This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Search for Related Content PubMed PubMed Citation

(Circulation. 1997;95:265-272.)
© 1997 American Heart Association, Inc.

Articles

Survivors of Out-of-Hospital Cardiac Arrest With Apparently Normal Heart

Need for Definition and Standardized Clinical Evaluation

Consensus Statement of the Joint Steering Committees of the Unexplained Cardiac Arrest Registry of Europe* and of the Idiopathic Ventricular Fibrillation Registry of the United States

Correspondence to Silvia G. Priori, MD, PhD, FESC, Molecular Cardiology Unit, Cardiovascular Laboratories, Fondazione S. Maugeri, IRCCS, and Department of Cardiology, Policlinico S. Matteo, IRCCS, Piazzale Golgi 2, 27100 Pavia, Italy.

	Abstract

Top Abstract Introduction Background Definitions Evaluation of the Arrhythmogenic... Use and Abuse of... Ischemic Heart Disease Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Arrhythmogenic Right Ventricular... LQTS/Prolonged-QT Interval Idiopathic Ventricular... Sudden Unexplained Nocturnal... Ventricular Preexcitation Myocarditis Infiltrative Diseases Minimal Diagnostic Requirements... Recognition and Interpretation... Importance of Accurate Follow-up Conclusions Appendix References

 
Background A wide variety of structural abnormalities are associated with the vast majority of cardiac arrests. However, there is no evidence of structural heart disease in 5% of victims of sudden death, indicating that cardiac arrest in the absence of organic heart disease is more common than previously recognized. The risk of recurrence and the acute and long-term response to therapy are important but unanswered questions. Data from the small series reported so far are of limited value because of the lack of uniform criteria to define and diagnose idiopathic ventricular fibrillation (IVF).

Methods and Results This report originates from a Consensus Conference convened by the Steering Committees of the European (UCARE) and North American (IVF-US) Registries on IVF under the auspices of the Working Group on Arrhythmias of the European Society of Cardiology. Its objective is to provide a unified definition of IVF and to outline the investigations necessary to make this diagnosis. Minimal diagnostic tests for the exclusion of an underlying structural heart disease include noninvasive (blood biochemistry, physical examination and clinical history, ECG, exercise stress test, 24-hour Holter recording, and echocardiogram) and invasive (coronary angiography, right and left ventricular cineangiography, and electrophysiological study) examinations. Programmed electrical stimulation, ventricular biopsy, and ergonovine test during coronary angiography are recommended but not mandatory.

Conclusions It is recognized that despite careful evaluation, conditions such as focal cardiomyopathy, myocarditis, or fibrosis and transient electrolyte abnormalities may remain silent. Therefore, patients should undergo careful follow-up, with noninvasive tests repeated every year. The existence of a unified terminology will allow meaningful comparison of data collected by different investigators and will thus contribute to a better understanding of IVF.

Key Words: fibrillation • death, sudden • arrhythmia • diagnosis

	Introduction

Top Abstract Introduction Background Definitions Evaluation of the Arrhythmogenic... Use and Abuse of... Ischemic Heart Disease Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Arrhythmogenic Right Ventricular... LQTS/Prolonged-QT Interval Idiopathic Ventricular... Sudden Unexplained Nocturnal... Ventricular Preexcitation Myocarditis Infiltrative Diseases Minimal Diagnostic Requirements... Recognition and Interpretation... Importance of Accurate Follow-up Conclusions Appendix References

 
More than 90% of sudden cardiac deaths occur in patients with known or previously unrecognized preexisting coronary heart disease or cardiomyopathies. Among the remainder, it has become evident that sudden arrhythmic death occurs with sufficient frequency in patients with an apparently normal heart to warrant the attention of the cardiological community. This is further supported by the tendency for such fatal events to occur in special groups, such as young, active, and otherwise healthy individuals.

The most pressing questions about this entity concern the risk of recurrence, the acute and long-term responses to the various therapies currently used, and the intriguing possibility that in some patients VF may represent the first clinical sign of structural disease that becomes manifest only several years later among survivors.

The Working Group on Arrhythmias of the European Society of Cardiology recognized the clinical relevance of these questions and in 1992 formally established a prospective long-term registry of this clinical entity with the goal of addressing this problem.¹ This project is named UCARE and has already enrolled more than 160 patients who survived an episode of IVF. Preliminary data^{2 3} suggest that IVF is associated with a high (25% to 30%) risk of recurrence of cardiac arrest. In 1994, a group of investigators in the United States decided to initiate a similar registry (IVF-US).

A clear and unified definition of "an apparently normal heart" is essential to avoid the misdiagnosis of IVF in a survivor of a cardiac arrest due to a specific clinical entity for which an appropriate treatment may have already been established. Accordingly, the Steering Committees of the European and the American registries formed a panel to establish the criteria necessary for the diagnosis of "cardiac arrest with an apparently normal heart." The meeting stimulated the creation of the present document, whose main objective is to propose a set of standardized diagnostic criteria.

	Background

Top Abstract Introduction Background Definitions Evaluation of the Arrhythmogenic... Use and Abuse of... Ischemic Heart Disease Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Arrhythmogenic Right Ventricular... LQTS/Prolonged-QT Interval Idiopathic Ventricular... Sudden Unexplained Nocturnal... Ventricular Preexcitation Myocarditis Infiltrative Diseases Minimal Diagnostic Requirements... Recognition and Interpretation... Importance of Accurate Follow-up Conclusions Appendix References

 
A wide variety of structural abnormalities are associated with the vast majority of cardiac arrests.⁴ However, it is necessary to deal with the fact that there are also functional causes not associated with pathological anatomic changes.

Sudden arrhythmic death in the absence of structural heart disease is an uncommon event. However, data from large series of patients resuscitated from cardiac arrest and necropsy data from victims of sudden death indicate that there is no evidence of structural heart disease in 5% of victims of sudden death.^{5 6 7 8 9 10 11 12} Thus, cardiac arrest in the absence of structural heart disease may be more common than previously recognized. This subgroup of survivors of out-of-hospital cardiac arrest deserves to be carefully evaluated to define their optimal long-term management and outcome,^{13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29} because their survival is largely related to potentially controllable electrophysiological disturbances, rather than limited by the competing risk of advanced myocardial disease.³⁰

The data already available in UCARE, based on >160 patients, represent the largest collective experience on IVF. According to the UCARE investigators, after 3 years from cardiac arrest, IVF patients have 30% recurrence of VF, syncope, and cardiac arrest, and prevention of recurrence is inadequate with the use of antiarrhythmic agents, including ß-blockers.² These data are at variance with the experience of Belhassen and Viskin,³¹ who reported favorable effects of sodium channel blockers, but they are in agreement with previous observations^{28 29} suggesting a high recurrence rate of malignant tachyarrhythmias in IVF survivors and raising the possibility that IVF patients should be considered candidates for an implantable defibrillator.² It is therefore important to produce guidelines to define the criteria to separate IVF from other conditions in which VF may be the first manifestation of the disease.

	Definitions

Top Abstract Introduction Background Definitions Evaluation of the Arrhythmogenic... Use and Abuse of... Ischemic Heart Disease Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Arrhythmogenic Right Ventricular... LQTS/Prolonged-QT Interval Idiopathic Ventricular... Sudden Unexplained Nocturnal... Ventricular Preexcitation Myocarditis Infiltrative Diseases Minimal Diagnostic Requirements... Recognition and Interpretation... Importance of Accurate Follow-up Conclusions Appendix References

 
Several terms have been proposed to describe those patients who survive an episode of ECG-documented VF with an apparently normal heart. The language used to define such patients is not merely semantic; it has operational connotations for both clinical and research purposes.

Primary electrical disease implies that there is no recognizable structural heart disease to account for the arrhythmic event and that an electrophysiological mechanism is solely responsible for the arrhythmic episode. The limitation of this definition is that it is impossible to exclude causes such as transient autonomic abnormalities as the initiating mechanism for the arrhythmia. Moreover, this definition could be extended to atrial arrhythmias such as lone atrial fibrillation and to benign idiopathic arrhythmias such as isolated premature ventricular complexes and idiopathic nonsustained VT.

Arrhythmic death without identifiable heart disease is another term that reflects the lack of identification of a cardiac disease. It has the advantage of considering that a minimal structural abnormality can be responsible for the development of the arrhythmia; however, "arrhythmic death" may also include arrhythmias other than VF, such as sinus arrest or complete AV block.

IVF is the terminology that best acknowledges our current inability to identify a causal relationship between the clinical circumstance and the arrhythmia. The advantage of this definition is that the term IVF does not imply that the heart of the patient is completely free of structural or definable functional abnormalities but simply that, if an abnormal finding (such as first-degree AV block or paroxysmal atrial fibrillation) is present, it is not considered responsible for the VF.

Thus, in the absence of clinical or laboratory findings that could account for the occurrence of major arrhythmic events, the diagnosis of IVF can be made once a survivor of cardiac arrest has been extensively studied.

These considerations emphasize the concept that there may be no distinct and fixed border between normal and frankly abnormal. Moreover, the border may change over time, and new data emerging on membrane-based functional^{32 33} or structural abnormalities^{34 35} may ultimately provide more specifically defined explanations.

A disease is "idiopathic" because present knowledge has not yet allowed identification of the underlying cause. Eventually, the cause of most idiopathic disorders will be known. For example, the LQTS, which was considered idiopathic until the three genes responsible for most cases were identified,^{36 37 38 39} is no longer so. Thus, IVF is an appropriate "initial" or "working" diagnosis that reflects our current inability to establish a link between clinical information obtained by detailed invasive or noninvasive examinations and a life-threatening arrhythmic event.

We include in the IVF group only individuals with a documented VF, even though it cannot be ruled out that the arrhythmic episode might have started as VT or even asystole. We believe that, despite being an arbitrary distinction, this criterion originates from the idea that it is the degeneration into VF that represents the common denominator for this group of patients.

	Evaluation of the Arrhythmogenic Substrate in Survivors of Cardiac Arrest

Top Abstract Introduction Background Definitions Evaluation of the Arrhythmogenic... Use and Abuse of... Ischemic Heart Disease Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Arrhythmogenic Right Ventricular... LQTS/Prolonged-QT Interval Idiopathic Ventricular... Sudden Unexplained Nocturnal... Ventricular Preexcitation Myocarditis Infiltrative Diseases Minimal Diagnostic Requirements... Recognition and Interpretation... Importance of Accurate Follow-up Conclusions Appendix References

 
IVF is a diagnosis of exclusion. Therefore, it is of pivotal importance to define the conditions that have to be excluded as well as the most appropriate techniques for excluding them.

There is no need to exclude every cardiac abnormality but rather only those conditions known to be associated with sudden death.

	Use and Abuse of Drugs

Top Abstract Introduction Background Definitions Evaluation of the Arrhythmogenic... Use and Abuse of... Ischemic Heart Disease Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Arrhythmogenic Right Ventricular... LQTS/Prolonged-QT Interval Idiopathic Ventricular... Sudden Unexplained Nocturnal... Ventricular Preexcitation Myocarditis Infiltrative Diseases Minimal Diagnostic Requirements... Recognition and Interpretation... Importance of Accurate Follow-up Conclusions Appendix References

 
Before any medical or invasive investigation is undertaken, it is critical to obtain a careful clinical history. Indeed, a link between the use of pharmacological substances and the development of VF may be suspected simply by questioning the patient with regard to exposure to substances or drugs in the days before the index event. Many drugs are known to favor development of torsade de pointes: among these are quinidine, phenothiazines, antibiotics like erythromycin and other macrolides,⁴⁰ and antihistamines,⁴¹ either alone or in combination with antifungal drugs of the "conazole" type.⁴²

The link between alcohol abuse and lethal ventricular tachyarrhythmias has been suggested but not conclusively demonstrated. A few studies^{43 44 45} reported that lethal ventricular arrhythmias may precede signs of alcoholic cardiomyopathy. It is important to obtain urine toxicology in patients suspected of drug abuse.

	Ischemic Heart Disease

Top Abstract Introduction Background Definitions Evaluation of the Arrhythmogenic... Use and Abuse of... Ischemic Heart Disease Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Arrhythmogenic Right Ventricular... LQTS/Prolonged-QT Interval Idiopathic Ventricular... Sudden Unexplained Nocturnal... Ventricular Preexcitation Myocarditis Infiltrative Diseases Minimal Diagnostic Requirements... Recognition and Interpretation... Importance of Accurate Follow-up Conclusions Appendix References

 
Coronary angiography is necessary for establishing the presence or absence of coronary heart disease and to detect congenital coronary anomalies. Among patients with typical angina pectoris or with multiple risk factors for ischemic heart disease, the results of noninvasive tests help to quantify the probability of ischemic heart disease. However, in the heterogeneous population of patients with unexplained cardiac arrest whose demographic and clinical profiles are often quite different from those of patients at risk for ischemic heart disease, the pretest probability of coronary artery disease is undefined. Thus, according to Bayesian theory, results of noninvasive tests such as exercise stress test and myocardial scintigraphy with thallium may not be helpful in the diagnostic process.⁴⁶ Therefore, it is recommended that coronary angiography be performed in all patients, of any age, with unexplained cardiac arrest to establish whether or not there is ischemic heart disease.

IVF will be excluded in the presence of (1) an unequivocal clinical history of ischemic heart disease, (2) definite evidence of acute myocardial ischemia or necrosis on the 12-lead ECG unless enzyme elevation is due to defibrillation shocks,⁴⁷ and (3) anatomic alterations in the coronary arterial tree that are considered to be clinically important.

It is reasonable to define a narrowing of 50% in at least one coronary artery as excluding the diagnosis of IVF.¹⁵ The significance of minor stenoses with narrowing in the range of 25% to 49% is difficult to assess, because they may be thrombogenic and/or favor coronary spasm. The definition of IVF in these cases must be left to the judgment of the responsible clinician. In this respect, testing for provocation of coronary artery spasm may be important to identify silent myocardial ischemia or atypical symptoms,⁴⁸ and patients with a positive test should be excluded. Careful follow-up of patients suspected of ischemic heart disease may identify signs and symptoms of ischemia shortly after the index event.

It has been suggested that myocardial perfusion heterogeneity and impaired perfusion reserve may be present in IVF survivors⁴⁹ ; however, no conclusive data have established a causal link between ventricular tachyarrhythmias and microvascular disease. At present, therefore, there is no indication for routine PET studies to exclude this condition.

Coronary arteries may be "bridged" by muscle bands.⁵⁰ Although systolic narrowing of normal coronary arteries does not result in myocardial ischemia in most individuals, in the absence of chest pain it is unlikely that bridging is the cause of asymptomatic ischemia precipitating cardiac arrest. When this abnormality is diagnosed or suspected at angiography, however, it is mandatory to exclude by scintigraphy the presence of myocardial ischemia.

	Dilated Cardiomyopathy

Top Abstract Introduction Background Definitions Evaluation of the Arrhythmogenic... Use and Abuse of... Ischemic Heart Disease Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Arrhythmogenic Right Ventricular... LQTS/Prolonged-QT Interval Idiopathic Ventricular... Sudden Unexplained Nocturnal... Ventricular Preexcitation Myocarditis Infiltrative Diseases Minimal Diagnostic Requirements... Recognition and Interpretation... Importance of Accurate Follow-up Conclusions Appendix References

 
The conventional diagnosis of myocardial disease depends on the demonstration of ventricular dilatation and reduced contractile function by ventriculography or two-dimensional echocardiography, in the absence of coronary artery disease. Assessment of ventricular function must be done 48 hours after the arrest, since prolonged (15 minutes) resuscitation in otherwise healthy subjects produces myocardial stunning that takes at least 48 hours to recover and is associated with transient systolic and diastolic dysfunction.⁵¹ In an early phase of the disease, there may be more subtle features, such as an ejection fraction <50% or mild cavity enlargement (increase of volumes <20%).

	Hypertrophic Cardiomyopathy

Top Abstract Introduction Background Definitions Evaluation of the Arrhythmogenic... Use and Abuse of... Ischemic Heart Disease Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Arrhythmogenic Right Ventricular... LQTS/Prolonged-QT Interval Idiopathic Ventricular... Sudden Unexplained Nocturnal... Ventricular Preexcitation Myocarditis Infiltrative Diseases Minimal Diagnostic Requirements... Recognition and Interpretation... Importance of Accurate Follow-up Conclusions Appendix References

 
Sudden cardiac death is a common initial presentation of hypertrophic cardiomyopathy, particularly in the young. The clinical diagnosis in survivors is based on history, physical examination, 12-lead ECG, and two-dimensional echocardiographic/Doppler evaluation.⁵² The majority of individuals who have suffered out-of-hospital VF from hypertrophic cardiomyopathy will fulfill conventional diagnostic criteria, eg, unexplained left ventricular hypertrophy. Occasionally, and particularly in those families with mutations in the cardiac troponin T gene, the echocardiographic features do not fulfill current diagnostic criteria.³⁵ In such instances, suggestive features such as mild increase in left ventricular wall thickening, small left ventricular cavity dimensions, incomplete systolic anterior motion of the mitral valve, or diastolic abnormalities including atrial enlargement should lead to consideration of the diagnosis, with particular attention to family history, symptoms (endurance exercise tolerance), and minor ECG abnormalities (repolarization changes, intraventricular conduction defects, abnormal Q waves).

A range of mutations in four different contractile protein genes have been shown to cause disease. It is technically possible to screen the ß-myosin heavy chain, cardiac troponin T, cardiac -tropomyosin, and myosin-binding protein C genes for mutations. This, however, is still a research procedure and at present cannot be offered as a routine clinical service. The identification of the remaining genes and more cost-effective ways of screening for mutations should in the future lead to a DNA diagnostic that could be applied to survivors of out-of-hospital VF in whom there is diagnostic uncertainty.

	Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

Top Abstract Introduction Background Definitions Evaluation of the Arrhythmogenic... Use and Abuse of... Ischemic Heart Disease Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Arrhythmogenic Right Ventricular... LQTS/Prolonged-QT Interval Idiopathic Ventricular... Sudden Unexplained Nocturnal... Ventricular Preexcitation Myocarditis Infiltrative Diseases Minimal Diagnostic Requirements... Recognition and Interpretation... Importance of Accurate Follow-up Conclusions Appendix References

 
The first clinical sign of ARVD, which is also called right ventricular cardiomyopathy, is often the occurrence of VT of right ventricular origin, frequently elicited by exercise; subtle abnormalities of the right ventricle may also be present, and cardiac arrest may be the presenting clinical manifestation.^{53 54} This diagnosis should always be sought among survivors of cardiac arrest.⁵⁵

The histological demonstration of (fibro)-fatty replacement of right ventricular myocardium allows definite diagnosis of right ventricular dysplasia/cardiomyopathy. The disease can be overlooked unless the right ventricle is specifically assessed during imaging studies. An echocardiogram of the right ventricle may reveal hypokinetic areas or dilatation in the free wall of the right ventricle and in the infundibulum. A normal echocardiogram does not exclude the diagnosis of ARVD. Right ventricular cineangiography with 30° right anterior oblique and 60° left anterior oblique views provides the most appropriate way to identify motion abnormalities of the right ventricle. ECG abnormalities such as inverted T waves in V₂ and V₃ in patients >12 years old without RBBB and prolongation of the QRS (>110 ms) in V₂ and V₃ have been suggested as major criteria for the diagnosis of ARVD by the Task Force of the Working Group for Myocardial and Pericardial Diseases.⁵³ In the less obvious forms of the disease, the diagnosis is based on the simultaneous presence of a constellation of abnormal findings that, by themselves, would be nondiagnostic. The role of MRI in the diagnosis of ARVD still needs to be defined^{56 57} ; therefore, this investigation cannot be considered necessary before this diagnosis has been excluded.

In 30% of cases the disease is familial, with an autosomal dominant inheritance; the genetic abnormality has been located in yet unknown genes on chromosome 14⁵⁸ and chromosome 1.⁵⁹

	LQTS/Prolonged-QT Interval

Top Abstract Introduction Background Definitions Evaluation of the Arrhythmogenic... Use and Abuse of... Ischemic Heart Disease Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Arrhythmogenic Right Ventricular... LQTS/Prolonged-QT Interval Idiopathic Ventricular... Sudden Unexplained Nocturnal... Ventricular Preexcitation Myocarditis Infiltrative Diseases Minimal Diagnostic Requirements... Recognition and Interpretation... Importance of Accurate Follow-up Conclusions Appendix References

 
QT-interval prolongation, history of stress-induced syncope, and family history are the mainstays for the diagnosis of the Romano-Ward form of the congenital LQTS.⁶⁰ In the presence of a markedly prolonged QT interval and of typical abnormalities of T-wave morphology, the diagnosis is rather straightforward. The problem remains the diagnosis of equivocal cases.

Careful evaluation of the 12-lead ECG is critical. QT and QT_c duration and dispersion⁶¹ should be assessed. QT_c values >440 ms for men and >460 ms for women are considered to be prolonged.⁶² The diagnosis of questionable LQTS cases is still problematic. Careful evaluation of repeated 12-lead ECGs of the patient and family members and repeated Holter monitoring remain of critical importance. In borderline cases, attention should be paid to identify abnormal T-wave morphologies, such as T-wave alternans⁶³ and notches on the T wave,^{64 65} and sudden pauses during Holter monitoring⁶⁰ that may contribute importantly to the diagnosis. An exercise stress test is also required because QT prolongation or T- or U-wave abnormalities may appear during exercise or at its cessation.

The recent identification of three of the genes responsible for LQTS cases^{36 37 38 39} opens the possibility for genetic diagnosis. However, molecular diagnosis is still largely a research tool.⁶⁶

Several drugs, including noncardiovascular drugs, prolong the QT interval and cause cardiac arrest^{40 41 42} ; a complete list of current medications should always be obtained in patients with QT prolongation and cardiac arrest. In addition, electrolyte imbalance, such as hypokalemia or hypocalcemia, can also prolong repolarization. Accordingly, the presence of a prolonged QT interval should be considered a strong factor against the diagnosis of IVF.

	Idiopathic Ventricular Tachycardia

Top Abstract Introduction Background Definitions Evaluation of the Arrhythmogenic... Use and Abuse of... Ischemic Heart Disease Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Arrhythmogenic Right Ventricular... LQTS/Prolonged-QT Interval Idiopathic Ventricular... Sudden Unexplained Nocturnal... Ventricular Preexcitation Myocarditis Infiltrative Diseases Minimal Diagnostic Requirements... Recognition and Interpretation... Importance of Accurate Follow-up Conclusions Appendix References

 
Several forms of VT are included in this group, such as verapamil-sensitive VT,⁶⁷ fascicular tachycardia of RBBB configuration with left or right axis deviation,⁶⁸ and right ventricular outflow tract tachycardia.⁶⁹ Irrespective of their site of origin, all these tachycardias share a benign prognosis.⁷⁰ In contrast, several types of polymorphic idiopathic VT have been described and are associated with a poor outcome.^{71 72 73} They can occur as sporadic or familial forms and are frequently precipitated by catecholamine release during physical or emotional stress, although this is not a consistent feature. The short-coupled variant of torsade de pointes⁷³ shares several clinical and ECG characteristics with those described in idiopathic VF by Belhassen et al.⁷⁴ On the other hand, the straightforward relationship between arrhythmia precipitation and stress, as well as the reproducible provocation of atrial and ventricular arrhythmias by exercise or isoproterenol infusion in children with the catecholaminergic polymorphic VT,⁷¹ merits a separate classification. Patients with catecholaminergic polymorphic VT have a favorable response to treatment with ß-blockers, whereas patients with idiopathic VF or short-coupled torsade de pointes do not.

	Sudden Unexplained Nocturnal Death Syndrome

Top Abstract Introduction Background Definitions Evaluation of the Arrhythmogenic... Use and Abuse of... Ischemic Heart Disease Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Arrhythmogenic Right Ventricular... LQTS/Prolonged-QT Interval Idiopathic Ventricular... Sudden Unexplained Nocturnal... Ventricular Preexcitation Myocarditis Infiltrative Diseases Minimal Diagnostic Requirements... Recognition and Interpretation... Importance of Accurate Follow-up Conclusions Appendix References

 
Sudden unexplained nocturnal death syndrome is a sudden unexplained nocturnal death in young, apparently healthy males^{75 76 77 78} of Southeast Asian origin. These deaths are named lai-tai (sleep death) in Laos, pokkuri (sudden and unexpected death) in Japan, and bangungut (to rise and moan in sleep) in the Philippines. Death is unexpected, because the victims are in apparently good health. The immediate symptoms are onset of agonal respiration during sleep. Some victims are revived by vigorous cardiac massage and then reported a sensation of airway obstruction, chest pressure, and numb or weak limbs. The cause for sudden unexplained nocturnal death syndrome is still unknown; however, the peculiar geographic distribution of these patients and the type of symptoms, including night terrors, nightmares, and nocturnal vocalizations,^{77 78} suggest that this diagnosis should be kept separate from IVF.

	Ventricular Preexcitation

Top Abstract Introduction Background Definitions Evaluation of the Arrhythmogenic... Use and Abuse of... Ischemic Heart Disease Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Arrhythmogenic Right Ventricular... LQTS/Prolonged-QT Interval Idiopathic Ventricular... Sudden Unexplained Nocturnal... Ventricular Preexcitation Myocarditis Infiltrative Diseases Minimal Diagnostic Requirements... Recognition and Interpretation... Importance of Accurate Follow-up Conclusions Appendix References

 
In patients with presumed IVF, the possibility of an accessory AV connection should include careful evaluation of the 12-lead surface ECG for the presence of a delta wave, and an electrophysiological study is suggested. The latter is important, considering that antegradely conducting accessory pathways, especially left-sided pathways, may not be apparent in a 12-lead ECG performed during sinus rhythm.⁷⁹ An electrophysiological study is performed to identify an accessory AV connection and recognize risk factors for sudden death⁸⁰ (short anterograde refractory period of the accessory pathway, ie, <250 ms; a preexcited RR interval of 250 ms during spontaneous or pacing-induced AF episodes; and fast AV reciprocating tachycardia associated with poor cardiac output). In nonconclusive cases, reassessment using isoproterenol infusion may be useful.⁸¹ Patients with supraventricular tachycardia but with a history of VF during exercise should be suspected of having supraventricular tachycardia degenerating into VF, because exercise enhances AV nodal conduction.

	Myocarditis

Top Abstract Introduction Background Definitions Evaluation of the Arrhythmogenic... Use and Abuse of... Ischemic Heart Disease Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Arrhythmogenic Right Ventricular... LQTS/Prolonged-QT Interval Idiopathic Ventricular... Sudden Unexplained Nocturnal... Ventricular Preexcitation Myocarditis Infiltrative Diseases Minimal Diagnostic Requirements... Recognition and Interpretation... Importance of Accurate Follow-up Conclusions Appendix References

 
The strongest evidence that subclinical myocarditis can be a cause of VF comes from an autopsy series⁸² on US army recruits in which 40% of those who died suddenly had histological evidence of myocarditis. However, in those subjects who were ostensibly normal before death, the status of ventricular function was unknown. Therefore, the question remains whether myocarditis can lead to VF when all other clinical parameters are normal.

The gold standard for the diagnosis of myocarditis remains myocardial biopsy (immunochemical stains are essential), which is highly specific.^{83 84} However, because of the patchy involvement of the myocardium, biopsies have a low sensitivity, and therefore a negative biopsy cannot be considered a definitive criterion for excluding myocarditis.^{85 86 87} In several cases, the origin of the arrhythmias defined during the electrophysiological study is not concordant with the site of histological abnormality; thus, it may be difficult to establish a causal relationship between bioptic findings and arrhythmias.

In the future, polymerase chain reaction gene amplification may allow identification of the viral genome from biopsy samples⁸⁸ and may help in interpreting borderline findings.

	Infiltrative Diseases

Top Abstract Introduction Background Definitions Evaluation of the Arrhythmogenic... Use and Abuse of... Ischemic Heart Disease Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Arrhythmogenic Right Ventricular... LQTS/Prolonged-QT Interval Idiopathic Ventricular... Sudden Unexplained Nocturnal... Ventricular Preexcitation Myocarditis Infiltrative Diseases Minimal Diagnostic Requirements... Recognition and Interpretation... Importance of Accurate Follow-up Conclusions Appendix References

 
Infiltrative diseases are generally detectable when major changes of the myocardial structure have occurred. In patients with sarcoidosis, a stepwise imaging investigation⁸⁹ could be performed to exclude cardiac involvement. Myocardial biopsy should also be considered for the diagnosis of sarcoidosis, even in the absence of pulmonary evidence of the disease or a negative response to a skin test.

	Minimal Diagnostic Requirements For the Diagnosis of IVF

Top Abstract Introduction Background Definitions Evaluation of the Arrhythmogenic... Use and Abuse of... Ischemic Heart Disease Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Arrhythmogenic Right Ventricular... LQTS/Prolonged-QT Interval Idiopathic Ventricular... Sudden Unexplained Nocturnal... Ventricular Preexcitation Myocarditis Infiltrative Diseases Minimal Diagnostic Requirements... Recognition and Interpretation... Importance of Accurate Follow-up Conclusions Appendix References

 
On the basis of the criteria outlined above, a panel of tests should be performed in patients with unexplained cardiac arrest to exclude clinical conditions associated with sudden cardiac death.

Although noninvasive tests might establish a diagnosis and avoid the need for invasive tests, the majority of patients without an obvious cause of cardiac arrest will undergo invasive testing (Table 1).

View this table: [in this window] [in a new window]   Table 1. Diagnostic Requirements

	Recognition and Interpretation of Minimal Cardiac Abnormalities

Top Abstract Introduction Background Definitions Evaluation of the Arrhythmogenic... Use and Abuse of... Ischemic Heart Disease Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Arrhythmogenic Right Ventricular... LQTS/Prolonged-QT Interval Idiopathic Ventricular... Sudden Unexplained Nocturnal... Ventricular Preexcitation Myocarditis Infiltrative Diseases Minimal Diagnostic Requirements... Recognition and Interpretation... Importance of Accurate Follow-up Conclusions Appendix References

 
One of the major steps in defining VF as "idiopathic" should be to clarify possible causal relationships that are currently unrecognized or controversial. In addition to nonspecific bioptic findings, the significance of minor hemodynamic abnormalities, such as borderline right and left ventricular indexes and subtle wall motion abnormalities, is unclear in survivors of IVF. Furthermore, the prevalence of subtle abnormalities in comparable individuals without life-threatening arrhythmias is not known.

An example of a minor abnormality frequently encountered in normal individuals that may pose the question of a causal relationship with cardiac arrest is mitral valve prolapse. A causal relationship between mitral valve prolapse and sudden death has not been established unless the prolapse is associated with valve redundancy, thickening, and regurgitation; QT prolongation; or ST-T wave changes.^{90 91 92 93 94 95} General agreement exists that paroxysmal and chronic atrial fibrillations have no specific relation to sudden death in the absence of the Wolff-Parkinson-White syndrome or hyperthyroidism or in subjects <70 years old; however, at least one study⁹⁶ showed that VT was easier to induce in the presence of atrial fibrillation than of sinus rhythm, and the Framingham study reported higher mortality in patients with chronic atrial fibrillation than in controls.⁹⁷ This raises the possibility that lack of significant risk may relate to inadequate evaluation of the issue.

Partial AV block (first-degree AV block or temporary second-degree AV block not associated with marked bradycardia), hypertension without LVH, and age >60 years as independent factors are not associated with sudden death and thus may be compatible with the diagnosis of IVF.

Similarly, isolated, modest thickening of the septum or free wall of the left ventricle (<10% greater than normal), regional dyskinesia, and isolated bundle-branch block do not identify a specific cause or association with sudden death and may therefore be considered compatible with the diagnosis of IVF.

RBBB associated with persistent ST-segment elevation has recently been defined as a form of IVF.²⁴ However, evidence by Corrado et al⁹⁸ suggests that this syndrome might represent one spectrum of right ventricular cardiomyopathy. These authors showed that within one family with right ventricular dysplasia, some members showed the ST-segment displacement, while others had the typical "epsilon" wave.⁹⁹ Until more data support this view, there is not enough evidence to consider RBBB and ST-segment displacement alone as diagnostic for ARVD; therefore, patients with only these features should be considered to have a variant of IVF, but careful evaluation of the right ventricle should be performed at follow-up (Table 2).

View this table: [in this window] [in a new window]   Table 2. Minimal Abnormalities Compatible With IVF

Even though as of today it remains unclear whether patients with "absolutely no evidence of heart disease" differ from those with "some evidence of cardiac abnormality," it is important that any even minimal abnormality be recorded and followed over time to allow prospective evaluation of its prognostic value.

Finally, there are some clinical conditions that will be difficult or impossible to exclude despite careful investigations (Table 3). For example, the interpretation of electrolyte disturbance in patients resuscitated from cardiac arrest is often equivocal because many patients are hypokalemic because of catecholamine release after the event. Thus, it is difficult to ascribe hypokalemia as a cause of IVF unless there is a history of electrolyte imbalance, the patients are receiving medications known to deplete potassium or are on liquid protein diets, or there is documentation of severe electrolyte abnormalities when the patient is in steady state.

View this table: [in this window] [in a new window]   Table 3. Potentially Silent Heart Disease in Survivors of IVF

The relationship between clinical findings and causation of cardiac arrest must take into account that there is a continuous spectrum from completely normal to the frankly abnormal. Judgment on the role of equivocal abnormalities in triggering or conditioning the cardiac arrest must be based on the severity of the abnormality and the strength of the evidence for a link between the abnormality and the occurrence of cardiac arrest. Moreover, abnormalities are not isolated in time: they may be transient or evolutionary and in the latter case may remain undetectable for a long time after the index clinical event.¹⁰⁰

	Importance of Accurate Follow-up

Top Abstract Introduction Background Definitions Evaluation of the Arrhythmogenic... Use and Abuse of... Ischemic Heart Disease Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Arrhythmogenic Right Ventricular... LQTS/Prolonged-QT Interval Idiopathic Ventricular... Sudden Unexplained Nocturnal... Ventricular Preexcitation Myocarditis Infiltrative Diseases Minimal Diagnostic Requirements... Recognition and Interpretation... Importance of Accurate Follow-up Conclusions Appendix References

 
Several findings may be present that cannot be considered sufficient for a diagnosis but that, nonetheless, are suspicious and may be forerunners of a structural heart disease that will become apparent only with time. In these cases, although an initial diagnosis of IVF may be acceptable, a careful follow-up of the patient is necessary. Even in the absence of symptoms or of arrhyth