Ventricular arrhythmias in ischemic heart disease

Classification according to tachycardia morphology

Monomorphic VT has a single stable QRS morphology from beat to beat, indicating repetitive ventricular depolarization with the same activation sequence ( Fig. 26.1 ). Some variability in QRS morphology at initiation is not uncommon, followed by stabilization of the QRS morphology.

Polymorphic VT has clearly defined QRS complexes with a continuously changing morphology or multiform QRS morphology (i.e., no constant morphology for more than five complexes, no clear isoelectric baseline between QRS complexes, or QRS complexes that have different morphologies in multiple simultaneously recorded leads), indicating a variable sequence of ventricular activation and no single site of origin.

Torsades de pointes is a polymorphic VT associated with a long QT interval and is electrocardiographically characterized by continually varying QRS complexes that appear to spiral around the baseline of the ECG lead in a sinusoidal pattern.

Multiple monomorphic VTs refer to more than one morphologically distinct monomorphic VT, occurring as different episodes or induced at different times.

Pleomorphic VT has more than one morphologically distinct QRS complex occurring during the same episode of VT, but the QRS morphology is not continuously changing as in polymorphic VT.

Bidirectional VT is a VT associated with a beat-to-beat alternation in the QRS frontal plane axis, often associated with digitalis toxicity or catecholaminergic VT.

Ventricular flutter (or preferably referred to as “monomorphic VT with indeterminate QRS morphology”) is a term that has been applied to a rapid VT (250–350 complexes/min) that has a sinusoidal QRS configuration that prevents clear identification of the QRS morphology.

Ventricular fibrillation (VF) is a rapid (usually >300 complexes/min), disorganized tachycardia defined on the surface ECG by undulations that are irregular in both timing and morphology, without discrete QRS complexes.

Classification according to tachycardia duration

Sustained VT lasts for more than 30 seconds or requires termination (e.g., cardioversion/defibrillation) in less than 30 seconds because of hemodynamic compromise, whereas nonsustained VT is a tachycardia at more than 100 beats/min lasting for three or more complexes but for less than 30 seconds and not requiring termination.

Repetitive polymorphic responses are also common (up to 50%) during programmed ventricular stimulation, especially in response to multiple (three or more) ventricular extrastimuli (VESs) with very short coupling intervals (less than 180 milliseconds). The clinical significance of induced polymorphic nonsustained VT is questionable.

Incessant VT is a continuous sustained VT that recurs promptly over several hours despite repeated interventions (e.g., electrical cardioversion) for termination. Less commonly, incessant VT manifests as repeated bursts of VT that spontaneously terminate for a few intervening sinus beats, followed by the next tachycardia burst. The latter form is more common with the idiopathic VTs (see Fig. 27.1 ).

Classification according to QRS morphology in lead V ₁

Monomorphic VT can be classified as having one of two patterns: right bundle branch block (RBBB)–like pattern or left bundle branch block (LBBB)–like pattern. VTs with an LBBB-like pattern have a predominantly negative QRS polarity in lead V ₁ (QS, rS, qrS), whereas VTs with a RBBB-like pattern have a predominantly positive QRS polarity in lead V ₁ (rsR′, qR, RR, R, RS). Importantly, this classification pertains to QRS morphology only in lead V ₁ ; the VT may not show features consistent with the same bundle branch block (BBB) configuration in other leads. Also, the determination that the VT has an RBBB-like pattern or an LBBB-like pattern does not, by itself, assist in making a diagnosis; however, this assessment should be made initially because it has further implications for evaluating several other features on the ECG, including the QRS axis, the QRS duration, and the QRS morphology.

Classification according to tachycardia mechanism

Focal VT has a point source of earliest ventricular activation with a centrifugal spread of activation from that site. The mechanism can be abnormal automaticity, triggered activity, or microreentry. Scar-related reentrant VT describes arrhythmias that have characteristics of reentry and originate from an area of myocardial scar identified from electrogram characteristics or myocardial imaging. Large reentry circuits that can be defined over several centimeters are commonly referred to as “macroreentry” circuits.

Mechanisms of ventricular arrhythmias associated with acute ischemia

Acute myocardial ischemia leads to local tissue hypoxia, depletion of adenosine triphosphate (ATP), and anaerobic glycolysis causing intracellular acidosis. ATP depletion impairs the function of the ATP-dependent Na ⁺ -K ⁺ pump, causing net K ⁺ leakage from the myocyte and elevation of extracellular K ⁺ concentration. This results in depolarization of the resting membrane potential of the surviving Purkinje fibers and, as a consequence, abnormal automaticity.

Additionally, intracellular acidification and accumulation of H ⁺ ions activate the Na ⁺ -H ⁺ exchanger, which extrudes H ⁺ in exchange for Na ⁺ entry, causing increased intracellular Na ⁺ concentration. The latter activates the Na ⁺ -Ca ²⁺ exchanger in the reverse mode, which extrudes Na ⁺ in exchange for Ca ²⁺ entry, causing intracellular Ca ²⁺ overload in the ischemic myocardium, which, in turn, leads to delayed afterdepolarizations and triggered arrhythmias.

Furthermore, membrane depolarization causes Na ⁺ channel inactivation and, as a result, reduced fast Na ⁺ current and reduced action potential upstroke, leading to slowed conduction and altered refractoriness.

Although an initial prolongation of the action potential duration can be observed (likely caused by an increase in the late Na ⁺ current), abbreviation of the action potential duration develops shortly afterward secondary to reduced Na ⁺ entry (due to Na ⁺ channel inactivation), reduced Ca ²⁺ entry (due to inhibition of Ca ²⁺ channels by acidosis), and enhanced K ⁺ efflux (due to activation of ATP-sensitive potassium current [I _KATP ] caused by reduced intracellular ATP).

Importantly, the effects of ischemia on the electrophysiological (EP) properties of myocardial cells are heterogeneous. Shortening of the action potential duration and reduction of upstroke velocity and amplitude are more pronounced within the central zone of ischemia and subepicardium than within the border zone and subendocardium. On the other hand, the surrounding normal myocardium can have an increase in conduction velocity (secondary to increased catecholamines) and decrease in refractoriness. This heterogeneity of action potential duration and dispersion of refractoriness provide a substrate for an injury current to flow between the ischemic and the nonischemic cells located at the border zone. In addition, myocardial ischemia causes disruption of gap junctions, leading to cellular uncoupling, with consequent slow and anisotropic conduction, and unidirectional conduction block, providing a substrate for reentry.

High levels of catecholamines, endothelin-1 activation, increased lysophosphatidylcholine (a phospholipid that accumulates in ischemic myocardium), mechanical stretch (induced by the viable myocardium surrounding the infarct zone), electrolyte abnormalities (particularly hypokalemia and hypomagnesemia), preexisting myocardial abnormalities (e.g., prior myocardial infarction [MI], hypertrophy, systolic dysfunction), and genetic predisposition (likely mediated by mutations or polymorphism in genes encoding ion channels), all can significantly modify the EP properties of the substrate and contribute to arrhythmogenesis. Prolonged and severe acute ischemia and delayed or unsuccessful revascularization increase the risk of ventricular arrhythmias during an acute ischemic event.

Experimental studies demonstrated that arrhythmia mechanisms undergo dynamic changes in the early minutes and hours after onset of myocardial ischemia. Two temporally distinct phases of ventricular arrhythmia develop in response to ischemic injury: phase 1 is the reversible phase of acute MI, whereas phase 2 is the infarct evolution phase ( eFigs. 26.1 and 26.2) .

Mechanisms of ventricular arrhythmias associated with healed infarction

The majority of post-MI SMVTs are caused by macroreentry involving the region of ventricular scar. Left ventricular (LV) remodeling begins almost immediately after acute MI. Experimental studies suggest that the EP substrate for monomorphic VT gradually forms in the subacute phase (in the first week) following acute MI and once established appears to remain stable into the chronic phase. EP and electroanatomical characteristics demonstrated no difference between VT induced during the subacute and chronic phases, with comparable sites of earliest presystolic activation. These sites are located predominantly in the border zone adjacent to dense injury areas at both phases.

A recent report using serial scar characterization (as identified with late gadolinium cardiac magnetic resonance [CMR] over a period of 4 years) following ST elevation MI in patients who underwent successful coronary revascularization found that scar remodeling is a dynamic process, starting within the first 6 months, but lasting during a more chronic phase of the healing process ( eFig. 26.3 ). A steady reduction in total scar mass and a reduction in the number, degree of transmurality, and mass of potentially arrhythmogenic border zone channels was observed over a 4-year period after an acute coronary event.

Persistent coronary occlusion typically leads to a central core of dense transmural scar in the territory supplied by the occluded artery, surrounded by a thin rim (border zone) where fibrotic tissue and viable myocardial more complex substrate, with nontransmural myocardial necrosis (primary subendocardial necrosis and variable epicardial sparing depending on the duration of coronary occlusion) and heterogeneous (and even patchy) scarring with multiple channels of viable myocardium embedded within the scar region, and complex border zones. The scar and fibrosis resulting from MI are distinctly different from nonischemic etiologies. Compared with post-MI VT, the scar in dilated cardiomyopathy tends to be smaller and less confluent, with less endocardial involvement, and less transmurality. Whereas ischemia produces a predictable wedge-shaped wavefront of necrosis progressing from subendocardium to epicardium (and scar areas larger endocardially than epicardially), usually confined to a specific coronary vascular territory, scars in nonischemic dilated cardiomyopathy have been shown to have a predilection for the midmyocardium and epicardium.

Generally, the reentrant circuit arises in areas of a dense fibrotic scar interspersed with branching and merging bundles of viable myocytes with poor intercellular coupling (due to altered gap junctions) and abnormal conduction properties, producing a zigzag course of activation along a pathway lengthened by branching and merging bundles of surviving myocytes, leading to nonuniform anisotropic conduction (see Fig. 4.17 ). Heterogeneity in tissue composition and autonomic innervation in these regions can create areas of slow conduction and block, which promote reentry. Buried in the arrhythmogenic substrate is the common central pathway (critical isthmus), which is a narrow path of tissue with abnormal conduction properties allowing reentry to occur. Depolarization of the small mass of tissue within the isthmus is usually not detectable on the surface ECG and constitutes the electrical diastole between QRS complexes during VT. The wavefront leaves the isthmus at the exit site and propagates out to depolarize the remainder of the ventricles, producing the QRS complex. After leaving the exit of the isthmus, the reentrant wavefront can return back to the entrance of the isthmus through an outer loop or an inner loop (see Fig. 6.20 ). Complex circuits can have multiple entrances and exits. Also, the isthmus itself can be surrounded by dead ends or branches that do not participate in the common pathway of the main reentrant circuit (bystander).

Although most reentry circuits appear to involve the subendocardium, intraoperative mapping and simultaneous endocardial and epicardial high-resolution mapping studies have demonstrated that scar-related reentrant VT is characterized by complex three-dimensional (3-D) activation patterns with nonuniform transmurality that is infrequently restricted to a single myocardial layer ( Fig. 26.2 ). The epicardium is a functional component of the circuit in the majority of postinfarct VTs. The exit region of myocardial activation during QRS onset is broad, frequently transmural (i.e., exhibits activation on both endocardium and epicardium during QRS onset), and often remote from the central isthmus (typically separated by 4 cm and can be as remote as over 10 cm).

The VT isthmus is protected by laterally opposing lines of anatomical or functional block. Recent studies suggest that conduction block at VT isthmus sites is largely a functional phenomenon; activation slowing or block during sinus rhythm was present in less than two-thirds of VT isthmus sites. Additionally, the barriers that define the VT isthmus often are tortuous rather than parallel, with activation wavefronts entering and exiting the protected isthmus at multiple points. The increasing evidence for the role of functional block in VT circuits provides an explanation for the observation of more than one VT breaking out from the same region of scar. A region of slow conduction that acts as a lateral border for one VT can potentially act as the entrance or exit zone for another. It has been suggested that there may be VT critical zones that serve as the anchors for wavefront slowing and curvature, which can lead to reentry in multiple different morphologies, leading to multiple VTs. In recent studies, shared isthmuses were demonstrated at 70% of VT circuits.

Importantly, conduction velocities within the reentrant circuit are dynamic and influenced by the vector of wavefront propagation, such that the zone of slow conduction is not geometrically fixed but rather influenced by properties of anisotropic conduction. Notably, critical zones of slow conduction within the reentrant circuit are observed at the entrance and exit sites, with relative preservation of conduction velocity in the mid isthmus ( Fig. 26.3 ). Wavefront curvature and anisotropy, as would be expected at the entrance (inward curvature) and exit (outward curvature) zones, underlie conduction slowing in these regions. ^,

Studies using electroanatomical substrate mapping found that ischemic cardiomyopathy patients without clinical sustained monomorphic VT (SMVT) had markedly smaller endocardial low-voltage areas, fewer scar-related electrograms (i.e., fractionated, isolated, and very late potentials, which represent electrically viable sites within the scar), and fewer putative conducting channels compared with patients with spontaneous SMVT, despite equally severe LV dysfunction as well as similar infarct age and distribution. These differences in the myocardial EP substrate can play an important role in VT arrhythmogenesis in the chronic post-MI context. Both the extent of the scar areas (electrogram voltage <0.5 mV) and the presence of numerous channels within this zone seem to be critical to the development of VT. Although the border zone region of the scar (electrogram voltage, 0.5–1.5 mV) did not differ in area between the two groups, this zone also had a significantly higher prevalence of putative conducting channels in the SMVT patients. This suggests a fundamentally different scar composition (more “arrhythmogenic”) in patients with SMVT. As noted, inhomogeneous scarring with varying degrees of subendocardial myocardial fiber preservation within dense zones of fibrosis leads to slowed conduction, nonuniform anisotropy, and the potential for channels within the scar zone—conditions necessary for the development of reentry.

It is common for patients with post-MI VT to have more than one VT morphology. Even in patients presenting with a single SMVT, multiple distinct uniform VTs can be induced in the EP laboratory, especially in patients receiving antiarrhythmic therapy. The arrhythmogenic substrate has the capability to support multiple reentrant circuits or different exit sites from a single circuit. As noted, distinct VT morphologies often share a common isthmus but differ in propagation direction or location across the isthmus perimeter during reentry but can also arise from distinct, usually adjacent, circuits.

A focal mechanism of VT (abnormal automaticity or triggered activity) has been implicated in the setting of acute ischemia. Focal VT can also occur in the absence of an acute ischemic event in patients with chronic ischemic heart disease. In one report, a focal mechanism was present in up to 9% of VTs that were induced in patients with ischemic heart disease during EP study for RF ablation.

Infrequently, SMVT in the setting of chronic coronary artery disease is related to a nonischemic arrhythmogenic substrate rather than a healed infarct. Coronary artery disease can coexist with nonischemic cardiomyopathy, in which setting arrhythmogenic substrate is inconsistent with the distribution of CAD, with VT morphologies originating in the periannular basal ventricular segments and frequent epicardial VT exits.

Premature ventricular complexes

Premature ventricular complexes (PVCs) are seen in the majority of cases of acute MI. Early PVCs (within the first 48 hours) do not appear to affect the prognosis. In contrast, repetitive complex PVCs (ventricular bigeminy, couplets, or multiform PVCs) occurring beyond 48 hours after acute MI can be associated with increased arrhythmic risk, particularly in patients with larger infarctions and impaired LV function.

Accelerated idioventricular rhythm

Accelerated idioventricular rhythm occurs in up to 50% of patients with acute MI, predominantly occurring in the first 12 hours after admission for acute MI. Although more common in patients with successful reperfusion therapy, accelerated idioventricular rhythm is neither a sensitive nor a very specific marker for successful reperfusion.

Reperfusion arrhythmias

Ventricular arrhythmias upon reperfusion typically manifest as bursts of PVCs with long coupling intervals and accelerated idioventricular rhythms occurring at the moment of reperfusion and are hemodynamically well tolerated. These arrhythmias originate within the reperfusion zone and likely reflect myocellular reperfusion injury. Reperfusion injury produces a second peak of myocardial necrosis, which depends on the duration of preceding ischemia. Alteration of the EP substrate and, in particular, intracellular Ca ²⁺ overload combined with increased catecholamines likely play a central role in reperfusion arrhythmias. Abnormal automaticity is the likely mechanism.

In conjunction with thrombolytic therapy, reperfusion ventricular arrhythmias were considered a noninvasive marker of successful infarct artery recanalization; however, current evidence suggests that those arrhythmias are neither specific nor sensitive. In the more contemporary era of primary percutaneous coronary intervention, the presence of ventricular arrhythmia bursts timed closely to reperfusion appears to predict larger infarct size in patients presenting with ST-segment elevation MI and treated with primary PCI resulting in brisk epicardial flow restoration (TIMI 3 flow) and rapid and complete ST-segment resolution.

Nonsustained ventricular tachycardia

Nonsustained VT is observed in 1% to 7 % of acute MI patients. Nonsustained VT occurring early (within the first 2–3 hours) following acute MI does not appear to predict poor prognosis. Arrhythmic episodes occurring later (after the first 24 hours, and particularly after the first week) in the course of acute MI portend a worse prognosis. Beyond the periinfarct period, nonsustained VT is common in chronic ischemic heart disease, recorded in 30% to 80% of patients during long-term ambulatory monitoring or detected by cardiac implanted devices.

Polymorphic ventricular tachycardia

Polymorphic VT usually is due to abnormal automaticity or triggered activity associated with acute ischemia or reperfusion. In the setting of coronary disease, polymorphic VT is generally considered a marker of ongoing ischemia and often is suppressed by antiischemic interventions. Unlike monomorphic VT, polymorphic VT is rarely seen in patients with healed MI in the absence of acute myocardial ischemia.

Ventricular fibrillation

VF occurs in 3.7% of all acute ST elevation Mis in the first 48 hours, and this is likely an underestimation, as prehospital events are not included. When all VF events, before and after 48 hours, were included, VF was found to occur in 6.7% of ST elevation MI patients and in 1.3% of non–ST elevation MI patients. The majority of VF episodes occur early (within the first 48 hours) in the course of acute MI.

Primary VF (i.e., VF that occurs during the first 48 hours of an uncomplicated MI, without recurrent ischemia or heart failure) is associated with an up to fivefold increase in hospital mortality (>50% due to LV failure or cardiogenic shock) but appears to have little effect on long-term mortality in patients who survived to hospital discharge. Conversely, nonprimary VF (i.e., VF that occurs beyond the first 48 hours following MI or in the setting of recurrent ischemia or heart failure) is associated with marked increases in both 30-day and 6-month mortality. The temporal cutoff between “early” and “late” arrhythmias at 48 hours following MI, however, is arbitrary to some extent; some data suggest that this cutoff should be at 24 hours or even earlier.

Several factors appear to be associated with an increased risk of early VF during the periinfarction period, including ST elevation myocardial MI, larger infarct size, inferoposterior MI, periinfarction angina, incomplete revascularization, hypokalemia, hypotension, male gender, younger age, and history of smoking.

Sudden cardiac death

Sudden cardiac death (SCD) accounts for up to 15% of total mortality in industrialized countries and claims the lives of more than 200,000 to 400,000 people per year in the United States (precise number not known and impacted by how estimates are obtained). SCD victims have known heart disease—most frequently coronary artery disease or prior MI. Approximately 50% of deaths in patients with prior MI occur suddenly and unexpectedly. Ventricular arrhythmias are responsible for most of these deaths in stable ambulatory populations.

Cardiac arrest is the initial manifestation of heart disease in approximately 50% of cases. Such patients are more likely to have single-vessel coronary disease and normal or mildly abnormal LV systolic function than cardiac arrest victims with prior MI. Although heart failure increases risk for both sudden and nonsudden death, a history of heart failure is present in only approximately 10% of cardiac arrest victims.

Acute MI is a common precipitant of out-of-hospital cardiac arrest, especially in older patients. About 40% of out-of-hospital cardiac arrest survivors develop overt signs of an MI (e.g., ST-segment elevation, Q waves, or elevated cardiac enzymes), and 50% are found to have an acutely occluded coronary vessel on coronary angiography.

The risk for arrhythmic and total mortality is highest in the first month and stays high during the first 6 months after acute MI. After the first year post-MI, there appears to be a relatively quiescent period of relatively low rates of SCD, followed by a second peak 4 to 10 years after acute MI. The later occurrence of SCD likely results from delayed ventricular remodeling resulting in the creation or activation of reentrant VT circuits on the infarct border as well as from heart failure developing late after MI.

Although cardiac arrest and SCD in post-MI patients are predominantly caused by VT or VF, several studies in patients with cardiac arrest have shown that VF as the causative rhythm appears to be decreasing, being replaced by pulseless electrical activity and asystole. The cause of this change is unknown, but it may reflect patients with sicker hearts who are living longer due to better therapy. Hearts with advanced disease may be more likely to develop pulseless electrical activity and asystole than VF.

Sustained monomorphic ventricular tachycardia

“Early” SMVT within the first 24 to 48 hours of acute MI is uncommon, occurring in about 2% to 3% of ST elevation MI patients and in less than 1% of non–ST elevation MI patients. Although early SMVT is associated with an increase in in-hospital mortality, studies showed mortality at 1 year (among 21- to 30-day survivors) is not increased, suggesting that the arrhythmogenic mechanisms can be transient in early post-MI SMVT. Nevertheless, it is important to understand that data are limited regarding the long-term prognostic significance of SMVT in the early post-MI setting, as most studies combined VT and VF or sustained and nonsustained VT without specifying the results for each arrhythmia. Many investigators consider SMVT, even when occurring in the early hours following MI, to be an indicator of the presence of an already established permanent substrate (developing necrosis or preexisting scar) and, hence, an indicator of high long-term risk for arrhythmic events.

On the other hand, the typical patient with SMVT occurring during the subacute and healing phases, beginning more than 48 hours after an acute MI, has had a large, often complicated infarct with a reduced LVEF, and such VT is a predictor of a worse prognosis. SMVT within 3 months of an MI is associated with a 2-year mortality rate of 40% to 50%, with most deaths being sudden. Predictors of increased mortality in these patients include anterior wall MI, frequent episodes of sustained or nonsustained VT, heart failure, and multivessel coronary disease, particularly in individuals with residual ischemia.

Early reperfusion of infarct-related arteries results in less aneurysm formation, smaller scars, and less extensive EP abnormalities, although a significant risk of late VT (often with rapid tachycardia cycle lengths [TCLs]) persists. In patients with ST elevation MI treated with primary percutaneous coronary intervention, delayed reperfusion (>5 hours after MI) was associated with a six-fold increase in the odds of inducible SMVT by programmed electrical stimulation (performed 6–10 days post-MI) as well as an increased risk of spontaneous ventricular arrhythmias and SCD (after a mean follow-up of 28 ± 13 months) compared with early reperfusion (≤3 hours), independent of LVEF. It was estimated that each 1-hour delay in reperfusion conferred a 10.4% increase in the odds of inducible VT.

Most episodes of post-MI SMVT occur during the chronic phase. Among all patients presenting with SMVT in the setting of significant structural heart disease, ischemic heart disease is the most frequent etiology, comprising 54% to 59% of patients for whom an implantable cardioverter-defibrillator (ICD) is implanted or who are referred for catheter ablation.

VT occurs in 1% to 2% of patients late after MI, but the time interval from MI to first episode of VT is highly variable. The first episode can be seen within the first year post-MI, but the median time of occurrence is about 3 years, and SMVT can occur as late as 10 to 15 years after an MI. Late SMVT often reflects significant LV dysfunction and the presence of a ventricular aneurysm or scarring. Late arrhythmias can also result from new cardiac events. The annual mortality rate for SMVT that occurs after the first 3 months following acute MI is approximately 5% to 15%. Predictors of life-threatening ventricular arrhythmias include residual ischemia in the setting of damaged myocardium, LVEF of less than 40%, and electrical instability, including inducible or spontaneous VT, particularly in those who present with cardiac arrest.

Recent evidence suggests that coronary revascularization before or shortly after ICD placement in high-risk post-MI patients with LV dysfunction and wide QRS duration can potentially reduce the risk for life-threatening ventricular arrhythmias and appropriate ICD shocks.

The relationship between SMVT and VF is uncertain, and it is not clear how often VF is triggered by SMVT rather than occurring de novo. SMVT can simply be the company kept by VF in a number of patients or, in the appropriate setting such as recurrent ischemia, a rapid VT can develop a wavefront that becomes fractionated, leading to VF.

Evaluation of type and burden of ventricular arrhythmias

Identifying and quantifying the types and burden of sustained and nonsustained VT and PVCs are necessary. In addition to 12-lead ECG, ambulatory cardiac monitoring or implantable loop recorders may be required to document the type, burden, and clinical impact of the arrhythmia. In patients with ICDs, stored device data such as electrogram morphology and TCL can be used to identify the clinical VT.

Evaluation of the triggers of ventricular arrhythmias

Initial testing in patients with post-MI VT should evaluate for reversible causes of the arrhythmia. These include electrolyte imbalances, acute ischemia, heart failure, hypoxia, hypotension, drug effects, and anemia.

Evaluation of myocardial ischemia

Although recurrent SMVT is rarely due to acute myocardial ischemia in patients with known coronary artery disease, diagnostic evaluation for acute or persistent ischemia is warranted to improve patient outcome, especially if the severity of coronary artery disease has not been previously established or prior episodes of VT caused hemodynamic compromise. This may include echocardiographic examination, cardiac stress testing, and coronary angiography. In patients with reversible myocardial ischemia, coronary revascularization may be warranted and can potentially reduce the risk of life-threatening ventricular arrhythmias. However, if the severity of coronary disease has been recently defined and symptoms and hemodynamic tolerance of VT do not suggest significant ischemia, repeat evaluation may not be required.

Role of electrophysiological testing

Invasive EP testing should be considered in post-MI patients presenting with unexplained syncope or sustained palpitations, and those with wide complex tachycardia of uncertain mechanism. Additionally, EP testing can be used for risk stratification late after MI in patients with ischemic cardiomyopathy and nonsustained VT (see below). However, EP testing is not recommended in patients with documented sustained VT unless catheter ablation is planned.

Programmed stimulation induces VT in over 90% of patients with a history of VT. Although the rate and QRS morphology of the induced VT can differ from that observed during spontaneous tachycardia, the induction of VT signifies the presence of a fixed anatomical substrate associated with an increased likelihood of future spontaneous events.

Ventricular arrhythmias

In general, on the basis of large thrombolytic trials, the occurrence of ventricular arrhythmias and cardiac arrest in the early course (within the first 24–48 hours) of an uncomplicated acute MI is associated with increased in-hospital and 30-day mortality but has not been considered a marker of long-term mortality beyond hospital discharge. Early ventricular arrhythmias likely represent a transient, reversible arrhythmogenic event caused by acute ischemia and reperfusion rather than a permanent arrhythmogenic substrate; hence, they do not predict an increased risk for recurrence of arrhythmic events in patients who are successfully revascularized. Nonetheless, the long-term prognostic significance of SMVT in the early hours post MI remains uncertain, as most studies combined VT and VF or sustained and nonsustained VT without specifying the results for each arrhythmia. Many investigators consider SMVT, even when occurring in the early hours following MI, to be an indicator of the presence of an already established permanent substrate (developing necrosis or preexisting scar) and, thus, an indicator of high long-term risk for arrhythmic events.

On the other hand, multiple studies confirmed that the occurrence of sustained ventricular arrhythmias (VT and VF) late (>48 hours following acute MI) or in the context of complicated MI is associated with significantly worse long-term prognosis and high risk of SCD, even after successful revascularization. The temporal cutoff between “early” and “late,” however, remains uncertain. Many investigators prefer a 24-hour (rather than 48-hour) cutoff. Furthermore, some more contemporary studies found that both early and late sustained VT/VF were associated with a markedly increased risk of all-cause death at 30 days and 1 year after discharge despite revascularization.

Repetitive complex PVCs (ventricular bigeminy, couplets, or multiform PVCs) occurring beyond 48 hours after acute MI can be associated with increased arrhythmic risk, particularly in patients with larger MIs and impaired LV function. In a recent report evaluating ventricular ectopy on Holter recordings obtained 6 weeks after acute MI in patients with LVEF of 40% or less, frequent PVCs (≥10 per hour), prevalence of repeating forms of PVCs, and low coupling interval variability were potentially useful risk markers of fatal or near-fatal arrhythmias after MI. However, the utility of these risk markers in guiding ICD implantation is limited.

The occurrence of nonsustained VT in the subacute and chronic phases post MI has been found to predict an increased risk of cardiovascular death. Nonsustained VT has been used for risk stratification but only in conjunction with moderate to severe LV dysfunction (LVEF ≤40%) and inducible VT at EP study. Nonetheless, the current guidelines do not recommend surveillance cardiac monitoring beyond 24 to 48 hours of hospitalization after an acute coronary event.

Syncope

Patients with syncope (that is thought to be due to ventricular tachyarrhythmia) in the setting of structural heart disease (including LV systolic dysfunction or prior MI) have an increased incidence of SCD and overall mortality. It is recommended that these patients undergo ambulatory cardiac monitoring or invasive EP testing. If sustained VT is detected on cardiac monitoring or is inducible with programmed ventricular stimulation, an arrhythmic cause of syncope should be considered, and ICD implantation is recommended.

Left ventricular ejection fraction

Multiple studies evaluating survival of patients with prior MI established a clear relationship between reduced LVEF and increased mortality ( eTable 26.1 , eFig. 26.4) . However, these trials were designed to evaluate the usefulness of ICD in high-risk groups, defined mainly by reduced LVEF, and not to evaluate different variables, including LVEF, as risk stratifiers. In essence, these studies show that a reduced LVEF is associated with an increased risk of SCD and that ICD therapy improves survival, but they do not establish LVEF as the optimal risk stratification variable for arrhythmic mortality.

LVEF behaves as a continuous variable, with gradually increasing mortality risk until the LVEF declines to 40% and then markedly increasing risk for values less than 40%. Nevertheless, the exact mechanisms involved in the strong correlation between decreased LV systolic function and increased incidence of SCD are not clearly defined.

Although low LVEF identifies one patient population at relatively increased risk for SCD, there are clear limitations to LVEF as the ideal risk stratification test for deciding whether to implant an ICD for primary prevention of SCD. LV systolic dysfunction lacks specificity. LVEF is a global measure of heart function and is only loosely correlated with the amount of myocardial scar. There is no evidence of any direct mechanistic link between low LVEF and mechanisms responsible for ventricular tachyarrhythmias and no study has demonstrated that reduced LVEF is specifically related to SCD. In fact, in studies that enrolled all patients after MI, patients with LVEF of less than 30% to 35% account for no more than 50% of sudden cardiac arrest victims. Thus, although LVEF is a good marker of risk for total mortality, it does not provide insight into how patients are likely to die (sudden versus nonsudden). Furthermore, patients with low LVEF are not uniform with regard to other prognostic markers, and not all are at high risk for SCD.

Another limitation of LVEF is its poor sensitivity. Although most studies have focused on patients with markedly reduced LVEF, this group currently accounts for only 10% to 15% of MI survivors, and most contemporarily managed post-MI patients who suffer a cardiac arrest have better-preserved LV systolic function (i.e., LVEF ≥35%).

It is also recognized that methods of LVEF determination lack precision. Different imaging modalities can produce significantly different LVEF values, and the accuracy of techniques varies among laboratories and institutions, and there is evidence that prognosis, and hence risk, depends on the method by which the LVEF is measured. It is therefore recommended to use the LVEF determination that clinicians believe is the most clinically accurate and appropriate in their institution.

Invasive electrophysiological testing

Inducibility of VT/VF during invasive EP testing identifies patients at risk of spontaneous ventricular tachyarrhythmia and, hence, can enhance the predictive accuracy of reduced LVEF for post-MI patients with high mortality risk. Programmed ventricular stimulation is probably the most effective stratification technique for identification of post-MI patients at high risk for development of monomorphic VT, but the sensitivity is inadequate to predict SCD, especially in patients with severe LV systolic dysfunction.

The first MADIT study demonstrated that those patients with inducible VT/VF and LVEF of 35% or less late after MI are likely to benefit from prophylactic ICD therapy. Moreover, the absolute mortality reduction in MADIT I (26.2% over 27 months) was substantially greater than what was found in either MADIT II or SCD-HeFT. Similar results were found in MUSTT. However, secondary analysis from MUSTT revealed that despite the significant difference in outcome between inducible patients enrolled in the trial and noninducible patients enrolled in a registry, EP inducibility was of limited value because the 5-year mortality rate in inducible patients was 48% compared with 44% in noninducible patients. Later, data from MADIT II showed that there is no need for additional risk stratifiers (including EP testing) when LVEF is so low. In more than 80% of patients randomized to the ICD arm of MADIT II, invasive EP testing with an attempt to induce tachyarrhythmias was performed at the time of ICD placement. VT inducibility, observed in 40% of studied patients, was not effective in identifying patients with cardiac events defined as VT, VF, or death. These observations from both MUSTT and MADIT II subanalyses suggest that in patients with substantially depressed LV function, EP inducibility should not be considered a useful predictor of outcome. It is possible, however, that inducibility might have much better predictive value in post-MI patients with LVEF greater than 30% or greater than 35%.

Furthermore, using inducible VT/VF to guide prophylactic ICD therapy is limited by low sensitivity. Post-MI patients with LVEF of 35% or less and no inducible VT/VF still appear to have a substantial (>25%) risk of serious events over the near term. Additionally, there are no data to support the use of invasive EP testing in post-MI patients with LVEF values greater than 40% or in the early post-MI period. In fact, the BEST-ICD trial found that inducible VT/VF early after MI does not predict benefit from ICD therapy. In contrast, the CARISMA study found that inducible VT identified 6 weeks following an acute MI was a strong predictor of future life-threatening arrhythmias. Additionally, EP testing is invasive and not practical for broad application as a screening tool.

Nonetheless, EP testing can be valuable when used in patients in whom the risk of sustained arrhythmias and SCD is intermediate, and the potential benefit of ICD therapy unclear. However, uncertainty remains regarding the precise ventricular stimulation protocol and the type of tachycardia induced. Inducibility of SMVT indicates an arrhythmogenic substrate and identifies patients at high risk of subsequent spontaneous arrhythmia, regardless of the method of induction. On the other hand, the induction of sustained VF or ventricular flutter (usually with a TCL <200 milliseconds) has been considered a rather nonspecific finding, especially when induced with three or more VESs.

Current guidelines recommend prophylactic ICD therapy in post-MI patients with nonsustained VT and LVEF less than 40% if sustained VT/VF is inducible at EP study. In patient with relatively preserved LV systolic function (LVEF >40%), the role of EP testing has not been established.

Measures of cardiac repolarization

Microvolt-level T wave alternans (TWA) has emerged as a promising noninvasive marker of risk for SCD. TWA, measured on the surface ECG, detects subtle beat-to-beat oscillations in cardiac repolarization and has been linked to cellular mechanisms of arrhythmogenesis. Initial clinical studies of TWA demonstrated a high negative predictive value (≥95%). Additionally, an abnormal TWA was associated with significantly increased mortality risk as well as risk of arrhythmic events, although the positive predictive values were far more variable, depending on the characteristics of the study populations and pretest probability. Although initial studies suggested that TWA could potentially provide prognostically useful information beyond the LVEF and help guide selection of appropriate patients for prophylactic ICD therapy, several large multicenter studies of TWA failed to support these findings. In fact, the latter studies strongly suggested that a negative TWA result should not be used to withhold ICD therapy among patients who meet other standard criteria.

Other noninvasive measures of dispersion of repolarization, including QT dispersion, QT variability, and QT dynamics, have had similar mixed predictive results in studies with limited clinical applicability.

Measures of autonomic imbalance

Methods to assess the autonomic nervous system, which has been thought to be a modulator between triggers of ventricular tachyarrhythmias and the underlying substrate (including heart rate variability, baroreflex sensitivity, heart rate turbulence, and deceleration capacity), have been evaluated for risk stratification of SCD. Multiple studies have correlated relative excess of sympathetic tone (or deficient parasympathetic tone) with increased mortality in post-MI patients as well as increased propensity for VF during acute ischemia. Although the majority of studies showed no significant difference in relative risk for SCD versus total mortality, a meta-analysis found that heart rate turbulence was a powerful predictor of both cardiac death and arrhythmic events following acute MI in patients with LVEF greater than 30%, and its performance was improved in combination with TWA. Nevertheless, these measures need further validation to support their use in guiding prophylactic ICD therapy.

Measures of myocardial conduction disorders

Increased QRS duration on a surface ECG has been associated with a higher risk of death after MI and appears to reflect greater LV dysfunction, but association with SCD has not been proven. Similarly, the presence of late potentials on signal-averaged ECG failed to identify patients likely to benefit from ICD therapy. Because of the lack of discrimination in the mode of death, these noninvasive markers of risk have not had widespread adoption.

Additionally, fragmentation of the QRS complex on the 12-lead surface ECG (filter range, 0.15–100 Hz; AC filter, 60 Hz, 25 mm/sec, 10 mm/mV), which likely signifies inhomogeneous ventricular activation due to myocardial scar or ischemia in patients with coronary artery disease, has been found to potentially predict increased risk of appropriate ICD therapies in patients who received an ICD for primary and secondary prevention. In a recent meta-analysis, fragmented QRS was found to be an indicator of all-cause mortality and SCD risk. The risk was greater in patients with LVEF 35% or less and in those with QRS duration exceeding 120 milliseconds. However, in the absence of a prospective study of ICD implantation randomized on the basis of fragmented QRS, it is not clear how the tool should be applied in clinical practice.

Genetic testing

There is compelling evidence that a genetic mechanism may increase patient susceptibility to SCD following MI, and genetic assessment may play a role in the future. However, there is presently no evidence for using genetic testing to identify post-MI patients at risk.

Cardiac magnetic resonance imaging

Characteristics of myocardial scar architecture and tissue heterogeneity in the periinfarct zone, as defined by contrast-enhanced CMR, can potentially identify a proarrhythmic substrate and appears to be a strong predictor of ventricular arrhythmias and appropriate ICD therapies. In patients with ischemic cardiomyopathy, nontransmural (rather than transmural) hyperenhanced areas were found to predict a higher risk of sustained VT. Current evidence, however, does not support the use of CMR for SCD prognostication. Large prospective trials are still required to evaluate the reliability of these techniques for risk stratification.

Risk stratification early postinfarction

The risk of SCD is greatest in the first month after MI and appears to decline in the first year after MI. Nevertheless, both prospective and retrospective studies have failed to show a reduction in all-cause mortality with prophylactic ICD therapy in early post-MI patients. The reasons for the lack of benefit of ICD implantation early after MI are unclear. The reduction in the rate of death due to arrhythmia associated with ICD therapy was offset by an increase in the rate of death from nonarrhythmic cardiac causes (e.g., LV rupture, acute mitral regurgitation) in the ICD groups ( eTable 26.1 , eFig. 26.4) . This discrepancy not only highlights the limitations of current risk stratification techniques but also reflects relative differences in the risk factors for SCD at different time points after MI and the fact that nonarrhythmic death accounts for an appreciable percentage of deaths during that time period. Additionally, some portion of the post-MI population will eventually recover LV function, rendering them at lower risk of SCD.

Heart rate and creatinine clearance measured at baseline are strongly associated with SCD during the in-hospital period, whereas recurrent cardiovascular events (including heart failure, MI, and rehospitalization) and a baseline LVEF of 40% or less are more strongly associated with the occurrence of SCD after discharge.

Whereas the cumulative incidence of SCD is greatest in post-MI patients with an LVEF of 30% or less, the incidence of SCD is higher in patients with an LVEF greater than 40% in the first 30 days after MI when compared with patients with an LVEF of 30% or less after 90 days. The strength of the association between LVEF and survival free from SCD appears to be greatest in long-term follow-up (>6 months). Currently, there is no strategy (invasive or noninvasive) that can reliably predict the risk for SCD or guide empiric ICD implantation soon after an MI. Data suggest it is best to wait 2 to 3 months after acute MI before performing risk stratification.

Some evidence suggests a potential benefit of EP testing in risk stratification in patients with ST elevation MI and LVEF less than 40% treated with primary percutaneous coronary intervention. Inducible SMVT by programmed electrical stimulation performed 6 to 10 days post-MI was associated with an increased risk of spontaneous VT/VF and SCD (after a mean follow-up of 28 ± 13 months). However, further evaluation in randomized clinical trials is required before adoption of this approach.

Pharmacological therapy

Implantable cardioverter-defibrillator

Secondary prevention

ICD therapy has a proven mortality benefit among patients with structural heart disease and a history of VT or VF, with a 7% absolute reduction and a 25% relative reduction in all-cause mortality (as compared with amiodarone therapy), due entirely to a 50% reduction in arrhythmic death.

Implantation of an ICD is recommended for secondary prevention in patients with prior cardiac arrest or sustained VT, even when systolic function is normal, and even in patients undergoing successful catheter ablation of the VT or responding to antiarrhythmic therapy, because the latter two approaches do not sufficiently reduce residual risk of SCD ( Table 26.1 ; Fig. 26.4 ). Also, ICD implantation is recommended in patients with syncope and inducible SMVT even if they do not otherwise meet criteria for primary prevention. Importantly, in patients with incessant VT or VF, an ICD should not be implanted until sufficient arrhythmia suppression is achieved (by drug therapy or ablation) to prevent repeated ICD shocks.

TABLE 26.1

AHA/ACC/HRS Recommendations for Prevention of SCD in Patients With Ischemic Heart Disease

From Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm. 2018;15(10):e73-e189.

Secondary Prevention
In patients with ischemic heart disease, who either survive SCA due to VT/VF or experience hemodynamically unstable VT or stable VT not due to reversible causes, an ICD is recommended if meaningful survival greater than 1 yr is expected.	Class I
In patients with ischemic heart disease and unexplained syncope who have inducible sustained monomorphic VT on electrophysiological study, an ICD is recommended if meaningful survival of greater than 1 yr is expected.	Class I
Primary Prevention
In patients with LVEF of 35% or less that is due to ischemic heart disease who are at least 40 days post-MI and at least 90 days postrevascularization, and with NYHA class II or III HF despite GDMT, an ICD is recommended if meaningful survival of greater than 1 yr is expected.	Class I
In patients with LVEF of 30% or less that is due to ischemic heart disease who are at least 40 days post-MI and at least 90 days postrevascularization, and with NYHA class I HF despite GDMT, an ICD is recommended if meaningful survival of greater than 1 yr is expected.	Class I
In patients with NSVT due to prior MI, LVEF of 40% or less and inducible sustained VT or VF at electrophysiological study, an ICD is recommended if meaningful survival of greater than 1 yr is expected.	Class I
In nonhospitalized patients with NYHA class IV symptoms who are candidates for cardiac transplantation or an LVAD, an ICD is reasonable if meaningful survival of greater than 1 yr is expected.	Class IIa
An ICD is not indicated for NYHA class IV patients with medication-refractory HF who are not also candidates for cardiac transplantation, an LVAD, or a CRT defibrillator that incorporates both pacing and defibrillation capabilities.	Class III

CRT , Cardiac resynchronization therapy; EP , electrophysiological; GDMT , guideline-directed management and therapy; HF , heart failure; ICD , implantable cardioverter-defibrillator; IHD , ischemic heart disease; LVAD , left ventricular assist device; LVEF , left ventricular ejection fraction; MI , myocardial infarction; NSVT , nonsustained ventricular tachycardia; NYHA , New York Heart Association; SCA , sudden cardiac arrest; SCD , sudden cardiac death; VF , ventricular fibrillation; VT , ventricular tachycardia; WCD , wearable cardioverter-defibrillator.

Although one report has questioned the benefit from an ICD compared with pharmacological therapy in patients with VT and LVEF exceeding 40%, the guidelines did not stratify recommendations based on the LVEF. This seems appropriate for two reasons: the prognostic importance of the LVEF was based on subset analysis and, given the current ease of ICD implantation, the potential adverse consequences of choosing a possibly less effective therapy are too great.

Sustained VT or VF occurring within the first 24 to 48 hours of an uncomplicated acute MI is usually considered to be a result of a transient, reversible arrhythmogenic event caused by acute ischemia rather than a permanent arrhythmogenic substrate; hence, they are thought to be relatively benign and do not predict an increased risk for recurrence arrhythmic events in patients who are successfully revascularized. Early ICD implantation is not recommended in those patients unless coronary revascularization is not possible and there is evidence of significant preexisting LV dysfunction. On the other hand, ICD implantation is recommended for all patients who develop sustained VT or VF beyond the first 48 hours following acute MI or in the context of a complicated MI, which are considered indicators of worse long-term prognosis and high risk of SCD, even after successful revascularization. Early ICD implantation (or the temporary use of a wearable cardioverter defibrillator) is usually recommended in those patients. It is worth noting that the temporal cutoff between “early” and “late,” however, is not clear. Many investigators prefer a 24-hour (rather than 48-hour) cutoff.

Importantly, prolonged episodes of sustained monomorphic VT or VF may be associated with a rise of cardiac enzymes related to myocardial supply-demand mismatch rather than a primary coronary event. Therefore, patients with coronary artery disease who present with sustained VT or VF and modest elevations of cardiac enzymes should not be assumed that a new MI was the cause of the VT or VF. If clinical evaluation for ischemia does not support the occurrence of a new MI, these patients should be treated similarly to patients who have sustained VT and no documented rise in cardiac enzymes, including ICD implantation for secondary prevention.

Although ICDs improve overall survival, they do not eliminate the substrate responsible for sustained arrhythmias and therefore do not prevent arrhythmias. Furthermore, ICD shocks, both appropriate and inappropriate, are associated with increased mortality and reduced quality of life. To reduce the risk of these events, ICD detection criteria and therapies should be programmed to minimize inappropriate shocks, prevent shocks for potentially self-terminating VTs, and favor antitachycardia pacing therapies when feasible. Long VT detection intervals prior to the delivery of ICD therapies and rapid VF detection rates reduce shocks and improve mortality in patients receiving an ICD for primary prophylaxis. The value of programming a long VT detection time in patients with a history of sustained VT or VF is less certain. Furthermore, while device programming can reduce the frequency of ICD shocks, it does not reduce the risk of VT recurrence or eliminate the symptoms associated with the arrhythmia, such as palpitations, dizziness, and syncope.

Primary prevention

Current guidelines recommend prophylactic ICD implantation in patients with prior MI and reduced LVEF (<35%) who are on optimal medical management ( Table 26.1 ; Fig. 26.5 ). These recommendations are based on the fundamental relationship that exists between reduced LVEF and cardiovascular mortality and the findings of MADIT II and SCD-HeFT. Both MADIT II and SCD-HeFT clearly demonstrated a mortality benefit from prophylactic ICD therapy in patients with a history of MI and severely reduced LVEF (≤30% and ≤35%, respectively). However, the absolute mortality reduction in these trials was modest: 5.6% over 27 months in MADIT II and 7.3% over 60 months in SCD-HeFT. Fewer than one in five ICD recipients in MADIT II and SCD-HeFT received appropriate ICD therapies over average follow-up periods of 20 and 60 months, respectively. Since appropriate ICD therapies overestimate the mortality benefit of ICD therapy by at least twofold, fewer than 1 in 10 patients who receive a prophylactic ICD for an LVEF of 35% or less post-MI are likely to receive a survival benefit in the near term. In two meta-analyses of these trials, ICD therapy in high-risk coronary artery disease patients resulted in a net risk reduction for total mortality of 20% to 30%.

EP testing appears most useful as an adjunct study in patients having equivocal results after noninvasive testing and in whom the potential benefit of ICD therapy is uncertain. Examples include patients with remote MI, nonsustained VT, and an LVEF between 30% and 40%, as suggested by the most recent guidelines, or in combination with other clinical risk factors or symptoms suggestive of ventricular tachyarrhythmias including palpitations, presyncope, and syncope. Patients with coronary artery disease who are found to have inducible monomorphic VT during programmed stimulation should be treated for the prevention of SCD. The mode of stimulation (burst pacing, single or double VESs versus triple VESs) of sustained VT does not influence prognosis and should not influence treatment decisions.

In the acute to subacute period after MI, arrhythmia substrate is dynamic. LV function can improve in up to 70% of patients post acute MI. Although the risk of SCD is highest in the first month after MI, there is currently no reliable risk stratification strategy that can guide early prophylactic ICD implantation. In fact, primary prevention trials with ICD have failed to show a reduction in all-cause mortality (despite a decrease in arrhythmic mortality) in early post-MI patients identified on the basis of the current risk stratifiers. SCD in this period may occur from not only arrhythmic but also nonarrhythmic (mechanical) causes, limiting ICD benefits. Accordingly, the current published guidelines recommend avoiding ICD implantations in the early post-MI phase. Therefore, in the early post-MI period, medical therapy and coronary revascularization, when feasible, should be optimized. The LVEF should then be measured at least 40 days after the MI and, if the LVEF remains 35% or less, the patient should be considered for prophylactic ICD implantation. Whether the 40-day waiting period still applies in patients with acute MI who have known LV dysfunction and who have previously satisfied criteria for implantation of a primary prevention ICD is still controversial. Since those patients have an increased rate of nonarrhythmic mortality that is unlikely to be significantly impacted by early ICD implantation, some investigators recommend implementing the 40-day waiting period in these patients.

It is important to understand, however, that the mere presence of elevated cardiac enzymes does not establish a diagnosis of acute MI. If clinical evaluation for ischemia does not support the occurrence of a new MI, early implantation of an ICD is recommended in patients who otherwise would be candidates for implantation on the basis of primary prevention or secondary prevention criteria. Similarly, the waiting period may not be mandated in patients who, within 40 days of an MI, require a nonelective permanent pacemaker implantation or present with syncope that is thought to be due to ventricular tachyarrhythmia (by clinical history, documented NSVT, or EP study), who also would meet primary prevention criteria for implantation of an ICD, and recovery of LV function is uncertain or not expected. Early ICD implantation with appropriately selected pacing capabilities is recommended in these patients.

Additionally, improvement of LVEF of 5% to 6% or more can be observed in 15% to 65% of patients following coronary revascularization. Therefore, LVEF should be reevaluated 6 to 12 weeks after coronary revascularization to assess potential indications of ICD implantation for primary prevention. As noted above, the waiting period may not be mandatory for patients in whom recovery of LV function is uncertain or not expected and either require a nonelective permanent pacemaker implantation or present with syncope that is thought to be due to ventricular tachyarrhythmia (by clinical history, documented NSVT, or EP study).

Wearable cardioverter defibrillators effectively terminate VT and VF and are a potential therapeutic option to bridge patients from hospital discharge until follow-up evaluation of LV function to assess the value of ICD for primary prevention of SCD. The wearable external defibrillator vest can provide protection from SCD during the early period after MI until arrhythmic risk may be reduced after improvement in LVEF, or until ICD implantation can be performed for those with persistently reduced LVEF. A series of observational studies and a prospective registry of 2000 patients found a significant value of wearable external defibrillators in the protection of patients during the 90-day high-risk post-MI period. On the other hand, the Vest Prevention of Early Sudden Death Trial (VEST), the only randomized clinical trial of wearable external defibrillators, compared the use of wearable external defibrillators plus guideline-directed medical therapy with guideline-directed medical therapy alone in patients who presented with an acute MI with LVEF of 35% or less. The wearable external defibrillator did not result in a statistically significant reduction in the primary endpoint of arrhythmic mortality compared to medical therapy during the first 90 days. Those findings could potentially be related to inadequate sample size and event rate for appropriate statistical power as well as to the lower-than-expected compliance with the use of wearable external defibrillators in the trial. Data reanalysis based on patient compliance suggests that use of the device could be of significant benefit in appropriately selected post-MI patients. Accordingly, an individualized approach needs to be considered, incorporating patient education as well as patient-specific factors related to compliance.

Catheter ablation

Catheter ablation of post-MI VT is generally indicated as a palliative and adjunctive therapy in post-MI patients with ICD who experience frequent recurrences of VT or ICD therapies. Recurrences of VT/VF causing frequent ICD therapies (including ICD shocks) are relatively common; approximately 20% to 35% of ICD recipients for primary prevention and up to 45% of those who receive an ICD for secondary prevention will receive an appropriate shock within 3 years of implantation.

Although ICD shocks for rapid VT or VF reduce the risk of SCD by approximately 60%, the occurrence of shocks can have deleterious consequences. ICD shocks are associated with progressive heart failure symptoms, a significant decline in psychosocial quality of life, and a two- to fivefold increase in nonarrhythmic mortality, despite termination of the acute arrhythmic event. The incidence of appropriate shocks can be reduced by using antitachycardia pacing in the VT or VF detection zones, or with up-titration of effective medical therapies. If optimization of pharmacological therapies and device programming fails to suppress appropriate ICD shocks for VT, or when ventricular arrhythmias precipitate significant symptoms, such as anginal, presyncope, syncope, or worsening heart failure, catheter ablation is recommended.

Compared to antiarrhythmic drug therapy, catheter ablation is significantly more effective in reducing the risk of VT recurrences in patients with ischemic cardiomyopathy and has emerged to become a standard of care to prevent medically refractory ICD shocks. Successful VT ablation can minimize long-term exposure to antiarrhythmic drugs or substantially reduce their dose requirement, which can potentially improve long-term outcomes. However, a reduction in overall mortality has yet to be demonstrated.

Catheter ablation reduces VT recurrences and thereby ICD interventions by more than 75% in patients after multiple ICD shocks. However, most patients with post-MI VT have multiple types of monomorphic VTs, and elimination of all VTs often is not feasible, and because the recurrence of an ablated VT or the onset of a new VT can be fatal, RF ablation is rarely used as the sole therapy for VT. Instead, VT ablation is typically used for patients with coronary artery disease as an adjunct to an ICD. In this patient population, the incidence of ablation procedure-related death ranges from 0% to 3%, and the incidence of major complications ranges from 3.6% to 10%.

Catheter ablation is necessary and can be life-saving in patients with electrical storm and incessant VT without any apparent correctable cause and despite adequate medical treatment. Repeated ICD shocks within a short time interval, known as an ICD “storm,” occur in 10% to 25% of patients. Accumulated evidence suggests that acute suppression of the VT in electrical storm can be achieved in up to 90% of patients. However, arrhythmic recurrences are frequent during follow-up. In the setting of incessant VT, catheter ablation is preferred over antiarrhythmic drug therapy. Catheter ablation may also be considered for patients with recurrent polymorphic VT or VF when those arrhythmias are triggered by PVCs of consistent QRS morphology. In this setting, ablation targets the arrhythmia trigger rather than the substrate.

The optimal timing of catheter ablation in ICD patients (after multiple ICD interventions or before any ICD intervention) remains unclear. Current guidelines recommend considering catheter ablation for VT that recurs despite antiarrhythmic drug therapy or when antiarrhythmic drugs are not tolerated or desired ( Table 26.2 ). In clinical practice, VT ablation is often not considered until pharmacological options have been exhausted, often after the patient has suffered substantial morbidity from recurrent episodes of VT and ICD shocks. However, recent studies suggest that catheter ablation should generally be considered early in the course treatment of post-MI VT, before escalating medication therapy.

The role of a preventive ablation strategy (i.e., after a first VT episode and before initiating antiarrhythmic drug therapy) has been investigated in recent studies. While such an approach significantly reduced VT recurrences and ICD therapies following ablation compared with conventional medical therapy, there was no mortality benefit favoring preventive ablation. Nonetheless, a preventive ablation strategy may have an important role for appropriately selected patients, such as those presenting with slow VT, which can potentially complicate ICD programming, and patients in whom long-term treatment with antiarrhythmic drugs such as amiodarone would not be tolerated.

ECG clues to the underlying substrate

VTs arising from normal myocardium typically have rapid initial forces, whereas slurring of the initial forces is frequently seen when the VT arises from an area of scar or from the epicardium. Additionally, VTs originating from very diseased hearts usually have lower amplitude complexes than those arising in normal hearts, and the presence of notching and fractionation of the QRS can be a sign of scar tissue with resultant disrupted wavefront propagation.

Whereas QS complexes can be seen in a variety of disorders, the presence of qR, QR, or Qr complexes in related leads is highly suggestive of the presence of an infarct. Sometimes it is easier to recognize the presence of MI during VT than during NSR (i.e., LBBB in NSR masking an infarct).

ECG localization of postinfarction ventricular tachycardia

QRS morphology in lead V ₁

Post-MI VTs with RBBB patterns always arise in the LV, and VTs with LBBB patterns almost always arise in or adjacent to the LV septum. Therefore, LBBB patterns have a higher predictive accuracy (regardless of the presence of anterior versus inferior MI) than RBBB patterns, which could be septal or located on the free wall. Most VTs with RBBB patterns associated with inferior MI are clustered in a small region but are more widely disparate with anterior MI ( eFigs. 26.5 and 26.6) .

Inferior myocardial infarction ventricular tachycardias

With inferior MI, most VTs have basal exit sites and thus have relatively preserved precordial R waves (that usually are present in leads V ₂ –V ₄ with the persistence of an r or R wave through lead V ₆ ). However, more extensive inferior MIs can result in apical exits ( Fig. 26.9 ).

Ventricular tachycardia with LBBB morphology

VTs with LBBB (especially when left axis deviation is present) have a characteristic location at the inferobasal septum ( eFig. 26.6 ). As the VT axis shifts to a more normal axis, the exit site moves higher up along the septum. Rarely, inferior MI VTs can have exit sites as high as the aortic valve along the septum. Very rarely, the VT can only be ablated from the RV.

Ventricular tachycardia with RBBB morphology

In VTs with RBBB, the R waves can persist across the precordium (positive concordance). When the VT originates near the posterior basal septum and when it arises more laterally (or posteriorly), there can be a decrease in the R wave amplitude across the precordium because the infarct can extend to the posterolateral areas ( eFig. 26.5 ). Left axis deviation is seen in inferior MI VTs when the exit site is near the septum. As the VT exit moves from the midline toward the lateral (i.e., posterior) wall, the QRS axis becomes directed more rightward or superior.

The mitral isthmus (between the mitral annulus and inferior infarct scar) contains a critical region of slow conduction in some patients with VT following inferior MI, providing a vulnerable and anatomically localized target for catheter ablation. This critical zone of slow conduction is activated parallel to the mitral annulus in either direction, resulting in two distinct QRS configurations not seen in VTs arising from other sites: LBBB pattern (rS in lead V ₁ , R in lead V ₆ ) with left superior axis, and RBBB pattern (R in lead V ₁ , QS in lead V ₆ ) and right superior axis.

The QRS axis–based algorithm

A new ECG algorithm was recently proposed to help regionalize the origin of LV VTs in patients with structural heart disease. This two-step algorithm is based on assessment of the QRS axis in the frontal plane to locate the VT origin in the LV short-axis plane (inferior versus anterior, septal versus lateral) and the polarity in the midprecordial leads (V ₃ and V ₄ ) for its location in the LV longitudinal plane (basal, medial, or apical).

In the first step, the ECG limb lead with the highest voltage magnitude (positive or negative) is identified and is used to indicate a more septal versus lateral and superior versus inferior VT segment of origin. If this magnitude is in lead I, II, or III, the adjacent leads must be considered, as the major axis is facing the boundary between the two groups of segments. The adjacent limb lead with higher magnitude will determine the group of segments where VT may originate. In the second step, the polarity in leads V ₃ and V ₄ is assessed and is used to indicate a basal (V ₃ and V ₄ positive) versus mid (only V ₃ positive) versus apical origin (V ₃ and V ₄ negative) ( Fig. 26.10 ; eFig. 26.7 ).

The algorithm’s diagnostic accuracy for regionalization of the VT segment of origin was 82%, which notably did not appear to depend on the type of cardiomyopathy, on the size or location of MI, or on an epicardial versus endocardial VT origin.

Epicardial ventricular tachycardias

Epicardial VT exits are uncommon in post-MI VT, because of the subendocardial nature of the underlying substrate. With all other factors being equal, an epicardial origin of ventricular activation widens the initial part of the QRS complex (pseudodelta wave). When the initial activation starts in the endocardium, rapid depolarization of the ventricles occurs along the specialized conducting system, resulting in a relatively narrower QRS on the surface ECG and the absence of a pseudodelta wave. In contrast, when the initial ventricular activation occurs in the epicardium, the intramyocardial delay of conduction produces a slurred initial part of the QRS complex.

Several ECG findings suggest an epicardial origin of the LV VT with an RBBB pattern, and all generally rely on the late engagement of rapidly conducting His-Purkinje fibers by tachycardia circuit exits on the epicardium, including the presence of a pseudodelta wave, very wide QRS complex (duration ≥200 milliseconds), long R-wave peak time in lead V ₂ , and shortest RS complex duration in any precordial lead longer than 120 milliseconds. However, the proposed 12-lead ECG features for differentiation of epicardial versus endocardial VT exit sites were assessed in patients without MI, and their utility for localization of post-MI VTs has not been validated. ECG criteria for identifying an epicardial origin of VT appear to be region and substrate specific. In fact, in a more recent study, these ECG characteristics failed to reliably identify post-MI VTs requiring epicardial ablation. Slow initial forces can be present during tachycardia at the MI scar region and, hence, not specific for epicardial origins. Furthermore, the presence of typical Q waves in the VT ECGs of patients with previous MI precludes the use of morphological ECG criteria, and when present in the precordial leads, Q waves can interfere with the measurement of all interval criteria.

It is also important to note that the VT 12-lead ECG provides information about the VT exit site from the scar border, which is generally not the ablation target. In post-MI VT, the critical isthmus constitutes the target for ablation, and this isthmus can be complex and can have an endocardial and epicardial trajectory permitting successful ablation from endocardium (especially in the presence of wall thinning) even in a VT with an epicardial exit. Therefore, endocardial mapping should be the first approach to catheter ablation for VTs in patients with ischemic heart disease, even when the surface ECG suggests an epicardial origin of the tachycardia.

Induction of tachycardia