2015 Update on Acute Adverse Reactions to Gadolinium based Contrast Agents in Cardiovascular MR. Large Multi-National and Multi-Ethnical Population Experience With 37788 Patients From the EuroCMR Registry.

OBJECTIVES: Specifically we aim to demonstrate that the results of our earlier safety data hold true in this much larger multi-national and multi-ethnical population. BACKGROUND: We sought to re-evaluate the frequency, manifestations, and severity of acute adverse reactions associated with administration of several gadolinium- based contrast agents during routine CMR on a European level. METHODS: Multi-centre, multi-national, and multi-ethnical registry with consecutive enrolment of patients in 57 European centres. RESULTS: During the current observation 37,788 doses of Gadolinium based contrast agent were administered to 37,788 patients. The mean dose was 24.7 ml (range 5-80 ml), which is equivalent to 0.123 mmol/kg (range 0.01 - 0.3 mmol/kg). Forty-five acute adverse reactions due to contrast administration occurred (0.12%). Most reactions were classified as mild (43 of 45) according to the American College of Radiology definition. The most frequent complaints following contrast administration were rashes and hives (15 of 45), followed by nausea (10 of 45) and flushes (10 of 45). The event rate ranged from 0.05% (linear non-ionic agent gadodiamide) to 0.42% (linear ionic agent gadobenate dimeglumine). Interestingly, we also found different event rates between the three main indications for CMR ranging from 0.05% (risk stratification in suspected CAD) to 0.22% (viability in known CAD). CONCLUSIONS: The current data indicate that the results of the earlier safety data hold true in this much larger multi-national and multi-ethnical population. Thus, the "off-label" use of Gadolinium based contrast in cardiovascular MR should be regarded as safe concerning the frequency, manifestation and severity of acute events.

Indications for cardiovascular magnetic resonance in children with congenital and acquired heart disease: an expert consensus paper of the Imaging Working Group of the AEPC and the Cardiovascular Magnetic Resonance Section of the EACVI.

This article provides expert opinion on the use of cardiovascular magnetic resonance (CMR) in young patients with congenital heart disease (CHD) and in specific clinical situations. As peculiar challenges apply to imaging children, paediatric aspects are repeatedly discussed. The first section of the paper addresses settings and techniques, including the basic sequences used in paediatric CMR, safety, and sedation. In the second section, the indication, application, and clinical relevance of CMR in the most frequent CHD are discussed in detail. In the current era of multimodality imaging, the strengths of CMR are compared with other imaging modalities. At the end of each chapter, a brief summary with expert consensus key points is provided. The recommendations provided are strongly clinically oriented. The paper addresses not only imagers performing CMR, but also clinical cardiologists who want to know which information can be obtained by CMR and how to integrate it in clinical decision-making.

[Cardiology]. / Cardiologie.

The present review provides a selected choice of clinical research in the field of interventional cardiology, heart failure and cardiac imaging. We also focused on the new guidelines published by the European society of cardiology in 2012.

[Cardiac MR in development: the large multicenter CMR studies in 2012]. / IRM cardiaque en évolution: de grandes études multicentriques en 2012.

The results of several large multicenter CMR studies were reported in 2012, thus, constantly corroborating the evidence on CMR performance. In this review, we present results of the MR-IMPACT programme and the CE-MARC study, which demonstrated the superiority of perfusion-CMR over gated SPECT for the workup of suspected CAD, the currently available data from the European CMR registry, comprising almost 30,000 patients from 57 participating centers in 15 European countries, and finally, the results of the Advisa-MRI study, which documented the safety of a MRI-compatible pacemaker system. These large trials and others set the basis for the recommendations in the new European guidelines on heart failure to use CMR as a first line method if echocardiographic quality is inadequate or the etiology of heart failure is unclear.

Cardiovascular magnetic resonance in autoimmune rheumatic diseases: a clinical consensus document by the European Association of Cardiovascular Imaging.

Autoimmune rheumatic diseases (ARDs) involve multiple organs including the heart and vasculature. Despite novel treatments, patients with ARDs still experience a reduced life expectancy, partly caused by the higher prevalence of cardiovascular disease (CVD). This includes CV inflammation, rhythm disturbances, perfusion abnormalities (ischaemia/infarction), dysregulation of vasoreactivity, myocardial fibrosis, coagulation abnormalities, pulmonary hypertension, valvular disease, and side-effects of immunomodulatory therapy. Currently, the evaluation of CV involvement in patients with ARDs is based on the assessment of cardiac symptoms, coupled with electrocardiography, blood testing, and echocardiography. However, CVD may not become overt until late in the course of the disease, thus potentially limiting the therapeutic window for intervention. More recently, cardiovascular magnetic resonance (CMR) has allowed for the early identification of pathophysiologic structural/functional alterations that take place before the onset of clinically overt CVD. CMR allows for detailed evaluation of biventricular function together with tissue characterization of vessels/myocardium in the same examination, yielding a reliable assessment of disease activity that might not be mirrored by blood biomarkers and other imaging modalities. Therefore, CMR provides diagnostic information that enables timely clinical decision-making and facilitates the tailoring of treatment to individual patients. Here we review the role of CMR in the early and accurate diagnosis of CVD in patients with ARDs compared with other non-invasive imaging modalities. Furthermore, we present a consensus-based decision algorithm for when a CMR study could be considered in patients with ARDs, together with a standardized study protocol. Lastly, we discuss the clinical implications of findings from a CMR examination.

[Cardiac MRI in the follow-up of adult congenital cardiomyopathy patients]. / IRM cardiaque dans le suivi des cardiopathies congénitales à l'âge adulte.

Magnetic resonance imaging is a rapidly developing modality in cardiology. It offers an excellent image definition and a large field of view, allowing a more accurate morphological assessment of cardiac malformations. Due to its unique versatility and its ability to provide myocardial tissue characterization, cardiac magnetic resonance (CMR) is now recognized as a central imaging modality for a wide range of congenital heart diseases, including assessment of post-surgical cardiac anatomy, quantification of valvular disease and detection of myocardial ischemia. CMR provides useful diagnostic information without any radiation exposure, and improves the global management of patients with congenital heart disease.

Churg-Strauss syndrome with cardiac involvement: case illustration and contribution of CMR in the diagnosis and clinical follow-up.

This report summarises three cases of Churg-Strauss syndrome (CSS) illustrating the diagnostic challenges associated with the cardiac manifestation of this disease. Here, we illustrate the role of cardiac magnetic resonance (CMR) for diagnosis and follow-up of CSS with a focus on new non-contrast T2-weighted imaging sequences for quantification of myocardial scar tissue and quantitative T2 mapping techniques, which allow the detection of myocardial edema.

Assessment of myocardial perfusion in coronary artery disease by magnetic resonance: a comparison with positron emission tomography and coronary angiography.

BACKGROUND: Monitoring contrast medium wash-in kinetics in hyperemic myocardium by magnetic resonance (MR) allows for the detection of stenosed coronary arteries. In this prospective study, the quality of a multislice MR approach with respect to the detection and sizing of compromised myocardium was determined and compared with positron emission tomography (PET) and quantitative coronary angiography. METHODS AND RESULTS: A total of 48 patients and healthy subjects were studied by MR using a multislice hybrid echo-planar pulse sequence for monitoring the myocardial first pass kinetics of gadolinium-diethylenetriamine pentaacetic acid bismethylamide (Omniscan; 0.1 mmol/kg injected at 3 mL/s IV) during hyperemia (dipyridamole 0.56 mg/kg). Signal intensity upslope as a measure of myocardial perfusion was calculated in 32 sectors per heart from pixelwise parametric maps in the subendocardial layer and for full wall thickness. Before coronary angiography, coronary flow reserve (hyperemia induced by dipyridamole 0.56 mg/kg) was determined in corresponding sectors by (13)N-ammonia PET. Receiver-operator characteristic analysis of subendocardial upslope data revealed a sensitivity and specificity of 91% and 94%, respectively, for the detection of coronary artery disease as defined by PET (mean coronary flow reserve minus 2SD of controls) and a sensitivity and specificity of 87% and 85%, respectively, in comparison with quantitative coronary angiography (diameter stenosis >/=50%). The number of pathological sectors per patient on PET and MR studies correlated linearly (slope, 0.94; r=0.76; P<0.0001). CONCLUSIONS: The presented MR approach reliably identifies patients with coronary artery stenoses and provides information on the amount of compromised myocardium, even when perfusion abnormalities are confined to the subendocardial layer. This modality may qualify for its clinical application in the management of coronary artery disease.

Myocardial first-pass perfusion magnetic resonance imaging: a multicenter dose-ranging study.

BACKGROUND: MRI can identify patients with obstructive coronary artery disease by imaging the left ventricular myocardium during a first-pass contrast bolus in the presence and absence of pharmacologically induced myocardial hyperemia. The purpose of this multicenter dose-ranging study was to determine the minimally efficacious dose of gadopentetate dimeglumine injection (Magnevist Injection; Berlex Laboratories) for detecting obstructive coronary artery disease. METHOD AND RESULTS: A total of 99 patients scheduled for coronary artery catheterization as part of their clinical evaluation were enrolled in this study. Patients were randomized to 1 of 3 doses of gadopentate dimeglumine: 0.05, 0.10, or 0.15 mmol/kg. First-pass perfusion imaging was performed during hyperemia (induced by a 4-minute infusion of adenosine at a rate of 140 microg x kg(-1) x min(-1)) and then again in the absence of adenosine with otherwise identical imaging parameters and the same contrast dose. Perfusion defects were evaluated subjectively by 4 blinded reviewers. Receiver-operating curve analysis showed that the areas under the receiver-operating curve were 0.90, 0.72, and 0.83 for the low-, medium-, and high-contrast doses, respectively, compared with quantitative coronary angiography (diameter stenosis > or =70%). For the low-dose group, mean sensitivity was 93+/-0%, mean specificity was 75+/-7%, and mean accuracy was 85+/-3%. CONCLUSIONS: First-pass perfusion MRI is a safe and accurate test for identifying patients with obstructive coronary artery disease. A low dose of 0.05 mmol/kg gadopentetate dimeglumine is at least as efficacious as higher doses.

Magnetic resonance-based assessment of global coronary flow and flow reserve and its relation to left ventricular functional parameters: a comparison with positron emission tomography.

BACKGROUND: Measurement of coronary sinus blood flow (CSF) by phase-contrast magnetic resonance (PC-MR) imaging at rest and during hyperemia may allow noninvasive assessment of global coronary hemodynamics. METHODS AND RESULTS: Sixteen healthy volunteers (age, 22 to 32 years) were examined with MR and PET in random order within 1 to 2 days. At rest and during hyperemia (dipyridamole 0.56 mg/kg), CSF was measured by a cine PC-MR technique (temporal resolution, 40 ms; spatial resolution, 1.25x0.8 mm(2)), and myocardial blood flow (MBF) was measured by [(13)N]NH(3) PET. PET and MR agreed closely for coronary flow reserve (CFR; mean difference, 2.2+/-14.7%; Bland-Altman method). CSF divided by either total left ventricular mass or an estimate of drained myocardium (LVM(drain)) correlated highly with PET flow data (r=0.93 and 0.95, respectively) and with measures of oxygen demand, ie, heart rate, afterload-corrected fiber shortening, and peak systolic stress determined by MR (overall correlation coefficients, 0.81 and 0.87, respectively, multivariate analysis). CSF/LVM(drain) did not differ significantly from PET-derived MBF (difference, 3.6+/-16.6%). In orthotopic heart transplant recipients (n=9), CFR was reduced and blood supply-demand relationships at rest were shifted toward higher flows (P<0.0001). CONCLUSIONS: This integrated MR approach allows comprehensive assessment of autoregulated and hyperemic coronary flow and is suitable for serial measurements in patients. In transplanted hearts, elevated resting flow is the major cause of reduced CFR.

Influence of severity of myocardial injury on distribution of macromolecules: extravascular versus intravascular gadolinium-based magnetic resonance contrast agents.

OBJECTIVES: This study sought to 1) compare the distribution of extravascular (573 Da) and intravascular (92 kDa) magnetic resonance (MR) contrast agents in reperfused infarcted myocardium, and 2) investigate the effect of injury severity on these distribution patterns. BACKGROUND: Myocardial distribution of low and high molecular weight contrast agents depends on vascular permeability, diffusive/convective transport within the interstitium and accessibility of the intracellular compartment (cellular integrity). METHODS: To vary the severity of myocardial injury, 72 rats were subjected to 20, 30, 45 or 75 min (n = 18, respectively) of coronary artery occlusion. After 2 h of reflow, the animals received either 0.05 mmol/kg of gadolinium-diethylenetriaminepentaacetic acid-bismethylamide (Gd-DTPA-BMA) (n = 24), (Gd-DTPA)30-albumin (n = 24) or saline (control group, n = 24). Three minutes after injection, the hearts were excised and imaged (spin-echo imaging parameters: repetition time 300 ms, echo time 8 ms, 2-tesla system), followed by triphenyltetrazolium chloride staining for infarct detection and sizing. RESULTS: Histomorphometric and MR infarct size (expressed as percent of slice surface) correlated well: r = 0.96 for Gd-DTPA-BMA; r = 0.95 for (Gd-DTPA)30-albumin. On Gd-DTPA-BMA-enhanced images, reperfused myocardial infarctions were homogeneously enhanced. The ratio of signal intensity of infarcted/ normal myocardium increased with increasing duration of ischemia (overall p < 0.0001, analysis of variance [ANOVA]), indicating an increase in the distribution volume of Gd-DTPA-BMA in postischemic myocardium. On (Gd-DTPA)30-albumin-enhanced images, reperfused infarctions consisted of a bright border zone and a less enhanced central core. The extent of the core increased with increasing duration of ischemia (overall p value < 0.0001, ANOVA). CONCLUSIONS: At 2 h of reperfusion, the distribution of MR contrast agents in postischemic myocardium is 1) specific for extravascular and intravascular agents, and 2) modulated by the duration of ischemia.

Indications for cardiovascular magnetic resonance in children with congenital and acquired heart disease: an expert consensus paper of the Imaging Working Group of the AEPC and the Cardiovascular Magnetic Resonance Section of the EACVI.

This article provides expert opinion on the use of cardiovascular magnetic resonance (CMR) in young patients with congenital heart disease (CHD) and in specific clinical situations. As peculiar challenges apply to imaging children, paediatric aspects are repeatedly discussed. The first section of the paper addresses settings and techniques, including the basic sequences used in paediatric CMR, safety, and sedation. In the second section, the indication, application, and clinical relevance of CMR in the most frequent CHD are discussed in detail. In the current era of multimodality imaging, the strengths of CMR are compared with other imaging modalities. At the end of each chapter, a brief summary with expert consensus key points is provided. The recommendations provided are strongly clinically oriented. The paper addresses not only imagers performing CMR, but also clinical cardiologists who want to know which information can be obtained by CMR and how to integrate it in clinical decision-making.

Integration of vascular biology and magnetic resonance imaging in the understanding of atherothrombosis and acute coronary syndromes.

The interaction between the vulnerable atherosclerotic plaque prone to disruption and thrombus formation is the cornerstone of acute coronary syndrome (ACS). Although distinct from one another, the atherosclerotic and thrombotic processes appear to be interdependent, hence the term atherothrombosis. Inflammation is a crucial common pathophysiological mechanism. Overall, the association of plaque vulnerability and ACS has been well documented. Given the multifactorial origin of atherothrombosis the best preventive approach should be aggressive management of all the risk factors. New interventions should be directed toward decreasing vulnerability of the lesions thereby decreasing the risk of ACS.

Effect of exercise training on postexercise oxygen uptake kinetics in patients with reduced ventricular function.

BACKGROUND: The time required for oxygen uptake (O(2)) to return to baseline level (recovery kinetics) is prolonged in patients with reduced ventricular function, and the degree to which it is prolonged is related to the severity of heart failure, markers of abnormal ventilation, and prognosis. In the present study, we sought to determine the effect of exercise training on O(2) recovery kinetics in patients with reduced ventricular function. METHODS: Twenty-four male patients with reduced ventricular function after a myocardial infarction were randomized to either a 2-month high-intensity residential exercise training program or to a control group. O(2) kinetics in recovery from maximal exercise were calculated before and after the study period and expressed as the slope of a single exponential relation between O(2) and time during the first 3 min of recovery. RESULTS: Peak O(2) increased significantly in the exercise group (19.4 +/- 3.0 mL/kg/min vs 25.1 +/- 4.7 mL/kg/min, p < 0.05), whereas no change was observed in control subjects. The O(2) half-time in recovery was reduced slightly after the study period in both groups (108.7 +/- 33.1 to 102.1 +/- 50.5 s in the exercise group and 122.3 +/- 68.7 to 107.5 +/- 36.0 s in the control group); neither the change within or between groups was significant. The degree to which O(2) was prolonged in recovery was inversely related to measures of exercise capacity (peak O(2), watts achieved, and exercise time; r = - 0.48 to - 0.57; p < 0.01) and directly related to the peak ventilatory equivalents for oxygen (r = 0.59, p < 0.01) and carbon dioxide (r = 0.57, p < 0.01). CONCLUSION: Two months of high-intensity training did not result in a faster recovery of O(2) in patients with reduced ventricular function. This suggests that adaptations to exercise training manifest themselves only during, but not in, recovery from exercise.

Assessment of early left ventricular remodeling in orthotopic heart transplant recipients with cine magnetic resonance imaging: potential mechanisms.

We performed short axis cine magnetic resonance imaging studies in 11 patients 2 months after they underwent orthotopic heart transplantation (OHT), and in 10 control subjects, to measure left ventricular (LV) volumes, mass, and end-systolic wall stress to assess ventricular remodeling after OHT. Although there were no significant differences in ventricular volumes and ejection fractions between heart transplant recipients and control subjects, heart transplant recipients had significantly higher LV mass (198 +/- 61 vs 132 +/- 27 gm, p = 0.001). As a consequence of myocardial hypertrophy, end-systolic wall stress was significantly reduced in heart transplant recipients compared with control subjects (34 +/- 16 vs 57 +/- 10 kdyne/cm2, p = 0.001). Moreover, heart transplant recipients had significantly reduced end-systolic wall stress/volume ratio when compared with control subjects (0.89 +/- 0.3 vs 1.26 +/- 0.3 kdyne/cm2/ml, p < 0.01), indicating an already reduced LV contractility 2 months after heart transplantation. Univariate regression analysis revealed a significant correlation between LV mass and averaged cyclosporine levels, but no correlation between LV mass and blood pressure, cold ischemic time, acute rejection, age, body mass, blood pressure, plasma catecholamine levels, or plasma renin activity. Magnetic resonance imaging demonstrates early LV remodeling after OHT with reduced myocardial contractility. Cyclosporine may be contributing to these changes.

Influence of felodipine on left ventricular hypertrophy and systolic function in orthotopic heart transplant recipients: possible interaction with cyclosporine medication.

BACKGROUND: Concentric left ventricular (LV) hypertrophy develops early in orthotopic heart transplant (OHT) recipients. To compare the effects of a calcium channel blocker, felodipine, versus diuretics on LV hypertrophy and LV systolic function repeated magnetic resonance imaging studies were performed in OHT recipients. Cyclosporine levels and neurohormones were also measured to explore potential interactions with treatment. METHODS: Twenty-two patients were randomized at baseline (2 months after OHT) to receive felodipine or diuretic treatment. Before and after 4 months of treatment (n = 19), LV dimensions and LV mass (Simpson's rule) were measured. The relationship between circumferential fiber shortening (two-shell cylindrical model) and end-systolic wall stress was used as a measure of load-independent LV contractility. Neurohormones were measured at the beginning and end of the treatment period, and cyclosporine levels and blood pressures were additionally measured during treatment. RESULTS: At baseline, the felodipine and diuretic groups did not differ in LV mass, wall stress, and fiber shortening. During felodipine treatment LV mass decreased (p < 0.01) and tended to increase during diuretics treatment (p = 0.06). Afterload-corrected fiber shortening did not change during felodipine treatment, but decreased (p < 0.01) with diuretics. Changes in LV mass were positively correlated with cyclosporine levels (r = 0.70) in the diuretics group, but not in the felodipine group. CONCLUSIONS: In OHT recipients during diuretic treatment, progression of LV hypertrophy occurs in relation to cyclosporine plasma levels and is accompanied by impairment of systolic contractile function. Felodipine induces regression of LV hypertrophy, while systolic contractile function is preserved. During felodipine treatment, regression of LV hypertrophy is unrelated to cyclosporine levels. Thus, felodipine seems to attenuate the hypertrophic effect of cyclosporine on transplanted hearts.

The internal mammary artery malperfusion syndrome: incidence, treatment and angiographic verification.

Internal mammary artery (IMA) malperfusion syndrome is caused by an acute imbalance between myocardial demand and nutritional support through the mammary artery. In a consecutive series of 2326 isolated myocardial revascularizations-with at least one IMA to the left anterior descending branch (LAD) in 91.3% (2125/2326)-we identified 45 patients (1.9%) with a perioperative course suggesting IMA malperfusion syndrome. Additional saphenous vein graft to the distal segment of the LAD was performed during normothermic ventricular fibrillation in all patients. Hospital mortality was 4.4% (2/45), intra-aortic balloon pumping was required in 15.5% (7/45) and anterior myocardial infarction occurred in 28.8% (13/45). Coronary angiography was performed in all survivors between 3 and 24 months postoperatively. Wide patent IMA graft and patent saphenous vein graft were observed in 56% (24/43), narrowed but patent IMA graft and patent vein graft in 35% (15/43), while patent vein graft and not visualized IMA in 7% (3/43); in one patient with severely diseased peripheral LAD, no flow could be demonstrated in the IMA graft or in the additional vein graft (1/43, 2.4%). No major differences were found between early and late coronary angiography in these patients. Additional vein graft to distal LAD is the treatment of choice in acute IMA malperfusion syndrome. Despite patent vein graft with superior blood flow, early and late postoperative IMA flow to LAD is maintained in the majority of patients.

Very fast cardiac imaging.

With very fast MR imaging techniques, myocardial perfusion can be assessed by monitoring the changes of myocardial signal intensity over time following bolus injection of a contrast medium. Very fast MR imaging techniques also allow for freezing of cardiac motion that is important for coronary MR angiography and their high temporal resolution allow for coronary flow reserve measurements. In the current overview, basic principles and strategies of very fast cardiac MR imaging are presented. In the second part, applications of these fast sequences in the fields of myocardial perfusion, coronary MR angiography, and low measurements are presented.

Quantification of aortic flow by phase-contrast magnetic resonance in patients with bicuspid aortic valve.

AIMS: Bicuspid aortic valve (BAV) causes complex flow patterns in the ascending aorta (AAo), which may compromise the accuracy of flow measurement by phase-contrast magnetic resonance (PC-MR). Therefore, we aimed to assess and compare the accuracy of forward flow measurement in the AAo, where complex flow is more dominant in BAV patients, with flow quantification in the left ventricular outflow tract (LVOT) and the aortic valve orifice (AV), where complex flow is less important, in BAV patients and controls. METHODS AND RESULTS: Flow was measured by PC-MR in 22 BAV patients and 20 controls at the following positions: (i) LVOT, (ii) AV, and (iii) AAo, and compared with the left ventricular stroke volume (LVSV). The correlation between the LVSV and the forward flow in the LVOT, the AV, and the AAo was good in BAV patients (r = 0.97/0.96/0.93; P < 0.01) and controls (r = 0.96/0.93/0.93; P < 0.01). However, in relation with the LVSV, the forward flow in the AAo was mildly underestimated in controls and much more in BAV patients [median (inter-quartile range): 9% (4%/15%) vs. 22% (8%/30%); P < 0.01]. This was not the case in the LVOT and the AV. The severity of flow underestimation in the AAo was associated with flow eccentricity. CONCLUSION: Flow measurement in the AAo leads to an underestimation of the forward flow in BAV patients. Measurement in the LVOT or the AV, where complex flow is less prominent, is an alternative means for quantifying the systolic forward flow in BAV patients.

Hypertrophic cardiomyopathy due to beta-myosin heavy chain mutation with extreme phenotypic variability within a family.

Hypertrophic cardiomyopathy (HCM) affects 1 in 500 persons and shows high variability in severity of disease, in genetic heterogeneity and phenotypic patterns. Many affected individuals remain undetected throughout their lives. In this case report a family with proven beta-myosin heavy chain mutation (MYH7) with 3 affected family members with huge phenotypic variability is described. The index patient (male, age 21 years) has severe phenotypic expression with a pathological ECG and maximal septal wall thickness of 29 mm, there is no significant obstruction in the left ventricular outflow tract. The sister (age 16 years), mutation carrier, has no detectable hypertrophy and no ECG changes. The mother (age 44 years), also carrying the mutation, has a normal ECG and shows only mild septal hypertrophy of 12 mm and systolic anterior motion of her mitral valve chordae with no gradient. The maternal grandmother died suddenly at age 65 years of presumed coronary artery disease, and the maternal great-grandmother had a sudden cardiac death at age 50 years of unknown etiology. To conclude, this family shows impressively the wide spectrum of phenotypic presentation and outcome in one family.