Reduction of left ventricular pressure gradient due to cibenzoline therapy in a 16-year-old girl with hypertrophic obstructive cardiomyopathy.

A 13-year-old girl was referred for closer examination of electrocardiographic abnormalities. She had a Levine 2/6 systolic murmur (SM) and a fourth heart sound. Electrocardiography findings showed poor R progression from V1 to V4 and negative T waves in the II, III, and aVF leads. Approximately 3.2 years later, her SM increased to Levine 3-4/6. Echocardiography indicated mitral regurgitation and left ventricular pressure gradient (LVPG) of 18.5 mmHg, together with a notch on the systolic wave in the apexcardiogram. We concluded that the electrocardiographic abnormalities were caused by hypertrophic cardiomyopathy. Approximately 6 months later, her SM further increased to Levine 4-5/6, and the voltage on the electrocardiogram increased. In carotid pulse tracing, steep upstroke and deflated percussion wave due to mitral regurgitation were noted. The LVPG was approximately 102 mmHg, and systolic anterior movement was confirmed. After the oral administration of 200 mg of cibenzoline, the LVPG decreased to approximately 48 mmHg. Subsequently, 300 mg/day of cibenzoline was administered. The LVPG further decreased, and her symptoms improved. Learning objectives: Clinical symptoms and left ventricular pressure gradient decrease can be ameliorated by cibenzoline therapy in patients with hypertrophic obstructive cardiomyopathy. This finding applies not only to adult patients but also to teen-aged patients.

Changes of left ventricular remodeling due to increased afterload in patients with essential hypertension.

BACKGROUND: It is unclear whether afterload mismatch occurs during the initial stage of essential hypertension (EHT). Additionally, critical left ventricular hypertrophy (LVH) between preserved and reduced systolic functions in hypertension is also unclear. Thus, we aimed to clarify these points. METHODS: Forty-five normal control subjects (NCS) and 140 EHT patients participated. EHT patients were subdivided into three groups: group I, without LVH (n = 37); group II, with LVH (n = 80); and group III, with LVH and LV heart failure (LVHF) (n = 23). Routine electrocardiographic and echocardiographic parameters, V5R/V6R ratio, relative wall thickness (RWT), LV mass (LVM) index, and peak systolic wall stress (PSWS) were measured. RESULTS: In group I, LV systolic functions were preserved despite the increase of PSWS. In group II, LVH advanced, but LV systolic functions remained normal. A negative T-wave was observed in 69% of group II and 100% of group III. A significant correlation between RWT and LVM index was seen in NCS and groups I and II (r2 = 0.545, P < 0.0001) but not in group III. Afterload mismatch occurred in group III due to the decrease in V5R/V6R ratio, the increase of LV end-diastolic dimension, and the LV systolic dysfunctions, which are caused by exhaustion of preload reserve. The boundary of the LVM index between groups II and III was approximately 180 g/m2. CONCLUSION: Afterload mismatch did not occur in group I, but it was observed in group III due to the exhaustion of preload reserve.

Impact of cibenzoline treatment on left ventricular remodelling and prognosis in hypertrophic obstructive cardiomyopathy.

AIMS: This study aimed to elucidate the long-term effect of cibenzoline therapy on cardiovascular complications and prognosis in patients with hypertrophic obstructive cardiomyopathy (HOCM). METHODS AND RESULTS: Eighty-eight patients with HOCM were treated with cibenzoline (Group A), and 41 patients did not receive cibenzoline (Group B). The changes in left ventricular (LV) remodelling, incidences of cardiovascular complications and deaths, were examined. The mean follow-up period was 15.8 ± 5.6 years in Group A and 17.8 ± 7.2 years in Group B. In Group A, the LV pressure gradient (LVPG) decreased immediately after treatment, and the reduction was maintained throughout the study. In Group B, the LVPG decreased gradually according to the deterioration of LV function. LV reverse remodelling was confirmed in Group A, and LV remodelling advanced in Group B. In Group A, the incidence of each cardiovascular complication was <10%. Only one patient experienced LV heart failure (LVHF). LVHF incidence and atrial fibrillation were higher in Group B than those in Group A (P < 0.0001). The incidence of death was 20.5% in Group A and 90.2% in Group B (P < 0.0001). The most frequent cause of death was sudden cardiac death (SCD) (38.9%) in Group A and LVHF (67.6%) in Group B. The incidence of SCD showed no significant difference between the two groups. The cumulative cardiac survival rate was higher in Group A than that in Group B (P < 0.0001). CONCLUSIONS: Cibenzoline treatment significantly reduced all cardiovascular complications and death due to LVHF and may be a promising treatment in patients with HOCM.

Predicting the clinical course in hypertrophic cardiomyopathy using thallium-201 myocardial scintigraphy.

AIMS: This study aimed to evaluate the changes in left ventricular remodelling with time in patients with hypertrophic cardiomyopathy (HCM) using thallium-201 myocardial scintigraphy. METHODS AND RESULTS: Forty-eight patients with HCM participated in the study. The extent score (ES) and a newly devised index termed the 'mean count change' (MCC) were used to evaluate the myocardial perfusion defects. Using the amount of thallium-201 uptake (TU), MCC (%) was calculated using the following formula: (last TU - initial TU)∕initial TU × 100. To confirm the site of the lesion, the left ventricle was divided into five segments: anterior, septal, inferior, lateral, and apex. Cardiovascular complications and deaths were recorded. The mean follow-up period was 8.6 ± 2.0 years. ES increased from 17.4 ± 13.7% to 44.0 ± 22.3% (P < 0.0001). MCC increased from 0% to 12.0 ± 9.0% (P < 0.0001). The apex was the most frequent site of lesion. Twenty-seven patients (56.3%) had experienced left ventricular heart failure (LVHF). Both ES and MCC were greater in patients with LVHF than in those without LVHF. An overlap between the two groups was greater in ES than in MCC. Patients with LVHF had a higher incidence of atrial fibrillation and apoplexy. Nineteen patients (39.6%) died during the study period; 14 died from LVHF, 3 from sudden cardiac death, and 2 from cancer. CONCLUSIONS: Thallium-201 myocardial scintigraphy is useful for detecting the severity of myocardial damage and for confirming the lesion site in patients with HCM. MCC may be superior to ES in the evaluation of these changes with time.

Coronary artery-left ventricular shunt: an important cause of chest pain in patients with hypertrophic cardiomyopathy.

The influence of shunts between the coronary artery (CA) and the left ventricle (LV), on chest pain (CP) in patients with hypertrophic cardiomyopathy (HCM) is unknown. We examined the incidence of CA-LV shunts and their influence on CP in HCM patients. Twenty normal control subjects (NCS), 3 with CP due to CA-LV shunts (CP patients), and 60 with HCM participated. Interventricular septal wall thickness (IVST), LV posterior wall thickness (LVPWT), cardiac and stroke indexes (CI and SI), LV end-diastolic pressure (LVEDP), and proximal diameters of the CA were measured. Twenty-five HCM patients had a CA-LV shunt (41.7%). Both IVST and LVPWT were greater in the HCM patients than in NCS and CP patients. These values showed no significant differences between the HCM with shunt and HCM without shunt groups. CI and SI were lower in the HCM patients than in NCS and CP patients. LVEDP was higher in the HCM and CP patients than in NCS. CA diameters were larger in the HCM and CP patients than in NCS. CP was found in 32 HCM patients (53%). The incidence of CP was greater in the HCM with shunt group than in HCM without shunt group (80 vs. 34%, p < 0.0005). There was no significant difference in CA diameters between the HCM patients with CP and those without CP. CA-LV shunts are often found in HCM patients and are closely related to CP. Thus, CA-LV shunts are an important factor behind CP in HCM patients.

Impact of chronic kidney disease on the diuretic response of tolvaptan in acute decompensated heart failure.

AIM: This study investigated the relationship between the initial diuretic response to tolvaptan and clinical predictors for tolvaptan responders in patients with acute decompensated heart failure (ADHF). METHODS AND RESULTS: Patients (153) with ADHF (clinical scenario 2 or 3 with signs of fluid retention) who were administered tolvaptan were enrolled. Tolvaptan (15 or 7.5 mg) was administered for at least 7 days to those patients in whom fluid retention was observed even after standard treatment. The maximum urine volume immediately after tolvaptan administration showed good correlations with the ejection fraction and estimated glomerular filtration rate that were independent predictors of the urine volume (UV) responders (≥1500 mL increase in urine volume). The diuretic response (in terms of maximum diuresis) diminished with advancing chronic kidney disease (CKD) stage and concomitant deterioration of the renal function. Furthermore, advanced CKD was a significant negative predictor for the body weight (BW) responders (2.0% decrease in the body weight within 1 week after starting tolvaptan). As compared with non-CKD, the presence of advanced CKD predicts poor diuretic response for both UV and BW responders. CONCLUSIONS: The diuretic response following tolvaptan administration gradually diminished with progressive deterioration of the CKD stage. Worsening renal function was not observed. Tolvaptan is effective in treating CS2 or CS3 ADHF patients who present fluid retention and congestion, suggesting its potential efficacy for fluid management in the ADHF patients with CKD without worsening the renal function.

Plasma levels of atrial and brain natriuretic peptides in apparently healthy subjects: Effects of sex, age, and hemoglobin concentration.

BACKGROUND: To examine whether the use of one value of natriuretic peptides to define "normal" is appropriate in all individuals, and to assess the influence of sex, age, and other variables on atrial and brain natriuretic peptides (ANP, BNP) levels. METHODS AND RESULTS: A total of 1375 apparently healthy people (women:155, men:1220), aged 18-70years were enrolled. Both ANP and BNP levels were higher in women than in men (ANP: 12.50±6.82pg/mL vs 8.18±4.19pg/mL; BNP: 9.85±7.63pg/mL vs 7.03±6.97pg/mL). The subjects were divided into three age groups: group I, 18-30years; group II, 30-50years; group III, 50-70years. First, the influence of age on ANP and BNP levels was examined. In women, both ANP and BNP levels were higher in groups II and III than those in group I. In men, ANP and BNP levels increased with age. Second, sex differences in ANP and BNP levels due to age were examined. ANP level was higher in women than that in men in all age groups. BNP level was higher in women than that in men in groups I and II. Multivariate analysis indicated that both ANP and BNP levels were influenced by age, hemoglobin level, and platelet counts. CONCLUSION: Because ANP and BNP levels in healthy subjects are influenced by sex, age, and hemoglobin levels, the use of a single value to define "normal" in all individuals is not appropriate.

Usefulness of Intravascular Ultrasound for Predicting Risk of Intraprocedural Stent Thrombosis.

Intraprocedural stent thrombosis (IPST) is a rare complication of percutaneous coronary intervention that leads to poor outcomes; however, the factors contributing to IPST remain largely unknown. Accordingly, we used intravascular ultrasound (IVUS) to examine the lesion characteristics in patients with IPST. We retrospectively analyzed 1,504 consecutive stent-implanted lesions in 1,324 patients (326 with ST-segment elevation myocardial infarction [STEMI], 403 patients with non-ST-segment elevation acute coronary syndrome [NSTE-ACS], and 595 patients with stable angina). Of these, IPST occurred in 5 patients during percutaneous coronary intervention (0.4% per patient; 3 with STEMI, 2 with NSTE-ACS). The IVUS characteristics of plaques that developed IPST were compared with those of controls without the evidence of IPST (non-IPST; n = 15) who were matched by age, gender, lesion location, and clinical presentation (STEMI, NSTE-ACS, or stable angina). All 5 lesions that led to IPST had ruptured plaques with positive remodeling and attenuation. Plaque rupture was also observed in 40% of the non-IPST group. Multiple plaque ruptures in the culprit lesion were more common in the IPST group (80% vs 7%; p <0.01). The maximum cavity area was larger in the IPST group than in the non-IPST group having plaque rupture (4.6 mm(2) [interquartile range, 4.3 to 6.5] vs 2.4 mm(2) [1.8 to 2.9]; p <0.01). In conclusion, we found using IVUS that multiple plaque ruptures with larger cavities more often evolved into IPST.

Elevated Cardiac Enzymes in Hypertrophic Cardiomyopathy Patients With Heart Failure - A 20-Year Prospective Follow-up Study.

BACKGROUND: To better understand the evolution of typical hypertrophic cardiomyopathy (HCM) to heart failure (HF), we investigated the relationship between serum biochemical abnormalities and changes in left ventricular (LV) remodeling. METHODS AND RESULTS: Seventy-seven HCM patients were followed for 20 years. Creatine kinase (CK), CK-MB, lactate dehydrogenase (LDH), LDH-1, troponin T and myosin light chain-1 (MLC-1) were measured. Abnormal CK-MB elevation was observed in 64% of HCM patients. LDH-1 was not significantly different compared with the control subjects. Troponin T elevation was observed in 3 HCM patients and MLC-1 elevation was not observed. According to median CK-MB, HCM patients were divided into 2 groups: group H (CK-MB ≥2.5%, n=33) and group L (CK-MB <2.5%, n=44). During the follow-up period in group H, LV end-diastolic dimension increased (P<0.0001), fractional shortening decreased (P<0.0004), and left atrial dimension increased (P<0.0001). The markers reflecting LV hypertrophy were significantly decreased. In group L, LV end-diastolic dimension increased (P<0.02) and left atrial dimension increased (P<0.0001). HF was observed in 18 patients in group H and in 4 in group L. There were 14 HF deaths in group H and 2 in group L, and 3 sudden cardiac deaths in group H. CONCLUSIONS: Persistent elevation of cardiac enzymes in HCM patients indicates ongoing myocardial injury, ultimately resulting in death by HF.

Impact of chronic use of cibenzoline on left ventricular pressure gradient and left ventricular remodeling in patients with hypertrophic obstructive cardiomyopathy.

BACKGROUND: Cibenzoline, a class Ia antiarrhythmic drug, is useful for reducing the left ventricular pressure gradient (LVPG) in patients with hypertrophic obstructive cardiomyopathy (HOCM). However, chronic effects of cibenzoline on LVPG and left ventricular (LV) remodeling are unknown. METHODS: Forty-one patients with HOCM participated in this study. Echocardiographic, electrocardiographic, and brain natriuretic peptide (BNP) data collected before and after cibenzoline treatment were compared. From the relation between LVPG and plasma concentration of cibenzoline, an efficacious plasma concentration of cibenzoline was estimated. RESULTS: The mean follow-up period was 74.2±47.1 months. The LVPG decreased from 104.8±62.6mmHg to 27.6±30.5mmHg (p<0.0001). The LV end-diastolic dimension increased from 42.8±5.8mm to 46.2±5.4mm (p<0.0001), but neither LV end-systolic dimension nor LV fractional shortening changed significantly. The left atrial dimension decreased from 40.0±4.7mm to 36.2±5.1mm (p<0.0001). The E-wave velocity/A-wave velocity ratio increased, early diastolic annular velocity (Ea) increased, and E/Ea ratio decreased. The interventricular septal wall thickness, LV posterior wall thickness, the Sokolow-Lyon index, and the depth of negative T wave decreased. The heart rate-corrected QT interval was shortened. Plasma BNP level decreased from 418.8±423.7pg/ml to 213.7±154.1pg/ml (p<0.02). The safe and efficacious plasma concentration of cibenzoline was between 300ng/mL and 1500ng/mL. CONCLUSIONS: Long-term treatment with cibenzoline attenuated LVPG, improved LV diastolic dysfunction, and induced LV hypertrophy regression in patients with HOCM without causing serious complications.

Successful treatment of cerebral emboli with tissue plasminogen activator in a patient with takotsubo cardiomyopathy: A case report.

Takotsubo cardiomyopathy is a cardiac syndrome characterized by reversible left ventricular wall motion abnormalities. It mimics the acute coronary syndrome; however, significant obstructive coronary artery disease is absent. The prognosis is relatively favorable in many cases, but complications may occur during the acute stage. Herein, we present a case of takotsubo cardiomyopathy in a 76-year-old woman. Three days after admission for persistent chest pains, the patient suddenly developed right hemiplegia, right homonymous hemianopsia, and aphasia. By diffusion-weighted magnetic resonance imaging and magnetic resonance angiography, we diagnosed acute-phase cerebral infarction caused by abrupt occlusion of the left middle cerebral artery by a thrombus, and treated it with intravenously administered tissue plasminogen activator. Three hours afterward, the patient's condition improved considerably. She was discharged 15 days after admission without any neurological sequelae. Thus, we show that takotsubo cardiomyopathy complicated by cerebral emboli can be successfully treated using tissue plasminogen activator. .

A case of coronary artery aneurysm after sirolimus-eluting stent implantation presenting with unstable angina due to progression of stent thrombosis: Concerns over sirolimus-eluting stents remain.

A 44-year-old man was implanted with a sirolimus-eluting stent in the proximal left anterior descending artery 8 years previously. Six years later, multi-slice computed tomography and angiography confirmed the formation of a coronary artery aneurysm around the stent. Optical coherence tomography revealed organized thrombi within the stent. Eight years after implantation, the patient presented with chest pain, and multiple imaging modalities revealed thrombotic occlusion within the stent. Surprisingly, the coronary artery aneurysm became a detour for distal flow from the occluded stent. Long-term follow-up after implantation of first-generation drug-eluting stents is mandatory, because unexpected reactions can suddenly occur. .

A Patient with Dengue Fever Presenting with Rhabdomyolysis.

A 16-year-old boy stayed in Tokyo near Yoyogi Park for extracurricular high school activities. After returning home, he experienced an episode of fever and visited our emergency outpatient unit. He initially exhibited symptoms of leukopenia, thrombocytopenia and concomitant rhabdomyolysis and after admission simultaneously developed a biphasic fever and systemic erythema. Based on the results of reverse transcription polymerase chain reaction testing, he was finally diagnosed with dengue fever. After an absence of 70 years, dengue fever has reemerged as a domestic infection. Awareness of this trend led to our diagnosis.