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Biomedical subjects

Lars Eckardt

Publications and source records attributed to Lars Eckardt.

At least 19 recordsLinked to original sources
PubMed2026

Catheter ablation for symptomatic atrial fibrillation (PVI-SHAM-AF): a randomised, double-blind, sham-controlled, multicentre trial.

BACKGROUND: Guidelines recommend catheter ablation for symptom relief in patients with atrial fibrillation. The aim of this trial was to ascertain whether catheter ablation improves atrial fibrillation-related quality of life more than a sham procedure. METHODS: PVI-SHAM-AF was a double-blind, multicentre, randomised trial conducted at nine study sites in Germany and Poland. Patients aged 18 years or older with symptomatic paroxysmal or persistent atrial fibrillation were randomly assigned in a 2:1 ratio to catheter ablation or a sham procedure using an automated online randomisation system with variable block sizes, stratified by trial site. The primary endpoint was the between-group difference in change from baseline to 6 months in the Atrial Fibrillation Effect on the Quality-of-life Questionnaire (AFEQT) summary score. The prespecified primary analysis was done in the intention-to-treat population and included all randomly assigned patients, with missing data handled by multiple imputation. This trial is registered with ClinicalTrials.gov (NCT05119231) and 12-month follow-up is ongoing. FINDINGS: Between Nov 12, 2021, and Nov 3, 2025, 1199 patients were invited to participate in the study and 262 patients consented and were randomly assigned: 173 patients to catheter ablation and 89 to sham. The median age was 67 years (IQR 62-73); 134 (51%) were female and 128 (49%) were male. Median follow-up was 184 days (IQR 181-191). At 6 months, the mean AFEQT summary score had increased from 61·3 (SD 20·1) to 81·1 (16·6) in the catheter ablation group and from 59·2 (19·0) to 74·9 (19·5) in the sham control group. The Hodges-Lehmann estimate of the between-group difference in change was 2·6 (95% CI -2·7 to 8·0; p=0·36). One death occurred in each group; neither was considered related to the study procedure. Serious adverse events adjudicated as related or possibly related to the study procedure occurred in ten unique patients: six patients in the catheter ablation group and four patients in the sham control group. One of these was an ischaemic stroke occurred in the sham control group. INTERPRETATION: Catheter ablation did not demonstrate superiority over a sham procedure for improving atrial fibrillation-related quality of life at 6 months. FUNDING: Helios Gesundheit (Förderung Leipziger Herzmedizin).

Humans↗
PubMed2006

Cardiovascular characterization of Pkd2(+/LacZ) mice, an animal model for the autosomal dominant polycystic kidney disease type 2 (ADPKD2).

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 or PKD2. Patients with ADPKD have an increased incidence of cardiac valve abnormalities and left ventricular hypertrophy. Systematic analyses of cardiovascular involvement have so far been performed only on genetically unclassified patients or on ADPKD1 patients, but not on genetically defined ADPKD2 patients. Even existing Pkd1 or Pkd2 mouse models were not thoroughly analyzed in this respect. Therefore, the aim of this project was the noninvasive functional cardiovascular characterization of a mouse model for ADPKD2. METHODS: Pkd2(+/LacZ) mice and wildtype controls were classified into 8 groups with respect to gender, age and genotype. In addition, two subgroups of female mice were analyzed for cardiac function before and during advanced pregnancy. Doppler-echocardiographic as well as histological studies were performed. RESULTS: Doppler-echocardiography did not reveal significant cardiovascular changes. Heart rate and left ventricular (LV) length, LV mass, LV enddiastolic and LV endsystolic diameters did not differ significantly among the various groups when comparing wildtype and knockout mice. There were no significant differences except for a tendency towards higher maximal early and late flow velocities over the mitral valve in old wildtype mice. CONCLUSIONS: Non-invasive phenotyping using ultrasound did not reveal significant cardiovascular difference between adult Pkd2(+/LacZ) and WT mice. Due to the lack of an obvious renal phenotype in heterozygous mice, it is likely that in conventional ADPKD knock out mouse models severe cardiac problems appear too late to be identified during the reduced lifespan of the animals.

Age Factors↗
PubMed2006

A prospective study on spontaneous fluctuations between diagnostic and non-diagnostic ECGs in Brugada syndrome: implications for correct phenotyping and risk stratification.

AIMS: Fluctuations between the diagnostic ECG pattern and non-diagnostic ECGs in patients with Brugada syndrome are known, but systematic studies are lacking. The purpose of this study was to prospectively evaluate the spontaneous ECG changes between diagnostic and non-diagnostic ECG patterns in patients diagnosed with Brugada syndrome. METHODS AND RESULTS: In 43 patients with Brugada syndrome (27 males; mean age 45+/-11 years), 310 resting ECGs were obtained during a median follow-up of 17.7 months. The ECGs were analysed for the presence of coved type, saddle-back type or no, respectively unspecific, changes. A coved-type ECG pattern with more than 2 mm ST-segment elevation in at least two right precordial leads was defined as diagnostic. The patients were compared for different clinical characteristics with respect to the pattern of fluctuations. Out of a total of 310 ECGs, 102 (33%) revealed a coved type, 91 (29%) a saddle-back type, and 117 (38%) a normal ECG. Fifteen patients (35%) initially presented with a diagnostic coved-type ECG. Fourteen patients (33%) with an initially coved-type ECG exhibited intermittently non-diagnostic ECGs during follow-up. Only one patient (2%) presented constantly with a coved-type ECG. Out of 28 patients (65%) with an initially non-diagnostic ECG, eight (19%) patients developed a diagnostic coved-type ECG during follow-up. Twenty patients (47%) revealed a coved-type ECG during ajmaline challenge, but never had a baseline coved-type ECG recorded. No significant differences were found in gender and clinical characteristics among patients with or without fluctuations between diagnostic and non-diagnostic basal ECGs. The rate of inducible ventricular fibrillation was significantly higher in patients with more than 50% coved-type ECGs than in patients with less than 50% diagnostic ECGs. CONCLUSION: The prevalence of fluctuations between diagnostic and non-diagnostic ECGs in patients with Brugada syndrome is high and may have an implication on the correct phenotyping and on the risk stratification in patients with Brugada syndrome without aborted sudden cardiac death. For correct phenotyping and risk stratification, repetitive ECG recordings seem to be mandatory.

Brugada Syndrome↗
PubMed2006

Electrocardiographic risk stratification in families with congenital long QT syndrome.

AIMS: The QT interval in the surface ECG is one of the most often used risk stratifiers in families with congenital long QT syndrome (LQTS). The best ECG lead for clinical management of LQTS families remains unclear. METHODS AND RESULTS: The predictive power of the QTc interval in all ECG leads was studied in 200 consecutive genotyped LQTS family members to identify mutation carriers (n = 103; age: 35+/-19 years) and high-risk LQTS patients (n = 16 with survived sudden cardiac arrest) using receiver operating curve (ROC) analysis (ROC = area under curve). Additionally, the risk for events (syncope and sudden cardiac arrest) was calculated for QTc decile in all individuals. The predictive power was highest in lead II and lead V5 for identifying carriers in LQTS families. These ECG leads were optimal for risk stratification (ROC range 0.83-0.87). In these leads, positive predictive value (PPV) and negative predictive value (NPV) were highest for suggested QTc cut-offs (440 and 500 ms) for identification of LQTS mutation carriers and high-risk patients (PPV between 78-81 and 73-80%, respectively). The risk for events in QTc deciles increased exponentially from 10 to 80% and was 40% for QTc > 500 ms. CONCLUSION: On the basis of these data, QTc is the best diagnostic and prognostic ECG parameter in LQTS families. A single measurement should be obtained in lead II if measurable and then in left precordial leads (preferably V5) as a second choice.

Adult↗
PubMed2006

Reduced repolarization reserve due to anthracycline therapy facilitates torsade de pointes induced by IKr blockers.

BACKGROUND: Cytostatic agents such as anthracyclines may cause changes in the electrophysiologic properties of the heart. We hypothesized that anthracyclines facilitate life-threatening proarrhythmic side effects of cardiovascular and non-cardiovascular repolarization prolonging drugs. METHODS AND RESULTS: The electrophysiologic effects of chronic administration of doxorubicin (Dox) were studied in ten rabbits, which were treated with Dox twice a week (1.5 mg/kg i.v.). A control group (11 rabbits) was given NaCl solution. Two of ten Dox rabbits died suddenly, the remaining animals showed mild clinical signs of heart failure after a period of six weeks. Echocardiography demonstrated a decrease in ejection fraction (pre treatment: 74 +/- 23% to post treatment: 63 +/- 16% (p <0.05)). In isolated hearts, action potential duration measured by eight simultaneously recorded monophasic action potentials (MAP) was similar in Dox and control hearts. However, in Dox rabbits, administration of the I(Kr)-blocker erythromycin (150-300 microM) led to a significant greater prolongation of the mean MAP duration (63 +/- 21ms vs 29 +/- 12 ms, p <0.05) and the QT interval (100 +/- 32ms vs 58 +/- 17 ms, p <0.05) as compared to control. Moreover, I(Kr)-block led to a more marked increase of dispersion of MAP(90) in the Dox group as compared to control hearts (23 +/- 7ms vs. 9 +/- 4 ms). In the presence of hypokalemia more episodes of early afterdepolarizations and torsade de pointes occurred (p <0.05). CONCLUSION: Even during the early phase of chemotherapeutic treatment,before significant QT-prolongation is present,anthracyclines lead to an increased sensitivity to the proarrhythmic potency of I(Kr)-blocking drugs. Thus, anthracycline therapy reduces repolarization reserve and thereby represents a novel contributing factor for the development of life-threatening proarrhythmia.

Action Potentials↗
PubMed2006

Doppler echocardiography and tissue Doppler imaging in the healthy rabbit: differences of cardiac function during awake and anaesthetised examination.

OBJECTIVE: In the past years, Doppler echocardiography has evolved into a commonly used technique. More recent sophisticated advances in imaging quality have substantially improved spatial and temporal resolution allowing the adaptation of this technique to small animal models, particularly in rabbits but even in mice. Recently, parameters obtained by Tissue Doppler Imaging (TDI) have been shown to be more independent of pre- and afterload than classic hemodynamic Doppler measurements. Exploration of animal models may require anaesthesia but there is only very little information on the effect of anaesthesia on echocardiographic parameters in rabbits. METHODS: We therefore performed Doppler-echocardiographic examinations of 20 wild-type New Zealand White rabbits in awake state and under light ketamine-xylazine anaesthesia. Special focus was put on the evaluation of global and regional left ventricular systolic and diastolic function using TDI and the myocardial performance index (Tei-index). RESULTS: Doppler-echocardiographic measurements including TDI in rabbits were feasible to assess cardiac morphology and function within a short examination time. There were some distinct changes of functional parameters during anaesthesia. Exemplary for systolic function, fractional shortening, cardiac output and systolic TDI velocity of the lateral wall decreased distinctly. Global left ventricular function measured by the Tei-index deteriorated. CONCLUSIONS: Doppler echocardiography and TDI can be performed easily, quickly and safely in the rabbit. Anaesthesia with the cardiodepressive ketamine-xylazine shows some distinct Doppler-echocardiographically measurable negative effects on cardiac function. Thus, echocardiography with less cardiodepressive anaesthetic regimes or even without anaesthesia after training of the animals should be considered as alternatives whenever possible.

Anesthesia↗
PubMed2006

LAMP-2 deficient mice show depressed cardiac contractile function without significant changes in calcium handling.

OBJECTIVE: Mutations in the highly glycosylated lysosome associated membrane protein-2 (LAMP-2) cause, as recently shown, familial Danon disease with mental retardation, mild myopathy and fatal cardiomyopathy. Extent and basis of the contractile dysfunction is not completely understood. METHODS: In LAMP-2 deficient mice, we investigated cardiac function in vivo using Doppler-echocardiography and contractile function in vitro in isolated myocardial trabeculae. RESULTS: LAMP-2 deficient mice displayed reduced ejection fraction (EF) (58.9+/-3.4 vs. 80.7+/-5.1%, P<0.05) and reduced cardiac output (8.3+/-3.1 vs. 14.7+/-3.6 ml/min, P<0.05) as compared to wild-type controls. Isolated multicellular muscle preparations from LAMP-2 deficient mice confirmed depressed force development (3.2+/-0.6 vs. 8.4+/-0.9 mN/mm2, P<0.01). All groups showed similar force-frequency behaviour when normalised to baseline force. Post-rest potentiation was significantly depressed at intervals>15 s in LAMP-2 deficient mice (P<0.05). Although attenuated in absolute force development, the normalised inotropic response to increased calcium and beta-adrenoreceptor stimulation was unaltered. Electron microscopic analysis revealed autophagic vacuoles in LAMP-2 deficient cardiomyocytes. Protein analysis showed unaltered levels of SERCA2a, calsequestrin and phospholamban. CONCLUSIONS: Cardiac contractile function in LAMP-2 deficient mice as a model for Danon disease is significantly attenuated. The occurrence of autophagic vacuoles in LAMP-2 deficient myocytes is likely to be causal for the depressed contractile function resulting in an attenuated cardiac pump reserve.

Animals↗
PubMed2006

Age and gender related reference values for transthoracic Doppler-echocardiography in the anesthetized CD1 mouse.

OBJECTIVE: Doppler-echocardiography of the mouse has evolved to a commonly used technique in the past years as recent advances in imaging quality have substantially improved spatial and temporal resolution allowing the adaptation of this technique to murine models. Although mouse echocardiography is widely used, there is only little information on reference data for wild-type animals available, particularly in older mice. METHODS: We therefore established a database with echocardiographic reference-values in a large set of young (8 weeks) and older adult (52 weeks) Swiss type CD1-mice of either sex. We performed a complete Doppler-echocardiographic examination under light Ketamine-Xylazine-anesthesia. LV-mass was calculated and compared with necropsy heart weights to validate the LV-mass calculation. RESULTS: Doppler-echocardiographic measurements in mice were feasible to assess cardiac morphology and function. Sonomorphological and functional parameters hardly changed between the age of 12 and 52 weeks. Wall thickness, LV-mass and cardiac output were stable with aging. There was a good relative correlation between echocardiographically estimated LV-mass and necropsy heart weight although absolute values differed. There were no significant echocardiographic differences between male and female mice. CONCLUSIONS: The reference values established in this study can be useful in recording and quantifying pathological changes in murine models of cardiovascular diseases. There is hardly any change of cardiac function between the age of 12 and 52 weeks.

Age Factors↗
PubMed2005

Role of sequence variations in the human ether-a-go-go-related gene (HERG, KCNH2) in the Brugada syndrome.

BACKGROUND: Brugada syndrome (BrS) is an inherited electrical disorder associated with a high incidence of sudden death. In a minority of patients, it has been linked to mutations in SCN5A, the gene encoding the pore-forming alpha-subunit of the cardiac Na(+) channel. Other causally related genes still await identification. We evaluated the role of HERG (KCNH2), which encodes the alpha-subunit of the rapid delayed rectifier K(+) channel (I(Kr)), in BrS. METHODS AND RESULTS: In two unrelated SCN5A mutation-negative patients, different amino acid changes in the C-terminal domain of the HERG channel (G873S and N985S) were identified. Voltage-clamp experiments on transfected HEK-293 cells show that these changes increase I(Kr) density and cause a negative shift of voltage-dependent inactivation, resulting in increased rectification. Action potential (AP) clamp experiments reveal increased transient HERG peak currents (I(peak)) during phase-0 and phase-1 of the ventricular AP, particularly at short cycle length. Computer simulations demonstrate that the increased I(peak) enhances the susceptibility to loss of the AP-dome typically in right ventricular subepicardial myocytes, thereby contributing to the BrS phenotype. CONCLUSION: Our study reveals a modulatory role of I(Kr) in BrS. These findings may provide better understanding of BrS and have implications for diagnosis and therapy.

Action Potentials↗
PubMed2005

Electrocardiography and Doppler echocardiography for risk stratification in patients with chronic heart failure: incremental prognostic value of QRS duration and a restrictive mitral filling pattern.

OBJECTIVES: This prospective study tested whether Doppler echocardiographic variables add incremental value to QRS duration in determining the prognosis of patients with chronic heart failure (CHF) and systolic dysfunction. BACKGROUND: Diastolic dysfunction frequently is observed in patients with CHF, but its prognostic impact relative to that of QRS duration is unknown. METHODS: A total of 193 patients with CHF and an ejection fraction <45% were enrolled prospectively. Echo measurements included left ventricular dimensions/volumes, ejection fraction, mitral early/late diastolic velocity ratio, deceleration time, and tissue Doppler mitral annular velocities. The mitral filling pattern was classified as either restrictive (RFP) or nonrestrictive. A cardiac event (cardiac death or urgent cardiac transplantation) was defined as combined study end point. RESULTS: During a follow-up of 385 +/- 270 days, 24 patients suffered an event (cardiac death, n = 21; urgent transplantation, n = 3). The RFP, QRS duration, left ventricular systolic diameter, and mitral annular early diastolic velocity were independent predictors of an event. In patients with QRS duration >144 ms, the outcome was markedly poorer in the presence of RFPs as compared with their absence. Similarly, despite a QRS duration <or =144 ms, the outcome was worse in the presence of a RFP. A risk-stratification model based on the three strongest independent predictors separated groups into those with good prognosis and those with high, intermediate, and low event-free survival rates. CONCLUSIONS: In subjects with CHF and systolic dysfunction, transmitral flow patterns add incremental value to QRS duration in determining the prognosis.

Chronic Disease↗
PubMed2005

A trial of self-adhesive patch electrodes and hand-held paddle electrodes for external cardioversion of atrial fibrillation (MOBIPAPA).

AIMS: External electrical cardioversion is the method of choice to terminate persistent atrial fibrillation. Whether the type of shock electrode affects cardioversion success is not known. We tested whether hand-held steel electrodes improve cardioversion outcome with monophasic or biphasic shocks when compared with adhesive patch electrodes. METHODS AND RESULTS: Two hundred and one consecutive patients with persistent atrial fibrillation (147 male, mean age 63+/-1 years, duration of atrial fibrillation 6.3+/-1 months) were randomly assigned to cardioversion using either a sinusoidal monophasic or a truncated exponential biphasic shock wave form. The first half of patients were cardioverted using adhesive patch electrodes, the second half using hand-held steel paddle electrodes, and all patients using an anterior-posterior electrode position. Paddle electrodes successfully cardioverted 100/104 patients (96%) and patch electrodes 85/97 patients (88%, P=0.04). This effect was comparable to that of biphasic shocks: biphasic shocks cardioverted 102/104 patients (98%) and monophasic shocks 83/97 patients (86%, P=0.001). A beneficial effect of paddle electrodes was observed for both shock wave forms. After cross-over from an ineffective monophasic to a biphasic shock, cardioversion was successful in 198/201 (98.5%) patients. Unsuccessful cardioversion after cross-over (3/201 patients) only occurred with patch electrodes (P=0.07). CONCLUSION: Hand-held paddle electrodes increase success of external cardioversion of atrial fibrillation in this trial. This increase is of similar magnitude as the increase in cardioversion success achieved with biphasic shocks. A combination of biphasic shocks, paddle electrodes, and an anterior-posterior electrode position renders outcome of external cardioversion almost always successful (104/104 patients in this trial).

Atrial Fibrillation↗
PubMed2005

Electrophysiological effects of flecainide and sotalol in the human atrium during persistent atrial fibrillation.

AIMS: Atrial fibrillation (AF) shortens the atrial action potential and the atrial refractory period. These changes promote persistence of AF. Pharmacological prolongation of atrial action potential duration (APD) may therefore help to prevent recurrent AF. In addition to prolonging APD, sodium channel blockers may prevent AF by inducing post-repolarization refractoriness (PRR). We studied whether two antiarrhythmic drugs (sotalol, flecainide) prolong APD or induce PRR in the fibrillating human atrium. METHODS: In 12 patients with persistent AF (11 male, 58 +/- 5 yrs, 27 +/- 7 months duration of AF), we recorded monophasic action potentials from the right atrial appendage and inferior right atrium at baseline and 15 minutes after intravenous administration of sotalol (1.5 mg/kg) or flecainide (2 mg/kg). APD and effective refractory periods (ERP) were determined. RESULTS: Both drugs prolonged APD90 during AF (flecainide from 109 +/- 7 ms to 137 +/- 10 ms, sotalol from 108 +/- 6 ms to 131 +/- 8 ms, both p < 0.05 vs. baseline). Sotalol prolonged ERP in parallel to APD (from 119 +/- 8 ms to 139 +/- 8 ms, p < 0.05). Flecainide induced PRR by prolonging ERP more than APD90 (from 134 +/- 9 ms to 197 +/- 28 ms, p < 0.05 vs. baseline and vs. sotalol). CONCLUSIONS: Flecainide and sotalol prolong the atrial action potential during atrial fibrillation in humans. In addition, flecainide induces atrial PRR. These electrophysiological effects may reduce AF recurrences and prevent their persistence.

Action Potentials↗
PubMed2005

Transmural dispersion of repolarization as a key factor of arrhythmogenicity in a novel intact heart model of LQT3.

BACKGROUND: Congenital and acquired long QT syndrome (LQTS) are caused by abnormalities of ionic currents underlying ventricular repolarization. For a better understanding of the mechanisms by which functional electrical instability at the level of the whole heart leads to torsade de pointes (TdP), a novel model of LQT3 was developed and the role of transmural dispersion of repolarization for the development of proarrhythmia was evaluated. METHODS AND RESULTS: In 11 Langendorff-perfused rabbit hearts, veratridine (0.1-0.5 microM), an inhibitor of sodium channel inactivation, led to a concentration-dependent increase in QT-interval and simultaneously recorded monophasic ventricular action potentials (MAPs) (p<0.05) and thereby mimicked LQT3. Veratridine reproducibly induced early afterdepolarizations (EADs) and TdP after lowering potassium concentration. In bradycardic (AV-blocked) hearts, the increase in MAP duration showed marked regional differences. It was significantly more pronounced on the left endocardium as compared to left or right epicardium. This resulted in a significant increase in dispersion of repolarization (24% at 0.1 microM, 92% at 0.25 microM, 208% at 0.5 microM; p<0.01). Left ventricular transmural dispersion of repolarization increased significantly more than interventricular dispersion (104 to 33 ms at 0.5 microM veratridine; p<0.05). CONCLUSION: By inhibition of sodium channel inactivation, veratridine mimics LQT3 in this intact heart model. In bradycardic, hypokalemic hearts, it reproducibly induced EADs and TdP in the setting of significantly increased left ventricular transmural dispersion of repolarization. Based on these experimental data, reduction of transmural dispersion of repolarization may be considered an important target for the prevention of TdP in patients with LQT3.

Action Potentials↗
PubMed2005

Long-term prognosis of individuals with right precordial ST-segment-elevation Brugada syndrome.

BACKGROUND: Brugada syndrome is an arrhythmogenic disease characterized by an ECG pattern of ST-segment elevation in the right precordial leads and an increased risk of sudden cardiac death as a result of ventricular fibrillation. Controversy exists with regard to risk stratification and therapeutic management, particularly in asymptomatic individuals. METHODS AND RESULTS: A total of 212 individuals (mean age, 45+/-6 years) with a type 1 Brugada ECG pattern were studied. Of these, 123 (58%) were asymptomatic, 65 (31%) had > or =1 syncope of unknown origin, and 24 (11%) had to be resuscitated because of ventricular fibrillation. In 125 individuals (59%), a spontaneous type 1 ECG was recorded. In the remaining, drug challenge with a class I antiarrhythmic agent unmasked a Brugada ECG. The mean ST elevation was 2.3+/-1.2 mm in symptomatic patients and 1.9+/-1.5 mm in asymptomatic individuals (P=0.04). During a mean follow-up of 40+/-50 months, 4 of the 24 patients (17%) with aborted sudden cardiac death and 4 of 65 (6%) with a prior syncope had a recurrent arrhythmic event, whereas only 1 of 123 asymptomatic individuals (0.8%) had a first arrhythmic event. Four of 9 patients with arrhythmic events during follow-up were not inducible during programmed electrical stimulation. A previous history of aborted sudden death or syncope and the presence of a spontaneous type 1 ECG were predictors of adverse outcome. CONCLUSIONS: The present study reports data on a large population of individuals with a type 1 Brugada ECG pattern with the longest follow-up reported so far. A very low incidence of severe arrhythmic events, particularly in asymptomatic individuals, was found during follow-up. In the presence of very few arrhythmic events on follow-up, programmed electrical stimulation showed very little accuracy in predicting outcome.

Adolescent↗
PubMed2005

[Long QT syndrome and Brugada syndrome. Drugs, ablation or ICD?].

Long QT syndrome and Brugada syndrome are potentially fatal inherited arrhythmogenic diseases. Thanks to the contribution of molecular genetics, the genetic bases, pathogenesis, and genotype-phenotype correlation of both diseases have been progressively unveiled and shown to have an extremely high degree of genetic heterogeneity. The clinical manifestation of the diseases is also highly variable. Symptomatic patients experience ventricular tachyarrhythmias which may lead to recurrent syncope and/or sudden cardiac death. In long QT syndrome patients with syncope, therapy with beta-blockers has proven effective. When, despite beta-blocker treatment, arrhythmia-related symptoms continue to occur, an implantable cardioverter defibrillator is indicated. Such a device should also be implanted in resuscitated patients. In symptomatic patients with Brugada syndrome, the implantable cardioverter defibrillator is the only life-saving option. In asymptomatic patients with a Brugada ECG pattern, risk stratification has become of utmost importance in order to discover which patients really need definitive treatment.

Anti-Arrhythmia Agents↗
PubMed2005

Arrhythmogenic right ventricular cardiomyopathy. Antiarrhythmic drugs, catheter ablation, or ICD?

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a major cause of sudden cardiac death and ventricular tachyarrhythmias in young, apparently healthy individuals and athletes. Myocardial atrophy with subsequent fibrofatty replacement predominantly affects right ventricular myocardium and results in global and regional dysfunction as well as areas of slow conduction and dispersion of refractoriness which are prerequisites for reentrant ventricular tachyarrhythmias. Patients affected with ARVC should be excluded from competitive sports and vigorous training. To provide optimal treatment, a detailed diagnostic evaluation and risk stratification are mandatory. Tailored treatment strategies aim at the suppression or effective termination of recurrent ventricular tachyarrhythmias and prevention of sudden death by antiarrhythmic drug therapy, catheter ablation, or implantation of a cardioverter defibrillator (ICD). Antiarrhythmic drugs may be used as a stand-alone treatment to suppress ventricular tachycardia (VT) recurrences in patients with ARVC and low risk of sudden death. Sotalol (preferred) or amiodarone in combination with beta-blockers showed the highest efficacy rates. In patients at higher risk, an ICD should be implanted and antiarrhythmic drugs be used only as an adjunct to prevent or suppress frequent VT recurrences and ICD discharges. Catheter ablation using conventional or electroanatomic mapping techniques yields good acute results for eliminating the targeted arrhythmia substrate. However, during the progressive long-term course of ARVC, VT recurrences from new arrhythmia foci are frequent and therefore limit the curative value of catheter ablation. In patients with frequent VT recurrences and ICD discharges, however, catheter ablation plays an important role as a palliative and adjunctive treatment option for arrhythmia suppression. ICD therapy has been increasingly used for secondary and also primary prevention of sudden death in patients with ARVC. In secondary prevention, the ICD has shown to improve the long-term prognosis of patients at high risk of sudden death by effective termination of life-threatening recurrences of ventricular tachyarrhythmias. However, adequate lead placement may be difficult and lead-related complications during long-term follow-up must be taken into account. The role of ICD therapy for primary prevention of sudden death in ARVC is not yet adequately defined. Ongoing international registries will provide important additional data to improve risk stratification and refine treatment algorithms in order to select the best individual treatment for arrhythmia suppression and prevention of sudden death in patients with ARVC.

Anti-Arrhythmia Agents↗