Effects of a combination of losartan and hydrochlorothiazide in patients with hypertension and a history of heart failure.

OBJECTIVES: To evaluate the switching from an angiotensin receptor blocker (ARB) to a drug combination containing an ARB and a diuretic drug in terms of effects on hypertension, cardiac load, and cardiac function. METHODS: In a study conducted on 82 patients with a history of heart failure and hypertension who had been treated with an ARB but failed to reach the target blood pressure, ongoing oral ARB treatment was switched to a drug combination of losartan and hydrochlorothiazide (HCTZ). Using ambulatory blood pressure monitoring (ABPM), the variations in blood pressure and the effects on cardiac load and cardiac function were evaluated before and after treatment. RESULTS: Comparison of the ABPM findings before and after switching treatment showed significant improvements in mean systolic and diastolic blood pressure, improvements in systolic and diastolic blood pressure 1 hour before getting out of bed, and improvements in the plasma levels of human brain natriuretic peptide as an indicator of cardiac load. CONCLUSION: The drug combination of losartan and hydrochlorothiazide showed a stronger antihypertensive effect than that of the conventional ARB and improved heart function.

Regional wall motion abnormality at the lateral wall disturbs correlations between tissue Doppler E/e' ratios and left ventricular diastolic performance parameters measured by invasive methods.

BACKGROUND: The impact of regional wall motion abnormality (RWMA) on the accuracy of heart failure with preserved ejection fraction (HFpEF) diagnosis using the E/e' ratio, which is a non-invasive parameter of left ventricular diastolic performance, is unknown. The purpose of this study was to elucidate the impact of RWMA of the lateral wall (RWMAlat) on the correlation between E/e' and invasive parameters of left ventricular diastolic performance. METHODS: Three hundred and eight consecutive patients undergoing tissue Doppler imaging and catheterization pressure examination were retrospectively analyzed. E/e' was calculated as the ratio of early diastolic transmitral flow velocity to mitral annular velocity at the lateral wall. Invasive parameters including left ventricular end-diastolic pressure (LVEDP) and isovolumetric relaxation time constant (τ) were assessed based on the left ventricular pressure study. Correlation coefficients between E/e' and these invasive parameters were analyzed and compared between cases with RWMAlat and without RWMA. RESULTS: LVEDP and τ correlated well with E/e' for all 308 patients (r = 0.51 and r = 0.65, respectively). Sixty-two patients had RWMA; the remaining 246 did not have RWMAlat. We confirmed that the presence of RWMAlat weakens both the correlations between E/e' and LVEDP (r = 0.574 vs. r = 0.381), and E/e' and τ (r = 0.729 vs. r = 0.461). CONCLUSIONS: Although E/e' correlates well with parameters of left ventricular diastolic performance assessed by invasive methods, the presence of RWMAlat worsens this correlation. In cases with RWMAlat, careful assessment is required for HFpEF diagnosis because the diagnostic value of the E/e' ratio could be decreased compared to patients without RWMAlat.

Identification of high-risk Brugada syndrome patients by combined analysis of late potential and T-wave amplitude variability on ambulatory electrocardiograms.

BACKGROUND: Risk stratification is important in the management of Brugada syndrome (BrS). Late potentials (LPs) and T-wave amplitude variability (TAV) in high-resolution ambulatory electrocardiography (ECG) were retrospectively investigated. METHODS AND RESULTS: One hundred and twenty-seven patients diagnosed with BrS on 12-lead ECG were classified into 3 groups: documented ventricular fibrillation (VF)/asystole (n=19), episodes of syncope alone (n=30), and asymptomatic (n=78). Healthy volunteers were enrolled as controls (n=25). In the BrS patients, LPs showed appreciable circadian periodicity; filtered QRS duration (fQRS) and duration of the terminal low-amplitude signal <40 µV (LAS40) increased, whereas root mean square voltage of the terminal 40 ms of the fQRS (RMS40) decreased at night compared with the day. TAV did not have such a circadian periodicity. LP-positive incidence (night-time) and peak TAV were as follows: VF/asystole>syncope/asymptomatic>control (P<0.001). VF/asystole was discriminated from control at a ratio of 81-84% by night-time LPs (fQRS >116 ms, LAS40 >35 ms, RMS40 <25 µV) or peak TAV (>54 µV); VF/asystole was discriminated from syncope/asymptomatic at a ratio of 60-69%, by night-time LPs (fQRS >122 ms, LAS40 >42 ms, RMS40 <18µV) or peak TAV (>58 µV). Combined analysis of LPs and peak TAV increased the discriminant ratio up to 93% and 77%, respectively. CONCLUSIONS: Analysis of both LPs and TAV (taking circadian periodicity into account) is useful in identification of high-risk BrS patients.

Longitudinal analysis of the depressive effects of intravenous amiodarone on depolarization and repolarization: a case report.

Intravenous amiodarone (AMD) induces multiple antiarrhythmic effects via blocking of Na(+), Ca(2+), and IKr channels, and beta receptors. A patient on chronic dialysis was administered AMD for nonsustained ventricular tachycardia after successful cardiopulmonary resuscitation. QT prolongation occurred 5 h after AMD administration. AMD was withdrawn at 24 h because of prolonged QTc interval (716 ms), which persisted for a further 48 h (661 ms). Ventricular premature contraction (VPC) was significantly decreased at 7h; however, VPC increased again after discontinuing AMD. Depolarization changes induced by the Na(+)-channel blocking action of AMD were analyzed. There was increasing filtered QRS-duration and duration of low-amplitude signals at voltage <40 µV, and decreasing root-mean-square voltage of signals in the last 40 ms of ventricular late potentials (LPs) within 7 h. However after stopping AMD, LPs were reversed. The blood concentration of AMD reached the effective level within 10 min but decreased immediately to an ineffective level. Onset and disappearance of the VPC-inhibiting effect corresponded to the depressive effect on depolarization but not with the increase in the prolonged repolarization effect and blood concentration. Even if the QT interval is sufficiently prolonged, the Na(+)-channel blocking action is required for AMD to induce the antiarrhythmic effect.

Circadian distribution of paroxysmal atrial fibrillation in patients with and without structural heart disease in untreated state.

BACKGROUND: This study aimed to compare the circadian distribution of the onset, maintenance and termination of paroxysmal atrial fibrillation (PAF) between structural and non-structural heart diseases (SHD and NSHD, respectively) in the untreated state. SUBJECTS AND METHODS: We included 217 patients with 338 PAF (79 SHD patients with 131 episodes; 138 NSHD patients with 207 episodes). The probabilities for the onset, maintenance and termination of PAF for each hour were analyzed using Holter monitoring data and harmonic models being fitted into a cosinusoidal function. RESULTS: The SHD group had a triphasic circadian pattern at the onset with higher peaks at midnight, in the early morning and in the late afternoon (p < 0.05), whereas the NSHD group showed a single peak at midnight (p < 0.01). The probability of maintenance revealed a single peak during midnight (SHD, p < 0.0001; NHD, p < 0.01). The termination showed a peak at noon in the SHD group (p < 0.05), whereas there was a double peak at 10:00 am and 8:00 pm in the NSHD group (p=0.06). RR intervals just after the PAF onset showed marked shortening in the daytime initiation PAF as compared to the nighttime initiation PAF in both SHD and NSHD groups (p < 0.01). CONCLUSION: These observations suggest that the SHD group has very complex onset hours, whereas the NSHD group shows complex termination hours. Reflexly accelerated sympathetic tone just after the PAF onset is suggested in the daytime initiation PAF.

Nifekalant hydrochloride administration during cardiopulmonary resuscitation improves the transmural dispersion of myocardial repolarization: experimental study in a canine model of cardiopulmonary arrest.

BACKGROUND: Because nifekalant hydrochloride (NIF) displayed a superior defibrillating effect on ventricular tachycardia/fibrillation (VT/VF) in cardiopulmonary arrest (CPA) patients, despite some QT prolongation, its effect on transmural dispersion of repolarization (TDR) in the left ventricle (LV) in an animal model of CPA was investigated. METHODS AND RESULTS: Eight beagle dogs were created with a myocardial infarction under anesthesia, and then VT/VF induction by continuous stimulation and cardiopulmonary resuscitation (CPR) were repeated. NIF (0.3 mg/kg) was administered under acidotic conditions (pH 7.26). The QTc interval measured by Y-lead ECG showed no significant prolongation before and after NIF. The activation recovery interval (ARI) measured by 64-lead LV surface mapping showed minimum ARI prolongation (40%) by NIF without maximum ARI prolongation, and as a result the ARI dispersion decreased by 67%. The repolarization time (RPT) with the plunge electrode showed 13-19% prolongation in the subendocardium and subepicardium with CPR, but NIF prolonged the RPT in the middle layer alone (17%), and as a result Plunge-TDR decreased by 82% (n=8, p<0.05). CONCLUSIONS: Administration of NIF during CPR decreased the TDR by RPT prolongation selectively in the middle layer. Because the subendocardial and subepicardial RPTs after CPR were already prolonged before NIF administration, it may have been the reason why the QT-prolonging effect of NIF was not reflected in the body surface ECG.

Hypertensive patients with carotid artery plaque exhibit increased platelet aggregability.

BACKGROUND: Platelets play an important role in myocardial infarction and ischemic stroke events, but whether platelet aggregability is related to early stage arteriosclerosis remains unclear. METHODS: We used a novel platelet counting system which makes it possible to detect spontaneous platelet aggregation, to evaluate the relationship between platelet aggregability and carotid artery arteriosclerosis in 125 outpatients with primary hypertension (46-73 years old: 65 men, 60 women). All subjects underwent carotid artery ultrasonography to determine whether plaque was present and to estimate intima-media thickness. RESULTS: Patients with carotid artery plaques (Plaque(+), n=63) were older and had higher systolic blood pressures than patients without plaques (Plaque(-), n=62), but no significant differences in sex, body mass index, diastolic blood pressure, plasma concentrations of glucose, total cholesterol, triglyceride, lipoprotein cholesterol, fibrinogen or the platelet count in whole blood were observed between Plaque(+) and Plaque(-) groups. Plaque(+) subjects showed greater spontaneous platelet aggregability and platelet aggregation induced by 2 microM or 0.5 microM of ADP or 0.3 microM of epinephrine than the Plaque(-) group. When age and systolic blood pressure were matched (n=52 in both groups), the Plaque(+) subjects exhibited greater platelet aggregability than the Plaque(-) subjects. Platelet aggregation induced by 2 microM of ADP showed statistical significant positive correlation coefficients with age, HbA1c and diastolic blood pressure. CONCLUSION: Our results indicate that hypertensive patients with carotid artery plaque have increased platelet aggregability. A prospective study is recommended to clarify whether this increase in platelet aggregability promotes the progression of arteriosclerosis.

Can nifekalant hydrochloride be used as a first-line drug for cardiopulmonary arrest (CPA)? : comparative study of out-of-hospital CPA with acidosis and in-hospital CPA without acidosis.

BACKGROUND: Early defibrillation of ventricular tachycardia and fibrillation (VT/VF) is an urgent and most important method of resuscitation for survival in cardiopulmonary arrest (CPA). We have previously reported that nifekalant (NIF), a specific I(Kr) blocker developed in Japan, is effective for lidocaine (LID) resistant VT/VF in out-of-hospital CPA (OHCPA). However, little is known about the differences in the effect of NIF on OHCPA with acidosis and in-hospital CPA (IHCPA) without acidosis. METHODS AND RESULTS: The present study enrolled 91 cases of DC shock resistant VT/VF among 892 cases of CPA that occurred between June 2000 and May 2003. NIF was used (0.15-0.3 mg/kg) after LID according to the cardiopulmonary resuscitation (CPR) algorithm of Tokai University. The defibrillation rate was higher in the NIF group for both OHCPA and IHCPA than for LID alone, and the VT/VF rate reduction effect could be maintained even with acidosis. However, sinus bradycardia in OHCPA, and torsades de pointes in IHCPA were occasionally observed. These differences in adverse effects might be related to the amount of epinephrine, serum potassium levels, serum pH, and interaction with LID. CONCLUSIONS: NIF had a favorable defibrillating effect in both CPA groups, and it shows promise of becoming a first-line drug for CPR.

[Efficacy of Nifekalant hydrochloride for life-threatening ventricular tachyarrhythmias in patients with resistance to lidocaine: a study of patients with out-of-hospital cardiac arrest].

OBJECTIVES: Class I antiarrhythmic agents are not always effective in the treatment of life-threatening ventricular tachycardia/ventricular fibrillation (VT/VF) especially in patients with cardiopulmonary arrest. Nifekalant hydrochloride(NIF) is a novel class III antiarrhythmic agent for malignant VT/VF. This study prospectively evaluated NIF efficacy for life-threatening VT/VF observed after cardiopulmonary arrest. METHODS: Thirty-two of 145 patients who were transferred to the emergency room in Tokai University Hospital showed VT/VF after resuscitation from cardiopulmonary arrest from June 2000 to March 2001. These 32 patients were treated with 12 mg (mean) epinephrine and 1.0-2.0 mg/kg lidocaine following direct current application(200 to 360J), and then classified into two groups. Eleven patients received intravenous 0.15 to 0.3 mg/kg NIF followed by intravenous infusion of 0.3 to 0.4 mg/kg/hr NIF(NIF group). The other 21 patients received 1.0 to 2.0 mg/kg of lidocaine(non-NIF group). RESULTS: Sinus rhythm was restored in the nine patients(82%) in the NIF group but only four patients (19%) in the non-NIF group. QTc was not prolonged(0.45 +/- 0.04 sec, n = 9) and no torsades de pointes was observed in the NIF group. Two patients survived but the remaining nine patients died in the NIF group. Five patients died of cardiac standstill following sinus bradycardia and repeated sinus arrest within 2 to 27 hr after admission, two patients died of sudden cardiac arrest from sinus rhythm, and two patients died of persistent VT/VF. In contrast, all 21 patients in the non-NIF group died. Seventeen patients died of persistent VT/VF before hospitalization, one patient died of recurrent VT/VF, and three patients died of cardiac standstill following sinus bradycardia. CONCLUSIONS: NIF effectively suppresses VT/VF which is refractory to direct current shock in patients with cardiopulmonary arrest. However, NIF may rather worsen electrophysiological function in the sinus node after administration of high doses of epinephrine, and may induce sinus bradycardia and/or sinus arrest. Careful observation, such as monitoring of electrocardiography and blood pressure and temporary cardiac pacemaker use, is needed to prevent death in patients surviving after cardiopulmonary arrest if NIF is administered following high dose epinephrine infusion.

Identification of Plesiomonas shigelloides Isolated from Freshwater Fish with the Microplate Hybridization Method.

A total of 74 strains were isolated from the intestines of seven freshwater fish and 10 water samples, and identified to the species level by the conventional method based on morphological, physiological and biochemical properties, and DNA-DNA hybridization method. Achromopeptidase treatment was found to be useful for the recovery of DNAs from Plesiomonas shigelloides cells because the amount of DNA obtained with this treatment was 3.1-7.2 times greater than with lysozyme. All the strains were identified as P. shigelloides on the basis of the mol% G + C contents of DNAs and homology values against the type strain of this microorganism, along with morphological, physiological, and biochemical properties. The P. shigelloides was detected in 29 out of 51 fish specimens and four out of 10 water samples. Black bass, Japanese eel, ayu, and tilapia harbored high densities of P. shigelloides , ranging from 104-108 CFU/g, with high frequencies of occurrence (73-100%). These results strongly suggested that the microplate hybridization method is an excellent procedure for the ecological study of P. shigelloides .