Images in cardiovascular medicine. Follow-up of cardiac sarcoidosis by magnetic resonance imaging.
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Adult↗
Biomedical subjects
Volker Kühlkamp
Publications and source records attributed to Volker Kühlkamp.
Long-term experience with subcutaneous ICD leads: a comparison among three different types of subcutaneous leads.
ICDs provide protection against sudden cardiac death in patients with life-threatening arrhythmias. Nevertheless, efficacy of defibrillation remains an important issue to guarantee the future safety of patients who receive an ICD. There is a significant number of patients who need an additional subcutaneous lead to obtain a defibrillation safety margin of at least 10 J between the maximum output of the ICD and the energy needed for ventricular defibrillation. However, few data exists about the long-term performance of different types of subcutaneous leads. Therefore, the aim of this study was to analyze the long-term experience with three different types of subcutaneous leads. The study included 132 patients (109 men, 23 women; mean age 59.8 years [SD +/- 10.7 years]). All of them received a subcutaneous lead in addition to a single chamber or dual chamber ICD between October 1990 and April 2002. Two patients received a second subcutaneous lead after the first lead had been removed so that a total of 134 subcutaneous leads were evaluated. Inclusion criteria for the implantation of an additional subcutaneous lead were (1) unsuccessful ventricular defibrillation at implant without a subcutaneous lead, (2) insufficient safety margin (< 10 J) between the maximum output of the ICD and the energy needed for ventricular defibrillation, or (3) clinical evaluation of a new subcutaneous lead (Medtronic 13014). There were no significant differences between the three study groups with regard to age, sex, underlying cardiac disease, left ventricular ejection fraction, NYHA class assessment and clinical arrhythmia. The results of the DFT testing during follow-up (prehospital discharge test and 1 and 3 years) were compared to the baseline value obtained during the implantation procedure. All lead related complications were analyzed. Eighty-two single element subcutaneous array electrodes (SQ-A1), 31 subcutaneous three-finger electrodes (SQ-A3), and 21 subcutaneous patch electrodes (SQ-P) were implanted during the study period. The median follow-up was 1,499 days (25th percentile: 798 days, 75th percentile: 1,976 days) in the SQ-A1 group, 2,209 days (25th percentile: 1,242 days, 75th percentile: 2,710 days) in the SQ-A3 group, and 1,419 days (25th percentile: 787 days, 75th percentile: 2,838 days) in the SQ-P group. None of the three groups had a significant change of the DFT during follow-up compared to baseline. Major complications occurred in six (7.3%) patients in group SQ-A1 and in two (9.5%) patients in group SQ-P. There were no major complications in group SQ-A3. Kaplan-Meier curves analyzing freedom from subcutaneous lead related complications did not show a significant difference between the three study groups (P = 0.16). SQ-A1, SQ-A3, and SQ-P leads provide stable DFTs during long-term follow-up. Major complications are rare. However, a careful follow-up including chest radiographs at regular intervals is needed to detect potentially fatal complications like lead fractures.
Defibrillators, Implantable↗
Atrial fibrillation--rate versus rhythm control.
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Adrenergic beta-Antagonists↗
Molecular mechanisms of early electrical remodeling: transcriptional downregulation of ion channel subunits reduces I(Ca,L) and I(to) in rapid atrial pacing in rabbits.
OBJECTIVES: The purpose of the study was to characterize the ionic and molecular mechanisms in the very early phases of electrical remodeling in a rabbit model of rapid atrial pacing (RAP). BACKGROUND: Long-term atrial fibrillation reduces L-type Ca(2+) (I(Ca,L)) and transient outward K(+) (I(to)) currents by transcriptional downregulation of the underlying ionic channels. However, electrical remodeling starts early after the onset of rapid atrial rates. The time course of ion current and channel modulation in these early phases of remodeling is currently unknown. METHODS: Rapid (600 beats/min) right atrial pacing was performed in rabbits. Animals were divided into five groups with pacing durations between 0 and 96 h. Ionic currents were measured by patch clamp techniques; messenger ribonucleic acid (mRNA) and protein expression were measured by reverse transcription-polymerase chain reaction and Western blot, respectively. RESULTS: L-type calcium current started to be reduced (by 47%) after 12 h of RAP and continued to decline as pacing continued. Current changes were preceded or paralleled by decreased mRNA expression of the Ca(2+) channel beta subunits CaB2a, CaB2b, and CaB3, whereas significant reductions in the alpha(1) subunit mRNA and protein expression began 24 h after pacing onset. Transient outward potassium current densities were not altered within the first 12 h, but after 24 h, currents were reduced by 48%. Longer pacing periods did not further decrease I(to). Current changes were paralleled by reduced Kv4.3 mRNA expression. Kv4.2, Kv1.4, and the auxiliary subunit KChIP2 were not affected. CONCLUSIONS: L-type calcium current and I(to) are reduced in early phases of electrical remodeling. A major mechanism appears to be transcriptional downregulation of underlying ion channels, which partially preceded ion current changes.
Analysis of Variance↗
Effects of the chromanol HMR 1556 on potassium currents in atrial myocytes.
PURPOSE: The chromanol HMR 1556 is a potent blocker of KvLQT1/minK potassium channels expressed in Xenopus oocytes. The compound is therefore a new class III antiarrhythmic drug with a distinct mechanism of action. However, the effect of HMR 1556 on atrial ion channels and the selectivity of block in the human heart has not been investigated. We tested the effects of HMR 1556 on repolarizing potassium currents in human and guinea pig atrial myocytes. METHODS AND RESULTS: Single atrial myocytes were isolated by enzymatic dissociation. Atrial potassium currents (I(Ks), I(Kr), in guinea pig, I(to), I(Kur), I(K1) in humans) were recorded at 36 degrees C in the whole cell mode of the patch clamp technique. HMR 1556 produced a concentration-dependent and reversible block of I(Ks) with a half maximal concentration (EC(50)) of 6.8 nmol/l. 10 micromol/l HMR 1556 almost completely inhibited I(Ks) (97.2+/-3.2%, n=6). Steady-state activation as well as kinetic properties of the current were not altered by HMR 1556. I(Kr) currents were not affected up to concentrations of 10 micromol/l. HMR 1556 did not inhibit other potassium currents in human atrium: I(to), I(Kur) and the classical inward rectifier potassium current I(K1) were not significantly affected up to concentrations that completely blocked I(Ks) (10 micromol/l). CONCLUSIONS: HMR 1556 is a highly-potent blocker of I(Ks) channels without exerting effects on other potassium currents involved in atrial repolarization. Given the potential advantages of I(Ks) vs. I(Kr) blockade, the drug's new mechanism of action warrants further investigation to clarify its role as an antiarrhythmic agent.
Aged↗
Delayed sodium channel inactivation mimics long QT syndrome 3.
DPI 201-106 delays sodium channel inactivation. Acute administration of DPI 201-106 prolonged the QT interval, provoked spontaneous torsades de pointes in one patient, and facilitated stimulation-induced polymorphic ventricular tachyarrhythmias in two patients. Similar to the observations in animal studies, delaying sodium channel inactivation is a new form of the acquired long QT syndrome, mimicking long QT syndrome type 3.
Cardiotonic Agents↗
[Quality of antithrombotic therapy in patients with chronic atrial fibrillation: the AFib Trial].
BACKGROUND: Large randomised studies have definitely shown that oral anticoagulation effectively reduces thromboembolic complications, e.g. stroke, in patients with chronic non-valvular atrial fibrillation (AFib). However, less than 50% of the eligible AFib patients receive anticoagulation, although their risk of thromboembolic disease is increased 5-7 fold as compared to individuals who have a regular sinus rhythm. This is the reason why undertreatment needs to be evaluated and addressed. In Germany, data on the antithrombotic therapy of these patients are sparse, national guidelines are lacking. AIM OF THE STUDY: This prospective cohort study is the first one to evaluate the quality of antithrombotic prevention in two groups of AFib outpatients in two different, socio-demographically comparable regions of Germany (Südbaden and Südwürttemberg) over a period of several years. Quality of care is defined as the percentage of AFib patients in a certain region treated according to international guidelines. If the percentage in both cohorts does not exceed 80%, guidelines are to be developed and implemented in Südwürttemberg on consideration of the specific treatment conditions in this region; their applicability is to be evaluated later. METHODS: Office-based specialists of internal and general medicine are currently recruiting 200 AFib patients in each study region for documentation of their clinical data. Besides the quality of antithrombotic chemoprevention, relevant problems emerging in antithrombotic therapy in an ambulant setting will be identified. In the area of intervention (Südwürttemberg) experts and office-based physicians will exclusively develop evidence-based guidelines and disseminate them among doctors. Six months after the implementation of these guidelines in Südwürttemberg, their influence on prescribing patterns will be determined by comparing the proportion of anticoagulated AFib patients in Südwürttemberg to that of the control cohort (Südbaden). In addition, secondary outcomes of interest include deaths, days of hospitalisation, and incidence of stroke or bleeding episodes for different antithrombotic treatments.
Atrial Fibrillation↗
Initial experience with an implantable cardioverter-defibrillator incorporating cardiac resynchronization therapy.
OBJECTIVES: The purpose of this study was to evaluate an implantable cardioverter-defibrillator (ICD) incorporating biventricular pacing. BACKGROUND: Biventricular pacing improves the symptoms of heart failure, a frequent problem in ICD recipients. METHODS: This prospective multicenter study evaluated the safety and efficacy of an ICD with biventricular pacing. RESULTS: A total of 84 patients with a standard ICD indication, symptomatic heart failure, left ventricular (LV) ejection fraction <35% and a QRS duration >130 ms were included in the trial. In 81 of 84 patients the LV lead was successfully implanted. Patients significantly improved in the 6-min hall-walk test (baseline 304 plus minus 131 m, three months 397 plus minus 142 m, p < 0.001), quality of life (baseline 38.9 plus minus 21.2, three months 26.5 plus minus 21.2, p < 0.001) and the New York Heart Association (NYHA) classification (baseline 2.8 plus minus 0.6, three months 2.2 plus minus 0.5). Left ventricular end-diastolic (from 79.6 plus minus 13.0 mm to 73.6 plus minus 12.9 mm, p = 0.002) and end-systolic (from 68.3 plus minus 13.5 mm to 63.9 plus minus 12.9 mm, p < 0.001) diameter decreased, and fractional shortening increased (from 16 plus minus 6% to 18 plus minus 6%, p = 0.018). Of the patients 26 experienced 472 episodes of spontaneous sustained ventricular tachyarrhythmias. All episodes were successfully terminated except for 16 episodes occurring in a patient with incessant ventricular tachycardia. Biventricular antitachycardia pacing was more effective than right ventricular antitachycardia pacing (p < 0.001). During follow-up (median 185 days, range 12 to 344 days) five patients died from progressive heart failure. CONCLUSIONS: Incorporating biventricular pacing in an ICD is feasible and leads to an improvement of heart failure symptoms. Therefore, this therapy may become an option for patients who need ICD therapy in the presence of severe heart failure.
Adult↗
[Remodeling in atrial fibrillation].
BACKGROUND: Atrial fibrillation is associated with alterations in atrial electrophysiology that facilitate the initiation and persistence of the arrhythmia. This process was termed electrical remodeling in atrial fibrillation. The underlying cellular and molecular mechanisms have intensively been investigated over the past few years in patients with atrial fibrillation and in different experimental models. The results, that have substantially improved the understanding of the pathophysiology of atrial fibrillation, are reviewed. CELLULAR AND MOLECULAR MECHANISMS: On the cellular level, atrial fibrillation leads to a strong shortening and an impaired rate adaptation of the action potential as well as to changes in action potential morphology. Atrial fibrillation is associated with an altered gene expression of the L-type calcium channel (ICa,L) and of potassium channels (Ito, IK1, IKACh). The molecular mechanisms of intraatrial conduction slowing are less well understood, changes in the expression or distribution of gap junction proteins or a decrease of the fast sodium inward channel (INa) have been reported in some studies. A trigger of initiation for electrical remodeling is an overload of the cytoplasm with Ca2+ and a consecutive decrease of the systolic calcium gradient, furthermore changes in calcium-handling proteins are detectable in atrial fibrillation. CONCLUSION: These changes in the cellular and molecular milieu importantly determine the clinical course and the efficacy of therapeutical interventions in atrial fibrillation. The clinical relevance and potential new therapeutic approaches are discussed in the last part.
Animals↗
beta3-Adrenergic regulation of an ion channel in the heart-inhibition of the slow delayed rectifier potassium current I(Ks) in guinea pig ventricular myocytes.
OBJECTIVES: I(Ks), the slow component of the delayed rectifier potassium current, underlies a strong beta-adrenergic regulation in the heart. Catecholamines, like isoproterenol, induce a strong increase in I(Ks). Recent work has pointed to an opposing biological effect of beta(1)- and beta(3)-adrenoceptors in the heart. However the role of these subtypes in the regulation of cardiac ion channel function is unknown. METHODS: We investigated the effects of beta(1)- and beta(3)-adrenoceptor modulation on I(Ks) in guinea-pig ventricular myocytes, using patch-clamp techniques. RESULTS: Superfusion with 100 nmol/l isoproterenol increased the step current amplitude by 81.3+/-8.0%. In contrast, after block of beta(1)- (1 micromol/l atenolol) and beta(2)-receptors (1 micromol/l ICI118,551), isoproterenol induced a reduction of the step current amplitude by 34.3+/-3.5%. The beta(3)-selective agonist BRL37344 significantly reduced the I(Ks) step current at +70 mV in a concentration-dependent manner (IC(50): 5.01 nmol/l). In the presence of bupranolol (beta(1)-, beta(2)- and beta(3)-adrenoceptor antagonist), the effect of BRL37344 was markedly attenuated, from 27.3+/-5.6% (100 nmol/l BRL37344 alone) to 4.0+/-1.3% (100 nmol/l BRL37344+1 micromol/l bupranolol). BRL37344 (100 micromol/) did not alter current amplitudes of KvLQT1/minK expressed in CHO cells or in Xenopus oocytes, excluding a direct effect of BRL37344 on the channel. 1 micromol/l BRL37344 mildly prolonged action potentials in guinea pig ventricle (APD(90):+7.8%) CONCLUSIONS: We have demonstrated a functional coupling between the beta(3)-adrenoceptor and ion channel function in the mammalian heart. Our findings point to a potential role for beta(3)-adrenoceptors in cardiac electrophysiology and pathophysiology.
Action Potentials↗
Experience with a dual chamber implantable defibrillator.
An implantable defibrillator with dual chamber pacing may have advantages for pacing, sensing, and detection of brady- and tachyarrhythmias. This study evaluates the safety and performance of a dual chamber implantable cardioverter defibrillator that incorporates an algorithm to discriminate supraventricular from ventricular arrhythmias. The 300 patients in this study had the device implanted for the following indications: ventricular tachycardia (47%), sudden cardiac death survivorship (51%), and prophylactic implants (2%). Patients received dual chamber pacing for accepted bradyarrhythmic (51.7%) or investigational indications. During a mean follow-up period of 1.7 months a total of 1,092 arrhythmia episodes in 96 patients were fully documented in the device memory: 66 patients experienced a total of 796 ventricular tachyarrhythmia episodes and 42 experienced a total of 296 supraventricular episodes. The device appropriately detected 100% of sustained ventricular tachyarrhythmias while reducing the inappropriate detection of supraventricular tachyarrhythmias by 72% compared to single chamber rate only detection. The positive predictive value was 90.5% for ventricular tachyarrhythmia detection in episodes that exceeded the tachycardia detection rate. Adverse events observed in at least 2% of the patients were incisional pain (22%), inappropriate ventricular detection (7%), atrial lead dislodgement (4%), atrial oversensing/undersensing (3%), hematoma (3%), incessant ventricular tachyarrhythmia (2%), and pneumothorax (2%). There were 13 deaths, none of which were attributed to device failure. The Gem DR is safe and effective for the detection and treatment of ventricular tachyarrhythmias. The dual chamber detection algorithm appropriately recognized supraventricular tachycardia with rapid ventricular rates 72% of the time while maintaining 100% detection of sustained ventricular tachyarrhythmias.
Adolescent↗
Efficacy of metoprolol and sotalol in the prevention of recurrences of sustained ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator.
ICDs provide protection against sudden cardiac death in patients with life-threatening ventricular arrhythmias. Nevertheless, most ICD recipients receive adjunctive antiarrhythmic drug therapy to reduce the number of recurrent episodes and ICD discharges. The aim of the study was to compare the efficacy of metoprolol and d,l-sotalol in preventing VT/VF recurrences in patients with an ICD in a prospective, randomized trial. One hundred patients (83 men, 17 women; mean age 59 years, SD +/- 11 years) were randomized to receive metoprolol or sotalol after implantation of an ICD. There were no significant differences between the two groups with regard to age, sex, underlying cardiac disease, left ventricular ejection fraction, NYHA class assessment and clinical arrhythmia. The median follow-up was 728 days (25th percentile: 530 days, 75th percentile: 943 days) in the metoprolol group and 727 days (25th percentile: 472 days, 75th percentile: 1,223 days) in the sotalol group (P = 0.52). Thirty-three patients treated with metoprolol and 30 patients receiving sotalol had at least one episode during the follow-up. Event-free survival curves were generated for the two treatment arms using the Kaplan-Meier method and showed no significant difference (P = 0.68). Eight patients treated with metoprolol and six patients treated with sotalol died during follow-up. Total mortality was not significantly different between the two study groups (P = 0.43). Metoprolol is as efficacious as sotalol in preventing VT/VF recurrences in patients with an ICD.
Defibrillators, Implantable↗
Is it safe to program a long tachycardia detection interval?
Implantable cardioverter defibrillator (ICD) therapy is used frequently in patients with "slow" ventricular tachycardia (VT). Hence, the tachycardia detection interval is programmed within the range of the physiologic heart rate, but this may cause serious problems. If a fast VT is converted to sinus tachycardia with a cycle length shorter than the tachycardia detection interval, the episode is not terminated and the success counter is not reset. If this happens repeatedly, therapies will be exhausted without termination of the episode. If VT recurs within such an episode, it will not be treated. This report describes a patient who died suddenly in a scenario similar to the one described. Although all documented VT/ventricular fibrillation episodes were terminated by the device, the episode was not terminated because of the ongoing supraventricular tachycardia. Therefore, no further therapies were available and the patient probably died of fast untreated VT. Programming of a long tachycardia detection interval is dangerous in currently available ICDs.
Aged↗
Use of beta-blockers in atrial fibrillation.
Atrial fibrillation is the most common arrhythmia in the general population and is frequently associated with organic heart disease. beta-adrenoceptor antagonists (b-blockers) are very effective in preventing atrial fibrillation after coronary artery bypass surgery. It has been shown recently that the beta-blocker metoprolol controlled release/extended release (CR/XL) is also effective in maintaining sinus rhythm after conversion of atrial fibrillation. There is concern that class I antiarrhythmic drugs, such as quinidine, disopyramide, and flecainide in particular, may increase mortality. The risk of proarrhythmia associated with beta-blocker treatment is very low. Therefore b-blockers, such as metoprolol CR/XL, may be the first line of treatment to maintain sinus rhythm, especially after myocardial infarction and in patients with chronic heart failure and in those with arterial hypertension. In patients with persistent atrial fibrillation, AV-nodal conduction-slowing drugs, such as calcium channel antagonists and beta-blockers are used to control the ventricular rate during atrial fibrillation. Several studies clearly show that beta-blockers alone, or in combination with digoxin are very effective in controlling the ventricular rate at rest and during exercise. beta-blockers are effective in maintaining sinus rhythm and controlling the ventricular rate during atrial fibrillation. Given these effects and their favorable effects on mortality, beta-blockers should be considered as first-line agents in the management of patients with atrial fibrillation.
Adrenergic beta-Antagonists↗