Clinical Features of Heart Failure in Patients With Hypertrophic Cardiomyopathy in a Regional Japanese Cohort　- Results From the Kochi RYOMA Study.

BACKGROUND: The clinical features of heart failure (HF) in patients with hypertrophic cardiomyopathy (HCM) in Japan have not been fully elucidated.Methods and Results: In 293 patients with HCM (median age at registration, 65 (57-72) years) in a prospective cardiomyopathy registration network in Kochi Prefecture (Kochi RYOMA study), HF events (HF death or hospitalization for HF) occurred in 35 patients (11.9%) (median age, 76 (69-80) years), including 11 HF deaths during a median follow-up of 6.1 years. The 5-year HF events rate was 9.6%. Atrial fibrillation, low percentage of fractional shortening, and high B-type natriuretic peptide level at registration were predictors of HF events. The combination of these 3 factors had a relatively high positive predictive value (55%) for HF events and none of them had a high negative predictive value (99%). There were 4 types of HF profile: left ventricular (LV) systolic dysfunction (40%), severe LV diastolic dysfunction (34%), LV outflow tract obstruction (LVOTO) (20%), and primary mitral regurgitation (MR) (6%). HF deaths occurred in patients with LV systolic dysfunction or LV diastolic dysfunction, but none of patients with LVOTO or primary MR due to additional invasive therapies. CONCLUSIONS: In a Japanese HCM cohort, HF was an important complication, requiring careful follow-up and appropriate treatment.

A Validation Study of the Mayo Clinic Phenotype-Based Genetic Test Prediction Score for Japanese Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal-dominant disorder mainly caused by mutations in sarcomere genes. Recently, a phenotype-based genetic test prediction score for patients with HCM was introduced by Mayo Clinic. The genotype score was derived on the basis of the predictive effect of 6 clinical markers, and the total score was shown to be correlated with the yield of genetic testing. However, it has not been determined whether this prediction model is useful in Japanese HCM patients.Methods and Results:The utility of the Mayo Clinic HCM genotype predictor score in 209 Japanese unrelated patients with a clinical diagnosis of HCM who had undergone genetic testing for 6 sarcomere genes was assessed. Overall, 55 patients (26%) had pathogenic or likely pathogenic variants (60% being genotype-positive in familial cases). We divided the patients into 6 groups (groups with scores of from -1 to 5) according to the prediction score. The yields of genetic testing in the groups with scores of -1, 0, 1, 2, 3, 4, and 5 were 8%, 16%, 24%, 48%, 50%, 100%, and 89%, respectively, with an incremental increase in yield between each of the score subgroups (P<0.001). CONCLUSIONS: The Mayo Clinic HCM genotype predictor score is useful for predicting a positive genetic test result in Japanese HCM Patients.

Hypertrophic Cardiomyopathy　- A Heterogeneous and Lifelong Disease in the Real World.

Hypertrophic cardiomyopathy (HCM) is the most frequent hereditary cardiomyopathy, showing an autosomal-dominant f inheritance. A great deal of attention has been paid to genetics, left ventricular tract obstruction and the prediction and prevention of sudden cardiac death in HCM. Needless to say, these are very important, but we should recognize the heterogeneity in etiology, morphology, clinical course and management of this unique cardiomyopathy. Another important perspective is that HCM causes left ventricular remodeling over time and is a disease that requires lifelong management in the real world.

Lifelong Clinical Impact of the Presence of Sarcomere Gene Mutation in Japanese Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is mainly caused by mutations in sarcomere genes. Regarding the clinical implications of genetic information, little is known about the lifelong clinical effect of sarcomere mutations in Japanese HCM patients.Methods and Results:We studied 211 consecutive Japanese patients with HCM who had agreed to genetic testing between 2003 and 2013. Genetic analyses were performed by direct DNA sequencing in the 6 common sarcomere genes (MYH7,MYBPC3,TNNT2,TNNI3,TPM1,ACTC). Through variant filtering, 21 mutations were identified in 67 patients. After excluding 8 patients whose variants were determined as having uncertain significance, finally 203 patients (130 men, age at study entry: 61.8±14.1 years) were investigated for clinical presentation and course. At the time of study entry, patients with mutations were younger, had more frequent non-sustained ventricular tachycardia, had greater interventricular wall thickness, were more frequently in the dilated phase and less frequently had apical HCM. Through their lifetimes, a total of 98 HCM-related morbid events occurred in 72 patients. Survival analysis revealed that patients with sarcomere gene mutations experienced those morbid events significantly more frequently, and this tendency was more prominent for lethal arrhythmic events. CONCLUSIONS: In our HCM cohort, patients with sarcomere gene mutations had poorer lifelong outcome. Genetic information is considered important for better management of HCM.

Clinical Profile of Thromboembolic Events in Patients With Hypertrophic Cardiomyopathy in a Regional Japanese Cohort　- Results From Kochi RYOMA Study.

BACKGROUND: There is limited information about the clinical profiles of patients with hypertrophic cardiomyopathy (HCM) and thromboembolic events in a community-based Japanese patient cohort.Methods and Results:In 2004, we established a cardiomyopathy registration network in Kochi Prefecture that comprised 9 hospitals, and finally 293 patients with HCM were followed. The mean age at registration was 63±14 years, and 197 patients (67%) were men. At registration, 86 patients (29%) had documented atrial fibrillation (AF). During a mean follow-up period of 6.1±3.2 years, thromboembolic events, including 3 embolic stroke deaths, occurred in 23 patients. The 5-year embolic event rate was 5.5%. During the follow-up period, an additional 31 patients (11%) had documentation of AF and finally a total of 117 patients (40%) developed AF. The 5-year embolic event rate in those 117 patients with AF was 12.3%. Of the 23 patients with embolic events, 12 had AF prior to the embolic complications and another 6 had documented AF after thromboembolism. AF was not detected in the remaining 5 patients. The CHADS2score did not correlate with the embolic outcome in HCM patients. CONCLUSIONS: In this community-based registry, thromboembolic events were not rare in patients with HCM. All patients with HCM in whom AF develops should be given anticoagulation therapy regardless of their CHADS2score.

Patients' Characteristics and Clinical Course of Hypertrophic Cardiomyopathy in a Regional Japanese Cohort　- Results From Kochi RYOMA Study.

BACKGROUND: There have been few studies on the clinical course of hypertrophic cardiomyopathy (HCM) in a community-based patient cohort in Japan.Methods and Results:In 2004, we established a cardiomyopathy registration network in Kochi Prefecture (the Kochi RYOMA study) that consisted of 9 hospitals, and finally, 293 patients with HCM were followed. The ages at registration and at diagnosis were 63±14 and 56±16 years, respectively, and 197 patients (67%) were male. HCM-related deaths occurred in 23 patients during a mean follow-up period of 6.1±3.2 years. The HCM-related 5-year survival rate was 94%. In addition, a total of 77 cardiovascular events that were clinically severe occurred in 70 patients, and the HCM-related 5-year event-free rate was 80%. Multivariate Cox proportional hazards model analysis showed that the presence of NYHA class III at registration was a significant predictor of HCM-related deaths and that the presence of atrial fibrillation, lower fractional shortening and presence of left ventricular outflow tract obstruction in addition to NYHA class III were significant predictors of cardiovascular events. CONCLUSIONS: In our unselected registry in an aged Japanese community, HCM mortality was favorable, but one-fifth of the patients commonly suffered from HCM-related adverse cardiovascular events during the 5-year follow-up period. Careful management of HCM patients is needed, particularly for those with the above-mentioned clinical determinants.

Prognostic Significance of Non-Dilated Left Ventricular Size and Mitral Regurgitation in Patients With Dilated Phase of Hypertrophic Cardiomyopathy.

Although a subtype of hypertrophic cardiomyopathy (HCM), dilated phase of HCM (D-HCM) characterized by left ventricular (LV) systolic dysfunction, has been reported to have a poor prognosis, some patients with D-HCM survive for a relatively long period. The degree of LV dilatation and functional mitral regurgitation (MR) are generally thought to be important predictors of poor prognosis in patients with LV systolic dysfunction. However, there is little information available on the relations among LV size, presence of significant MR, and prognosis in D-HCM patients.We retrospectively studied 31 patients with D-HCM to determine whether echocardiographic assessment of LV size and MR provides incremental prognostic information.During a follow-up period of 5.6 ± 4.2 years, there were 13 cardiovascular deaths. When the patients were divided into two groups by LV size at diagnosis of D-HCM, a non-dilated LV group (LV end-diastolic diameter (LVEDD) < 50 mm, n = 9) and a dilated LV group (LVEDD ≥ 50 mm, n = 22), the clinical course in the non-dilated LV group was significantly worse. As for the clinical impact of MR, no patient in the non-dilated LV group showed significant MR and 7 of the patients with dilated LV size showed significant MR during follow-up. Once significant MR was reached, cardiovascular deaths were significantly more frequent in patients with MR.Patients with D-HCM, particularly those with less LV dilatation at diagnosis of dilated phase and with significant MR during follow-up, have a poor prognosis.

Early Invasive Strategy for Octogenarians and Nonagenarians With Acute Myocardial Infarction.

Background: Older adults with acute myocardial infarction (AMI) are currently a rapidly growing population. However, their clinical presentation and outcomes remain unresolved. Methods and Results: A total of 268 consecutive AMI patients were analyzed for clinical characteristics and outcomes with major adverse cardiovascular events (MACE) and all-cause mortality within 1 year. Patients aged ≥80 years (Over-80; n=100) were compared with those aged ≤79 years (Under-79; n=168). (1) Primary percutaneous coronary intervention (PCI) was frequently and similarly performed in both the Over-80 group and the Under-79 group (86% vs. 89%; P=0.52). (2) Killip class III-IV (P<0.01), in-hospital mortality (P<0.01), MACE (P=0.03) and all-cause mortality (P<0.01) were more prevalent in the Over-80 group than in the Under-79 group. (3) In the Over-80 group, frail patients showed a significantly worse clinical outcome compared with non-frail patients. (4) Multivariate analysis revealed Killip class III-IV was associated with MACE (odds ratio [OR]=3.51; P=0.02) and all-cause mortality (OR=9.49; P<0.01) in the Over-80 group. PCI was inversely associated with all-cause mortality (OR=0.13; P=0.02) in the Over-80 group. Conclusions: The rate of primary PCI did not decline with age. Although octogenarians/nonagenarians showed more severe clinical presentation and worse short-term outcomes compared with younger patients, particularly in those with frailty, the prognosis may be improved by early invasive strategy even in these very old patients.

Influences of donepezil on cardiovascular system--possible therapeutic benefits for heart failure--donepezil cardiac test registry (DOCTER) study.

To study prospectively influences of donepezil, an acetylcholinesterase inhibitor against Alzheimer disease, on cardiovascular system, we evaluated cardiovascular changes occurring during new initialized treatment with donepezil in 49 dementia patients over 6 months. No patient suffered from cardiovascular events. In clinical changes between baseline and the first evaluation after donepezil treatment, heart rate and plasma brain natriuretic peptide (BNP) levels as a marker for heart failure did not change (BNP: 59.62 ± 62.71 pg/mL at baseline to 53.18 ± 42.34 pg/mL at first evaluation; P = 0.262). We further examined plasma BNP levels in 2 groups into which the patients were divided at baseline according to the cut-off plasma BNP level of 60 pg/mL. In patients with high level of BNP, the BNP levels decreased after administration of donepezil (116.39 ± 76.58 pg/mL at baseline to 82.24 ± 46.64 pg/mL at first evaluation; P = 0.011) with the tendency to be reduced in the follow-up period. BNP did not change in patients with low level of BNP. Donepezil seemed to be safe in patients with dementia without symptomatic heart disease and significantly decreased plasma BNP levels in patients with subclinical chronic heart failure.

Prevalence and distribution of sarcomeric gene mutations in Japanese patients with familial hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM), which is inherited as an autosomal dominant trait, is the most prevalent hereditary cardiac disease. Although there are several reports on the systematic screening of mutations in the disease-causing genes in European and American populations, only limited information is available for Asian populations, including Japanese. METHODS AND RESULTS: Genetic screening of disease-associated mutations in 8 genes for sarcomeric proteins, MYH7, MYBPC3, MYL2, MYL3, TNNT2, TNNI3, TPM1, and ACTC, was performed by direct sequencing in 112 unrelated Japanese proband patients with familial HCM; 37 different mutations, including 13 novel ones in 5 genes, MYH7, MYBPC3, TNNT2, TNNI3, and TPM1, were identified in 49 (43.8%) patients. Among them, 3 carried compound heterozygous mutations in MYBPC3 or TNNT2. The frequency of patients carrying the MYBPC3, MYH7, and TNNT2 mutations were 19.6%, 10.7%, and 8.9%, respectively, and the most frequently affected genes in the northeastern and southwestern parts of Japan were MYBPC3 and MYH7, respectively. Several mutations were found in multiple unrelated proband patients, for which the geographic distribution suggested founder effects of the mutations. CONCLUSIONS: This study demonstrated the frequency and distribution of mutations in a large cohort of familial HCM in Japan.

Usefulness of high-sensitive cardiac troponin T for evaluating the activity of cardiac sarcoidosis.

Since early intervention using corticosteroids improves prognosis in some patients with cardiac sarcoidosis, early and accurate diagnosis of this clinical condition is important. However, it is still not easy to evaluate the activity of cardiac sarcoidosis in clinical practice. The aim of this study was to determine whether high-sensitive cardiac troponin T (hscTnT) is useful as an additional parameter to standard assessment in patients with cardiac sarcoidosis. Twelve patients who were diagnosed as having cardiac sarcoidosis at our institution were retrospectively studied. Evaluation of patients included clinical examinations, electrocardiography, echocardiography, 67-gallium-citrate (Ga) scintigraphy, 18F-fluoro2-deoxyglucose positron emission tomography (18F-FDG PET) and laboratory data including hs-cTnT, angiotensin-converting enzyme (ACE), lysozyme and B-type natriuretic peptide (BNP). The activity of cardiac sarcoidosis was judged mainly by using 18F-FDG PET. Localized uptake of 18F-FDG, which was considered to be active cardiac sarcoidosis, was seen in 8 patients. Based on the findings of 18F-FDG PET, hs-cTnT was considered to be a reliable parameter: sensitivity and specificity were 87.5% and 75.0%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) were 87.5% and 75.0%, respectively. On the other hand, these values in lysozyme and BNP markers were not as high as those in hs-cTnT. Although an ACE marker and Ga-67 scintigraphy showed specificity and PPV of 100%, both sensitivity and NPV were less than 50%. Furthermore, hs-cTnT levels decreased after steroid therapy in some patients. Hs-cTnT seems to be a useful marker for evaluating the activity of cardiac sarcoidosis.

Very long-term prognosis in patients with hypertrophic cardiomyopathy: a longitudinal study with a period of 20 years.

AIMS: We aim to clarify the prognosis on patients with hypertrophic cardiomyopathy (HCM) for a follow-up period of more than 10 years. METHODS AND RESULTS: We retrospectively analysed 102 consecutive patients with HCM diagnosed by 31 December 2000. Complete and detailed clinical records were obtained for 93 (91%) of the 102 patients. Sixty-three (68%) of the 93 patients were men, and the mean age of the patients at the initial evaluation was 51.5 ± 13.0 years. During the mean follow-up period of 19.6 ± 8.1 years (median 20.1 years), HCM-related deaths occurred in 20 patients (21% [1.1%/year]). HCM-related adverse events (including HCM-related deaths and nonfatal HCM-related events: hospitalization for heart failure, embolic stroke admission, and sustained ventricular tachycardia with haemodynamic instability or appropriate implantable cardioverter-defibrillator discharge) occurred in 45 patients (48%). The first HCM-related adverse events occurred in approximately 20% of the patients in every decade, the first decade to the third decade, from the initial evaluation. Forty-seven patients (51%) had documentation of atrial fibrillation at the last follow-up. There were seven patients in the end-stage HCM group at the initial evaluation, and 22 patients (24%) had progression to end-stage HCM during the follow-up period. CONCLUSIONS: In our cohort of patients, HCM-related mortality was relatively favourable. However, approximately half of the patients suffered from HCM-related adverse events during the follow-up period of 20 years. It is important for HCM patients to be carefully followed up over the long-term because HCM is a lifelong disease.

Combined measurements of cardiac troponin I and brain natriuretic peptide are useful for predicting adverse outcomes in hypertrophic cardiomyopathy.

BACKGROUND: Although serum cardiac troponin I (cTnI) and plasma brain natriuretic peptide (BNP) have become clinically important tools as diagnostic and prognostic markers for ischemic heart disease and heart failure, the usefulness of these biomarkers for risk stratification of hypertrophic cardiomyopathy (HCM) is not clear. METHODS AND RESULTS: We studied 167 patients with HCM, and cTnI and BNP were measured. During follow-up (38.5 months), 20 patients suffered from cardiovascular events: HCM-related deaths in 6, hospitalization for heart failure in 8, embolic stroke in 5 and 1 patient with spontaneous sustained ventricular tachycardia. Patients with high cTnI values (≥0.04 ng/ml) had more frequent cardiovascular events than did those with low cTnI values (P=0.008). Similarly, there were more frequent adverse events in the high BNP group (≥200 pg/ml) than in the low BNP group (P=0.002). When groups were allocated according to both cTnI and BNP measurements, serum cTnI used in conjunction with BNP further improved the prognostic value; patients with both high cTnI and BNP values had an 11.7-fold increased risk of cardiovascular events compared with those with both low cTnI and BNP values. CONCLUSIONS: CTnI and BNP are useful parameters for identifying patients at risk for clinical deteriorations, and combined measurements of these biomarkers further improves the prognostic value of increased cardiovascular events in HCM.

Genetic screening and double mutation in Japanese patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal-dominant pattern of inheritance mainly caused by single heterozygous mutations in sarcomere genes. Although multiple gene mutations have recently been reported in Western countries, clinical implications of multiple mutations in Japanese subjects are not clear. METHODS AND RESULTS: A comprehensive genetic analysis of 5 sarcomere genes (cardiac ß-myosin heavy chain gene [MYH7], cardiac myosin-binding protein C gene [MYBPC3], cardiac troponin T gene [TNNT2], α-tropomyosin gene [TPM1] and cardiac troponin I gene [TNNI3]) was performed in 93 unrelated patients and 14 mutations were identified in 28 patients. Twenty-six patients had single heterozygosity (20 in MYBPC3, 4 in MYH7, 1 in TNNT2, 1 in TNNI3), whereas 2 proband patients with familial HCM had double heterozygosity: 1 with P106fs in MYBPC3 and R869C in MYH7 and 1 with R945fs in MYBPC3 and E1049D in MYH7. From the results of the family survey and the previous literature on HCM mutations, P106fs, R945fs and R869C seemed to be pathological mutations and E1049D might be a rare polymorphism. The proband patient with P106fs and R869C double mutation was diagnosed as having HCM at an earlier age (28 years of age) than her relatives with single mutation, and had greater wall thickness with left ventricular outflow obstruction. CONCLUSIONS: One double mutation was identified in a Japanese cohort of HCM patients. Further studies are needed to clarify the clinical significance of multiple mutations including phenotypic severity.

Importance of Paroxysmal Atrial Fibrillation and Sex Differences in the Prevention of Embolic Stroke in Hypertrophic Cardiomyopathy.

Background: Although atrial fibrillation (AF) is a well-known risk factor for embolic stroke in hypertrophic cardiomyopathy (HCM), there is a paucity of information derived from HCM patients who have experienced embolic stroke. Methods and Results: From 141 consecutive HCM patients who had been hospitalized between 2000 and 2018, the clinical characteristics and management of 86 patients with AF were analyzed retrospectively. The incidence of embolic stroke was 36% (n=31 patients). The median (interquartile range) age of embolic stroke was younger in male than female HCM patients (71 [64-80] vs. 83 [77-87] years, respectively; P=0.009). The prevalence of paroxysmal AF (74%) was significantly higher than that of chronic AF (26%) in 31 patients with embolic stroke (P=0.007). The CHADS2 score in patients with embolic stroke was not particularly useful in predicting the occurrence of embolic stroke. Conclusions: One-third of HCM patients with AF developed embolic stroke, and male HCM patients were younger at the time of the embolic stroke than female HCM patients. The prevalence of paroxysmal AF was significantly higher than that of chronic AF in patients with AF and embolic stroke. Early introduction of anticoagulation therapy is recommended at the first documentation of paroxysmal AF.

Clinical significance of new-onset atrial fibrillation in patients with hypertrophic cardiomyopathy.

AIMS: There is limited information about the clinical significance of atrial fibrillation (AF), particularly new-onset AF, in patients with hypertrophic cardiomyopathy (HCM) in a community-based patient cohort. This study was carried out to clarify the prevalence and prognostic impact of AF in Japanese HCM patients. METHODS AND RESULTS: In 2004, we established a cardiomyopathy registration network in Kochi Prefecture as a prospective study, and finally, 293 patients with HCM were followed. In the patients' cohort, we recently reported the clinical outcomes including mortality and HCM-related morbid events. HCM-related adverse cardiovascular events were defined in the following: (i) sudden cardiac death (SCD)-relevant events including SCD, spontaneous sustained ventricular tachycardia, and appropriate implantable cardioverter defibrillator discharge; (ii) heart failure (HF) events with the composite of HF death and hospitalization for HF; and (iii) embolic events included embolic stroke-related death and admission for embolic events. In the present study, we focused on AF and conducted a detailed investigation. At registration, the mean age of the patients was 63 ± 14 years, and 86 patients (29%) had documented AF including paroxysmal AF. Patients with AF at registration were characterized by worse clinical profiles including more advanced age, more symptomatic, more advanced left ventricular, and left atrial remodelling at registration. During a mean follow-up period of 6.1 ± 3.2 years, a total of 77 HCM-related adverse events occurred, and the presence of AF at registration was associated with an increased risk of HCM-related adverse events, particularly heart failure events. During the follow-up period, an additional 31 patients (11%) had documentation of AF for the first time, defined as new-onset AF, with an annual incidence of approximately 1.8%, and finally, a total of 117 patients (40%) showed AF. The presence of palpitation and enlarged left atrial diameter, particularly left atrial diameter ≥50 mm, at registration were significant predictors of new-onset AF. Importantly, the incidence of overall HCM-related adverse events was further higher in patients with new-onset AF observed from AF onset than in patients with AF at registration. CONCLUSIONS: In our HCM registry in an aged Japanese community, a significant proportion developed AF. The presence of AF, particularly new-onset AF, was associated with increased incidence of HCM-related events. AF may not be just a marker of disease stage but an important trigger of adverse events.

Impact of metalloproteinases on left ventricular remodeling and heart failure events in patients with hypertrophic cardiomyopathy.

BACKGROUND: The impact of matrix metalloproteinase (MMP) on left ventricular (LV) remodeling and heart failure events is unresolved in patients with hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: Plasma levels of MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and clinical findings and heart failure events were evaluated in 41 HCM patients, including 8 with LV systolic impairment. Plasma B-type natriuretic peptide (BNP) levels were also measured. MMP-2 levels in patients with severe symptoms were higher than that in those with no or mild symptoms. The levels of MMP-2 and TIMP-1 were positively related to LV end-systolic and left atrial dimensions, and inversely related to LV ejection fraction. MMP-2 levels were positively related to BNP levels (r=0.52, P=0.0009). However, MMP-9 levels were not related to echocardiographic parameters and plasma BNP levels. Six patients had complicated heart failure events during the follow-up period of 3.2+/-0.7 years. Patients with high plasma MMP-2 levels (>1,170 ng/ml) revealed a poorer prognosis than those with low MMP-2 levels. CONCLUSIONS: Elevated levels of MMP-2 were related to LV remodeling and poor prognosis in patients with HCM. These results suggest that regulation of the extracellular collagen matrix might be one of the therapeutic targets in patients with HCM.

A Novel Disease Entity in Search of Its Own Identity　- Takotsubo Syndrome. Is It Really "Cardiomyopathy"?

Background: The term "takotsubo cardiomyopathy" is commonly used in clinical practice. However, there is conceptual problem with the term "cardiomyopathy" in this context because "cardiomyopathy" implies a primary and chronic myocardial disease of unknown etiology. In this study we reviewed the literature related to takotsubo cardiomyopathy to investigate whether it is appropriate to use the term "cardiomyopathy" for this condition. Methods and Results: A literature review revealed that this condition was originally described in 1990 in Japan as postischemic myocardial stunning with unique left ventricular apical ballooning and that it gradually gained global attention thereafter. Subsequently, the term "takotsubo cardiomyopathy" was introduced to describe this heart failure phenotype. However, this term has been called into question because several recent studies investigating the mechanism underlying this condition have provided evidence of myocardial ischemia possibly due to microvascular dysfunction. The term "takotsubo syndrome" was suggested to describe this microvascular acute coronary syndrome, which is in agreement with the original description of the condition as myocardial stunning following acute myocardial ischemia. Conclusions: Based on the accumulating evidence of acute myocardial ischemia due to microvascular dysfunction as the mechanism underlying this condition, in addition to the fact that the term "cardiomyopathy" literally implies a primary and chronic myocardial disease, it is advisable that the term "takotsubo syndrome" is used until the etiology and underlying mechanism of this condition are fully clarified.

Elevation of high-sensitivity cardiac troponin T and left ventricular remodelling in hypertrophic cardiomyopathy.

AIMS: Hypertrophic cardiomyopathy (HCM) is generally associated with mild disability and normal life expectancy. On the other hand, once the end-stage phase of HCM characterized by left ventricular (LV) ejection fraction < 50% is established, patients with this subtype have a poor prognosis. This study clarifies the clinical parameters associated with progression to end-stage HCM. METHODS AND RESULTS: We retrospectively studied 157 HCM patients (age 59.9 ± 14.2 years, 104 men) with preserved LV systolic function in whom subsequent echocardiographic data were obtained for a period of >1 year. HCM progressed to end-stage HCM in 13 patients (8.3%) of the 157 patients during a mean follow-up period of 6.3 ± 2.8 years. Compared with patients who did not reach end-stage HCM at the last evaluation, patients with progression to the end-stage phase had lower ejection fraction, larger LV size, more enlarged left atrial diameter, longer follow-up period, and higher frequency of an elevated concentration of high-sensitivity cardiac troponin T (hs-cTnT; >0.014 ng/mL) at registration. Multivariate analysis revealed that elevated hs-cTnT was a significant predictor independent of lower LV ejection fraction for progression to end-stage HCM. Furthermore, in patients with elevated hs-cTnT levels, LV ejection fraction became significantly lower, LV end-diastolic diameter increased, and LV wall thickness decreased during the follow-up period, whereas those parameters did not change in the normal hs-cTnT group. CONCLUSIONS: In patients with HCM, an elevated hs-cTnT was associated with progression of LV remodelling, and this biomarker can be useful for predicting progression to the end-stage phase.

Sudden Cardiac Death-Relevant Events of Hypertrophic Cardiomyopathy in a Regional Japanese Cohort　- Results From the Kochi RYOMA Study.

Background: Sudden cardiac death (SCD) is a most devastating complication of hypertrophic cardiomyopathy (HCM). The aim of this study was to clarify the clinical features of HCM in patients who experienced SCD-relevant events in an aged Japanese community. Methods and Results: In 2004, we established a cardiomyopathy registration network in Kochi Prefecture, and herein report on 293 patients with HCM who are followed as part of the registry. The mean (±SD) age at registration and diagnosis was 63±14 and 56±16 years, respectively. SCD-relevant events occurred in 19 patients during a mean follow-up period of 6.1±3.2 years (incidence rate 1.0%/year): sudden death in 9 patients, successful recovery from cardiopulmonary arrest in 4 patients, and appropriate implantable cardioverter-defibrillator discharge in 6 patients. At registration, 13 patients were in the dilated phase of HCM (D-HCM). During the follow-up period, HCM developed to D-HCM in 21 patients; thus, 34 patients in total had D-HCM. Multivariate analysis revealed that D-HCM at registration or during follow-up and detection of non-sustained ventricular tachycardia (NSVT) during follow-up were significant predictors of SCD-relevant events. Conclusions: In this HCM population in an aged Japanese community, the annual rate of SCD-relevant events was 1.0%. HCM developed to D-HCM in a considerable number of patients, and D-HCM and NSVT were shown to be independently associated with an increased risk of SCD-relevant events.