Statistical analysis of the DIAMOND MI study by the multipole method.

We present a new method to describe the dynamics of the beat-to-beat RR time series. The classification of the phase-space plots obtained from RR time series is performed by a calculation of parameters which describe the features of the two-dimensional plot. We demonstrate that every parameter has its specific consequence on the evaluation of the state of the cardiac function. By applying the method to the DIAMOND MI study we demonstrate that these parameters have more prognostic power than previously suggested risk markers. The results suggest that the RR intervals constitute a highly complex time series which necessitates the use of refined mathematical-statistical methods in order to reveal pathologies in the heart rate.

Long QT syndrome patients may faint due to neurocardiogenic syncope.

AIMS: Syncope in long QT syndrome (LQTS) is expected to be due to Torsades de Pointes ventricular tachycardia (TdP). Often these patients faint in situations with emotional stress. The aim of the present study was to evaluate whether neurocardiogenic syncope occurs in LQTS. METHODS AND RESULTS: Ten untreated consecutive LQTS patients (age 11-72 years, median 37.5 years, five males and five females from five different families (one KvLQT1 mutation, two HERG mutations in three families and one without established genetic background)) were examined by a head-up tilt-table test (HUT). If syncope did not occur within 25 min, the patient received 0.25 mg nitroglycerine sublingually and the HUT was continued for 20 min. Nine out of 10 patients had a positive HUT. The syncope resulted from a combined vasodepressor and bradycardiac response. There were no cases of TdP. No syncope occurred in a 42-year-old asymptomatic male LQTS patient with a borderline prolonged QTc of 0.45 s and a HERG mutation. In 11 of 21 patients referred for syncope without LQTS a positive HUT was found (P < 0.10). CONCLUSION: Syncope in LQTS can be of neurocardiogenic origin and is not necessarily due to TdP. The reason for neurocardiogenic syncope in LQTS is unknown, but involvement of the autonomic nervous system outside the heart is possible.

Quality assessment of pacemaker implantations in Denmark.

AIMS: Quality assessment of therapeutic procedures is essential to insure a cost-effective health care system. Pacemaker implantation is a common procedure with more than 500,000 implantations world-wide per year, but the general complication rate is not well described. We studied procedure related complications for all implantations performed in an entire nation over a 3-year period. METHODS AND RESULTS: A prospective study of complications related to 99% of the 5648 primary pacemaker implantations performed in the 12 Danish pacemaker centres in 1997-1999 was carried out. Overall 76% of the patients received a physiological pacemaker system and 91% received the optimal pacing mode according to international guidelines. Perioperative complications requiring reoperation were: haematoma 0.3%, atrial lead related 1.9%, ventricular lead related 1.7%. Late complications requiring reoperation were: infection 02%, atrial lead related 13%, ventricular lead related 1.2%. The complication rate decreased over the study period, but overall the complication rate was higher than expected and showed considerable variation between centres. CONCLUSIONS: Our results demonstrate that sensitive data such as complications related to pacemaker implantations can be collected on a national basis. We suggest that a reoperation rate higher than 3% for atrial as well as ventricular pacing electrodes in the individual implanting centre should cause the centre to evaluate carefully the procedure as well as the performance of the individual implanter.

Effects of intravenous dofetilide on induction of atrioventricular re-entrant tachycardia.

OBJECTIVE: To assess the efficacy and safety of intravenous dofetilide in preventing induction of atrioventricular re-entrant tachycardia. DESIGN: A multicentre, open, dose ranging trial. Fifty one patients with electrically inducible atrioventricular re-entrant tachycardia were allocated to one of five doses of dofetilide (1.5, 3, 6, 9, and 15 microgram/kg), two thirds of the dofetilide dose being given over a 15 minute loading period and the remainder over a 45 minute maintenance period. MAIN OUTCOME MEASURE: Responders were defined as patients in whom dofetilide prevented reinduction of atrioventricular re-entrant tachycardia at the end of the infusion. RESULTS: Intravenous dofetilide had no effect on tachycardia inducibility at the two lower doses (1.5 and 3 microgram/kg) but prevented the reinduction of tachycardia at the three higher doses (6, 9, and 15 microgram/kg) at a rate of 36% (11/31). There was a clear relation between plasma dofetilide concentrations and efficacy (p = 0.009). In non-responders, dofetilide increased the cycle length of induced atrioventricular re-entrant tachycardia. Dofetilide increased the atrial and ventricular effective refractory periods, as well as the antegrade and retrograde effective refractory period of the accessory pathway. Treatment related side effects were reported in four patients, one with a new sustained incessant supraventricular tachycardia. CONCLUSIONS: Dofetilide shows promise as an agent for the prevention of atrioventricular re-entrant tachycardia in patients without structural heart disease.

[Dofetilide to patients with heart failure and left ventricular dysfunction]. / Dofetilid til patienter med hjerteinsufficiens og dårligt fungerende venstre ventrikel.

INTRODUCTION: Dofetilide, a new class III antiarrhythmic drug, was tested for its ability to reduce mortality and morbidity in patients with congestive heart failure and left ventricular dysfunction. METHODS: In 34 Danish centers, 1518 patients with NYHA class III or IV heart failure and wall motion index of the left ventricle < or = 1.2 (ejection fraction < or = 35%) were randomized to receive dofetilide or placebo in a double blind study. The dose of dofetilide was adjusted to renal function and the QT interval. Patients were monitored continuously with ekg during the first three days in the study. Minimum follow up was one year. RESULTS: Dofetilide did not affect mortality. Hospitalizations for worsening of heart failure were reduced significantly, hazard ratio 0.75 (0.63-0.89) Dofetilide effectively converted atrial fibrillation to sinus rhythm. After one year, 61% of patients with atrial fibrillation had converted on dofetilide and 33% on placebo (p < 0.001). DISCUSSION: Dofetilide can be used to convert atrial fibrillation to sinus rhythm and to maintain sinus rhythm in patients with congestive heart failure and left ventricular dysfunction. Dofetilide does not affect mortality.

Effect of dofetilide in patients with recent myocardial infarction and left-ventricular dysfunction: a randomised trial.

BACKGROUND: Arrhythmias cause much morbidity and mortality after myocardial infarction, but in previous trials, antiarrhythmic drug therapy has not been convincingly effective. Dofetilide, a new class III agent, was investigated for effects on all-cause mortality and morbidity in patients with left-ventricular dysfunction after myocardial infarction. METHODS: In 37 Danish coronary-care units, 1510 patients with severe left-ventricular dysfunction (wall motion index < or = 1.2, corresponding to ejection fraction < or = 0.35) were enrolled in a randomised, double-blind study comparing dofetilide (n=749) with placebo (n=761). The primary endpoint was all-cause mortality. Secondary endpoints included cardiac and arrhythmic mortality and total arrhythmic deaths. Analyses were by intention to treat. FINDINGS: No significant differences were found between the dofetilide and placebo groups in all-cause mortality (230 [31%] vs 243 [32%]), cardiac mortality (191 [26%] vs 212 [28%]), or total arrhythmic deaths (129 [17%] vs 140 [18%]). Atrial fibrillation or flutter was present in 8% of the patients at study entry. In these patients, dofetilide was significantly better than placebo at restoring sinus rhythm (25 of 59 vs seven of 56; p=0.002). There were seven cases of torsade de pointes ventricular tachycardia, all in the dofetilide group. INTERPRETATION: In patients with severe left-ventricular dysfunction and recent myocardial infarction, treatment with dofetilide did not affect all-cause mortality, cardiac mortality, or total arrhythmic deaths. Dofetilide was effective in treating atrial fibrillation or flutter in this population.

Dose-related cardiac electrophysiological effects of intravenous magnesium. A double-blind placebo-controlled dose-response study in patients with paroxysmal supraventricular tachycardia.

AIMS: The role of magnesium as an antiarrhythmic drug is yet not conclusive. Therefore, we performed a double-blind, randomized, placebo-controlled dose-response study of cardiac electrophysiological effects of intravenous magnesium. METHODS AND RESULTS: Thirty-six patients undergoing an electrophysiological evaluation for paroxysmal supraventricular tachycardia were randomized to one of the following dosages of intravenous magnesium (0, 5, 10 or 20 mmol). Conventional electrophysiological variables for sinus node function, atrial, atrioventricular node and ventricular conduction and refractoriness were measured before and after magnesium administration. Prolongation of the atrial-His interval was found at 5 mmol of magnesium compared with placebo and no further prolongation was observed at higher doses (-3 +/- 8, 11 +/- 9, 7 +/- 15, 11 +/- 16, for the dosages of 0, 5, 10 and 20 mmol of magnesium, respectively, P < 0.05). Measures of sinus node function, intra-atrial conduction and conduction through the Purkinje system were unaffected by magnesium. Male gender was associated with prolongation in atrial effective refractory period, in contrast to shortening in females: 2 +/- 43, 35 +/- 44, 36 +/- 33, 13 +/- 12 ms for males and 3 +/- 6, -12 +/- 11, -13 +/- 12, 0 +/- 23 ms for females, respectively (P < 0.001). CONCLUSION: Atrioventricular node conduction was prolonged by 5 mmol intravenous magnesium and no further prolongation was observed at higher dosages. At dosages of 5 and 10 mmol magnesium the atrial effective refractoriness was prolonged in males and shortened in females.

Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group.

BACKGROUND: Atrial fibrillation occurs frequently in patients with congestive heart failure and commonly results in clinical deterioration and hospitalization. Sinus rhythm may be maintained with antiarrhythmic drugs, but some of these drugs increase the risk of death. METHODS: We studied 1518 patients with symptomatic congestive heart failure and severe left ventricular dysfunction at 34 Danish hospitals. We randomly assigned 762 patients to receive dofetilide, a novel class III antiarrhythmic agent, and 756 to receive placebo in a double-blind study. Treatment was initiated in the hospital and included three days of cardiac monitoring and dose adjustment. The primary end point was death from any cause. RESULTS: During a median follow-up of 18 months, 311 patients in the dofetilide group (41 percent) and 317 patients in the placebo group (42 percent) died (hazard ratio, 0.95; 95 percent confidence interval, 0.81 to 1.11). Treatment with dofetilide significantly reduced the risk of hospitalization for worsening congestive heart failure (risk ratio, 0.75; 95 percent confidence interval, 0.63 to 0.89). Dofetilide was effective in converting atrial fibrillation to sinus rhythm. After one month, 22 of 190 patients with atrial fibrillation at base line (12 percent) had sinus rhythm restored with dofetilide, as compared with only 3 of 201 patients (1 percent) given placebo. Once sinus rhythm was restored, dofetilide was significantly more effective than placebo in maintaining sinus rhythm (hazard ratio for the recurrence of atrial fibrillation, 0.35; 95 percent confidence interval, 0.22 to 0.57; P<0.001). There were 25 cases of torsade de pointes in the dofetilide group (3.3 percent) as compared with none in the placebo group. CONCLUSIONS: In patients with congestive heart failure and reduced left ventricular function, dofetilide was effective in converting atrial fibrillation, preventing its recurrence, and reducing the risk of hospitalization for worsening heart failure. Dofetilide had no effect on mortality.

[Right bundle branch block, ST segment elevation and sudden cardiac death. A clinical and electrocardiographic syndrome--Brugada syndrome]. / Højresidigt grenblok, ST-segment-elevation og pludselig hjertedød. Et klinisk og elektrokardiografisk syndrom-Brugadas syndrom.

The association of an abnormal electrocardiogram (ecg) consisting of right bundle branch block and ST segment elevation in leads V1-V3 and sudden arrhythmic death has been described in patients with no demonstrable structural heart disease. A patient with these ecg findings and aborted sudden death is presented. The patient had no structural heart disease and received an implantable cardioverter-defibrillator which seems to be the treatment of choice.

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.

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.

Heart failure and echocardiographic changes during long-term follow-up of patients with sick sinus syndrome randomized to single-chamber atrial or ventricular pacing.

BACKGROUND: In patients with sick sinus syndrome, choice of pacing mode has been implicated in the development of congestive heart failure. METHODS AND RESULTS: A total of 225 consecutive patients with sick sinus syndrome and intact atrioventricular conduction were randomized to either single-chamber atrial pacing (n = 110) or single-chamber ventricular pacing (n = 115). Clinical assessment included New York Heart Association classification, medication, and M-mode echocardiography before pacemaker implantation, after 3 months, and subsequently once every year. At long-term follow-up (mean, 5.5+/-2.4 years), NYHA class was higher in the ventricular group than in the atrial group (NYHA class I/II/III/IV: 65/44/4/0 versus 84/22/2/1 patients, P=.010). Increase in NYHA class during follow-up was observed in 35 of 113 patients in the ventricular group versus 10 of 109 in the atrial group (P<.0005). Increase in dose of diuretics from randomization to last follow-up was significantly higher in the ventricular group than in the atrial group (21+/-49 versus 8+/-42 mg furosemide/d, P=.033). The left ventricular fractional shortening decreased significantly in the ventricular group (from 0.36+/-0.12 to 0.31+/-0.08, P<.0005) but not in the atrial group (from 0.35+/-0.13 to 0.33+/-0.09, P=.087). The left atrial diameter increased significantly in both treatment groups (ventricular group: from 34+/-7 to 41+/-7 mm, P<.0005; atrial group: from 34+/-6 to 37+/-7 mm, P=.002), but the increase was significantly higher in the ventricular group than in the atrial group (P<.0005). CONCLUSIONS: During long-term follow-up, ventricular pacing is associated with a higher incidence of congestive heart failure and consumption of diuretics than atrial pacing. This is accompanied by a decrease in left ventricular fractional shortening and an increased dilatation of the left atrium in the ventricular paced patients.

Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick-sinus syndrome.

BACKGROUND: In a previous study of 225 patients with sick-sinus syndrome randomised to either single-chamber atrial pacing (n=110) or single-chamber ventricular pacing (n=115), we found that after a mean follow-up of 3.3 years, atrial pacing was associated with significantly less atrial fibrillation and thromboembolism whereas there was no significant difference in mortality and heart failure between the two groups. We aimed to find out whether this beneficial effect of atrial pacing is maintained during extended follow-up of up to 8 years. METHODS: Follow-up visits for all patients were at 3 months, 12 months, then once a year at which patients had a physical examination, ECG recording, and pacemaker check-up. Endpoints were mortality, cardiovascular death, atrial fibrillation, thromboembolic events, heart failure, and atrioventricular block. Data was analysed on Dec 31, 1996. FINDINGS: At long-term follow-up, 39 patients from the atrial group had died versus 57 from the ventricular group (relative risk 0.66 [95% CI 0.44-0.99]; p=0.045). 19 patients from the atrial group and 39 patients from the ventricular group died from a cardiovascular cause (0.47 [0.27-0.82]; p=0.0065). The cumulative incidences of atrial fibrillation and chronic atrial fibrillation were also significantly lower in the atrial group than in the ventricular group (0.54 [0.33-0.89], p=0.012 and 0.35 [0.16-0.76], p=0.004, respectively). Thromboembolic events occurred in 13 patients in the atrial group and 26 in the ventricular group (0.47 [0.24-0.92], p=0.023). Heart failure was less severe in the atrial group than in the ventricular group (p<0.05). In multivariate analysis, atrial pacing was significantly associated with freedom from thromboembolic events (0.47 [0.24-0.92], p=0.028) and survival from cardiovascular death (0.52 [0.30-0.91], p=0.022), but no longer with overall survival (0.71 [0.46-1.08], p=0.11) or chronic atrial fibrillation (0.45 [0.20-1.05], p=0.063). Atrioventricular block occurred in four patients in the atrial group (0.6% annual risk). INTERPRETATION: The beneficial effect of atrial pacing found in our previous study is enhanced substantially over time. Patients with sick-sinus syndrome should be treated with an atrial rather than ventricular-pacing system because after long-term follow-up, atrial pacing is associated with a significantly higher survival, less atrial fibrillation, fewer thromboembolic complications, less heart failure, and a low-risk of atrioventricular block.

[Atrial fibrillation after coronary artery bypass surgery. The significance of preoperative vagus modulation and ectopic atrial activity]. / Atreiflimren efter koronar bypass-kirurgi. Betydningen af proeoperativ vagusmodulation og ektopisk atrieaktivitet.

To investigate the impact of pre-operative autonomic balance and atrial ectopic activity on the risk of atrial fibrillation or flutter after aorto-coronary artery bypass surgery 24-hour Holter monitoring was analyzed in 102 patients before coronary artery bypass grafting. Index for vagal tone was calculated as % successive RR-interval differences > 6%. Twenty-nine (28%) of the 102 patients developed atrial fibrillation or flutter. Independent predictors (90% confidence interval) of postoperative atrial fibrillation or flutter were identified by logistic regression analysis: the independent predictors were older age, relative risk 1.07/year (1.02-1.12), vagal index < 10%, relative risk 4.50 (1.40-14.5), > or= 10 ectopic supraventricular beats/24 hour, relative risk 3.03 (1.05-8.72), and one or more event of non-sustained supraventricular tachycardia, relative risk 3.02 (1.11-8.22). Thus, age of the patient, attenuated preoperative cardiac vagal modulation, ectopic supraventricular beats, and paroxysmal non-sustained supraventricular tachycardia are independent risk factors for the development of atrial fibrillation or flutter after coronary artery bypass surgery.