Dilated cardiomyopathy is characterized by ventricular dilation with systolic dysfunction of cardiac muscle. Recent genetic studies have revealed that mutations in genes for cytoskeleton proteins distributed in the Z-disc and/or intercalated discs of the cardiac muscle are major predictors of cardiomyopathy. However, as mutations in these genes can account for only a part of the patient population, there should be another diseasecausing gene(s) for cardiomyopathy. Cypher/ZASP appears to be an ideal candidate for the cardiomyopathy causative gene, because Cypher/ZASP encodes a Z-disc associated protein, and recent studies have demonstrated that Cypher/ZASP knock-out mice develop cardiomyopathy. In this study, we searched for sequence variations in Cypher/ZASP in 96 unrelated Japanese patients with dilated cardiomyopathy. A D626N mutation located within the third LIM domain was identified in a familial case but not found in the unrelated controls. A family study of the patient showed that all affected siblings tested had the same mutation. Clinical information of the affected family members suggested that the mutation was associated with late onset cardiomyopathy. To reveal the biochemical changes due to the mutation, we performed a yeast two-hybrid assay and a pull-down assay. It was demonstrated by both assays that the D626N mutation of Cypher/ZASP increased the affinity of the LIM domain for protein kinase C, suggesting a novel biochemical mechanism of the pathogenesis of dilated cardiomyopathy. Dilated cardiomyopathy (DCM)1 is characterized by ventricular dilation accompanied by systolic dysfunction in the absence of known causes that affect the cardiac function. Family studies of DCM patients have demonstrated that 20 -35% of DCM is caused by inherited gene mutations (familial DCM) (1). Although familial DCM can be transmitted as autosomal recessive, X-linked, or through mitochondrial traits, it is evident that autosomal dominant inheritance occurs the most (2, 3). Missense mutations in genes for cardiac ␣-actin, desmin, lamin A/C, ␦-sarcoglycan, ␤-cardiac myosin heavy chain, cardiac troponin T, ␣-tropomyosin, metavinculin, titin, muscle LIM protein (MLP), Tcap/telethonin, and phospholamban are all associated with autosomal dominant DCM (4 -15). However, mutations in the known causative genes can be found only in a part of the patient population. In addition, linkage studies in multiplex families have suggested that there are several other disease loci of which the gene responsible for causing DCM remains to be identified, including one mapped on 10q21-q23 (16).Abnormalities in Z-disc-related cytoskeletal proteins are associated with DCM also in animal models. For example, mice lacking MLP display many characteristic features of human DCM (17). Similarly, loss of ␦-sarcoglycan results in DCM in a hamster model (18), and a mouse knock-out for the actininassociated LIM protein develops DCM (19). These observations suggest that abnormalities in cytoskeletal proteins expressed in cardiac muscle cause DCM (20).Myo...

Background: Although previous studies have suggested a certain prevalence of Fabry disease (FD) in left ventricular hypertrophy (LVH) patients, the screening of FD is difficult because of its wide-ranging clinical phenotypes. We aimed to clarify the utility of combined measurement of plasma globotriaosylsphingosine (lyso-Gb3) concentration and α-galactosidase A activity (α-GAL) as a primary screening of FD in unexplained LVH patients. Methods and Results: Between 2014 and 2016, both lyso-Gb3 and α-GAL were measured in 277 consecutive patients (male 215, female 62, age 25-79 years) with left ventricular wall thickness >12 mm on echocardiogram: 5 patients (1.8%) screened positive (2 (0.7%) showed high lyso-Gb3 and 4 (1.4%) had low α-GAL levels). Finally, 2 patients (0.7%) were diagnosed with clinically significant FD. In 1 case, a female heterozygote with normal α-GAL levels had genetic variants of unknown significance and was diagnosed as FD by endomyocardial biopsy. The other case was a male chronic renal failure patient requiring hemodialysis, and he had a p.R112H mutation. In both cases there were high lyso-Gb3 levels. Conclusions: The serum lyso-Gb3 level can be relevant for clinically significant FD, and combined measurement of lyso-Gb3 and α-GAL can provide better screening of FD in unexplained LVH patients.

SUMMARYA 45-year-old Japanese man with paroxysmal atrial fibrillation (AF) developed acute anteroseptal myocardial infarction (MI). He had used 1 % topical minoxidil (RiUP ® ) once a day for 4 months before the onset of MI for treatment of baldness. Coronary angiography demonstrated severe stenosis at the proximal portion of the left anterior descending coronary artery with a filling defect. Electrocardiographic monitoring revealed paroxysmal AF and sinus bradycardia with sinus arrests, suggestive of sick sinus syndrome. Topical minoxidil is now widely used for the treatment of male pattern baldness. Although it may be difficult to relate topical use of minoxidil to myocardial ischemia, a greater awareness of its toxicity will be necessary, and patients with cardiovascular disorders should be excluded from the therapy. (Jpn Heart J 2000; 41: 519-523)

ObjectiveThe prognosis of apical hypertrophic cardiomyopathy (APH) has been benign, but apical myocardial injury has prognostic importance. We studied functional, morphological and electrocardiographical abnormalities in patients with APH and with apical aneurysm and sought to find parameters that relate to apical myocardial injury.MethodsStudy design: a multicentre trans-sectional study. Patients: 45 patients with APH and 5 with apical aneurysm diagnosed with transthoracic echocardiography (TTE) in the database of Hamamatsu Circulation Forum. Measure: the apical contraction with cine-cardiac MR (CMR), the myocardial fibrotic scar with late gadolinium enhancement (LGE)-CMR, and QRS fragmentation (fQRS) defined when two ECG-leads exhibited RSR’s patterns.ResultsCine-CMR revealed 27 patients with normal, 12 with hypokinetic and 11 with dyskinetic apical contraction. TTE misdiagnosed 11 (48%) patients with hypokinetic and dyskinetic contraction as those with normal contraction. Apical LGE was apparent in 10 (83%) and 11 (100%) patients with hypokinetic and dyskinetic contraction, whereas only in 11 patients (41%) with normal contraction (p<0.01). Patients with dyskinetic apical contraction had the lowest left ventricular ejection fraction, the highest prevalence of ventricular tachycardia, and the smallest ST depression and depth of negative T waves. The presence of fQRS was associated with impaired apical contraction and apical LGE (OR=8.32 and 8.61, p<0.05).ConclusionsCMR is superior to TTE for analysing abnormalities of the apex in patients with APH and with apical aneurysm. The presence of fQRS can be a promising parameter for the early detection of apical myocardial injury.

elayed enhancement magnetic resonance imaging (DE-MRI) has excellent spatial resolution and compared with other cardiac imaging techniques, such as echocardiography and single photon emission computed tomography (SPECT), it can detect a small or a subendcadial myocardial infarction (MI). 1 Here we report a case of cardiac tamponade in which the cause was initially unknown and DE-MRI was useful to detect a cardiac rupture due to a small transmural infarction. Case ReportA 76-year-old man was admitted to hospital after losing consciousness during exercise. He had complained of back pain that continued all night for 1 week before the admission. His blood pressure was 66/30 mmHg and heart rate was regular and 101 beats/min. The echocardiogram showed an echo-free space in the cardiac circumference, although the global left ventricular wall motion was almost normal and there was no segmental wall motion abnormality (Fig 1). His electrocardiogram recorded a counter-clockwise rotation of the QRS complex, an abnormal Q wave only in the aVL lead, and ST elevation in the inferior and anterior leads (Fig 2). The patient was diagnosed as having cardiac tamponade of unknown causes and underwent pericardiocentesis immediately. After the removal of 100 ml of bloody fluid, his systolic blood pressure rose to 130 mmHg and he regained consciousness. His leukocyte count was 6,800 cells/ l, and the serum concentrations of aspartate aminotransferase, creatine kinase and lactate dehydrogenase were 54 IU/L, 234 IU/L and 243 IU/L, respectively. Additionally, the qualitative troponin T test was positive. From the results, it was suspected that the cardiac tamponade was the result of a cardiac rupture caused by a recent MI. He was then treated with angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker and -blocker, and his systolic blood pressure was controlled between 100 and 120 mmHg.After 4 weeks, he underwent both DE-MRI and dipyridamole stress 201 Tl myocardial SPECT. The magnetic resonance imaging (MRI) used a 1.5 T MR system with the combined use of 8-channel cardiac phased array coil (Signa Infinity Twinspeed, GE Medical Systems, WI, USA). DE-MRI was based on the inversion recovery prepared fast gradient echo sequence. Five to 9 slices of 10 mm in thickness were used to cover the entire heart. Contrast agent (0.2 mmol/kg Gd-DTPA-BMA; Daiichi Pharma, Tokyo, Japan) was intravenously injected, and DE-MRI was performed after 15 min. A transmural enhancement was clearly detected in a very narrow range of the lateral wall of left ventricle (Fig 3), although dipyridamole stress 201 Tl myocardial SPECT indicated only a slight hypoperfusion in the posterolateral segment (Fig 4). Re-distribution of 201 Tl was observed in the rest image, suggesting a significant coronary stenosis in a branch of the left coronary artery. Coronary angiography revealed a severely stenotic lesion in the obtuse marginal branch of the left circumflex artery. There were no significant stenotic lesions in the left anterior descending artery or th...