Task Force Criteria

In many of these individuals, the clinical findings were more subtle than those reported by Marcus et al. [1], and yet they appeared to be affected by a variant of the same condition. In some of those identified at postmortem, clinical findings antemortem had perhaps not been recognized or interpreted appropriately, and opportunities to institute potentially life-saving measures were missed. The gold standard for making a diagnosis of ARVC/D is accepted as the demonstration of transmural fibrofatty replacement of right ventricular myocardium, determined at either postmortem or surgery. This definition presents an obvious limitation in normal clinical practice. Even using endomyocardial biopsies as a diagnostic tool, by definition the sample is not transmural and it is usually taken from the interventricular septum, not recognized as part of the triangle of dysplasia; as such, absence of characteristic changes would not exclude the diagnosis. Reliance on an invasive and potentially high risk procedure as a sole diagnostic tool, given the known morphological abnormalities encountered in the right ventricle, is not practical for screening in large populations. The other features documented in patients with ARVC/D are variably lacking in specificity for the condition. As a result of these difficulties in clinically diagnosing ARVC/D, a Task Force of experienced clinicians in the field of cardiomyopathy was convened under the auspices of the European Society of Cardiology (Working Group on Myocardial and Pericardial Diseases) and the International Society and Federation of Cardiology (Scientific Council). The remit of this Task Force was to agree criteria on clinical evaluation that would delineate the spectrum of disease that justifiably can be called right ventricular dysplasia in clinical practice [28].

Based on the contemporaneously available evidence, the Task Force looked at clinical criteria in six different groupings. Diagnostic criteria were assigned major or minor status according to their specificity for the condition. A diagnosis of ARVC/D was to be considered fulfillled by the presence of different groups of two major criteria, one major and two minor criteria, or four minor criteria (Table 10.1).

Right ventricular morphological abnormalities, as defined by echocardiography, angiography, magnetic resonance imaging or nuclear scintigraphy, are perhaps the most difficult to standardize. The identification of regional wall motion abnormalities still to this day requires a subjective judgement, and is therefore open to over- and under-reporting. The measurement of right ventricular volumes, dimensions, and ventricular function is problematic, as the structure of the right ventricle is not amenable to the same mathematical assumptions which permit analogous measurements in the left ventricle. Definition of the normal reference range for the right ventricle in each of these parameters is based on a relatively

Table 10.1 • Task force criteria for diagnosis of ARVC/D. Adapted from [28]

I. Global and/or regional dysfunction and structural alterations*

IV. Depolarisation/conduction abnormalities

Major:

Major:

Severe dilatation and reduction in systolic function of

Epsilon waves or localised prolongation of the

RV with no (or only mild) impairment of LV

QRS complex in V1-V3 (>110 ms)

Localised RV aneurysms (akinetic or dyskinetic areas

Minor:

with diastolic bulging)

Late potentials demonstrated on signal

Severe segmental dilatation of the RV

averaged ECG

Minor:

Mild global RV dilatation and /or reduction in ejection

fraction with normal LV

Mild segmental dilatation of RV

Regional RV hypokinesia

II.Tissue characterisation of walls

V. Arrhythmias

Major:

Minor:

Fibrofatty replacement of myocardium demonstrated

Sustained and non-sustained ventricular

on endomyocardial biopsy

tachycardia with left bundle branch block

morphology (documented on ECG, Holter or

exercise testing)

Frequent ventricular extrasystoles (>1000 over

24 hrs Holter monitoring)

III. Repolarisation abnormalities

VI. Family history

Minor:

Major:

Inverted T-waves in right precordial leads (V2 and V3)

Familial disease confirmed at necropsy or

(individuals >12 years of age; in the absence of right

surgery

bundle branch block)

Minor:

Family history of premature sudden death (<35

years) due to suspected right ventricular dysplasia

Family history of clinical diagnosis based on the

present criteria

ECG, electrocardiogram; LV, left ventricle; RV, right ventricle

* Morphological changes in I as detected by echocardiography, angiography, cardiac magnetic resonance imaging or

radionuclide scintigraphy

small study of 41 patients using multiple tomo-graphic planes to overcome the difficulties relating to structure [29]. Dilation of a segment or the whole right ventricle was defined as being mild if measured dimensions were 2-3 standard deviations, and severe if >3 standard deviations greater than normal, based on evidence from studies of ARVC/D patients evaluated by echocardiography and/or angiography [8, 30-33]. In an effort to improve the specificity of the criteria it was stipulated that the finding of morphological or functional abnormalities of the right ventricle must be in the absence of any more than mild left ventricular systolic impairment. This was in an effort to avoid inclusion of dilated cardiomyopa-thy with right ventricular involvement under the diagnostic umbrella of ARVC/D. When these criteria were written, dilated cardiomyopathy and ARVC/D were considered to be entirely distinct entities, although evidence of considerable overlap in pheno-typic presentation has come to light, mostly in the last decade [17, 18, 34-37]. By definition, therefore, the diagnostic criteria allow for only mild left ventricular involvement, which does not reflect currently available information on the prevalence of left ventricular involvement in ARVC/D.

Endomyocardial biopsy findings of fibrofatty replacement are rarely diagnostic, although this was given major status as a diagnostic criterion as it would strongly support any findings on the other clinical investigations. Specific histomorphometric parameters of myocytes, interstitium, fibrous and fatty tissue were evaluated on biopsy samples by the Padua Group, and threshold values of <45% area of myocytes, >40% fibrous, and >3% fatty tissue were defined as diagnostic of ARVC/D with 67% sensitivity and over 90% specificity for at least one parameter [38].

Repolarization abnormalities on ECG, consisting of T-wave inversion in the right precordial leads (beyond V1 to include V2 and V3) was quite a consistent finding in earlier reported case series (over 85% as reported by Marcus et al. [1]). Subsequent case series have described a variable prevalence of right precor-

dial T-wave inversion, ranging from 19% to 94% [3942]. The lower prevalence rates are often seen on evaluation of familial ARVC/D (less than 20% of living relatives in 37 families [42]), while higher rates are often seen in case series of unrelated probands (81% in the recently published US experience [43]). This is probably explained partly by inclusion bias in those diagnosed on clinical criteria alone with no obvious family history, and partially by incomplete penetrance in familial forms of the disease. T-wave inversion can be a normal feature of the ECG in childhood or in the transitional phase from childhood to adult ECG pattern, and thus this finding is not considered diagnostic in those age 12 years of age and under. For similar reasons, T-wave inversion is not considered a diagnostic feature in the presence of right bundle branch block on the resting ECG. Although a consistent feature in many case series, the differential for the presence of T-wave inversion in right precordial leads can include right ventricular overload, such as in major pulmonary embolus, atrial septal defect or any intracardiac right to left shunt, or it may develop following intracranial haemorrhage, postulated to be a consequence of adren-ergic responses to the cerebral insult. It is therefore a relatively nonspecific finding and is thus relegated to the status of a minor criterion (Fig. 10.1).

The presence of epsilon waves in the right precordial leads reflects delayed activation of some right ventricular fibers. This may be a function of infiltration of the right ventricle by fibrofatty tissue. Definitions vary, but the currently accepted definition of an epsilon wave is any electric potential in V1 to V3 exceeding the QRS duration in V6 by more than 25msec occurring after the end of the QRS complex [44]. This has been found to be highly specific for the diagnosis of ARVC/D, and is therefore afforded major status, although it is observed in only 25%-33% of ARVC/D patients using standard ECG [40, 45]. A modified method of lead placement as described by Fontaine [44] will improve the demonstration of epsilon waves to a prevalence of over 60% [40]. Localized prolongation of the QRS complex in V1 to V3 beyond 110msec in duration is also considered to be a major criterion. In one study this was found in 70% of affected patients [40]. Varying degrees of delayed right ventricular activation, from incomplete in up to 18% of cases to complete right bundle branch block in up to 15% of cases, have been identified [44]. A related phenomenon, the difference in QRS duration between right precordial leads and V6 (termed QRS dispersion) has been shown to be a strong independent predictor of sudden death at values >40 msec [45].

The detection of late potentials on signal-averaged ECG is the surface counterpart of delayed or late potentials detected during endocardial or epicardial mapping. They are frequently found in patients with documented ventricular tachycardia but lack specificity, being found in other settings such as in the postmy-ocardial infarction setting [46,47], and are thus considered a minor criterion. The prevalence in ARVC/D series ranges from 50% to 80% [48,49], the variation possibly relating to disease severity as a positive cor

Left Ventricular Ectopic Beats
Fig. 10.1 • ECG from a patient with a confirmed mutation in plakophilin-2 showing localized QRS prolongation in right precordial leads,associated with characteristic T-wave inversion extending to V4. A single ventricular ectopic beat is also seen

relation has been found between late potentials and extent of right ventricular fibrosis, reduced right ventricular systolic function and significant morphological abnormalities on imaging [50,51] (Fig. 10.2).

Ventricular arrhythmias of left bundle branch block morphology can occur in the presence of ischemic heart disease (although right bundle branch block arrhythmia predominates in this case), bundle branch re-entry arrhythmia or Right Ventricular Outflow Tract Ventricular Tachycardia (RVOT VT), a supposedly prognostically benign condition. While their occurrence (either as sustained or nonsustained VT detected on ECG, exercise test or ambulatory monitoring) should raise suspicion of a possible diagnosis of ARVC/D, it is not a finding specific to the condition. Equally the finding of frequent ventricular ectopics (>1000 over 24h) on ambulatory ECG monitoring, while frequently found in association with ARVC/D, may be found in patients with is-chemic heart disease or other conditions [52] and therefore constitute a minor criterion only.

The inclusion of family history as a diagnostic criterion reflects the growing awareness that ARVC/D is frequently an inherited (dominant) condition [42, 53]. Pathological confirmation of transmural fibrofatty replacement of ventricular myocardium, from either surgically resected or postmortem tissue, is the gold standard for diagnosing ARVC/D, and not surprisingly, if a relative is so diagnosed, it is considered as a major criterion in the diagnosis of their relatives. As postmortem evaluations are not always performed by expert cardiac pathologists, too often the right ventricle is inadequately sampled and a diagnosis may be missed. For this reason a premature (<35 years) sudden death in the family thought, but not proven, to be due to ARVC/D is considered a minor criterion. Equally as a clinical diagnosis in a family member usually lacked histopathological confirmation, it was considered only a minor criterion when considering diagnosis in other family members.

In proposing the diagnostic criteria, the Task Force authors considered the resulting diagnostic criteria to be a "working framework to improve understanding of this condition." They postulated that increased characterization of familial disease, the identification of a gene or genes responsible, and in time a more de

Fig. 10.2 • Signal averaged ECG from a female patient with ARVC/D who presented with cardiac arrest and was found to have biventricular involvement. A desmoglein-2 mutation has been confirmed. Recorded at the 40-Hertz filter, the vector output is positive for late potentials with the root mean square voltage of the terminal 40ms <20 ^V and the duration of the low-amplitude signal >41 ms

Fig. 10.2 • Signal averaged ECG from a female patient with ARVC/D who presented with cardiac arrest and was found to have biventricular involvement. A desmoglein-2 mutation has been confirmed. Recorded at the 40-Hertz filter, the vector output is positive for late potentials with the root mean square voltage of the terminal 40ms <20 ^V and the duration of the low-amplitude signal >41 ms tailed understanding of the natural history of the condition would promote evolution of the criteria to allow a more succinct clinical or genetic diagnosis. Some of the limitations of the criteria are detailed above.

Was this article helpful?

0 0

Post a comment