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Zorzi, Alessandro (2017) Non-ischemic left ventricular scar: an emerging cause of ventricular arrhythmias and sudden death in the young and athlete. [Ph.D. thesis]

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Abstract (english)

BACKGROUND: The clinical relevance of isolated non-ischemic left-ventricular (LV) scar as a cause of ventricular arrhythmias and sudden death in the young and athlete remains to be established. Contrast-enhanced cardiac magnetic resonance (CE-CMR) is increasingly used in the clinical work-up of athletes with apparently idiopathic ventricular arrhythmias (VA) and can reveal LV scar in the form of late gadolinium enhancement (LGE).
AIMS: we aimed to: 1) evaluate the incidence and causes (with particular reference to non-ischemic LV scar) of out-of-hospital cardiac arrest (OHCA) in people 1-40 year-old in the Padua province in the modern era; 2) assess the clinical profile and outcome of athletes referred to our Institution for non-ischemic LV scar as suggested by LGE at CE-CMR, which was performed for evaluation of apparently idiopathic VA and/or ECG abnormalities; 3) evaluate whether a strategy consisting of 24-hours 12-leads ambulatory ECG monitoring as first-line investigation and CE-CMR as second line investigation may improve our ability to identify concealed LV scar in apparently healthy athletes.
METHODS: we performed three different studies: 1) we recorded all cases of OHCA which occurred during the period 2011-2015. The study population included all residents in the province of Padua 1-40 year-old who suffered OHCA, either resuscitated or not, of presumed cardiovascular origin. The cause of OHCA was ascertained clinically in survivors and at postmortem investigation in victims of sudden death; 2) we compared the clinical profile and outcome of 35 athletes with VA and isolated non-ischemic (subepicardial/midmyocardial) LGE on CE-CMR suggesting myocardial scar with 38 athletes with VA and no LGE and 40 healthy control athletes; 3) we offered a 12-leads 24-hours ambulatory ECG monitoring to apparently healthy athletes ≥16 year-old, who performed at least 6 hours of physical exercise per week and who have been considered eligible at preparticipation screening within 1 year. Athletes were selected to undergo CE-CMR if they showed >29 premature ventricular beats (PVBs) of “uncommon morphology” (i.e. excluding those with a morphology suggestive of right ventricular outflow tract or fascicular origin) or repetitive VA (excluding isolated couplets with a morphology suggestive of right ventricular outflow tract origin).
RESULTS: the main results for each study were: 1) the incidence of OHCA in the Padua province was 3.5/100.000 residents/year and was significantly lower among screened athletes than among non-athletes (1.1/100.000/year vs. 3.9/100.000/year, p<0,001). A final diagnosis was reached in 40 (83%) subjects while in 8 (17%) victims of sudden death the autopsy was not performed. The most frequent diagnosis were coronary artery atherosclerosis (23%) and structurally normal heart (23%) while cardiomyopathies accounted for 10% of cases. The most frequent cardiomyopathy (3 of 7 cases) was the non-ischemic LV scar; 2) a “stria” LGE pattern with subepicardial/midmyocardial distribution, mostly involving the lateral LV wall, was found in 27 (77%) of athletes with VA versus 0 controls (p<0.001). All athletes with “stria” LGE pattern showed VA with a predominant right-bundle-branch-block morphology (suggesting LV origin) but only 5/27 (19%) showed hypokinesis of the lateral LV wall at echocardiography. During a follow-up of 38±25 months, 6/27 (22%) athletes with a “stria” LGE pattern experienced major arrhythmic events (including 1 sudden death) compared with none of athletes with no or LGE-“spotty” pattern; 3) PVBs were rare in apparently healthy athletes (median 1/day) and their number and complexity significantly correlated with age. The prevalence of frequent or repetitive PVBs with “uncommon” morphology was 28/384 (7.3%) apparently healthy athletes. In this group, 3/28 (11%) showed non-ischemic LV scar at CE-CMR.
CONCLUSIONS: the non-ischemic LV scar with a “stria” pattern may be associated with life-threatening VA and sudden death in the young athlete and cannot be simply dismissed as a sign of a previous healed myocarditis. Because of its subepicardial/midmyocardial location, the LV scar is often undetectable by echocardiography, and athletes with PVBs with right-bundle-branch-block morphology, particularly if exercise-induced or associated with ECG abnormalities, should undergo CE-CMR to exclude an underlying pathological myocardial substrate.

Abstract (italian)

INTRODUZIONE: la rilevanza clinica della cicatrice miocardica non-ischemica del ventricolo sinistro (VS) come causa di aritmie ventricolari e morte improvvisa nel giovane della atleta rimane da stabilire. La risonanza magnetica cardiaca con mezzo di contrasto (CE-CMR) è sempre più utilizzata nella valutazione diagnostica dei pazienti con aritmie ventricolari (AV) apparentemente idiopatiche e può rilevare deposito miocardico di gadolinio (late enhancement) suggestivo di cicatrice miocardica.
SCOPO: lo scopo è stato di 1) valutare l'incidenza e le cause (con particolare riguardo alla cicatrice non-ischemica del VS) di arresto cardiaco (AC) extraospedaliero in persone di età 1-40 anni nella provincia di Padova; 2) valutare il profilo clinico e la prognosi di atleti riferiti al nostro Centro per cicatrice non-ischemica alla CE-CMR, che era stata prescritta per la valutazione di AV apparentemente idiopatiche e/o anomalie all'elettrocardiogramma; 3) valutare se una strategia che consiste nell'esecuzione di una registrazione ECG-Holter 24 ore a 12 derivazione come indagine di prima linea e di una CE-CMR come indagine di seconda linea sia in grado di migliorare la nostra abilità di identificare cicatrici del VS occulte in atleti apparentemente sani.
METODI: sono stati eseguiti tre differenti studi: 1) sono stati raccolti tutti i casi di AC extraospedaliero nel periodo storico 2011-2015. La popolazione dello studio ha incluso tutti i residenti della provincia di Padova di età 1-40 anni che hanno avuto un AC, sia resuscitato sia no, di presunta origine cardiovascolare. La causa dell'evento è stata indagata clinicamente nei sopravvissuti e mediante autopsia nei deceduti; 2) abbiamo confrontato il profilo clinico e la prognosi di 35 atleti con AV e cicatrice non-ischemica (subepicardica/mediomurale) del VS alla CE-CMR con 38 atleti con AV ma non cicatrice e 40 controlli sani; 3) abbiamo offerto un holter ECG delle 24 ore a 12 derivazioni ad atleti apparentemente sani di età maggiore o uguale a 16 anni che svolgono almeno 6 ore di attività fisica alla settimana e che sono stati considerati idonei alla visita medico-sportiva nell'ultimo anno. Gli atleti sono stati selezionati per la CE-CMR se mostravano >29 extrasisitoli ventricolari (EV) di morfologia non comune (cioè escludendo quelle con morfologia suggestiva di origine dal tratto di efflusso del ventricolo destro o fascicolare) or AV ripetitive (escludendo coppie isolate con morfologia suggestiva di origine dal tratto di efflusso.
RISULTATI: i risultati principali per ciascuno studio sono stati: 1) l'incidenza di AC extraospedaliero nella provincia di Padova è stato di 3,5/100.000 residenti/anno ed è risultata significativamente inferiore negli atleti rispetto ai non atleti (1,1/100.000/anno vs. 3.9/100.000/anno, p<0,001). Una diagnosi definitiva è stata raggiunta in 40 (83%) persone, mentre in 8 (17%) vittime di morte improvvisa l'autopsia non è stata eseguita. La più frequente diagnosi è stata la coronaropatia aterosclerotica (23%) ed il cuore strutturalmente normale (23%), mentre le cardiomiopatie rendevano conto del 10% dei casi. La più frequente cardiomiopatia (3 casi su 7) è risultata la cicatrice del VS non-ischemica; 2) una stria di late-enhancement a distribuzione subepicardica/mediomurale, coinvolgente soprattutto la parete laterale del VS, è stata riscontrata in 27 (77%) atleti con AV contro 0 controlli (p<0,001). Tutti gli atleti con una "stria" di late-enhancement aveva AV con una morfologia predominante tipo "blocco di branca destra" (suggestiva di origine dal VS) ma solo 5/27 (19%) dimostravano ipocinesia della parete laterale del VS all'ecocardiogramma. Durante un follow-up di 38+/-25 mesi, 6/27 (22%) atleti con "stria" di late enhancement hanno avuto eventi aritmici maggiori (inclusa 1 morte improvvisa) contro nessun atleta senza late enhancement o con late enhancement giunzionale; 3) le EV sono risultate rare in atleti apparentemente sani (mediana 1/giorno) ed il loro numero e complessità correlava significativamente con l'età. La prevalenza di EV frequenti o ripetitive con morfologia non comune tra atleti apparentemente sani è stata di 28/384 (7,3%). In questo gruppo, 3/28 (11%) mostravano una cicatrice del VS alla CE-CMR.
CONCLUSIONI: la cicatrice "non ischemica" del VS con un pattern a stria può essere associata con AV minacciose e morte improvvisa nel giovane atleta e non può essere semplicemente considerata come un segno di una pregressa miocardite. A causa della sua distribuzione subepicardica/mediomurale, la cicatrice del VS è spesso impossibile da diagnosticare con l'ecocardiogramma, e gli atleti con EV con morfologia tipo blocco di branca destra, particolarmente se indotte dall'esercizio o associate a anomalie dell'ECG, dovrebbero essere sottoposti a CE-CMR per escludere un sottostante substrato patologico.

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EPrint type:Ph.D. thesis
Tutor:Corrado, Domenico
Ph.D. course:Ciclo 29 > Corsi 29 > SCIENZE MEDICHE, CLINICHE E SPERIMENTALI
Data di deposito della tesi:30 January 2017
Anno di Pubblicazione:30 January 2017
Key Words:Athletes, arrhythmias, cardiac magnetic resonance, electrocardiogram, preparticipation screening, sports cardiology, sudden cardiac death
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/11 Malattie dell'apparato cardiovascolare
Struttura di riferimento:Dipartimenti > Dipartimento di Scienze Cardiologiche, Toraciche e Vascolari
Codice ID:10137
Depositato il:02 Nov 2017 17:13
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