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Scarring of the left atrial (LA) wall from atrial ablation (AF) leads to the development of stiff LA syndrome. Multiple ablation treatments have been considered to be associated with the development of LA calcification (LAC). We report a case of wild-type transthyretin cardiac amyloidosis (CA) who presented with worsening heart failure due to stiff LA syndrome despite the condition after initial ablation for AF. The case had LAC along the ablation point, a reduced LA reservoir strain by echocardiography, and a characteristic pulmonary artery wedge pressure waveform with markedly elevated v wave by right cardiac catheter examination consistent with stiff LA syndrome. Notably, in patients with CA, there may be a causal relationship between ablation for AF and LAC and development of stiff LA syndrome. When we encounter patients with worsening heart failure with CA after AF ablation, we should pay additional attention to stiff LA syndrome. • In the case of worsening heart failure in patients who have undergone left atrial (LA) catheter ablation, the possibility of stiff LA syndrome due to calcification of the LA should be considered. • A detailed assessment of hemodynamics by echocardiography and right heart catheterization is useful for diagnosis of stiff LA syndrome. • In patients with cardiac amyloidosis treated with radiofrequency catheter ablation for atrial fibrillation, additional attention should be given to calcification of the LA and stiff LA syndrome. [ABSTRACT FROM AUTHOR]

The relationships between electrocardiography (ECG) findings and echocardiographic profiles in patients with hypertrophic cardiomyopathy (HCM) are not fully understood. One hundred forty patients (mean age: 62.9 ± 15.3 years, 96 men) with HCM were studied. We assessed the associations between ECG findings and echocardiographic findings including maximum left ventricular wall thickness, HCM subtypes and distribution of left ventricular hypertrophy (LVH): the LV was divided into basal, mid, and apical segments by dividing it into thirds along the long axis. In ECG, LVH by voltage criteria, abnormal Q wave, negative T wave, and giant negative T wave (GNT) were observed in 74 (53 %), 30 (21 %), 132 (94 %), and 25 (18 %) of the patients, respectively. In two groups with and without an LVH pattern according to voltage criteria in ECG, there were no significant differences in maximum LV wall thickness, subtype of HCM, and distribution of LVH. Regarding an abnormal Q wave, the proportion of patients with LVH in the basal segment was significantly higher in patients with an abnormal Q wave than in patients without an abnormal Q wave (87 % vs 61 %, p = 0.008). An abnormal Q wave was not observed in patients with LVH confined to the apex. Patients with a GNT included patients with LVH located at only the apex (apical HCM), LVH from the mid segment to apex, and LVH from the base to apex. No GNT was found in patients with hypertrophy located in the upper region from the base to mid segment of the LV. In patients with HCM, there was no significant correlation between the presence of LVH by voltage criteria in ECG and echocardiographic findings. An abnormal Q wave was associated with disproportionate hypertrophy of the basal wall and a GNT reflected the presence of LVH in the apical segment. [Display omitted] • The relationships between electrocardiographic (ECG) findings and echocardiographic findings in hypertrophic cardiomyopathy • No correlation between the presence of left ventricular hypertrophy (LVH) in ECG and echocardiographic findings. • Q wave was associated with disproportionate hypertrophy of the basal wall. • A giant negative T wave reflected the presence of LVH in the apical segment. [ABSTRACT FROM AUTHOR]

• The use of genetic testing in routine practice is presently limited in Japan. • A genetic diagnosis is useful for early diagnosis through cascade genetic screening in the family, differentiating secondary cardiomyopathies and predicting prognosis. • It is necessary to develop an ethnicity-specific genetic database of cardiomyopathy, including a catalog of variants with well-evaluated pathogenicity. Although many causative genes for primary cardiomyopathy have been identified, the use of genetic testing in routine practice is limited in Japan presently. Genetic diagnosis has been reported to be useful for early diagnosis through cascade genetic screening in the family, differentiating secondary cardiomyopathies, and predicting prognosis in some patients; nonetheless, the acquisition of genetic information for cardiomyopathy is stagnating in actual clinical practice. There seem to be a number of reasons for this phenomenon, and although the use of next-generation sequencers has resolved some of the past issues, the importance of pathogenicity studies of variants that are identified is growing. To ensure that patients with cardiomyopathy and their relatives can receive precision medicine, the results of genetic analysis linked to clinical information need to be collected, and a database of variants in Japanese people needs to be established. [Display omitted] [ABSTRACT FROM AUTHOR]

The current state of knowledge related to disease management of heart failure (HF) and information coordination practices provided by non-physician healthcare professionals such as nurses and therapists working at home-visit nursing stations in Japan are not well known. A questionnaire survey of healthcare professionals working at home-visit nursing stations was conducted in Kochi Prefecture. Data collected from 151 nurses and therapists were analyzed. Regarding the basic characteristics of the respondents, the majority were in their 30s and 40s, and approximately 75 % were nurses. In terms of HF knowledge, 53.7 % of respondents said that they "knew" about the New York Heart Association classification. A total of 40.0 % of respondents said that they were "aware of the existence of the HF handbook", and only 29.3 % of respondents said that they "knew" the classification of HF stages. When they were asked about their level of satisfaction related to all medical information provided by the hospital and hospital wards, no one was "very satisfied", and the most common response (66.2 %) was "not very satisfied". In the essential medical information that respondents wanted to obtain from hospitals and hospitals wards for managing HF patients at home, "medication at discharge", "current medical history", "fluid intake and restrictions", "symptoms, signs, and response to exacerbation", and "ideal body weight" were the top five contents. In the cross-sectional study targeted healthcare professionals working at home-visit nursing stations in Kochi Prefecture, the current state of knowledge related to HF and information coordination practices among healthcare professionals were not fully satisfactory in HF management. It is necessary to increase educational opportunities regarding HF for them and further promote information sharing. [Display omitted] • A questionnaire survey at home-visit nursing stations regarding heart failure (HF) management • Of the respondents, 40 % recognized the existence of the HF handbook. • Fewer than 30 % of the respondents knew the classification of HF stages. • Information coordination practices were not fully satisfactory in HF management. [ABSTRACT FROM AUTHOR]

Limited data are available regarding therapies for hypertrophic cardiomyopathy (HCM). This study assessed the prevalence, clinical characteristics, and treatment patterns of HCM in Japan. This retrospective database study analyzed data from 438 hospitals in the Japan Medical Data Vision database from 2016 to 2020. We identified 3913 patients (15 %) with obstructive HCM (oHCM) and 21,714 patients (85 %) with nonobstructive HCM (nHCM). The estimated total number of patients with oHCM and nHCM in 2020 among Japanese hospitals was 8500 and 43,500, respectively. The prevalence of oHCM and nHCM steadily increased by 27 % and 12 %, respectively, from 2016 to 2020, with a 1:5.2 ratio of oHCM to nHCM in 2020. The mean age of the oHCM and nHCM populations was 72 and 70 years, respectively, and comorbidities included atrial fibrillation (AF) (oHCM, 33.8 %; nHCM, 32.2 %), other arrythmia (30.1 %; 27.6 %), and stroke (16.6 %; 16.4 %). Furthermore, 45.0 % of oHCM and 37.7 % of nHCM patients had undergone at least one hospitalization. A substantial number of HCM patients aged between 20 and 59 years reported AF (oHCM, 17–37 %; nHCM, 4–24 %) and stroke (oHCM, 0–12 %; nHCM, 3–10 %). β-blockers (oHCM, 64.0 %; nHCM, 42.1 %) were the most frequently prescribed treatment, followed by Na channel blockers (29.5 %; 5.7 %), calcium channel blockers (18.1 %; 8.8 %), direct oral anticoagulants (14.5 %; 15.2 %), and warfarin (11.0 %; 11.4 %). This study provides important information on the current epidemiological and clinical characteristics of HCM in Japan. [Display omitted] • Patients with hypertrophic cardiomyopathy in Japan have increased 2-fold since 1999. • The ratio of obstructive and nonobstructive hypertrophic cardiomyopathy was 1:5.2. • The prevalence of atrial fibrillation was 32–33 %. • Around 16 % of patients experienced stroke. • Substantial numbers of patient <40-years-old had atrial fibrillation and stroke. [ABSTRACT FROM AUTHOR]

The prevalence of Fabry disease (FD) in male patients with left ventricular hypertrophy (LVH) is about 1%. From the perspective of performing more efficient screening with measurement of α-galactosidase (α-Gal) activity, it is important to raise the pretest probability. We retrospectively investigated the prevalence of FD in 701 male patients with LVH who already had been screened by measurement of α-Gal activity in eight hospitals. From the viewpoint of enzymatic screening, we validated previously reported clinical features of FD including the electrocardiographic and echocardiographic characteristics with comparing each clinical determinant between patients with FD and non-FD patients. We finally aimed to establish a new screening approach for the detection of patients at high risk of FD. There were five FD patients (0.7%) in the 701 male patients with LVH. Those five patients with FD all had the cardiac variant type and age at detection of LVH was ≥35 years in all patients. In LVH patients with LV ejection fraction (EF) ≥ 50%, Pend-Q interval < 40 msec, SV1 + RV5 > 4.0 mV, and diffuse LVH were important determinants of FD. In LVH patients with LVEF < 50%, asymmetric septal hypertrophy and posterior wall motion abnormality seemed to be associated with FD. In our retrospective study, the prevalence of FD in male patients with LVH was found to be 0.7%. We established the efficient combinations of clinical determinants using age at detection of LVH, Pend-Q interval, high voltage, and LVH pattern in an echocardiogram. [Display omitted] • A retrospective study to establish new screening approach for Fabry disease in left ventricular hypertrophy (LVH) • Of the 701 male patients with LVH screened by enzyme activity, 0.7% had Fabry disease. • All five patients with Fabry disease had the cardiac variant type with late-onset. • Pend-Q interval, high voltage, and LVH morphology were important in detecting Fabry disease. [ABSTRACT FROM AUTHOR]

• We validated the Kumamoto criteria for prediction of technetium-99m pyrophosphate (99mTc-PYP) positivity. • The Kumamoto criteria were useful to predict 99mTc-PYP positivity in our cohort. • Notably, high-sensitivity cardiac troponin T ≥0.0308 ng/ml had a high potential to predict 99mTc-PYP positivity. Early diagnosis of transthyretin cardiac amyloidosis (ATTR-CA) is important. The aim of this study was to validate the 'Kumamoto criteria' for prediction of technetium-99m pyrophosphate (99mTc-PYP) scintigraphy positivity. One hundred fifty patients (median age: 79.4 years, 117 males) with the possibility of ATTR-CA who underwent 99mTc-PYP scintigraphy were assessed. We divided the patients into 4 groups (groups with score of 0–3) according to the Kumamoto criteria by total points for the following 3 factors: high-sensitivity cardiac troponin T (hs-cTnT) ≥0.0308 ng/ml, left ventricle posterior wall thickness ≥13.6 mm, and wide QRS (QRS ≥ 120 ms). Seventy patients (46.7%) were positive for 99mTc-PYP scintigraphy. 99mTc-PYP positivity rates in the groups with score of 0, 1, 2, and 3 were 4%, 39%, 69%, and 89%, respectively. Compared with the original Kumamoto cohort, our patients in the score 1 group showed a relatively high rate of 99mTc-PYP positivity because hs-cTnT as one of the positive factors had high ability to discriminate the disease. The sensitivity and negative predictive value of hs-cTnT ≥0.0308 ng/ml for 99mTc-PYP positivity were 97.1% and 93.9%. In the Kochi validation cohort, the Kumamoto criteria were useful for predicting 99mTc-PYP positivity. However, patients in the score 1 group should be assessed cautiously for the possibility of ATTR-CA if the hs-cTnT value is high. [ABSTRACT FROM AUTHOR]

Echocardiography is useful for making a diagnosis of atrial septal defect (ASD) by directly visualizing the shunt flow. Herein, we present a case in which a single ostium secundum type ASD masqueraded as multiple defects on color flow imaging by transthoracic echocardiography. We confirmed by transesophageal echocardiography that this patient actually had a single ASD. An echocardiographic refraction artifact was considered to be the cause of this phenomenon. We need to be aware of the existence of this artifact to avoid misdiagnosis. 〈 Learning objective: Echocardiography is useful for making a diagnosis of atrial septal defect (ASD). We present the case with a single ostium secundum type ASD which masqueraded as multiple defects on color flow imaging due to a refraction artifact. Refraction artifacts can make multiple false flow signals on color imaging. This case emphasizes the importance of an understanding of the existence of this artifact in not only B mode imaging but also color Doppler imaging.〉 [ABSTRACT FROM AUTHOR]

99mTechnetium pyrophosphate (99mTc-PYP) scintigraphy has shown utility for diagnosis of transthyretin (ATTR) cardiac amyloidosis with a high sensitivity and specificity. However, in clinical practice, a protocol and a method of analysis of this modality are not yet unified. We present a case of ATTR cardiac amyloidosis showing a positive cardiac uptake in planar imaging but no myocardial uptake in single-photon emission computed tomography/computed tomography (SPECT/CT) fusion imaging on 99mTc-PYP scintigraphy. We considered this tracer accumulation in the cardiac blood pool to be an inconclusive study. In this report, we focus on an inconclusive study case as a potential pitfall of 99mTc-PYP scintigraphy and discuss the interpretation of 99mTc-PYP scintigraphy findings with using both planar and SPECT/CT imaging for improvement of diagnostic accuracy for ATTR cardiac amyloidosis. < Learning objective: The present report describes the importance of distinguishing myocardial uptake from the cardiac blood pool by both planar and single-photon emission computed tomography/computed tomography fusion imaging on 99mtechnetium pyrophosphate (99mTc-PYP) scintigraphy for diagnosis of transthyretin cardiac amyloidosis. To improve diagnostic accuracy, the 99mTc-PYP scintigraphy protocol including the method of evaluation and interpretation of the findings should be unified.> [ABSTRACT FROM AUTHOR]

• Diagnosing wild-type transthyretin cardiac amyloidosis (ATTRwt) is challenging. • High-sensitivity cardiac troponin T and 99mTc-pyrophosphate scintigraphy are important diagnostic modalities. • An integrated diagnostic approach increases the diagnostic rate of ATTRwt. • This combined approach has high potential to identify ATTRwt with atypical phenotype. The diagnosis of wild-type transthyretin cardiac amyloidosis (ATTRwt) is frequently missed or delayed because of the limited specificity of manifestations. We investigated the utility of combined assessment of high-sensitivity cardiac troponin T (hs-cTnT) measurement and 99mTc-pyrophosphate (99mTc-PYP) scintigraphy as diagnostic modalities in ATTRwt. We divided 39 consecutive ATTRwt patients into two groups depending on whether serum hs-cTnT measurement and 99mTc-PYP scintigraphy were adopted as diagnostic tools: group A patients (n = 8) who were diagnosed before the introduction of these two tools and group B patients (n = 31) who were diagnosed after the introduction of the two tools. We retrospectively evaluated the two groups. Diagnostic yield was higher in group B than in group A (1.2 vs. 5.4 ATTRwt patients per 1000 hospitalized patients, p < 0.01). Group B patients presented broad clinical features that were different from group A patients with classical characteristics. Atrial fibrillation was more frequent (12.5% vs. 58.1%, p = 0.044) and inter-ventricular septum (IVS) thickness and relative wall thickness (RWT) were smaller in group B patients than in group A patients (IVS thickness: 16.1 ± 2.4 mm vs. 13.6 ± 2.8 mm, p = 0.023; RWT: 0.71 ± 0.11 mm vs. 0.58 ± 0.13 mm, p = 0.014). Furthermore, left ventricular hypertrophy (LVH) (IVS thickness ≥15 mm) was more frequent in patients in group A than in patients in group B (87.5% vs. 33.3%, p = 0.013). No significant difference was observed in the mean value of left ventricular ejection fraction (LVEF), whereas the dispersion of LVEF was high in group B (interquartile range: 47–58% vs. 39–57%). An integrated approach consisting of hs-cTnT measurement and 99mTc-PYP scintigraphy significantly increases the diagnostic rate of ATTRwt and has a high potential to identify ATTRwt patients with a variety of clinical phenotypes. [ABSTRACT FROM AUTHOR]

• Serum angiotensin-converting enzyme (ACE) levels are decreased by ACE inhibitors. • Three-fourths of Japanese patients with sarcoidosis have normal ACE values (<25.0 IU/L). • The possibility of sarcoidosis cannot be ruled out with the current standard value. • The sensitivity to detect sarcoidosis increases using the cut-off value of 17.7 IU/L. • Careful interpretation of this biomarker is needed. In clinical practice, we frequently experience patients with sarcoidosis who show relatively high but normal values of angiotensin-converting enzyme (ACE). The objective of this study was to reconsider the cut-off value of ACE. We studied 79 Japanese patients who were diagnosed as having sarcoidosis at our hospital. We excluded patients who had taken steroids or ACE inhibitors and patients with renal impairment. We respectively evaluated ACE values and performed receiver operating characteristic (ROC) analysis from a comparison with data for 299 normal Japanese subjects who showed ACE values in the current Japanese standard normal range (7.0–25.0 IU/L). Patients with sarcoidosis had higher ACE values than those in normal subjects (ACE: 20.3 IU/L [IQR, 16.0–24.4] vs. 15.4 IU/L [IQR, 12.8–18.5]; p < 0.001). However, 62 patients (78.5%) had normal ACE levels (cut-off value <25.0 IU/L), and the sensitivity of ACE level for detecting sarcoidosis was only 21.5%. From ROC analysis, a cut-off value of 17.7 IU/L (AUC: 0.727, 95% CI: 0.660–0.794, p < 0.001) was the best cut-off value for detecting sarcoidosis and sensitivity increased to 67.0%. The possibility of sarcoidosis cannot be ruled out by using the current Japanese standard value even in patients who have normal ACE levels. Careful interpretation of this biomarker is needed. [ABSTRACT FROM AUTHOR]

Objective Although several studies have demonstrated that noncardiac surgery in patients with hypertrophic cardiomyopathy (HCM) is safe, the long-term outcomes remain unclear. Therefore, the authors investigated the postoperative long-term outcomes of patients with HCM who underwent noncardiac surgery at their hospital. Design Retrospective review. Setting Single university hospital. Participants Seventy-two consecutive patients with HCM who underwent noncardiac surgery. Intervention No intervention. Measurements and Main Results The incidence of HCM-related events during the patient's hospital stay were evaluated as the short-term outcomes, and HCM-related events after discharge were evaluated as the long-term outcomes. HCM-related events were defined as sudden death, implantable cardioverter-defibrillator discharge with successful recovery from cardiopulmonary arrest, death due to heart failure, hospitalization for heart failure, myocardial infarction, and thrombosis caused by atrial fibrillation. The median postoperative follow-up was 1,382 days (3.8 years). Short-term mortality and morbidity rates were both 1.3%, whereas long-term mortality and morbidity rates were 4.2% and 15%, respectively. The 5-year event-free rate was 76%, whereas the postoperative HCM-related mortality rate was 4.2%. Conclusions This study suggests that noncardiac surgery in patients with HCM is safe in terms of both short- and long-term outcomes. To confirm the findings, additional studies, such as prospective, multicenter, observational studies, should be conducted. [ABSTRACT FROM AUTHOR]

Background Intravascular hemolysis has been reported in patients with cardiac valve prostheses, but intravascular hemolysis in patients with mitral regurgitation with native valve has not been evaluated in detail. We designed a study to elucidate the impact of regurgitation flow on intravascular hemolysis in patients with primary mitral regurgitation by measuring erythrocyte creatine. Methods Erythrocyte creatine was enzymatically assayed in 29 patients with moderate to severe primary mitral regurgitation and 12 age-matched healthy volunteers. The size and characteristics of mitral regurgitation were determined by color Doppler echocardiography. Results Erythrocyte creatine was significantly higher in patients with eccentric jet ( n = 17, 2.64 ± 0.77 μmol/g Hb) than that of central jet ( n = 12, 1.68 ± 0.13 μmol/g Hb) and control subjects (1.39 ± 0.25 μmol/g Hb). Patients with eccentric jet had a significantly lower erythrocyte count and hemoglobin (385 ± 58 x10 4 /μL and 116 ± 19 g/l) compared to those with central jet (450 ± 47 × 10 4 /μL and 137 ± 14 g/l) and control subjects (433 ± 31 × 10 4 /μL and 134 ± 19 g/l). There were no significant differences in age, estimated glomerular filtration rate, pulmonary artery systolic pressure, left atrial size and left ventricular end-diastolic dimension between patients with eccentric jet and central jet. Conclusions Intravascular hemolysis associated with subclincal anemia in patients with eccentric jet was due to the destruction of erythrocyte by collision of the eccentric jet to the atrial wall. [ABSTRACT FROM AUTHOR]

A 49-year-old man presented with flu-like symptoms of two weeks. Electrocardiogram showed diffuse ST elevation. Blood samples revealed severe renal failure and moderate inflammatory results. Echocardiogram showed large pericardial effusion, dilated inferior vena cava, but no right ventricular collapse. The patient underwent hemodialysis, after which he developed clinical signs of cardiac tamponade with echocardiographic features of collapse of the right ventricle. Pericardial drainage was then performed revealing purulent fluid of 800 ml. Streptococcus agalactiae was found in the cultures of urine, blood, and pericardial fluid. Despite removal of the pericardial fluid, echocardiogram failed to show any improvement in dilated inferior vena cava and estimated right atrial pressure remained elevated. Thus, a diagnosis of subacute effusive-constrictive pericarditis was made. Following antibiotic treatment for purulent pericarditis, early pericardiectomy was performed under transesophageal echocardiographic monitoring which successfully guided surgeons to careful removal of thick and adhesive visceral pericardium as well as an additional Waffle procedure resulting in significant clinical and hemodynamic improvement. Echo-guided approach is most practical in establishing the diagnosis of effusive-constrictive pericarditis and also most helpful in obtaining successful surgical results. < Learning objective: Diagnosis of effusive-constrictive pericarditis is difficult and is not often made because of mixtures of clinical findings associated with effusion/tamponade and constriction. Echo-guided approach is most practical in establishing the diagnosis by detecting absence of normalization in dilatation of the inferior vena cava after pericardial drainage. Also, since careful removal of visceral pericardium is mandatory, transesophageal echocardiographic monitoring during pericardiectomy plays an essential role in obtaining successful surgical results.> [ABSTRACT FROM AUTHOR]

Background The prevalence of Fabry disease (FD) in Japanese patients presenting with unexplained left ventricular hypertrophy (LVH) has remained unclear. Methods We measured plasma α-galactosidase A activity in 177 men with a diagnosis of hypertrophic cardiomyopathy (HCM) (maximum LV wall thickness ≥15 mm). Results Two patients (1.1%) showed very low α-galactosidase A activity [0.0 and 0.3 nmol/hr/ml (normal range: 3.6–17.6 nmol/hr/ml)], and a clinical diagnosis of cardiac variant of FD was finally made. One patient was a 55-year-old man who came to our hospital because of abnormal results of electrocardiography and showed concentric LVH in echocardiography. A missense mutation, R112L, was identified. The other was a 74-year-old man who had been diagnosed with HCM at the age of 60 years in another hospital and was referred for evaluation of repeated hospitalization for heart failure. Although echocardiography revealed asymmetric septal hypertrophy (ASH) with interventricular septal wall thickness of 16 mm and posterior wall thickness of 11 mm and reduced LV ejection fraction with hypokinetic posterior wall motion, his echocardiographic findings at the initial diagnosis of HCM were not ASH but concentric LVH with normal LV systolic function. A splicing mutation, IVS4+919G>A, was identified. Conclusions The prevalence of FD in Japanese male patients with a clinical diagnosis of HCM was found to be 1.1%. These patients showed late onset and concentric LVH at initial presentation. [ABSTRACT FROM AUTHOR]

Background Erythrocyte creatine, a marker of erythrocyte age that increases with shortening of erythrocyte survival, has been reported to be a quantitative and reliable marker for intravascular hemolysis. We hypothesized that hemolysis could also occur due to intraventricular obstruction in patients with hypertrophic cardiomyopathy (HCM). The purpose of this study was to examine the presence of subclinical hemolysis and the relation between intravascular hemolysis and intraventricular pressure gradient (IVPG). Methods and results We measured erythrocyte creatine in 92 HCM patients. Twelve patients had left ventricular outflow tract obstruction (LVOTO), 4 had midventricular obstruction (MVO), and the remaining 76 were non-obstructive. Erythrocyte creatine levels ranged from 0.92 to 4.36 μmol/g hemoglobin. Higher levels of erythrocyte creatine were associated with higher IVPG ( r = 0.437, p < 0.001). If erythrocyte creatine levels are high (≥1.8 μmol/g hemoglobin), subclinical hemolysis is considered to be present. Half of LVOTO patients and no MVO patients showed high erythrocyte creatine levels. Although non-obstructive patients did not show significant intraventricular obstruction at rest, some showed high erythrocyte creatine levels. When LVOT-PG was measured during the strain phase of the Valsalva maneuver in 20 non-obstructive patients, 7 of those 20 patients showed LVOTO. In the 20 patients, there was no relation between erythrocyte creatine levels and LVOT-PG before the Valsalva maneuver ( r = 0.125, p = 0.600), whereas there was a significant correlation between erythrocyte creatine and LVOT-PG provoked by the Valsalva maneuver ( r = 0.695, p = 0.001). Conclusions There is biochemical evidence of subclinical hemolysis in patients with HCM, and this hemolysis seems to be associated with LVOTO provoked by daily physical activities. [ABSTRACT FROM AUTHOR]

Background Although gender may be one of the important factors modifying phenotypic expression in hypertrophic cardiomyopathy (HCM), there has been little information on it. Methods and results We investigated gender differences in the clinical features of HCM caused by cardiac myosin-binding protein C gene ( MYBPC3 ) mutations. Sixty-one subjects (28 families) carrying MYBPC3 mutations were studied. Of the 61 subjects with MYBPC3 mutations, 50 patients including 23 female patients were phenotype-positive by echocardiography. Disease penetrance in subjects aged ≤40 years old was 92% in males and 67% in females. Females showed delayed onset of left ventricular hypertrophy compared with males in subjects who were genotype-positive. Female patients were more symptomatic at diagnosis than were males (mean New York Heart Association class: 1.7 ± 0.8 versus 1.2 ± 0.4, p = 0.012). From a longitudinal point of view by age, no significant gender difference in cardiovascular deaths or cardiovascular events was found. During the follow-up period after diagnosis of HCM (13 ± 8 years), female patients who were phenotype-positive had significantly more frequent heart failure events than did phenotypically affected male patients ( p = 0.028). Conclusions Although females with MYBPC3 mutations showed later onset of the disease, female patients were more symptomatic at diagnosis and had more frequent heart failure events once they had developed hypertrophy. [ABSTRACT FROM AUTHOR]

A 68-year-old man was admitted to our hospital for the further examination of intermittent claudication. He had been on continuous ambulatory peritoneal dialysis for 2 years. Screening transthoracic echocardiography (TTE) revealed a club-shaped tumor and a round-shaped tumor attached to mitral annulus calcification (MAC). The club-shaped tumor was swinging and plunged into the left ventricle at diastolic phase. Because of the risk of fatal embolism, we planned early surgical resection of the tumors. However, 13 days after admission, his intermittent claudication was getting worse and some part of the club-shaped tumor had vanished by TTE. Urgent iliac angiography showed that the tumor had embolized the right common iliac artery. Although we tried embolectomy using a Fogarty catheter, it was unsuccessful. We therefore treated the iliac artery stenosis by endovascular therapy and the procedure was successful. Three months later, he suffered from unstable angina and was treated by percutaneous coronary intervention. However, subacute stent thrombosis occurred after one month. After urgent treatment, we decided to treat him by coronary artery bypass graft and surgical resection of the residual tumor on MAC. The operation was performed successfully. Finally, the tumor was diagnosed as cardiac calcified amorphous tumor by its histologic features. < Learning objective: Cardiac calcified amorphous tumor (CAT) is a rare, non-neoplastic cardiac tumor. Mobile and pedunculated cardiac CAT is considered to be an important risk of systemic embolism. Based on our case and previous reports we reviewed cardiac CAT, especially MAC-related CAT, and it appears to be related to end-stage renal disease and may grow within a short duration. It is important to perform routine serial echocardiography for hemodialyzed patients in whom MAC has been identified.> [ABSTRACT FROM AUTHOR]

Background: Parenteral nutrition (PN) is indispensable for meeting the caloric and substrate needs of patients who cannot receive adequate amounts of enteral nutrition. However, PN decreases hepatic mononuclear cell (MNC) numbers and impairs their functions. We examined the effects of various ratios of ω-3 to ω-6 polyunsaturated fatty acids on hepatic MNC number and function in a murine model. We focused on serum liver enzymes, lipid metabolism, cytokine production, histopathology, and the outcomes of an intraportal bacterial challenge. Material and methods: In experiment 1, male Institute of Cancer Research mice were randomized to CHOW, 67%, 33%, 16%, 8%, 4%, and 0% fish oil (FO)-PN groups. After receiving their respective diets for 5 days, 1.0 × 107 Pseudomonas aeruginosa were delivered by intraportal injection. Survival was observed ≤7 days after injection. Liver histologies after intraportal bacterial challenge were examined in the CHOW, 33%, 8%, and 0% FO-PN groups. In experiment 2, the mice were divided into 4 groups: CHOW, 33%, 8%, and 0% FO-PN. After the mice had been fed for 5 days, MNC were isolated. Hepatic MNC were counted and cytokine productions (tumor necrosis factor [TNF]-α and interleukin [IL]-10) by MNC in response to lipopolysaccharide (LPS) were measured. Blood samples were analyzed for lipid metabolism and hepatobiliary biochemical parameters. Liver histologies were also examined. Results: In experiment 1, survival times were significantly shorter in the 4% and 0% FO-PN groups than in the CHOW group. Survival rates at 168 hours were 100%, 64%, 86%, 73%, 67%, 11%, and 13% in the CHOW, 67%, 33%, 16%, 8%, 4%, and 0% FO-PN groups, respectively. At 72 hours after intraportal bacterial challenge, the 0% FO-PN group showed severe tissue damage, whereas such damage was reduced in the 8% and 33% FO-PN groups. In experiment 2, the CHOW, 33%, 8%, and 0% FO-PN groups showed LPS dose-dependent increases in TNF-α levels. IL-10 levels were also LPS dose-dependently increased in the CHOW and 33% FO-PN groups. However, no marked changes were observed in response to LPS stimulation in either the 8% or the 0% FO-PN group. There were no differences in serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, or total bilirubin among these 4 groups. In the 0% FO-PN group, serum total cholesterol levels were greater than those in the 8% and 33% FO-PN groups. Without bacterial challenge, livers from the 0% FO-PN group showed steatosis, but these changes were attenuated in the 8% and 33% FO-PN groups. Conclusion: The 30–40% ratio of FO to soybean oil with 20% of total calories supplied by lipid seems to be the best PN for preservation of hepatic MNC number and function. [Copyright &y& Elsevier]

Background and purpose: Although serum tenascin-C (TN-C) levels are related to left ventricular (LV) remodeling in patients with myocardial infarction and are useful as a prognostic biomarker of heart failure in patients with dilated cardiomyopathy, the clinical significance of TN-C levels has not yet been studied in patients with hypertrophic cardiomyopathy (HCM). Therefore, the purpose of this study is to elucidate whether serum TN-C levels are a prognostic biomarker for heart failure in patients with HCM. Methods: The relationship between serum TN-C levels and heart failure events was studied in 36 patients with HCM during follow-up. Results: Levels of serum TN-C were 28 ± 13ng/ml (range 11-80ng/ml). Although patients with LV systolic impairment showed higher TN-C levels than those with preserved LV systolic function (33±11 ng/ml vs. 27±14ng/ml; p = 0.16), TN-C levels were not related to any echocardio-graphy parameters. During the follow-up period of 4.8 ±1.4 years, heart failure events were observed in six patients and TN-C levels in patients with events were higher than those in patients without events. Kaplan-Meier analysis showed that the prognosis was worse in patients with high TN-C levels (>39.2 ng/ml) than in those with low TN-C levels. Conclusions: Heart failure events were more frequently observed in patients with high serum TN-C levels than in those with low TN-C levels. Serum TN-C levels may be a new prognostic biomarker for heart failure in patients with HCM. [ABSTRACT FROM AUTHOR]

Background and purpose: Although it has been reported that matrix metalloproteinases (MMPs) are associated with left ventricular (LV) remodeling in patients with hypertrophic cardiomyopa-thy (HCM), the impact of plasma AAMP levels in patients with HCM is somewhat vague. Methods and subjects: Plasma levels of MMP-2, MMP-9, and clinical/echocardiographic findings were evaluated in 16 HCM patients with preserved LV ejection fraction (defined as LV ejection fraction more than 50%) caused by an identical frameshift mutation (S593fs: a one-base deletion of a thymidine at nucleotide 11,645) in the cardiac myosin-binding protein C gene. Results: MMP-2 levels were inversely related to LV ejection fraction (r2 = --37, p = 0.01). MMP-9 levels were inversely related to LV end-diastolic dimension (r2 = -0.24, p = 0.06) and posi-tively related to the maximum LV wall thickness (r2 =0.25, p = 0.04). During follow-up period of 4.1 ±1.2 years, LV ejection fraction decreased from 68.5±7.4% to 64.9±9% (p = 0.03). Among clinical, echocardiographic findings at baseline and levels of biomarkers, high MMP-9 levels were only related to the decrease of LV ejection fraction from baseline to follow-up (r2 =0.39, p = 0.009). Conclusions: MMP-2 levels are related to reduced LV systolic function in HCM patients with preserved LV ejection fraction caused by an identical cardiac myosin-binding protein C gene abnormality. On the other hand, MMP-9 levels are associated with small LV size and the degree of LV hypertrophy and related to the deterioration in LV systolic function during follow-up. These results suggest that MMPs are important in the process of LV remodeling in HCM. [ABSTRACT FROM AUTHOR]

Summary: Objectives: A few studies reported that some mutations in the cardiac myosin-binding protein C (MyBPC) gene were associated with dilated phase of hypertrophic cardiomyopathy (D-HCM) resembling dilated cardiomyopathy (DCM). We studied 5 unrelated cardiomyopathy probands caused by an identical mutation in the MyBPC gene. The results of clinical and genetic investigations in these patients are presented in this paper. Methods: We analyzed MyBPC gene in DCM patients as well as patients with HCM. Results: An R945fs/105 mutation, 2-base deletion at nucleotides 18,535 and 18,536, was identified in 4 of the 176 HCM probands and in 1 of the 54 DCM probands. Genetic analysis in relatives of those probands revealed another one member with this mutation. A total of 6 subjects had R945fs/105 mutation. The mean age of these six patients at diagnosis was 61 years. At initial evaluation, three of them were diagnosed as having HCM with normal left ventricular (LV) systolic function. The other two patients already had D-HCM. The remaining one patient was diagnosed as having DCM because of reduced LV systolic function (ejection fraction=31%) without increased LV wall thickness. During follow-up (7.6 years), all three patients with impaired LV systolic function were admitted for treatment of heart failure and/or sustained ventricular tachycardia. Finally, one patient with the diagnosis of D-HCM died of heart failure. Conclusions: The patients with this mutation may develop LV systolic dysfunction and suffer from cardiovascular events through mid-life and beyond. [Copyright &y& Elsevier]

Summary: Background: Mutations in the cardiac myosin-binding protein C gene (MYBPC3) have been reported to be associated with delayed expression of hypertrophic cardiomyopathy (HCM) and a relatively good prognosis. Purpose: The aim of this study was to evaluate clinical manifestations in patients with familial HCM caused by a novel nonsense mutation, S297X, in MYBPC3. Methods: We analyzed the sarcomere protein genes in 93 probands with HCM. Results: The nonsense mutation S297X in MYBPC3 was present in nine subjects from two unrelated families. Eight of those nine subjects with this mutation were found to be phenotype-positive and the remaining individual was not affected phenotypically. The age range at diagnosis was 9–75 years. There was no family history of sudden death in either family. At presentation, there were various left ventricular hypertrophy (LVH) patterns, including Maron type III hypertrophy from the LV base to apex, hypertrophy confined to the anterolateral wall at the basal LV wall. Two patients showed a significant LV outflow tract gradient and one patient showed intra-right-ventricular obstruction. During follow-up, one patient was repeatedly hospitalized for the treatment of heart failure after development of paroxysmal atrial fibrillation at the age of 86 years and the remaining eight subjects were in relatively stable condition and did not require hospitalization for the treatment of HCM-related events. Conclusion: The novel mutation S297X in MYBPC3 causes HCM in a broad range of ages and heterogeneous clinical manifestations, though the clinical course in patients with this mutation seems to be benign. [ABSTRACT FROM AUTHOR]

Summary: A 66-year-old woman was referred for further evaluation and treatment of normocytic and normochromic anemia with hemoglobin level of 8.6g/dL. A peripheral blood smear showed fragmented erythrocytes. The patient was then referred to the department of cardiology because of systolic murmur, ECG abnormality, and red cell fragmentation. Transthoracic echocardiography revealed hypertrophic cardiomyopathy with particularly increased interventricular septal thickness of 24mm and a hyperkinetic wall motion, resulting in marked obstruction to left ventricular outflow tract (pressure gradient of 200mmHg). Mitral regurgitation due to systolic anterior motion of the mitral valve leaflets was also seen. The cause of anemia was thought to be mechanical intravascular hemolysis due to left ventricular outflow tract obstruction and mitral regurgitation. She was treated with atenolol and the class Ia antiarrhythmic drug cibenzoline to relieve the outflow tract obstruction, and the pressure gradient was reduced to 70mmHg. After 3 months of treatment, her hemoglobin level had increased to 11.4g/dL without additional treatment for anemia. [Copyright &y& Elsevier]

Summary: Background: Recent reports suggest that left ventricular diastolic function assessed by tissue Doppler imaging (TDI) and plasma B-type natriuretic peptide (BNP) levels can relate to functional status in patients with hypertrophic cardiomyopathy (HCM). However, it is unclear which is more useful to predict the exercise capacity in HCM patients without systolic impairment and/or atrial fibrillation, TDI or BNP levels. Purpose: The present study directly compared the clinical relevance of assessing diastolic function using TDI and measuring the plasma BNP level in patients with HCM. Methods and subjects: We evaluated diastolic function using TDI as well as plasma BNP levels in 31 patients (52.2±16.9 years of age; 20 males) with HCM and examined the relationship of these values to exercise capacity (peak O2 consumption (VO2)) measured by cardiopulmonary exercise tests. Results: Average peak VO2 was 18.5±4.7ml/(kgmin). Although the E/A ratio by transmitral flow was not correlated with peak VO2, the lateral E/E a ratio assessed by TDI was significantly correlated with peak VO2 (r =−0.52, p =0.003). On the other hand, plasma BNP level was not significantly related to peak VO2 but NYHA class. Conclusions: Assessment of diastolic function using TDI, not plasma BNP levels, is more useful for predicting objective exercise capacity in HCM patients without systolic impairment and/or atrial fibrillation. [Copyright &y& Elsevier]

Summary: Background and purpose: Although dilated cardiomyopathy (DCM) had a poor prognosis in the past, recent studies have shown better survival. However, little is known about the improvement of prognosis in the elderly. This study sought to clarify the changes in prognosis in elderly patients with DCM over the past 20 years. Methods and subjects: We studied 54 consecutive patients with DCM (38 men and 16 women, aged 65–83 years) who were diagnosed at over 65 years of age. The patients were divided into two groups (group A: 12 patients diagnosed before 1990; group B: 42 patients diagnosed after 1990) because after 1990, based on growing evidence from large-scale, randomized clinical studies, we intentionally increased the use of angiotensin-converting enzyme inhibitors (ACEI) and then β-blockers at our hospital. Results: There were no significant differences in age, gender, NYHA functional class, and the prevalence of atrial fibrillation and ventricular tachycardia between the two groups. Left ventricular (LV) size assessed by echocardiography was larger (LV end-diastolic diameter, 67±5.9 versus 62±6.6mm; p =0.039) and LV ejection fraction measured by left ventriculography was lower (ejection fraction, 24±9 versus 35±10%; p =0.004) in group A. ACEI/angiotensin II type 1 receptor blockers (ARB) (0% versus 88%) or β-blockers (0% versus 52%) were more frequently used in group B. Antiarrhythmics (class Ia or Ib) (75% versus 14%) were less often used in group B. The 5- and 10-year event-free survival rates for cardiac death were 75.4% and 22.0% in group A versus 81.2% and 71.3% in group B (log-rank test, p = 0.014). Conclusions: The prognosis of DCM patients in the elderly has significantly improved over the past 20 years. The advances in the pharmacologic treatment and earlier diagnosis may have contributed to the better survival. [Copyright &y& Elsevier]

Summary: Objectives: The present study sought to investigate the echocardiographic features of hypertrophic cardiomyopathy (HCM) with mild left ventricular (LV) remodeling, particularly in relation to wall motion abnormalities. Methods: Among the 137 consecutive patients with HCM, 13 patients (mean age 52±13 years) who progressed to mild LV systolic dysfunction (LV ejection fraction (LVEF) of 35–50%) were studied. By reviewing the echocardiograms of these patients, wall motion score index (WMSI) was scored using 16 segments model. Results: HCM patients with mild LV systolic dysfunction exhibited mild LV dilatation, mild left atrial dilatation, septal hypertrophy, and LV wall motion impairment localized in the septal and apical regions (septal WMSI 1.94±0.33 vs. total WMSI 1.51±0.25 and posterior WMSI 1.02±0.07; p <0.001). During follow-up, further deterioration of LV systolic function (LVEF<35%) was noted in five patients, who had less severe hypertrophy at the initial echocardiograms. These patients developed progressive LV cavity enlargement and more severe and extensive wall motion abnormalities, accompanied by septal akinesis and wall thinning, although posterolateral wall motion impairment was relatively mild (posterior WMSI 1.80±0.27 vs. septal WMSI 2.95±0.11; p <0.001). Conclusions: Septal and apical wall motions are reduced in HCM with mild LV remodeling. As LV dysfunction progresses, septal akinesis and wall thinning develop and LV cavity enlargement becomes more prominent, though posterolateral wall motion impairment is relatively mild. [Copyright &y& Elsevier]

Idiopathic dilated cardiomyopathy is a common cause of heart failure. Half of cases are believed to be hereditary, and mutations in cardiac sarcomeric contractile protein genes have been reported with autosomal dominant inheritance. We used mutation analysis suitable for identification of both dominant and recessive mutations to investigate the sarcomeric gene for cardiac troponin I (TNNI3) in 235 patients with dilated cardiomyopathy. We identified a novel TNNI3 mutation in a family with recessive disease. Functional studies showed impairment of troponin interactions that could lead to diminished myocardial contractility. TNNI3 is the first recessive gene identified for this condition, and we suggest that other such genes could be pinpointed by mutation analyses designed to identify homozygous mutations. [Copyright &y& Elsevier]