Heart rate variability as a predictor of successful catheter-guided pulmonary vein isolation for atrial fibrillation.

BACKGROUND: This retrospective observational study investigated the relationship between heart rate variability (HRV) and atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) by cryoballoon or radiofrequency ablation (RF). METHODS: We enrolled 497 patients who underwent PVI using first-generation cryoballoon (CB1), second-generation cryoballoon (CB2), or RF. We analyzed HRV as a surrogate for modulation of the intrinsic autonomic nervous system using 24­h Holter recordings 1 or 2 days after the procedure and compared the recurrence and non-recurrence group with regard to ablation methods. Furthermore, we calculated recurrence-free survival (RFS) below/over HRV cut-off values for the whole study population and separately for each ablation method. RESULTS: All except one of the five time-based HRV parameters analyzed were significantly lower in the non-recurrence group than in the recurrence group after CB2. Only a trend toward lower HRV for the non-recurrence group was found after RF and no remarkable differences were detected after CB1. The HRV parameters below their calculated cut-off were associated with a significantly higher RFS rate 2 years after CB2. This also applied to root mean sum of squared distance (rMSSD) and the percentage of adjacent NN interval differences greater than 50 ms (pNN50) after RF. No differences were found regarding CB1. Concerning rMSSD, the sensitivity, specificity, and difference in RFS increased when using cut-offs that were calculated including only CB2 patients. Multivariate cox regression analysis showed that low rMSSD values could independently predict AF recurrence after adjusting for covariates (hazard ratio: 0.50; p < 0.001). CONCLUSION: Low values of rMSSD early after a PVI could independently predict AF recurrence, especially after CB2.

Transcoronary pacing : Reliability during myocardial ischemia and after implantation of a coronary stent.

BACKGROUND: Transcoronary pacing is a useful therapeutic option for the treatment of unheralded bradycardias in the setting of percutaneous coronary interventions (PCI). OBJECTIVES: In the present study, we investigated the influence of stent implantation and transient myocardial ischemia on the feasibility of transcoronary pacing in a porcine model. METHODS: 7 adult pigs underwent a percutaneous coronary intervention with implantation of a coronary stent under general anaesthesia in an animal catheterization laboratory. Transcoronary pacing was established by using a standard guidewire isolated with an angioplasty balloon positioned in the periphery of the right coronary artery serving as the cathode. As the indifferent anode, a skin patch electrode at the back of the animal was used. The reliability of transcoronary pacing was assessed by measurement of threshold and impedance data and the magnitude of the epicardial electrogram at baseline, after implantation of a coronary stent and finally during myocardial ischemia. RESULTS: Effective transcoronary pacing could be demonstrated in all cases with the standard unipolar transcoronary pacing setup yielding a low pacing threshold at baseline of 1.3 ± 0.8 V with an impedance of 283 ± 67 Ω. Implantation of a coronary stent did not influence the pacing threshold (1.0 ± 0.4 V) and impedance (262 ± 63 Ω). Acute myocardial ischemia lead to a significant but clinically nonrelevant increase of the pacing threshold to 2.0 ± 0.6 V and a drop in pacing impedance (137 ± 39 Ω). CONCLUSIONS: Transcoronary pacing in the animal model is not affected by implantation of a coronary stent in the same vessel used for pacing. Despite a significant increase in pacing threshold, the transcoronary pacing approach is reliable in acute myocardial ischemia during a percutaneous coronary intervention.

The double guidewire approach for transcoronary pacing in a porcine model.

BACKGROUND: Transcoronary pacing is used for treatment of unheralded bradycardias in the setting of percutaneous coronary interventions (PCI). OBJECTIVES: In the present study we introduced a new concept - the double guidewire approach - for transcoronary pacing in a porcine model. METHODS: Transcoronary pacing was applied in 16 adult pigs under general anaesthesia in an animal catheterization laboratory. A special guidewire with electrical insulation by PTFE coating except for the distal part of the guidewire was positioned in the periphery of a coronary artery serving as the cathode. As the indifferent anode, an additional standard floppy tip guidewire was advanced into the proximal part of the same coronary vessel. The efficacy of double guidewire transcoronary pacing was assessed by measurement of threshold and impedance data and the magnitude of the epicardial electrogram compared with unipolar transcoronary pacing using a standard cutaneous patch electrode as indifferent anode. RESULTS: Transcoronary pacing was effective in all cases. Pacing thresholds obtained with the double guidewire technique (1.5 ± 0.9 V) were similar to those obtained by standard unipolar transcoronary pacing with a cutaneous patch electrode (1.2 ± 0.7 V) and unipolar transvenous pacing against the same cutaneous patch electrode (1.5 ± 1.0 V). Bipolar transvenous pacing yielded the lowest pacing threshold at 0.8 ± 0.4 V. CONCLUSIONS: Transcoronary pacing in the animal model with the novel "double guidewire approach" is a simple and effective pacing technique with comparable pacing thresholds obtained by standard unipolar transcoronary and transvenous pacing.

Acute myocardial infarction and cardiogenic shock: prognostic impact of cytokines: INF-γ, TNF-α, MIP-1ß, G-CSF, and MCP-1ß.

BACKGROUND: The IABP SHOCK trial was designed as a morbidity-based randomized controlled trial to determine the effect of intraaortic balloon pulsation (IABP) in patients with infarct-related cardiogenic shock (CS). The primary endpoint was the change in the APACHE II score over a 4-day period. The prospective hypothesis was that adding IABP therapy to "standard care" would reduce CS-triggered multiorgan dysfunction syndrome (MODS). The primary endpoint showed no difference between conventionally managed cardiogenic shock patients and those with additional IABP support. In an inflammatory marker substudy, we analyzed the prognostic value of the cytokines interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-1ß (MIP-1ß), granulocyte-colony stimulating factor (G-CSF), and monocyte chemoattractant protein-1ß (MCP-1ß). We also investigated the influence of IABP support, age, and gender on cytokine levels. DESIGN: The inflammatory marker substudy of the prospective, randomized, controlled, open label IABP SHOCK Trial (ClinicalTrials.gov ID NCT00469248). MATERIALS AND METHODS: A prospective, randomized, single-center study in a 12-bed intensive care unit at a university hospital was performed. A total of 40 consecutive patients were enrolled. The observational period was 96 h. RESULTS: The investigated cytokines showed a significant contribution in the prediction of mortality. Initial (on admission) and maximal cytokine levels during the observational period showed a similar predictive power. Patients with elevated levels of pro- and antiinflammatory cytokines had a higher risk of dying. The maximal level measured over the observation period in the hospital was also suited to identify the survivors. Close correlations between maximal cytokine levels resulted in the choice of only one independent marker (MIP-1ß) into the multivariate model (OR 1.024, 95% CI 1.005-1.043). Initial cytokine levels were also suitable to predict the survivors; the risk of death significantly increases with increasing IFN-γ level (OR 1.119, 95% CI 1.005-1.246). Cytokine levels were not affected by the presence of IABP support. Age (< 75 or > 75 years) and gender did not have a clinically relevant effect on INF-γ, TNF-α, MIP-1ß, G-CSF, and MCP-1 in CS patients. CONCLUSION: The inflammatory response in patients with myocardial infarction complicated by CS, as reflected by the inflammatory markers INF-γ, TNF-α, MIP-1ß, G-CSF, and MCP-1ß, have been shown to be of prognostic value in estimating clinical outcome.

[Patients with implanted devices in intensive care medicine]. / Der Patient mit implantiertem Device in der Intensivmedizin.

The management of intensive care patients with implanted devices requires the knowledge of the type of device (e.g. pacemaker, defibrillator, device for cardiac contractility modulation or event recorder). An electrocardiogram (ECG) and chest-X-ray can be helpful for identification of the type and manufacturer of the device. Information concerning the programmed parameters can be obtained by device interrogation. The establishment of invasive monitoring can be complicated by the intracardiac electrodes of the devices and requires a careful selection of the venous access site. In cases of external cardioversion/defibrillation there are some specific considerations to be made to avoid damage of the implanted device. Finally, adaption of device programming to the special circumstances in the intensive care unit may help patient and physician.

Multiple AV nodal pathways in patients with AV nodal reentrant tachycardia--more common than expected?

AIMS: It was the purpose of this study to determine the incidence of more than two AV nodal pathways in patients with AVNRT. METHODS AND RESULTS: In 78 consecutive patients with AV-nodal reentrant tachycardias (AVNRT) (50 females, 28 males, mean age 52.8 +/- 14.6 years), the number of sudden AH increases by 50 ms or more (AH-jump) was analysed during atrial extrastimulation. The incidence of two AV nodal pathways was accepted to be present in patients with AVNRT without an AH-jump ('smooth curve'). The following forms of tachycardia were induced: a typical AVNRT (slow-fast) in 67 patients, an atypical AVNRT (fast-slow) in 12 patients and a slow-slow-AVNRT in 4 patients. Five patients had two forms of AVNRT. 47 patients (60.3%) showed two AV nodal pathways, 27 patients (34.6%) had three AV-nodal pathways and 4 patients (5.1%) exhibited four AV-nodal pathways. For successful catheter ablation of AVNRT in patients with more than two pathways, more radiofrequency energy applications were required (9.2 +/- 6.3) compared with patients with only two pathways (6.7 +/- 4.8). Furthermore, in patients with more than two AV-nodal pathways, the catheter intervention resulted more frequently in a modulation of slow pathway conduction than in an ablation of the slow pathway(s). CONCLUSION: The incidence of more than two AV-nodal pathways in patients with AVNRT was unexpectedly high at about 40%. Thus, these tachycardias require a meticulous electrophysiological evaluation for successful ablation.

[Terminating supraventricular tachycardia with adenosine--comparing the effectiveness of 12 mg and 18 mg]. / Terminierung supraventrikulärer Tachykardien durch Adenosin--Vergleich der Wirkung von 12 mg und 18 mg.

OBJECTIVES: This study was done to answer the question if intravenous application of 18 mg adenosine is superior to 12 mg adenosine for the termination of supraventricular tachycardias. PATIENTS AND METHODS: 31 patients (17 men, 14 women, mean age 53 +/- 15 years [range 15-76 years]) had electrophysiological tests. In 25 patients AV nodal reentrant tachycardias were induced during programmed stimulation, 6 patients had inducible AV reentrant tachycardias with an accessory pathway. After induction of the supraventricular tachycardia (mean rate 183 +/- 29/minute, range 115-240/minute), in each patient 12 or 18 mg adenosine was applied in a bolus for terminating of the tachycardia. After the second induction of the tachycardia, a dose of 18 or 12 mg adenosine was given. The different doses of adenosine were chosen in a randomized and prospective manner in a crossover design. RESULTS: In 25 of the 31 patients (81%) the tachycardia was terminated by 12 mg adenosine. In 29 of the 31 patients (94%) the induced tachycardia was terminated by the application of 18 mg adenosine (no significant difference). In one patient, the tachycardia cessation was observed after 12 mg adenosine, but not after 18 mg adenosine. In another patient the tachycardia was not terminated by either 12 mg or by 18 mg adenosine. The termination of the tachycardia was seen after 25 +/- 8 seconds (13-51 seconds) when 12 mg adenosine was given. After the application of 18 mg adenosine the tachycardia ended after 25 +/- 8 seconds (14-44 seconds) (not significant). The asystole directly after tachycardia termination was 976 +/- 63 milliseconds (540-1700 milliseconds) with 12 mg adenosine, and 1070 +/- 628 milliseconds (530-4000 milliseconds) after the application of 18 mg adenosine (not significant). The longest asystole after termination of a tachycardia by 18 mg adenosine was 9.03 seconds. In one patient the tachycardia was reinitiated by spontaneous atrial extrasystoles after 12 mg adenosine, and reinduction of tachycardia was seen twice after 18 mg adenosine. After the administration of 18 mg adenosine, atrial fibrillation was observed in one patient. No serious complication occurred. CONCLUSIONS: In AV nodal reentrant tachycardias and AV reentrant tachycardias with an accessory pathway, which can not be terminated by the administration of adenosine in a dose of 12 mg, the tachycardia can be terminated more effectively by the application of 18 mg adenosine.

[Acute beta 1-selective beta-receptor blocker nebivolol poisoning in attempted suicide]. / Akute Intoxikation mit dem beta 1-selektiven beta-Rezeptorenblocker Nebivolol in suizidaler Absicht.

HISTORY AND ADMISSION FINDINGS: A 17-year-old girl had swallowed 80-100 tablets of Nebivolol, 5 mg each, with suicidal intent. She was referred to hospital 8 hours later by an emergency duty physician. On admission she was sweaty and pale, but there were no other obvious abnormalities. Neurological examination revealed decreased responsiveness and slowed movements. She was known to have type 1 diabetes mellitus. INVESTIGATIONS: Blood pressure was 105/55 mmHg, the ECG showed sinus bradycardia of 55 beats/min. Biochemical tests revealed hypoglycaemia (2.1 mmol/l), hypokalaemia (3.4 mmol/l) and respiratory failure (pO2 6.16 kPa, O2 saturation 82%, pCO2 6.55 kPA). Heart and lung were unremarkable on physical examination as were chest radiogram and echocardiogram. Plasma level of nebivolol was 480 ng/ml on admission (therapeutic range 88-195 ng/ml). TREATMENT AND COURSE: After gastric lavage and administration of charcoal and sodium sulphate a temporary pacemaker was connected and glucagon infused intravenously as an antidote. The cardiovascular state stabilized with falling plasma level of nebivolol. Glucose was administered initially, but transient intravenous insulin infusion became necessary to counteract hyperglycaemia. The patient was transferred from the intensive care unit in a stable cardiovascular state after 2 days. CONCLUSION: This case demonstrates that swallowing 400-500 mg nebivolol, resulting in a plasma level of 480 ng/ml, need not be fatal. But the outcome in this patient should not be taken as necessarily applying to similar cases. It depends on the individual patient's metabolic state whether higher plasma levels might be reached with the same amount of ingested nebivolol.

[The heart in infection and MODS (multiple organ dysfunction syndrome)]. / Das Herz bei Sepsis und MODS.

Dysfunctioning of the heart forms part of the multiple organ dysfunction syndrome (MODS) in sepsis and SIRS. This acute septic cardiomyopathy is often underestimated in degree and relevance, although yet in fact 10% of all sepsis fatalities are due to intractable heart failure. This potentially reversible cardiomyopathy is characterized by a considerable pump failure, is not primarily ischemic, coronary blood flow being normal or even enhanced; left and right ventricle are enlarged as a consequence of an increased ventricular compliance. Damage of the heart can further be aggravated in case of an additional right ventricular impairment due to pulmonary hypertension in ARDS. SIRS-cardiomyopathy in non-infectious MODS has common traits with acute septic cardiomyopathy. The pathogenesis of heart disease in sepsis and SIRS is multifactorial, the endotoxin/TNF-alpha/NO/cGMP-cascade representing a main negative inotropic axis. Therapy of acute septic cardiomyopathy and SIRS-cardiomyopathy at present still is mainly symptomatic (volume substitution, inotropic/vasoactive agents), causal therapeutic principles are, however, put to test in the context of a comprehensive concept of causal sepsis treatment.

Calcium dynamics in cardiac myocytes as a target of dichloromethane cardiotoxicity.

The purpose of the present study was to determine if cardiac actions of dichloromethane (DCM) in vivo correlate with in vitro alterations of Ca2+ dynamics in cardiac myocytes. Neonatal rat ventricular myocytes were obtained from 2- to 4-day-old rats, and electrically induced fluctuations of cytosolic free Ca2+ concentration ([Ca2+]i) in single cardiomyocytes were investigated using spectrofluorometric analysis of fura-2-[Ca2+]i binding. In cultured myocytes, cumulative exposure to 0.64-40.96 mM DCM resulted in a concentration-dependent and reversible decrease in the magnitude of [Ca2+]i transients with IC10 and IC50 values of 7.98 and 18.82 mM, respectively. Total inhibition of [Ca2+]i transients and cessation of beating were observed at 40.96 mM DCM. Suffusion with DCM for 40 min did not cause morphological alterations of the myocytes. In a urethane-anesthetized rat model, left ventricular pressure was measured by introducing a tip catheter via the carotid artery into the left ventricle, the ECG was recorded by two needle electrodes applied subcutaneously to the chest wall, and arterial pressure was measured via the femoral artery. Oral administration of 3.1-12.4 mmol DCM/kg resulted in DCM blood concentrations between 1.0 and 1.6 mM, accompanied by a dose-dependent decrease in contractile force and heart rate without influencing blood pressure and ECG tracings. Moreover, DCM treatment provided significant protection against arrhythmia development due to CaCl2-infusion. In spite of the slight discrepancy between DCM blood concentrations and in vitro concentrations of DCM for [Ca2+]i transient inhibition, present data are consistent with the view that cardiac effects after DCM exposure are mediated by alterations of Ca2+ dynamics during excitation-contraction coupling.

Cardiotoxicity of dichloromethane in rats and in cultured rat cardiac myocytes.

The purpose of the present study was to examine whether cardiac actions of dichloromethane (DCM) in vivo correlate with in vitro alterations of Ca(2+) dynamics in cardiac myocytes. Electrically induced fluctuations of cytosolic free Ca(2+) concentration ([Ca(2+)](i)) were investigated in neonatal rat ventricular myocytes using spectrofluorometric analysis of fura-2 binding. [Ca(2+)](i) transients were inhibited in a concentration-dependent and reversible manner with IC(10) and IC(50)values of 3.2 and 18.1 mm. Complete inhibition of [Ca(2+)](i) transients and cessation of beating were observed at 40.96 mm without morphological alterations. Left ventricular pressure in urethane-anaesthetized rats was measured by introducing a tip catheter by way of the carotid artery into the left ventricle and ECG (lead II) was recorded by two needle electrodes. Administration of 3.1, 6.2 or 12.4 mmol DCM/kg orally resulted in DCM blood concentrations between 1.0 and 1.6 mm accompanied by a dose-dependent decrease of contractility parameters. Moreover, DCM administration provided protection against arrhythmia development due to CaCl(2) infusion. These observations are consistent with the view that both the negative inotropic effects of DCM and the protection from CaCl(2)-induced arrhythmia are mediated by an inhibition of Ca(2+) dynamics in cardiomyocytes.

Depression of calcium dynamics in cardiac myocytes--a common mechanism of halogenated hydrocarbon anesthetics and solvents.

Individual halogenated hydrocarbons (HC) have recently been demonstrated to depress Ca2+ dynamics in cardiomyocytes during excitation-contraction coupling. In the present study, eight widely used HC were systematically compared for their effects on Ca2+ dynamics in neonatal rat cardiomyocytes by means of spectrofluorometric analysis of fura-2-Ca(2+)-binding. Cells were exposed to dichloromethane (DCM), dichloroethane (DCE), 1,1,2-trichloroethane (112-TCE), trichloroethylene (TRI), halothane (HAL), 1,1,1-trichloroethane (111-TCE), perchloroethylene (PER), or pentachlorethane (PCE) in an environmentally controlled chamber. All HC tested decreased the height of electrically induced cytosolic free Ca2+ ([Ca2+]i) transients in a concentration-dependent and reversible manner (IC50 0.15-18.06 mM) without significant effects on diastolic [Ca2+]i. The increase in [Ca2+]i induced by depolarization with 90 mM KCl was inhibited to a lesser degree. Investigations with thapsigargin (100 nM) and ryanodine (1 microM)-inhibitors of Ca2+ release from the sarcoplasmic reticulum-provided evidence that the tonic Ca2+ response after KCl depolarization depends mainly on sarcolemmal Ca2+ influx. The potency of the eight HC to inhibit Ca2+ dynamics in cardiomyocytes correlated with their octanol/water partition coefficients. Results support the hypothesis that alteration of Ca2+ dynamics in cardiomyocytes is a common mechanism of cardiotoxic HC actions.