Introduction
The relationship between coronary heart disease (CHD) and sudden cardiac death (SCD) has long been recognized, with an initial description by Leonardo Da Vinci in the 15th century of an SCD, which he witnessed and attributed at autopsy to a “parched and shrunk and withered . . . artery that feeds the heart.” Research over the past 50 years allowed improved characterization and understanding of CHD as a substrate for SCD. Many pathophysiologic processes underlying the vulnerability to SCD in CHD have been increasingly recognized, including the impact of CHD burden, vascular pathophysiology, the role of ischemia and scarring, the electrophysiologic abnormalities of the myocardial substrate, and the role of ischemic cardiomyopathy and left ventricular (LV) dysfunction. This has allowed significant advancements in medical and interventional therapies to prevent and treat SCD.
Definition and Epidemiology
SCD is defined as death from otherwise unexpected sudden circulatory collapse from a cardiovascular cause. Generally, this includes SCD events that are witnessed, occurring within 1 hour of change in clinical status, or nonwitnessed death, which has occurred within the preceding 24 hours. As such, the estimates of SCD in the community have varied based on definitions and ascertainment of events. In the United States, it is estimated that 300,000 to 350,000 SCD cases occur every year.
The exact contribution of CHD to the population of SCD cases is not clearly defined and remains a subject of debate. In fact, SCD estimates in the United States are largely based on the retrospective review of death certificates or extrapolation to the general population from smaller well-studied communities. Nonetheless, it is generally accepted that approximately 80% of all SCD cases are related to CHD and that SCD accounts for approximately 50% of all deaths from CHD. Improvements in primary and secondary prevention measures have led to significant declines in CHD-related mortality since the 1980s, but the rates of sudden and unexpected deaths from CHD have declined to a lesser extent. This reflects two challenging aspects in risk stratification: SCD is the initial clinical manifestation of CHD in a substantial proportion of SCD events, and accurate SCD risk prediction in patients with established CHD remains suboptimal. As such, individual risk assessment in clinical practice remains difficult with the currently available tools and strategies.
Similarly, it remains difficult to ascertain age, gender, and racial differences in CHD-related SCD events. However, it is likely that similar trends would be observed due to the substantial contribution of CHD to the overall SCD burden. In general, the incidence of SCD increases with age regardless of gender or race. However, by age groups, the proportion of overall deaths classified as SCDs appears to be more significant in the young. Women, in general, have a lower incidence of SCD than do men which may reflect the lower or delayed burden of CHD in women. There also appear to be some racial differences in SCD epidemiology. Black Americans are at higher risk compared to white Americans, and Hispanic Americans are at lower risk than are non-Hispanic Americans. Whether these variations are related to genetic or socioeconomic differences is not clear.
Pathophysiology
The pathophysiology of SCD is complex but is believed to reflect the interaction of the vascular substrate, the myocardial substrate, and systemic modulation. SCD events typically require a substrate and a trigger, which lead to electrical instability and lethal ventricular arrhythmia, which result in hemodynamic collapse and death ( Fig. 22.1 ). Both the substrate and the triggers are dynamic, contributing to the clinical challenges in risk stratification.
Historically, SCD events were viewed as a function of the severity of chronic CHD atherosclerotic lesions, but the understanding of the vascular substrate, as a dynamic component, has evolved over the years. Whereas the severity and distribution of significant coronary stenoses is important for the pathogenesis of SCD, the dynamic variations in plaque properties, inflammation, or vulnerability to rupture may significantly contribute to SCD. An unstable plaque, even in the absence of acute coronary syndrome (ACS) from significant lumen occlusion, may lead to spasm and could trigger arrhythmias. As such, the identification of a culprit vessel, especially postmortem, is not an easy task even in the presence of a severely stenotic vessel. Similarly, the myocardial substrate, which is to a degree dependent on the dynamic vascular substrate, could generate ventricular arrhythmias independently of the status of blood supply, such as in scar-dependent arrhythmia circuits. This myocardial substrate is dynamic as well, such as in transient ischemia or in postinfarct scar remodeling, especially in the border zones between scar and normal myocardium. The dynamic changes affecting the myocardium and its vulnerability to arrhythmias include mechanical stress and autonomic influences, which may result in transient ischemia or vulnerability of a static scar to electrical reentry and arrhythmogenesis.
The contribution of CHD to SCD encompasses the spectrum of CHD and its effect on the myocardium as an arrhythmogenic substrate. Clinical settings include: (1) SCD as the initial clinical manifestation of CHD, (2) acute myocardial infarction (MI) or ACSs, (3) acute myocardial ischemia without infarction, (4) myocardial convalescence post-MI, and (5) CHD-related structural changes, such as scar formation or ventricular dilatation from prior infarction or chronic ischemia. In the latter, there is a particular role for the severity of LV dysfunction and heart failure in SCD pathogenesis.
It is estimated that approximately 25% of CHD-related SCD patients have evidence of myocardial necrosis on autopsy studies. In sudden cardiac arrest survivors, biomarker evidence of MI is present in approximately 40% of patients, which suggests that acute MI contributes to some but not all CHD-related SCD. In non-MI CHD-related SCD, the underlying mechanism is ventricular arrhythmia caused by ischemic or other arrhythmogenic triggers with an underlying diseased substrate.
Sudden Cardiac Death as the Initial Clinical Manifestation of Coronary Heart Disease
This is perhaps the most challenging group for both clinicians and researchers. It is estimated that this first event category contributes approximately one-third of all SCD events, accounting for over 100,000 cases every year in the United States. Unfortunately, strategies are lacking for risk stratification and identification of subjects at risk in the general population. Risk assessment relies primarily on identifying high-risk pockets within low-risk groups. The presence of CHD risk factors carries a risk of future SCD even in the absence of clinically recognized CHD, emphasizing the importance of risk factor control to prevent SCD in the general population.
Sudden Cardiac Death at the Time of Acute Myocardial Infarction or Acute Coronary Syndromes
This typically refers to the initial 24- to 48-hour period after the onset of an MI. Whereas it shares some features related to SCD from ischemia without infarction, elevated risk in this setting is characterized by a dynamic substrate, which is a manifestation of acute loss of blood supply; ischemia and cardiomyocyte death; abnormal local electrical activation patterns; reperfusion and dynamic heterogeneities in electrical properties in the infarct and peri-infarct zones; and systemic factors, such as inflammation, hemodynamic alterations, and neurohormonal alterations. The endpoint of these phenomena is predisposition to electrical reentry and vulnerability to ventricular arrhythmias.
The burden of arrhythmias in the acute phase of MI appears to have decreased with early interventions to restore blood flow that may reverse or at least stabilize the local arrhythmogenic process.
Ventricular arrhythmias occurring in the early phase after an acute MI have been considered transient without prognostic implications for long-term risk of recurrence. This is likely related to the multitude and dynamic nature of factors that contribute to arrhythmogenesis in the acute phase of MI. However, it has been suggested in some studies that a cardiac arrest in the early phase of acute MI might indicate some long-term risk ; however, it remains unknown whether this is related to individual predisposition, recurrent ischemia, subsequent remodeling, or further deterioration in LV function. Nevertheless, ventricular arrhythmias in the first 48 hours after MI do not serve as an indication for defibrillator implantation for secondary prevention purposes.
Sudden Cardiac Death from Acute Myocardial Ischemia Without Infarction
SCD from acute myocardial ischemia without infarction is typically from a supply-demand mismatch that results in transient ischemia and increased arrhythmic risk. Scenarios include either plaque rupture with acute thrombosis limiting blood flow, or vasospasm resulting in the same, as well as high-grade stable lesions in the setting of a sudden increase in demand. The abnormalities in myocardial perfusion and associated regional variations in ischemia and reperfusion result in regional heterogeneities in electrical properties and cell membrane electrophysiology with resultant vulnerability to triggered electrical activity, reentry, and SCD.
In transient ischemic states, both the ischemia and reperfusion phases are important in arrhythmogenesis, the former by creating electrical gradients across the myocardium and areas of inexcitability and the latter by affecting repolarization dispersion in affected areas. Triggered activity from this phenomenon typically generates polymorphic ventricular tachycardia (VT) that can degenerate into ventricular fibrillation (VF) and SCD.
Sudden Cardiac Death During Convalescence Post–Myocardial Infarction
This phase typically starts beyond the first 48 hours after MI and extends for weeks, months, or even years with continuing vascular and myocardial remodeling. Ventricular arrhythmias that occur during this phase, in contrast to arrhythmic events in the early post-MI phase, are strongly associated with risk of clinical recurrence of ventricular arrhythmias and with SCD. This risk appears to be further increased by the degree of LV dysfunction and remains elevated despite modern therapies.
Of note, not all SCD events in the early convalescence phase post-MI are arrhythmic in nature and many could be attributed to mechanical complications of the infarction, such as myocardial rupture. Nonetheless, arrhythmic SCD risk in the early convalescence phase post-MI remains high and predicts later events. However, defibrillator implants early after MI showed no significant benefit in terms of all-cause survival in two separate trials (Defibrillator in Acute Myocardial Infarction Trial [DINAMIT] and Immediate Risk Stratification Improves Survival Trial [IRIS]). Although both trials showed a benefit of implantable cardioverter defibrillator (ICD) implantation in reduction of arrhythmic deaths, this was counterbalanced by a higher rate of nonarrhythmic death.
In the late convalescence period after MI, typically referring to months or years after the index event, there continues to be a risk of SCD likely related to ischemic cardiomyopathy, continued remodeling, and heart failure. This risk is lower than the early convalescence period but is primarily a function of the degree of LV dysfunction.
Sudden Cardiac Death from Coronary Heart Disease–Related Structural Changes
Such changes include scar formation or ventricular dilatation from prior infarction or chronic ischemia. Whereas one-quarter of SCD cases occur in the first 3 months after an acute MI, half of all SCD cases occur beyond the year after the index event. The incidence of SCD after acute MI appears to be similar in ST elevation and non-ST elevation MIs. The risk is highest in the acute phase as previously noted but decreases gradually over time.
A prior history of an MI increases the risk of SCD 4-fold in women and 10-fold in men. The incidence rates of SCD after MI have declined over time with recent estimates of 1% per year in patients receiving optimal medical therapy and revascularization. Despite improvements in overall mortality rates in MI survivors and the decline in SCD rates, there are still subsets of MI survivors who are considered to be at a particularly high risk. The most powerful risk factors for SCD in chronic CHD are LV dysfunction and New York Heart Association (NYHA) functional class, which thus form the basis for why these were used as entry criteria for clinical trials of ICDs and therefore are the primary factors affecting decisions for defibrillator implants for the primary prevention of SCD. The impact of these factors reflects their nature as clinical markers of CHD burden and the extent of damaged myocardium. However, whereas they identify high-risk subgroups in CHD, the absolute number of SCD cases from these subgroups account for only a minority of all CHD-related SCDs. Furthermore, many patients who receive defibrillators for primary prevention purposes never require therapy from their devices. These caveats emphasize the need for better strategies for risk stratification.
Risk stratification remains a topic of intense research. Multiple noninvasive markers have been evaluated for the purpose of improving individual risk prediction, including clinical, imaging, electrophysiologic, genetic, and biologic markers. Although high-risk markers can be identified, clinical relevance is limited by an absence of evidence supporting use of these risk factors for selection of patients for risk-reducing therapies, such as ICD implantation. For example, in chronic ischemic heart disease and in post-MI patients, the presence of late potentials on signal-averaged electrocardiogram (ECG), reduced heart rate variability, and T-wave or repolarization alternans have been found to have significant associations with SCD, but available data have not supported incorporating these factors into the clinical criteria for ICD implantation ( Table 22.1 ).
| Technique | Conclusion |
|---|---|
| Imaging | |
| LVEF | Low LVEF is a well-demonstrated risk factor for SCD. Although low LVEF has been effectively used to select high-risk patients for application of therapy to prevent sudden arrhythmic death, LVEF has limited sensitivity: the majority of SCDs occur in patients with more preserved LVEF. |
| ECG | |
| QRS duration | Most retrospective analyses show increased QRS duration is likely a risk factor for SCD. Clinical utility to guide selection of therapy has not been tested. |
| QT interval and QT dispersion | Data from some retrospective analyses show that abnormalities in cardiac repolarization are risk factors for SCD. Clinical utility to guide selection of therapy has not yet been tested. |
| SAECG | An abnormal SAECG is likely a risk factor for SCD, based predominantly on prospective analyses. Clinical utility to guide selection of therapy has been tested, but not yet demonstrated. |
| Short-term HRV | Limited data link impaired short-term HRV to increased risk for SCD. Clinical utility to guide selection of therapy has not yet been tested. |
| Long-Term Ambulatory ECG Recording (Holter) | |
| Ventricular ectopy and NSVT | The presence of ventricular arrhythmias (VPBs, NSVT) on Holter monitoring is a well-demonstrated risk factor for SCD. In some populations, the presence of NSVT has been effectively used to select high-risk patients for application of therapy to prevent sudden arrhythmic death. This may also have limited sensitivity. |
| Long-term HRV | Low HRV is a risk factor for mortality, but unlikely to be specific for SCD. Clinical utility to guide selection of therapy has been tested, but not demonstrated. |
| Heart rate turbulence | Emerging data show that abnormal heart rate turbulence is a likely risk factor for SCD. Clinical utility to guide selection of therapy has been tested, but not yet demonstrated. |
| Exercise Test/Functional Status | |
| Exercise capacity and NYHA class | Increasing severity of heart failure is a likely risk factor for SCD, although it may be more predictive of risk for progressive pump failure. Clinical utility to guide selection of therapy has not yet been tested. |
| Heart rate recovery and recovery ventricular ectopy | Limited data show that low heart rate recovery and ventricular ectopy during recovery are risk factors for SCD. Clinical utility to guide selection of therapy has not yet been tested. |
| T-wave alternans | A moderate amount of prospective data suggests that abnormal T-wave alternans is a risk factor for SCD. Clinical utility to guide selection of therapy has been evaluated, but the results to date are inconsistent. |
| BRS | A moderate amount of data suggests that low BRS is a risk factor for SCD. Clinical utility to guide selection of therapy has not yet been tested. |
Ischemic Cardiomyopathy, Heart Failure, and Sudden Cardiac Death
Ventricular arrhythmias are common in patients with heart failure and range from asymptomatic premature ventricular contractions to sustained VT, VF, or SCD. In patients with heart failure, progressive pump failure accounts for only one-third of all cardiovascular deaths, whereas SCD accounts for the other two-thirds and the latter is split equally between unexpected SCD or SCD during episodes of clinical worsening of heart failure. The most common mechanism of SCD in this population is VT degenerating into VF.
The severity of heart failure correlates with higher overall mortality and absolute rates of SCD, but the proportion of total deaths classified as SCD decreases with worsening NYHA class. For example, in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF), NYHA class II, III, and IV were associated with 1-year mortality rates of 6.3%, 10.5%, and 18.6%, respectively, but the proportions of total deaths classified as SCDs were 64%, 59%, and 33%, respectively. Also, not all sudden deaths in patients with heart failure are due to arrhythmia. In the Acute Infarction Ramipril Efficacy (AIRE) trial, only 39% of all SCD cases were thought to be due to arrhythmias. Other observations in the literature suggest that arrhythmic SCD cases account for most but not all unwitnessed deaths and deaths occurring within 1 hour of onset of symptoms.
Secondary Prevention of Sudden Cardiac Death
Secondary prevention aims to prevent SCD in patients who have survived a prior sudden cardiac arrest or sustained VT.
Sudden Cardiac Arrest from Transient or Reversible Causes
Experts agree, based on available evidence, that the primary goal of management in patients who survived a sudden cardiac arrest from a transient or reversible cause is to address the underlying condition or disease process. There are, however, caveats to this approach, and decision-making in clinical practice may not be straightforward. For example, it has been traditionally thought that ventricular arrhythmias in the setting of acute ischemia have low risk for future SCD and as such may not benefit from ICD implants. The reality is that these patients may have experienced a prior MI or have a significant burden of coronary disease and despite revascularization may still have a myocardial scar or large myocardial territory at risk that would be a substrate for recurrent ventricular arrhythmia. Studies have indeed demonstrated increased subsequent risks in patients with ventricular arrhythmias in the setting of acute ischemia. Furthermore, in a subsequent analysis of the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial, the mortality rate of patients who were included in the AVID registry but not randomized due to a transient or correctable cause for VT/VF was no different, or was perhaps even worse, than that of the population considered to have high-risk VT/VF in the randomized trial.
As such, a careful approach to risk stratification and identification of both reversible and nonreversible causes on a case-by-case basis is valuable to optimize patient outcomes. In the specific setting of coronary disease, scar-dependent ventricular arrhythmias are mostly monomorphic tachycardia in nature, whereas arrhythmias related to acute ischemia are mostly polymorphic VT or VF. In general, patients with polymorphic VT or VF in the setting of acute ischemia should be treated with revascularization for the purpose of reducing the risk of SCD. Sustained monomorphic VTs in the setting of electrolyte abnormalities or antiarrhythmic drug use should be treated by identifying and correcting the underlying condition, but it is important not to assume that these were the only cause of sustained monomorphic VT.
Implantable Cardioverter Defibrillators for Secondary Prevention of Sudden Cardiac Death
The role of ICDs is well established for the purpose of secondary SCD prevention based on the results of randomized clinical trials ( Table 22.2 ), which have demonstrated that implantation of ICDs in patients who have survived a sudden cardiac arrest or experienced sustained VT results in reductions in SCD and total mortality compared to antiarrhythmic medications. An algorithm for ICD use for secondary prevention of SCD in patients with coronary artery disease (CAD) is presented in Fig. 22.2 . The use of ICDs for secondary prevention of SCD within 40 days after MI or 90 days after coronary revascularization is shown in Figs. 22.3 and 22.4 .
| N | % CHD | Design | Population | HR | |
|---|---|---|---|---|---|
| AVID (1997) | 1016 | > 80% | ICD vs. class III AAD | Resuscitated VF, cardioverted VT, VT with syncope or VT with LVEF ≤ 40% and symptoms of hemodynamic compromise | 0.62 ( p < 0.02) |
| CASH (2000) | 288 | > 70% | ICD vs. amiodarone vs. metoprolol | Resuscitated cardiac arrest from documented sustained ventricular arrhythmias | 0.77 ( p = 0.08) |
| CIDS (2000) | 659 | > 80% | ICD vs. amiodarone | Resuscitated VF or VT or unmonitored syncope | 0.80 ( p = 0.1) |
AVID: Antiarrhythmics Versus Implantable Defibrillators Trial
In the pivotal secondary prevention randomized trial, AVID, 1016 patients with resuscitated VF, sustained VT with syncope or sustained VT with hemodynamic compromise or symptoms suggesting hemodynamic instability in the setting of LV dysfunction (left ventricular ejection fraction [LVEF] < 40%) were randomized to treatment with a de-fibrillator implant or antiarrhythmic medications sotalol or amiodarone. The primary endpoint of the trial was all-cause mortality. The majority of patients enrolled in this trial had coronary disease (81% in both arms), prior MI (67% in both arms), or significant LV dysfunction (median LVEF 31%).
The overall survival was greater with ICDs, with unadjusted estimates of 89.3% versus 82.3% in the antiarrhythmic drug group at 1 year, 81.6% versus 74.7% at 2 years, and 75.4% versus 64.1% at 3 years ( p < 0.02). This corresponded to relative reductions in mortality of 39%, 24%, and 31% at 1, 2, and 3 years, respectively. In subset analyses, the benefit of de-fibrillator therapy was primarily in patients with CHD as the underlying cause of their arrhythmias. The trial was stopped prematurely due to the observed significant survival benefit with ICD implants. The primary effect of ICDs was prevention of arrhythmic death compared with antiarrhythmics, but the rates of nonarrhythmic death were equivalent in the treatment arms. To be noted also was that patients treated with antiarrhythmics appeared to be at greater risk of noncardiac death, such as deaths related to pulmonary or renal disease.
A subsequent analysis of AVID found that in patients with LVEF greater than 35%, there were no differences in outcomes between the treatment arms, whereas in patients with LVEF values between 20% and 35%, there was a clear and significant survival benefit of ICDs over medical therapy at 2 years (83% vs. 72%). The same extent of difference was observed in the small subset with LVEF less than 20% but the analysis did not have enough power to detect statistical difference.
CASH: Cardiac Arrest Survival in Hamburg Trial
CASH was a prospective, multicenter, randomized trial for the comparison of implantable defibrillators versus antiarrhythmic drug therapy in survivors of cardiac arrest secondary to documented ventricular arrhythmias. The study randomized 349 survivors of cardiac arrest from documented VT or VF to treatment with an ICD, metoprolol, propafenone, or amiodarone. Assignment to propafenone was discontinued during the trial due to an observed 61% higher all-cause mortality rate in propafenone versus ICD patients upon follow-up of 11.3 months. The primary endpoint of the trial was all-cause mortality. Coronary disease was present in approximately 75% of the patients enrolled in the trial. Over a mean follow-up of 57 months, the all-cause death rates were 36.4% in the ICD arm and 44.4% in the amiodarone/metoprolol arm. The overall survival was higher in the ICD arm but did not reach statistical significance likely due to lack of power, as the mean LVEF was 46%, indicating a healthier population than in AVID, and accordingly the 19.6% 2-year mortality rate was under half that used to calculate trial sample size. Nevertheless, the secondary endpoint of SCD was significantly reduced with ICD implants compared to medical therapy (13% vs. 33%). The trial also noted that the benefit of ICD therapy appears to be primarily during the first 5 years after the index event.
CIDS: Canadian Implantable Defibrillator Study
CIDS randomized 659 patients with resuscitated VF or VT or with unmonitored syncope to treatment with ICD implant or amiodarone. The primary outcome of the trial was all-cause mortality, and the secondary outcome was arrhythmic death. The proportion of patients with coronary disease exceeded 80% in both the ICD and medical therapy arms, with the majority having experienced a prior MI. Over 5 years of follow-up, the trial found a nonsignificant reduction in the risk of death with ICD therapy with a 19.7% relative risk reduction, as well as a nonsignificant reduction in the risk of arrhythmic death with 32.8% relative risk reduction.
Cumulative Data of Landmark Trials and Generalizability of Outcomes
Whereas AVID showed a statistically significant benefit with ICD implant versus medical therapy, CIDS and CASH showed a nonsignificant trend toward benefit, which may have reflected a beta error and lack of statistical power to detect significance in the magnitude of benefit that was observed, different patient populations, or longer follow-up time in CIDS. It is also possible that patients who were considered by their managing physicians to be better candidates for ICD therapy than antiarrhythmics may have been referred for defibrillator implant rather than enrollment in the trial with randomization. This would introduce a bias that may have favored the outcomes in the medical intervention arm.
Conclusive evidence regarding the benefit of ICDs in these patients was observed in a meta-analysis of the three major trials and a fourth trial with a smaller population ( Fig. 22.5 ). When combined in a meta-analysis, data showed that patients with ICDs had a survival advantage over those treated with medical therapy with a 25% reduction in relative risk. This was primarily related to a positive effect on SCD rates, with a 50% relative risk reduction from this mode in death with ICDs. An important observation is that of an absolute risk reduction of 7% in all-cause mortality, which translates into a number needed to treat of 15 that supersedes most clinical trials in modern cardiovascular medicine.
The findings were reproduced in a second meta-analysis of AVID, CIDS, and CASH with a 28% relative risk reduction in all-cause mortality and a 50% reduction in sudden arrhythmic death and a superior benefit in patients with LVEF below 35% compared to those with LVEF above 35%. The generalizability of these benefits was explored by examining the effectiveness of defibrillators as applied in routine medical practice in a large cohort of patients from the National Veterans Administration database. For 3 years the study followed 6996 patients with new-onset ventricular arrhythmia and preexisting ischemic heart disease and congestive heart failure, of which 1442 received an ICD. The main finding was that ICD recipients had lower all-cause (odds ratio 0.52) and cardiovascular mortality (odds ratio 0.56) in multivariable analyses but no difference in noncardiovascular mortality. These benefits were observed despite a significantly lower frequency of use of angiotensin-converting enzyme inhibitors (ACE-I), β-blockers, and statins. An important observation was that the magnitude of benefit of ICD therapy was similar to or even greater than that observed in the clinical trials, with a finding that one death was prevented in this population for every four to five patients receiving an ICD over three years of follow-up.
Sudden Cardiac Death in Defibrillator Recipients
SCD due to nonarrhythmic causes (such as pulseless electrical activity, pulmonary embolus, or aortic dissection) or SCD from terminal cardiac arrhythmias can still occur in ICD recipients. In the secondary prevention trials of SCD, up to one-third of all deaths in the ICD treatment arms were SCD. The most common cause of SCD in these patients was VT or VF, which is treated appropriately by a defibrillator shock but is followed by electromechanical dissociation and pulseless electrical activity.
Refractory arrhythmias are observed in terminal stages of heart failure and may still occur in patients with ICDs despite the proper function of ICDs. In this population, further treatment options include advanced heart failure therapies and consideration for heart transplant. Other factors that could lead to SCD despite ICD implants include ventricular arrhythmias, which fall under the detection limit of the device, and very rarely failure of the ICD in detecting the arrhythmia or delivering appropriate therapy.
Adjunctive Medical Therapies in Sudden Cardiac Arrest Survivors
No medical therapy is considered to be an acceptable alternative to ICD implants in SCD survivors. That being said, optimal medical therapy to address specific underlying conditions may contribute to further reductions in both cardiovascular mortality and SCD in this population.
Antiarrhythmic Drugs
In patients who have survived a sudden cardiac arrest or experienced sustained ventricular arrhythmias but have declined ICD implants, antiarrhythmic drugs could be used as an alternative to ICDs to reduce arrhythmia burden. Among patients who receive ICDs for the secondary prevention of SCD, many experience recurrent ventricular arrhythmias that trigger appropriate defibrillator shocks. Antiarrhythmic medications may reduce the need for de-fibrillator shocks in these patients and therefore improve the quality of life. In this population with structural heart disease, antiarrhythmic medication options are limited to amiodarone, sotalol, or mexilitene, with amiodarone being the preferred agent due to superior efficacy and lower proarrhythmic effects compared to sotalol. However, amiodarone’s side effects profile with long-term use of this medication make sotalol and mexiletine acceptable alternatives in select scenarios, despite lower efficacy. Amiodarone can raise the defibrillation threshold, whereas sotalol may decrease it, and these effects may be important in patients with high defibrillation thresholds. Also, the potent β-blockade effects of sotalol can limit its use in patients with marginally or poorly compensated heart failure.
The need for adjunctive antiarrhythmic therapy in patients who have received an ICD for the secondary prevention of SCD is not uncommon and was reported to have been used in the ICD therapy arms in 22% of AVID patients at 2 years and 28% of CIDS patients at 5 years.
The addition of antiarrhythmic medications aims primarily to improve quality of life and reduce shocks, but shock prevention has not been found to improve survival in a systematic review that included 6000 ICD recipients.
In this population of patients, antiarrhythmic drugs might also be indicated for the treatment of supraventricular arrhythmias, which could lead to inappropriate defibrillator shocks, especially for atrial fibrillation. With modern programming, there have been reductions in the rates of inappropriate shocks, but control of supraventricular arrhythmias might improve quality of life for patients regardless of reduction of inappropriate shocks.
β-Blockers
Among patients with coronary disease, those with prior MI and LV dysfunction or heart failure may derive survival benefit from β-blocker therapy, which may also include improvement in SCD risk as a subset of modes of death. In patients with recurrent ventricular arrhythmias, β-blockers may suppress the adrenergic drive associated with these arrhythmias. Moreover, in many patients with heart failure, β-blocker therapy may prevent recurrent clinical heart failure episodes, which are known to be periods of increased risk of arrhythmia recurrence. Furthermore, β-blockers may reduce inappropriate shocks from atrial fibrillation or sinus tachycardia with rapid ventricular rates in these patients.
In patients who survived a sudden cardiac arrest but were not enrolled in AVID, β-blocker use was associated with a survival benefit. The same study found that this protective effect was not prominent in patients already receiving amiodarone or a defibrillator.
Lipid-Lowering Medications
Patients with coronary disease should be treated with lipid-lowering agents in concordance with the corresponding clinical guidelines. The use of lipid-lowering agents for the purpose of reducing SCD remains controversial but available data suggest benefit. In patients with CHD who have received an ICD in AVID, lipid-lowering therapy was found to be associated with a 60% relative reduction in the probability of VT/VF recurrence. Another observational study showed that the use of lipid-lowering drugs was associated with a reduction of recurrences of ventricular arrhythmias in patients with coronary disease and ICD implants.
To date, there are no clinical trial data to suggest an independent antiarrhythmic benefit from use of statins. Similarly, regarding antiarrhythmic benefits of fish oil, a meta-analysis showed no reduction in defibrillator discharges with use of fish oil or omega-3 fatty acids.
Adjunctive Nonpharmacologic Therapies in Sudden Cardiac Arrest Survivors
Catheter Ablation
Catheter ablation is a treatment option for ventricular arrhythmias. In patients with CHD who had survived a sudden cardiac arrest, catheter ablation for ventricular arrhythmias could be performed as adjunctive therapy for frequent ventricular arrhythmias triggering ICD shocks, as an alternative for patients who decline ICD implantation, or in patients with cardiomyopathy and bundle branch reentrant VT, which is typically treated by ablation of the right bundle.
Catheter ablation has been associated with better outcomes for VTs from ischemic heart disease versus nonischemic substrate. In patients with prior MI, sustained monomorphic VTs typically originate from a scar substrate, primarily in the border zone areas of the scar where scar tissue is dispersed among surviving bundles of myocytes. This substrate is amenable to endocardial catheter ablation, which would ideally target the critical isthmus of reentry when addressing the clinical VT. Additional substrate modification is performed by many experts in the field. A trial published in 2015 showed that an extensive substrate-based ablation approach is superior to ablation targeting only clinical and stable VTs in patients with ischemic cardiomyopathy presenting with tolerated VT. In our practice, every effort is made to map and target the clinical VT in addition to substrate modification.
Catheter ablation may also be effective for the treatment of VF that is triggered by premature ventricular depolarizations, especially if they appear to be uniform in morphology. Such triggers could originate from the His-Purkinje system in patients with coronary disease, especially the posterior fascicle. Whereas ischemia in this territory could be the underlying cause of premature ventricular depolarizations leading to VF, there are instances with no identifiable revascularization target or persistence of the problem despite revascularization. Catheter ablation targeting the premature ventricular depolarization trigger may be successful in abolishing recurrent VF in these patients.
Catheter ablation has also been evaluated as a prophylactic adjunctive therapy in patients who had experienced sustained VT and received ICD therapy. A meta-analysis of these studies showed that prophylactic VT ablation decreased VT recurrence but had no effect on mortality.
Surgical Interventions
With advancements in defibrillator therapies and catheter intervention, surgery for ventricular arrhythmia is rarely performed nowadays and is typically reserved for patients with recurrent ventricular arrhythmias and defibrillator shocks who have failed adjunctive medical therapies and catheter ablation. Surgical approaches to ventricular arrhythmias in patients with prior MI include resection of the scar substrate or aneurysm surgery with or without concomitant mapping.
In refractory cases, cardiac transplantation may be indicated in select candidates. Conversely, in patients awaiting cardiac transplantation who experience a sudden cardiac arrest or sustained ventricular arrhythmias, ICD implantation may be used as a bridge to transplantation with resultant improvement in survival.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
