CARDIAC PACING AND DEFIBRILLATION

Rahul Mehra, Ph.D.
Medtronic Inc, 7000 Central Av Northeast
Minneapolis, MN 55432, USA

Abstract: Electrical stimulation of the human heart was first demonstrated in the late 1920s. Scientific and technological advancements have occurred at a rapid pace since then, resulting in more than 700,000 implants of pacemakers and defibrillators last year for management of patients with bradycardia and tachyarrhythmias. The population of patients in whom these devices improve mortality or quality of life i.e. their clinical indications, continues to expand as a result of large clinical trials. Inspite of this growth, significant scientific and technological challenges remain such as increasing the therapeutic efficacy, detection accuracy, monitoring capabilities and usability of these devices. The utilization of pacemakers and defibrillators varies dramatically across the world due to differences in expenditures in health care.

Introduction

Mark Lidwill and A.S. Hyman first demonstrated successful cardiac stimulation of the human heart around 1929 when they used partially insulated needle electrodes that were plunged directly into the heart. Since the pacemaker was to be used for emergency applications and external batteries had a relatively short life span at that time, the Hyman pacemaker was manually powered. The pacemaker delivered current from a hand-cranked spring wound magneto-motor that could provide pacing for about 6 minutes. From those early days, the pacemaker technology has progressed rapidly as the awareness of the problem of bradycardia has intensified. This technology was spurred by growth in microelectronics in the late 1940s and the development of long lasting Lithium cell in 1968, which overcame the shortcomings of the Mercury-Zinc battery. This has resulted in the development of pacemakers today that are about 12 cc in size and can last 7-10 years.

Around the late 1960s, sudden cardiac death was also beginning to gain attention as a major public health problem. Although the idea of an automatic external defibrillator was known, Michel Mirowski championed and began the development of an automatic internal defibrillator following sudden death of a close friend and mentor .Today, with rapid development of the microcircuits, capacitor technology and use of biphasic shocks, these devices can pace and deliver 30-40 Joule shocks, are less than 40 cc in size and also have a longevity of 6-8 years. It is estimated that in the year 2001, about 640,000 pacemakers and 84,000 defibrillators were implanted worldwide with more than 90% in the developed countries.

In the 1990’s, another type of technology was developed to meet a growing clinical problem of undiagnosed syncope (fainting). To help diagnose the cause of syncope, this small implantable device only monitored signals from subcutaneous electrodes. It did not deliver any electrical therapy and therefore no intracardiac leads were required. This technology is slowly gaining acceptance. Diagnostic devices with additional sensors are likely to play an increasing role in the future for management of public health problems such as heart failure and atrial fibrillation.

In-spite of all these developments, significant technical, clinical and economic challenges still remain. The challenges consist of increasing the therapeutic efficacy, improving detection and monitoring capabilities, making them easier to use, expanding the clinical indications of use and ensuring that patients who need these devices get them.

1. Therapeutic efficacy

Increasing therapeutic efficacy implies obtaining the desired clinical outcome with the least amount of energy. For cardiac pacing the outcome would be the optimal atrial and ventricular hemodynamic response and restoration of sustained normal rhythm with defibrillation. The device may deliver the desired outcome alone or with hybrid therapy where drugs play a conjunctive role.  Over the last two decades, the therapeutic efficacy of pacemakers has improved with development of sensors to change pacing rate and development of steroid electrodes to reduce the pacing threshold. However, it still takes about a micro-joule per pulse to stimulate the heart. Optimal electrode materials and shape, placement of leads, detection of the response of the stimulus on tissue in order to continuously iterate the stimulus amplitude will further increase the therapeutic efficacy.

For implantable defibrillators, reducing the frequency of shocks and the discomfort associated with them as well as reducing their size can make a significant impact on their acceptability. Optimizing pacing techniques to increase the efficacy of  pacing to terminate atrial and ventricular tachyarrhythmias would reduce shock frequency. In some implantable defibrillators, the shocks are not only utilized for termination of ventricular but atrial fibrillation also. The problem of shock acceptance is more significant with atrial defibrillation since atrial fibrillation does not lead to immediate mortality and the desired outcome is to improve quality of life and to keep these patients from being hospitalized frequently.

2. Detection

A high sensitivity and specificity of detection of ventricular and atrial arrhythmias is required in implantable devices. In order to deliver the appropriate therapy when a rapid ventricular rate is detected, it is important to determine whether its origin is ventricular or atrial.  Discrimination algorithms have been developed that utilize atrial and the ventricular information. In most implantable defibrillators, the sensitivity of detection of true ventricular tachyarrhythmias approaches 100% but the incidence of delivery of inappropriate therapy to the ventricles i.e. false positive rate is about 10-25%. This false positive rate needs to be reduced to avoid delivery of inappropriate shocks to the patient.

In an attempt to separate signal from noise, all pacemakers and defibrillators incorporate “blanking periods” during which no signals are detected or “refractory periods” during which the detected information is not used to alter the timing of the subsequent pacing stimulus. These blanking and refractory periods help reject noise but can compromise true signal detection also. For example, after an atrial stimulus there is typically a blanking period of 150-200 msec to avoid detecting the polarization potential (noise) generated at the electrode tissue interface. If the stimulus were ineffective in capturing the tissue, it would be important to detect it during this period to alter the timing of the subsequent stimuli. Complex blanking and refractory periods have been developed to minimize the problem of signal rejection. The challenge is to eliminate these periods and use signal processing techniques to discriminate signal from noise. This will help reduce the false positive rate of detection.  

a) Ventricular tachycardia and fibrillation discrimination: It is well established that sustained ventricular tachycardia can be terminated by anti-tachycardia pacing whereas shocks are required to terminate ventricular fibrillation.  In order to reduce the use of painful shocks, the implantable device need to incorporate effective algorithms to discriminate tachycardia from fibrillation so that shocks are only delivered for episodes of true ventricular fibrillation.

b) Atrial tachycardia/flutter and fibrillation discrimination: As in the ventricles, atrial flutter/tachycardia can frequently be pace terminated whereas atrial fibrillation is converted by shocks. Again, to reduce the need for shocks and increase efficacy of termination of atrial tachyarrhythmias by painless therapies, algorithms should discriminate the two rhythms.  One of the unique challenges in atrial detection is the presence of “far-field” ventricular signals, which need to be processed appropriately if they are detected.

c) Capture detection: By keeping the energy of the pacing stimulus slightly above threshold, the longevity of implantable devices can be increased. This requires continuous monitoring of the response of the pacing stimulus so that the amplitude can be increased if the tissue is not captured and reduced if the amplitude is significantly above the threshold.   

d) Detection for monitoring devices with subcutaneous sensing electrodes: The new generations of implantable devices, which detect signals only from subcutaneous electrodes, pose a unique set of challenges. The QRS complex recorded by these closely spaced electrodes can be detected well but the P waves tend to be relatively small and can sometimes fall within noise. The noise is typically due to skeletal muscle activation. Therefore, the challenge has been to detect bradycardia, ventricular and atrial tachyarrhythmias and discriminate between them using QRS detection only. Recent studies have demonstrated a high sensitivity for detection of bradycardia and ventricular tachyarrhythmias with these devices.

3. Monitoring

With development of low current drain memory and new sensors, the implantable devices can now monitor large amounts of information for management of the patient as well as optimal programming of the device for detection and therapy. With less than a kilobyte of memory in devices before 1985, today’s devices can have close to a megabyte of

memory. The challenge now is to decide what is meaningful to display and in a manner that is easy to review and clinically useful. Devices can easily record signals from intracardiac electrodes or “far-field” signals from electrodes distant from the cardiac tissue. 

At the same time, new implantable sensors such as pressure sensors and those that monitor mixed venous oxygen saturation chronically have been incorporated in implantable devices for management of patients with heart failure. With advances in home-based interrogation of the device and communication via the Internet, the provider will have access to large amounts of information for patient management. We need to demonstrate that this information is valuable and changes the clinical outcome of the patients.   

4. Ease of Use

The cost and time pressures on the physicians and their staff are increasing due to the high cost of health care delivery in the developed countries. With the expansion of the information provided by these devices and an increase in their complexity, there is increasing need to make these devices easy to implant and follow-up. The information needs to be presented in a concise and clinically meaningful manner that is easy to review by the physician or their support staff. The information should focus on the management of the patient as well as the device. 

5. New indications FOR IMPLANTATION

One of the more rapid areas of growth in recent years has been the development of new indications for implantation of pacemakers and defibrillators for management of large public health problems.  Atrial fibrillation and congestive heart failure have been referred to as the epidemics of cardiovascular disease in the new millennium.  Atrial fibrillation affects about 2.2 million patients in US and is a disease of the elderly, occurring in almost 7% of patients greater than 65 years of age. About 2.5 million US patients are afflicted with heart failure and has become the single most cause of hospitalization in patients 65 or older.

In the past, the classical indication for a pacemaker implant was in patients with symptomatic bradycardia i.e. slow heart rate. Pacemakers have now been developed for management of patients with heart failure and atrial tachyarrhythmias. Instead of pacing at a single site in the ventricle, recent clinical studies indicate that patients with heart failure and wide QRS morphology can benefit from bi-ventricular pacing i.e. pacing from the right as well as the left ventricle. The left ventricular lead is introduced through the coronary sinus and the electrode tip is located in the left ventricular wall.  This new indication poses some new challenges regarding delivery of the left ventricular lead. New pacemakers have also been developed that detect, monitor and terminate atrial tachyarrhythmias by anti-tachycardia pacing. In patients with bradycardia, the progression of atrial tachyarrhythmias can be prevented by sustained atrial as opposed to ventricular pacing.

For implantable defibrillators, the indications continue to expand also. Instead of implanting defibrillators only in patients who have survived a nearly fatal episode of ventricular tachyarrhythmia, the focus has been to define subgroup of patients with a high likelihood of dying from ventricular tachyarrhythmias. Recent large trials indicate that patients with poor ejection fraction and non-sustained ventricular tachyarrhythmias or prior myocardial infarction could also benefit with respect to improved survival.  Patients with atrial tachyarrhythmias can also benefit from the use of Dual defibrillators that terminate atrial and ventricular tachyarrhythmias with pacing and defibrillation. Termination of atrial tachyarrhythmias reduces the percent of time they spend in atrial fibrillation, which is associated with reduced quality of life, and increased risk of stroke. Recent trials are evaluating the value of implantable defibrillators in heart failure patients.

6.  DEVICE UTILIZATION

Recent data indicates that there is significant underutilization of implantable defibrillators.  It is estimated that about 0.1% of the US population would benefit from implantable defibrillators with about a third of the patients receiving the devices presently (416/million). With the expansion of indications based on some of the recently completed trials, the underutilization could be significantly greater. This underutilization is even greater in other countries including Canada and Europe. For example in Canada, utilization rate is at between 50-70/million and in European countries it varies significantly between 20-120/million. There are several reasons for underutilization; which include health care budgets, cost effectiveness of ICDs, availability of implanting centers and physician education. Several studies indicate that the cost effectiveness of implantable defibrillators range between $20,000 - $60,000 per life year saved.  The utilization rates are much higher for pacemakers. It is about   75% in US and between 50-75% in most European countries.

The utilization of ICDs and pacemakers is extremely low in the developing countries. It is important to keep in perspective that in developed countries like the US, the daily expenditure on health care is about $6/capita/day whereas in developing countries like China and India, it is less than 20 cents/capita/day. In developing countries, a lack of widespread use of health insurance programs limits the use of the devices in patients who could benefit from them.

FUTURE ADVANCEMENTS

In the future, scientific and technological innovation will drive the efficacy of these devices while reducing their size. Novel indications for implantable devices will continue to expand based on clinical trials, especially for patients with heart failure and atrial fibrillation. With the availability of new sensors and the ability to monitor these devices from home, the near term challenge will be to provide significantly greater information for management of the patients in a manner that is relatively easy to utilize and provides value. In developing countries, the cost effectiveness of this technology will continue to be a challenge until there is an increase in health care expenditure.