Importance of beta-blocker dose in prevention of ventricular tachyarrhythmias, heart failure hospitalizations, and death in primary prevention implantable cardioverter-defibrillator recipients: a Danish nationwide cohort study.

Aims: There is a paucity of studies investigating a dose-dependent association between beta-blocker therapy and risk of outcome. In a nationwide cohort of primary prevention implantable cardioverter-defibrillator (ICD) patients, we aimed to investigate the dose-dependent association between beta-blocker therapy and risk of ventricular tachyarrhythmias (VT/VF), heart failure (HF) hospitalizations, and death. Methods and results: Information on ICD implantation, endpoints, comorbidities, beta-blocker usage, type, and dose were obtained through Danish nationwide registers. The two major beta-blockers carvedilol and metoprolol were examined in three dose levels; low (metoprolol ≤ 25 mg; carvedilol ≤ 12.5 mg), intermediate (metoprolol 26-199 mg; carvedilol 12.6-49.9 mg), and high (metoprolol ≥ 200 mg; carvedilol ≥ 50 mg). Time to events was investigated utilizing multivariate Cox models with beta-blocker as a time-dependent variable. From 2007 to 2012, 2935 first-time ICD devices were implanted. During follow-up, 399 patients experienced VT/VF, 728 HF hospitalizations and 361 died. As compared with patients not on beta-blockers, low, intermediate, and high dose had significantly reduced risk of HF hospitalizations {hazard ratio (HR) = 0.68 [0.54-0.87], P = 0.002; HR = 0.53 [0.42-0.66], P < 0.001; HR = 0.43 [0.34-0.54], P < 0.001} and death (HR = 0.47 [0.35-0.64], P < 0.001; HR = 0.29 [0.22-0.39], P = 0.001; HR = 0.24 [0.18-0.33], P < 0.001). For the endpoint of VT/VF, only intermediate and high dose beta-blocker was associated with significantly reduced risk (HR = 0.58 [0.43-0.79], P < 0.001; HR = 0.53 [0.39-0.72], P < 0.001). No significant difference was found between comparable doses of carvedilol and metoprolol on any endpoint (P = 0.06-0.94). Conclusion: In primary prevention ICD patients, beta-blocker therapy was associated with significantly reduced risk of all endpoints, as compared with patients not on beta-blocker, with the suggestion of a dose-dependent effect. No detectable difference was found between comparable doses of carvedilol and metoprolol.

Optimal radiologic position of an umbilical venous catheter tip as determined by echocardiography in very low birth weight newborns.

OBJECTIVE: To compare chest X-ray with echocardiogram (ECHO) in the localization of an umbilical venous catheter (UVC) tip in very low birth weight infants (VLBW). Secondary objectives determined the association between techniques for tip placement by the vertebral body level on X-ray, as well as the length of the thoracic inferior vena cava-right atrial (TIVC-RA) junction by ECHO. STUDY DESIGN: Prospective, sequentially enrolled, masked, single regional perinatal center study. Shortly after birth, one or more anterior-posterior X-rays were ordered by the clinical team to verify that the UVC tip was fixed in the central right atrium (cRA) or at the TIVC-RA junction. An echocardiogram was performed as soon as possible after the last X-ray and UVC tip location was interpreted by a pediatric cardiologist. The pediatric radiologist and cardiologist were masked with regard to each other's reading. RESULTS: The newborns (n = 51) were 27 (±3) weeks by gestational age with birth weights of 1029 (±288) grams (mean±SD). The radiologist read 50 UVC tips (98%) in the cRA or TIVC-RA junction and 1 (2%) in the LA. The cardiologist read 22 (43%) in the cRA or TIVC-RA, 21 (41%) in the LA and 8 (16%) tips could not be located in the heart. When the UVC tip was interpreted by X-ray as located in the TIVC-RA junction 8/29 (28%) were in the LA by echocardiogram. There was no agreement between vertebral level and tip position in the TIVC-RA junction, RA or LA. The TIVC-RA junction measured 6±1 mm and correlated with birth weight r = 0.54 (p < 0.001). CONCLUSION: In VLBW newborns, placement of the UVC tip into the cRA or TIVC-RA junction by X-ray does not avoid misplacement in the left atrium as demonstrated by echocardiography. For VLBW infants, it is suggested that echocardiography may be helpful in verifying that the original placement or migration of the UVC tip into the LA has not occurred.

Population Exposure-Response Modeling of Naloxegol in Patients With Noncancer-Related Pain and Opioid-Induced Constipation.

Naloxegol is a polyethylene glycol derivative of naloxone approved in the US as a once-daily oral treatment for opioid-induced constipation (OIC) in adults with chronic noncancer pain. Population exposure-response models were constructed based on data from two phase III studies comprising 1,331 adults with noncancer pain and OIC. In order to characterize the protocol-defined naloxegol responder rate, the number of daily spontaneous bowel movements (SBMs) was characterized by a longitudinal ordinal nonlinear mixed-effects logistic regression dose-response model, and the incidence of diary entry discontinuation was described by a time-to-event model. The mean number of SBMs per week increased with increasing naloxegol dose. The predicted placebo-adjusted responder rates (90% confidence interval) were 10.4% (4.6-13.4%) and 11.1% (4.8-14.4%) for naloxegol 12.5 and 25 mg/day, respectively. Model-predicted response to naloxegol was influenced by the baseline SBM frequency and characteristics of the opioid treatment.

Plasma pharmacokinetics of two consecutive doses of ferumoxytol in healthy subjects.

Intravenous (IV) iron is used to treat iron-deficiency anemia in patients with chronic kidney disease (CKD). Ferumoxytol is a novel iron formulation administered rapidly as two IV boluses of 510 mg each. In this placebo-controlled, double-blind, parallel-group study, 58 healthy volunteers received ferumoxytol in two 510 mg doses administered 24 h apart. Population pharmacokinetics (PK) analysis was conducted, and a two-compartment open model with zero-order input and Michaelis-Menten elimination was found to best describe the data. The population mean estimates for volume of distribution of the central compartment (V(1)), maximal elimination rate (V(max)), and ferumoxytol concentration at which rate of metabolism would be one-half of V(max) (K(m)) were 2.71 l, 14.3 mg/h, and 77.5 mg/l, respectively. When the effect of body weight on V(1) was added in the analysis, interindividual variability was found to be reduced. A noncompartmental analysis of two simulated 510-mg ferumoxytol doses was also performed to provide clinically interpretable data on half life and exposure. Ferumoxytol given as two consecutive 510-mg doses was well tolerated.

Prophylactic cavotricuspid isthmus block during atrial fibrillation ablation in patients without atrial flutter: a randomised controlled trial.

OBJECTIVES: This randomised trial evaluated if patients with atrial fibrillation (AF) and no history of atrial flutter (AFL) had any benefit of prophylactic cavotricuspid isthmus block (CTIB) in addition to circumferential pulmonary vein ablation (CPVA). METHODS: 149 patients with AF (54% paroxysmal) were randomised to CPVA and CTIB (group CTIB+, n = 73) or CPVA alone (group CTIB-, n = 76). Patients were followed for 12 months with repetitive 7-day Holter monitoring after 3, 6 and 12 months. RESULTS: Six patients (4%) had cardiac tamponade, and one patient had a stroke. No difference was found in the cumulative AFL-free rate between the two treatment groups (CTIB+: 88% vs CTIB-: 84%, hazard ratio (HR) 0.80, 95% CI (0.34 to 1.90), p = 0.61). There was no difference in the cumulative AF-free rate between the groups (CTIB+: 34% vs CTIB-: 32%, HR 0.93, 95% CI (0.63 to 1.38), p = 0.71). Overall, 33% of the patients were free of AF after a single procedure. Including reprocedures, a complete or partial beneficial effect was noted in 62% of the patients at 12 months. At 12-month follow-up, 24 (50%) patients with documented AF or AFL in the Holter recordings were asymptomatic. CONCLUSIONS: It was not possible to demonstrate any beneficial effect of CTIB in addition to CPVA with regard to AFL or AF recurrences during follow-up. Repetitive long-term Holter monitoring demonstrated a 33% rate of freedom from AF during a 1-year follow-up. Including additional CPVA procedures, a clinical effect was noted in 62% of the patients at 12 months. Patients with AF or AFL recurrences were often asymptomatic.

Incidence of atrial fibrillation and thromboembolism in a randomised trial of atrial versus dual chamber pacing in 177 patients with sick sinus syndrome.

OBJECTIVE: To analyse the occurrence of atrial fibrillation (AF) and thromboembolism in a randomised comparison of rate adaptive single chamber atrial pacing (AAIR) and dual chamber pacing (DDDR) in patients with sick sinus syndrome and normal atrioventricular (AV) conduction, in which left atrial dilatation and decreased left ventricular fractional shortening had been observed in the DDDR group. METHODS: 177 consecutive patients with sick sinus syndrome (mean (SD) age 74 (9) years, 104 women) were randomly assigned to treatment with one of three pacemakers: AAIR (n = 54), DDDR with a short rate adaptive AV delay (n = 60) (DDDR-s); or DDDR with a fixed long AV delay (n = 63) (DDDR-l). Analysis was intention to treat. RESULTS: Mean follow up was 2.9 (1.1) years. AF at one or more ambulatory visits was significantly less common in the AAIR group (4 (7.4%) v 14 (23.3%) in the DDDR-s group v 11 (17.5%) in the DDDR-l group; p = 0.03, log rank test). The risk of developing AF in the AAIR group compared with the DDDR-s group was significantly decreased after adjustment for brady-tachy syndrome in a Cox regression analysis (relative risk 0.27, 95% confidence interval (CI) 0.09 to 0.83, p = 0.02). The benefit of AAIR was highest among patients with brady-tachy syndrome. Brady-tachy syndrome and a thromboembolic event before pacemaker implantation were independent predictors of thromboembolism during follow up (relative risk 7.5, 95% CI 1.6 to 36.2, p = 0.01, and relative risk 4.7, 95% CI 1.2 to 17.9, p = 0.02, respectively). CONCLUSIONS: During a mean follow up of 2.9 years AAIR was associated with significantly less AF. The beneficial effect of AAIR was still significant after adjustment for brady-tachy syndrome. Brady-tachy syndrome was associated with an increased risk of thromboembolism.

Selecting the appropriate pacing mode for patients with sick sinus syndrome: evidence from randomized clinical trials.

Several observational studies have indicated that selection of pacing mode may be important for the clinical outcome in patients with symptomatic bradycardia, affecting the development of atrial fibrillation (AF), thromboembolism, congestive heart failure, mortality and quality of life. In this paper we present and discuss the most recent data from six randomized trials on mode selection in patients with sick sinus syndrome (SSS). In pacing mode selection, VVI(R) pacing is the least attractive solution, increasing the incidence of AF and-as compared with AAI(R) pacing, also the incidence of heart failure, thromboembolism and death. VVI(R) pacing should not be used as the primary pacing mode in patients with SSS, who haven't chronic AF. AAIR pacing is superior to DDDR pacing, reducing AF and preserving left ventricular function. Single site right ventricular pacing-VVI(R) or DDD(R) mode-causes an abnormal ventricular activation and contraction (called ventricular desynchronization), which results in a reduced left ventricular function. Despite the risk of AV block, we consider AAIR pacing to be the optimal pacing mode for isolated SSS today and an algorithm to select patients for AAIR pacing is suggested. Trials on new pacemaker algorithms minimizing right ventricular pacing as well as trials testing alternative pacing sites and multisite pacing to reduce ventricular desynchronization can be expected within the next years.

The effect of oxygen on the survival of non-Saccharomyces yeasts during mixed culture fermentations of grape juice with Saccharomyces cerevisiae.

AIMS: The effect of oxygen on the survival of Torulaspora delbrueckii and Kluyveromyces thermotolerans during mixed culture fermentations in grape juice with Saccharomyces cerevisiae was investigated. METHODS AND RESULTS: Fermentations were carried out in two simple fermentation systems differing in the availability of oxygen. At low available oxygen conditions, T. delbrueckii and K. thermotolerans began to die off after two days of mixed culture fermentation. In filtrates from 2-day-old mixed cultures, single cultures of T. delbrueckii and K. thermotolerans survived and actively produced ethanol to concentrations of approx. 65 and 70 g l-1, respectively, at low available oxygen conditions. Oxygen clearly increased the survival time and decreased the death rate of T. delbrueckii and K. thermotolerans in mixed cultures, whereas it did not affect the growth and survival of S. cerevisiae. CONCLUSION: Our results show that the deaths of T. delbrueckii and K. thermotolerans in mixed cultures at low available oxygen conditions are not due to toxic metabolites produced by the yeasts but rather to the lack of oxygen. Furthermore, they indicate that T. delbrueckii and K. thermotolerans are less tolerant to low available oxygen conditions than S. cerevisiae. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study reveals new knowledge on the mechanisms underlying the succession of yeasts during wine fermentations. This knowledge may be of importance when creating defined, mixed starter cultures for the controlled production of wines with a wide range of flavour compositions.

AV block and changes in pacing mode during long-term follow-up of 399 consecutive patients with sick sinus syndrome treated with an AAI/AAIR pacemaker.

This retrospective study included a large cohort of consecutive patients primarily implanted at Skejby University Hospital with an AAI/AAIR pacemaker because of sick sinus syndrome (SSS) from July 1981 to July 1999. The primary aim of the study was to analyze the risk of developing AV block during long-term follow-up. A secondary aim was to study the incidence and reasons for changes in pacing mode caused by other than AV block. A total of 399 patients (231 women, mean age 71 +/- 13.5 years) were identified. Mean follow-up was 4.6 +/- 3.4 years and occurred at death, reoperation with mode change, pacemaker explant, or end of study. During follow-up, 44 patients had a ventricular lead implanted with a mean delay of 2.8 +/- 3.1 years (range 1 day-10.4 years) after the primary implantation. A total of 30 patients received a ventricular lead because of AV block or AF with bradycardia (annual incidence 1.7%). Another 14 patients received a ventricular lead without having documented AV block or AF with pauses (annual incidence 0.8%). The present observational study documents that in patients with SSS treated with AAI/AAIR pacing, AV block requiring implantation of a ventricular lead occurs at a rate of 1.7% per year. It is considered that AAI/AAIR pacing is safe and reliable as treatment for patients with SSS and normal AV conduction.

Serial changes and prognostic implications of a Doppler-derived index of combined left ventricular systolic and diastolic myocardial performance in acute myocardial infarction.

The purpose of this study was to investigate the serial changes and prognostic value of a nongeometric Doppler-derived index of myocardial function that combines systolic and diastolic time intervals of the left ventricle in acute myocardial infarction (AMI). The Doppler index was measured in 60 consecutive patients with AMI and in 30 patients admitted to hospital with suspected but disproved AMI who served as controls. The patients were studied at days 1, 5, 90, and 360 after arrival in the coronary care unit. The index was defined as the sum of isovolumetric contraction time, and isovolumetric relaxation time divided by ejection time was measured from mitral inflow and left ventricular outflow Doppler velocity profiles. The index was significantly higher in patients with AMI than in control subjects at days 1 and 360 (day 1, 0.58 +/- 0.09 vs 0.41 +/- 0.08, p <0.0001; day 360, 0.50 +/- 0.09 vs 0.39 +/- 0.07, p <0.01, respectively). The index decreased significantly in patients with AMI during follow-up (p <0.01). The index was significantly higher in patients who developed congestive heart failure or died compared with survivors who were free of congestive heart failure (day 1, 0.63 +/- 0.10 vs 0.53 +/- 0.10, p <0.01; day 360, 0.56 +/- 0.08 vs 0.48 +/- 0.10, p <0.01, respectively). During 20.2 +/- 8.5 months' follow-up, 10 patients died of cardiac causes and 13 developed congestive heart failure. Univariate analyses demonstrated that the Doppler index > or =0.60 (chi-square 8.3, p <0.0001), deceleration time < or =140 ms (chi-square 8.5, p <0.0001), ejection fraction < or =0.40% (chi-square 3.3, p <0.005), anterior wall AMI (chi-square 3.2, p <0.01), and age (chi-square 1.06/ year increase, p <0.01) were significant predictors of outcome. Multivariate stepwise analysis showed that the index < or =0.60 (chi-square 3.4, p <0.05), deceleration time < or =140 ms (chi-square 4.2, p <0.02), and age (chi-square 1.06/year increase, p <0.02) were independent predictors of outcome. The Doppler index reflects severity of left ventricular function and has incremental prognostic value in patients with AMI.

Regional myocardial blood flow in patients with sick sinus syndrome randomized to long-term single chamber atrial or dual chamber pacing--effect of pacing mode and rate.

OBJECTIVES: This study aimed to evaluate regional myocardial blood flow (MBF) and global left ventricular ejection fraction (LVEF) during chronic pacing in patients with sick sinus syndrome (SSS) randomized to either single chamber atrial (AAI) or dual chamber (DDD) pacing. BACKGROUND: Experimental studies indicate that chronic pacing in the right ventricular apex changes regional MBF, thereby compromising left ventricular function. METHODS: Thirty patients (age 74 +/- 10 years) were randomized to AAI (n = 15) or DDD (n = 15) pacemakers. After 22 +/- 7 months of pacing, MBF was quantified with 13N-labeled ammonia positron emission tomography scanning at 60 beats per min and 90 beats per min. Patients in the DDD group furthermore underwent MBF measurement at temporary AAI pacing, 60 beats per min. Myocardial blood flow was assessed in the anterior, lateral, inferior and septal regions, and the global mean MBF was calculated. Left ventricular ejection fraction was determined by echocardiography at pacemaker implantation and at the time of MBF measurements. RESULTS: Myocardial blood flow at rates 60 and 90 beats per min did not differ between the AAI and DDD groups. During temporary AAI pacing in the DDD group, MBF was significantly higher than during DDD pacing in both the inferior (p = 0.001) and septal (p = 0.004) regions and also globally (0.61 +/- 0.15 vs. 0.53 +/- 0.13 mL x g(-1) x min(-1), p = 0.005). In the DDD group, LVEF decreased from pacemaker implantation to time of MBF measurements (0.61 +/- 0.09 vs. 0.56 +/- 0.07, p = 0.013). Left ventricular ejection fraction during temporary AAI pacing at time of MBF measurements was not different from LVEF at pacemaker implantation. CONCLUSIONS: In patients with SSS, chronic DDD pacing reduced inferior, septal and global mean MBF as well as LVEF, as compared with temporary AAI pacing. The LVEF reversed to baseline level during temporary AAI pacing despite 22 months of permanent ventricular pacing preceding it. Augmenting pace rate to 90 beats per min increased MBF equally in the two treatment groups.

The influence of heart rate on the Doppler-derived myocardial performance index.

The Doppler-derived myocardial performance index (MPI), defined as the sum of isovolumetric contraction and relaxation durations divided by ejection time and reflecting both systolic and diastolic myocardial function, has been found to be related to morbidity and mortality in cardiac diseases. The MPI is easily obtained, reproducible, and has a narrow range in healthy subjects. The goal of this study was to study the influence of heart rate changes on the MPI. Thirty patients with sick sinus syndrome treated with a pacemaker with a right atrial lead were studied. The patients were paced at increasing rates from 50 to 100 bpm. The MPI increased on average 0.02 +/- 0.03 per 10-bpm increase in rate. The correlation between MPI and heart rate was weak (rho = 0.31, P <.01).

Clinical assessment of indication for ACE-inhibitor treatment early after acute myocardial infarction.

An investigation was conducted to assess whether an algorithm based on simple clinical information would suffice to classify patients with acute myocardial infarction, with respect to indication for angiotensin-converting-enzyme inhibitor treatment. One hundred consecutive patients with myocardial infarction were prospectively studied. Based on clinical, radiological, electrocardiographic and biochemical information, the patients were classified as having (a) significantly depressed left ventricular function (ejection fraction < or = 40%) justifying treatment with angiotensin-converting-enzyme inhibitors (ACEI), (b) preserved ventricular function (ejection fraction > 40%) making ACEI unnecessary, or (c) indeterminate ventricular function, requiring further examination. Using a blinded design, ejection fraction was determined by echocardiography and radionuclide ventriculography. A clinical assumption of reduced left ventricular function had a predictive value of an echocardiographically determined ejection fraction < or = 40% of 83% (n = 23). Clinical criteria of good ventricular function had a predictive value of ejection fraction > 40% of 96% (n = 24). In these two groups clinical misclassification occurred in five patients with ejection fraction within the range of 39-45%. Left ventricular function was found to be clinically indeterminate in 53 of the 100 patients. Ejection fraction values assessed by radionuclide ventriculography (n = 44) were on average 9.3%-points lower than echocardiographic values. The indication for ACEI can apparently be determined on the basis of readily available clinical information in approximately 50% of patients with acute myocardial infarction.

Arterial thromboembolism in patients with sick sinus syndrome: prediction from pacing mode, atrial fibrillation, and echocardiographic findings.

OBJECTIVE: To evaluate whether thromboembolism in sick sinus syndrome can be predicted by pacing mode, atrial fibrillation, or echocardiographic findings. METHODS: Patients were randomised to single chamber atrial (n = 110) or ventricular (n = 115) pacing. They were divided into subgroups with and without brady-tachy syndrome at time of randomisation. The occurrence of atrial fibrillation and thromboembolism during follow up were investigated and compared with echocardiographic findings. RESULTS: The annual risk of thromboembolism was 5.8% in patients with brady-tachy syndrome randomised to ventricular pacing, 3.2% in patients without brady-tachy syndrome randomised to ventricular pacing, 3% in patients with brady-tachy syndrome randomised to atrial pacing, and 1.5% in patients without brady-tachy syndrome randomised to atrial pacing. In atrial paced patients without brady-tachy syndrome at randomisation and without atrial fibrillation during follow up, the annual risk of thromboembolism was 1.4%. Left atrial size measured by M mode echocardiography was of no value in predicting thromboembolism. CONCLUSIONS: Arterial thromboembolism in patients with sick sinus syndrome is very common and is associated primarily with brady-tachy syndrome at randomisation and with ventricular pacing. The risk of thromboembolism is small in atrial paced patients in whom atrial fibrillation has never been documented.

[Single-chamber atrial pacing is better than single chamber ventricular pacing in patients with sick sinus syndrome. Results of long-term follow up in a prospective randomized study]. / Etkammer-atriepacing er bedre end etkammer-ventrikelpacing hos patienter med syg sinusknude. Resultatet af langtidsopfølgning i en prospektiv, randomiseret undersøgelse.

In a study of 225 patients with sick sinus syndrome randomized to single chamber atrial pacing (n = 110) or ventricular pacing (n = 115), atrial pacing was associated with less atrial fibrillation and thromboembolism after 3.3 years follow-up. To determine whether this beneficial effect of atrial pacing is maintained at long-term, follow-up was extended. Follow-up visits were at 3 months, 12 months, and then once every year, and included physical examination, ECG, and pacemaker check-up. After 5.5 years follow-up, all-cause mortality, cardiovascular deaths, atrial fibrillation, thromboembolism, and heart failure were significantly less in the atrial group. AV block occurred in four patients in the atrial group. The beneficial effect of atrial pacing observed previously is enhanced substantially after extended follow-up. Patients with sick sinus syndrome should be treated with an atrial pacing system.

Control of flavor development in wine during and after malolactic fermentation by Oenococcus oeni.

During malolactic fermentation in wine by Oenococcus oeni, the degradation of citric acid was delayed compared to the degradation of malic acid. The maximum concentration of diacetyl, an intermediary compound in the citric acid metabolism with a buttery or nutty flavor, coincided with the exhaustion of malic acid in the wine. The maximum concentration of diacetyl obtained during malolactic fermentation was strongly dependent on the oxygen concentration and the redox potential of the wine and, to a lesser extent, on the initial citric acid concentration. The final diacetyl concentration in the wine was also dependent on the concentration of SO2. Diacetyl combines rather strongly with SO2 (Kf = 7.2 x 10(3) M(-1) in 0.1 M malate buffer [pH 3.5] at 30 degrees C). The reaction is exothermic and reversible. If the concentration of SO2 decreases during storage of the wine, the diacetyl concentration increases again.

Programming a fixed long atrioventricular delay is not effective in preventing ventricular pacing in patients with sick sinus syndrome.

AIM: Most patients with sick sinus syndrome (SSS) and normal atrioventricular (AV) conduction receive dual chamber (DDDR) pacemakers. Programming a long AV delay has been proposed to avoid ventricular pacing. The present study aimed to evaluate ventricular stimulation in SSS patients with DDDR pacemakers with a long AV delay. METHODS AND RESULTS: Thirty eight patients treated with DDDR pacemakers with a fixed long AV delay (300 ms) were studied. Data from the pacemaker event recorder were retrieved after 3 months and every year after implantation. Ten patients underwent 24 h Holter recording. Mean follow-up was 11.9 +/- 8.3 months. Median daily number of paced events in the ventricle was 2659 (25th-75th percentiles: 775-21 315) with a large inter-individual variation. The proportion of paced events in the ventricle correlated weakly with the baseline PQ interval (Spearman's rho 0.331, P = 0.043). In 12/38 patients the mean daily number of paced events in the ventricle exceeded 10,000. During 24 h Holter recording, pacemaker arrhythmias caused by repetitive retrograde atrioventricular conduction, known as VA (ventriculoatrial) conduction, occurred in five out of 10 patients. CONCLUSION: DDDR pacing with a fixed long AV delay is inefficient in reducing ventricular pacing in one third of patients and is associated with a high risk of arrhythmias caused by repetitive retrograde AV conduction, and therefore cannot be recommended for general use in SSS patients.

Atrioventricular conduction during long-term follow-up of patients with sick sinus syndrome.

BACKGROUND: It has been claimed that patients with sick sinus syndrome have an increased risk of developing AV block, but this has never been assessed prospectively. The aim of the present study was to evaluate in a prospective trial AV conduction during the long-term follow-up of patients with sick sinus syndrome. METHODS: Two hundred twenty-five consecutive patients with sick sinus syndrome and intact AV conduction were randomized to undergo single-chamber atrial pacing (110 patients) or single-chamber ventricular pacing (115 patients). Follow-up after 3 months and then yearly included measurement of the PQ interval and, in patients with atrial pacemakers, determination of the atrial stimulus-Q intervals at pacing rates of 100 and 120 bpm. The occurrence of AV block in the atrial group was recorded. During follow-up (mean, 5.5+/-2.4 years), there was no change in PQ interval in either group and no change in atrial stimulus-Q intervals or Wenckebach block point in the atrial group. Four of 110 patients in the atrial group developed grade 2 to 3 AV block that required upgrading of the pacemaker (0.6% per year). Two of these 4 patients had right bundle-branch block at pacemaker implantation. CONCLUSIONS: AV conduction, estimated as PQ interval and atrial stimulus-Q interval at atrial pacing rates of 100 and 120 bpm and the Wenckebach block point, remains stable during long-term follow-up. Thus, treatment with single-chamber atrial pacing is safe and can be recommended to patients with sick sinus syndrome without bundle-branch block.