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Thomas Wichter

Publications and source records attributed to Thomas Wichter.

At least 37 records · Page 2Linked to original sources

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↗

Abnormal myocardial presynaptic norepinephrine recycling in patients with Brugada syndrome.

BACKGROUND: Life-threatening ventricular tachyarrhythmias can occur in young patients without structural heart disease (idiopathic forms). In many patients, these are typically triggered by an increased sympathetic tone, eg, by physical or mental stress. In contrast, in Brugada syndrome, ventricular tachyarrhythmias more often occur during rest or sleep when the vagal tone is predominant. Furthermore, adrenergic agonists can reduce the level of ST-segment elevation, whereas it is increased by parasympathetic agonists or adrenergic antagonists. The aim of this study was to investigate presynaptic and postsynaptic myocardial sympathetic function in patients with Brugada syndrome. METHODS AND RESULTS: Nine patients with Brugada syndrome (6 male, 3 female; age, 41+/-13 years) were enrolled in this study. The cardiac autonomic nervous system was assessed noninvasively, quantifying myocardial presynaptic and postsynaptic sympathetic function by means of positron emission tomography with the norepinephrine analogue 11C-Hydroxyephedrine (11C-HED) and the nonselective beta-blocker 11C-CGP 12177 (11C-CGP). Presynaptic sympathetic norepinephrine recycling, assessed by 11C-HED, was globally increased in patients with Brugada syndrome compared with a group of age-matched healthy control subjects (92.9+/-16.2 mL/g versus 69.1+/-14.2 mL/g; P<0.05), whereas postsynaptic beta-adrenoceptor density, assessed by 11C-CGP, was similar in patients and control subjects (10.4+/-6.7 pmol/g versus 10.2+/-2.9 pmol/g; P=NS). CONCLUSIONS: The present study on autonomic innervation in Brugada syndrome describes an enhanced presynaptic norepinephrine recycling with preserved beta-adrenoceptor density, further supporting the hypothesis of an autonomic dysfunction in Brugada syndrome. This is a further step toward the understanding of the pathophysiology of the disease with potential future impact on therapeutic strategies.

Adult↗

Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with fibrofatty replacement of cardiac myocytes, ventricular tachyarrhythmias and sudden cardiac death. In 32 of 120 unrelated individuals with ARVC, we identified heterozygous mutations in PKP2, which encodes plakophilin-2, an essential armadillo-repeat protein of the cardiac desmosome. In two kindreds with ARVC, disease was incompletely penetrant in most carriers of PKP2 mutations.

Adolescent↗

Implantable cardioverter/defibrillator therapy in arrhythmogenic right ventricular cardiomyopathy: single-center experience of long-term follow-up and complications in 60 patients.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a major cause of ventricular tachycardia (VT) and cardiac arrest in young patients. We hypothesized that treatment with implantable cardioverter/defibrillators (ICDs) is safe and improves the long-term prognosis of ARVC patients at high risk of sudden death. METHODS AND RESULTS: Sixty patients with ARVC (aged 43+/-16 years) were treated with transvenous ICD systems. Despite a higher number of right ventricular sites tested for adequate lead positions (P<0.05), lower R-wave amplitudes (P<0.001) were achieved in ARVC patients compared with other entities. During follow-up of 80+/-43 months (396 patient-years), event-free survival was 49%, 30%, 26%, and 26% for appropriate ICD therapies and 79%, 64%, 59%, and 56% for potentially fatal VT (>240 bpm) after 1, 3, 5, and 7 years, respectively. Multivariate analysis identified extensive right ventricular dysfunction as an independent predictor of appropriate ICD discharge. Fifty-three adverse events occurred in 37 patients during the perioperative (n=10) or follow-up (n=43) period, mainly related to the leads (n=31 in 21 patients). No lead perforation was observed. Freedom from adverse events was 90%, 78%, 56%, and 42% and freedom from lead-related complications was 95%, 85%, 74%, and 63% after 1, 3, 5, and 7 years, respectively. CONCLUSIONS: These results strongly suggest an improvement in long-term prognosis by ICD therapy in high-risk patients with ARVC. However, meticulous placement and long-term observation of transvenous lead performance with focus on sensing function are required for the prevention and/or early recognition of disease progression and lead-related morbidity during long-term follow-up of ICD therapy in ARVC.

Adolescent↗

Usefulness of tissue Doppler imaging for estimation of filling pressures in patients with primary or secondary pure mitral regurgitation.

Mitral annular velocities derived from tissue Doppler (S', E', A') and left ventricular (LV) end-diastolic pressures were obtained in 11 patients with significant primary mitral regurgitation (MR), 26 patients with significant MR secondary to ischemic or dilated cardiomyopathy, and in 29 asymptomatic controls. The mitral E/E' ratio was related significantly to LV end-diastolic pressure in patients with secondary, but not in patients with primary MR. In patients with secondary MR, a mitral E/E' ratio >15 predicted an elevated LV end-diastolic pressure with a sensitivity of 80% and a specificity of 100%. Thus, the mitral E/E' ratio is a reliable estimate of filling pressures only in subjects with significant secondary, but not with significant, primary MR.

Adult↗

Tissue Doppler imaging in patients with moderate to severe aortic valve stenosis: clinical usefulness and diagnostic accuracy.

BACKGROUND: Mitral annular velocities derived from tissue Doppler imaging (TDI) provide information about left ventricular (LV) long-axis function and allow for the assessment of LV filling pressures in selected subsets of patients. It was the aim of this study to assess the usefulness of TDI in patients with moderate to severe aortic valve stenosis (AS). METHODS: Twenty-three patients with moderate to severe AS (mean aortic valve area 0.8 +/- 0.4 cm2), in whom coronary artery disease had been ruled out, and 36 asymptomatic age-matched control subjects underwent assessment of ejection fraction, fractional shortening, and mitral inflow (E, A, E/A ratio). TDI velocities (S', E', A') were derived from the septal mitral annulus. In patients with AS, LV pressure before atrial contraction (LV pre-A pressure), LV end-diastolic pressure, and cardiac index were measured during cardiac catheterization. RESULTS: In patients with AS, systolic (S') and early diastolic mitral annular velocities (E') were significantly reduced in comparison to control subjects (systolic, 5.5 +/- 1.2 vs 8.3 +/- 1.3 cm/s; early diastolic, 5.6 +/- 1.6 vs 10.2 +/- 3.0 cm/s, P <.001 for both comparisons), but ejection fraction, fractional shortening, and cardiac index were normal. In patients with AS, LV pre-A pressures (14 +/- 4 mm Hg) and end-diastolic pressures were high (19 +/- 7 mm Hg). In such patients, the mitral E/E' ratio was significantly related to LV pre-A pressure (r = 0.75, P <.001) and to LV end-diastolic pressure (r = 0.78, P <.001). In patients with AS, an E/E' ratio > or =13 identified an LV end-diastolic pressure >15 mm Hg, with a sensitivity of 93% and a specificity of 88%. CONCLUSIONS: In patients with moderate to severe AS, TDI allows for a reliable, noninvasive estimation of filling pressures. In such patients, systolic long-axis function is impaired even in the presence of normal ejection fraction and cardiac index. Thus, TDI integrates information about systolic and diastolic performance and may be a useful addition in the echocardiographic workup and care of patients with AS.

Aged↗

Direct epicardial mapping predicts the recovery of left ventricular dysfunction in chronic ischaemic myocardium.

AIMS: This study investigated the hypothesis that direct epicardial bipolar mapping is able to predict the recovery of left ventricular (LV) dysfunction in ischaemic myocardium. METHODS AND RESULTS: In 34 patients with CAD, a maximum of 102 bipolar epicardial electrograms per patient (n=3468 electrograms) were simultaneously recorded with a ventricular jacket array intraoperatively immediately prior to revascularization. Only LV electrograms with good myocardial contact (n=1813, 52+/-14 per patient, mean+/-SD) were analyzed. In accordance to the position of each electrode, segmental myocardial function was assessed by transthoracic echocardiography before and 7+/-2 months (mean+/-SD; range 3-10 months) after CABG using a wall motion score. Preoperatively dysfunctional segments (n=700) were classified as viable (improvement in wall motion score of at least 20% following CABG, n=424) or non-viable (no improvement, n=276). Bipolar voltage was significantly lower in non-viable when compared to viable myocardium (P<0.001, ANOVA) At a cut-off value of 5.9mV, ROC-curve analysis for bipolar voltage (to discriminate between viable and non-viable myocardium) revealed a sensitivity of 83% at a specificity of 83% (area under the ROC-curve of 0.92+/-0.01, mean+/-SE). CONCLUSIONS: Direct epicardial mapping is able to predict the recovery of chronically ischaemic dysfunctional myocardium and thereby proves the presence of myocardial viability.

Analysis of Variance↗

Chronic electrical stimulation during the absolute refractory period of the myocardium improves severe heart failure.

AIM: In experimental studies, nonexcitatory electrical stimulation delivered at the time of absolute myocardial refractoriness resulted in cardiac contractility modulation (CCM) with improved systolic function. This study reports the initial experience with CCM in patients with chronic heart failure. METHODS AND RESULTS: Twenty-five patients, 23 males, with a mean age of 62+/-9 years and drug-refractory NYHA class III heart failure were assigned to CCM-generator implantation. The underlying heart disease was idiopathic dilated cardiomyopathy in 12 patients and coronary heart disease in 13 patients. Acute efficacy of CCM with 7.73-V stimuli delivered via two right ventricular leads was evaluated by measuring the time derivative of left ventricular pressure (dP/dt). After implantation, the CCM generator was activated for 3 h daily over 8 weeks. In 23/25 patients the CCM system was implanted successfully. Heart failure significantly improved from NYHA class III to class II in 15 patients and to class I in 4 patients (p < 0.000001), left ventricular ejection fraction improved from 22+/-7% to 28+/-8% (p = 0.0002), and the Minnesota Living with Heart Failure Score improved from 43+/-22 to 25+/-18 (p = 0.001). The 6-min walk test increased from 411+/-86 to 465+/-81 m (p= 0.02). Nine patients (39%) had intermittent sensations associated with CCM delivery. There were two (8%) non-device-related deaths during follow-up. CONCLUSIONS: These preliminary data indicate that CCM by delivery of intermittent nonexcitatory electrical stimuli is a promising technique for improving ventricular systolic function and symptoms in patients with drug-refractory NYHA class III heart failure.

Cardiomyopathy, Dilated↗

Aminoterminal pro type B natriuretic peptide as a predictive and prognostic marker in patients with chronic heart failure.

BACKGROUND: B-type natriuretic peptide (BNP) is released from the cardiac ventricles in response to increased wall tension. We studied the relation of NT-proBNP to Heart Failure Survival Score (HFSS) and New York Heart Association (NYHA) class in patients with chronic heart failure (CHF). We also studied the impact for recipient selection for cardiac transplant and assessed it as a predictive and prognostic marker of CHF. METHODS: A total of 550 patients with dilative cardiomyopathy (n = 323), and coronary artery disease (n = 227) were prospectively examined. All patients underwent spiroergometry, echocardiography, right heart catheterization, and electrocardiogram. Routine blood levels and NT-proBNP were measured. The clinical selection for cardiac transplant candidates was adjudicated by 2 independent cardiologists who were blinded to the results of NT-proBNP assays. Clinical outcome and predictive power of NT-proBNP were analyzed. RESULTS: NT-proBNP levels in patients clinically considered for cardiac transplantation were significantly higher (2293 ng/ml vs 493 ng/ml; p < 0.001). The receiver operating characteristic (ROC) analysis regarding transplant candidacy showed an area under the ROC curve (AUC) of 0.84 +/- 0.01 for HFSS, 0.86 +/- 0.001 for NYHA, and 0.96 +/- 0.01 for NT-proBNP. Patients with increasing NT-proBNP levels or remaining elevated levels despite adequate heart insufficiency treatment were maintained with left ventricular assist device implantation (n = 10) or urgent heart transplantation (n = 2). Patients with NT-proBNP levels above 5000 pg/ml had a mortality rate of 28.4% per year. Twenty-eight patients died during the observation period; all these patients were within NYHA Classes 3 and 4 (NT-proBNP 5423 +/- 423 ng/ml). CONCLUSIONS: NT-proBNP discriminates patients at high likelihood of being a candidate for transplantation and provides prognostic informations in patients with CHF. NT-proBNP levels above 5000 pg/ml at admission were associated with death, and these levels markedly discriminated candidates for left ventricular assist devices or urgent transplantation.

Cardiac Catheterization↗

T wave alternans does not assess arrhythmic risk in patients with Brugada syndrome.

BACKGROUND: Brugada syndrome is associated with a risk for sudden death, but the arrhythmic risk in an individual Brugada syndrome patient is difficult to predict. Pathologic changes in the early repolarization phase of the ventricular action potential probably constitute part of the arrhythmogenic substrate in Brugada syndrome. Microvolt T wave alternans (TWA) assesses dynamic beat-to-beat changes in repolarization and has been suggested as a marker for repolarization-related sudden death. We therefore tested whether TWA is an indicator for arrhythmias in Brugada syndrome with a focus on right precordial ECG leads. METHODS: We assessed TWA in nine symptomatic, inducible patients with established Brugada syndrome and in seven healthy controls. TWA was assessed at rest and during exercise using both standard methods and an algorithm that assesses TWA in the early ST segment and the right precordial leads. RESULTS: None of the Brugada patients developed TWA in this study irrespective of analysis at rest or during exercise, neither using standard methods nor when the early ST segment was included in the analysis. When the early ST segment was included in the analysis, nonsustained TWA was found in three out of seven, and sustained TWA in one control. CONCLUSION: T wave alternans is not an appropriate test to detect arrhythmic risk in patients with Brugada syndrome.

Adult↗

The identification of right-to-left shunts using contrast transcranial Doppler ultrasound: performance and interpretation modalities, and absence of a significant side difference of cardiac micro-emboli.

Cardiac and extracardiac right-to-left shunts can be identified by transesophageal echocardiography (TEE) as well as by transcranial Doppler ultrasound (TCD) using contrast agents that do not pass the lungs. Currently, the appropriate performance of a Valsalva manoeuvre (VM) to provoke the shunt, the use of different contrast agents and the classification of the TCD results are still under debate. In this study, we looked also at possible side effects of provoked cardiac micro-emboli in the left and right hemisphere. Seventy-one patients were investigated by both TEE and bilateral TCD of the middle cerebral arteries. The following protocol was applied in a randomized way: (1) Echovist-300 without VM; (2) Echovist-300, VM for 5 seconds starting 5 seconds after the beginning of contrast injection; (3) repetitive short VMs in between 2 and 13 seconds after the beginning of Echovist-300 injection; and (4) repetitive short VMs in between 2 and 13 seconds after the beginning of agitated saline injection. Only if one of the tests (2-4) was negative, this particular negative test was repeated. Use of Echovist-300, but not of saline yielded 100% sensitivity in the detection of TEE-proven shunts. The repetitive VM was slightly superior to the conventional VM. Introduction of a threshold of two or even three microbubbles produced less falsely positive TCD results in comparison to the TEE. There was no difference in microbubbles. TCD using Echovist-300 is a sensitive method to identify TEE-proven cardiac right-to-left shunts. Repetitive VM is an alternative to conventional VM.

Adult↗

Right-to-left-shunts detected by transesophageal echocardiography and transcranial Doppler sonography.

BACKGROUND: Transesophageal echocardiography (TEE) and transcranial Doppler sonography (TCD) can identify right-to-left-shunts that predispose to paradoxical embolism. In a large cohort we compared the results of both techniques. METHODS: 222 patients were investigated by both techniques using the contrast agent Echovist-300 and performing each test once without and once with the Valsalva maneuver (VM). RESULTS: TEE-proven right-to-left-shunts were detected by TCD with a high sensitivity of 94%. In addition, TCD revealed shunts not noted during TEE in about 20% of all patients studied. These shunts are in general smaller than those concordantly identified; however, 9% of the patients without a TEE-proven shunt presented with a shunt that allows a considerable amount of contrast medium to pass. There were 12% more microbubbles detected in the right middle cerebral artery than in the left middle cerebral artery during the TCD test performed with VM, but not during the TCD test performed without VM. CONCLUSIONS: Contrast-enhanced TEE and TCD are complementary methods in the assessment of stroke and stroke-prone patients. The side difference of microbubbles may indicate a selective streaming of cardiac emboli during VM.

Adolescent↗

Multi-detector row CT of left ventricular function with dedicated analysis software versus MR imaging: initial experience.

PURPOSE: To determine left ventricular (LV) volumetric and functional parameters from retrospectively electrocardiographically gated multi-detector row computed tomography (CT) by using semiautomated analysis software and to correlate results with those of magnetic resonance (MR) imaging. MATERIALS AND METHODS: In 30 patients (mean age, 59.2 years +/- 7.1 [SD]) known to have or suspected of having coronary artery disease, four-channel multi-detector row CT was performed with standard technique, and diastolic and systolic image reconstructions were generated. With commercially available analysis software capable of semiautomated contour detection, end diastolic and end systolic LV volumes were determined from short-axis secondary CT reformations. Steady-state free-precession cine MR images were acquired in short-axis orientation within 48 hours and analyzed by using dedicated software. Bland-Altman analysis was performed to calculate limits of agreement and systematic errors between CT and MR imaging. RESULTS: Mean end diastolic (138.8 mL +/- 31.9) and end systolic (53.9 mL +/- 21.2) LV volumes as determined with CT correlated well with MR imaging measurements (142.0 mL +/- 32.5 [r = 0.93] and 54.9 mL +/- 22.8 [r = 0.94], respectively [P <.001]). LV ejection fraction (61.6% +/- 10.6 for CT vs 62.3% +/- 10.1 for MR imaging; r = 0.89) and stroke volume (84.6 mL +/- 20.9 for CT vs 86.9 mL +/- 21.5 for MR imaging; r = 0.88) also showed good correlation (P <.001). Bland-Altman analysis showed acceptable limits of agreement (+/-9.8% for ejection fraction) without systematic errors. CONCLUSION: In selected patients, semiautomated analysis software enables LV volumetric and functional analysis based on multi-detector row CT data sets, the results of which correlate well with MR imaging findings.

Aged↗

Design of new beta1-selective adrenoceptor ligands as potential radioligands for in vivo imaging.

In general, the failing human heart is characterized by a selective reduction in beta(1)-adrenoceptors (beta(1)-ARs) without change in beta(2)-AR density. Medical imaging techniques, either single photon emission computed tomography (SPECT) or positron emission tomography (PET) with appropriate radioligands, offer the possibility of assessing beta-adrenoceptor density non-invasively in humans. To date, neither a SPECT nor a PET radioligand is available for the selective imaging of cardiac beta(1)-ARs. The aim of this study was to develop potential high affinity beta(1)-selective AR radioligands for the non-invasive in vivo imaging of the beta(1)-AR density in the human heart using SPECT or PET. A variety of racemic N-aryl-N'-[2-[3-aryloxy-2-hydroxy-propylamino]-ethyl]-urea derivatives and chain-elongated analogues, related to the established beta(1)-AR antagonist, ICI 89,406 8i, were synthesized. Competition studies using the non-selective AR ligand, [(125)I]iodocyanopindolol ([(125)I]ICYP), and ventricular membrane preparations of wild-type mice revealed nine ligands with higher beta(1)-AR affinities (up to 76-fold) and beta(1)-AR selectivities (up to 139-fold) than 8i. Mostly, these ligands possess a 2-substituted phenoxy group and a 4-substituted phenyl residue in contrast to the lead compound 8i. The non-radioactive counterparts of the desired SPECT- and PET-radiotracers were synthesized as reference compounds [e.g., 8f, 8g, 8h and 8l as the non-radioactive analogues of the radioiodinated SPECT radioligands, 8e and 8h as the non-radioactive compounds of C-11 labelled PET-tracers (C-11 in the methoxy group)]. The established library of high affinity beta(1)-selective AR antagonists was screened for chemical precursors for the radiosynthesis of the mentioned radioligands. Furthermore, the library consists of some comparison compounds that are unsubstituted, allyl- and alkyl-substituted or chain-elongated (e.g., 8a, 8j, 8o and 8r-t). Future steps will include radiolabelling and pharmacokinetic evaluation of the beta(1)-selective target compounds, which could be applied as sympathetic innervation agents for in vivo investigations and diagnostics in patients suffering from cardiac diseases like heart failure and ventricular arrhythmias.

Adrenergic beta-1 Receptor Antagonists↗

Sodium channel gene (SCN5A) mutations in 44 index patients with Brugada syndrome: different incidences in familial and sporadic disease.

The Brugada syndrome (BS) is a distinct form of idiopathic ventricular fibrillation and may cause sudden cardiac death in healthy young individuals. In the surface ECG, BS can be recognized by an atypical right bundle branch block and ST-segment elevation in the right precordial leads. Mutations in the cardiac sodium channel gene SCN5A are only known to cause BS. In a multi-center effort, we have collected clinical data on 44 unrelated index patients and family members and performed a complete genetic analysis of SCN5A. In 37% the disease was familial, whereas in the majority it was sporadic (63%). Five novel SCN5A mutations (2602delC, resulting in: E867X; 2581_2582del TT: F861fs951X; 2673G>A: E1225K; 4435_4437delAAG: K1479del; and 5425C>A: S1812X) were found and were randomly located in SCN5A. Mutation frequencies (SCN5A+) differed significantly between familial (38%) and sporadic disease (0%) (p=0.001). Disease penetrance was complete in the SCN5A+ adult patients, but incomplete in SCN5A+ children (17%). Genetic testing of SCN5A is especially useful in familial disease to identify individuals at cardiac risk. In sporadic cases, however, a genetic basis and the value of mutation screening has to be further determined. These results are in line with a possibly genetic and clinical heterogeneity of BS.

Adolescent↗

Haemoglobin-related mortality in patients undergoing percutaneous coronary interventions.

AIMS: It has recently been proposed that anaemia is an independent risk factor for development of cardiovascular disease in the general population. The impact of anaemia on long-term survival of patients with manifest coronary heart disease (CHD) has not been assessed so far. In this study, we examined the influence of haemoglobin concentrations on the outcome after percutaneous coronary interventions (PCI). METHODS AND RESULTS: In a retrospective cohort study, we analysed in-hospital and long-term mortality in all male patients admitted to our institution for elective PCI from 1998 to 1999. In 689 cases, complete follow-up information could be obtained (98.4%). Depending on their baseline haemoglobin, patients were divided in quintiles. In all subgroups, angiographic success after PCI (90-94%) was comparably high and in-hospital mortality was low (0-0.7%). During follow-up (median 697 days), patients in the lowest haemoglobin quintile (</=12.9g/dl) were significantly more likely to suffer from all-cause death (22.2%) than those of the other quintiles (3.7-12.1%; estimated mortality rates from Kaplan-Meier models, P<0.0001, log rank test). In more detail, we found a U-shaped relationship between mortality and haemoglobin strata in steps of 1g/dl (P<0.0001, log rank test). After adjustment for potential co-variates, patients of the lowest haemoglobin quintile showed in Cox regression analysis a markedly higher risk for death (adjusted hazard rate ratio (HRR) 4.09, 95% confidence interval (CI) 1.52-11.05) compared to the quintile with a haemoglobin concentration of 14.6-15.2g/dl. CONCLUSIONS: These results indicate that anaemia is associated with markedly reduced survival in patients with CHD after elective PCI. Since PCI is a common intervention and anaemia is a frequent condition in the general population, strategies for the management of anaemic PCI patients and treatment of anaemic patients with CHD should be developed.

Analysis of Variance↗

The ajmaline challenge in Brugada syndrome: diagnostic impact, safety, and recommended protocol.

AIMS: The diagnostic ECG pattern in Brugada syndrome (BS) can transiently normalize and may be unmasked by sodium channel blockers such as ajmaline. Proarrhythmic effects of the drug have been well documented in the literature. A detailed protocol for the ajmaline challenge in Brugada syndrome has not yet been described. Therefore, we prospectively studied the risks of a standardized ajmaline test. METHODS AND RESULTS: During a period of 60 months, 158 patients underwent the ajmaline test in our institution. Ajmaline was given intravenously in fractions (10mg every two minutes) up to a target dose of 1mg/kg. In 37 patients (23%) the typical coved-type ECG pattern of BS was unmasked. During the test, symptomatic VT appeared in 2 patients (1.3%). In all other patients, the drug challenge did not induce VT if the target dose, QRS prolongation >30%, presence/appearance of the typical ECG, or the occurrence of premature ventricular ectopy were considered as end points of the test. A positive response to ajmaline was induced in 2 of 94 patients (2%) with a normal baseline ECG, who underwent evaluation solely for syncope of unknown origin. CONCLUSION: The ajmaline challenge using a protocol with fractionated drug administration is a safe method to diagnose BS. Because of the potential induction of VT, it should be performed under continuous medical surveillance with advanced life-support facilities. Due to the prognostic importance all patients with aborted sudden death or unexplained syncope without demonstrable structural heart disease and family members of affected individuals should presently undergo drug testing for unmasking BS.

Adolescent↗