High-intensity interval training improves peak oxygen uptake and muscular exercise capacity in heart transplant recipients.

Heart transplant (HTx) recipients usually have reduced exercise capacity with reported VO(2peak) levels of 50-70% predicted value. Our hypothesis was that high-intensity interval training (HIIT) is an applicable and safe form of exercise in HTx recipients and that it would markedly improve VO(2peak.) Secondarily, we wanted to evaluate central and peripheral mechanisms behind a potential VO(2peak) increase. Forty-eight clinically stable HTx recipients >18 years old and 1-8 years after HTx underwent maximal exercise testing on a treadmill and were randomized to either exercise group (a 1-year HIIT-program) or control group (usual care). The mean ± SD age was 51 ± 16 years, 71% were male and time from HTx was 4.1 ± 2.2 years. The mean VO(2peak) difference between groups at follow-up was 3.6 [2.0, 5.2] mL/kg/min (p < 0.001). The exercise group had 89.0 ± 17.5% of predicted VO(2peak) versus 82.5 ± 20.0 in the control group (p < 0.001). There were no changes in cardiac function measured by echocardiography. We have demonstrated that a long-term, partly supervised and community-based HIIT-program is an applicable, effective and safe way to improve VO(2peak) , muscular exercise capacity and general health in HTx recipients. The results indicate that HIIT should be more frequently used among stable HTx recipients in the future.

Molecular genetic analysis of long QT syndrome in Norway indicating a high prevalence of heterozygous mutation carriers.

Mutations in the KCNQ1, HERG, SCN5A, minK and MiRP1 genes cause long QT syndrome (LQTS), of which there are two forms: the Romano Ward syndrome and the Jervell and Lange-Nielsen syndrome. We have performed DNA sequencing of the LQTS-associated genes in 169 unrelated patients referred for genetic testing with respect to Romano Ward syndrome and in 13 unrelated patients referred for genetic testing with respect to Jervell and Lange-Nielsen syndrome. A total of 37 different mutations in the 5 genes, of which 20 were novel, were identified. Among patients with the most stringent clinical criteria of Romano Ward syndrome, a mutation was identified in 71%. Twelve of the 13 unrelated patients referred for genetic testing with respect to Jervell and Lange-Nielsen syndrome were provided with a molecular genetic diagnosis. Cascade genetic screening of 505 relatives of index patients with molecularly defined LQTS identified 251 mutation carriers. The observed penetrance was 41%. Although caution must be exerted, the prevalence of heterozygotes for mutations in the LQTS-associated genes in Norway could be in the range 1/100-1/300, based on the prevalence of patients with Jervell and Lange-Nielsen syndrome.

[Severe ibutilide-induced arrhythmia in patients with heart failure]. / Alvorlig arytmi utløst av ibutilid hos hjertesviktpasienter.

BACKGROUND: Ibutilide is a novel class III antiarrhythmic agent used for the termination of atrial flutter and atrial fibrillation. It mainly affects membrane potassium currents (IKr) and prolongs the cardiac action potential. This effect is reflected as QT-interval prolongation in the ECG. Drugs that affect IKr-currents are known to cause malignant ventricular arrhythmia. MATERIAL AND METHODS: We report three patients with heart failure where ibutilide triggered malignant ventricular arrhythmias (sustained torsades de pointes). RESULTS: All patients experienced dramatic haemodynamic deterioration. One patient died because of sustained arrhythmia. Mode of action for ibutilide is described. Precautions that should be observed when using ibutilide are outlined. INTERPRETATION: Ibutilide is contraindicated in patients with heart failure and should be used with caution in patients with ischaemic heart disease or previous myocardial infarction. Ibutilide-induced ventricular arrhythmias may be particularly difficult to treat in patients with heart failure.

When should heparin preferably be administered during radiofrequency catheter ablation?

RF catheter ablation is complicated by thromboembolism in about 1% of patients. Limited knowledge exists concerning when and how to use anticoagulation or antithrombotic treatment. We studied the activation of coagulation (prothrombin fragment 1 + 2 [PF1 + 2] and D-dimer), platelets (beta-thromboglobulin [beta-TG]) and fibrinolysis (plasmin-antiplasmin complexes [PAP]) during RF ablation of accessory pathways in 30 patients. They were randomized to receive heparin (100 IU/kg, intravenously) (1) immediately after introduction of the femoral venous sheaths (group I) or (2) after the initial electrophysiological study, prior to the delivery of RF current (groups II and III). Group II additionally received saline irrigation of all femoral sheaths. After the initial bolus, 1,000 IU of heparin was supplied hourly in all groups. Within groups II and III, median plasma values of PF1 + 2 and beta-TG more than tripled (P < or = 0.007) during the diagnostic study and gradually declined during heparin administration despite RF current delivery. Median D-dimer tripled (P = 0.005) and PAP doubled (NS) before heparin administration; then both remained around the upper reference values. In the early heparin group, however, PF1 + 2, D-dimer, and PAP did not rise at all, and beta-TG showed only a slight increase towards the end of the procedure. The differences between group I versus groups II and III were statistically significant prior to the first RF current delivery (PF1 + 2, D-dimer, and beta-TG) and by the end of the procedure (PF1 + 2, D-dimer, and PAP). In conclusion, "late" heparin administration allows hemostatic activation during the initial catheterization and diagnostic study. By administering intravenous heparin immediately after introduction of the venous sheaths, hemostatic activation is significantly decreased. Saline irrigation of the venous sheaths added nothing to late heparin administration.

Duration of preoperative electrocardiographic QRS complex and the incidence of heart arrest after aorto coronary bypass surgery.

Sudden heart arrest (HA) in the early phase after aorto coronary bypass surgery represents a serious event necessitating resuscitation, and for those who survive usually also an extra stay in the coronary care unit. Since such episodes of heart standstill may be related to conduction defects, a study was conducted to determine whether the duration of the QRS complex on the preoperative ECG is a marker for this morbid event. A cohort of 1011 consecutive patients operated on between 1982 and 1986 and followed to January 1st, 1993 were included in the study. Incidence of lethal or non-lethal HA during the first 4 weeks after surgery was considered as the primary endpoint and total mortality as the secondary endpoint. The incidence of HA was 40/1011 = 4%, with the majority of events (60%) being lethal. Independent risk factors of HA using the multivariate logistic model were previous coronary artery bypass surgery, presence of mitral regurgitation, left ventricular ejection fraction and the intraoperative cross-clamp time of aorta. Adjusting for the effect of confounder variables showed that the gradient effect of QRS complex duration on the endpoint HA was still present (p = 0.012). The duration of the QRS complex taken from the preoperative ECG had a gradient effect on the incidence of HA. With a baseline level of QRS <70 ms, the following odds ratios (OR) for HA were found: OR = 1.38 (95% CI 0.60-3.31) for QRS 70-80 ms; OR = 2.27 (95% CI 0.87-5.90) for QRS >90-120 ms; and OR = 3.38 (95% CI 1.06-11.50) for QRS > 120 ms, when adjusting for the risk factors. Cumulative survival at 5 years after surgery was 28+/-7.1% for patients experiencing HA versus 87+/-1.2% for patients free from this event. Our results underline the importance of the QRS complex duration as a preoperative marker for HA after aorta coronary bypass surgery, when adjusting for other risk factors. Although the one-year survival is poor for patients experiencing HA, there is no increase in mortality during the late follow-up.

Temperature-controlled radiofrequency catheter ablation with a 10-mm tip electrode creates larger lesions without charring in the porcine heart.

BACKGROUND: Radiofrequency catheter ablation of atrial flutter, atrial fibrillation or ventricular tachycardia may be favoured by large lesions. We compared lesions created in unipolar mode using 10-mm/8 F electrodes with those of 4-mm/7 F catheters. METHODS: Ablations were first performed in porcine hearts in vitro (70 degrees C, 60 s, tangential catheter tip-tissue orientation). Anaesthetized pigs were thereafter ablated with 10- or 4-mm catheters in the right atrial free wall (RAFW), inferior vena cava-tricuspid valve (IVC-TV) isthmus and left ventricle (LV). RESULTS: In vitro, lesion length doubled and lesion volume tripled using the 10-mm catheter. Average power supply was 69 (SD12) (10-mm tip) versus 26 (SD7) W (4-mm tip). In vivo, lesion length increased by 50% and lesion volume fivefold. Charring at the lesion surface or sudden impedance rises were not observed in vivo. Histologically, coagulation necrosis and minor haemorrhages were found. One RAFW lesion (10-mm) showed a dissection approaching the epicardium. Fibrinous platelet clots or overt thromboses covered the endocardial surface in half of all lesions. Three 10-mm electrode isthmus lesions extended to the right descending posterior artery and one LV lesion to the left anterior descending artery, but there was no damage to the arterial walls. Following six ablations with the 10-mm electrode and two with the 4-mm tip, injury to the adjacent lung tissue of 0.5 to 6.0 mm depth was found (p = 0.22). CONCLUSION: RF ablation using 10-mm/8 F electrodes created significantly larger lesions. 10-mm electrodes appeared safe in the porcine IVC-TV isthmus and LV, but not in the RAFW.

The activation of platelet function, coagulation, and fibrinolysis during radiofrequency catheter ablation in heparinized patients.

INTRODUCTION: Catheter ablation may be complicated by clinical thromboembolism in about 1% of patients. METHODS AND RESULTS: We studied the activation of coagulation (prothrombin fragment 1+2 [PF1+2]), platelets (beta-thromboglobulin [beta-TG])) and fibrinolysis (plasmin-antiplasmin complexes [PAP] and D-dimer) during radiofrequency (RF) ablation in 13 patients. They received heparin 100 U/kg intravenously after the initial electrophysiologic study, prior to the delivery of RF current; thereafter 1,000 U/hour throughout the procedure. PF1+2 increased fourfold (P < 0.001) during the diagnostic study, but gradually declined to upper reference value during heparin administration. There was a strong correlation between procedure duration prior to heparin bolus (range 39 to 173 min); and (a) the maximal rise of PF1+2 (r = 0.83, P < 0.001) and (b) the increase of PF1+2 from baseline to end of the procedure (r = 0.74, P = 0.004). There was no correlation between postheparin changes of PF1+2 and (a) postheparin procedure duration (range 40 to 317 min), (b) number of RF pulses (range 1 to 16), or (c) RF current duration (range 46 to 687 sec). Plasma beta-TG concentration showed similar trends. Fibrinolytic activity increased moderately from baseline until heparin administration; then remained around the upper reference values. PAP at the end of procedure and D-dimer at the time of heparin administration both correlated with preheparin procedure duration (r = 0.70, P = 0.007 and r = 0.69, P = 0.01, respectively). All parameters were normal the next morning. CONCLUSION: Procedure duration prior to heparin administration, and not the delivery of RF current per se, determines activation of hemostasis and fibrinolysis during RF ablation.

Bipolar radiofrequency catheter ablation creates confluent lesions at larger interelectrode spacing than does unipolar ablation from two electrodes in the porcine heart.

AIMS: Radiofrequency catheter ablation of atrial flutter and fibrillation may be favoured by large, elongated lesions. We compared bipolar ablation with unipolar ablation from one or two electrodes in the porcine heart. METHODS AND RESULTS: In vitro, confluent lesions were reliably created by a 'dielectrode' catheter (energy delivered simultaneously (in parallel) from two 4 mm electrodes spaced 1 mm apart, towards an indifferent electrode), and a 'bipolar' catheter (energy delivered (in series) between two 4 mm electrodes spaced 5 mm apart). Sixteen anaesthetized pigs were randomized to standard unipolar (4), dielectrode (6) or bipolar (6) ablation. Two radiofrequency current deliveries of 30 s duration (70 degrees C) were administered to the inferior vena cava-tricuspid valve isthmus and two to the right atrial free wall in all animals. After 4 h, the lesions were examined macroscopically and histologically. Mean (SD) endocardial lesion length x width x depth measured 7.4 (2.4) x 5.4 (2.2) x 2.8 (0.8) mm in the standard unipolar mode, 10.2 (1.4) x 6.3 (0.7) x 3.3 (1.1) mm in the dielectrode mode and 14.0 (3.6) x 6.0 (1.7) x 3.8 (1.2) mm in the bipolar mode. Thus lesion length increased significantly through the three groups (P < 0.001), while width and depth did not. CONCLUSION: Both dielectrode and bipolar ablation were feasible in porcine right atrial ablation, and created longer lesions than the standard unipolar mode. By allowing a larger interelectrode distance, bipolar ablation created the longest lesions and may be favourable when linear lesions are necessary.

Radiofrequency current ablation of porcine right atrium: increased lesion size with bipolar two catheter technique compared to unipolar application in vitro and in vivo.

Interruption of atrial flutter and fibrillation by RF catheter ablation may be favored by large, elongated lesions. We administered RF current in unipolar and bipolar mode in porcine right atrium. Bipolar ablation was performed between the tip electrodes of two serially coupled catheters. With 4-mm tip electrodes in vitro, lesion length increased from a mean (SD) of 7.9 (1.2) mm at 3 mm-interelectrode distance (i.e.d.) to 13.3 (3.3) mm at 9-mm IED, but decreased at 12-mm IED due to nonconfluent lesions (P < 0.0001). With 4 mm distal electrodes and 8 mm IED, bipolar lesions were 65% longer than corresponding unipolar ablations. Switching to bipolar mode increased the lesion length more than increasing electrode tip length to 6 mm in unipolar mode. Power and temperature controlled ablation created equally sized lesions. Twelve anesthetized pigs were randomized to unipolar or two catheter bipolar temperature controlled ablation of the right atrial free wall. Bipolar ablation created confluent lesions with endocardial length x width of 13.5 (5.8) x 7.3 (3.7) mm, unipolar ablation 6.4 (2.8) x 4.6 (1.4) mm (P < 0.001 when comparing length and P = 0.013 for lesion width). The atrial lesions in both groups were transmural and extended into hilar lung lesions with maximal depth of 3.0 (1.1) and 2.6 (1.0) mm, respectively (P = 0.44). Five bipolarly and four unipolarly ablated pigs developed right diaphragmal paresis. We conclude that bipolar ablation may be preferable in situations where large, elongated lesions are favorable. The two catheter technique is feasible in porcine right atrium. Both bipolar and unipolar ablation of the porcine right atrial free wall may frequently be complicated by injury to the phrenic nerve and adjacent lung tissue.

Temperature guided radiofrequency catheter ablation of myocardium: comparison of catheter tip and tissue temperatures in vitro.

Temperature monitoring during RF ablation has been proposed as a means of controlling the creation of the lesion. However, in vivo studies have shown poor correlation between lesion size and catheter tip temperature. Thus, we hypothesized a difference between catheter tip and tissue temperatures during RF catheter ablation, and that this difference may depend on flow passing the ablation site, tip electrode length, and catheter-tissue orientation. In vitro studies were performed using four different ablation catheters (tip electrode length: 2, 4, or 6 mm) with a thermistor or a thermocouple as temperature sensor. Set temperature was 70 degrees C and pulse duration was 30 seconds. Pieces of porcine left ventricle were immersed in a bath of isotonic saline-dextrose solution at 37 degrees C. The ablation catheters were positioned perpendicularly, obliquely, or parallel to the endocardium. A temperature sensor was inserted from the epicardial side and positioned 1 mm beneath the catheter-tissue interface. Experiments were made with a flow of 200 mL/min passing the ablation site or with no flow. The catheter tip and tissue temperatures differed significantly (P < 0.0001) during ablation. This difference increased with time, with flow passing the ablation site, with the length of the tip electrode, and when the catheter was positioned perpendicularly or obliquely to the endocardium as compared to the parallel catheter-tissue orientation (P < 0.05). In conclusion, the tissue temperature may far exceed the catheter tip temperature, and intramyocardial superheating resulting in steam formation and popping may occur despite a relatively low catheter tip temperature.

[Heart rate variability. Parameters for risk stratification after myocardial infarction]. / Hjertefrekvensvariabilitet. Parameter for risikostratifisering etter hjerteinfarkt.

Reduced heart rate variability (HRV) is an independent risk factor after myocardial infarction, indicating higher risk of fatal and nonfatal arrhythmias and of cardiac death in general. Analysis of HRV is also a valuable tool in clinical research, providing a non-invasive measurement of fluctuations in sympathetic and parasympathetic activation. We expect increased use of these methods, since new 24-hour: ECG-monitoring equipment is to be delivered with software for HRV as an option. Statistical time domain analysis of the whole 24-hour system of recording is very suitable for stratifying risk after myocardial infarction. Frequency domain analysis requires manual as well as automatic editing, but is the method of choice in clinical research involving short-term recordings and standardized conditions.

Effects of combined radiofrequency and direct current energy catheter ablation on ventricular myocardium in pigs.

When radiofrequency catheter ablation of ventricular arrhythmias is unsuccessful, an option may be to combine it with direct current energy. We therefore investigated the effects of such a combination. Radiofrequency energy was delivered in a bipolar or unipolar fashion to the left and right ventricles through an ablation catheter with a tip electrode 2 mm long, using a temperature-guided radiofrequency generator. Radiofrequency ablation was followed by a single cathodal direct current shock (66 J) with the ablation catheter positioned similarly in six closed-chest pigs. In a control group (six animals) only direct current ablation was performed, with one or two energy applications (66 J) in each ventricle. Two of six animals in the radiofrequency/direct current group died due to perforation in the follow-up period, 1 and 3.5 h after the direct current ablation, respectively. Gross pathological examination of the hearts revealed transmural lesions in all animals. In the radiofrequency/direct current group four lesions were perforated, three of which were located in the left ventricle. There was a significant increase in the number of perforations in the radiofrequency/direct current group compared to the control group, where perforation was never observed. Haemorrhagic pericardial fluid was found in five of the six animals in the radiofrequency/direct current group compared to none in the control group. These findings show that myocardial ablation with radiofrequency energy followed by direct current energy in the same session may have a high complication rate.

Power and temperature guided radiofrequency catheter ablation of the right atrium in pigs.

The aim of the present study was twofold: to assess the safety of ablating the atrial free wall using RF current; and to assess the effect of a single dose of intravenous heparin followed by aspirin once daily to prevent thrombus formation after RF ablation. Temperature and power guided catheter ablation were evaluated. Twenty pigs were randomized to power or temperature guided unipolar RF catheter ablation. Ten animals received a bolus of heparin (150 U/kg) followed by 150-mg aspirin daily, and ten served as controls. A mid-sternal thoracotomy was performed 5-7 days later. The ability of a lesion to resist an increased transmural atrial pressure was examined by inflating a cuff around the pulmonal artery. Transmural lesions were found in all animals. Right atrial pressure was increased from 5 to 30 mmHg with no sign of perforation. In 11 of 20 (55%) animals, 1-3 lesions were found in the lungs (diameter 4-18 mm). The localization of these lesions corresponded to the lesions in the atria. There were no differences in the energy delivery modes with regard to the number of animals with lung lesions. Lesions with thrombus formation were found in four animals in the heparin/aspirin group and in nine animals in the control group. The incidence of thrombi was significantly smaller in the treatment group. There were no differences between temperature and power guided catheter ablation with regard to the size of the atrial lesions or to the incidence of thrombus formation. Transmural lesions induced in the right atrium by RF energy are resistant to increases in transmural pressure. However, lung tissue overlying the ablated target may be injured by the RF energy delivered. The combination of a single dose intravenous heparin followed by aspirin daily may reduce the incidence of thrombus formation.

[Guidelines for use of amiodarone (Cordarone). A potent anti-arrhythmic agent that may have problematic adverse effects]. / Retningslinjer for bruk av amiodaron (Cordarone). Et potent antiarytmikum som kan gi problematiske bivirkininger.

The authors discuss the potent antiarrhythmic drug amiodarone, with emphasis on indications, efficacy and side effects. At present the drug can be prescribed only by specialists in internal medicine. In order to monitor the efficacy of the drug and any side effects the patient should preferably be evaluated every three to six months. Use of intravenous amiodarone in hospital is effective in many cases but, so far, documentation on this treatment is limited.

The effect of temperature-guided radiofrequency ablation of ventricular myocardium.

The safety and feasibility of temperature-guided radiofrequency (RF) ablation of ventricular myocardium were assessed in an open-chest animal model. RF ablation was performed in the ventricles of 19 pigs using ablation catheters with a tip electrode of 2 or 4 mm length. The energy was delivered in a bipolar (2 mm tip electrode only) or unipolar configuration. Set temperature ranged from 60 to 90 degrees C. Pulse duration was 30 s. Histological examination showed coagulation necrosis with a haemorrhagic zone. However, lesions with a deep cleavage were found after five unipolar (2 mm tip electrode) energy applications. No such lesions were found after unipolar energy applications with a 4 mm tip electrode. During or shortly after ablation, premature ventricular beats and non-sustained VT were frequently observed and in some instances ventricular fibrillation. In the bipolar mode we found a positive correlation between lesion area/volume and peak temperature with a correlation coefficient of 0.48 and 0.56, respectively (P < 0.05). However no correlation was found between lesion size and applied energy. In the unipolar configuration there was no correlation between lesion size and these parameters. Median depth and area were: bipolar: 4.0 mm/23.5 mm2, unipolar (2 mm tip electrode): 3.5 mm/12.2 mm2, unipolar (4 mm tip electrode): 4.0 mm/15.7 mm2. We conclude that in a beating heart it is difficult to predict lesion size from temperature or energy.