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Aims: The aim of this study was to determine the net clinical benefit (NCB) of rivaroxaban compared with warfarin in patients with atrial fibrillation., Methods: This was a retrospective analysis of 14,236 patients included in ROCKET AF who received at least one dose of study drug. We analyzed NCB using four different methods: (1) composite of death, stroke, systemic embolism, myocardial infarction, and major bleeding; (2) method 1 with fatal or critical organ bleeding substituted for major bleeding; (3) difference between the rate of ischemic stroke or systemic embolism minus 1.5 times the difference between the rate of intracranial hemorrhage; and (4) weighted sum of differences between rates of death, ischemic stroke or systemic embolism, intracranial hemorrhage, and major bleeding., Results: Rivaroxaban was associated with a lower risk of the composite outcome of death, myocardial infarction, stroke, or systemic embolism (rate difference per 10,000 patient-years [RD]=-86.8 [95% CI -143.6 to -30.0]) and fatal or critical organ bleeding (-41.3 [-68 to -14.7]). However, rivaroxaban was associated with a higher risk of major bleeding other than fatal or critical organ bleeding (55.9 [14.7 to 97.2]). Method 1 showed no difference between treatments (-35.5 [-108.4 to 37.3]). Methods 2-4 favored treatment with rivaroxaban (2: -96.8 [-157.0 to -36.8]; 3: -65.2 [-112.3 to -17.8]; 4: -54.8 [-96.0 to -10.2])., Conclusions: Rivaroxaban was associated with favorable NCB compared with warfarin. The NCB was attributable to lower rates of ischemic events and fatal or critical organ bleeding., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Atrial fibrillation and coronary artery disease are highly prevalent diseases in an aging population. They share risk factors and are frequently associated. Beyond their mere association, they impact on each other. The positive feed-back between atrial fibrillation and acute myocardial ischemia involves sympathetic activation and may result in sudden death., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Background: Permanent AV-block is a recognized and feared complication of slow pathway modulation for AVNRT. We aimed to assess incidence of transient and permanent AV-block as well as consequences of transient AV-block in a large contemporary AVNRT ablation cohort., Methods: We searched our single center prospective ablation database for occurrence of transient and permanent AV-block during slow pathway modulation between January 2004 and October 2015. We analyzed patients' and procedural characteristics as well as outcome of patients in whom transient or permanent AV-block occurred., Results: Of 9170 patients who underwent a catheter ablation at our institution between January 2004 and October 2015, 2101 patients (64% women, mean age 50±18years) underwent slow pathway modulation. In three patients, permanent AV-block occurred during RF application. Additional two patients had transient AV-block that recovered (after a few minutes and 25min), but recurred within two days of the procedure. All five patients underwent dual chamber pacemaker implantation (0.2%). Transient AV-block related to RF delivery occurred in 44 patients (2%). Transient mechanical AV-block occurred in additional 17 patients (0.8%). In 12 patients, ablation was continued despite transient AV-block. One of these patients developed permanent AV-block., Conclusion: Permanent AV-block following slow pathway modulation is a rare event, occurring in 0.2% of patients in a large contemporary single center cohort. Transient AV-block is more frequent (2%)., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Chronic kidney disease (CKD) and coronary artery disease (CAD) are strongly associated. CAD is the most frequent cause of cardiovascular death in patients with CKD., Methods: The prospective observational nationwide multicenter Coronary Artery Disease and REnal Failure (CAD-REF) Registry enrolled 3352 patients with angiographically documented CAD classified according to their baseline estimated glomerular filtration rate (eGFR) into 5 groups according to the K/DOQI-guidelines. Patients were followed for two years. The aim of this study was the analysis of outcome and the identification of risk factors for two-year mortality in patients with both CKD and CAD., Results: With decreasing renal function, patients had more often diabetes mellitus, hypertension, peripheral artery disease, and previous cardiovascular events and interventions. The amount of diseased vessels increased with decreasing renal function. For the whole cohort, two-year mortality was 6.5%. Kaplan-Meier-curves showed highest mortality in patients with CKD stages 4 and 5 (22.4%). In multivariate Cox-regression analyses, significant risk factors for two-year all-cause mortality were lower eGFR, current smoking, left ventricular ejection fraction, diabetes mellitus treated with oral medication or insulin, age, and peripheral artery disease. Coronary status missed the level of statistical significance as a risk factor for mortality in multivariable regression analysis. An eGFR reduction of 10ml/min/1.73m 2 increased the risk of mortality by 19% regardless of other risk factors., Conclusions: Two-year morbidity and mortality increased with the degree of renal impairment. To improve survival of patients with CAD and CKD, nephroprotection is urgently needed especially for patients with atherosclerotic burden., Clinical Trial Registration Number: NCT00679419, http://clinicaltrials.gov/., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: The authors assessed the use of dual antiplatelet therapy (DAPT) and outcomes in patients undergoing percutaneous coronary intervention (PCI) during the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation)., Background: The frequency, patterns, and outcomes when adding DAPT to non-vitamin K antagonist oral anticoagulants in the setting of PCI in patients with AF are largely unknown., Methods: The study population included all patients in the treatment group of the ROCKET AF trial divided by the receipt of PCI during follow-up. Clinical characteristics, PCI frequency, and rates of DAPT were reported. Clinical outcomes were adjudicated independently as part of the trial., Results: Among 14,171 patients, 153 (1.1%) underwent PCI during a median 806 days of follow-up. Patients treated with rivaroxaban were significantly less likely to undergo PCI compared with warfarin-treated patients (61 vs. 92; p = 0.01). Study drug was continued during PCI in 81% of patients. Long-term DAPT (≥30 days) was used in 37% and single antiplatelet therapy in 34%. A small number switched from DAPT to monotherapy within 30 days of PCI (n = 19 [12.3%]) and 15% of patients received no antiplatelet therapy after PCI. Rates of stroke/systemic embolism and major bleeding events were high in post-PCI patients (4.5/100 patient-years and 10.2/100 patient-years) in both treatment groups., Conclusions: In patients with AF at moderate to high risk for stroke, PCI occurred in <1% per year. DAPT was used in a variable manner, with the majority of patients remaining on study drug after PCI. Rates of both thrombotic and bleeding events were high after PCI, highlighting the need for studies to determine the optimal antithrombotic therapy., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Patients, their relatives, as well as medical specialists from the fields of paediatric cardiology, cardiology and cardiac surgery were surveyed to investigate the current research needs in the field of congenital heart disease (CHD) focussing specifically on the needs of those affected., Material and Methods: An online survey including four groups of patients with CHD (Fontan circulation, transposition of the great arteries [TGA] after atrial switch [AS] and after arterial switch operation [ASO], tetralogy of Fallot [TOF]) was performed. Each questionnaire comprised twelve topics. Persons affected (patients and relatives) were surveyed by means of CHD group specific questionnaires. Participants were recruited through the German National Register for Congenital Heart Defects., Results: N=596 affected persons (Fontan circulation: n=189; TGA after AS: n=64; TGA after ASO: n=90; TOF: n=253) and 75 physicians (57.3% paediatric cardiologists, 28.0% cardiologists, 10.7% cardiac surgeons, 4.0% other) participated. In general, those affected assume a greater need for research than physicians. Regarding the CHD related topics to be the focus of future research, those affected largely agreed with the participating physicians, although with a different ranking of research topics., Conclusions: Based on the results of our study the challenges immanent in routine care for the CHD patient groups investigated can be identified. Accordingly, these topics should be prioritized in the research of the coming years., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To investigate the relevance of atrial fibrillation or flutter (AF) for outcome of patients who are hospitalized for peripheral artery disease (PAD) and/or critical limb ischemia (CLI)., Methods and Results: We compared baseline data, co-morbidities, procedural data as well as in-hospital and long-term outcome of 41,882 patients who were hospitalized with PAD or CLI between 2009 and 2011 according to whether they did or did not have atrial fibrillation/flutter. Follow-up was available until December 2012. Of these, 5622 patients (13.4%) had AF. AF patients were significantly older (78±9 vs. 70±11years) and had significantly more comorbidities, such as diabetes (40.8 vs. 31.1%), chronic kidney disease (40.1 vs. 19.0%), coronary artery disease (38.0 vs. 23.0%) and chronic heart failure (26.9 vs. 7.2%, each p<0.001). They had more advanced PAD as shown by higher Rutherford classes. In-hospital complications including acute renal failure, myocardial infarction, stroke sepsis and death occurred significantly more often (each p<0.001). Duration of hospital stay was significantly longer and costs were markedly higher in patients with AF (each p<0.001). Using multivariate Cox regression analyses regarding long-term outcomes, AF was an independent predictor for death (HRR 1.46; 95% CI 1.39-1.52, p<0.001), ischemic stroke (HRR 1.63; 95% CI 1.44-1.85) and amputation (HRR 1.14; 95% CI 1.07-1.21)., Conclusion: Presence of AF in patients admitted for PAD and CLI is associated with worse in-hospital and long-term outcome than in patients without AF. This effect was independent of numerous other comorbidities and stage of vascular disease., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Digoxin is a widely used drug for ventricular rate control in patients with atrial fibrillation (AF), despite a scarcity of randomised trial data. We studied the use and outcomes of digoxin in patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)., Methods: For this retrospective analysis, we included and classified patients from ROCKET AF on the basis of digoxin use at baseline and during the study. Patients in ROCKET AF were recruited from 45 countries and had AF and risk factors putting them at moderate-to-high risk of stroke, with or without heart failure. We used Cox proportional hazards regression models adjusted for baseline characteristics and drugs to investigate the association of digoxin with all-cause mortality, vascular death, and sudden death. ROCKET AF was registered with ClinicalTrials.gov, number NCT00403767., Findings: In 14,171 randomly assigned patients, digoxin was used at baseline in 5239 (37%). Patients given digoxin were more likely to be female (42% vs 38%) and have a history of heart failure (73% vs 56%), diabetes (43% vs 38%), and persistent AF (88% vs 77%; p<0·0001 for each comparison). After adjustment, digoxin was associated with increased all-cause mortality (5·41 vs 4·30 events per 100 patients-years; hazard ratio 1·17; 95% CI 1·04-1·32; p=0·0093), vascular death (3·55 vs 2·69 per 100 patient-years; 1·19; 1·03-1·39, p=0·0201), and sudden death (1·68 vs 1·12 events per 100 patient-years; 1·36; 1·08-1·70, p=0·0076)., Interpretation: Digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF. This association was independent of other measured prognostic factors, and although residual confounding could account for these results, these data show the possibility of digoxin having these effects. A randomised trial of digoxin in treatment of AF patients with and without heart failure is needed., Funding: Janssen Research & Development and Bayer HealthCare AG., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality but there are few studies available about atrial fibrillation, the most frequent arrhythmia in CKD, and the applied treatment. Based on the prospective German Competence NETwork on Atrial Fibrillation, data of 3138 patients with atrial fibrillation were analyzed and categorized by their estimated glomerular filtration rate (stages 1-3 and 4 plus 5). With advanced CKD, significantly more patients suffered from a more severe form of atrial fibrillation. Despite significantly higher CHADS2 scores in advanced CKD, oral anticoagulation was not prescribed more frequently while antiarrhythmic drugs and catheter ablations were used significantly less often, in contrast to more pacemaker implantations. However, in multivariate hierarchical logistic regression analyses of in-hospital treatments and complications, only hemorrhages and pacemaker implantations turned out to be independently and significantly associated with higher CKD stages. This nationwide study shows that patients with CKD and atrial fibrillation suffer from a markedly higher comorbidity. Thus, while CKD patients have received cardioversions, ablations, antiarrhythmic, or anticoagulation drugs significantly less often in their history, current treatments were not different if adjusted for multiple comorbidities. This might indicate an improvement in the often reported therapeutic nihilism in CKD.

Background: Antiarrhythmic drugs (AADs) and anticoagulation are mainstays of atrial fibrillation (AF) treatment., Objective: To study the use and outcomes of AAD therapy in anticoagulated patients with AF., Methods: Patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation trial (N = 14,264) were stratified by AAD use at baseline: amiodarone, other AAD, or no AAD. Multivariable adjustment was performed to compare stroke, bleeding, and death across AAD groups as well as across treatment assignment (rivaroxaban or warfarin)., Results: Of 14,264 patients randomized, 1681 (11.8%) were treated with an AAD (1144 [8%] with amiodarone and 537 [3.8%] with other AADs). Amiodarone-treated patients were less often female (38% vs 48%), had more persistent AF (64% vs 40%), and more concomitant heart failure (71% vs 41%) than were patients receiving other AADs. Patients receiving no AAD more closely resembled amiodarone-treated patients. Time in therapeutic range was significantly lower in warfarin-treated patients receiving amiodarone than in those receiving no AAD (50% vs 58%; P < .0001). Compared with no AAD, neither amiodarone (adjusted hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.74-1.31; P = .9) nor other AADs (adjusted HR 0.66; 95% CI 0.37-1.17; P = .15) were associated with increased mortality. Similar results were observed for embolic and bleeding outcomes. Treatment effects of rivaroxaban vs warfarin in patients receiving no AAD were consistent with results from the overall trial (primary end point: adjusted HR 0.82; 95% CI 0.68-0.98; Pinteraction = .06; safety end point: adjusted HR 1.12; 95% CI 0.90-1.24; Pinteraction = .33)., Conclusion: Treatment with AADs was not associated with increased morbidity or mortality in anticoagulated patients with AF. The effect of amiodarone on outcomes in patients receiving rivaroxaban requires further investigation., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Current recommendations for anticoagulation management during cardioversion are largely based on historical data and expert consensus., Methods and Results: To characterize current practice of anticoagulation during and after elective cardioversion for AF and the risk of stroke and bleeding events, all patients enrolled into the Flec-SL trial were analyzed for stroke/transient ischemic attack and major bleeds after cardioversion. Flec-SL (ISRCTN62728743, NCT00215774) enrolled 635 patients (mean age 63.7 ± 10.9, 66% male). 629 (99.1%) patients received periprocedural anticoagulation, 556 (87.6%) were adequately anticoagulated following current recommendations. 202 (31.8%) patients underwent transesophageal echocardiography-guided cardioversion. Electrical cardioversion was used in 508 patients (80.0%), pharmacological cardioversion in 127 (20%). Six patients suffered from stroke (n = 5) or transient ischemic attack (3 TIAs in 1 patient, event rate 0.9%, 95% CI 0.4-2.1), five others from major bleeds (event rate 0.8%, 95% CI 0.3-1.9), consistent with the low reported event rates in prior studies. Three strokes occurred in the first 5 days after cardioversion. Events were independent of type of cardioversion or the use of TEE to exclude thrombi., Conclusion: Strokes are rare in this large, prospectively followed cohort of patients undergoing cardioversion for AF and receiving antithrombotic therapy following local routine. These results support adherence to current recommendations for anticoagulation during cardioversion of AF., (© 2013.)

Objectives: The purpose of this study was to evaluate clinical and electrophysiologic characteristics of AT in patients after surgical ASD repair as well as outcome after ablation., Background: Atrial tachycardias (AT) are a common complication after surgical closure of an atrial septal defect (ASD)., Methods: From a prospective ablation database we analyzed data of patients with a history of ASD repair who presented to our institution for AT ablation. We investigated ECG characteristics and the electrophysiologic mechanism of AT in this collective and analyzed follow-up data., Results: Data of 54 patients (47.3 ± 14.5 years, 35 females) were included. In 30 patients (55.6%) ASD had been closed by direct suture, 24 patients (44.4%) had a patch for ASD repair without significant difference in terms of gender and age at the time of the procedure (p=0.234, p=0.231). In 42 patients (77.8%), electrophysiological studies were performed in AT. All patients had right atrial macro-reentrant AT. The leading mechanism was isthmus-dependent right atrial flutter in 29 patients (69.0%) with clockwise atrial activation in 41%. The mechanism of AT (typical atrial flutter (n=29), atriotomy-dependent flutter (n=7), and double loop flutter (n=5)) did not differ with regard to type of surgery. Only 70.6% of patients with proven isthmus dependent counter-clockwise atrial flutter presented with an ECG morphology typical for this mechanism. However, all clockwise typical atrial flutter patients showed the characteristic positive P-waves in the inferior leads. Of note, 83.3% of clockwise typical flutter ECGs had long isoelectric lines (mean 74.5 ms). Follow-up was complete in 45 of 54 patients. During a mean follow-up of 7.7 ± 3.7 years, 27 patients (60%) remained free of any arrhythmia, two patients had AT recurrence with different mechanisms compared to the first procedure and underwent successful ablation. Five patients (11%) developed atrial fibrillation., Conclusion: Isthmus dependent right atrial flutter is the leading AT mechanism in patients with a history of ASD repair. The mechanism of atrial flutter did not differ in relation to the mode of ASD closure (direct suture versus patch closure). ECG characteristics of the tachycardia may be misleading as they are more often atypical in patients after ASD repair., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Recent evidence suggests that cardiac sarcoidosis (CS) and arrhythmogenic right ventricular cardiomyopathy (ARVC) can manifest very similarly., Objective: To investigate whether there are significant demographic and electrophysiological differences between patients with CS and ARVC., Methods: We prospectively compared patients with proven CS or ARVC who underwent radiofrequency catheter ablation of ventricular tachycardias by using 3-dimensional electroanatomical mapping. Furthermore, we evaluated whether the diagnostic criteria for ARVC would have excluded ARVC in patients with CS., Results: Eighteen patients (13 men; mean age 44.9 years) were included. All 18 patients had mild to moderately reduced right ventricular ejection fraction. Patients with cardiac sarcoidosis (n = 8) had a significantly lower mean left ventricular ejection fraction (35.6±19.3 vs 60.6±9.4; P = .002). Patients with CS had a significantly wider QRS (0.146 vs 0.110s; P = .004). Five of 8 (63%) patients with CS fulfilled the diagnostic ARVC criteria. Ventricular tachycardias (VTs) with a left bundle branch block pattern were documented in all but one patient (with CS). Programmed ventricular stimulation induced an average of 3.7 different monomorphic VTs in patients with CS vs 1.8 in patients with ARVC (P = .01). VT significantly more often originated in the apical region of the right ventricle in CS vs ARVC (P = .001), with no other predilection sites. Ablation success and other electrophysiological parameters were not different., Conclusions: The current diagnostic ARVC guidelines do not reliably exclude patients with CS. Clinical and electrophysiological parameters that were characteristic of CS in our patients include reduced left ventricular ejection fraction, a significantly wider QRS, right-sided apical VT, and more inducible forms of monomorphic VT., (Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Ranolazine exhibits a synergistic effect in combination with class III drugs to suppress atrial fibrillation., Objective: To investigate whether a combination therapy affects repolarization and provokes ventricular tachyarrhythmias (VT) in a sensitive model of proarrhythmia., Methods: Thirty-seven rabbits were assigned to 3 groups and fed with amiodarone (50 mg/kg/d; n = 10) or dronedarone (50 mg/kg/d; n = 10) over a period of 6 weeks. A third group was used as control (n = 17). After obtaining baseline data in Langendorff-perfused control hearts, sotalol (100 μM) was administered in this group. Thereafter, ranolazine (10 μM) was additionally infused on top of amiodarone, dronedarone, or sotalol., Results: Chronic treatment with amiodarone or dronedarone as well as sotalol significantly increased action potential duration at 90% repolarization (APD(90)). Additional treatment with ranolazine further increased APD(90) in amiodarone- and dronedarone-pretreated hearts but not in sotalol-treated hearts. Ranolazine increased postrepolarization refractoriness as compared with amiodarone or dronedarone alone owing to a marked effect on the refractory period. In contrast to amiodarone and dronedarone, acute application of sotalol increased dispersion of repolarization (P < .05). Additional treatment with ranolazine did not further increase spatial or temporal dispersion. After lowering extracellular [K(+)] in bradycardic hearts, no proarrhythmia occurred in amiodarone- or dronedarone-treated hearts whereas 11 of 17 sotalol-treated hearts showed early afterdepolarizations and subsequent polymorphic VT. Additional treatment with ranolazine reduced the number of VT episodes in sotalol-treated hearts and did not cause proarrhythmia in combination with amiodarone or dronedarone., Conclusions: Application of ranolazine on top of class III drugs does not cause proarrhythmia despite a marked effect on ventricular repolarization. The effect of ranolazine on the repolarization reserve is associated with the lack of effect on early afterdepolarizations and dispersion of repolarization., (Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Antiarrhythmic drugs prolong the atrial action potential and refractory period, and thereby prevent recurrent atrial fibrillation after cardioversion. The atrial action potential normalises after 2-4 weeks of sinus rhythm, suggesting that antiarrhythmic drugs might not be needed beyond that period. Therefore, we investigated whether short-term antiarrhythmic drug treatment after cardioversion is non-inferior to long-term treatment., Methods: We enrolled patients in a prospective, randomised, open-label, blinded endpoint assessment trial between May 4, 2007, and March 12, 2010, at 44 centres in Germany. Eligible patients were adults with persistent atrial fibrillation undergoing planned cardioversion. After successful cardioversion, patients were randomly assigned in permuted blocks of six per centre to: no antiarrhythmic drug treatment (control); treatment with flecainide (200-300 mg per day) for 4 weeks (short-term treatment); or flecainide for 6 months (long-term treatment). The primary endpoint was time to persistent atrial fibrillation or death. Patients and clinicians were unmasked to group assignment and treatment. The primary outcome was assessed in a core laboratory, members of which were masked to treatment group. Patients were monitored for 6 months by daily telemetric electrocardiograph (ECG) and centrally adjudicated Holter ECG recordings whenever atrial fibrillation was noted in two consecutive ECGs. Analyses were per protocol. This trial is registered, number ISRCTN62728742., Findings: After assay sensitivity was established with 4-week follow-up data from 242 patients showing that flecainide was superior to no treatment (Kaplan-Meier survival 70·2%vs 52·5%; p=0·0160), the trial continued to compare short-term versus long-term treatment. The primary outcome occurred in 120 (46%) of 261 patients receiving short-term treatment and in 103 (39%) of 263 patients receiving long-term treatment (event-free survival 48·4% [95% CI 41·9-55·0] vs 56·4% [49·1-63·6]; Kaplan-Meier estimate of difference 7·9% [-1·9 to 17·7]; p=0·2081 for non-inferiority; margin prespecified at 12%). In a post-hoc landmark analysis of patients who had not reached the primary endpoint in the first month, long-term treatment was superior to short-term treatment (Kaplan-Meier estimate of difference 14·3% [5·1-23·6]; hazard ratio 0·31 [0·18-0·56]; p=0·0001)., Interpretation: Short-term antiarrhythmic drug treatment after cardioversion is less effective than is long-term treatment, but can prevent most recurrences of atrial fibrillation., Funding: The German Federal Ministry of Education and Research, Deutsche Forschungsgemeinschaft, 3M Medica, and MEDA Pharmaceuticals., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Electrophysiologic characteristics, mapping strategies, and acute success rates of radiofrequency catheter ablation of atriofascicular accessory pathways are well described. However, data on long-term prognosis and predictors for freedom from arrhythmias are lacking., Objective: To report our 20-year single-center experience on ablation of atriofascicular fibers., Method: Between 1992 and 2010, 34 patients with atriofascicular accessory pathways underwent catheter ablation at our institution because of symptomatic antidromic atrioventricular reentrant tachycardias. Radiofrequency procedures were retrospectively analyzed, and patients were followed for recurrences of tachyarrhythmias. Electrocardiograms (before and after ablation and at follow-up) were analyzed for each patient., Results: Successful catheter ablation of the atriofascicular fiber was achieved in 23 (68%) patients. Mechanical block during mapping occurred in 3 (9%) patients, and in 2 of them ablation was performed at the site of mechanical block. Mere modification of conduction properties of the pathway without complete block was achieved in 5 patients (15%). Fast pathway ablation was performed in 2 (6%) of the patients ablated in the early 1990s. During follow-up of 9.3 ± 5.5 years, 24 patients (71%) remained free of tachyarrhythmias, 7 reported significant improvement, and 3 (9%) had no change in symptoms after ablation. Long-term success was identical between patients from the first (1992-1999) and second (2000-2010) decade (12 of 17 [71%] vs 12 of 17 [71%]). It was 87% in those with complete block of the atriofascicular fiber while all patients with mechanical block during mapping reported recurrences. Fast pathway ablation was complicated by complete atrioventricular block in 1 patient, who required pacemaker implantation 18 years after ablation owing to loss of conduction properties of the atriofascicular fiber over the years. On analyzing patients with preexcitation before ablation (n = 16; 47%), we found that the PR interval after ablation was significantly longer only in those without recurrence (162 ± 21 ms vs 134 ± 21 ms; P = .042). None of the other analyzed electrocardiographic parameters, including PR, QRS duration, and preexcitation, had prognostic impact., Conclusion: Acute success of complete ablation of atriofascicular pathways is associated with excellent long-term success (87%). Mere modification of conduction properties of atriofascicular fibers or ablation at the sites of mechanical block are less promising end points of ablation with high recurrence rates. Technical innovations during decades may not further improve long-term outcome in these patients., (Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Molecular remodeling in heart failure includes slowing of repolarization, leading to proarrhythmia., Objective: To evaluate the effects of Na(+)/Ca(2+) exchanger (NCX) inhibition on repolarization as a novel antiarrhythmic concept in chronic heart failure (CHF)., Methods and Results: CHF was induced by rapid ventricular pacing in rabbits. Left ventricular function was assessed by echocardiography. Monophasic action potentials (MAPs) showed a prolongation of repolarization in CHF after atrioventricular block and stimulation at different cycle lengths. Sotalol (100 μM, n = 13) or veratridine (0.5 μM; n = 15) resulted in a further significant increase in the MAP duration. CHF was associated with an increased dispersion of repolarization, as compared with sotalol-treated (+22 ± 7 ms; P < .05) and veratridine-treated (+20 ± 6 ms; P < .05) sham hearts. In the presence of a low potassium concentration, sotalol and veratridine reproducibly induced early afterdepolarizations (EADs) and polymorphic ventricular tachyarrhythmias (VTs). SEA0400 (1 μM), a pharmacological inhibitor of NCX, significantly shortened the MAP duration (P < .01) and reduced dispersion (P < .05). It suppressed EAD in 6 of 13 sotalol-treated failing hearts and in 9 of 10 veratridine-treated failing hearts, leading to a reduction in VT (60% in sotalol-treated failing hearts and 83% in veratridine-treated failing hearts). Simulations using a mathematical model showed a reduction in the action potential duration and the number of EADs by the NCX block in all subgroups., Conclusions: In an experimental model of CHF, the acute inhibition of NCX (1) reduces the MAP duration, (2) decreases dispersion of repolarization, and (3) suppresses EAD and VT. Our observations indicate for the first time that pharmacological NCX inhibition increases repolarization reserve and protects against VTs in heart failure., (Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of the present study was to assess the feasibility and safety of target-directed sampling of right ventricular (RV) endomyocardial biopsies (EMB) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC)., Background: EMB is an integral part of the diagnostic evaluation of ARVC. Due to safety concerns, EMB are often obtained from the RV septum, which is usually spared from characteristic alterations. At our institution, EMB in ARVC patients were sampled target-directed from predilection areas and areas with abnormal contraction., Methods: Under fluoroscopic guidance, 3,777 EMB samples from 6 different RV sites were obtained in 482 patients who were evaluated for unclear cardiomyopathy (n = 280; 58%), assumed myocarditis (n = 59; 12%), or unexplained ventricular tachyarrhythmias (n = 143; 30%). Complication rates were compared with those from exclusively septal EMB procedures (n = 2,321) in 271 patients after heart transplantation (HTx)., Results: Overall, no procedure-related deaths or sustained ventricular tachyarrhythmias occurred. A pericardial effusion was reported in 6 of 161 patients with the final diagnosis of ARVC (3.7%) needing no further intervention in all but 1 patient (0.6%) who required pericardiocentesis. Among the non-ARVC patients (n = 321), the incidence of a minor pericardial effusion (3.9%) and cardiac tamponade (2.2%) was comparable to that in ARVC (p = NS) but was higher when compared with HTx (p < 0.001). A transient complete atrioventricular block occurred in 1 of 321 non-ARVC (0.3%) and 2 of 271 HTx patients (0.1%)., Conclusions: Multisite target-directed EMB sampling in ARVC is a safe procedure when performed by experienced interventionalists. The procedure-related complication rates were low and comparable to those in other cardiomyopathies., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Torsades de pointes (TdP) are induced by early afterdepolarizations (EADs) in the presence of an increased dispersion of repolarization. Free polyunsaturated fatty acids (PUFAs) have been suggested to influence cardiac repolarization., Objective: The purpose of this experimental study was to investigate the electrophysiologic effects of PUFAs in a model of LQT2 and LQT3., Methods: We investigated the acute antiarrhythmic potential of α-linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) in a whole-heart model of long QT2 (LQT2) and long QT3 (LQT3) syndrome., Results: In 123 Langendorff-perfused rabbit hearts, the I(Kr)-blocking drug erythromycin (E; 300 μM) or veratridine (V; 0.5 μM), an inhibitor of sodium channel inactivation, significantly increased monophasic ventricular action potentials (MAPs), thereby mimicking LQT2 and LQT3 syndrome. In atrioventricular-blocked hearts, 8 epicardial and endocardial MAPs demonstrated a significant increase in spatial and temporal dispersion. After lowering potassium concentration, E led to EADs and TdP in 44 and 41 of 53 hearts, respectively. Pretreatment with V led to EAD (TdP) in 39 (32) of 43 hearts. Additional treatment with ALA, DHA, or EPA (10 to 20 μM) in the LQT2 model, randomly assigned to 3 groups, suppressed EAD in 72% of ALA-treated hearts and in all hearts that were treated with EPA or DHA. This led to a reduction of TdP of 67% (ALA) and to complete abolishment of TdP in all hearts that were treated with EPA or DHA. A comparable finding was seen in V-pretreated hearts. In addition, DHA and EPA significantly shortened MAP duration and reduced spatial and temporal dispersion of repolarization (P <.01)., Conclusion: The present study showed for the first time that PUFAs are effective in preventing TdP in an experimental model of LQT2 and LQT3 syndrome due to a reversion of AP prolongation, a reduction of spatial and temporal dispersion of repolarization and a suppression of EAD. The PUFA effect is stronger in LQT2 than in LQT3 syndrome, and the antitorsadogenic effect is more remarkable with DHA and EPA as compared with ALA., (Copyright © 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background/objectives: The number of adult congenital heart disease (ACHD) patients will be larger in the medium to long term than that of children and adolescents with congenital heart disease. The present structures for the medical care of ACHD patients are not sufficient and need to be improved. Therefore the task force's assignment and objective was to develop recommendations for the structure of the interdisciplinary medical care of adults with congenital heart disease (GUCH)., Methods: The members of the interdisciplinary task force were selected on the basis of their special clinical, scientific and organizational expertise. Initially, a sub-group of the interdisciplinary task force compiled a draft version of these recommendations, with reference to international recommendations. It was circulated and then agreed with all task force members in two joint meetings. The recommendations were then submitted to the relevant committees of all participating societies and groups and approved following detailed discussion., Results: With the publication of this document the interdisciplinary task force considers its first task as completed., Conclusions: The compiled recommendations for the structure of the interdisciplinary medical care of adults with congenital heart disease (GUCH) should ensure that the structural and medical pre-conditions for comprehensive GUCH medical care are created., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: The number of adult congenital heart disease (ACHD) patients will be larger in the medium to long term than that of children and adolescents with congenital heart disease. The present structures for the medical care of ACHD patients are not sufficient and need to be improved. Therefore the Task Force aimed at developing recommendations for adult and paediatric cardiologists to acquire the additional qualification "Adults with Congenital Heart Disease" (ACDH)., Methods: The members of the interdisciplinary Task Force were selected on the basis of their special clinical, scientific and organisational expertise. The leading author submitted a draft version, which was revised by a sub-group of the interdisciplinary Task Force. It was subsequently agreed upon and re-circulated by all the members of the Task Force. The recommendations were then presented to the relevant committees of all participating associations and groups and approved following detailed discussion., Results: A training programme for acquiring an additional qualification in the treatment of adults with congenital heart disease was created successfully., Conclusions: The medical care of adults with congenital heart disease is a sub-speciality in the border area between adult cardiology and paediatric cardiology. ACHD cardiologists are to be specially trained experts with appropriate knowledge and special skills and experience in the diagnosis and therapy of congenital heart disease in adults. ACHD cardiologists should be able to recognise and treat problems that occur in adulthood in connection with congenital heart disease., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Patients with long QT syndrome (LQTS) are at increased risk not only for ventricular arrhythmias but also for atrial pathology including atrial fibrillation (AF). Some patients with "lone" AF carry Na(+)-channel mutations., Objective: The purpose of this study was to determine the mechanisms underlying atrial pathology in LQTS., Methods: In mice with a heterozygous knock-in long QT syndrome type 3 (LQT3) mutant of the cardiac Na(+) channel (ΔKPQ-SCN5A) and wild-type (WT) littermates, atrial size, function, and electrophysiologic parameters were measured in intact Langendorff-perfused hearts, and histologic analysis was performed., Results: Atrial action potential duration, effective refractory period, cycle length, and PQ interval were prolonged in ΔKPQ-SCN5A hearts (all P < .05). Flecainide (1 μM) reversed atrial action potential duration prolongation and induced postrepolarization refractoriness (P < .05). Arrhythmias were infrequent during regular rapid atrial rate in both WT and ΔKPQ-SCN5A but were inducible in 15 (38%) of 40 ΔKPQ-SCN5A and 8 (29%) of 28 WT mice upon extrastimulation. Pacing protocols generating rapid alterations in rate provoked atrial extrasystoles and arrhythmias in 6 (66%) of 9 ΔKPQ-SCN5A but in 0 (0%) of 6 WT mice (P < .05). Atrial diameter was increased by nearly 10% in ΔKPQ-SCN5A mice > 5 months old without increase in fibrotic tissue., Conclusion: Murine hearts bearing an LQT3 mutation show abnormalities in atrial electrophysiology and subtle changes in atrial dimension, including an atrial arrhythmogenic phenotype on provocation. These results support clinical data suggesting that LQTS mutations can cause atrial pathology and arrhythmogenesis and indicate that murine sodium channel LQTS models may be useful for exploring underlying mechanisms., (Copyright © 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Vascular remodeling is influenced by trauma and proatherogenic factors such as cholesterol. It has been shown that cholesterol exerts a direct effect on vessel wall structure. In this study we evaluated the effects of vascular trauma and cholesterol treatment on vascular remodeling and plaque integrity in carotid ligated ApoE-deficient mice. The right carotid artery was ligated in mice fed regular chow or cholesterol and fat containing diet. After 4 weeks left (non-ligated) and right (ligated) carotids were prepared. For studying vascular remodeling the vascular areas were evaluated morphometrically by calculating the areas from circumference measurements on Verhoff-van Gieson stains. The cellular and structural features of the plaque were analyzed by histological staining and immunohistochemistry. Under regular chow total vessel area decreased by 35% (p<0.001); cholesterol-rich diet led to an increase by 20% (p<0.05). In both feeding groups ligated carotids presented neointima development. The medial area increased only in mice fed regular chow. The luminal area was reduced by 80% (regular chow: p<0.001) and by 90% (cholesterol-rich diet: p<0.01). Regular chow led to structured plaques showing the typical features of stable plaques. Under cholesterol diet well defined plaque structures were missing. These lesions were characterized by numerous macrophages, few mostly PCNA positive smooth muscle cell (SMC) and less collagen particularly in the shoulder region. Our data indicate that in ApoE-deficient mice both direction of the remodeling response and lesion integrity are due to the diet applied: regular chow led to constrictive remodeling, whereas cholesterol and fat containing diet was associated with an adaptive response. Our data further indicate that the direction of response is not only related to the macrophage content but also to a proliferative intimal SMC-phenotype. Our data implicate that high serum cholesterol levels are not only inducers of plaque instability but also of the so far "positively recorded" compensatory remodeling.

Background: Among the numerous studies concerning contrast media-induced nephropathy (CIN), there was no prospective trial that provided data on the long-term outcomes., Objectives: To prospectively assess predictors of CIN and long-term outcomes of affected patients., Methods: Four hundred twelve consecutive patients with serum creatinine levels of 115 micromol/L to 309 micromol/L (1.3 mg/dL to 3.5 mg/dL) undergoing elective coronary angiography were included. Patients were randomly assigned to periprocedural hydration alone, hydration plus one-time hemodialysis or hydration plus N-acetylcysteine., Results: Multivariate logistic regression identified the following as predictors of CIN within 72 h (equivalent to an increase in creatinine 44.2 micromol/L [0.5 mg/dL] or more) : prophylactic postprocedural hemodialysis (OR 2.86, 95% CI 1.07 to 7.69), use of angiotensin-converting enzyme inhibitors (OR 6.16, 95% CI 2.01 to 18.93), baseline glomerular filtration rate (OR 0.94, 95% CI 0.90 to 0.98) and the amount of contrast media given (OR 1.01, 95% CI 1.00 to 1.01). With regard to long-term outcome (mean follow-up 649 days), multivariate Cox regression models found elevated creatinine levels at 30 days (hazard rate ratio [HRR] 5.48, 95% CI 2.85 to 10.53), but not CIN within 72 h (HRR 1.12, 95% CI 0.63 to 2.02), to be associated with increased mortality. In addition, independent predictors for death during follow-up included left ventricular ejection fraction lower than 35% (HRR 4.01, 95% CI 2.22 to 7.26), serum phosphate (HRR 1.64, 95% CI 1.10 to 2.43) and hemoglobin (HRR 0.80, 95% CI 0.67 to 0.96)., Conclusion: From the present prospective trial, performance of postprocedural hemodialysis, use of angiotensin-converting enzyme inhibitors, reduced baseline glomerular filtration rate and amount of contrast media were independent predictors of CIN within 72 h after catheterization. Assessing renal function after 30 days, rather than within 72 h, seemed to be more predictive for patients' long-term survival.

Background: Long QT syndrome (LQTS) is associated with sudden cardiac death resulting from torsades de pointes (TdP), which are triggered by early afterdepolarizations (EADs). The cardiac Na(+)/Ca(2+) exchanger (NCX) has been suggested to work as a trigger for EADs., Objective: The purpose of this study was to test the hypothesis that inhibition of NCX with a newly developed selective NCX inhibitor (SEA0400) reduces TdP., Methods and Results: In 34 Langendorff-perfused rabbit hearts, the I(Kr)-blocker sotalol (100 microM; n = 18) as well as veratridine (0.5 microM; n = 16), an inhibitor of sodium channel inactivation, led to a significant increase in monophasic action potential (MAP) duration thereby mimicking LQTS2 and LQTS3. In bradycardic hearts, recordings of eight MAPs demonstrated an increased dispersion of repolarization (sotalol: 67%; veratridine: 89%; P <.05). After lowering of potassium concentration, sotalol (56%) and veratridine (63%) induced TdP. Perfusion with SEA0400 (1 microM) suppressed EADs in 15 of 16 sotalol hearts and in seven of 13 veratridine hearts. SEA0400 significantly shortened MAP duration and reduced dispersion of repolarization in both groups (P <.05). This reduced TdP incidence in the sotalol group (100%) and in the veratridine group (77%). To investigate the effects of NCX inhibition on the cellular level, we used a computer model of the rabbit ventricular myocyte. I(Na) and I(Kr) were modified to mimic the effects of veratridine and sotalol, respectively. Consistent with our in vitro experiments, reduction of NCX activity accelerated repolarization of the cellular action potential and prevented EADs., Conclusion: In an intact rabbit heart model of LQT2 and LQT3 as well as in a computer model of the rabbit cardiac myocyte, inhibition of NCX is effective in preventing TdP due to a suppression of EADs, a reversion of action potential prolongation, and a reduction of dispersion of repolarization. Our observations suggest a therapeutic benefit of selective NCX inhibition in LQTS.

Background: In patients with chronic heart failure (CHF), chronic kidney disease (CKD) is associated with increased morbidity and mortality, but contributing mechanisms are not well defined. This study tested the impact of CKD on intracardiac conduction, diastolic function and prognosis in patients with underlying CHF., Methods: We prospectively enrolled 269 patients with stable CHF, of whom 135 had CKD (estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m(2)). Echo measurements comprised left ventricular dimensions/volumes, ejection fraction, mitral E/A-ratio, deceleration time and tissue Doppler mitral annular velocities (S', E', A'). PQ and QRS intervals were derived from the 12-lead ECG. A cardiac event (cardiac death or urgent cardiac transplantation) was defined as combined study end point., Results: Patients with CKD had longer PQ and QRS intervals, and were in a poorer NYHA functional class as compared to patients without CKD. In patients with CKD, the mitral annular E' velocity was lower, the mitral E/E'-ratio was higher and a restrictive mitral filling pattern was more frequent. By linear regression analysis, PQ and QRS intervals and the mitral E/E'-ratio were inversely related to the eGFR. During a follow-up of 507+/-375 days, 39 patients suffered a cardiac event. In CKD patients, outcome was markedly poorer as compared to those without CKD (event-free survival rate 51% vs. 87% in those without KD, p=0.001), Conclusions: In patients with CHF, CKD is associated with impaired intracardiac conduction and progressive diastolic dysfunction. Both mechanisms may contribute to increased morbidity and mortality of such patients.

Atrial fibrillation (AF) is a chronic, often progressive disease. Despite the ongoing concerted effort to improve AF therapy, often there is no remedy for curing AF and preventing the deleterious effects of the arrhythmia on health. Antiarrhythmic drug therapy is likely to remain the mainstay of therapy for many patients in the foreseeable future. Available antiarrhythmic drugs are moderately effective, which is important for patients who respond, especially given the chronic and often progressive nature of the disease. This article describes emerging concepts under clinical evaluation that attempt to improve the safety of available antiarrhythmic drugs in the treatment of recurrent AF. Two concepts are reviewed: (1) combination of an antiarrhythmic drug with a calcium channel blocker to reduce proarrhythmic side effects, and (2) "intelligent" reduction of the duration of antiarrhythmic drug therapy targeted to periods of symptomatic or likely AF recurrence.

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.

Background: In patients with chronic heart failure (CHF), N-terminal pro-brain natriuretic peptide (NT-proBNP) provides relevant prognostic information, but its usefulness in the presence of kidney disease has been questioned., Methods: We prospectively enrolled 142 patients with stable CHF and a wide spectrum of renal function (estimated glomerular filtration rates [eGFRs] ranging from 17.1 to 100.3 ml/min/1.73 m2). Chronic kidney disease, defined as eGFR < 60 ml/min/1.73 m2, was present in 63 patients (44%). NT-proBNP measurements were carried out on a bench-top analyzer (Elecsys 2010). Cardiac death or urgent cardiac transplantation were considered as a combined study end-point., Results: During a follow-up of 383 +/- 237 days, 19 patients underwent a cardiac event (cardiac death, n = 17; urgent cardiac transplantation, n = 2). By multivariate Cox analysis, including clinical and laboratory variables, NT-proBNP and serum hemoglobin were independent prognostic predictors. In patients with NT-proBNP > 1,129 pg/ml, outcome was significantly worse compared to patients with NT-proBNP < 1,129 pg/ml (event-free survival rate 67% vs 94% in those with NT-proBNP < 1,129 pg/ml, p = 0.001). By linear regression analysis, NT-proBNP levels were related to New York Heart Association (NYHA) functional class (R = 0.41, p < 0.001), and inversely related to eGFR (R = -0.29, p = 0.001) and to left ventricular ejection fraction (R = -0.43, p < 0.001)., Conclusions: In CHF patients with and without kidney disease, NT-proBNP provides independent prognostic information. In such patients, NT-proBNP levels are not only reflective of a reduced clearance (i.e., a lower eGFR) but also of the severity of the underlying structural heart disease.

Background: Because of the scarcity of donor hearts, surgical alternatives to heart transplantation, such as partial left ventriculectomy (PLV), were introduced for treatment of advanced heart failure. Here, we report our experience with this procedure performed in combination with mitral valve repair., Methods: Twelve patients with dilated cardiomyopathy (DCM), New York Heart Association (NYHA) class exceeding III on maximal medical therapy, cardiac index of 2.5 liter/min/m2 or less, VO2max of 14 ml/kg/min or less, left ventricular end-diastolic diameter (LVEDD) of 7.0 cm or more, and grade II or greater mitral incompetence, were selected for PLV and mitral valve reconstruction (MVR). Echocardiography, hemodynamics, spiroergometry, and clinical assessment were performed before and 1 year after the operation., Results: One-year survival was 83.3%. All 10 surviving patients were free from failure of the procedure 1 year post-operatively. From pre-operatively to 1 year post-operatively, NYHA functional class improved from 3.3 +/- 0.3 to 1.9 +/- 0.2 (p < 0.001), cardiac index increased from 2.0 +/- 0.2 liter/min/m2 to 2.9 +/- 0.2 liter/min/m2 (p < 0.001), stroke volume index from 25.9 +/- 4.8 ml/m2 to 40.3 +/- 7.3 ml/m2 (p = 0.008), and VO2max from 10.9 +/- 2.4 ml/kg/min to 16.0 +/- 3.6 ml/kg/min (p = 0.016), whereas LVEDD decreased from 8.4 +/- 0.6 cm to 6.6 +/- 0.3 cm (p < 0.001), left ventricular end-systolic diameter from 6.8 +/- 0.8 cm to 5.3 +/- 0.5 cm (p < 0.001), and mitral incompetence from 2.4 +/- 0.6 to 0.9 +/- 0.6 (p < 0.001). Pulmonary pressures and fractional shortening did not change significantly (p > 0.05). Four patients received an implantable cardioverter/defibrillator as a result of their pathologic electrophysiologic examination., Conclusions: In carefully selected patients, PLV combined with MVR achieves short-term results comparable to that after heart transplantation. However, long-term results and multicenter evaluation will be needed to define its place in the treatment of advanced heart failure.

Background: The prognostic value of tissue Doppler imaging (TDI) in patients with chronic congestive heart failure (CHF) has not been compared against conventional measures of systolic, diastolic and overall left ventricular LV performance. The aim of this study was to assess the prognostic value of TDI-derived parameters in patients with CHF., Methods: One hundred thirty-two subjects with chronic CHF [due to ischemic (n=82) or dilated (n=50) cardiomyopathy, 101 males, mean age 57+/-11 years] underwent conventional two-dimensional/Doppler echocardiography and assessment of the Tei-index (isovolumic contraction time and isovolumic relaxation time divided by ejection time). Systolic, early and late diastolic mitral annular velocities (S', E' and A') were derived from pulsed TDI. A cardiac event (cardiac death, urgent cardiac transplantation or hospitalization due to decompensated CHF) was defined as the combined study endpoint., Results: The patients were followed for a mean of 224+/-123 days. Thirty-one patients suffered an event (cardiac death, n=5; urgent cardiac transplantation, n=2; hospitalization due to CHF, n=24). In patients with event, ejection fraction was lower (25+/-10 vs. 32+/-9%), mitral deceleration time was shorter (138+/-58 vs. 193+/-72 ms), and the peak mitral E/E'-ratio (16.1+/-6.6 vs. 10.6+/-5.0) was significantly elevated as compared to patients free of events (p<0.001 for all comparisons). In those patients, the Tei-index was elevated (1.09+/-0.39 vs. 0.86+/-0.26, p<0.01), and a restrictive mitral filling pattern was more frequent (51.6 vs. 17.5%, p<0.001). Stepwise multivariate analysis identified the mitral E/E'-ratio (p<0.001) and the Tei-index (p=0.019) as the only independent predictors of a combined event. E/E'-ratio was the best predictor of hospitalization due to CHF also. In patients with mitral E/E'-ratio>12.5 or Tei-index>0.90, outcome was poor., Conclusions: In subjects with chronic CHF, the mitral E/E'-ratio is a stronger predictor of future cardiac events than conventional parameters of systolic, diastolic or overall LV performance. The E/E'-ratio may be a useful addition in the routine follow-up of such patients.

Objectives: The purpose of this study was to evaluate retrospectively a single-center experience with the use of ICDs in patients with long QT syndrome (LQTS) concerning outcome, complications, and optimal programming., Background: Use of implantable cardioverter-defibrillator (ICD) in patients with congenital LQTS is controversial but is generally accepted in high-risk patients., Methods: We enrolled 27 symptomatic patients with LQTS undergoing ICD therapy (QTc 540 +/- 64 ms(1/2); 85% female, 63% cardiac arrest; 33% syncope despite beta-blockers; 4% with severe phenotype) and 81 genotyped patients with LQTS undergoing conventional drug therapy (28 LQT1, 39 LQT2, 1 LQT3, 13 LQT5). During a mean follow-up of 65 +/- 34 months, one death occurred in the ICD group that was not LQTS related. A total of 178 appropriate shocks were observed in 10/27 patients (37%), mostly in survivors of cardiac arrest (in 58% of cardiac arrest patients vs. in 20% of non-cardiac arrest patients)., Results: In a logistic regression analysis, only QTc interval (121/178 shocks (68%) for QTc > 500 ms(1/2)) and "survived cardiac arrest" were prognostic for ICD shocks. In 30% of patients in the ICD group, multiple shocks occurred and could be reduced after increase of antibradycardia pacing rate, adding beta-blocker therapy, or starting the rate-smoothing algorithm (average 7.1 shocks before to 0.75 shocks after additional intervention annually)., Conclusion: ICD therapy is a safe and useful tool in high-risk patients with LQTS. QTc interval and cardiac arrest survivors were prognostic factors for appropriate ICD shocks. The results of this large single-center experience suggest that beta-blockers should always be added to ICD therapy. In addition, some patients might benefit from additional antibradycardia pacing, prolonged detection time, and a rate-smoothing algorithm to prevent recurrent episodes.

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.

Increased expression of connexin43 gap junctions in smooth muscle cells (SMC) is implicated in the response to primary arterial injury and in the early stages of human coronary atherosclerosis, but the relevance of these findings to restenosis is unknown. Here we investigated the expression of connexin43 gap junctions in restenotic aortas of cholesterol-fed double injured rabbits. Immunofluorescence confocal microscopy was used to evaluate temporal and spatial expression patterns and to characterize the major expressing cell type. Parallel studies were conducted by electron microscopy, in situ hybridization and Northern blot analysis. Connexin43 gap junctions- and connexin43 mRNA-expressing cells were abundant in the media of non-injured control aorta. Following primary injury and 6 weeks cholesterol diet, connexin43 gap junctions were found distributed throughout the primary intimal layer; although medial expression was reduced, the overall mRNA expression level remained similar to that of non-injured controls. After secondary injury, no major change in distribution pattern of connexin43 gap junctions occurred up to day 10, when marked neointimal labeling was observed. This overall pattern persisted, though with some diminution, at later stages. On the mRNA level total connexin43 mRNA expression declined to about 40% of control values within 4 days after secondary injury (P < 0.05), but subsequently increased four-fold, attaining levels double that of non-injured controls in the 10-day group (P < 0.005 versus control and 4 days). At later stages mRNA expression levels returned to values similar to those of non-injured controls. At all stages, connexin43 gap junctions were localized to the SMC, not to macrophages. We conclude that the enhanced gap junction formation may contribute to the coordination of the response of SMC after secondary injury, particularly in the early phase of restenosis.

Background: Vasoactive peptides are accepted indicators of the degree of heart failure and its progression or improvement following medical therapy. Normalization of cardiac hemodynamics by cardiac transplantation (HTx) may lead to normalization of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) plasma levels shortly after the procedure., Methods: Long-term follow-up was done for 14 consecutive patients, 12 men and 2 women, 49 years of age (range 24 to 64 years). ANP and BNP were measured by radioimmunoassay (RIA) in central venous plasma samples (before breakfast, at steady state) at the following intervals after HTx: 7 to 30 (1), 31 to 60 (2), 61 to 90 (3), 120 to 180 (4) and 210 to 365 (5) days., Results: During follow-up, ANP decreased significantly within 2 months after HTx and continued of this level, whereas BNP decreased continuously without reaching normal values. The mean ratio of ANP:BNP increased from 3.23 to 8.01 during follow-up. Whereas right atrial pressure (RAP), right ventricular pressure (RVP), right ventricular end-diastolic pressure (RVEDP) and pulmonary capillary wedge pressure (PCWP) did not change during follow-up, cardiac output (CO) improved slightly, but significantly from 5.21 liters/min to 5.9 liters/min (p = 0.035)., Conclusions: Normalization of left ventricular function after orthotopic HTx does not induce an early diminution of ANP and BNP plasma levels to normal concentrations. Although elevated ANP concentrations showed only minimal changes within 1 year, BNP decreased significantly as early as 2 months after HTx, without reaching normal values during the year of follow-up. Also, the ratio of ANP and BNP increased significantly from 3.23 to 8.01. These results demonstrate the contribution of other factors beyond cardiac function that determine the levels of these peptides.

Background: Sirolimus-eluting stents have been developed to prevent restenosis in the treatment of coronary artery disease. We investigated the risk of restenosis with use of sirolimus-eluting stents compared with bare-metal stents to assess possible differences., Methods: We enrolled 352 patients in whom one coronary artery required treatment, with diameter 2.5-3.0 mm and lesion length 15-32 mm. We randomly assigned patients sirolimus-eluting stents (n=175) or bare-metal stents (control, n=177). At 8 months we assessed differences in minimum lumen diameter and binary restenosis within the lesion (restenosis of > or =50% diameter, including 5 mm vessel segments proximal and distal to stented segment). Patients were also followed up for 9 months for major adverse cardiac events. Analysis was by intention to treat., Findings: Stent implantation was successful in 100% of sirolimus-stent patients and 99.4% of controls. The mean diameter of treated coronary arteries was 2.55 mm (SD 0.37) and mean lesion length was 15.0 mm (6.0). Multiple stents were implanted in 170 (48%) patients. At 8 months, minimum lumen diameter was significantly higher with sirolimus-eluting stents than with control stents (2.22 vs 1.33 mm, p<0.0001). The rate of binary restenosis was significantly reduced with sirolimus-eluting stents compared with control stents (5.9 vs 42.3%, p=0.0001). Significantly fewer patients with sirolimus-eluting stents had major adverse cardiac events at 9 months than did controls (8.0 vs 22.6%, p=0.0002), due mainly to a lower need for target-lesion revascularisations (4.0 vs 20.9%, p<0.0001)., Interpretation: Sirolimus-eluting stents are better than bare-metal stents for treatment of single long atherosclerotic lesions in a coronary vessel smaller than 3 mm in diameter.

Background: Patients with moderate chronic renal failure have recently been identified to suffer from a markedly higher mortality after percutaneous coronary intervention (PCI). We focused on the outcome of PCI patients with just mildly elevated creatinine levels of 1.1 to 1.5 mg/dL., Methods: Data of all PCI patients of the years 1998 to 1999 were analyzed. Follow-up was performed by a questionnaire sent to all patients., Results: During this period, PCI was performed in 1049 patients. Long-term follow-up (1184 +/- 10 days) was 99.6% complete. Total mortality increased continuously by each creatinine increment of 0.1 mg/dL above 1.0 mg/dL, with a significant difference at 1.3 mg/dL compared to patients with

Background: External cardioversion is a readily available treatment for persistent atrial fibrillation. Although anatomical and electrophysiological considerations suggest that an anterior-posterior electrode position should create a more homogeneous shock-field gradient throughout the atria than an anterior-lateral position, both electrode positions are equally recommended for external cardioversion in current guidelines. We undertook a randomised trial comparing the two positions with the endpoint of successful cardioversion., Methods: 108 consecutive patients (mean age 60 years [SD 16]) with persistent atrial fibrillation (median duration 5 months, range 0.1-120) underwent elective external cardioversion by a standardised step-up protocol with increasing shock strengths (50-360 J). Electrode positions were randomly assigned as anterior-lateral or anterior-posterior. If sinus rhythm was not achieved with 360 J energy, a single cross-over shock (360 J) was applied with the other electrode configuration. A planned interim analysis was done after these patients had been recruited; it was by intention to treat., Findings: Cardioversion was successful in a higher proportion of the anterior-posterior than the anterior-lateral group (50 of 52 [96%] vs 44 of 56 [78%], difference 23.7% (95% CI 9.1-37.8, p=0.009). Cross-over from the anterior-lateral to the anterior-posterior electrode position was successful in eight of 12 patients, whereas cross-over in the other direction was not successful (two patients). After cross-over, cardioversion was successful in 102 of 108 randomised patients (94%)., Interpretation: An anterior-posterior electrode position is more effective than the anterior-lateral position for external cardioversion of persistent atrial fibrillation. These results should be considered in clinical practice, for the design of defibrillation electrode pads, and when guidelines for cardioversion of atrial fibrillation are updated.

Left ventricular assist devices (LVADs) are an established surgical therapy for patients with end-stage heart failure as a bridge to cardiac transplantation. Major disadvantages of these devices are thromboembolic events, bleeding complications, infections, and malfunctions. We report on our experiences with DeBakey LVAD malfunctions requiring LVAD exchange in 4 patients. All patients underwent subsequent cardiac transplantation and are doing well now.

We have recently reported that the activation of mitogen-activated protein kinase (MAPK) through specific protein kinase C (PKC) isoforms is required for basic fibroblast growth factor (bFGF)-induced proliferation of coronary smooth muscle cells (cSMC). In this study, we investigated the effects of the 3hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase inhibitor lovastatin on bFGF-induced signal transduction in cSMC. The present study shows that lovastatin inhibits bFGF-stimulated DNA synthesis in cSMC, and that this inhibition is reversed by mevalonate (50 micromol/l) and by geranylgeranyl-pyrophosphate (1-5 micromol/l). Although lovastatin prevented Ras farnesylation the amount of bFGF-stimulated MAPK phosphorylation decreased only partially after lovastatin treatment. In addition, lovastatin pretreatment resulted in a sustained phosphorylation of MAPK. We observed a dose-dependent lovastatin-dependent increase in PKC activity, which could be prevented by mevalonate. This increase was comparable to the one induced by calyculin A (2 nmol/l), an inhibitor of protein phosphatase PP-1 and PP-2A. Lovastatin inhibited the expression of the PP-1 protein, which is involved in bFGF-induced DNA synthesis in cSMC. Thus, our data suggest that, lovastatin possibly affects the dephosphorylation processes of PKC and MAPK by inhibition of PP-1/PP-2A protein phosphatases which are involved in the bFGF-induced mitogenesis in cSMC.

Background: We assessed the impact of patient and procedural characteristics on the outcome after emergency coronary artery bypass grafting (CABG) for failed percutaneous transluminal coronary angioplasty (PTCA) and temporal changes in these factors., Methods: Patients who underwent PTCA and subsequent emergency CABG were identified from the databases of the Departments of Cardiology and Cardiothoracic Surgery., Results: Two periods of clinical practice were compared. In 1989 to 1993, 2,880 PTCAs were performed, 64 patients underwent emergency CABG (2.3%), and 7 patients died (10.9%). During 1994 to 1998, 46 patients of 3,801 PTCAs underwent emergency CABG (1.2%, p < 0.01), and 7 patients died (15.2%, NS). The average rate of stenting increased from 0.8% to 24% in 1994 to 1998 as well as the frequency of arterial bypass grafts (0% vs 39%). In the latter period, patients were older, were more often females, had more cardiovascular risk factors, a higher Cleveland score (each p < 0.05), and suffered more often from periprocedural myocardial infarctions (p < 0.001) and nonfatal periprocedural complications (p < 0.01)., Conclusions: Although the frequency of emergency CABG after failed PTCA declined, perioperative mortality tended to increase according to an unfavorable shift in patient risk factors and morbidity.