Prognostic impact of frailty based on a comprehensive frailty assessment in patients with heart failure.

AIMS: This study aimed to evaluate the impact of frailty and living function domains based on the Kihon Checklist (KCL), a questionnaire for a comprehensive frailty assessment, on prognosis in patients with acute heart failure (AHF). METHODS AND RESULTS: The Kochi Registry of Subjects with Acute Decompensated Heart Failure (Kochi YOSACOI) study was a prospective multicentre cohort study enrolling 1061 patients hospitalized for AHF from May 2017 to December 2019 in Japan. We divided patients into three groups according to the severity of frailty using the KCL and compared clinical outcomes after discharge. The primary endpoint was all-cause death, and the secondary outcomes were cardiovascular death, heart failure (HF) rehospitalization, and the composite event of cardiovascular death and HF rehospitalization. Of 936 patients (median age, 81 years; 48.9% women) who could be assessed for frailty, we identified frailty in 501 patients (53.5%), prefrailty in 290 patients (31.0%), and non-frailty in 145 patients (15.5%). Compared with prefrail and non-frail patients, frail patients were older (83 vs. 79 and 72 years, P < 0.001), were more likely to be women (53.9% vs. 43.1% and 43.4%, P = 0.005), and were more likely to have a history of previous HF hospitalization (35.4% vs. 25.3% and 19.6%, P < 0.001) and multimorbidity (90.8% vs. 81.0% and 73.8%, P < 0.001). Frail patients had a lower rate of discharge to home (79.7% vs. 94.8% and 96.5%, P < 0.001). During the 2 year follow-up period, frail patients had a higher incidence rate of all-cause death, cardiovascular death, and HF rehospitalization (log-rank P < 0.001, P < 0.001, and P = 0.003, respectively). After adjusting for other prognostic factors, multivariate analysis showed that frailty was associated with all-cause death [adjusted hazard ratio (HR): 2.917, 95% confidence interval (CI): 1.326-6.417, P = 0.008] and cardiovascular death (adjusted HR: 7.026, 95% CI: 1.700-29.030, P = 0.007). Among all domains of the KCL, the cognitive function domain was associated with a higher risk of all-cause death (P = 0.004) and cardiovascular death (P < 0.001). The depression domain remained associated with a higher risk of HF rehospitalization (P = 0.045). The risk for all-cause death increased with an increase in total KCL score (adjusted HR: 1.819, 95% CI: 1.300-2.547, P < 0.001). CONCLUSIONS: The KCL is a useful tool for risk stratification of adverse outcomes in patients with AHF. Functional declines in psycho-emotional domains including cognitive function and depressed mood contribute to adverse outcomes.

Frailty interferes with the guideline-directed medical therapy in heart failure patients with reduced ejection fraction.

AIMS: Guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF) is recommended in clinical guidelines, but elderly patients have not fully received GDMT in the clinical situation. The aim of this study was to determine the clinical characteristics of patients who have not received GDMT and the association between implementation of GDMT at discharge and physical frailty in patients with HFrEF who were hospitalized for acute decompensated heart failure (ADHF). METHODS AND RESULTS: This study was a cross-sectional study with a retrospective analysis of the Kochi YOSACOI study, a prospective multicentre observational study that enrolled 1061 patients hospitalized for ADHF from May 2017 to December 2019 in Japan. Of 339 patients (32.0%) with HFrEF, 268 patients who were assessed for physical frailty by the Japanese version of the Cardiovascular Health Study criteria were divided into two groups: those with GDMT (135 patients, 50.4%) and those without GDMT (133 patients, 49.6%). GDMT was defined as the prescription of a combination of renin-angiotensin system (RAS) inhibitors (angiotensin-converting inhibitors or angiotensin receptor blockers) and beta-blockers. The median age of patients with HFrEF was 76 years (interquartile range, 67-83 years). Patients without GDMT were older than patients with GDMT (73 years vs. 78 years, P < 0.001). Patients without GDMT tended to have more prior HF admission than did patients with GDMT (P = 0.004), and patients without GDMT had lower levels of estimated glomerular filtration rate (P < 0.001) than those in patients with GDMT. Physical frailty was observed in 54.1% of the patients without GDMT and in 38.5% of the patients with GDMT (P = 0.014). Patients without GDMT had a higher rate of cognitive impairment than that in patients with GDMT (P = 0.009). RAS inhibitors only, beta-blockers only, and both RAS inhibitors and beta-blockers were less frequently prescribed in patients with physical frailty than in patients with physical non-frailty (52.0% vs. 86.7%, P < 0.05; 70.1% vs. 100.0%, P < 0.05; 42.5% vs. 86.7%, P < 0.01, respectively). In logistic regression analysis, compared with physical non-frailty, physical frailty was significantly associated with no implementation of GDMT (odds ratio: 6.900, 95% confidence interval: 1.420-33.600; P = 0.017), independent of older age and severe renal dysfunction. CONCLUSIONS: The results of this study suggest that physical frailty is one of the factors that may withhold GDMT in patients with HFrEF.

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.

Clinical characteristics and frailty status in heart failure with preserved vs. reduced ejection fraction.

AIMS: The aim of this study was to elucidate the clinical characteristics, including frailty status, of patients with heart failure with preserved ejection fraction (HFpEF) in comparison with those in patients with heart failure with reduced ejection fraction (HFrEF) in a super-aged region of Japan. METHODS AND RESULTS: Of the 1061 Japanese patients enrolled in the Kochi YOSACOI study, a multicentre registry, we divided 645 patients (median age of 81 years [interquartile range, 72-87 years]; women, 49.1%) into two groups, HFpEF patients (61.2%) and HFrEF patients (38.8%). Physical frailty was diagnosed on the basis of the Japanese version of Cardiovascular Health (J-CHS) Study criteria. Patients for whom left ventricular ejection fraction data were not available (n = 19), patients with heart failure with mildly reduced ejection fraction (n = 172), and patients who were not assessed by the J-CHS criteria (n = 225) were excluded. The median ages of the HFpEF and HFrEF patients were 84 and 76 years, respectively. The proportion of patients with HFpEF gradually increased with advance of age. The proportion of patients with three or more comorbidities was larger in HFpEF patients than in HFrEF patients (77.9% vs. 65.6%, P = 0.003). Handgrip strength was significantly lower in HFpEF patients than in HFrEF patients for both men (P < 0.001) and women (P = 0.041). Comfortable 5 m walking speed was significantly slower in HFpEF patients than in HFrEF patients (P < 0.001). The proportions of patients with physical frailty were 55.2% in HFpEF patients and 46.8% in HFrEF patients, and the proportion was significantly higher in HFpEF patients (P = 0.043). In multivariate analysis, physical frailty was associated with advanced age [odds ratio (OR), 1.030; 95% confidence interval (CI), 1.010-1.050; P = 0.023] and low albumin level (OR, 0.334; 95% CI, 0.192-0.582; P < 0.001) in HFpEF patients, and physical frailty was associated with women (OR, 2.150; 95% CI, 1.030-4.500; P = 0.042) and anaemia (OR, 2.840; 95% CI, 1.300-6.230; P = 0.003) in HFrEF patients. CONCLUSIONS: In a super-aged population of HF patients in Japan, HFpEF patients are more likely to be frail/have a high frailty status compared with HFrEF patients. The results suggested that physical frailty is associated with extracardiac factors in both HFpEF patients and HFrEF patients.

Assisted Living and Medication Adherence in Super-aged Patients With Heart Failure in the Japanese Population.

ABSTRACT: Poor adherence to medication in patients with heart failure (HF) is associated with poor clinical outcomes. Although social support has been reported to improve medication adherence in patients with HF, the detailed underlying mechanism of this association is unclear. This study investigated appropriate social support types to ensure medication adherence, as well as patient characteristics that benefit from such social support in patients with HF. This was a retrospective observational study investigating the association of social support with medication adherence in 824 patients with HF who were registered in a prospective multicenter database. First, we analyzed the association between social support types and poor medication adherence leading to hospitalization. An interaction analysis was performed to detect patients' characteristics that benefited most from social support in terms of medical adherence. Fifty patients (6.1%) were hospitalized for poor adherence to medications. Multivariable analysis revealed that not receiving assisted living, which was defined as having supporting individuals at least once a week, was independently associated with poor medication adherence-related hospitalization. An interaction analysis revealed that patients with dementia benefited from assisted living significantly, whereas male patients or current smokers did not. Summarily, assisted living at least once a week was appropriate for improving medication adherence in patients with HF and was particularly effective in patients with dementia. Performed in a super-aging region in Japan, this study may also suggest the relevance of social support in preventing HF exacerbation in other developed countries that will experience an aging society in the near future.

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.

Frailty in patients with acute decompensated heart failure in a super-aged regional Japanese cohort.

AIMS: The aim of this study was to investigate clinical characteristics of frail patients based on a comprehensive frailty assessment in patients hospitalized for acute decompensated heart failure (HF) (ADHF) in super-aged regional Japanese cohort. METHODS AND RESULTS: We established the Kochi Registry of Subjects with Acute Decompensated Heart Failure (Kochi YOSACOI) study, which was a prospective multicentre community-based cohort study in six participating hospitals in Kochi Prefecture, Japan. We enrolled 1061 patients (median age, 81 years; 50.0% men) hospitalized for ADHF between June 2017 and December 2019 in this registry. Patients were classified into the three groups by the severity of frailty using the Kihon Checklist: we identified frailty in 510 patients (53.7%), prefrailty in 293 patients (30.9%), and non-frailty in 146 patients (15.4%). Compared with prefrail and non-frail patients, frail patients were older (84 years interquartile range [IQR, 77-88] vs. 79 years [IQR, 69-86] and 72 years [IQR 65-81], P < 0.001) and more often had prior HF hospitalization (29.6% vs. 21.8% and 16.4%, P < 0.05), chronic kidney disease (81.6% vs. 71.7% and 61.0%, P < 0.01), anaemia (75.3% vs. 61.4% and 50.0%, P < 0.001), cerebrovascular accident (19.0% vs. 9.9% and 4.1%, P < 0.01). The proportion of patients with three or more comorbidities was larger in the frailty group than in the other groups (78.0% vs. 67.2% and 63.0%, P < 0.01). The frequency of functional decline in all domains increased with frailty status. Approximately 70% of frail patients were identified as functional decline in physical function and socialization domains. Fifty to sixty per cent of frail patients had functional decline in instrumental activities of daily living, cognitive function, and depression domains. The percentage of worsening walking ability during hospitalization was increasing with the frailty status (frailty, 27.5%; prefrailty, 21.8%; non-frailty, 8.9%). In multivariate logistic regression analysis, frailty was associated with age [odds ratio (OR) 1.031, 95% confidence interval (CI) 1.011-1.052, P = 0.003], prior HF hospitalization (OR 1.789, 95% CI 1.165-2.764, P = 0.008), brain natriuretic peptide level at discharge (OR 1.001, 95% CI 1.000-1.001, P = 0.020) and prior cerebrovascular accident (OR 2.549, 95% CI 1.484-4.501, P < 0.001). CONCLUSIONS: More than half of patients with ADHF were frail and had functional decline across multiple domains, not only physical function domain. The Kihon Checklist provided useful and valuable information for easily identifying frail patients and comprehensive management of HF.

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.

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.

Multidisciplinary approach for primary cardiac lymphoma associated with hemodynamic failure caused by tricuspid valve obstruction.

Primary cardiac lymphoma (PCL) comprises rare cardiac tumors and exhibits rapid growth and poor prognosis. We report the case of a 65-year-old man with PCL associated with unstable hemodynamics caused by tricuspid valve obstruction. Generally, chemotherapy is the first choice of treatment for patients with PCL. This patient required emergency tumor reduction as he was at risk of having acute hemodynamic failure caused by tricuspid valve obstruction. Therefore, he underwent a 2-staged treatment: urgent surgery to avoid sudden death by tricuspid valve obstruction as well as pulmonary embolism during chemotherapy, followed by early chemotherapy. Pathological findings showed diffuse large B-cell lymphoma, and rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, prednisolone (R-CHOP) therapy was initiated to treat any residual tumor infiltrating the myocardial wall. The patient showed a marked clinical improvement. We conclude that surgical tumor reduction and early chemotherapy might be an effective treatment for PCL patients with hemodynamic compromise. .

Inferior acute myocardial infarction due to acute cardiac herniation after right pneumonectomy.

A 69-year-old man underwent right intrapericardial pneumonectomy for lung cancer. After 24 h, he went into shock with inferior acute myocardial infarction. We performed urgent coronary angiography, which revealed total occlusion of the mid-right coronary artery. Intravascular ultrasound showed that the artery seemed to be compressed from the pericardial side. We implanted a coronary stent because the lesion was refractory to balloon dilatation. After the procedure, we performed computed tomography and cardiac herniation was diagnosed. Emergency thoracotomy was performed to return the herniated heart to its normal position. This patient was discharged 38 days after initial surgery.

Postinfarct cardiac free wall rupture detected by multidetector computed tomography.

Cardiac free wall rupture after myocardial infarction is one of the life-threatening complications, which often results in sudden onset of cardiogenic shock caused by cardiac tamponade. Multidetector computed tomography (MDCT) provides valuable information in any clinical setting. There have been a few case reports on detecting cardiac rupture by means of CT. We report here a rare case of postinfarct cardiac free wall rupture, whose myocardial tear could be detected by MDCT.

Abdominal visceral fat thickness measured by ultrasonography predicts the presence and severity of coronary artery disease.

Abdominal visceral fat plays a critical role in the pathogenesis of metabolic syndrome, which is a risk factor for coronary artery disease (CAD). Ultrasonography (US) distinctively quantifies visceral fat and subcutaneous fat. We measured the maximum preperitoneal visceral fat thickness (Vmax) and the minimum subcutaneous fat thickness (Smin) by US in 185 patients who underwent coronary angiography. Although the 144 patients with CAD had larger Vmax (8.8 ± 3.6 vs. 6.4 ± 2.8 mm; p < 0.001) than those without, there was no difference in Smin. Vmax of 6.9 mm or higher was an independent predictor of CAD (odds ratio, 3.710, p = 0.008) by multiple logistic regression analysis. Vmax significantly correlated with the number of diseased vessels. Assessment of abdominal visceral fat by US gives us incremental information beyond conventional risk factors for predicting CAD in routine clinical practice.

Gender-specific differences in the clinical features of hypertrophic cardiomyopathy in a community-based Japanese population: results from Kochi RYOMA study.

OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with a broad spectrum of clinical features. Although gender may be one of the important modifying factors in HCM, there has been little information on gender differences. METHODS: We investigated gender-specific differences in the clinical features of HCM in a community-based Japanese population. We established cardiomyopathy registration in Kochi Prefecture named Kochi RYOMA study consisting of 9 hospitals as an unselected regional Japanese population. RESULTS: 261 patients with diagnosis of HCM were registered. At registration, 88 patients (34%) were women. Female patients were more frequently diagnosed as having HCM at ≥65 years (41% versus 27%) and had a higher ratio of familial HCM (35% versus 19%). More female patients had diagnosis of HCM due to cardiac symptoms (64% versus 40%) and were symptomatic both at diagnosis and at registration. Although the prevalence of atrial fibrillation was not different between males and females, embolic events occurred less frequently in female patients at registration than in male patients (2% versus 10%). In female patients, there were more obstructive HCM patients and fewer patients with apical HCM. Left ventricular and left atrial diameters were smaller and fractional shortening was higher in females than in males. CONCLUSIONS: The manifestations of HCM in unselected Japanese patients differed in men and women, which suggest that hormonal, social, and genetic factors may influence the clinical presentation of HCM.

Clinical features of the dilated phase of hypertrophic cardiomyopathy in comparison with those of dilated cardiomyopathy.

BACKGROUND: Although the dilated phase of hypertrophic cardiomyopathy (D-HCM) characterized by left ventricular (LV) systolic dysfunction and cavity dilatation has been reported to be a poor prognosis, this is now in contrast to the improved prognosis of dilated cardiomyopathy (DCM) in the era of advancements in heart failure management. There has been no investigation of the clinical features of D-HCM compared with those of DCM from the point of management of systolic dysfunction. HYPOTHESIS: The aim of this study was to investigate the clinical features of D-HCM in comparison with those of DCM in a single institute. METHODS: We studied 20 consecutive patients with D-HCM (global ejection fraction < 50%) and 115 consecutive patients with DCM. RESULTS: At diagnosis of D-HCM, 8 (40%) of the D-HCM patients already experienced dyspnea (New York Heart Association [NYHA] class >or= III). Left atrial diameter was larger and prevalence of atrial fibrillation was higher in the D-HCM group, although LV size was larger and LV ejection fraction was lower in the DCM group. During the follow-up period (4.0 years), 11 (55%) of the patients with D-HCM died. The 5-year survival rate from all-cause mortality including cardiac transplantation was 45.6% in patients with D-HCM vs 81.6% in patients with DCM (log-rank P = .0001). CONCLUSIONS: Patients with D-HCM were more symptomatic at diagnosis, although LV dilatation and impaired fractional shortening seemed more severe in patients with DCM. The prognosis for D-HCM patients was worse than that for patients with DCM despite similar or even more intensive treatment for heart failure.

A novel cardiac myosin-binding protein C S297X mutation in hypertrophic cardiomyopathy.

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.

Hemolytic anemia in a patient with hypertrophic obstructive cardiomyopathy.

A 66-year-old woman was referred for further evaluation and treatment of normocytic and normochromic anemia with hemoglobin level of 8.6 g/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 24 mm and a hyperkinetic wall motion, resulting in marked obstruction to left ventricular outflow tract (pressure gradient of 200 mmHg). 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 70 mmHg. After 3 months of treatment, her hemoglobin level had increased to 11.4 g/dL without additional treatment for anemia.

Clinical profiles of hypertrophic cardiomyopathy with apical phenotype--comparison of pure-apical form and distal-dominant form.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) with an apical phenotype, in which hypertrophy of the myocardium predominantly involves the apex of the left ventricle, is not uncommon in Japan, but its morphologic variations are not well recognized. The aim of this study was to investigate if these variations have different clinical characteristics although they are still confused to be the same. METHODS AND RESULTS: Patients with the apical phenotype were divided into 2 groups, the "pure-apical" form and the "distal-dominant" form, and their clinical profiles were compared. From the study cohort of 264 patients with HCM, 80 (30%) were classified as having the apical phenotype: 51 with the pure-apical form and 29 with the distal-dominant form. The age at diagnosis was approximately 60 years, and in both groups the majority were male. The distal-dominant group had a significantly larger left atrial diameter (43 vs 39 mm) and higher ratio of proven familial HCM (28 vs 6%), and were more symptomatic (New York Heart Association >or=3) at presentation (17 vs 0%). The event-free rate of cardiovascular events in patients with the distal-dominant form was significantly worse (log-rank P=0.012) than that in patients with the pure-apical form (follow-up period: asymptotically approximately 5 years). CONCLUSIONS: The 2 phenotypes of apical HCM should be recognized and distinguished clinically.