Steen M. Jensen

Electrocardiographic and Clinical Predictors of Torsades de Pointes Induced by Almokalant Infusion in Patients with Chronic Atrial Fibrillation or Flutter: A Prospective Study

The aim of this study was to identify predictors of torsades de pointes (TdP) in patients with atrial fibrillation (AF) or flutter exposed to the Class III antiarrhythmic drug almokalant. TdP can be caused by drugs that prolong myocardial repolarization. One hundred patients received almokalant infusion during AF (infusion 1) and 62 of the patients during sinus rhythm (SR) on the following day (infusion 2). Thirty‐two patients converted to SR. Six patients developed TdP. During AF, T wave alternans was more common prior to infusion (baseline) in patients developing TdP (50% vs 4%, P < 0.01). After 30 minutes of infusion 1, the TdP patients exhibited a longer QT interval (493 ± 114 vs 443 ± 54 ms [mean ± SD], P < 0.01), a larger precordial QT dispersion (50 ± 74 vs 27 ± 26 ms, P < 0.05), and a lower T wave amplitude (0.12 ± 0.22 vs 0.24 ± 0.16 mV. P < 0.01). After 30 minutes of infusion 2, they exhibited a longer QT interval (672 ± 26 vs 489 ± 74 ms, P < 0.001), a larger QT dispersion in precordial (82 ± 7 vs 54 ± 52 ms, P < 0.01) and extremity leads (163 ± 0 vs 40 ± 34 ms, P < 0.001), and T wave alternans was more common (100% vs 0%, P < 0.001). Risk factors for development of TdP were at baseline: female gender, ventricular extrasystoles, and treatment with diuretics; and, after 30 minutes of infusion: sequential bilateral bundle branch block, ventricular extrasystoles in bigeminy, and a biphasic T wave. Patients developing TdP exhibited early during almokalant infusion a pronounced QT prolongation, increased QT dispersion, and marked morphological T wave changes.

Long-Term Follow-Up of Patients Treated By Radiofrequency Ablation of the Atrioventricular Junction

JENSEN, S.M., et al.: Long‐Term Follow‐Up of Patients Treated By Radiofrequency Ablation of the Atrioventricular Junction. Radiofrequency ablation of the AV conduction tissue (His‐bundle ablation) is an accepted treatment for therapy resistant atrial fibrillation/flutter. However, data on the long‐term effects of the procedure are limited. We followed 50 patients for a mean of 17 months after AV junction ablation. The indication was treatment resistant atrial fibrillation or flutter. The patients underwent a standardized interview performed by two nurses. Health care was studied via the in‐patient register. Subjective improvement was reported by 88% and the number of days in hospital per year was reduced from 17 to 7. The use of antiarrhythmic drugs was reduced by 75%. If the reduction in costs of drugs and days in hospital is compared with the cost of the ablation and the pacemaker implantation, breaking even is achieved after 2.6 years. We could not confirm that patients with paroxysmal atrial fibrillation note less improvement than those with chronic fibrillation. Conclusion: Ablation of the AV junction is a cost effective treatment with good long‐term results and relatively few complications. Recommendations: Chronic atrial fibrillation: If sinus rhythm cannot be established and in cases in which heart rate regulating drugs have been ineffective, ablation of the AV junction with implantation of a VVIR pacemaker is recommended. Paroxysmal atrial fibrillation: If the patient despite treatment with antiarrhythmic drugs continues to have symptomatic episodes of atrial fibrillation, then AV junction ablation with implantation of a permanent pacemaker is recommended. Patients who have self‐limiting episodes of atrial fibrillation should be given a DDDR pacemaker with an automatic mode switch. Patients who do not have self‐limiting attacks and require DC conversion, should receive a VVIR pacemaker

Liver transplantation does not prevent the development of life-threatening arrhythmia in familial amyloidotic polyneuropathy, Portuguese-type (ATTR Val30Met) patients

Background. Orthotopic liver transplantation (OLT) is today the only available treatment to halt the progress of familial amyloidotic polyneuropathy (FAP). Because heart arrhythmia and conduction disturbances are well-known manifestations of FAP, the aim of this study was to investigate the occurrence and development of heart conduction and rhythm disturbances in Swedish FAP patients who underwent liver transplantation. Methods. Ambulatory 24-hour electrocardiography (ECG) recordings (Holter-ECGs) were available from 30 patients, who had been investigated before and reexamined after OLT. Results. The number of patients with abnormalities on their ECG recordings increased after OLT. Four patients developed serious arrhythmia after transplantation that necessitated the insertion of a pacemaker 40 months or longer after OLT. Conclusions. The development of cardiac conduction disturbances and arrhythmias appear not to be halted by liver transplantation, indicating that the physician should be aware of the potential risk for FAP patients receiving transplants to develop fatal arrhythmia. The follow-up after liver transplantation should include Holter-ECG recordings.

Changes in ventricular repolarization during percutaneous transluminal coronary angioplasty in humans assessed by QT interval, QT dispersion and T vector loop morphology

Abstract. Nowinski K, Jensen S, Lundahl G, Bergfeldt L (Karolinska Hospital, Stockholm, Norrlands University Hospital, Umeå and Ortivus AB, Täby, Sweden). Changes in ventricular repolarization during percutaneous transluminal coronary angioplasty in humans assessed by QT interval, QT dispersion and T vector loop morphology. J Intern Med 2000; 248: 126–136.

Atorvastatin and persistent atrial fibrillation following cardioversion: a randomized placebo-controlled multicentre study

AIMS To evaluate the effect of atorvastatin in achieving stable sinus rhythm (SR) 30 days after electrical cardioversion (CV) in patients with persistent atrial fibrillation (AF). METHODS AND RESULTS The study included 234 patients. The patients were randomized to treatment with atorvastatin 80 mg daily (n = 118) or placebo (n = 116) in a prospective, double-blinded fashion. Treatment was initiated 14 days before CV and was continued 30 days after CV. The two groups were well-balanced with respect to baseline characteristics. Mean age was 65 +/- 10 years, 76% of the patients were male and 4% had ischaemic heart disease. Study medication was well-tolerated in all patients but one. Before primary endpoint 12 patients were excluded. In the atorvastatin group 99 patients (89%) converted to SR at electrical CV compared with 95 (86%) in the placebo group (P = 0.42). An intention-to-treat analysis with the available data, by randomization group, showed that 57 (51%) in the atorvastatin group and 47 (42%) in the placebo group were in SR 30 days after CV (OR 1.44, 95%CI 0.85-2.44, P = 0.18). CONCLUSION Atorvastatin was not statistically superior to placebo with regards to maintaining SR 30 days after CV in patients with persistent AF.

Heart complications in familial transthyretin amyloidosis: impact of age and gender.

Heart arrhythmia is common in Swedish patients with familial amyloidotic polyneuropathy (FAP), as well as cardiomyopathy. We investigated the relationship between Holter ECG and echocardiographic findings in 108 FAP patients, with particular focus on age and gender differences. Female patients were younger than male patients at symptom onset (p < 0.01). Only 4 of 39 patients with septal hypertrophy were females. Regression analysis showed that age of onset, gender and duration of disease were significantly related with intraventricular septum (IVS) thickness. Sixty-five patients (25 females) presented with abnormal 24-h ECG recordings. IVS thickness was not significantly related to conduction disturbances or the presence of ventricular arrhythmia (VA). However, IVS thickness and atrial dimension were both related to increased rate of supraventricular arrhythmia (SVA). Male gender was clearly associated with more pronounced septal thickness of the heart. Conduction disturbances were not related to IVS thickness, indicating that the distribution and extent of infiltration of the heart by amyloid are heterogeneous and related to gender and age of onset. These findings highlight the necessity of 24-h ECGs to detect conduction disturbances, due to their occurrence in the absence of echocardiographic evidence of amyloid deposition in the myocardium.

Effect of right atrial overdrive pacing in the prevention of symptomatic paroxysmal atrial fibrillation: a multicenter randomized study, the PAF-PACE study.

The aim of this study was to assess if right atrial overdrive pacing can suppress symptomatic episodes of paroxysmal atrial fibrillation (PAF) in patients without bradyarrhythmias. Forty‐two patients with frequent and symptomatic PAF without other pacing indication had a pacemaker implanted after a 4‐week run‐in period, during which the frequency of symptomatic PAF episodes and the mean heart rate were objectively documented. Depending on the mean heart rate recorded during run‐in, the pacemaker was programmed in random order to right atrial AAI pacing at 10–19 beats/min > mean heart rate (medium overdrive [MO]), at 20–29 beats/min > mean heart rate (high overdrive [HO]) and to no pacing (OAO mode) for 4–12 weeks each using a crossover design. In the 35 patients who completed the protocol, the number of symptomatic episodes of PAF (>30‐second duration) per week was significantly lower during MO pacing (median 0.88, P = 0.001, n = 35) and during HO pacing (median 0.75, P = 0.002, n = 20) than during OAO (median 2.02 and 2.04, respectively). There was no difference between MO and HO pacing in the 20 patients paced at both rates (0.97 vs 0.75, P = 0.33). Seven patients did not complete the protocol due to persistent atrial fibrillation (n = 4), angina pectoris requiring surgery (n = 1), and unwillingness to continue the study due to improvement (n = 1) or worsening (n = 1) of symptoms during the study periods. Right atrial overdrive pacing can reduce the number of symptomatic PAF episodes in patients with frequent and drug refractory PAF but without bradyarrhythmias. (PACE 2003; 26:1841–1848)

Abnormal heart rate variability and subtle atrial arrhythmia in patients with familial amyloidotic polyneuropathy.

Background: Cardiac autonomic dysfunction is a common complication of familial amyloidotic polyneuropathy (FAP), but cardiac arrhythmia and conduction disturbances are also common. We analyzed heart rate variability (HRV) in FAP patients using power spectrum analysis and Poincaré plot analysis.

On-Line Computerized Vectorcardiography: Influence of Body Position, Heart Rate, Radiographic Contrast Fluid and Myocardial Ischemia

UNLABELLED On-line computerized vectorcardiography (cVCG) is increasingly being used for continuous monitoring of myocardial ischemia, however, little is known about factors other than ischemia causing electrocardiographic abnormalities. This paper describes how three important cVCG parameters, STC-VM, ST-VM and QRS-VD, are affected by different body positions, myocardial ischemia, contrast injection and increasing heart rate in patients with and without coronary artery disease. The main findings of the study are: contrast injection and different body positions caused major changes in QRS-VD but affected ST-VM and STC-VM to a minor degree. Increasing heart rate by atrial pacing produced substantial changes in all three parameters. Ischemia during angioplasty also produced changes in all three parameters, STC-VM being the most sensitive parameter. IN CONCLUSION (1) STC-VM (> or = 50 microV) is the most valuable parameter for monitoring ischemia; (2) we propose ST-VM > or = 50 microV as criterion instead of previously used 25 microV; (3) QRS-VD cannot be used as a single marker of ischemia, and (4) electrocardiographic changes induced by increased heart rate should be taken into account during interpretation.

Prevalence, mutation spectrum, and cardiac phenotype of the Jervell and Lange-Nielsen syndrome in Sweden

AIMS To explore the national prevalence, mutation spectrum, cardiac phenotype, and outcome of the uncommon Jervell and Lange-Nielsen syndrome (JLNS), associated with a high risk of sudden cardiac death. METHODS AND RESULTS A national inventory of clinical JLNS cases was performed. Genotype and area of origin were ascertained in index families. Retrospective clinical data were collected from medical records and interviews. We identified 19 cases in 13 Swedish families. A JLNS prevalence >1:200 000 was revealed (five living cases <10 years of age). The mutation spectrum consisted of eight KCNQ1 mutations, whereof p.R518X in 12/24 alleles. Geographic clustering of four mutations (20/24 alleles) and similarities to Norways mutation spectrum were seen. A high prevalence of heterozygotes was suggested. Three paediatric cases on β-blockers since birth were as yet asymptomatic. Seven symptomatic cases had suffered an aborted cardiac arrest and four had died suddenly. QTc prolongation was significantly longer in symptomatic cases (mean 605 ± 62 vs. 518 ± 50 ms, P = 0.016). β-Blockers reduced, but did not abolish, cardiac events in any previously symptomatic case. β-Blocker type, dosage, and compliance probably affect outcome significantly. Implantable cardioverter-defibrillator therapy (ICD, n = 6) was associated with certain complications; however, no case of sudden death. CONCLUSION Founder effects could explain 83% of the Swedish JLNS mutation spectrum and probably contribute to the high JLNS prevalence found in preadolescent Swedish children. Due to the severe cardiac phenotype in JLNS, the importance of stringent β-blocker therapy and compliance, and consideration of ICD implantation in the case of therapy failure is stressed.