Influence of smoking dosage and chronic obstructive lung disease on the incidence of appropriate therapies and mortality in patients with structural heart disease and an implantable cardioverter defibrillator.

BACKGROUND: Smoking is known as a relevant risk factor for severe cardiac morbidities and mortality. This study was initiated to explore the influence of smoking dosage and presence of chronic obstructive lung disease (COPD) on the incidence of appropriate implantable cardioverter defibrillator (ICD) interventions and on mortality. METHODS: Prior studies on patients equipped with an ICD suggested that nicotine consumption increases the risk of experiencing an appropriate ICD therapy. There is no substantial data regarding the influence of cigarette smoking dosage on overall mortality in such endangered patients. A total of 349 patients with structural heart disease, either coronary artery disease or nonischemic cardiomyopathy equipped with an ICD, were included. Every patient answered a questionnaire regarding his smoking status and performed a spirometry and body plethysmography. RESULTS: A total of 104 patients (30%) suffered from COPD. Fifty-eight patients (17%) were "current smokers," 196 patients (56%) were revealed as "former smokers," while 93 (27%) patients were registered as "never smokers." A total of 163 patients (47%) received at least one appropriate ICD intervention during follow-up (median 48 ± 8 months). Twenty-three patients died during this study (6.6%). There was no association of COPD with the incidence of appropriate ICD therapies or mortality. Smoking dosage revealed as a significant risk factor for both appropriate ICD interventions (hazard ratio [HR] 1.5 for 60 pack years [PY] P = 0.04) and mortality (HR 2.3 for 60 PY P = 0.02). CONCLUSION: This study demonstrates a dose-related increased risk of smokers for appropriate ICD interventions and mortality. The results of this trail urge a strict nicotine abstinence, especially in patients with a structural heart disease undergoing ICD therapy.

Interleukin-6 is the strongest predictor of 30-day mortality in patients with cardiogenic shock due to myocardial infarction.

INTRODUCTION: Cardiogenic shock (CS) remains the leading cause of death in patients hospitalized for myocardial infarction (MI). Systemic inflammation with inappropriate vasodilatation is observed in many patients with CS and may contribute to an excess mortality rate. The purpose of this study was to determine the predictive role of serial measurements of Nt-proBNP, interleukin-6 (IL-6), and procalcitonin (PCT) for 30-day mortality in patients with CS due to MI. METHODS: The present study is a prospective single-center study including 87 patients with MI complicated by CS treated with acute revascularization and intraaortic balloon counterpulsation (IABP) support. Predictive values of plasma levels at admission (T0), after 24 hours (T1), and after 72 hours (T2) were examined according to 30-day mortality. RESULTS: Significant differences between survivors (n = 59) and nonsurvivors (n = 28) were seen for Nt-proBNP at T0, for IL-6 at T0 and T1, and for PCT at T1 and T2. According to ROC analyses, the highest accuracy predicting 30-day mortality was seen at T0 for IL-6, at T1 for PCT, and at T2 for PCT. In univariate analysis, significant values were found for Nt-proBNP at T1, and for IL-6 and PCT at all points in time. Within the multivariate analysis, age, creatinine, and IL-6 were significant determinants of 30-day mortality, in which IL-6 showed the highest level of significance. CONCLUSIONS: In patients with MI complicated by CS, IL-6 represented a reliable independent early prognostic marker of 30-day mortality. PCT revealed a significant value at later points in time, whereas Nt-proBNP seemed to be of lower relevance.

Prevalence of asymptomatic upper extremity venous obstruction in 302 patients undergoing first implantation of cardioverter defibrillator.

BACKGROUND: Little is known about the prevalence of upper extremity vein obstruction or anomalies in patients before first implantation of implantable cardioverter defibrillator (ICD). It remains unclear in which patients contrast venography is warranted before implantation procedure. METHODS: Results of clinical data and contrast venography of 302 consecutive patients scheduled for first ICD implantation were analyzed. RESULTS: Prevalence of upper vein obstruction was 6.6% (20/302 patients) in a typical patient population undergoing first ICD implantation. Age, left ventricular ejection fraction, underlying heart disease, prior open-heart surgery, or cardiopulmonary resuscitation were not predictors of obstruction. Patients with previous cardiac pacemaker implantation had a higher rate of obstruction, though this was not statistically significant (20% vs 15.7%, P = 0.54). Persistent left vena cava was found in 0.7%. CONCLUSION: There is no clinical parameter sufficient enough to predict upper extremity venous obstruction. Contrast venography may be considered in patients with previous pacemaker placement but should not be a routine diagnostic tool in unselected patients prior to first ICD-implantation procedure.

Rationale and design of the OPTION study: optimal antitachycardia therapy in ICD patients without pacing indications.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) represent the treatment of choice for primary and secondary prevention of sudden cardiac death but ICD therapy is also plagued by inappropriate shocks due to supraventricular tachyarrhythmias. Dual-chamber (DC) ICDs are considered to exhibit an enhanced discrimination performance in comparison to single-chamber (SC) ICDs, which results in reduction of inappropriate detections in a short- to mid-term follow-up. Comparative data on long-term follow-up and especially on inappropriate shocks are limited. METHODS: The aim of the OPTION study is to assess whether an optimized treatment with DC ICDs improves patient outcome and decreases the rate of inappropriate shocks in comparison to SC ICDs. DC ICD therapy optimization is achieved by optimal customizing of antitachycardia therapy parameters, activation of discrimination algorithms, antitachycardia pacing in the slow ventricular tachycardia zone, and avoidance of right ventricular pacing with the SafeR algorithm mode. The OPTION study, a prospective, multicenter, randomized, single-blinded, parallel study, will randomize 450 patients on a 1:1 allocation to either an SC arm with backup pacing at VVI 40 beats per minute (bpm) or to the DC arm with SafeR pacing at 60 bpm. Patients will be followed for 27 months. Primary outcome measure is the time to first occurrence of inappropriate shock and a combined endpoint of cardiovascular morbidity and all-cause mortality. CONCLUSION: The study will evaluate the relative performance of DC in comparison to SC ICDs in terms of inappropriate shock reduction and patient outcome.

[Present and future relevance of telemedicine in cardiac arrhythmia emergencies]. / Derzeitige und zukünftige Bedeutung der Telemedizin im Arrhythmienotfall.

BACKGROUND: The use of remote monitoring has increased due to recently published randomised studies. However, its benefit during acute rhythm disorders still remains controversial. OBJECTIVES: The current review describes the current status and highlights possible application of telemedicine during acute rhythm disorders. MATERIALS AND METHODS: The prerequisites, structural properties of the sender/patient and the receiver of the data/physician are examined and the results of the current literature are presented. RESULTS: Telemedicine during emergency rhythm disorders are normally reserved for specific scenarios. The lack of 24/7 staff of the receiver/hospital represents the main barrier. CONCLUSIONS: Remote medicine in the current form is not yet ready to be implemented for acute rhythm disorders. Expansion of currently existing chest pain units (CPUs) might enable this 24/7 service in the near future.

Cardiac resynchronization therapy and atrial overdrive pacing for the treatment of central sleep apnoea.

AIMS: The combined therapeutic impact of atrial overdrive pacing (AOP) and cardiac resynchronization therapy (CRT) on central sleep apnoea (CSA) in chronic heart failure (CHF) so far has not been investigated. We aimed to evaluate the effect of CRT alone and CRT + AOP on CSA in CHF patients and to compare the influence of CRT on CHF between CSA positive and CSA negative patients. METHODS AND RESULTS: Thirty patients with CRT indication underwent full night polysomnography, echocardiography, exercise testing, and neurohumoral evaluation before and 3 months after CRT implantation. In CSA positive patients (60%), two additional sleep studies were conducted after 3 months of CRT, with CRT alone or CRT + AOP, in random order. Cardiac resynchronization therapy resulted in significant improvements of NYHA class, left ventricular ejection fraction, N-terminal pro-brain natriuretic peptide, VO(2)max, and quality of life irrespective of the presence of CSA. Cardiac resynchronization therapy also reduced the central apnoea-hypopnoea index (AHI) (33.6 +/- 14.3 vs. 23.8 +/- 16.9 h(-1); P < 0.01) and central apnoea index (17.3 +/- 14.1 vs. 10.9 +/- 13.9 h(-1); P < 0.01) without altering sleep stages. Cardiac resynchronization therapy with atrial overdrive pacing resulted in a small but significant additional decrease of the central AHI (23.8 +/- 16.9 vs. 21.5 +/- 16.9 h(-1); P < 0.01). CONCLUSION: In this study, CRT significantly improved CSA without altering sleep stages. Cardiac resynchronization therapy with atrial overdrive pacing resulted in a significant but minor additional improvement of CSA. Positive effects of CRT were irrespective of the presence of CSA.

Advanced mapping techniques in atrial fibrillation.

Catheter ablation has emerged as an excellent treatment option for atrial fibrillation especially in patients with paroxysmal AF. Several obstacles however remain regarding ablation strategies for persistent and chronic AF. In this setting, adequate success rates can only be achieved with left atrial ablation in addition to complete PV isolation. Important techniques in this regard are mapping of complex fractionated atrial electrograms as well as identification of atrial sites serving as sources of persistent AF. Other mapping techniques reviewed in this article are rapid geometry acquisition with spiral catheters and the Ensite/NAVX system, the 64-pole Constellation basket catheter as well as the MESH Mapper catheter.

[Latest proceedings: remote medicine - ready for clinical practice?!]. / Telemedizin in der Kardiologie - Relevanz für die Praxis?!

Changes in the demographic structure, increasing multimorbidity in connection with a rise in the number of chronic illnesses and the absence of an effective coordination of the different levels of healthcare services with its discontinuous processes and redundancies will increase the economic burdens in the German health-care system. Recent developments and appropriate logistic premises nowadays offer a realistic basis for implementing remote medicine as a central service and information tool as well as an instrument controlling the information and data flow between patient, hospital and medical practitioner. This article highlights current and future strategies including diagnostic and therapeutic options. The focus will concentrate on patients with heart rhythm disturbances, advanced congestive heart failure, and patients with implantable devices, i.e., pacemaker and implantable cardioverter defibrillator (ICD).

[ECG telemonitoring]. / EKG-Telemonitoring : Nucleus der Arbeitsgruppe "Telemonitoring" der Deutschen Gesellschaft für Kardiologie - Herz- und Kreislaufforschung.

ECG telemonitoring is the application of single- or multichannel ECGs transmitted by telephone to the physician or an expert center. This enables the control of the health status despite the spatial separation of patient and physician. Cardiac arrhythmias, palpitations of unknown causes, the outcome of antiarrhythmic drug therapy or interventional ablation therapy can be diagnosed using ECG telemonitoring. Even asymptomatic arrhythmias, e.g. paroxysmal atrial fibrillation, may be detected. The use of a multichannel ECG facilitates the early prehospital diagnosis of an acute coronary syndrome and thus helps to optimize the chain of rescue. The telemonitoring of the ECG and additional physiological data enables the tele-care of patients with chronic heart failure. New types of implanted pacemaker or cardioverter/defibrillator devices allow telemonitoring of device data or ECG data for close control.

Circumferential pulmonary vein mapping and ablation in focal atrial fibrillation: single catheter technique.

BACKGROUND: Atrial fibrillation (AF) can be cured in a subgroup of patients performing catheter ablation and eliminate trigger arrhythmias mainly originating in the pulmonary veins (PV's). CASE REPORT: This case report describes the use of a novel catheter design combining both, circumferential mapping and radiofrequency delivery capabilities to perform pulmonary vein ablation in patients with focal AF. It could be demonstrated that this catheter was able to eliminate pulmonary vein potentials in a single left atrial catheter technique without acute evidence for PV stenosis. In two PV's of a second patient, where the Helix catheter was placed in a very ostial position, it was not possible to completely eliminate the PV signal component of the ostial electrogram. Long-term follow-up with AF recurrence documentation will clarify whether ostial PV signal amplitude reduction may serve as an acceptable procedural endpoint. CONCLUSION: PV potential elimination is feasible using this novel catheter design; safety and long-term efficacy of this single catheter approach will be evaluated in a multicenter study (BITMAP study: Breakthrough and Isolation Trial: Mapping and Ablation of Pulmonary Veins).

Decremental pulmonary venous pulse propagation: impact for catheter ablation in focal atrial fibrillation.

BACKGROUND: Electrical isolation of pulmonary veins (PV's) is crucial to achieve success in catheter ablation for trigger elimination in focal atrial fibrillation (AF). To guide ostial PV radiofrequency (RF) delivery, it is necessary to identify the electrical breakthrough (EBT) between PV and left atrium. For this purpose, coronary sinus (CS) fixed rate pacing is commonly used. This study evaluated, whether CS extrastimulus pacing is superior in identifying the EBT area as compared to fixed rate pacing. METHODS: In 9 patients (51 +/- 10 years) undergoing a left sided electrophysiological study for AF ablation, 25 PV's (10 right and 15 left-sided PV's) were mapped using a 4 French fixed-wire catheter with eight 6 mm coiled Platinum electrodes in a distal looped configuration (Revelation Helix, Cardima Inc.). For mapping and ablation the electrode loop was positioned in the PV ostium rectangular to the longitudinal PV axis. EBT area was identified as those electrodes indicating the earliest PV signals during CS pacing. We measured number of EBT electrodes and time between EBT and the latest activated bipoles at the electrode loop during fixed rate and extrastimulus pacing. The reduction of two or more EBT electrodes was defined as a significant benefit in EBT identification. RESULTS: In 22 of 25 PV's mapped PV potentials could be observed. Performing fixed rate pacing the EBT area was identified in a mean of 4.2 +/- 1 electrodes, whereas using extrastimulus pacing, EBT area could be significantly reduced to 2.3 +/- 0.8 electrodes. The time between EBT and latest electrode activated increased from 14 +/- 7 ms to 22 +/- 10 ms indicating an intrapulmonary conduction delay during extrastimulus pacing. In 13 of 22 PV's mapped (59%), extrastimulus pacing was beneficial in the identification of the EBT, as the primary target for RF delivery. CONCLUSIONS: CS extrastimulus pacing induces intra-PV decremental conduction properties allowing one to identify a more localised and smaller EBT area as the primary target for RF delivery. Performing PV ablation to treat focal AF, extrastimulus maneuvers allow to unmask the "true" EBT and thus may help to limit intrapulmonary RF delivery.

Usefulness of sleep-disordered breathing to predict occurrence of appropriate and inappropriate implantable-cardioverter defibrillator therapy in patients with implantable cardioverter-defibrillator for primary prevention of sudden cardiac death.

Advanced heart failure (HF) is associated with severe sleep-disordered breathing (SDB). In addition, most patients with HF are treated with an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death. The incidence of ICD therapy in such a patient cohort with SDB has never been investigated. The present study sought to determine the effect of SDB on the incidence of appropriate and inappropriate ICD therapy in patients with a categorical primary prevention ICD indication. A total of 133 consecutive ICD patients with New York Heart Association class II-III HF and depressed left ventricular function (≤35%) with no history of ventricular arrhythmia underwent a sleep study before ICD implantation and were followed for 24 ± 8 months, prospectively. A relevant SDB was defined as an apnea-hypopnea index of ≥10 events/hour. Of these 133 patients, 82 (62%) had SDB. Overweight (body mass index >29.1 vs 24.7 kg/m(2); p <0.001) was identified as the only independent risk factor for SDB. Appropriate ICD therapy intervention was significantly greater among patients with SDB than among patients without SDB (54% vs 34%, p = 0.03). Inappropriate ICD therapy intervention was documented more often in patients with SDB (n = 24 [29%] vs 7 [14%]; p = 0.04). An apnea-hypopnea index >10 events/hour was an independent predictor of appropriate ICD therapy on multivariate analysis (odds ratio 2.5, 95% confidence interval 1.8 to 4.04; p = 0.01). In conclusion, the present study is the first trial exploring the effect of SDB on the incidence of appropriate and inappropriate ICD therapy in patients with HF with a primary prevention indication. These results indicate that a preimplantation sleep study will identify patients with HF prone to receive appropriate and inappropriate ICD therapy.

Prognostic value of cerebral injury following transfemoral aortic valve implantation.

AIMS: To evaluate the impact of serological, imaging and clinical measures of cerebral injury on patient self-sufficiency and survival after transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: Before and three days after TAVI, neuron-specific enolase (NSE), cerebral diffusion-weighted magnetic resonance imaging (DW-MRI) and neurological performance utilising National Institutes of Health Stroke Scale (NIHSS) were assessed. Self-sufficiency was determined with established score systems (instrumental activities of daily living score, Barthel Index). Parameters of cerebral injury were investigated for their impact on self-sufficiency and all-cause mortality after 30 days and one year. Sixty-one patients were enrolled (logistic EuroSCORE: 26.4±18.1, STS score: 7.9±5.7), of whom 39 completed the imaging protocol. The incidences of NSE increase, new embolic events in DW-MRI, and neurological deficit early after TAVI were 52.4%, 71.8% and 6.6%, respectively. The degree of concomitant comorbidities, reflected by higher risk scores, had significant impact on outcome. Plasma levels of NSE and new emboli in DW-MRI were neither related to self-sufficiency nor to survival one year after TAVI. CONCLUSIONS: In this observational pilot study, "silent" cerebral injury is neither related to dependent lifestyle nor to mortality during the first year after TAVI. However, long-term follow-up is needed to elucidate fully the impact of silent stroke. Clinical trials number: NCT00883285.

Cognitive trajectory after transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is known to be associated with silent cerebral injury, which could contribute to cognitive impairment. Considering its increasing use, thorough longitudinal investigation of cognitive trajectory after TAVI is pivotal. METHODS AND RESULTS: Repeatable battery for the assessment of neuropsychological status was performed before (E1), 3 days (E2), 3 months (E3), 1 (E4) year, and 2 years (E5) after TAVI. Baseline characteristics, procedural data, imaging parameters of brain injury (diffusion-weighted MRI), and the use of conceivable neuroprotective approaches were investigated for their effect on cognitive function. Cognitive performance was investigated in 111 patients (mean log EuroSCORE, 30±13%). Global cognitive function (repeatable battery for the assessment of neuropsychological status total score) increased transiently at E2 (P=0.02) and was comparable with baseline levels at E3, E4, and E5. Six patients (5.4%) demonstrated early cognitive decline. Persistence and late onset were seen infrequently (n=3, 2.7% and n=4, 3.6%, respectively). Hence, early cognitive decline was ruled out in 105 patients (94.6%), and a majority of patients (91%) demonstrated sustained cognitive performance throughout all investigated time points. Interestingly, only patient age (P=0.012), but not prior cerebrovascular events, cognitive status, direct TAVI, cerebral embolism in diffusion-weighted MRI, or the use of a cerebral embolic protection device was found to be independently associated with cognitive decline, linking higher age to cognitive impairment along the first 2 years after TAVI. CONCLUSIONS: Long-term cognitive performance was preserved in the great majority (91%) of patients throughout the first 2 years after TAVI, despite the high intrinsic risk for cognitive deterioration. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00883285.

Prognostic value of cerebral injury following transfemoral aortic valve implantation.

Aims: To evaluate the impact of serological, imaging and clinical measures of cerebral injury on patient self-sufficiency and survival after transcatheter aortic valve implantation (TAVI). Methods and results: Before and three days after TAVI, neuron-specific enolase (NSE), cerebral diffusion-weighted magnetic resonance imaging (DW-MRI) and neurological performance utilising National Institutes of Health Stroke Scale (NIHSS) were assessed. Self-sufficiency was determined with established score systems (instrumental activities of daily living score, Barthel Index). Parameters of cerebral injury were investigated for their impact on self-sufficiency and all-cause mortality after 30 days and one year. Sixty-one patients were enrolled (logistic EuroSCORE: 26.4±18.1, STS score: 7.9±5.7), of whom 39 completed the imaging protocol. The incidences of NSE increase, new embolic events in DW-MRI, and neurological deficit early after TAVI were 52.4%, 71.8% and 6.6%, respectively. The degree of concomitant comorbidities, reflected by higher risk scores, had significant impact on outcome. Plasma levels of NSE and new emboli in DW-MRI were neither related to self-sufficiency nor to survival one year after TAVI. Conclusions: In this observational pilot study, "silent" cerebral injury is neither related to dependent lifestyle nor to mortality during the first year after TAVI. However, long-term follow-up is needed to elucidate fully the impact of silent stroke. Clinical trials number: NCT00883285.

Risk and fate of cerebral embolism after transfemoral aortic valve implantation: a prospective pilot study with diffusion-weighted magnetic resonance imaging.

OBJECTIVES: The aim of this study was prospective investigation of silent and clinically apparent cerebral embolic events and neurological impairment after transfemoral aortic valve implantation (TAVI). BACKGROUND: TAVI is a novel therapeutic approach for multimorbid patients with severe aortic stenosis. We investigated peri-interventional cerebral embolism with diffusion-weighted magnetic resonance imaging (DW-MRI) and its relationship to clinical and serologic parameters of brain injury. METHODS: Cerebral DW-MRI was performed before, directly, and 3 months after TAVI with the current third-generation self-expanding CoreValve (Medtronic, Minneapolis, Minnesota) prosthesis. At the timepoints of the serial MRI studies, focal neurological impairment was assessed according to the National Institutes of Health Stroke Scale (NIHSS), and serum concentration of neuron-specific enolase (NSE), a marker of the volume of brain tissue involved in an ischemic event, were determined. RESULTS: Thirty patients were enrolled; 22 completed the imaging protocol. Three patients (10%) had new neurological findings after TAVI, of whom only 1 (3.6%) had a permanent neurological impairment. Of the 22 TAVI patients with complete imaging data, 16 (72.7%) had 75 new cerebral lesions after TAVI presumed to be embolic. The NIHSS and NSE were not correlated with DW-MRI lesions. CONCLUSIONS: The incidence of clinically silent peri-interventional cerebral embolic lesions after TAVI is high. However, in this cohort of 30 patients, the incidence of persistent neurological impairment was low. (Incidence and Severity of Silent and Apparent Cerebral Embolism After Conventional and Minimal-invasive Transfemoral Aortic Valve Replacement; NCT00883285).

Comparison of microvolt T-wave alternans measurements using atrial pacing compared to atropine administration.

BACKGROUND: Microvolt T-wave alternans (MTWA) has been associated with malignant ventricular arrhythmias in patients (pts) with structural heart disease. MTWA has been shown to be a strong heart rate-dependent arrhythmia marker. However, in clinical practice some pts in which MTWA should be assessed are unable to perform physical exercise to increase heart rate due to various reasons. METHODS: In this study, we investigated the feasibility of noninvasive MTWA measurement by using intravenous atropine to increase heart rate and compared the results to MTWA measurement by right atrial (RA) pacing during electrophysiologic (EP) study in 27 consecutive pts (53 +/- 14 years; nine women). Determining the arrhythmia event-rate, a follow-up of 18 months was performed in all pts. RESULTS: Using atropine, five pts (18%) did not reach the target heart rate (105 bpm). In the remaining group of pts, concordant results for MTWA assessment could be found in 21 pts (96%). Comparing MTWA positive tests there were slightly higher amplitudes using right atrial (RA) pacing than atropine (7.0 +/- 2.3 microV vs 6.3 +/- 2.2 microV, P = 0.03; r = 0.97). During follow-up all pts with a positive MTWA test had documented ventricular arrhythmias. There were no arrhythmic events in the MTWA negative group. CONCLUSION: Whenever target heart rate for MTWA evaluation is obtained by intravenous atropine, the results are comparable to RA pacing. In using atropine there has been observed no pharmacologically influenced increase of MTWA voltage leading to false positive MTWA results. Therefore the use of atropine can be recommended as a safe, non-invasive, and reliable method for MTWA assessment.

Connexin31 cannot functionally replace connexin43 during cardiac morphogenesis in mice.

In the gastrulating mouse embryo, the gap junction protein connexin43 is expressed exclusively in cells derived from the inner cell mass, whereas connexin31 is expressed in cells of the trophoblast lineage. Since connexin43 and connexin31 do not form heterotypic gap junction channels in exogenous expression systems, such as HeLa cells and Xenopus oocytes, previous studies have suggested that the incompatibility of these two connexins could contribute to the separation of connexin43-expressing and connexin31-expressing compartments between embryo and extraembryonic tissues at gastrulation, respectively. Thus, we have generated connexin43 knock-in connexin31 mice, in which the coding region of the connexin43 gene was replaced by that of connexin31. Interbreeding of heterozygous connexin43 knock-in connexin31 mice resulted in homozygous connexin43 knock-in connexin31 mice, but none of them survived to adulthood. As these mice were born at the expected Mendelian frequency, we conclude that the reported incompatibility of connexin43 and connexin31 to form heterotypic gap junction channels does not interfere with normal embryonic development. Neonatal homozygous connexin43 knock-in connexin31 hearts showed malformation in the subpulmonary outlet of the right ventricle, similar to general connexin43-deficient mice. Electrocardiograms of neonatal hearts in homozygous connexin43 knock-in connexin31 mice revealed significantly low voltage of the QRS complex. This is in contrast to previous results from our laboratory which showed that replacement of connexin43 by connexin40 resulted in morphologically and functionally normal hearts. We conclude that connexin31 cannot functionally replace connexin43 during cardiac morphogenesis.

Transient ST-segment-elevation during pulmonary vein ablation using circumferential coiled microelectrodes in a prospective multi-centre study.

AIMS: Paroxysmal atrial fibrillation (PAF) is predominantly triggered by focal ectopies located within the pulmonary veins (PV). The BITMAP Study (Breakthrough and Isolation Trial: Mapping and Ablation of Pulmonary Veins) investigated prospectively the safety and efficacy of a catheter design with circumferential mapping and ablation electrodes. We report the phenomenon of ST-segment-elevation during catheter placement in the left atrium (LA) and superior PVs in this multi-centre study. METHODS AND RESULTS: Forty-three patients (57+/-10 years) with PAF were included in this study. Radiofrequency catheter (RFC) ablation supported by the 4F REVELATION Helix microcatheter (Cardima Inc., Freemont, CA, USA) with eight distal-coiled microelectrodes for bipolar mapping and ablation. RFC was applied at the ostial region of PV (30 W, 45-50 degrees C) with a maximum of four RFC applications per electrode. In four of the 43 patients from three centres, we recorded the occurrence of ST-segment-elevation greater than 0.2 mV and accompanying left thoracic discomfort. The ECG changes and the symptoms started abruptly and lasted for 4.2+/-2.2 min. Pericardial effusion could instantaneously be excluded by echocardiography in all cases. Coronary angiograms were performed in three patients with the longest episodes; no thrombotic material or air emboli were present. The symptoms and the ECG changes resolved completely in all patients. CONCLUSION: The phenomenon of ST-segment-elevation during LA- and PV-mapping in patients with PAF may be a common occurrence. In this prospective multi-centre trial, we demonstrated the reversibility of this phenomenon; no cardiovascular or cerebral damage was reported during both the procedure and the follow-up. Although the mechanism is still unclear, vasospasm may contribute to this phenomenon because of autonomic dysregulation.