Tachycardia Termination by Shocks and Pacing

Introduction

The burden of tachyarrhythmias has been well described, both in the United States and around the world. Sudden cardiac death is responsible for an estimated 184,000 to 400,000 deaths annually in the United States alone. Of these, the majority are due to ventricular tachyarrhythmias such as ventricular tachycardia (VT) and ventricular fibrillation (VF). Even under the best of circumstances, when the arrest is witnessed and the initial rhythm is a shockable rhythm such as VT or VF, the survival to hospital discharge is only approximately 30%. Although less fatal, atrial fibrillation (AF) is even more common and comes with a multitude of attendant costs and complications associated with both the disease and its treatment. Current estimates place the prevalence of AF in the United States at approximately 5 million patients as of 2010. There are more than 1 million new cases diagnosed each year, with the total prevalence expected to grow to greater than 10 million by the year 2030. Therapies for these arrhythmias have seen great progress in the past several decades and have come in the form of pharmacologic treatments, ablation procedures, and device-based therapies. Although these have all contributed significantly to preventing sudden death and ameliorating symptoms, we still have much to understand regarding the fundamental mechanisms of fibrillation before we can arrive at a truly effective, low-cost, and ideally, low-energy and painless treatment for tachyarrhythmias.

Indeed, although arguably the single most important advancement in the prevention of sudden death, current implantable cardiac defibrillator (ICD) therapy comes with its own significant drawbacks. In 2004, the MADIT II investigators were the first to demonstrate that mortality was significantly increased at 1 year after receiving ICD therapy for VT or VF. This was followed by a robust analysis by Poole et al in 2008 demonstrating that in heart failure patients undergoing implantation of a primary prevention ICD, mortality was over five-fold higher in patients that received one or more appropriate shocks versus those that received none. In addition, patients that received only inappropriate shocks still had a risk of death that was nearly doubled. Further increases in mortality were seen as the number of shocks increased. In 2010, the findings of the MADIT II investigators and Poole et al were confirmed in the ALTITUDE study. This was the largest registry to date, examining survival in nearly 200,000 unselected ICD patients undergoing implantation of a device for primary or secondary prevention of sudden death. The findings were similar and indicated a significantly increased risk of mortality associated with receiving appropriate or inappropriate ICD shocks ( Fig. 6-1 ). This work, along with that of many others, has led to the prevailing thought that although ICD shocks are often life-saving, they also portend a worse outcome and may have direct deleterious effects.

Basic Mechanisms of Tachycardia and Fibrillation

Cardiac fibrillation is a well-described entity that has been recognized since possibly as early as 3500 BCE when the Ebers papyrus stated:

“When the heart is diseased, its work is imperfectly performed: the vessels proceeding from the heart become inactive, so that you cannot feel them … If the heart trembles, has little power and sinks, the disease is advancing and death is near.”

Its more rigorous, scientific recognition, however, did not come until 1842 with the work of Erichsen. He was the first to demonstrate that coronary ligation led to “tumultuous,” “tremulous,” and “irregular” behavior of the ventricles. VF was first observed and recorded using Ludwig's “kymograph” (mechanical wave recorder) after electrical stimulation by Hoffa and Ludwig in 1850. These were described as irregular contractions induced by “faradization” (electrical stimulation), which persisted even after the termination of electrical stimulation and resulted in cardiac arrest that could not be checked by vagal stimulation. Although these were certainly accurate phenomenological observations of VF, coining of the term “fibrillation” would have to wait until 1874 when Vulpian referred to the arrhythmia as “ mouvement fibrillaire. ” In 1912 Hoffman documented the first electrocardiogram to show VF in man. Shortly thereafter, in 1913, Mines published his seminal study “On Dynamic Equilibrium in the Heart” describing and explaining the mechanisms of circus movement reentry. In this work, he noted, “ordinarily, in the naturally beating heart, the wave of excitation is so long and so rapid that it spreads all over the ventricle long before it has ceased in any one part. Under the altered conditions of increased frequency it is possible that this should be no longer the case, and thus that, the wave being slow and short, more than one could exist at one time in a single chamber …” This work, performed in isolated rings of cardiac tissue from tortoise and rays, was the first detailed description of anatomic reentry ( Fig. 6-2 ). The following year, Garrey noted similar findings, stating “tissue rings cut from fibrillating hearts of marine turtles ceased fibrillating, but the contraction waves continued, repeating the circuit about the ring in co-ordinate ‘circus contractions’ ” and that these circus contractions were “fundamentally essential to the fibrillary process.” Several years later, in 1930, Wiggers further characterized VF using high-speed cinematography and electrocardiography. He described VF as proceeding through four stages, now referred to as Wiggers stages of fibrillation. The first Wiggers stage, described as the tachysystolic, or undulatory phase, is quite brief, consisting of only 2 to 8 “peristaltic waves” sweeping rapidly across the ventricles. Wiggers stage 2 is described as “convulsive incoordination” and lasts 15 to 40 seconds. This stage is characterized by “large, rather violent oscillations” of more frequent contractions over a smaller area of myocardium. Then follows Wiggers stage 3, “tremulous incoordination,” lasting from 2 to 4 minutes and involving yet more frequent contractions of smaller amplitude and over an even smaller area. This eventually gives way to Wiggers stage 4, atonic coordination. This final stage of VF is characterized by extremely weak and slow contractions proceeding over very short distances. There are increasing areas of quiescence, until eventually all myocardium ceases to contract.

Functional Reentry

Although the mechanistic underpinnings of VF and anatomic reentry had made much progress during the early half of the 20th century, it was not until the middle part of the century that the distinct concept of nonanatomic based reentry or “functional reentry” was conceived. This came about in 1946 with the seminal theoretical work of Wiener and Rosenblueth. They described a mechanism by which successive stimulation at two overlapping sites in a single two-dimensional (2D) sheet of excitable tissue lacking anatomic obstacles could result in a reentrant wave. Although this long mathematical paper focused largely on the mechanisms for initiation of fibrillation and flutter in the presence of obstacles, it was the first description of the mechanistic possibility of functional reentry and set the stage for Selfridge's work two years later. Selfridge refined Wiener and Rosenblueth's work, describing how “perpetual flutter can happen in a sheet of muscle which is simply-connected, and therefore free of internal obstacles.” He also recognized, however that “any such flutter is unstable: an infinitesimal increase in the refractory period stifles it.” Unfortunately, both the papers of Wiener & Rosenblueth and Selfridge were unknown to the scientific community for several decades, because they were published in an obscure journal and thus had little influence on the evolution of understanding mechanisms of reentry. Nearly 30 years later, Allessie et al validated this theory in an experimental model of rabbit atria. This seminal experimental work introduced the “leading circle” concept and found that even without a central anatomic obstacle, a reentrant atrial tachycardia (AT) could be induced with a center that was invaded by multiple centripetal wavelets ( Fig. 6-3 ).