Italian registry of cardiac magnetic resonance

European Journal of Radiology 83 (2014) e15–e22

Contents lists available at ScienceDirect

European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad

Italian registry of cardiac magnetic resonance Marco Francone a,1 , Ernesto Di Cesare b,∗,1 , Filippo Cademartiri c,d , Gianluca Pontone e , Luigi Lovato f , Gildo Matta g , Francesco Secchi h , Erica Maffei c,d , Silvia Pradella i , Iacopo Carbone a , Riccardo Marano j , Lorenzo Bacigalupo k , Elisabetta Chiodi l , Rocco Donato m , Stefano Sbarbati n , Francesco De Cobelli o , Paolo di Renzi p , and CMR Italian Registry Group, Guido Ligabue q , Andrea Mancini q , Francesco Palmieri r , Gennaro Restaino s , Giovanni Puppini t , Maurizio Centonze u , Wiliam Toscano v , Carlo Tessa w , Riccardo Faletti x , Massimo Conti y , Arnaldo Scardapane z , Salvatore Galea aa , Carlo Liguori ab , Marzio Pagliacci ac , Domenico Lumia ad , Marco di Girolamo ae , Andrea Romagnoli af , Alessandro Guarise ag , Stefano Cirillo ah , Biagio Gagliardi ai , Claudia Borghi aj , Matteo Quarenghi ak , Franco Contin al , Fiorenzo Scaranello am , Armando Tartaro an , Carlo Marinucci ao , Lorenzo Monti ap a

Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Italy Dipartimento di Scienze Cliniche Applicate e Biotecnologie, Università di L’Aquila, Italy Cardio-Vascular Imaging Unit, Giovanni XXIII Hospital, Monastier di Treviso, TV, Italy d Erasmus Medical Center University, Rotterdam, The Netherlands e IRCCS Centro Cardiologico Monzino, Italy f Policlinico S. Orsola Bologna, Italy g Azienda ospedaliera G Brotzu Cagliari, Italy h IRCCS Policlinico San Donato, Radiology Unit, Milan, Italy i Azienda Ospedaliera Universitaria Careggi, Italy j Policlinico Gemelli, Università Cattolica Roma, Italy k Ospedale Galliera, Genova, Italy l Ospedale S. Anna Ferrara, Italy m Azienda Ospedaliera Universitaria G. Martino, Me, Italy n Ospedale Madre Giuseppina Vannini, Roma, Italy o IRCCS S. Raffaele, Università Vita Salute, Milano, Italy p Fate Bene Fratelli Isola tiberina, Roma, Italy q Azienda Ospedaliera-Universitaria Policlinico di Modena, Italy r Diparimento di Diagnostica per immagini e radiologia interventistica, Ospedale S. Maria delle Grazie, Pozzuoli, Napoli, Italy s Università Cattolica Campobasso, Italy t UOC Radiologia, Polo Chirurgico Confortini, Azienda Ospedaliera Universitaria IntegrataVerona, Italy u Radiologia OC S. Chiara Trento, Italy v UOC di Radiologia OspCattinara Trieste, Italy w Ospedale Verilia Ca Maiore Lucca, Italy x Radiologia università Torino, Italy y Cardiologia-Radiologia Guastalla AUSL Reggio Emilia, Italy z UOC di Radiodiagnostica Universitaria Bari, Italy aa Ospedale Lamezia Terme. ASP Catanzaro, Italy ab Area di Diagnostica per Immagini, Università Campus Biomedico Roma, Italy ac Ospedale Infermi Rimini, Italy ad Ospedaledi Circolo Fondazione Macchi-Università degli Studi dell’InsubriaVarese, Italy ae Università “Sapienza” Radiologia A.O. Sant’ Andrea Roma, Italy b

c

Abbreviations: CAD, coronary artery disease; CMP, cardiomyopathy; CMR, cardiac magnetic resonance; SIRM, Italian Society of Medical Radiology. ∗ Corresponding author at: Università di L’Aquila, Via Vetoio 1, 67100 L’Aquila, Italy. Tel.: +39 0862 368306; fax: +39 0862 369797. E-mail address: [email protected] (E. Di Cesare). 1 These authors contributed equally to this work. 0720-048X/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejrad.2013.10.006

e16

M. Francone et al. / European Journal of Radiology 83 (2014) e15–e22

af

Policlinico Universitario Tor Vergata Roma, Italy Bassano Del Grappa Vicenza, Italy ah Ospedale Mauriziano Umberto I Torino, Italy ai Azienda ospedaliera G Moscati Avellino, Italy aj Radiologia Ospedale Valduce, Como, Italy ak Policlinico, Monza, Italy al Alto Vicentino Thiene Schio, Italy am Ospedale S. Maria della Misericordia Rovigo, Italy an Istituto Tecnologie Avanzate Biomediche Università Chieti -Pescara, Italy ao Ospedale Mazzoni Ascoli Piceno, Italy ap IRCCS Istituto Clinico Humanitas, Rozzano Milano, Italy ag

a r t i c l e

i n f o

Article history: Received 25 March 2013 Received in revised form 11 September 2013 Accepted 9 October 2013 Keywords: CMR-registry Clinical indications Safety profile Acquisition protocols Patient’s management

a b s t r a c t Objectives: Forty sites were involved in this multicenter and multivendor registry, which sought to evaluate indications, spectrum of protocols, impact on clinical decision making and safety profile of cardiac magnetic resonance (CMR). Materials and methods: Data were prospectively collected on a 6-month period and included 3376 patients (47.2 ± 19 years; range 1–92 years). Recruited centers were asked to complete a preliminary general report followed by a single form/patient. Referral physicians were not required to exhibit any specific certificate of competency in CMR imaging. Results: Exams were performed with 1.5 T scanners in 96% of cases followed by 3 T (3%) and 1 T (1%) magnets and contrast was administered in 84% of cases. The majority of cases were performed for the workup of inflammatory heart disease/cardiomyopathies representing overall 55.7% of exams followed by the assessment of myocardial viability and acute infarction (respectively 6.9% and 5.9% of patients). In 49% of cases the final diagnosis provided was considered relevant and with impact on patient’s clinical/therapeutic management. Safety evaluation revealed 30 (0.88%) clinical events, most of which due to patient’s preexisting conditions. Radiological reporting was recorded in 73% of exams. Conclusions: CMR is performed in a large number of centers in Italy with relevant impact on clinical decision making and high safety profile. © 2013 Elsevier Ireland Ltd. All rights reserved.

1. Introduction

2. Materials and methods

CMR has evolved in recent years from an effective research tool into a clinically proven, safe and comprehensive imaging modality, with established guidelines and appropriateness criteria covering a wide spectrum of clinical indications and an increasing number of centers organizing fully dedicated scanning sessions being carried out either by radiologists and/or cardiologists [1,2]. Most information about its use and diagnostic performances however, is currently derived from very few large clinical trials or from selected populations enrolled in highly specialized centers with relatively limited knowledge of its day-to-day utilization. The only available register is the EuroCMR, which was recently completed with 27,000 patients and was promoted and organized by the European Society of Cardiology Working Group of “Cardiovascular Magnetic Resonance”, with obvious predominant involvement of CMR-dedicated cardiological centers [3–5] EuroCMR results convincingly showed that the exam has evolved from the status of “a niche modality” [6] with limited number of cases performed by few tertiary/academic referral into a routine imaging modality, homogeneously diffused and representing an extremely valuable diagnostic support to solve common clinical problems [3,4]. The Italian registry of CMR is an open-access study (no restriction criteria or proof of specific competence were required to participating centers) which was set up to provide a national overview of its utilization, offering a more “radiological” point of view of its current clinical role in daily practice, and was promoted by the sub-society of cardiac radiology of SIRM (Società Italiana di Radiologia Medica), which has currently almost 700 members (www.sirm.org/sottositi/cardio). Forty different centers were involved in this multicenter and multivendor registry, which sought to evaluate clinical indications, spectrum of acquisition protocols, impact on clinical decisionmaking and safety profile of CMR.

2.1. Data collection The data were prospectively collected during a 6-month period (January–June 2011) and included a population of 3376 consecutive patients who underwent CMR in one of the 40 participating sites. Centers were initially recruited via email from the mailing list of the SIRM members (approximately 8000 members) and each site, after acceptance, appointed a referral physician (radiologist or cardiologist) who was locally responsible for the data integrity, interpretation and collection and represented the direct contact for the steering committee of the study. Referral physicians were not required to exhibit any specific sub-specialty based certificate of competency in CMR imaging as the aim of present registry was to provide a realistic “snapshot” of CMR utilization in Italy, without limiting patient’s enrollment only to most-experienced national groups. Similarly, acquisition protocols were individually defined and tailored by each center according to the main clinical request, without following any established, predefined standardized protocol. 2.2. Patients form A preliminary general report and a case-report form (CRF) were completed in each center. In each electronic form, the following sections had to the filled: (1) Patient’s data, including demographics, patient’s source (outpatient, day hospital or hospitalized) and clinical priority (defined as urgent vs. elective exam). (2) Clinical indications to the exam, which were listed and readapted following the ACCF/ACR/SCCT/SCMR/ASNC/NASCI/ SCAI/SIR appropriateness criteria for cardiac computed tomography and cardiac magnetic resonance imaging published

M. Francone et al. / European Journal of Radiology 83 (2014) e15–e22

(3)

(4)

(5)

(6) (7)

(8)

in 2006 and using the same organization proposed in the EuroCMR study, in order to obtain reproducible and comparable data [7]. Acquisition data concerning model and field strength of the scanner adopted, type and dose of contrast agents adopted and presence/absence (and type of drug) of pharmacological stress. Adverse events occurring during or immediately after the examination, attributable to contrast agent administration and/or pharmacological stress and/or patient’s basal condition. Complications caused by acute adverse reactions to contrast media (i.e. within 60 min after administration) were defined according to the American College of Radiology criteria [8]. Incidents were scored as mild, moderate or severe using the following predefined criteria readapted from Dorfman et al. [9]: (a) Mild: Transient change in condition, not life threatening and rapidly returning to baseline, required monitoring and/or minor intervention such as holding a medication, obtaining lab test(s), application of heat or cold. (b) Moderate: Transient change in condition, may be life threatening if not treated, returning to baseline if properly treated and required monitoring and/or intervention such as reversal agent, additional medication, or transfer to ICU. (c) Severe: Change in condition, life threatening if not treated and potentially permanent, may have required hospitalization or transfer to ICU, required monitoring and/or major intervention such as invasive procedure, intubation, hemodynamic support and blood transfusion. In case of death, patients were excluded from the registry, recording cause of the exitus. Image quality of the exam was also evaluated on a 5-point scale from excellent to inadequate as follows: (1) insufficient: defined as “major artifacts exist leading to nondiagnostic images”; (2) ‘poor’ defined as “major artifacts present limiting clinical use of images”; (3) ‘fair’ defined as “borderline clinical use due to adequate image quality”; (4) ‘good’ defined as “only minor artifacts present with no/minimal impact on clinical use”; (5) ‘excellent’ defined as “no artifacts”. Result of the exam according to the main clinical request (i.e. positive, negative or non-diagnostic/inconclusive). Clinical impact on patient’s management (meaning therapeutic impact or requiring further management) which was assessed by the local referral physician in consensus with patient’s referring physician and classified as follows: (a) Non diagnostic or inconclusive exam. (b) Relevant but without impact on patient’s management. (c) Relevant with impact on patient’s management, consisting in changes in the therapeutic (pharmacological or surgical) or diagnostic (further procedures performed) management and/or patient’s discard or hospitalization following the exam. Specialty of the reading and reporting physician.

3. Data extraction All the data were collected via email on a monthly basis by trained personnel and manually stored in an electronic database provided by the University of L’Aquila for evaluation (Microsoft Excel version 2007).

e17

Table 1 Demographic, clinical and acquisition data. Study population (n)

3376 (100%)

Geographic distribution of participating centers and % of patient’s enrolled

- 21 North (46.3%) - 14 Center (36.8%) - 5 South and Islands (16.9%)

Gender

Male: 2254 (67.0%); Female: 1122 (33.0%)

Mean age (years)

47.2 ± 19.3 (1–92)

Body mass index (kg/m2 )

24.8 ± 2.2 (21.6–27.4)

Patient’s source

Outpatients: 2070 (61.0%) Day hospital: 232 (7.0%) Hospitalized: 1050 (31.0%) Non-specified: 23 (1.0%)

Clinical priority

Urgent: 6.5%; elective (91.6%)

Scanner type (patient’s enrolled and %)

1.0 T: 25 (0.7%) 1.5 T: 3257 (96.5%) 3.0 T: 92 (2.8%)

4. Statistical analysis Due to the descriptive nature of present registry, all collected data are expressed in terms of absolute numbers and corresponding percentages using means with standard deviation (SD) when appropriate. This study was approved by local institutional review boards. 5. Results 5.1. Patient’s data Database of present registry includes 3376 patients who were prospectively enrolled during the study period. The average number of patients enrolled per center was 84.4 ± 57.3 SD with a range between 3 and 425. Mean age (SD) was 47.2 ± 19 years, range 1–92 years; 2254 (67.0%) patients were males and 1112 (33.0%) were female. Concerning geographic distribution of patient’s population, there was a clear north-to-south gradient, with the largest proportion of patients (46.3%) enrolled from the north of the country (46.3%) followed by central regions (36.8%) whereas south and islands contributed for 16.9% of overall population. Detailed patients’ data, are reported in Table 1. Clinical priority to the exam was defined urgent in 6.5% of patients and elective in 91.6% of cases whereas no information was available in the remaining 1.8%. Urgent exams were mostly required for the evaluation of acute patients (myocarditis and acute infarct patients in 70% of cases) or following a surgical procedure (21.0%). Most of the examinations (2094 patients; 62.0%) were performed for outpatients, 232 were in a day hospital (7.0%) regimen and 1050 were hospitalized (31.0%). 5.2. Clinical indications to the exam The majority of exams were performed for the workup of inflammatory heart disease/cardiomyopathies representing overall 55.7% of cases followed by the assessment of myocardial viability and acute infarction (respectively 6.9% and 5.9% of patients). Most frequent clinical indications were substantially balanced within the first group and included arrhythmogenic right ventricular cardiomyopathy (AVRC; 11.2%) iron overload quantification (9.9%), acute myocarditis (9.8%), hypertrophic and dilated CMPs (9.2% and 8.7% respectively). Detailed results are reported in Table 2.

e18

M. Francone et al. / European Journal of Radiology 83 (2014) e15–e22

Table 2 Clinical indications to CMR with corresponding examination’s results. Clinical indication

Prevalence

ARVC Iron Overload Acute myocarditis HCM DCM Viability AMI Ischemia/stress Non-compaction Myocardial storage disease Cardiac and pericardial masses Tako-tsubo Congenital disease Valvular disease Pericardial disease Pulmonary hypertension Biventricular function

11.2% 9.9% 9.8% 9.2% 8.7% 6.9% 5.9% 3.0% 3.0% 2.2% 1.8% 1.1% 0.6% 0.5% 0.4% 0.4% 0.3%

Negative 72.0% 14.7% 31.1% 21% 16.0% 17.7% 14.0% 47.0% 45.7% 42.0% 20.3% 17.0% 6.0% 3.0% 19.0% 9.0% 37.5%

Positive

Non-diagnostic

Non specified

23.1% 84.3% 67.1% 75.4% 78.0% 78.9% 84.2% 49.0% 51.0% 56.0% 76.7% 73.0% 93.0% 96.0% 80.0% 90.0% 62.5%

2.6% 0.7% 0.9% 2.0% 3.0% 0.7% 0.9% – 1.1% 0.4% 2.0% 2.0% 1.0% 1.0% 1.0% 1.0% –

2.3% 0.3% 0.9% 1.6% 3.0% 2.7% 0.9% 4.0% 2.2% 1.6% 1.0% 8.0%

–

ARVC, arrhythmogenic right ventricular cardiomyopathy; HCM, hypertrophic cardiomyopathy; DCM, dilated cardiomyopathy; AMI, acute myocardial infarction.

5.3. Acquisition data Most of investigations were performed with 1.5 T scanners (96.5%), followed by 3 T (2.7%) and 1 T systems (0.8%) (Table 2) and contrast agent was administered in 84.8% of the exams. A pharmacologic stress test, using dipyridamole, adenosine or dobutamine, was conducted on 87 cases (3.0%) (Table 3). Stress imaging mostly consisted in rest/stress perfusion studies with adenosine or dipyridamole (overall 93.0% of exams) whereas dobutamine administration was used in only 7.0% of cases. List and average amount of contrast agents administered in both rest and stress CMR examinations coupled with pharmacologic stress protocols adopted are reported in Table 3. Acquisition time ranged between 3 and 150 min with an average scanning duration of 43 ± 13 min per exam; differences in average examination time significantly varied between non-contrast vs. rest vs. stress exams ranging between 35, 44 and 54 min respectively (detailed data are reported in Table 4) 5.4. Safety evaluation Safety assessment revealed 30 (0.9%) adverse clinical events occurred during or immediately after the procedure (i.e.<60 min), most of which were attributed to patient’s poor clinical conditions prior to the examination (n = 20; 66.6% of the events) (Fig. 1). Among this first group of patients, events were scored as moderate in two cases due to the occurrence of arrhythmia in acute infarct patients, and mild in the remaining eighteen patients mostly

consisting in dyspnea and claustrophobia almost exclusively observed in acute infarct patients (n = 17 plus 1 patient with HCM). Contrast media-related adverse events were reported in only six cases (0.1%), and scored as mild in five (83.0%) and moderate in one patient presenting with vomit, facial swelling and bronchospasm after contrast administration which required short-term observation. In the remaining four cases, adverse effects occurred during dipyridamole stress CMR and two were directly related to the drug administration with angina whereas claustrophobia was referred in the remaining two. No severe reactions or cases of death were reported during or because of the CMR procedure. 5.5. Result of the exam, image quality and impact on patient’s management Image quality was scored from excellent to good in 82% of cases (fair: 7.1%; poor: 6.3%; insufficient: 2.2%) and no information were available in 96 patients (2.0%). In 65.0% of cases, CMR was positive and the final diagnosis obtained was considered clinically relevant in 85.4% of the cases providing significant impact on clinical/therapeutic management in 49.4% of patients. Overall, only 6.0% of the diagnoses had no clinical relevance and approximately 1% of exams were not diagnostic (Fig. 2). The highest prevalence of negative examinations was observed in patients with suspected ARVD (72.0%), followed by those with non-compacted myocardium (45.4%). The highest impact on patient’s management was reported in stress examinations for CAD (68.0% of the cases), followed by the assessment and quantification of iron overload (64.0% of cases), suspected acute myocarditis (60% of cases), and dilated cardiomiopathy (54.0%), whereas in 61.1% and 52.3% of patients with respectively Tako-tsubo CMP and acute myocardial infarction the examination was found to have no impact on clinical and diagnostic workup. 6. Reporting physicians

Fig. 1. Bar chart plotting type and severity of adverse clinical events occurred during or immediately after (i.e.<60 min) CMR examination.

Overall 80.1% of the exams were reported by radiologists alone (12.9% with double specialization in radiology/cardiology) and 17.0% by radiologists and cardiologists in consensus whereas, in our series, cardiologists alone represented 2.6% of reporting physicians.

M. Francone et al. / European Journal of Radiology 83 (2014) e15–e22

e19

Table 3 Contrast administration protocols in rest and stress exams. Gadolinium chelate Gadoteric acid Gadopentetate dimeglumine Gadobenate dimeglumine Gadobutrol Gadodiamide Gadoteridol Gadoversetamide Non-specified

Patients (n) 170 619 776 1257 4 5 11 534

Min. dose (mmol/kg)

Max. dose (mmol/kg)

Average dose (mmol/kg)

Stress

0.1 0.1 0.05 0.05 0.1 0.2 Non spec –

0.2 0.2 0.25 0.3 0.2 0.2 Non spec –

0.18 0.16 0.16 0.22 0.17 0.2 Non spec –

3 35 41 8 0 0 0

Table 4 CMR protocols and acquisition time. CMR Protocol

N

%

Minimal acquisition time

Maximal acquisition time

Average

No stress no Gadolinium No stress + gadolinium Stress + no gadolinium Stress + gadolinium Total

726 2420 7 91 3244

22.0 75.0 .02 0.3 –

3 6 20 25 16

70 150 60 90 94

35 44 43 54 44

7. Discussion This Italian CMR survey was designed to evaluate diffusion and geographic distribution of the various national centers performing the exam, verifying technical equipment, protocols adopted, safety profile and spectra of clinical indications. Besides providing “locally” useful data however, this registry represents a large patient’s database recruited in a relatively short time interval (3376 patients during a six-month period of enrollment) and derived from the experiences of forty different centers, using multivendor equipment and contrast agents and covering variable levels of CMR expertise due to the open-access nature of the study. A further element of evaluation is the predominant radiological involvement of participating sites characterized by 80.1% of exams read and reported by radiologists (including 12.9% of double specialty physicians) plus 17.0% of cases performed in consensus

with cardiologists with relevant differences from the Euro-CMR data in which role of radiologists was limited to only 2.6% of cases with an additional 26.7% of cases read by a combined team of cardiologist and radiologists [3]. This discrepancy can be attributed to a “specialty-oriented” bias in the selection of referring centers related to the different background of groups who initiated and promoted both registries representing respectively the CMR working group of the European Society of Cardiology and the Working Group of the Cardiac Radiology Section of the SIRM. Radiologically “imbalanced” data were also published in 2006 by Levin and coll. who reported a 91% prevalence of exams performed by radiologist in a large Medicare-based patient’s database of 110,743 CMR studies analyzed [1]. An additional general bias of any registry like ours regards the intrinsic impossibility to determine the exact degree of completeness of patient’s enrollment per center with obvious potential and unpredictable impact on prevalence of indications and on results in general.

Fig. 2. Bar chart showing impact of CMR examination on patient’s clinical and therapeutic management for the most frequent indications.

e20

M. Francone et al. / European Journal of Radiology 83 (2014) e15–e22

7.1. Technical equipment and acquisition protocols State of the art of CMR imaging is performed in Italy using 1.5 T magnets in the vast majority of cases (96.5% of exams) whereas use of 3 T scanners was limited in our database to 2.7% of patients. These results are substantially in line with those of the EuroCMR (0.5% of studies performed with 3 T machines) and confirm that both the higher scanners’ costs and technical challenges (field homogeneity reduction with increased susceptibility artifacts and radiofrequency-induced power deposition) associated with high field systems are still perceived as major drawbacks by most centers limiting their diffusion and utilization in the territory only to few research sites regardless significant recent improvements and potential advantages of 3 T imaging in CMR [5,10,11]. Most of the examinations were performed with intravenous administration of contrast agents (84.8%), confirming that CMR is a contrast-dependent technique in most of the cases and its ability in tissue characterization is further enhanced by use of gadolinium and late enhancement techniques allowing to characterize myocardial disease with different late enhancement patterns in a large variety of clinical conditions [12–15]. Pharmacological stress was performed in only 3.0% of our patients’ population as compared to the Euro-CMR registry in which perfusion and/or functional stress protocols were used in 34.2% of cases to rule out myocardial ischemia and viability [5]. Stress imaging mostly consisted in rest/stress perfusion studies with adenosine or dipyridamole (overall 93.0% of exams) whereas dobutamine administration was used for the assessment of inducible ischemia in only 7.0% of cases likely as a consequence of the lower safety profile of the drug at higher doses, with major events reported in 3–21% of patients and requiring resuscitation MR-compatible equipment and medications managed by dedicated medical staff [16]. The low prevalence of stress exams in our patient’s population highlights an important feature of present registry, which mainly reports activity, performed in radiological units as compared to the prominent clinical/cardiological background of the EuroCMR. This observation accounts the different attitude of cardiologists toward use of stress imaging for the evaluation of CAD and a probably deeper clinical comprehension of the added value of MR in this clinical setting as compared to echocardiography or SPECT [17]. An additional issue to consider in this regard, concerns the extremely variable experience of the centers involved which might have oriented a different pathology focus in less specialized sites in favor of more manageable and easily approachable indications (see Section 7.2). The direction to follow is also likely to further educate referral physicians regarding CMR added clinical value in the clinical setting of myocardial ischemia. 7.2. Clinical indications and impact on patient’s management The majority of exams were performed for the evaluation of inflammatory heart disease/cardiomyopathies, representing overall 55.7% of cases as compared to the respectively 6.9% and 5.9% of patients addressed for myocardial viability assessment and acute myocardial infarction (Table 2). These indications again show a remarkable difference from the recently updated results of the Euro-CMR registry, in which ischemia and suspected CAD surpassed myocarditis/cardiomyopathies (respectively 34.2% vs. 32.2%) with an additional 14.6% of patients examined for myocardial viability assessment [5]. Rather than a single predominant clinical request, there were five substantially balanced most frequent indications in our series, ranging between 11.2% and 8.7% of cases and represented (in order) by ARVC, iron overload quantification, acute myocarditis, hypertrophic and dilated CMPs.

Aortic disease was not included in the list of our exams as we meant to specifically focus on cardiac pathology referring to great vessels only in presence of predominant myocardial involvement (like in congenital heart disease and pulmonary hypertension). Interestingly, list of indications reported in Table 2 accounts for only 74.9% of all the exams recorded in our registry and highlights that there was a significant 25.1% of studies which were classified as “others indications” or “non-specified clinical request”. The reason for this result might be either attributable to the lack of clinical information at the moment of CMR examination or more likely simply reflects a high rate of incomplete filling of patient’s electronic forms by referring centers. ARVC was the first indication of our registry (11.2% of exams), which is partially explainable with the relatively high prevalence of this disease in the Italian territory [18,19] and most likely depends on the unique diagnostic contribution offered by CMR in this cardiomyopathy allowing to identify the various morphological and functional hallmarks of the disease [20–22]. Despite the low incidence of disease, we had an unexpected prevalence of 23.0% positive cases in our patient’s population representing an unlikely false positive rate likely attributable to the trend to over-reading and over-diagnose ARVD in less experienced operators which was previously described by Sen-Chowdhry et al. [23]; this trend may be caused by the difficulty in recognizing and discriminating normal vs. abnormal morphological and functional findings within the thin-walled, trabeculated, complex anatomy of the right ventricle. Second CMR indication of our database (9.9%) was the evaluation of patients with primary or secondary forms of myocardial siderosis in which use of multiecho gradient echo T2* sequences allows to diagnose and quantify myocardial iron overload in a preclinical stage and to monitor effects of chelation therapy offering important insights for understanding the pathophysiology of iron accumulation and the complex dynamics of its pharmacological clearance [24,25]. The high prevalence of this request in our patient’s cohort also probably depends on the epidemiology of ␤-thalassemia in Italy, which is endemic in specific areas of the country including major islands (Sicily and Sardinia), the lower Po valley and the regions of Lazio, Puglia and Calabria [26]. Impact of the exam in this clinical setting was regarded among the highest of our patient’s cohort (only following the relatively limited number of stress-exams performed) with a significant influence on patient’s management in 64.0% of the cases which indirectly confirms the importance to routinely (at least on an annual base) evaluate cardiac T2* of all chronically transfused patients [27]. A further common and high-impact indication was the evaluation of patients with suspected acute myocarditis (9.8% of exams), in which CMR addressed a different therapeutic/diagnostic/clinical management in 60% of cases in recognition of the high sensitivity of the exam to detect signs of active inflammation represented by edema, capillary leakage and fibrosis/necrosis [16]. Diagnostic workup of dilated and hypertrophic CMPs was also frequently required in our series (respectively 9.2% and 8.7%) with an important contribution acknowledged to the exam (relevant and with impact on management in respectively 54% and 41% of cases) reflecting its role in the differential diagnosis between the various types of dilated and hypertrophic phenotypes of disease and its important prognostic implications [28–30].

7.3. Safety profile Our patient’s cohort data confirm the high safety profile of CMR examination with overall only 30 (0.9%) adverse mild or moderate clinical events recorded during or immediately after the procedure without occurrence of severe reactions/death.

M. Francone et al. / European Journal of Radiology 83 (2014) e15–e22

Most of the events were observed in patients with acute myocardial infarction (17 cases) and were related to patient’s baseline clinical conditions with onset of arrhythmias and/or dyspnea during CMR requiring to end the examination. Contrast media related adverse effects were reported in only 0.18% (n = 6) of administrations mostly consisting in mild reactions (n = 5) with only one patient presenting a moderate anaphylactoid reaction requiring short-term monitoring before discharge. Our results are completely in line with the recently published data extracted from the Euro-CMR study in which 30 acute adverse reactions (0.17%) occurred in a large cohort of 17,767 doses administered [31]. Similar findings were reported in larger studies analyzing the incidence of gadolinium-related contrast media reactions reporting event rates ranging between 0.04 and 2.2% [32–34]. We could not analyze differences in reaction rates between the various gadolinium-based contrast molecules due to the limited number of events observed in our population although a lower adverse reactions incidence for nonionic gadolinium-based contrast agents has been reported in literature as compared to ionic linear or macrocyclic agents [32]. Our study design did also not include patient’s follow-up after contrast administration, thus excluding the possibility to identify late contrast-related adverse reactions such as nephrogenic systemic fibrosis (NSF), which has been however virtually eliminated by preventive measures including screening for the presence of renal dysfunction in all patients requiring gadolinium-enhanced MR evaluation. Adverse events related to pharmacological-stress were reported in four cases and attributed to drug’s collateral effects only in two patients undergoing dypiridamole stress myocardial perfusion and scored as mild (angor in both cases). The limited number of stress exams performed in our registry limits any safety profile evaluation although both perfusion and functional stress CMR have been reported to be safe, accurate and with minimal side effects in several studies and literature metanalysis [16,35].

8. Conclusions Our registry has shown a wide diffusion of cardiac MR-dedicated centers in Italy which are mostly conduicted by radiologist. Relevant differences have emerged in terms of clinical indications between the SIRM and Euro-CMR databases as a result of the different clinical and cultural backgrounds of the groups and sites involved, but also reflecting different diseases epidemiology, with a prevalence of exams addressed for iron-overload assessment and suspected ARVD and a limited number of stress-studies performed in our patient’s cohort. In most cases, diagnostic contribution provided by the examination was regarded as signficant and with impact on clinical management. The limited incidence and low severity of adverse clinical events observed in our registry confirms that CMR is a safe examination with a low rate of acute contrast-related adverse reactions which was similar in our patient’s database to literature data. Further research focus of CMR registries would probably require systematic clinical follow-up of patient’s enrolled in order to analyze mid- and long-term implications of CMR findings providing wider comprehension of its clinical role in the complex scenario of cardiovascular diseases.

References [1] Levin DC, Rao VM, Frangos AJ, Parker L, Sunshine JH. The controversy over advanced cardiovascular imaging: relative roles of radiologists, cardiologists, and other physicians in CT and MRI of the cardiovascular system. Journal of the American College of Radiology: JACR 2006;3(1):16–8.

e21

[2] Di Cesare E, Cademartiri F, Carbone I, et al. Clinical indications for the use of cardiac MRI. By the SIRM study group on cardiac imaging. Radiol Med 2013;118(5):752–98. [3] Bruder O, Schneider S, Nothnagel D, et al. EuroCMR (European cardiovascular magnetic resonance) registry: results of the German pilot phase. Journal of the American College of Cardiology 2009;54(15):1457–66. [4] Bruder O, Wagner A, Mahrholdt H. Lessons learned from the European cardiovascular magnetic resonance (EuroCMR) registry pilot phase. Current Cardiovascular Imaging Reports 2010;3(3):171–4. [5] Bruder O, Wagner A, Lombardi M, et al. European cardiovascular magnetic resonance (EuroCMR) registry – multi national results from 57 centers in 15 countries. Journal of Cardiovascular Magnetic Resonance: Official Journal of the Society for Cardiovascular Magnetic Resonance 2013;15:9. [6] Thomas B, Tavares NJ. Do the results of the German pilot phase of the EuroCMR Registry indicate that the chasm has been crossed? Journal of the American College of Cardiology 2010;55(4):412. [7] Hendel RC, Patel MR, Kramer CM, et al. ACCF/ACR/SCCT/SCMR/ASNC/NASCI/ SCAI/SIR 2006 appropriateness criteria for cardiac computed tomography and cardiac magnetic resonance imaging: a report of the American College of Cardiology Foundation Quality Strategic Directions Committee Appropriateness Criteria Working Group, American College of Radiology, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, American Society of Nuclear Cardiology, North American Society for Cardiac Imaging, Society for Cardiovascular Angiography and Interventions, and Society of Interventional Radiology. Journal of the American College of Cardiology 2006;48(7):1475–97. [8] American College of Radiology. Manual on contrast media: version 9 —2013 [book online]. Reston, VA: American College of Radiology. 2013. http://www.acr.org/∼/media/ACR/Documents/PDF/QualitySafety/Resources/ Contrast%20Manual/13 Contrast Media.pdf [9] Dorfman AL, Odegard KC, Powell AJ, Laussen PC, Geva T. Risk factors for adverse events during cardiovascular magnetic resonance in congenital heart disease. Journal of Cardiovascular Magnetic Resonance: Official Journal of the Society for Cardiovascular Magnetic Resonance 2007;9(5):793–8. [10] Oshinski JN, Delfino JG, Sharma P, Gharib AM, Pettigrew RI. Cardiovascular magnetic resonance at 3.0 T: current state of the art. Journal of Cardiovascular Magnetic Resonance: Official Journal of the Society for Cardiovascular Magnetic Resonance 2010;12:55. [11] Hays AG, Schar M, Kelle S. Clinical applications for cardiovascular magnetic resonance imaging at 3 tesla. Current Cardiology Reviews 2009;5(3):237–42. [12] Vermes E, Carbone I, Friedrich MG, Merchant N. Patterns of myocardial late enhancement: typical and atypical features. Archives of Cardiovascular Diseases 2012;105(5):300–8. [13] Hunold P, Schlosser T, Vogt FM, et al. Myocardial late enhancement in contrastenhanced cardiac MRI: distinction between infarction scar and non-infarctionrelated disease. American Journal of Roentgenology 2005;184(5):1420–6. [14] Ordovas KG, Higgins CB. Delayed contrast enhancement on MR images of myocardium: past, present, future. Radiology 2011;261(2):358–74. [15] Masci PG, Francone M, Desmet W, et al. Right ventricular ischemic injury in patients with acute ST-segment elevation myocardial infarction: characterization with cardiovascular magnetic resonance. Circulation 2010;122(14):1405–12. [16] American College of Cardiology Foundation Task Force on Expert Consensus D, Hundley WG, Bluemke DA, et al. ACCF/ACR/AHA/NASCI/SCMR 2010 expert consensus document on cardiovascular magnetic resonance: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. J Am Coll Cardiol 2010;55(23):2614-62. [17] Schwitter J, Wacker CM, van Rossum AC, et al. MR-IMPACT: comparison of perfusion-cardiac magnetic resonance with single-photon emission computed tomography for the detection of coronary artery disease in a multicentre, multivendor, randomized trial. European Heart Journal 2008;29(4):480–9. [18] Nava A, Thiene G, Canciani B, et al. Familial occurrence of right ventricular dysplasia: a study involving nine families. Journal of the American College of Cardiology 1988;12(5):1222–8. [19] Thiene G, Corrado D, Basso C. Arrhythmogenic right ventricular cardiomyopathy/dysplasia. Orphanet Journal of Rare Diseases 2007;2:45. [20] Jain A, Tandri H, Calkins H, Bluemke DA. Role of cardiovascular magnetic resonance imaging in arrhythmogenic right ventricular dysplasia. Journal of Cardiovascular Magnetic Resonance: Official Journal of the Society for Cardiovascular Magnetic Resonance 2008;10:32. [21] Castillo E, Tandri H, Rodriguez ER, et al. Arrhythmogenic right ventricular dysplasia: ex vivo and in vivo fat detection with black-blood MR imaging. Radiology 2004;232(1):38–48. [22] Marcus FI, McKenna WJ, Sherrill D, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. European Heart Journal 2010;31(7):806–14. [23] Sen-Chowdhry S, Prasad SK, Syrris P, et al. Cardiovascular magnetic resonance in arrhythmogenic right ventricular cardiomyopathy revisited: comparison with task force criteria and genotype. Journal of the American College of Cardiology 2006;48(10):2132–40. [24] Anderson LJ, Holden S, Davis B, et al. Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. European Heart Journal 2001;22(23):2171–9. [25] Ooi GC, Khong PL, Chan GC, et al. Magnetic resonance screening of iron status in transfusion-dependent beta-thalassaemia patients. British Journal of Haematology 2004;124(3):385–90.

e22

M. Francone et al. / European Journal of Radiology 83 (2014) e15–e22

[26] Silvestroni E, Bianco I. Screening for microcytemia in Italy: analysis of data collected in the past 30 years. American Journal of Human Genetics 1975;27(2):198–212. [27] Wood JC. Impact of iron assessment by MRI, Hematology/the education program of the American society of hematology. American Society of Hematology Education Program 2011;2011:443–50. [28] Elliott P, Andersson B, Arbustini E, et al. Classification of the cardiomyopathies: a position statement from the European society of cardiology working group on myocardial and pericardial diseases. European Heart Journal 2008;29(2):270–6. [29] Rapezzi C, Arbustini E, Caforio AL, et al. Diagnostic work-up in cardiomyopathies: bridging the gap between clinical phenotypes and final diagnosis. A position statement from the ESC working group on myocardial and pericardial diseases. European Heart Journal 2012. [30] Flett AS, Westwood MA, Davies LC, Mathur A, Moon JC. The prognostic implications of cardiovascular magnetic resonance. Circulation Cardiovascular Imaging 2009;2(3):243–50.

[31] Bruder O, Schneider S, Nothnagel D, et al. Acute adverse reactions to gadolinium-based contrast agents in CMR: multicenter experience with 17,767 patients from the EuroCMR registry. JACC Cardiovascular Imaging 2011;4(11):1171–6. [32] Prince MR, Zhang H, Zou Z, Staron RB, Brill PW. Incidence of immediate gadolinium contrast media reactions. AJR American Journal of Roentgenology 2011;196(2):W138–43. [33] Hunt CH, Hartman RP, Hesley GK. Frequency and severity of adverse effects of iodinated and gadolinium contrast materials: retrospective review of 456,930 doses. AJR American Journal of Roentgenology 2009;193(4):1124–7. [34] Abujudeh HH, Kosaraju VK, Kaewlai R. Acute adverse reactions to gadopentetate dimeglumine and gadobenate dimeglumine: experience with 32,659 injections. AJR American Journal of Roentgenology 2010;194(2):430–4. [35] Wahl A, Paetsch I, Gollesch A, et al. Safety and feasibility of high-dose dobutamine-atropine stress cardiovascular magnetic resonance for diagnosis of myocardial ischaemia: experience in 1000 consecutive cases. European Heart Journal 2004;25(14):1230–6.