B-type natriuretic peptide levels are decreased by reducing dietary salt intake in patients with compensated heart failure with preserved ejection fraction.

BACKGROUND: Dietary salt restriction is believed to be a mainstay in the management of patients with heart failure. However, the effect of salt intake on heart failure has not been well evaluated in outpatient medical practice. AIMS: The aim of the present study was to assess the hypothesis that B-type natriuretic peptide (BNP) level, as an objective marker of heart failure, is associated with salt intake in patients with heart failure. METHODS: One hundred and thirteen consecutive patients with mild compensated heart failure (77 ± 10 years old, 51 female) were included. We estimated dietary salt intake by the concentration of sodium and creatinine in spot urine. We measured BNP at the time of urine sampling and assessed the relationship between the % changes in BNP levels (%ΔBNP) and the changes in the estimated daily salt excretion (ΔNaCl) during the follow-up period. RESULTS: The baseline median BNP level was 150 (interquartile range: 83-263) pg/mL and the estimated daily salt excretion was 162 ± 45 mmol/day. There was a positive correlation between %ΔBNP and ΔNaCl (r = 0.61, P < 0.01). Multiple regression analysis revealed that %ΔBNP was associated with ΔNaCl (P < 0.01), but not with changes in systolic blood pressure and bodyweight. CONCLUSIONS: Changes in BNP levels were associated with changes in the estimated daily salt excretion in outpatients with compensated heart failure. Salt restriction may be beneficial for the management of patients with heart failure.

Altered diurnal variation of blood pressure in elderly subjects with decreased activity of daily living and impaired cognitive function.

Activity of daily living (ADL) and cognitive are indices of physical and psychological activity in elderly subjects. The present study was performed to clarify the relationship among ADL, cognitive function, and ambulatory blood pressure (ABP) in the elderly. Study subjects were 77 females and 22 males (aged 60 to 101 years) with various levels of ADL and cognition, who were in nursing homes or geriatric hospitals. ABP was recorded every 30 min for 24 h by a noninvasive device. Mini-mental state examination (MMSE) and Barthel index measurement were used to evaluate cognitive function and ADL, respectively. Both the MMSE and Barthel index values showed a significant positive correlation with daytime ABP but not with nighttime ABP. The dip in nighttime BP correlated negatively with age, and positively with MMSE and Barthel index. In the multiple regression analysis, age and Barthel index values remained significant determinants of the dip in nighttime BP. Presence of stroke and MMSE became significant when the Barthel index values were removed from the analyses. When subjects were classified by tertiles of MMSE or Barthel index, subjects in the lowest MMSE group and those in the lowest Barthel index group had both lower daytime ABP and smaller nighttime BP dip than those of the other groups. A low BP level during the daytime was associated with altered diurnal variation of BP in elderly subjects with greater age, impaired cognitive function, and/or decreased ADL. ADL had a greater influence on diurnal BP variation than did cognitive function.

Superselective embolisation for intractable idiopathic epistaxis.

37 patients with intractable idiopathic epistaxis were treated with superselective embolisation between 1995 and 1999. A total of 40 embolisations was performed, including three procedures for recurrence. The embolic material was gelatin sponge in 27 procedures, microcoils in 9 and both gelatin sponge and microcoils in 4. Immediate cessation of nasal bleeding was obtained in all patients after embolisation. Recurrent epistaxis occurred in 2 (5.4%) of the 37 patients within 7 days after initial embolisation, giving a short-term success rate of 94.6%. The long-term follow-up ranged from 1-51 months (mean 21.6 months). Late re-bleeding occurred in two patients, giving a long-term success rate of 94.6%. Two patients underwent re-embolisation; it was necessary to embolise the ipsilateral facial artery and/or the contralateral internal maxillary as well as the ipsilateral maxillary artery. Although the overall complication rate was 45.0%, no major complications occurred. Superselective embolisation with gelatin sponge is an effective and safe treatment technique for intractable idiopathic epistaxis.

Repetitive monomorphic ventricular tachycardia of left coronary cusp origin.

Repetitive monomorphic ventricular tachycardia with a morphology of inferior axis and left bundle branch block pattern in patients without structural heart disease commonly originates from the right ventricular outflow tract. We report the case of a 22-year-old man with an incessant, monomorphic ventricular tachycardia with a similar morphology originating from the left coronary cusp, which was confirmed by perfect pace mapping, local ventricular activation preceding the onset of QRS by 25 mse, and eliminated by a single delivery of low-energy (11 W) radiofrequency currents.

Assessment of reverse use-dependent blocking actions of class III antiarrhythmic drugs by 24-hour Holter electrocardiography.

OBJECTIVES: This clinical study was designed to compare rate-dependent effects of class III agents on QT prolongation. BACKGROUND: Clinical data that compare the electrophysiologic differences among class III agents with different selectivity for potassium channels are still lacking. METHODS: QT intervals were measured over a wide range of preceding RR intervals during sinus rhythm by 24-h Holter electrocardiography before and after oral administration of four class III agents: E4031, dofetilide, MS551 and d-sotalol. Rate-dependent changes in the QT interval were assessed by the slope of the linear regression line estimating the QT-square root of RR relation. RESULTS: All agents significantly increased the mean slope: E4031 increased the mean [+/- SD] value from 0.32 +/- 0.05 to 0.42 +/- 0.13 (p < 0.01), dofetilide from 0.32 +/- 0.03 to 0.50 +/- 0.12 (p < 0.03), MS551 from 0.35 +/- 0.06 to 0.45 +/- 0.10 (p < 0.02) and d-sotalol from 0.31 +/- 0.05 to 0.33 +/- 0.04 (p < 0.05). However, in those patients given either E4031, dofetilide or MS551, the degree of QT prolongation was smaller at shorter square root of RR intervals and was better preserved at shorter square root of RR intervals by d-sotalol, with a smaller increase in slope (p < 0.02 vs. dofetilide and MS551). CONCLUSIONS: On ambulatory electrocardiography, reverse use dependence in QT prolongation was least prominent with d-sotalol among the four study drugs. In the range of physiologic heart rates, class III agents could manifest different profiles of rate dependence in their QT-prolonging effect.

Rate-dependent anisotropic conduction property in the epicardial border zone of canine myocardial infarcts and its modification by moricizine.

We evaluated anisotropic conduction properties, different conduction velocities depending on fiber orientation, in normal and infarcted myocardium and the effects of moricizine on anisotropic conduction. Various cycle lengths of stimulation were applied to 15 mongrel dogs, and epicardial mapping was performed using a 96-channel mapping electrode. Moricizine was then administered to seven dogs and the same procedure was performed. Conduction velocities were calculated from these maps. Programmed electrical stimulations were performed before and after moricizine administration to induce ventricular arrhythmias. Before moricizine administration, a rate-dependent decrease in longitudinal conduction velocity was observed in the infarcted zone. Moricizine suppressed longitudinal conduction in the normal zone significantly at 300 msec pacing, but not at slower rates. Moricizine at a dose of 4 mg/kg, on the other hand, suppressed longitudinal conduction in the infarcted zone significantly at all pacing cycle lengths. The effect of moricizine on transverse conduction was inconsistent. In three dogs, sustained ventricular tachycardia (VT) was induced either before or after moricizine administration. The mean cycle length of sustained VT was prolonged from 202 msec to 291 msec after 4 mg/kg of moricizine. Thus, the changes in cycle length of ventricular tachycardia observed were most likely the result of slowing of conduction velocity, especially in the longitudinal direction, in the infarcted myocardium. We conclude that the electrophysiologic nature of the subacute ischemic model was modified by moricizine, leading to depression of the conduction velocity of longitudinal conduction and the inducibility of ventricular arrhythmias.

Ischemia enhances use-dependent sodium channel blockade by pilsicainide, a class IC antiarrhythmic agent.

OBJECTIVES: The aim of this study was to elucidate whether the electrophysiologic properties of pilsicainide, a novel class IC drug with slow kinetic properties, could be altered in the presence of acute myocardial ischemia. BACKGROUND: An increase in the rate of sudden death in patients taking flecainide and encainide has been reported by the Cardiac Arrhythmia Suppression Trial (CAST), implying a proarrhythmic effect that may be due to the interaction between ischemia and class IC antiarrhythmic drugs. METHODS: Thirty-five patients and 16 age-matched control patients performed a treadmill exercise test and were assigned to four study groups: group A = 16 control patients; group B = 15 patients with ischemic ST segment depression; group C = 11 patients receiving pilsicainide without ST segment depression; and group D = 9 patients receiving pilsicainide with ischemic ST segment depression. The QRS duration was measured at rest and at heart rates of 80, 100 and 120 beats/min. RESULTS: There were no changes in the QRS duration as heart rates increased to 120 beats/min in the control patients. Ischemia, however, independently caused a significant increase in QRS duration at a heart rate of 120 beats/min. Pilsicainide produced a rate-dependent prolongation of the QRS duration in patients without ST segment depression as the heart rate increased to 100 beats/min. The combination of ischemia and pilsicainide led to a much greater rate-dependent prolongation of the QRS duration. CONCLUSIONS: Combination of a class IC drug and acute ischemia could lead to additive rate-dependent ventricular conduction slowing. This may be one plausible mechanism for the induction of proarrhythmias noted in the CAST study.

Sympathetic denervation of the epicardial border zone in the genesis of dispersion of refractoriness and arrhythmogenesis in a 7-day-old canine myocardial infarction model.

BACKGROUND: The purpose of this study was to clarify whether sympathetic denervation occurs in the infarcted heart and contributes to the dispersion of the effective refractory period (ERP) and arrhythmogenesis. METHODS: ERP was measured at 47 epicardial sites in 13 dogs with 7-day-old infarctions after proximal ligation of the left anterior descending artery. To delineate the sympathetic innervation, the effects of ansae subclaviae stimulation (ASS), norepinephrine infusion, and prazosin infusion on ERP were tested. RESULTS: The per cent change in ERP (delta ERP) induced by ASS was significantly lower at test sites where the surviving epicardial myocardial thickness (Th) was 2 mm or less than at those with a Th of more than 2 mm and the normal zone. Eleven out of 179 sites (6.1%) overlying the infarct showed no ERP change after ASS. ASS paradoxically prolonged ERP at 29 sites (16.2%). In contrast, norepinephrine infusion produced a greater delta ERP in the infarct zone than in the normal zone. Prazosin shortened ERP at sites where ASS prolonged it, but had no effect at sites where ASS shortened ERP. ASS increased both the degree of ERP dispersion and inducibility of ventricular tachycardias or ventricular fibrillation (VT/VF), whereas norepinephrine increased VT/VF inducibility despite a reduction in ERP dispersion. CONCLUSIONS: We conclude that heterogeneous sympathetic denervation contributed to a prolongation and dispersion of ERP in the surviving epicardium overlying the infarct. Furthermore, a supersensitive response to norepinephrine with resultant ERP shortening and a paradoxical ERP prolongation during ASS caused by alpha-receptor mechanisms that may be related to increased electrical instability were observed.

Clinical evaluation of the use-dependent QRS prolongation and the reverse use-dependent QT prolongation of class I and class III antiarrhythmic agents and their value in predicting efficacy.

We measured the QRS duration during a treadmill exercise test and the QT interval using a 24-hour Holter electrocardiogram at various heart rates to identify use-dependent QRS prolongation and reverse use-dependent QT prolongation of class I and III antiarrhythmic drugs. Use-dependent QRS prolongation was detected in 61%, 53%, and 64% of patients receiving disopyramide, mexiletine, and pilsicainide, respectively. Reverse use-dependent QT prolongation was found in 40% and 70% of patients receiving disopyramide and E4031. Drugs suppressed > or = 75% of the total premature ventricular contractions in all patients who had both use-dependent QRS prolongation and reverse use-dependent QT prolongation, in 79% of patients with use-dependent QRS prolongation alone, in 70% with reverse use-dependent QT prolongation alone, and in 11% with neither use-dependent QRS prolongation nor reverse use-dependent QT prolongation. Use-dependent QRS prolongation and reverse use-dependent QT prolongation were identified noninvasively and were useful in evaluating antiarrhythmic efficacy.

Quantitative indices of dispersion of refractoriness for identification of propensity to re-entrant ventricular tachycardia in a canine model of myocardial infarction.

STUDY OBJECTIVE: To identify propensity to re-entry in a canine model of 7 day old myocardial infarction, the sensitivity and specificity of five indices of dispersion of refractoriness (ERP) were investigated. DESIGN: With an epicardial patch electrode containing 47 electrodes, ERP was measured by S1-S2 method at each site overlying the infarct. ERP range, maximum adjacent dispersion, difference between mean ERPS of the infarct and normal zones, standard deviation (sigma) of the mean ERP, and sigma/mean ERP X 100 were calculated. EXPERIMENTAL MATERIAL: 42 dogs were divided into three groups; 20 dogs with epicardial functional block on induction of sustained ventricular tachycardia or fibrillation, 10 dogs with inducible ventricular tachycardia or fibrillation but without epicardial functional block, and 12 control dogs without ventricular tachycardia, fibrillation or block. MEASUREMENTS AND MAIN RESULTS: All five indices were significantly greater in the 20 dogs with ventricular tachycardia or fibrillation than in control dogs. A receiver operating characteristic curve analysis of the five indices showed that sigma was the most sensitive and specific index for discriminating these 20 dogs. The sensitivity and specificity of a sigma value greater than 14 ms (the mean value plus two SD of the control dogs) were 70% and 100%, respectively.

Electrophysiological and anatomical substrates for late potential recorded by signal averaging in seven-day-old myocardial infarction in dogs.

A filtered QRS (fQRS) was recorded by signal averaging in 7-day-old myocardial infarction (MI) in dogs to detect late potential (LP). The criteria for the LP included a duration of fQRS (D) greater than or equal to 60 msec and a voltage in the last 15 msec (V15) less than or equal to 10 microV. These parameters were determined from the control data from 15 dogs without infarction (D: 45 to 60 msec and V15: 12.0 to 83.6 microV). On the seventh day of infarction, the D had increased from 53.5 +/- 4.7 to 62.2 +/- 9.6 msec (P less than 0.05) and the V15 decreased from 38.6 +/- 19.5 to 18.4 +/- 16.0 microV (P less than 0.01). Of 23 dogs, 14 met the LP criteria (group A) and 9 did not (group B). Sustained ventricular tachycardia (SVT) was induced in 12 group A dogs and in none of the group B dogs. The delayed epicardial activation (DEA) was recorded after the end of QRS at 5.1 +/- 4.7 sites in group A dogs and 1.3 +/- 1.8 sites in group B dogs (P less than 0.05). The maximum value of epicardial activation time was more prolonged in group A than in group B (70.0 +/- 28.3 vs 44.4 +/- 9.8 msec, P less than 0.01). The area of MI was more extensive in dogs with DEA than those without (24.9 +/- 5.8% vs 10.3 +/- 9.0% of the total left ventricular weight, P less than 0.01). In 72 of 90 sites with DEA, the thickness of the surviving epicardial muscle was less than or equal to 1 mm. The sensitivity and specificity of the criteria for LP in detecting DEA were 71.4% and 55.6%, and 100% and 81.8% for predicting inducibility of SVT. It was thus concluded that LP, reflected the DEA, was identified from infarct areas of slow conduction within a reentry circuit of SVT.