The D-HCM score, a new diagnostic tool for distinguishing hypertrophic cardiomyopathy from hypertensive cardiopathy.

AIM: The diagnosis of hypertrophic cardiomyopathy (HCM) with moderate hypertrophy is challenging. Hypertensive heart disease (HHD) is the most common differential diagnosis that mimics the LVH of HCM. The aim of this study was to compare the QRS duration in HCM and HHD to create a novel diagnostic tool to identify primary HCM. METHODS AND RESULTS: We conducted an international retrospective multicentre study enrolling patients with true HCM and HHD. A total of 547 individuals with HCM and 139 with HHD were included. The median QRS duration was significantly shorter in HCM than in HHD (88 ms [80-94] vs. 98 ms [88-108]; P < 0.01). Multivariable logistic regression identified for the novel diagnostic HCM (D-HCM) score: absence of antihypertensive drugs (+2); family history of unexplained sudden death (+2); QRS duration [<95 ms] = +1; maximum wall thickness (mm) [≥17] = +1. A cumulative QRS-HCM score ≥2 supports the diagnostic certainty of true HCM with a sensitivity of 79%, specificity of 99%, negative predictive value (NPV) of 55%, and positive predictive value (PPV) of 99%. CONCLUSION: The QRS duration in patient with HCM is significantly shorter compared with patients with HHD-related LVH. QRS duration can be used as a diagnosis marker to distinguish between HCM and HHD. The D-HCM score is a novel, simple, and accurate diagnosis tool for HCM patients with mild to moderate phenotypes.

[Radiofrequency ablation of left premature ventricular complex from the papillary muscle]. / Ablation par radiofréquence d'un foyer d'extrasystoles ventriculaires gauches du muscle papillaire.

BACKGROUND: Radiofrequency ablation for incessant and symptomatic premature ventricular complex (PVC) localized in a left papillary muscle is uncommon. 3D mapping and cardiac MRI may be useful to achieve ablation success. CLINICAL CASE: A fifty-four-years-old man was referred for palpitations. His medical history included placement of a right coronary artery stent six years before and a normal ejection fraction (EF). The Holter monitoring under beta-blocker therapy (46% PVCs) and ECG showed monomorphic PVCs with a right bundle branch block, positive concordance with V5 transition and a superior axis, with no R/T phenomenon. During two separate electrophysiologic procedures (recurrence), a 3D mapping (Velocity, ST-Jude Medical™) system was used combined with an irrigated tip catheter. The earliest site of PVC activation documented with the mapping system was near the posterior papillary muscle. Pace mapping in this area showed nearly 90% concordance. After 2126 seconds of radiofrequency applications, there were no more PVC and no inducible arrhythmia. Post procedure cardiac MRI showed scar in the inferior-lateral area of the left ventricle including a section of the posterior papillary muscle. Scar included 50% of the thickness of the wall (previous 2005 myocardial infarction and radiofrequency lesions). Residual EF was 55%. At 2 months of follow-up, the patient was asymptomatic, with only 53 PVCs on 24-hour Holter monitoring. Patient was maintained under beta-blocker therapy for his coronary artery disease. At six-month follow-up, he is still asymptomatic. CONCLUSION: This case report stresses the role of cardiac MRI and 3D cartography systems for successful treatment of papillary muscle PVCs associated with ischemic cardiomyopathy, which still represent a therapeutic challenge.

Usefulness of cardiac resynchronisation therapy in patients with right bundle branch block: is viability an important piece of the puzzle?

BACKGROUND: Benefits of cardiac resynchronisation therapy (CRT) in patients with heart failure (HF) and left bundle branch block (LBBB) have been well established. The presence of asynchronism and viability predicts response to CRT with good accuracy. Viability in the region of the pacing lead as predictor of response to CRT in patients with HF, intraventricular asynchrony and right bundle branch block (RBBB) has never been evaluated. METHODS: We studied 4 consecutive patients with RBBB (QRS>120 ms) advanced ischemic HF, low ejection fraction (≤35%) and intraventricular asynchrony ≥50 ms scheduled for CRT. Dobutamine stress echocardiography (DSE) was performed within the week before CRT. Viability was defined as increased wall thickening during DSE. Viability in the region of left ventricular (LV) pacing lead was defined as the presence of viability in 2 contiguous segments. Response was defined by LV reverse remodeling (i.e. ≥15% reduction in LV end-systolic volume) 3-6 months after CRT. RESULTS: Three patients demonstrated LV reverse remodeling at follow-up. Responders showed LV end-systolic volume decrease of -31 ± 16% from baseline to follow-up whereas no change was observed in the non responder patient. Similar LV asynchronism was found in all patients. All responders had viability in ≥2 segments in the region of LV pacing. CONCLUSION: This preliminary report suggests that similar reverse remodeling can be observed in RBBB patients as patients with LBBB after CRT. Intraventricular asynchrony and RBBB, viability in the region of pacing lead may help to predict response to CRT in patients with HF.

Intraoperative study of polarization and evoked response signals in different endocardial electrode designs.

Some new generation pacemakers use an algorithm based on evoked response (ER) detection to verify beat-to-beat capture and to enable automatic adjustment of output. This is a prospective acute study of polarization signal (PS) and ER in nine currently available electrodes. Intraoperative testing of ventricular bipolar electrodes used the Autocapture (AC) algorithm. The intrinsic R wave, PS, ER, acceptance of AC function, and stimulation thresholds (STs) were obtained. Ventricular electrodes were categorized as follows: titanium nitride (TiN)-coated passive and active fixation, high impedance (HI), passive fixation (VP), iridium oxide-coated titanium (IROX) (VI), and platinum helix (PH) active fixation. Acute testing was performed in 217 patients with an average age of 74.26 years, 59.6% were men with primary pacing indication-SSS (46.3%). There were no significant differences found with respect to R wave and threshold between the various electrodes. PH active-fixation electrodes had significantly higher ER and PS than other groups including the TiN-coated active-fixation electrodes. TiN-coated electrodes (active and passive fixation) had significantly lower PS than other electrodes. As a result, TiN electrodes had a significantly higher functional rate of AC (91.7%), whereas PH had the lowest rate (0%). In conclusion, (1) polarization characteristics are significantly different for commercially available ventricular electrodes, (2) certain physical features at the tissue to electrode interface like TiN coating appears to be more important in determining PS than electrode tip size and fixation method, and (3) the current algorithm for AC requires electrodes that provide low polarization for satisfactory performance.

Circadian variation of paroxysmal atrial fibrillation. PA3 Investigators. Atrial Pacing Peri-ablation for Prevention of Atrial Fibrillation Trial.

The circadian variation of paroxysmal atrial fibrillation (AF) was studied in 67 patients who received a dual-chamber pacemaker 3 months before a planned atrioventricular node ablation. A distinct circadian variation of AF was observed with 2 time peaks in initiation (1 in the early morning and 1 in the early evening hours), which was modulated by atrial pacing, the duration of AF, and the use of beta-adrenergic blocking agents.

Transvenous biventricular defibrillation.

The recent success of biventricular pacing with transvenously implantable left ventricular leads suggests that left ventricular leads may be useful for other modes of therapy. Animal studies showed small leads inserted into a left ventricular vein dramatically reduced defibrillation strength requirements. This article describes a human investigation of the feasibility of biventricular defibrillation. Fifty-one patients undergoing implantable cardioverter defibrillator (ICD) implantation were enrolled. After insertion of a standard ICD lead, a prototype over-the-wire left ventricular defibrillation lead was inserted through the coronary sinus and into a vein on the left ventricle. Lead insertion was guided by retrograde venography. The left ventricular lead's location was randomized to the anterior or posterior vein. Randomized, paired defibrillation threshold (DFT) testing was performed to compare a standard ICD shock configuration (Control: right ventricle- --> superior vena cava+ + CAN+) to 1 of 3 biventricular shock configurations. In the anterior vein, the left ventricular lead was tested with either a single biphasic shock from right ventricle + left ventricle- --> superior vena cava+ + CAN+ or a dual biphasic shock. In the posterior vein, the left ventricular lead was tested with a dual biphasic shock. Dual shocks consisted of a 40% tilt biphasic shock from right ventricle- --> superior vena cava+ + CAN+ followed by another 40% tilt biphasic shock from left ventricle- --> superior vena cava+ + CAN+, delivered from a single 225 microF capacitance. Left ventricular lead positioning was successful in 41 of 46 patients (89%). Mean left ventricular lead insertion time was 17 +/- 17 minutes and 13 +/- 15 minutes for anterior and posterior locations, respectively. Mean DFTs were not statistically lower for the left ventricular shock configurations, but retrospective analysis showed a well-defined region of the posterolateral left ventricle where consistent DFT reduction was achieved with dual shocks (14.0 +/- 2.7 J vs 7.8 +/- 0.9 J; n = 5; p = 0.04). There were no adverse events requiring intervention due to the use of the left ventricular lead. Biventricular defibrillation is feasible and safe under the conditions used in this study. Additional studies are needed to verify whether dual shocks with posterolateral left ventricular lead positions consistently reduce DFTs.

Randomized crossover comparison of DDDR versus VDD pacing after atrioventricular junction ablation for prevention of atrial fibrillation. The atrial pacing peri-ablation for paroxysmal atrial fibrillation (PA (3)) study investigators.

BACKGROUND: Some clinical data suggest that atrial-based pacing prevents paroxysmal atrial fibrillation (AF). This study tested the hypothesis that DDDR pacing compared with VDD pacing prevents AF after atrioventricular (AV) junction ablation. METHODS AND RESULTS: Patients were randomized to DDDR pacing (n=33) or to VDD pacing (n=34) after AV junction ablation and followed every 2 months for 6 months. Patients then crossed over to the alternate pacing mode and were followed for an additional 6 months. Primary analysis included the time to first recurrence of sustained AF (duration >5 minutes), total AF burden, and the development of permanent AF. The time to first episode of AF was similar in the DDDR group (0.37 days, 95% CI 0.1 to 1.3 days) and the VDD pacing group (0.5 days, 95% CI 0.2 to 1.7 days, P=NS). AF burden increased over time in both groups (P<0.01). At the 6-month follow-up, AF burden was 6.93 h/d (95% CI 4. 37 to 10.96 h/d) in the DDDR group and 6.30 h/d (95% CI 3.99 to 9.94 h/d) in the VDD group (P=NS). Twelve (35%) patients in the DDDR group and 11 (32%) patients in the VDD group had permanent AF within 6 months of ablation. Within 1 year of follow-up, 43% of patients had permanent AF. CONCLUSIONS: DDDR pacing compared with VDD pacing does not prevent paroxysmal AF over the long term in patients in the absence of antiarrhythmic drug therapy after total AV junction ablation. Many patients have permanent AF within the first year after ablation.

Ischemia-induced action potential shortening is blunted by d-sotalol in a pig model of reversible myocardial ischemia.

The purpose of this study was to investigate, in an anesthetized pig model of low-flow myocardial ischemia, the electrophysiologic effects of the class III drug d-sotalol during myocardial ischemia. Serial monophasic action potential (MAPD90) recordings and refractory period determinations from the anterior and posterior left ventricular wall were taken in 25 pigs during baseline, after low-flow posterior wall ischemia, after d-sotalol infusion under nonischemic conditions, and after repeated posterior wall ischemia while continuing the drug. Measurements were done at 60 and 150 beats/min after radiofrequency ablation of atrioventricular conduction. At baseline, MAPD90 and refractory periods were comparable in the anterior and posterior wall (323 +/- 15 vs. 318 +/- 10 ms, and 267 +/- 10 vs. 262 +/- 11 ms at 60 beats/min, respectively). In the absence of d-sotalol, low-flow regional ischemia was associated with a significant shortening of MAPD90 in the posterior versus the anterior wall (267 +/- 20 vs. 317 +/- 20 ms at 60 beats/min; p = 0.006). Similarly, ischemia-induced shortening of the refractory periods in the posterior wall was apparent (230 +/- 16 ms in the posterior wall vs. 274 +/- 14 ms in the anterior wall at 60 beats/min). In contrast, ischemia was no longer associated with shortening of MAPD90 (360 +/- 17 ms posterior wall and 360 +/- 20 ms anterior wall at 60 beats/min) and refractory periods (304 +/- 19 ms posterior wall vs. 316 +/- 15 ms anterior wall at 60 beats/min) during combined posterior wall ischemia and d-sotalol infusion. Similar findings were obtained during pacing at 150 beats/min. d-Sotalol attenuates ischemia-induced action potential shortening. This property should decrease dispersion of cardiac repolarization and be antiarrhythmic. On the other hand, longer APD under ischemic conditions may favor calcium overload, which may trigger new arrhythmias.

Guidelines for pacemaker follow-up in Canada: a consensus statement of the Canadian Working Group on Cardiac Pacing.

A survey on Canadian pacing practices conducted in 1997 revealed a widespread desire for national guidelines on pacemaker follow-up. The present guidelines for pacemaker follow-up are a consensus statement of the Canadian Working Group on Cardiac Pacing. Direct patient follow-up rather than transtelephonic monitoring is desirable. Patients should be assessed at a minimum of within 72 h of implantation, at two to 12 weeks and at six months following implantation, and annually thereafter. More frequent assessments may be required for some patients. This depends on associated cardiovascular problems and specific devices. A typical follow-up visit should include a targeted cardiovascular assessment, interrogation of the pacing system, review of telemetered data, assessment of the underlying rhythm, assessment of pacing and sensing thresholds, and appropriate reprogramming of pacing parameters to optimize device function and longevity.

Lignes directrices pour le suivi des cardiostimulateurs au canada : consensus du groupe de travail canadien sur la cardiostimulation

Un sondage sur les pratiques de cardiostimulation au Canada effectue en 1997 a revele un profond desir pour des lignes directrices nationales sur le suivi des cardiostimulateurs. Ces lignes directrices sur le suivi des cardiostimulateurs representent une declaration de consensus du Groupe de travail canadien sur la cardiostimulation. Le suivi des patients en personne plutot que par moyens transtelephoniques est preferable. Les patients devraient etre examines au minimum dans les 72 heures suivant l'implantation, 2 a 12 semaines et 6 mois apres l'implantation, et annuellement par la suite. Des examens plus frequents peuvent etre requis pour certains patients. Ceci dependra des problemes cardiovasculaires associes et des appareils en particulier. Une visite de suivi typique devrait comprendre un examen cardiovasculaire oriente, l'interrogation du systeme de cardiostimulation et une revue des donnees de telemetrie, un examen du rythme sous-jacent, un examen des seuils de stimulation et de detection et une reprogrammation adequate des parametres pour optimaliser le fonctionnement et la longevite de l'appareil.

Atrial pacing periablation for prevention of paroxysmal atrial fibrillation.

BACKGROUND: This study tested the hypothesis that rate-adaptive atrial pacing would prevent paroxysmal atrial fibrillation (PAF) in patients with frequent PAF in the absence of symptomatic bradycardia. METHODS AND RESULTS: Patients (n=97) with antiarrhythmic drug-refractory PAF received a Medtronic Thera DR pacemaker 3 months before planned AV node ablation. Patients were randomized to no pacing (n=48) or to atrial rate-adaptive pacing (n=49). After a 2-week stabilization period, patients were followed up for an additional 10 weeks. The time to first recurrence of sustained PAF, the interval between successive episodes of PAF, and the frequency of PAF were compared between the 2 groups in intention-to-treat analysis. Time to first episode of sustained PAF was similar in the no-pacing (4.2 days; 95% CI, 1.8 to 9.5) and the atrial-pacing (1.9 days; 95% CI, 0.8 to 4.6; P=NS) groups. PAF burden was lower in the no-pacing (0.24 h/d; 95% CI, 0.10 to 0.56) than in the atrial-pacing (0.67 h/d; 95% CI, 0.30 to 1.52; P=0.08) group. Paired crossover analysis in 11 patients revealed that time to first PAF was shorter during atrial pacing (1.6 days; 95% CI, 0.6 to 4.9) than with no pacing (6.0 days; 95% CI, 2.4 to 15.0; P=0.13), and PAF burden was greater during atrial pacing (1.00 h/d; 95% CI, 0.35 to 2.91) than with no pacing (0.32 h/d; 95% CI, 0.09 to 1.13; P<0.016). CONCLUSIONS: Atrial rate-adaptive pacing does not prevent PAF over the short term in patients with antiarrhythmic drug-resistant PAF without symptomatic bradycardia.

The influence of sensor orientation on activity-based rate responsive pacing. Sensor Orientation Study Group.

Piezoelectric activity-based rate responsive pacemakers are commonly implanted with the sensor facing inward. This study was conducted to assess the safe and effective rate response of an activity-based rate responsive pacemaker implanted with the sensor facing outward. A comparison were made to a previously studied patient group with sensor facing inward. Patient and pacemaker data was collected at predischarge and 2-month follow-up. Two-minute hall walks in conjunction with programmer-assisted rate response assessment were utilized to standardize initial rate response parameter settings for both patient groups. At 2-month follow-up, sensor rate response to a stage 3 limited CAEP protocol was recorded. Adequate sensor rate response was achieved for both patient groups. No difference was noted in reported patient complications for both groups. A statistically significant difference in programmed rate response curve setting and activity threshold for the two groups was noted at 2-month follow-up. Adequate sensor rate response was achieved for a patient population implanted with an activity-based rate responsive pacemaker with sensor facing outward. In this orientation, one higher rate response curve setting and an activity threshold one value more sensitive were required on average when compared to the normal sensor orientation group.

Cardiac pacing in Canada in 1998: working towards optimal pacing therapy. Canadian Working Group on Cardiac Pacing.

The Canadian Working Group on Cardiac Pacing (CWGCP) was formed in 1996 with the primary goal of promoting optimal pacing therapy in Canada. In 1997, the CWGCP conducted a survey of pacing practices across Canada. Ninety-two of 125 implanting programs (74%) responded. Implant rates vary by province--from 39 per 100,00 population in Ontario to 63 per 100,000 population in Nova Scotia and Prince Edward Island. Variations in regional implant rates persist even after correcting for the age of the population. Physiological pacing was used for 35% of all implants in Canada in 1996/97. There were marked differences across Canada in the mode of pacing selected. In western Canada, 39.5% of pacing systems implanted were physiological compared with 18.2% in Atlantic Canada and 29% in Quebec. There were also differences in follow-up practices. Approximately 40% of centres follow patients with single chamber pacemakers annually, whereas most other centres still follow these patients every six months. Economic constraints, the size of pacing programs and the involvement of committed pacing physicians are factors that may influence the regional differences in cardiac pacing across Canada.

The risk of atrial fibrillation following radiofrequency catheter ablation of atrial flutter.

BACKGROUND: Although radiofrequency catheter ablation of atrial flutter is associated with a high rate of initial success, several clinical issues regarding this therapy remain to be defined. For example, the risks of recurrent atrial flutter and of developing atrial fibrillation after flutter ablation are unknown. In addition, it is not known whether elimination of atrial flutter will modify the natural history of atrial fibrillation in patients who experience both of these arrhythmias. The purpose of the present study was to determine the actuarial freedom from recurrent or new atrial arrhythmias in patients with atrial flutter undergoing catheter ablation. METHODS AND RESULTS: The study population consisted of 59 consecutive patients (mean age, 61.9 +/- 12.6 years) with typical atrial flutter who underwent catheter ablation of the reentrant circuit. Catheter ablation was not advised for patients in whom paroxysmal atrial fibrillation had been a major clinical problem. The inducibility of atrial fibrillation and atrial flutter was assessed after successful atrial flutter ablation with programmed atrial stimulation and rapid atrial pacing to a cycle length of 180 ms or 2:1 atrial capture. Atrial flutter was successfully ablated and rendered noninducible in 53 of 59 patients (90%). Over a mean follow-up period of 13.2 +/- 6.6 months, atrial flutter recurred in 5 patients (9.4%). Atrial fibrillation occurred in 14 of 53 patients after successful ablation (26.4%). Four clinical variables were associated by univariate analysis with the late occurrence of atrial fibrillation: (1) the presence of structural heart disease, (2) a history of atrial fibrillation before ablation of atrial flutter, (3) inducible sustained atrial fibrillation after ablation, and (4) a greater number of failed antiarrhythmic drugs. By multivariate analysis, only the persistent inducibility of sustained atrial fibrillation predicted the later development of atrial fibrillation. CONCLUSIONS: Although atrial flutter ablation is highly effective and associated with a low risk of recurrent atrial flutter, atrial fibrillation continues to be a long-term risk for individuals undergoing this procedure. The risk of later atrial fibrillation is especially high for patients in whom sustained atrial fibrillation remains inducible after ablation of atrial flutter.

Differential effect of esmolol on the fast and slow AV nodal pathways in patients with AV nodal reentrant tachycardia.

INTRODUCTION: AV nodal reentrant tachycardia (AVNRT) usually involves anterograde conduction over a slowly conducting ("slow") pathway and retrograde conduction over a rapidly conducting ("fast") pathway. A variety of drugs, such as beta blockers, digitalis, and calcium channel blockers, have been reported to prolong AV nodal refractoriness in both the anterograde and retrograde limbs of the circuit. However, few data are available that address whether the fast and slow pathways respond in a quantitatively different manner to drugs such as beta-adrenergic antagonists. In addition, it is not known whether the effects of these agents on refractoriness parallel the effects on conduction in the fast and slow pathways. The present study was performed to measure the effect of the intravenous beta-adrenergic agent, esmolol, on refractoriness and conduction in both the fast and slow AV nodal pathways in patients with AVNRT. METHODS AND RESULTS: Thirteen patients with discontinuous AV nodal conduction properties and typical AVNRT were studied. Anterograde and retrograde AV nodal functional assessment was performed at baseline and following steady-state drug infusion of intravenous esmolol at a dose of 500 micrograms/kg for 1 minute, 150 micrograms/kg per minute for the next 4 minutes, followed by a continuous maintenance infusion of 50 to 100 micrograms/kg per minute. The anterograde effective refractory period of the fast pathway increased from 381 +/- 75 msec at baseline to 453 +/- 92 msec during the infusion of esmolol (P = 0.003). The anterograde effective refractory period of the slow pathway was also prolonged by esmolol, from 289 +/- 26 msec to 310 +/- 17 msec (P = 0.005). However, the absolute magnitude of the change in the anterograde effective refractory period of the fast pathway (+72 +/- 59 msec) was significantly greater than the change in anterograde effective refractory period of the slow pathway (+21 +/- 16 msec, P = 0.01). The mean retrograde effective refractory period of the fast pathway increased from 276 +/- 46 msec to 376 +/- 61 msec during esmolol infusion (P = 0.03). Retrograde slow pathway conduction that could not be demonstrated at baseline became manifest in three patients during esmolol infusion. In contrast to the effects of esmolol on refractoriness, the AH interval during anterograde slow pathway conduction prolonged to a far greater extent (+84 msec) than the HA interval associated with retrograde fast pathway conduction (+5 msec, P = 0.04). CONCLUSION: The beta-adrenergic antagonist, esmolol, has a quantitatively greater effect on anterograde refractoriness of the fast than the slow AV nodal pathway. However, the effects on conduction intervals during AVNRT are greater in the anterograde slow pathway than in the retrograde fast pathway. These observations suggest that the fast and slow pathways may have differential sensitivities to autonomic influences. This difference in the response to beta-adrenergic antagonists may be exploited as a clinically useful method for demonstrating slow pathway conduction in some individuals with AVNRT.

Rate modulated pacing based on right ventricular dP/dt: quantitative analysis of chronotropic response.

Right ventricular contractility increases in response to catecholamine stimulation and greater ventricular preload, factors that increase with exercise workload. Thus, the maximum systolic dP/dt may be a potentially useful sensor to control the pacing rate of a permanent pacing system. The present study was designed to test the long-term performance of a permanent pacemaker that modulates pacing rate based on right ventricular dP/dt and to quantitatively analyze the chronotropic response characteristics of this sensor in a group of patients with widely varying structural heart diseases and degrees of hemodynamic impairment. A permanent pacing system incorporating a high fidelity pressure sensor in the lead for measurement of right ventricular dP/dt was implanted in 13 patients with atrial arrhythmias and AV block, including individuals with coronary artery disease, hypertension, severe obstructive pulmonary disease with prior pneumonectomy, atrial septal defect, dilated cardiomyopathy, restrictive cardiomyopathy, and mitral stenosis. Patients underwent paired treadmill exercise testing in the VVI and VVIR pacing modes with measurement of expired gas exchange and quantitative analysis of chronotropic response using the concept of metabolic reserve. The peak right ventricular dP/dt ranged from 238-891 mmHg/sec with a pulse pressure that ranged from 19-41 mmHg. There was a positive correlation between the right ventricular dP/dt and pulse pressure (r = 0.70, P = 0.012). The maximum pacing rate and VO2max were 72 +/- 6 beats/min and 12.61 +/- 4.0 cc O2/kg per minute during VVI pacing and increased to 124 +/- 18 beats/min and 15.89 +/- 5.9 cc O2/kg per minute in the VVIR pacing mode (P < 0.0003 and P < 0.002, respectively). The integrated area under the normalized rate response curve was 96.7 +/- 45.7% of expected during exercise and 100.1 +/- 43.4% of expected during recovery. One patient demonstrated an anomalous increase in pacing rate in response to a change in posture to the left lateral decubitus position. Thus, the peak positive right ventricular dP/dt is an effective rate control parameter for permanent pacing systems. The chronotropic response was proportional to metabolic workload during treadmill exercise in this study population with widely varying forms of structural heart disease.

Stereoselective disposition of (+/-)-sotalol at steady-state conditions.

The objective of this study was to assess, under steady-state conditions, the stereoselective disposition of (+/-)-sotalol in man. In all patients studied (n = 7) values of oral clearance (137 +/- 51 ml min-1), renal clearance (96 +/- 42 ml min-1) and nonrenal clearance (41 +/- 25 ml min-1) of (-)-sotalol were greater than those for (+)-sotalol (123 +/- 45 ml min-1, 89 +/- 39 ml min-1 and 34 +/- 23 ml min-1, respectively; P < 0.05, Student's paired t-test). Binding to plasma proteins was greater for (+)-sotalol (38 +/- 9% vs 35 +/- 9% for the (-)-enantiomer; P < 0.05) such that unbound oral clearance (+)/(-) ratio (0.95 +/- 0.06) and unbound renal clearance (+)/(-) ratio (0.97 +/- 0.06) were not stereoselective. In contrast, estimated unbound nonrenal clearance, which represents approximately 25% of the total unbound clearance of the drug, was greater for the (-)-enantiomer (64 +/- 42 ml min-1) compared with (+)-sotalol (57 +/- 42 ml min-1; P < 0.05). The difference in the pharmacokinetics of sotalol enantiomers is mainly related to stereoselectivity in plasma protein binding.