True idiopathic ventricular fibrillation in out-of-hospital cardiac arrest survivors in the Swiss Canton Ticino: prevalence, clinical features, and long-term follow-up

Introduction

Out-of-hospital cardiac arrest (OHCA) remains a high priority public health problem. It is more frequently caused by sustained ventricular arrhythmias (VT/VF) in the context of structural heart disease.¹ Cardiac arrest due to ventricular arrhythmias in the absence of evident structural heart disease is uncommon: its arrhythmic substrate includes primary electrical disorders and subclinical structural abnormalities.^1–3 Intensive diagnostic management, including pharmacological challenges and advanced cardiac imaging techniques, reduces the number of cases remaining unexplained.⁴ Moreover, repeated assessment of electrocardiographic (ECG) phenotype of those patients with a previously unexplained OHCA may lead to a change in initial diagnosis in up to 20% of cases.⁵

Occasionally, there are OHCA survivors in whom the arrhythmic event remains unexplained, and it is defined as idiopathic ventricular fibrillation (IVF). Idiopathic ventricular fibrillation has been frequently associated to early repolarization (ER) pattern in inferior and/or lateral leads of standard 12-lead ECG, which confers a higher risk of further arrhythmic events.⁶

In some patients with IVF, however, 12-lead ECG continues to be normal.⁷ Current clinical practice guidelines recommend the implantation of a cardioverter-defibrillator (ICD) in all patients with IVF. Those patients with IVF in whom standard ECG remains normal over time poses a substantial dilemma when the ICD has to be replaced or removed for different reasons, especially when no arrhythmia has been documented over follow-up. Prevalence of IVF in OHCA survivors without ER is currently unknown. Very little, if any information, is available on the clinical features, evolution of ECG, possible changes of echocardiographic parameters over the time, or recurrence of ventricular arrhythmias during long-term follow-up in this patients' subgroup. The purpose of this study was to investigate prevalence, clinical features, and long-term prognosis of IVF in OHCA survivors with otherwise normal ECGs.

Methods

Study population

We reviewed the medical records of all OHCAs occurring between 1 January 2000 and 31 December 2014, and selected those who survived a cardiac arrest due to ventricular tachycardia (VT) or ventricular fibrillation (VF). Of these patients, we considered those who presented with IVF.

Ventricular fibrillation was considered idiopathic if a cardiac, respiratory, metabolic, and toxicological aetiology was excluded, and the patient maintained a normal 12-lead ECG throughout follow-up. All recordings of automated external defibrillators used at the time of OHCA were reviewed and classified by two investigators. Idiopathic ventricular fibrillation patients presenting with signs of ER, Brugada type 1 or 2 ECG, prolonged corrected QT interval (QTc > 450 ms for men and QTc > 460 ms for women), short QT interval (QTc < 320 ms), Wolff–Parkinson–White syndrome, and atrioventricular conduction abnormalities at the hospital admission or on the day immediately before ICD implantation were not included in the ‘truly’ IVF cohort. A complete medical history, physical examination, metabolic and toxicological screening, baseline 12-lead ECG, 2-dimensional echocardiography (2D-TTE), 24-h Holter monitoring, and a coronary angiogram were obtained to rule out structural abnormalities or other aetiologies as cause of OHCA. A biopsy was done if clinically indicated. Moreover, starting from 2008, all patients with VT/VF and no overt structural disease underwent a cardiovascular magnetic resonance (CMR) imaging. An electrophysiological study (EPS) was performed at the investigators' preference to evaluate inducibility and characteristics of sustained VT/VF. Ajmaline challenge was performed in any case of suspected Brugada syndrome (BS) and non-diagnostic baseline ECG. Ajmaline was administered intravenously over a 5 min period at a dose of 1 mg/kg. The test was considered positive for BS only if coved type 1 ECG was documented in ≥1 right precordial leads (V1–V3). Moreover, an exercise stress test was performed in any case of suspected long QT syndrome.

A web-based cardiac arrest registry was established on 1st January 2002; consecutive and audited data have been entered starting on 1st January 2005.⁸ It contains a record of every individual who presented a cardiac arrest regardless of the aetiology and includes patient's demographic data, comprehensive Emergency medical system (EMS)-related data, circumstances of OHCA, and first documented rhythm at EMS arrival. Out-of-hospital cardiac arrest was defined as cessation of cardiac mechanical activity confirmed by the absence of signs of circulation occurring outside of a hospital setting. Sustained ventricular arrhythmia was defined as an episode of VT or VF during at least 30 s or requiring intervention for termination. Patients were excluded if they had no available documentation of the shockable rhythm which led to OHCA.

Twelve-lead electrocardiogram analysis

All baseline and follow-up ECGs were recorded at a paper speed of 25 mm/s and amplitude of 10 mm/mV. Two experienced electrophysiologists independently reviewed all ECGs; in case of disagreement, the ECG was reviewed by a third electrophysiologist.

Early repolarization pattern was considered in the presence of QRS slurring (a smooth transition from the QRS segment to the ST segment) or notching (a positive J deflection of at least 1 mm inscribed on the S wave) in the inferior leads (II, III, and aVF), lateral leads (I, aVL, and V4–V6), or both. An ECG was considered diagnostic of BS (type 1) if a coved type ST elevation ≥2 mm was documented in ≥1 lead from V1 to V3 in the presence or absence of a sodium-channel blocker agent.⁹ Abnormal fragmentation of the QRS complex (f-QRS) was defined as the presence of multiple spikes within the QRS (≥4 spikes in 1 or ≥8 spikes in all of the leads V1, V2, and V3).¹⁰ Atrioventricular conduction abnormalities were considered as bundle branch block of any type or first-degree AV block.

Cardioverter-defibrillator implantation and programming

A single- or dual-chamber ICD was implanted in all OHCA survivors according to available clinical practice guideline recommendations. A monitor zone (>150 bpm), fast VT zone (180–200 bpm) with anti-tachycardia pacing (ATP) and shocks, and VF detection zone (>200 bpm) with shocks were programmed in all cases. Supraventricular tachycardia discrimination was always on. Implantable cardioverter-defibrillator programming was adjusted based on the individual clinical history and availability of new clinical evidence for device programming in secondary prevention patients.^11–14

Follow-up

Clinical follow-up of patients consisted of physical examination and ECG performed at least every 6 months. Follow-up of the device was performed at 1 and 3 months after ICD implantation and thereafter every 6 months either in person or remotely. All stored electrograms were independently reviewed and classified by two investigators. Appropriate therapies were defined as shocks or ATP delivered for VT or VF; inappropriate therapies were defined as those delivered for other causes than VT/VF. An electrical storm was considered when three or more sustained episodes of VT, VF, or ICD appropriate shocks occurred within 24 h.

Statistical analysis

Continuous data are presented as median and 25th–75th percentiles (IQR) and categorical data as counts and percentages; they were compared with the Mann–Whitney U test and the Fisher exact test, respectively. Event-free survival was estimated by Kaplan–Meier method and compared by log-rank test. Median follow-up (IQR) was computed with the inverse Kaplan–Meier method. The prevalence of IVF was computed as the ratio of the total number of true IVF over the total number of OHCAs in which resuscitation was attempted, OHCAs of cardiac origin and OHCAs of cardiac origin with shockable first rhythm. Statistical analyses were conducted using the Stata 13 software (Stata Corporation College Station, TX, USA). A two-sided P-value <0.05 was considered statistically significant.

Results

A total of 3407 OHCAs occurred in Canton Ticino (Switzerland) from 2000 to 2014 (Figure 1). Out of 237 patients discharged alive, an arrhythmic event occurred in 163 patients in the context of acute coronary syndrome, whereas in the remaining 74 patients an ICD was deemed appropriate and implanted in all before discharge. Seventy-one patients presented with VF as first-shockable rhythm. The underlying aetiology of VF was coronary artery disease in 42 patients, idiopathic dilated cardiomyopathy in 16 patients, arrhythmogenic right ventricle cardiomyopathy in 1 patient, and a chronic myocarditis in another patient (Figure 1). In 15 patients (21%), a moderately reduced left ventricular systolic function (LVEF ranging between 41 and 53%) was recorded; in one patient with normal LVEF, a sub-endocardial diffuse fibrosis was documented by CMR. All these latter patients were considered to have a subclinical disease thus were excluded from the IVF group. In the remaining 11 patients (15%), VF was considered idiopathic at the time of the initial evaluation (Table 1). After OHCA, all these patients were discharged with a good cerebral status (CPC 1 or 2) which remained unchanged during the long-term follow-up. Over time, an ECG was found abnormal in three cases (Figure 2). One patient presented with Brugada type 1 ECG (Figure 2, Patient 5) and another one with J waves in inferior leads (Figure 2, Patient 8) after 8 and 24 months from ICD implantation, respectively. The other patient showed long QT interval (>500 ms) appearing after 6 months from ICD implantation (Figure 2, Patient 9). The remaining eight patients were considered as ‘truly’ IVF since no ECG or structural abnormality was detected either at baseline or at latest follow-up evaluations.

Table 1

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Clinical and instrumental characteristics of patients with IVF as initial diagnosis

Pt .	Gender .	Age .	Family history of SD .	Previous AF .	Time (year of event) .	Circumstances .	Ajmaline test .	Inducible VA at EP study .	CMR .	EF (%) .	LVEDV (mL) .	LVESV (mL) .	PWT (mm) .	IVS (mm) .	LVMI (g/m2) .	Type of ICD .	New ECG findings at FU .
1	M	38	no	no	9.40 AM (2000)	Rest	np	np	np	63	130	42	10	9	67	Single-ch	no
2	M	62	no	no	10.25 AM (2004)	Rest	np	np	np	56	148	65	10	10	63	Dual-ch	no
3	M	59	no	yes	7.11 AM (2004)	Driving	np	no	np	59	115	52	9	8	59	Dual-ch	no
4	M	43	no	no	7.41 AM (2006)	Rest	np	no	np	58	98	46	8	9	65	Dual-ch	no
5	M	33	no	no	6.59 AM (2009)	Rest	np	np	yes	58	95	35	10	9	59	Dual-ch	Brugada type1 ECG
6	F	48	no	no	7.25 PM (2010)	Rest	yes	np	yes	60	154	61	9	9	106	Dual-ch	no
7	M	62	no	no	11.00 AM (2010)	Driving	yes	np	yes	57	134	57	10	10	77	Dual-ch	no
8	M	28	no	no	2.00 PM (2012)	Rest	yes	np	yes	60	148	49	9	9	85	Dual-ch	J-wave pattern
9	M	73	no	no	12.12 PM (2012)	Driving	np	np	yes	60	118	51	11	10	74	Dual-ch	Long-QT interval
10	F	37	no	no	1.30 PM (2013)	Effort	yes	np	yes	55	120	49	9	8	51	Dual-ch	no
11	M	39	yes	no	10.30 AM (2014)	Effort	yes	no	yes	62	149	60	10	10	85	s-ICD	no

Pt .	Gender .	Age .	Family history of SD .	Previous AF .	Time (year of event) .	Circumstances .	Ajmaline test .	Inducible VA at EP study .	CMR .	EF (%) .	LVEDV (mL) .	LVESV (mL) .	PWT (mm) .	IVS (mm) .	LVMI (g/m2) .	Type of ICD .	New ECG findings at FU .
1	M	38	no	no	9.40 AM (2000)	Rest	np	np	np	63	130	42	10	9	67	Single-ch	no
2	M	62	no	no	10.25 AM (2004)	Rest	np	np	np	56	148	65	10	10	63	Dual-ch	no
3	M	59	no	yes	7.11 AM (2004)	Driving	np	no	np	59	115	52	9	8	59	Dual-ch	no
4	M	43	no	no	7.41 AM (2006)	Rest	np	no	np	58	98	46	8	9	65	Dual-ch	no
5	M	33	no	no	6.59 AM (2009)	Rest	np	np	yes	58	95	35	10	9	59	Dual-ch	Brugada type1 ECG
6	F	48	no	no	7.25 PM (2010)	Rest	yes	np	yes	60	154	61	9	9	106	Dual-ch	no
7	M	62	no	no	11.00 AM (2010)	Driving	yes	np	yes	57	134	57	10	10	77	Dual-ch	no
8	M	28	no	no	2.00 PM (2012)	Rest	yes	np	yes	60	148	49	9	9	85	Dual-ch	J-wave pattern
9	M	73	no	no	12.12 PM (2012)	Driving	np	np	yes	60	118	51	11	10	74	Dual-ch	Long-QT interval
10	F	37	no	no	1.30 PM (2013)	Effort	yes	np	yes	55	120	49	9	8	51	Dual-ch	no
11	M	39	yes	no	10.30 AM (2014)	Effort	yes	no	yes	62	149	60	10	10	85	s-ICD	no

NP, not performed; SD, sudden death; AF, atrial fibrillation; VA, ventricular arrhythmia; CMR, cardiac magnetic resonance; EF, ejection fraction; LVEDV, left ventricle end-diastolic volume; LVESV, left ventricle end-systolic volume; PWT, posterior wall thickness; IVS, interventricular septum; LVMI, left ventricle mass index; ICD, implantable cardioverter-defibrillator; s-ICD, subcutaneous ICD; ECG, electrocardiogram; FU, follow-up.

Table 1

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Clinical and instrumental characteristics of patients with IVF as initial diagnosis

Pt .	Gender .	Age .	Family history of SD .	Previous AF .	Time (year of event) .	Circumstances .	Ajmaline test .	Inducible VA at EP study .	CMR .	EF (%) .	LVEDV (mL) .	LVESV (mL) .	PWT (mm) .	IVS (mm) .	LVMI (g/m2) .	Type of ICD .	New ECG findings at FU .
1	M	38	no	no	9.40 AM (2000)	Rest	np	np	np	63	130	42	10	9	67	Single-ch	no
2	M	62	no	no	10.25 AM (2004)	Rest	np	np	np	56	148	65	10	10	63	Dual-ch	no
3	M	59	no	yes	7.11 AM (2004)	Driving	np	no	np	59	115	52	9	8	59	Dual-ch	no
4	M	43	no	no	7.41 AM (2006)	Rest	np	no	np	58	98	46	8	9	65	Dual-ch	no
5	M	33	no	no	6.59 AM (2009)	Rest	np	np	yes	58	95	35	10	9	59	Dual-ch	Brugada type1 ECG
6	F	48	no	no	7.25 PM (2010)	Rest	yes	np	yes	60	154	61	9	9	106	Dual-ch	no
7	M	62	no	no	11.00 AM (2010)	Driving	yes	np	yes	57	134	57	10	10	77	Dual-ch	no
8	M	28	no	no	2.00 PM (2012)	Rest	yes	np	yes	60	148	49	9	9	85	Dual-ch	J-wave pattern
9	M	73	no	no	12.12 PM (2012)	Driving	np	np	yes	60	118	51	11	10	74	Dual-ch	Long-QT interval
10	F	37	no	no	1.30 PM (2013)	Effort	yes	np	yes	55	120	49	9	8	51	Dual-ch	no
11	M	39	yes	no	10.30 AM (2014)	Effort	yes	no	yes	62	149	60	10	10	85	s-ICD	no

Pt .	Gender .	Age .	Family history of SD .	Previous AF .	Time (year of event) .	Circumstances .	Ajmaline test .	Inducible VA at EP study .	CMR .	EF (%) .	LVEDV (mL) .	LVESV (mL) .	PWT (mm) .	IVS (mm) .	LVMI (g/m2) .	Type of ICD .	New ECG findings at FU .
1	M	38	no	no	9.40 AM (2000)	Rest	np	np	np	63	130	42	10	9	67	Single-ch	no
2	M	62	no	no	10.25 AM (2004)	Rest	np	np	np	56	148	65	10	10	63	Dual-ch	no
3	M	59	no	yes	7.11 AM (2004)	Driving	np	no	np	59	115	52	9	8	59	Dual-ch	no
4	M	43	no	no	7.41 AM (2006)	Rest	np	no	np	58	98	46	8	9	65	Dual-ch	no
5	M	33	no	no	6.59 AM (2009)	Rest	np	np	yes	58	95	35	10	9	59	Dual-ch	Brugada type1 ECG
6	F	48	no	no	7.25 PM (2010)	Rest	yes	np	yes	60	154	61	9	9	106	Dual-ch	no
7	M	62	no	no	11.00 AM (2010)	Driving	yes	np	yes	57	134	57	10	10	77	Dual-ch	no
8	M	28	no	no	2.00 PM (2012)	Rest	yes	np	yes	60	148	49	9	9	85	Dual-ch	J-wave pattern
9	M	73	no	no	12.12 PM (2012)	Driving	np	np	yes	60	118	51	11	10	74	Dual-ch	Long-QT interval
10	F	37	no	no	1.30 PM (2013)	Effort	yes	np	yes	55	120	49	9	8	51	Dual-ch	no
11	M	39	yes	no	10.30 AM (2014)	Effort	yes	no	yes	62	149	60	10	10	85	s-ICD	no

NP, not performed; SD, sudden death; AF, atrial fibrillation; VA, ventricular arrhythmia; CMR, cardiac magnetic resonance; EF, ejection fraction; LVEDV, left ventricle end-diastolic volume; LVESV, left ventricle end-systolic volume; PWT, posterior wall thickness; IVS, interventricular septum; LVMI, left ventricle mass index; ICD, implantable cardioverter-defibrillator; s-ICD, subcutaneous ICD; ECG, electrocardiogram; FU, follow-up.

Figure 1

OHCAs in which resuscitation was attempted between 2000 and 2014 in Canton Ticino.

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Figure 2

ECG of patients in whom the initial diagnosis changed over time.

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Overall, prevalence of IVF in OHCA in which resuscitation was attempted and of IVF in OHCAs of cardiac origin was 0.2% (95% CI 0.1–0.5) and 0.4% (95% CI 0.2–0.7), respectively; while in OHCAs due to cardiac origin and presenting with ventricular tachyarrhythmia as first rhythm, it was 1.2% (95% CI 0.5–2.4).

Clinical features of patients with idiopathic ventricular fibrillation

Demographic and ECG characteristics of patients with IVF are summarized in Table 2 and are compared with the remaining OHCA survivors presenting with VF and cardiac disease. No significant difference was found in the gender, family history of sudden death, and the symptom status before ICD implantation between patients with IVF and those with an established cardiac disease.

Patients with IVF were predominantly males (75%) and significantly younger compared with those with VF from other causes (median age: 45 years, IQR 38–60 vs. 65 years, IQR 58–70; P: 0.002). They had higher median LVEF (60%, IQR 57–60 vs. 40% IQR 30–50; P < 0.001).

Sudden cardiac arrest occurred at rest in four patients (50%), during exercise in two (25%), and while driving in other two individuals (25%). No episode of VF was related to a febrile status. Circadian distribution of IVF is shown in Figure 3; most of arrhythmic episodes (75%) occurred during the morning hours, between 7.00 and 11.00 AM. All patients received a 24-h ECG Holter monitoring with no evidence of short-coupled premature ventricular complexes occurrence. Three patients (37%) underwent programmed ventricular stimulation which did not induce any sustained VT/VF. One patient (12.5%) received a single-chamber transvenous device, six (75%) a dual-chamber transvenous ICD implantation, and one a totally subcutaneous ICD system. No patient experienced any device-related early complication. Furthermore, no drug therapy was prescribed at the time of discharge.

Figure 3

Circadian distribution of OHCAs of cardiac origin witnessed by bystander with first rhythm VT/VF (n = 644) and of OHCAs due to true IVF (n = 8, red dots). The position of red dots corresponds to the exact time of the event.

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Long-term follow-up

After a mean follow-up time of 85 ± 47 months (median: 42 months, IQR 12–85), no IVF patient died. No spontaneous sustained VT/VF, syncope, or appropriate ICD intervention was documented in any patient with IVF. There was a non-significant trend towards worse outcome in those patients with known cardiac disease (Figure 4). One of the eight patients with IVF experienced a new episode of paroxysmal atrial fibrillation and drug therapy with sotalol was initiated; none had inappropriate shocks. One patient developed a first-degree AV block. At last follow-up visit, no new echocardiographic findings were found and LVEF remained unchanged in all patients.

Figure 4

Kaplan–Meier survival estimate by diagnosis. Overall survival due to true IVF is shown as BLUE line; overall survival of patients with VF due to an established aetiology before ICD implantation is shown as RED line.

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Discussion

To best of our knowledge, this is the first study that has systematically assessed the prevalence, clinical features, and prognosis of patients with IVF, normal baseline 12-lead ECG, and otherwise normal heart. Despite the initial presentation, all these patients had no further events including ICD shocks. Although these data are somehow reassuring for this subgroup of OHCA survivors, it remains unknown the trigger of the dramatic clinical presentation, the truly underlying disease/diagnosis, and the outcome beyond 7 years.

Prevalence of idiopathic ventricular fibrillation in out-of-hospital cardiac arrest survivors and importance of diagnostic re-evaluation over follow-up

Ventricular fibrillation is the most common arrhythmia leading to OHCA. Although the therapeutic management with ICD therapy is straightforward in OHCA survivors with an established cause, the aetio-pathogenesis of the arrhythmic event is sometimes challenging, thus leaving the cause of OHCA in occasional cases as undefined. Moreover, ∼18% of autopsies of sudden cardiac arrest victims younger than 40 years cannot reveal any structural cardiac abnormality.³

Previously, Nam reported a prevalence of 8.4% of IVF in survivors of sudden cardiac death with otherwise normal ECGs who received an ICD implantation.¹⁵ Similarly, in our study, the prevalence of true IVF over OHCAs survivors undergoing ICD implantation was 10.8%.

Moreover, in this study, the overall prevalence of IVF in a large series of patients with cardiac origin OHCA and documented first-rhythm VT/VF was 1.2%. Prevalence of IVF could be difficult to be established as patient's phenotype might change during the follow-up. In fact, in our study, initial diagnosis changed over the time in 27% of patients initially considered as having experienced IVF.

Diagnostic re-evaluation of ICD patients is usually not performed throughout follow-up; thus, the initial event considered as idiopathic remains unexplained in most of cases. Our study confirms the importance of re-evaluation of the diagnosis in IVF patients, which may have significant consequences for assessment of patient's prognosis, for family screening, and possibly family counselling. Matassini et al.⁵ have recently reported a change in initial diagnosis in up to 20% of patients presenting with unexplained cardiac arrest. The CASPER study showed that use of systematic non-invasive and invasive testing, including drug provocation, and the use of advanced cardiac imaging, may lead to precise diagnosis in 56% of unexplained cardiac arrest due to VT/VF in patients with preserved LVEF and normal coronary arteries.⁴ Of them, 75% of patients are diagnosed with a primary electrical disease and the remaining 25% presents a structural heart disease. In good agreement with other experiences, initial diagnosis changed over the time in 27% of patients initially considered as having experienced IVF. Although baseline 12-lead ECG is already useful to identify channelopathies, drug challenge shall also be considered. This latter point is not sufficiently emphasized in the most recent EHRA/HRS/APHRS expert consensus on ventricular arrhythmias and shall be considered in future documents.

The value of CMR has been already reported for detection of the morphological substrate and/or underlying cardiac condition in patients with VT/VF without previously known cardiac conditions.¹⁶ All patients presenting with IVF should, therefore, undergo CMR, prior to ICD implantation, to determine whether subtle structural abnormalities are present, even if they present with a completely normal 2D-TTE.

Clinical characteristics

The present study expands the knowledge about clinical and ECG presentation of IVF patients demonstrating the heterogeneity of this patient group and of the associated outcome. More commonly, IVF patients show ER on 12-lead ECG and a minority has AV conduction disturbances.^6,7,17,18 In this study, we reported the clinical features of a very peculiar group of patients with IVF presenting with completely normal baseline ECG. Sekiguchi et al.⁷ have previously reported male predominance in patients with IVF and ER and nearly equal distribution in males and females presenting with IVF in the absence of ER. Conversely, in our study, male predominance was observed.

Another interesting finding concerned the circadian distribution of IVF. It has been reported a higher incidence of nocturnal VF in patients with IVF and ER pattern.¹⁹ In contrast in our patients, no VF occurred during nocturnal hours, but the VF incidence increased in the morning hours following the same circadian pattern as all other OHCAs.²⁰ Although this difference may be due to under-reporting, noteworthy >70% of OHCAs in Canton Ticino are bystander witnessed.⁸ Our circadian distribution is closer to that reported for non-fatal myocardial infarction, thus suggesting a relationship with the surge of the enhanced adrenergic tone during the morning hours of the day.²¹ An alternative mechanism of IVF could be a coronary spasm, a well-recognized cause of cardiac arrest. Although a pharmacological challenge for testing coronary artery reactivity was not performed in our patients, no patient experienced further event in the absence of any cardioactive medication. In contrast, patients with coronary spasm who do not receive adequate pharmacological therapy have recurrent events.²²

Long-term prognosis

This is the first study reporting the long-term prognosis of IVF with a normal ECG. Previously, Haïssaguerre et al.⁶ described a higher incidence of ER pattern in OHCA survivors and a worse outcome of patients in the presence of such abnormalities. In contrast, our study population which addressed IVF with a normal ECG presented a particularly benign outcome during a follow-up approaching 7 years. This observation might be due to a completely different pathophysiological substrate between our patients and those with ER pattern who experience IVF.

Based on this initial experience, no final conclusion or recommendation could be drawn on the long-term arrhythmic risk and the implications of ICD removal at the time of replacement. Further studies with larger populations and longer follow-up might help in establishing the lifelong risk of arrhythmias of these patients. Therefore, as recommended by current guidelines, implantation of an ICD should be performed in all patients with IVF. The choice between single- and dual-chamber devices should be driven by the presence of previous episodes of supraventricular arrhythmias or the evidence of sinus node dysfunction or atrioventricular conduction disease. A subcutaneous system might be an option for these patients with normal baseline ECG. However, the implantation should be preceded by an EPS to evaluate the inducibility of sustained VT and/or supraventricular tachycardia. Moreover, as the initial diagnosis may change over time, the S-ICD morphology analysis should be performed even during pharmacological challenge to detect potential drug-induced ECG modifications.

Limitations

Our study has certain limitations. It is a retrospective, single-centre experience conducted, due to the rarity of the condition, in a small population of patients with heterogeneous clinical characteristics.

Furthermore, in patients with a lifelong risk of arrhythmias, a mean follow-up of 7 years might be considered short. The prevalence of IVF might be underestimated since our study selected only OHCA survivors presented with documented shockable rhythm. The intermittent nature of certain ECG abnormalities (such as BS type 1 ECG, ER pattern, or long-QT interval) as well as the fact that CMR and pharmacological challenge were not performed in all patients could have led to an increased number of cases considered as idiopathic. Moreover, EP study with PVS and genetic test was not performed in all patients.

Conclusions

Idiopathic ventricular fibrillation with normal baseline ECG is a rare disease, and it is diagnosed in ∼1.2% of all OHCA survivors presenting with a shockable rhythm. A systematic re-evaluation shall be carried out in all IVF survivors, because the initial diagnosis can change in up to 27% of cases. Patients with IVF and normal ECG have a good prognosis during the long-term follow-up, which is a very important and possibly reassuring finding for the patient and his/her family. Larger and longer studies are needed to confirm our results.

Funding

The study was supported by a grant of the Swiss Heart Foundation “Incidence and prognosis of idiopathic ventricular fibrillation in Canton Ticino”.

Conflict of interest: A.A. Sorin Group, Medtronic, Biotronik, Resmed, DC Devices, EBR Systems, Biosense Webster, Biologics Delivery Systems Group, Brystol-Myers Squibb, Leadxx; F.R. Medtronic, Bayer, Daiichi Sankyo, Sorin Group.

References