Readiness of Advance Care Planning Among Patients With Cardiovascular Disease.

Background: Advance care planning (ACP) is a widely advocated strategy to improve outcomes at end-of-life care for patients suffering from heart failure (HF). However, finding the right time to start ACP is challenging for healthcare providers because it is often a sensitive issue for patients with HF and their families. We interviewed patients with cardiovascular diseases regarding ACP readiness and investigated the relationship between the ACP desire and multiple clinical prognostic parameters. Method: Eighty-one patients (average age 81.8 ± 10.3 years old, 42 men, 62 cases of HF) who introduced cardiac rehabilitation were inquired about previous ACP experience, a desire for ACP, understanding of their cardiovascular diseases, and lifestyle-associated questionnaires. Multiple logistic regression analyses were employed to identify the clinical parameters associated with ACP desire. Patients who desired ACP were also asked about their preferences for medical care at the end-of-life. Results: Nine patients (11.1%) had previous experience with ACP, and 28 (34.6%) preferred to implement ACP. Patients who did not want to implement ACP were 54.3%. Patients with HF showed a higher acceptance rate of ACP (odds ratio [OR] 5.56, p = 0.015). Interestingly, patients harboring skeletal muscle frailty showed lower ACP acceptance, while patients with non-frailty rather positively wanted to implement ACP. Two types of prognosis evaluation scales, such as the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) risk score and the Japanese Version of Supportive and Palliative Care Indicators Tool (SPICT-JP), identified 31 patients (38.3%) needing ACP; however, 19 (61.3%) did not want ACP. The wish not to attempt resuscitation and life-prolonging treatment at the end-of-life reached approximately 70% among patients who requested ACP. Conclusions: Although patients with HF tended to be ready for implementing ACP, the presence of skeletal muscle frailty was negatively associated with ACP preference. Indeed, patients who should be considered ACP were not carried out and did not desire it. Earlier introduction of ACP into patients before having skeletal muscle frailty may be considered.

Impact of milrinone on mitral annular velocity in patients with congestive heart failure.

PURPOSE: The purpose of this study is to assess the impact of milrinone on mitral annular velocity in patients with congestive heart failure. METHOD: We studied 27 patients with congestive heart failure. All patients underwent transthoracic echocardiography both before and after administration of milrinone. We measured the early transmitral velocity (E) and the mitral annular early diastolic velocity (Ea). The ratio of E to Ea (E/Ea) was calculated. After the baseline echocardiography, milrinone was administered as a continuous infusion at a rate of 0.25 µg/kg/min. Echocardiographic measurements were repeated 4 h after milrinone was begun. RESULTS: After administration of milrinone, Ea was significantly increased, while E/Ea was significantly decreased. The population of 27 patients was divided into 20 (74 %) with left ventricular ejection fraction (LVEF) <50 % and seven (26 %) with LVEF ≥50 %. Ea was significantly increased in both groups, while E/Ea was significantly decreased. CONCLUSION: Even low-dose milrinone produced an improvement in left ventricular (LV) diastolic function, as evidenced by an increase in Ea, and falls in LV filling pressures, as determined by a decrease in E/Ea, in patients with congestive heart failure throughout a wide range of LV systolic function.

Nonbacterial thrombotic endocarditis demonstrated by repeat echocardiography.

We report a case of nonbacterial thrombotic endocarditis (NBTE) in a patient with bladder cancer presenting with multiple cerebral infarctions. Initial transthoracic and transesophageal echocardiography did not show any abnormalities. However, repeat transthoracic and transesophageal echocardiography demonstrated a vegetation on the anterior leaflet of the mitral valve with mild mitral regurgitation and no evidence of leaflet destruction. Persistent high-grade fevers and leukocytosis were observed. The patient was suspected to have infective endocarditis. However, abdominal ultrasound and computed tomography scan revealed multiple metastatic masses, and serial blood cultures were negative. The patient was ultimately diagnosed with NBTE associated with multiple metastases of bladder cancer. This case suggests that even if echocardiography does not initially demonstrate any abnormalities in patients with embolism, it must be repeated at the recurrence of embolism, and that even if clinical signs of infection are documented, NBTE should be suspected in any cancer patient with thromboembolic events.

Donepezil-induced torsades de pointes without QT prolongation.

We report a case of torsades de pointes (TdP) induced by donepezil without QT prolongation. An 86-year-old woman was admitted to our hospital because of a syncopal attack. She had been treated for Alzheimer's disease with donepezil. Initial 12-lead electrocardiogram showed atrial fibrillation and normal corrected QT interval. After admission, atrial fibrillation spontaneously recovered to normal sinus rhythm on electrocardiographic monitoring. On the second day, electrocardiographic monitoring documented TdP. We discontinued donepezil immediately. After washout of donepezil, TdP was not observed again. Corrected QT interval was normal throughout hospitalization. This case suggests that donepezil may cause life-threatening ventricular arrhythmias without QT prolongation. Even if corrected QT interval is normal in patients taking donepezil and experiencing symptoms associated with TdP, electrocardiographic monitoring is recommended. .

Effects of mineralocorticoid receptor antagonist spironolactone on atrial conduction and remodeling in patients with heart failure.

BACKGROUND: Spironolactone was shown to reduce mortality in patients with heart failure (HF). However, the effect of spironolactone on the incidence of atrial fibrillation remains unknown. Therefore, we examined the effects of spironolactone on atrial conduction and remodeling in patients with HF. METHODS AND RESULTS: A total of 21 patients with HF were divided into either spironolactone group (n=11) or control group (n=10). The patients were followed up for 12 months. Blood examination, echocardiogram, and signal-averaged electrocardiogram were performed at study enrollment and after 3 and 12 months of treatment. In the spironolactone group, atrial natriuretic peptide tended to reduce, left atrium dimension was significantly smaller, the ratio of E wave to A wave tended to improve, and P-duration was significantly shortened. CONCLUSIONS: Spironolactone improves atrial conduction and remodeling in patients with HF.

Defibrillation efficacy of a subcutaneous array lead: A case report.

We report a case of Brugada syndrome with a high defibrillation threshold (DFT) in whom a subcutaneous array lead was used to lower the DFT in combination with a transvenous right ventricular defibrillation lead. The patient had previously received pacemaker implantation due to sick sinus syndrome. An implantable cardioverter defibrillator (ICD) with a transvenous right ventricular defibrillation lead alone required a high DFT. A subcutaneous array lead improved defibrillation efficacy in combination with a right ventricular lead. These data suggest that a subcutaneous array lead facilitates implantation of an effective ICD lead system in patients requiring a high DFT.

Cardio-ankle vascular index is superior to brachial-ankle pulse wave velocity as an index of arterial stiffness.

Both cardio-ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV) are noninvasive methods to estimate arterial stiffness. The purpose of this study is to determine whether CAVI or baPWV is superior as an index of arterial stiffness. One hundred and thirty patients with chest pain syndrome who underwent coronary angiography (CAG) were included in this study. We obtained intima-media-thickness (IMT) and the stiffness parameter beta of the carotid artery by carotid ultrasounds (CU). The peak early diastolic velocity (E), deceleration time of E (EDCT), peak atrial systolic velocity (A) of transmitral flow and left ventricular mass index (LVMI) were obtained by echocardiography. CAVI, baPWV, total cholesterol (T-C), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were measured before CAG. There was a significant correlation between CAVI and baPWV (r = 0.64, p < 0.01). Both CAVI and baPWV were significantly correlated with age, IMT and beta (age: r = 0.64, p < 0.01 for CAVI, and r = 0.48, p < 0.01 for baPWV; IMT: r = 0.40, p < 0.01, and r = 0.31, p < 0.01; beta: r = 0.36, p < 0.01 and r = 0.25, p < 0.01). However, only CAVI was correlated with the parameters of left ventricular diastolic indices from echocardiography (E/A: r = 0.44, p < 0.01; EDCT: r = 0.36, p < 0.01). Additionally, LDL-C and T-C/HDL-C were also associated with only CAVI (LDL-C: r = 0.26, p < 0.02; T-C/HDL-C: r = 0.30, p < 0.01), not baPWV. Finally, only CAVI was significantly higher in the group with angina pectoris than in the normal group (9.708 +/- 1.423 vs. 9.102 +/- 1.412; p = 0.0178). All parameters associated with atherosclerosis suggested that CAVI was superior to baPWV as a parameter of arterial stiffness.

Cardio-ankle vascular index is a new noninvasive parameter of arterial stiffness.

BACKGROUND: Beta is an index of arterial stiffness independent of blood pressure. Beta of the thoracic descending aorta (TDA) has been obtained by transesophageal echocardiography (TEE) and the cardio-ankle vascular index (CAVI) is a new noninvasive estimation of beta. METHODS AND RESULTS: The purpose of this study was to evaluate the accuracy and usefulness of CAVI and to compare it with other parameters of arteriosclerosis by carotid ultrasound (CU). The instantaneous dimensional change of the TDA on TEE was measured simultaneously with systemic pressure of the brachial artery in 70 patients in sinus rhythm. There were significant correlations between CAVI and age (r=0.65, p<0.01), and CAVI and the beta from TEE (Aobeta) (r=0.67, p<0.01). Next, 110 patients with chest pain syndrome underwent CU and measurement of CAVI, intima - media thickness (IMT), plaque score and beta. There were significant relationships between CAVI and IMT (r=0.42, p<0.01), and between CAVI and beta (r=0.39, p<0.01). CAVI of the group diagnosed with plaque was significant higher than that of the normal group (9.872+/-1.464 vs 9.038+/-1.377, p=0.0039). CONCLUSIONS: CAVI is measured easily and noninvasively and is a new index of arterial stiffness that is independent of blood pressure.

[Cardioversion of amiodarone-insensitive atrial fibrillation by bepridil in heart failure: two case reports].

Two patients presented with atrial fibrillation which was refractory to amiodarone but successfully treated with bepridil. A 76-year-old man with ischemic cardiomyopathy, non-sustained ventricular tachycardia (NSVT) and atrial fibrillation received amiodarone for NSVT, which disappeared but atrial fibrillation was sustained. A month after receiving amiodarone, interstitial pneumonia occurred. Interstitial pneumonia was improved after amiodarone was discontinued, but NSVT occurred again. He received bepridil, when NSVT and atrial fibrillation disappeared. An 83-year-old man with dilated cardiomyopathy, NSVT, and atrial fibrillation received amiodarone for NSVT, which disappeared but atrial fibrillation was sustained. Five months after receiving amiodarone, interstitial pneumonia occurred. Interstitial pneumonia was improved after amiodarone was discontinued, but NSVT occurred again. He received bepridil, when NSVT and atrial fibrillation disappeared.

Complete proximal occlusion of all three main coronary arteries complicated with a left main coronary aneurysm: a case report.

A 68-year-old woman with recurrent chest pain was referred to our institution. Coronary angiography showed 100% obstruction of the left main trunk, the proximal right coronary artery with good collaterals to the left anterior descending artery and left circumflex artery along the conus artery. Emergency surgical revascularization was undertaken with two saphenous vein grafts. The saphenous vein grafts were placed in the left anterior descending artery, obtuse marginal branch and the posterolateral and posterior descending coronary arteries with excellent flow. The postoperative course was uneventful and follow-up angiography was obtained 20 days after the surgery. Coronary angiography demonstrated a saccular aneurysm (10 x 9 mm) originating at the distal segment of the left main coronary artery with 90% stenosis, and excellent patency of both saphenous vein grafts. Follow-up angiography was performed 1 and 3 years after the surgery. The size of the left main coronary aneurysm remained unchanged at both examinations. The patient did well with no further cardiac symptoms after 5 years.

ERK1/2 regulates intracellular ATP levels through alpha-enolase expression in cardiomyocytes exposed to ischemic hypoxia and reoxygenation.

Extracellular signal-regulated kinase 1/2 (ERK1/2) is known to function in cell survival in response to various stresses; however, the mechanism of cell survival by ERK1/2 remains poorly elucidated in ischemic heart. Here we applied functional proteomics by two-dimensional electrophoresis to identify a cellular target of ERK1/2 in response to ischemic hypoxia. Approximately 1500 spots were detected by Coomassie Brilliant Blue staining of a sample from unstimulated cells. The staining intensities of at least 50 spots increased at 6-h reoxygenation after 2-h ischemic hypoxia. Of the 50 spots that increased, at least 4 spots were inhibited in the presence of PD98059, a MEK inhibitor. A protein with a molecular mass of 52 kDa that is strongly induced by ERK1/2 activation in response to ischemic hypoxia and reoxygenation was identified as alpha-enolase, a rate-limiting enzyme in the glycolytic pathway, by liquid chromatography-mass spectrometry and amino acid sequencing. The expressions of the alpha-enolase mRNA and protein are inhibited during reoxygenation after ischemic hypoxia in the cells containing a dominant negative mutant of MEK1 and treated with a MEK inhibitor, PD98059, leading to a decrease in ATP levels. alpha-Enolase expression is also observed in rat heart subjected to ischemia-reperfusion. The induction of alpha-enolase by ERK1/2 appears to be mediated by c-Myc. The introduction of the alpha-enolase protein into the cells restores ATP levels and prevents cell death during ischemic hypoxia and reoxygenation in these cells. These results show that alpha-enolase expression by ERK1/2 participates in the production of ATP during reoxygenation after ischemic hypoxia, and a decrease in ATP induces apoptotic cell death. Furthermore, alpha-enolase improves the contractility of cardiomyocytes impaired by ischemic hypoxia. Our results reveal that ERK1/2 plays a role in the contractility of cardiomyocytes and cell survival through alpha-enolase expression during ischemic hypoxia and reoxygenation.

[Hypertrophic obstructive cardiomyopathy with ruptured mitral chordae tendineae: a case report].

A 61-year-old man was treated medically under a diagnosis of hypertrophic obstructive cardiomyopathy 7 years previously. He was transferred to our hospital because of sudden onset of dyspnea. Chest radiography showed marked pulmonary congestion. Echocardiography revealed hypertrophic obstructive cardiomyopathy, with a left ventricular pressure gradient of 120 mmHg, accompanied by severe mitral regurgitation due to ruptured chordae tendineae. Mitral valve replacement and the Morrow operation were performed. After the operation, no left ventricular outflow pressure gradient was detected by echocardiography and cardiac catheterization. The patient did well and no further cardiac symptoms were detected for 3 years.

Effects of flecainide on the electrophysiological properties of atrial vulnerability in humans.

The aims of this study were to evaluate the changes in the electrophysiological characteristics of the right atrium after the administration of flecainide and to clarify whether flecainide has a selective effect on human atrial tissue. Electrophysiological measurements were made in 38 patients, before and after intravenous administration of flecainide (2 mg/kg per 10 min). The effective refractory period of the right atrium (ERP-A), maximum conduction delay (Max.CD), repetitive atrial firing zone (RAFZ), fragmented atrial activity zone (FAAZ), and conduction delay zone (CDZ) were studied in the patients who were divided into 2 groups based on whether repetitive atrial firing (RAF) was induced in the baseline study. Flecainide significantly prolonged the ERP-A (202+/-22 to 238+/-33 ms, p<0.001) and shortened Max.CD (77+/-17 to 63+/-32 ms, p<0.05) in the patients with RAF, but not in those without RAF in the baseline study. After flecainide administration, there were significant reductions in the RAFZ (43+/-22 to 13+/-19 ms, p<0.0001), FAAZ (51+/-22 to 28+/-26 ms, p<0.001) and CDZ (70+/-21 to 48+/-30 ms, p<0.01) in the patients with RAF. However, atrial fibrillation (AF) was induced by stimulation after flecainide in 2 patients without RAF in the baseline study. There was a significant negative correlation between the ERP-A in the baseline study and the change in the ERP-A upon flecainide administration (r=0.45, p<0.01). Flecainide may preferentially activate the substrate for AF and RAF, but that action is mainly based on the electrophysiological characteristics found in the baseline study.

Beta-blocker decreases the increase in QT dispersion and transmural dispersion of repolarization induced by bepridil.

Bepridil is effective for intractable cardiac arrhythmia, but in rare cases will induce torsades de pointes (TdP) associated with QT interval prolongation. Beta-blockers will effectively prevent TdP in some clinical settings, so the effect of beta-blocker on the change in QT interval, QT dispersion and transmural dispersion of repolarization (TDR) induced by bepridil was investigated in 10 patients (7 male, 3 female; 62+/-6 years old) with intractable paroxysmal atrial fibrillation. The QTc interval, QTc dispersion and TDR were measured before and after 1 month of administration of bepridil, and then a beta-blocker was added and the QTc interval, QTc dispersion and TDR re-measured 1 month later. Bepridil significantly prolonged the QTc interval (0.42+/-0.05 to 0.50+/-0.08; p<0.01), and increased both the QT dispersion (0.07+/-0.05 to 0.14+/-0.08; p<0.01) and TDR (0.10+/-0.04 to 0.16+/-0.05; p<0.01). The addition of a beta-blocker decreased the QTc interval (0.50+/-0.08 to 0.47+/-0.04; p=0.09) and significantly decreased both the QTc dispersion (0.14 +/-0.08 to 0.06+/-0.02; p<0.01) and TDR (0.16+/-0.05 to 0.11+/-0.04; p<0.001). Compared with the control, the combination therapy significantly prolonged the QTc interval, but did not increase either QTc dispersion or TDR, and so was effective in all patients with intractable AF. The findings suggest that beta-blocker reduces the increase in QT dispersion and TDR induced by bepridil, and combined therapy with bepridil and beta-blocker might thus be useful for intractable atrial fibrillation.

Effect of ischemic preconditioning and mitochondrial KATP channel openers on chronic left ventricular remodeling in the ischemic-reperfused rat heart.

The influence of ischemic preconditioning (IP) and mitochondrial ATP-sensitive potassium (mito-KATP) channel openers on chronic left ventricular (LV) remodeling remains unknown, so the effect of IP and mito-KATP channel openers on the LV pressure-volume curve was assessed in rats subjected to 30 min ischemia followed by a 3-week reperfusion. Infarct size was histologically determined at 3 weeks after reperfusion. The LV pressure-volume curve was significantly shifted left by IP, diazoxide and nicorandil compared with the controls. These effects were blocked by the selective mito-KATP channel blocker 5-hydroxydecanoate. The LV remodeling and the infarct size at 3 weeks after reperfusion correlated well, indicating that the reduction of LV remodeling in the ischemic-reperfused model was strongly influenced by attenuation of the ischemic injury. LV remodeling in the chronic phase is attenuated by IP and mito-KATP channel openers with concomitant reduction of infarct size.