitors cardiac rhythm and detects abnormalities. ICDs are programmed to recognize and differentiate between ventricular tachycardia (VT) and ventricular fibrillation (VF), after which they deliver therapy in the form of a low- or high-energy electric shock or programmable overdrive pacing to restore sinus rhythm – in the case of ventricular tachycardia, to break the tachycardia before it progresses to fibrillation. Overdrive or anti-tachycardia pacing (ATP) is effective only against VT, not ventricular fibrillation.

Defibrillation now almost 70 years old

The first defibrillation of a human heart dates to 1947, when Claude Beck, an American surgeon at Western University in Ohio, sought to revive a 14-year-old boy whose pulse had stopped during wound closure, following cardiothoracic surgery. Cardiac massage was attempted for 45 minutes, but failed to restart the heart. Ventricular fibrillation was confirmed by ECG. Beck saw no other choice but to deliver a single electric shock. This did not work. However, along with intracardiac administration of procaine hydrochloride, a second shock restored sinus rhythm. Beck’s success led to worldwide acceptance of defibrillation. However, his alternating current (AC) device (subsequently commercialised by RAND Development Corporation) was capable of defibrillating only exposed hearts.

Merging defibrillation and cardioversion
On its part, the pioneering of cardioversion (and the coining of this term) is credited to Bernard Lown, a physician at the Peter Bent Brigham Hospital in Boston. Lown merged defibrillation and cardioversion, and coupled these to portability. In 1959, he successfully applied transthoracic AC shock via a defibrillator to a patient with recurrent bouts of ventricular tachycardia (VT), who had failed to respond to intravenous procainamide. This was the first termination of an arrhythmia other than VF.
Two years later, Lown joined a young electrical engineer called Barouh Berkovitz, who had been researching a relatively safer direct current (DC) defibrillator – based on earlier work in the Soviet Union and Czechoslovakia.
Together, Lown and Berkovits pioneered the concept of synchronizing delivery of an electric shock with the QRS complex sensed by ECG, and a monophasic waveform for shock delivery during a rhythm other than VF. Their work led to launch of the first DC cardioverter-defibrillator in patients.

The implantable ICD device: parallel pathways
The Lown-Berkovits effort was confined to external devices. The concept of an implantable, automated cardiac defibrillator dates to work by Michel Mirowski at Israel’s Tel Hashomer Hospital in the mid-1960s. Mirowski moved to the US in 1968, where he joined forces with Morton Mower, a cardiologist at Sinai Hospital in Baltimore. The two tested a prototype automated defibrillator on dogs.
As often happens in science, another researcher had also been approaching the challenge on a parallel path. In 1970, Dr. John Schuder from the University of Missouri successfully tested an implanted cardiac defibrillator, again in a dog. Schuder also developed the low-energy, high voltage, biphasic waveforms which paved the way for current ICD therapy.
The first human ICD, however, was credited to Mirowski and Mower, along with Dr. Stephen Heiman, owner of a medical technology business called Medrac. In 1980, a defibrillator based on their design was implanted in a patient at Johns Hopkins University, followed shortly afterwards by a model incorporating a cardioverter. The ICD obtained approval from the US Food and Drug Administration (FDA) in 1985.

From thoracotomy to transvenous implantation
The first generation of ICDs were implanted via a thoracotomy, using defibrillator patches applied to the pericardium or epicardium, and connected by transvenous and subcutaneous leads to the device, which was contained in a pocket in the abdominal wall.
ICDs have since become smaller and lighter (thicknesses below 13 mm and weights of 70-75 grams). They are typically implanted transvenously with the device placed, like a pacemaker, in the left pectoral region. Defibrillation is achieved via intravascular coil or spring electrodes.

ICDs versus pharmacotherapy
Over the past two decades, clinical trials have demonstrated the benefits of ICDs compared to antiarrhythmic drugs (AADs). Three randomized trials, known as AVID (Antiarrhythmic versus Implantable Devices), the Canadian Implantable Defibrillator (CIDS) study, and Cardiac Arrest Study Hamburg (CASH), were initiated between the late 1980s and early 1990s in the US, Canada and Europe, respectively.
In 2000, a meta-analysis of the three studies was published in European Heart Journal.’ This found that ICDs reduced the relative risk of recurrent sudden cardiac death by 50% and death from any cause by 28%.

Use after myocardial infarction, quality of life issues
Follow-on initiatives looked at other issues. The Multicenter Automatic Defibrillator Implantation Trial (MADDIT) found that ICD benefited patients with reduced left ventricular function after myocardial infarction (MI). In 2005, the Sudden Cardiac Death in Heart Failure trial (SCD-HeFT) established that ICD reduced all-cause death risk in heart failure patients by 23% as compared to a placebo and absolute mortality by 7.2% after five years.
Quality-of-life (QoL) issues have also assisted acceptance of ICDs. In 2009, psychologists and cardiologists at universities in North Carolina and Florida concluded that QoL in ICD patients was at least equal to, or better than, that of AAD users.

Guidelines on ICD use – differences between US and Europe
Professional bodies have established guidelines on the use of ICDs and routinely provide updates. In the US, these originate from the American College of Cardiology, American Heart Association and the Heart Failure Society of America, and in Europe from the European Society of Cardiology.
Although there are many areas of agreement, some differences exist between the US guideline and the European Society of Cardiology. One difference is that in the US guideline, cardiac resynchronization therapy (CRT) is recommended in New York Heart Association (NYHA) class I patients who have LVEF ≤30%, have ischemic heart disease, are in sinus rhythm, and have a left bundle branch block (LBBB) with a QRS duration ≥150 ms. There is no similar recommendation in the European Society of Cardiology document.

The European Society of Cardiology recommendations include patients with QRS duration <120 ms. The US does not recommend CRT for any functional class or ejection fraction with QRS durations <120 ms. ICD and magnetic resonance
The biggest driver of ICD use in recent years, however, may consist of compatibility with magnetic resonance (MR) imaging. Like other metallic objects, ICDs have been contraindicated for MR. This is however set to change, after the first MR-compatible ICD (Medtronic’s Evera SureScan) received FDA approval in September 2016.
The relevance of MR was researched in significant depth by a team at Pittsburgh’s Allegheny General Hospital, led by Dr. Robert Biederman, medical director of its Cardiovascular MRI Center. The study covered patients in three implantable cardiac device case groups, namely cardiovascular, musculoskeletal and neurology.
The findings were conclusive. In 92-100% of cardiac and musculoskeletal, and 88% of neurology cases, MR exam provided value for the final diagnosis. In 18% of neurology cases, the MR exam altered the diagnosis entirely. In the bulk of cases, said Dr. Biederman, the information could not be obtained with cardiac catheterization, echo or nuclear. In addition, patients were saved from a biopsy of the heart muscle, with all its attendant risks.

The launch of leadless, subcutaneous ICDs
Meanwhile, other factors too are driving development of ICDs. One of the biggest shortcomings of ICDs is the need to run an electric lead through blood vessels. These are susceptible to breakages.
In 2012, Boston Scientific received FDA approval for the world’s first leadless, subcutaneous ICD (S-ICD). Rather than leads, the device uses a pulse generator and electrode beneath the skin with a shocking coil implanted under the left arm. A second-generation S-ICD system, branded Emblem, was approved in 2015.
Nevertheless, S-ICDs have drawbacks. Lacking a lead in sufficient contact with the heart, they cannot pace patients out of bad heart rhythms. S-ICDs are also not MR compatible.

The challenge of battery life

Many experts believe that the principal challenge facing ICDs is battery life. According to the Mayo Clinic, batteries in an ICD ‘can last up to seven years.’ It recommends monitoring battery status every 3-6 months during routine checkups, and states when the battery is ‘nearly out of power,’ the old shock generator needs to be ‘replaced with a new one during a minor outpatient procedure.’
Nevertheless, there has recently been some attention about the risk of the latter. In 2014, a research team led by Daniel B. Kramer of Harvard Medical School studied 111,826 patients in the US National Cardiovascular Data Registry (NCDR) who had end-of-battery life ICD generator replacements. They found more than 40% of patients died within five years of ICD generator replacement, and almost 10% within a year. The authors, however, emphasized that atrial fibrillation, heart failure, and left ventricular ejection fraction were independently associated with poorer survival as were noncardiac co-morbidities (chronic lung disease, cerebrovascular disease, diabetes and kidney conditions). What was needed, they concluded, would be a non-ICD control group.
A recent article in the British Medical Journal’ (BMJ) suggests that battery life needs to be extended to 25 years or more to avoid the risks associated with replacement. The author, Dr. John Dean, a cardiologist at Royal Devon and Exeter Hospital in the UK, points out that 1-5% of battery replacements also carry infection risk for patients.

The future: patient needs and superior waveforms
Ultimately, it is patient needs which will drive the next wave in ICD development. While the medical devices industry has focused on device miniaturization, longer battery life is also clearly a priority. Indeed, a 2004 study in Pacing and Clinical Electrophysiology’ found 90% of ICD patients saying they would trade off smaller ICDs for longer-lasting models.
ICD manufacturers are also looking at developing more sophisticated cardioversion/defibrillation waveforms in order to reduce the threshold of defibrillation, and thereby reduce pain and discomfort.