Altered values of heart rate variability in patients with relapse of atrial fibrillation during the first week after electrical cardioversion: preliminary data.

BACKGROUND: It has not so far been elucidated whether the autonomic nervous system plays a role in the pathogenesis of atrial fibrillation relapse after electrical cardioversion. METHODS: In 40 consecutive patients with atrial fibrillation (22 males, 18 females, mean age 60 +/- 2 years) submitted to successful electrical cardioversion (external in 26 and low-energy internal in 14) we evaluated the heart rate variability (24-hour Holter recording) immediately after restoration of sinus rhythm in order to assess the cardiac sympatho-vagal drive. RESULTS: Patients with atrial fibrillation relapse within the first week of electrical cardioversion were characterized by a significantly higher low/high frequency ratio. CONCLUSIONS: Despite the heterogeneity of the studied population (concerning both the therapy and etiology of atrial fibrillation), our data strongly suggest that the evaluation of the low/high frequency ratio by means of power spectral analysis immediately after electrical cardioversion is a useful tool for the identification of those patients who are prone to atrial fibrillation recurrence. Our conclusions are supported by the finding of high positive and negative predictive values for the low/high frequency ratio both in the 24-hour period and during daytime.

Renal endothelin in heart failure and its relation to sodium excretion.

BACKGROUND: Recent studies have shown that endothelin-1 (ET-1) antagonists increase sodium excretion and improve renal blood flow in experimental heart failure (HF). However, despite a number of investigations that have reported a significant increase in ET-1 plasma levels in patients with HF, it is still not known whether increased renal synthesis and urinary excretion of ET-1 occur. Our aim was to investigate renal ET-1 formation and its relation to sodium excretion in patients with HF. METHODS: One hundred forty-seven patients with HF, subdivided according to New York Heart Association (NYHA) functional classes, and 28 healthy controls were studied. ET-1 and big ET-1 were measured in plasma and in 24-hour urine by radioimmunoassay. Atrial and brain natriuretic peptide, arginine vasopressin, plasma renin activity, and hemodynamic variables were also investigated. RESULTS: Urinary ET-1 excretion was already increased in NYHA class II patients (P <.001 vs controls), whereas plasma ET-1 increased only in NYHA class III and IV patients (P <.001). In the 71 subjects who were not receiving diuretic treatment, urinary ET-1 was selected as the strongest predictor of sodium excretion by multivariate stepwise analysis. CONCLUSIONS: Urinary ET-1 excretion increases in an earlier phase of HF than plasma ET-1 and appears to be closely correlated with sodium excretion, indicating renal ET-1 is a target for ET-1 antagonists in patients with HF.

Prevention of short term reversible chronic atrial fibrillation by permanent pacing at the triangle of Koch.

OBJECTIVES: The purpose of this study was to investigate if single lead interatrial septum pacing could be effective in maintaining sinus rhythm in patients in whom restoration of sinus rhythm was only possible for a period of 2-24 hours after one or more previous electrical cardioversions, and in whom a sinus bradycardia was documented before arrhythmia restarted. The two hours limit was chosen because it was considered a sufficient time to implant a dual chamber pacemaker. BACKGROUND: Alternative atrial pacing techniques have been demonstrated to be successful in preventing recurrences of atrial fibrillation (AF) in patients with sinus bradycardia. Excluding the AF occurring after only a few sinus beats, at 24 hours from electrical cardioversion an early restart of chronic AF has been reported in 12% to 17% of the patients. METHODS: After sinus rhythm was restored by internal electrical cardioversion, 17 patients, 7 ablated at the AV junction, underwent a dual chamber rate response (DDDR) pacemaker implantation with a screw-in atrial lead placed in the interatrial septum. RESULTS: After a follow-up period of 17+/-5 months (range 12 to 27 months) persistence of sinus rhythm was observed in 11 patients (65%). Six patients (35%) had recurrences of paroxysmal attacks, while five (30%) were totally free of AF. Recurrence of chronic AF was observed in six cases (35%) after 2 days-12 months from implantation. No dislodgements of the atrial lead and no complications were observed at implantation and during follow-up. CONCLUSIONS: Interatrial septum pacing is a safe and feasible technique with a satisfying success rate (65%) in long-term maintaining sinus rhythm in previously unsuccessfully cardioverted patients.

Atrioventricular interval optimization in the right atrial appendage and interatrial septum pacing: a comparison between echo and peak endocardial acceleration measurements.

Interatrial septum pacing (IASP) reduces interatrial conduction time and consequently may interfere with atrioventricular delay (AVD) optimization. We studied 14 patients with an implanted BEST Living system device able to measure peak endocardial acceleration (PEA) signal. The aims of our study were to compare the (1) optimal AVD (OAVD) in right atrial appendage pacing (RAAP) and IASP, and (2) OAVD derived by the PEA signal versus OAVD derived by Echo/Doppler evaluation of the left ventricular filling time (LVFT) and cardiac output (CO). Measurements were performed in DDD VDD modes Eight patients (group A) had RAAP and six patients (group B) had IASP. In group A, OAVD measured by LVFT, CO, and PEA was 185 +/- 23 ms, 177 +/- 19 ms, and 192 +/- 23 ms in DDD and 147 +/- 19 ms, 135 +/- 27 ms, and 146 +/- 20 ms in VDD, respectively. OAVD measured by LVFT, CO, and PEA was significantly longer in DDD mode than in VDD (P < 0.01, P < 0.01, P < 0.001). In group B, OAVD measured by LVFT, CO, and PEA was 116 +/- 19 ms, 113 +/- 10 ms, and 130 +/- 30 ms in DDD and 106 +/- 16 ms, 96 +/- 15 ms, and 108 +/- 26 ms in VDD, respectively. No statistical differences were observed between DDD and VDD. Significant correlations between OAVDs PEA derived and OAVDs LVFT and CO derived were observed (r = 0.71, r = 0.69, respectively). When new techniques of atrial stimulation, as IASP, are used an OAVD shorter and similar in VDD and DDD has to be considered. The BEST Living system could provide a valid method to ensure, in every moment, the exact required OAVD to maximize atrial contribution to CO.

Interatrial septum pacing: a new approach to prevent recurrent atrial fibrillation.

BACKGROUND: There are a variety of approaches to the prevention of atrial fibrillation (AF) with pacing. Aim of this study was to test the safety and feasibility of interatrial septum pacing at the posterior triangle of Koch for AF prevention and to exclude potential arrhythmic effects. MATERIAL AND METHODS: Interatrial septum pacing was performed in 34 patients (21 males, 13 females, mean age 69 +/- 12 years): 9 without a history and clinical evidence of atrial fibrillation (AF) (6 with sinus bradycardia, 2 with second-degree AV block, and 1 with carotid sinus hypersensitivity) and 25 with sinus bradycardia and paroxysmal atrial fibrillation (PAF) (mean symptomatic episodes/month 6.2 +/- 10). In all patients a screw-in bipolar lead was positioned in the interatrial septum superiorly to the coronary sinus. RESULTS: At implant the mean P wave amplitude was 2.5 +/- 1.5 mV, the pacing threshold was 1 +/- 0.6 V and the impedance was 907 +/- 477 Ohm. Mean P wave duration was 118 +/- 17 ms in sinus rhythm and 82 +/- 15 during interatrial septum pacing (p < 0.001). During a mean follow-up period of 10 +/- 7 months, no patients without atrial tachyarrhythmias before implantation experienced AF. During a 9 +/- 6 months follow-up we observed only 2 symptomatic arrhythmia recurrences between AF patients (mean symptomatic episodes/month 0.006 +/- 0.0022) (p < 0.01 vs before implant period). CONCLUSIONS: Our data indicate that interatrial septal pacing is safe and feasible. A significant less incidence of arrhythmic episodes has been observed during follow-up. Further controlled randomized prospective studies are necessary to establish the exact role of this technique respect to conventional or multisite stimulation when patients with paroxysmal AF need to be permanently paced.

Increased renal endothelin formation is associated with sodium retention and increased free water clearance.

To investigate whether renal endothelin (ET)-1 participates in water and sodium handling, we investigated the influence of different sodium intakes on renal production of ET-1 in eight healthy subjects. The functional relationship with the renin-angiotensin system was also studied. Renal ET-1 formation is affected by sodium intake, because 1 wk of high sodium decreased urinary ET-1 excretion (-34%, P < 0.05), whereas a low-sodium diet increased ET-1 excretion (66%, P < 0.05) and mRNA expression for preproendothelin-1 in epithelial cells of medullary collecting ducts and endothelial cells of the peritubular capillary network. Increased ET-1 renal synthesis was associated with sodium retention and increased free water clearance. Urinary ET-1 excretion changes from normal to low-sodium diet were negatively related to contemporary changes in sodium excretion (r = 0.97, P < 0.05) and were positively correlated with free water clearance (r = 0.97, P < 0.05). These correlations were maintained during angiotensin-converting enzyme inhibition, which only partially reduced ET-1 renal excretion. These results indicate that renal ET-1 production is indeed modulated by varying sodium intakes and may exert a role in sodium and water handling.

Spectral analysis of 24 h blood pressure monitoring in the assessment of trough: peak ratio. A randomized, placebo-controlled, cross-over comparison of ramipril and enalapril.

BACKGROUND: The ratio between the magnitude of blood pressure reduction during the steady-state dosage interval (trough) and the maximum blood pressure reduction (peak) is an integrated in-vivo index both of the pharmacokinetic properties and of pharmacodynamic activity of an antihypertensive drug. Angiotensin converting enzyme inhibitors are often characterized by a low (often lower than 50%) trough: peak ratio but no direct drug comparisons are available. OBJECTIVE: To compare the absolute blood pressure reduction and the trough: peak ratio of daily doses of two angiotensin converting enzyme inhibitors, 5 mg ramipril and 10 mg enalapril. METHOD: After a 1-month wash-out and a 2-week placebo run-in, 25 mild hypertensives aged 47 +/- 4 years (17 men and eight women) were randomly assigned to treatments separated by a 2-week interval. Ambulatory blood pressure monitoring was performed and trough: peak ratio was calculated by the fast Fourier transform analysis of placebo-effect-subtracted data. RESULTS: After 1 month of ramipril treatment, 24 h blood pressure decreased from 139 +/- 10 to 129 +/- 11 mmHg for systolic (P < 0.05) and from 89 +/- 8 to 81 +/- 5 mmHg for diastolic blood pressure (P < 0.01). Also enalapril treatment caused a significant 24 h reduction in blood pressure both for systolic (to 132 +/- 7 mmHg, P < 0.05) and for diastolic blood pressure (to 84 +/- 5 mmHg, P < 0.05). Placebo caused a 24 h reduction in blood pressure (to 136 +/- 8 mmHg for systolic and 87 +/- 5 mmHg for diastolic blood pressure, NS, versus wash-out period). The two drugs were equally effective in reducing ambulatory blood pressure, but ramipril produced a trough: peak ratio significantly higher than that with enalapril both for systolic (48 +/- 11%, range 34-74%, versus 38 +/- 11%, range 21-67%, P < 0.005)and for diastolic blood pressure (47 +/- 11%, range 30-79 %, versus 37 +/- 12%, range 21-68%, P < 0.05). CONCLUSION: The low trough : peak ratios could have been due to the daily pattern of blood pressure of mild hypertensives, many of whom are normotensives at night-time, so that the main antihypertensive effect is exerted during daytime rather than during the night or early morning.

Clinical evaluation of the QuietTrak blood pressure recorder according to the protocol of the British Hypertension Society.

METHODS: The QuietTrak ambulatory blood pressure recorder (Tycos-Welch-Allyn, Arden, North Carolina, USA) was evaluated according to the protocol of the British Hypertension Society (BHS). QuietTrak, a lightweight (355 g), automatic, programmable device, uses an auscultatory measuring system. The protocol of the BHS was composed of subsequent phases with QuietTrak and two observers taking simultaneous measurements on the same arm. RESULTS: No interdevice differences were observed at analysis of variance test either before or after a 1-month period of routine clinical use. The average difference between mercury sphygmomanometer and QuietTrak for systolic and diastolic blood pressures was -0.6+/-3.6 and -0.4+/- 3.6 mmHg before and -0.7+/- 3.3 mmHg and 0.6+/- 3.8 mmHg after the 1-month use. At the main static device validation procedure, performed in 85 subjects, the average difference between observers and QuietTrak was -0.3+/- 3.4 and 0.1+/- 3.5 mmHg for systolic and diastolic blood pressures. Eighty-nine per cent and 99% of systolic and 88% and 98% of diastolic QuietTrak readings were within 5 and 10 mmHg of obsevers, determinations (Class A). In children (n = 33) 87% of systolic and 90% of diastolic QuietTrak readings differed by less than 5 mmHg from the observers' readings (average difference -1.1+/-3.9 and 0.1+/- 3.6 mmHg, respectively). In the elderly (n = 30), 95% and 92% of systolic and diastolic readings were within 5 mmHg of mercury column determinations (average difference -0.8+/-3.2 and -0.2+/-4.5 mmHg). In pregnancy (n = 30), 93% of systolic and 100% of diastolic readings were within 5 mmHg of mercury column determination (average difference -0.3+/-3.4 and 0.1+/- 2.9 mmHg). Device reliability was not affected by posture. Ninety-six per cent and 89% of systolic and diastolic readings differed by less than 5 mmHg from the mercury column determinations in the supine position, 90% and 90% in the standing position, and 88% and 90% in the sitting position. During the treadmill exercise (Bruce protocol), 69% and 88% of systolic and 56% and 83% of diastolic QuietTrak readings differed by less than 5 and 10 mmHg from the observers' measurements. CONCLUSION: The QuietTrak achieved A rating for systolic blood pressure and A rating for diastolic blood pressure according to the criteria of the BHS protocol. The device was acceptable to patients because of its small size, light weight and noiseless performance.

Increased number of thromboxane A2-prostaglandin H2 platelet receptors in active unstable angina and causative role of enhanced thrombin formation.

The current study was designed to investigate the number and affinity of platelet thromboxane A2/prostaglandin H2 (TxA2/PGH2) receptors in patients with unstable angina and, if any, the role played by the increased thrombin formation that is a common finding in these patients. Measurements taken during active unstable angina but not those taken during inactive angina showed an increase number (p < 0.001), without changes in affinity, of platelet TxA2/PGH2 receptors, evaluated as the binding capacity of iodine 125-PTA-OH, a stable TxA2 analogue. Moreover patients with active angina had higher plasma concentrations of fibrinopeptide A (FPA) (p < 0.0001), which were significantly related to the number of platelet TxA2/PGH2 receptors (r = 0.76; p < 0.01). Heparin infusion but not aspirin treatment promptly normalized the number of TxA2/PGH2 receptors and significantly reduced plasma FPA concentrations. In an in-vitro study thrombin in a concentration similar to that found in vivo significantly increased the number of platelet TxA2/PGH2 receptors (p < 0.01), whereas heparin did not affect TxA2/PGH2 receptors. These results have important therapeutic implications and indicate the preferential use of heparin rather than aspirin during the acute phase of unstable angina.

Plasma endothelin and renal endothelin are two distinct systems involved in volume homeostasis.

This study of seven healthy young subjects was designed both to establish whether endothelin-1 (ET-1) is involved in the homeostasis of blood volume and to clarify the relationship between plasma and urinary ET-1. Acute volume expansion (+17%) caused increases in venous blood pressure (+4.4 mmHg) and the plasma concentration of ET-1 (+129%) and a decrease (-99%) in the urinary excretion of ET-1. Volume depletion (-8.5%) provoked an increase in the plasma concentration of ET-1 without altering the urinary excretion of ET-1. Passive elevation of an arm resulting in a local decrease of venous blood pressure (-17 mmHg) elicited an increase of the local formation of ET-1, with a 10-fold increase in the venous-arterial gradient compared with the opposite arm, which lay at the level of the heart. The increased local formation of ET-1 was blunted by volume expansion. The results indicate that 1) plasma ET-1 and urinary ET-1 represent two different endothelin-generating systems, both of which are involved in the regulation of blood volume, and 2) plasma ET-1 appears to be an important mechanism for the long-lasting adaptations of venous wall tension to changes in blood volume.

Binding kinetics and antiplatelet activities of picotamide, a thromboxane A2 receptor antagonist.

1. Picotamide was shown to inhibit platelet binding of thromboxane A2 (TxA2)-mimetics and to cause a reduction of TxA2 platelet receptors after in vivo administration. The present study aimed to investigate directly [3H]-picotamide binding to human platelets and in particular the relationship between binding kinetics and antiaggregating properties. 2. [3H]-picotamide time-dependently bound to a single class of platelet TxA2 receptors with a KD of 325 nmol l-1 at equilibrium. The binding was displaceable by TxA2 analogues U46619 and ONO11120 (Ki 19 and 28 nmol l-1 respectively) but not by prostacyclin (PGI2), prostaglandin E2 (PGE2) and TxB2. Antiaggregating activity and TxA2 formation inhibition paralleled with binding kinetics. 3. By prolonging the incubation time from 30 to 120 min, picotamide showed a progressively increasing non-displaceable binding, whereas specific displaceable binding decreased in comparison to the values reached at 30 min. Non displaceable binding was specific, temperature-dependent saturable and followed a Michaelis-Menten kinetic (Vmaxapp = 130 fmol per 10(8) platelets h-1, KMapp = 330 nmol l-1). Picotamide progressively underwent a specific stable interaction with its platelet receptor. 4. In conclusion, after an initial reversible binding, a progressive stabilization of picotamide binding takes place resulting in a progressively more stable interaction with platelets.