Cardiac biomarkers for risk stratification of arrhythmic death in patients with heart failure and reduced ejection fraction.

Objectives. Patients with heart failure and reduced left ventricular ejection fraction (HFrEF) are prone to ventricular tachyarrhythmias. We tested whether biomarkers C-terminal Endothelin 1 (CT-ET1), midregional pro atrial natriuretic peptide (MR-proANP) and midregional pro adrenomedullin (MR-proADM) might improve risk stratification for arrhythmic death.Methods: This prospective observational study included 160 heart failure patients with ischaemic cardiomyopathy (ICM) or non-ischaemic, dilated cardiomyopathy (DCM) and 30 control patients without heart disease. Primary endpoint was arrhythmic death (ArD) or resuscitated cardiac arrest (resCA).Results: A total of 61 patients died during the median follow-up of 7.0 [5.2-8.4] years. An ArD or resCA was observed in 48 patients. Plasma levels of CT-ET1 (p = 0.002), MR-proANP (p < 0.001) and MR-proADM (p = 0.013) were significantly higher in ICM or DCM patients compared to controls. MR-proANP levels in ICM patients were associated with a significantly increased risk for ArD or resCA (hazard ratio (HR) = 1.42, [95%CI: 1.08-1.85], p = 0.011) in a multivariable Cox regression model. Plasma levels of CT-ET1 (HR = 1.07 [0.98-1.17], p = 0.113) and MR-proADM (HR = 1.80 [0.92-3.55], p = 0.087) were not associated with ArD or resCA in ICM patients. No significant association with ArD or resCA was found in DCM patients. Multivariable Cox regression showed that CT-ET1 (HR = 1.14 [1.07-1.22], p < 0.001), MR-proANP (HR = 1.64 [1.29-2.08], p < 0.001) and MR-pro ADM (HR = 2.06 [1.12-3.77], p = 0.020) were associated with a higher risk for overall mortality.Conclusion: Patients with HFrEF had elevated levels of CT-ET1, MR-proANP and MR-proADM. Plasma levels of MR-proANP are useful as predictor for arrhythmic death in patients with ICM.

High incidence of atrial fibrillation after successful catheter ablation of atrioventricular nodal reentrant tachycardia: a 15.5-year follow-up.

Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common type of supraventricular tachycardia. Slow pathway (SP) ablation is the treatment of choice with a high acute success rate and a negligible periprocedural risk. However, long-term outcome data are scarce. The aim of this study was to assess long-term outcome and arrhythmia free survival after SP ablation. In this study, 534 consecutive patients with AVNRT, who underwent SP ablation between 1994 and 1999 were included. During a mean follow-up of 15.5 years, 101 (18.9%) patients died unrelated to the procedure or any arrhythmia. Data were collected by completing a questionnaire and/or contacting patients. Clinical information was obtained from 329 patients (61.6%) who constitute the final study cohort. During the electrophysiological study, sustained 1:1 slow AV nodal pathway conduction was eliminated in all patients. Recurrence of AVNRT was documented in 9 patients (2.7%), among those 7 patients underwent a successful repeat ablation procedure. New-onset atrial fibrillation (AF) was documented in 39 patients (11.9%) during follow-up. Pre-existing arterial hypertension (odds ratio 2.61, 95% CI 1.14-5.97, p = 0.023), age (odds ratio 1.05, 95% CI 1.02-1.09, p = 0.003) and the postinterventional AH interval (odds ratio 1.02, 95% CI 1.00-1.04, p = 0.038) predicted the occurrence of AF. The present long-term observational study after successful SP ablation of AVNRT confirms its clinical value reflected by low recurrence and complication rates. The unexpectedly high incidence of new-onset AF (11.9%) may impact long-term follow-up and requires further clinical attention.

Implantable loop recorder in unexplained syncope: classification, mechanism, transient loss of consciousness and role of major depressive disorder in patients with and without structural heart disease.

OBJECTIVE: To stratify mechanisms and predictors of unexplained syncope documented by an implantable loop recorder (ILR) in patients with and without structural heart disease (SHD). DESIGN AND SETTING: Prospective study in consecutive patients of a university cardiac centre. PATIENTS AND METHODS: An ILR was implanted in 70 patients (34 male/36 female, aged 55 (17) years) in whom syncope remained unexplained after thorough testing. SHD was present in 33 patients (ischaemic cardiomyopathy in 16, dilated cardiomyopathy in 9 and hypertrophic cardiomyopathy in 8) and absent in 37 patients (mean (SD) left ventricular ejection fraction 46 (4)% vs 61 (7)%, respectively). RESULTS: A syncopal recurrence occurred during 16 (8) months in 30 patients (91%) with SHD and in 30 patients (81%) without SHD. Fifteen patients (45%) versus 19 patients (51%), respectively, had an ILR-documented arrhythmia at the time of recurrence which led to specific treatment. The remaining 15 patients (45%) with SHD and 11 patients (30%) without SHD had normal sinus rhythm at the time of the recurrence. On stepwise multivariate analysis only major depressive disorder was predictive for early recurrence during ILR follow-up (p = 0.01, hazard ratio = 3.35, 95% CI 1.1 to 7.1). Fifty seven per cent of patients with major depressive disorder had sinus rhythm during recurrence compared with 31% of patients without the disorder (p = 0.01). Conversely, no patient with major depressive disorder had asystole compared with 33% without (p<0.001). CONCLUSIONS: The presence of SHD has little predictive value for the occurrence or type of arrhythmia in patients with unexplained syncope. Patients with major depressive disorder are prone to early recurrence of symptoms and have no evidence of arrhythmia in most cases. The ILR leads to specific treatment in half of all patients.

Core and skin surface temperature course after normothermic and hypothermic cardiopulmonary bypass and its impact on extubation time.

BACKGROUND AND OBJECTIVE: Cardiopulmonary bypass is associated with temperature pertubations that influence extubation time. Common extubation criteria demand a minimum value of core temperature only. The aim of this prospective study was to test the hypothesis that changes in core and skin surface temperature are related to extubation time in patients following normothermic and hypothermic cardiopulmonary bypass. METHODS: Forty patients undergoing cardiac surgery were studied; 28 patients had normothermic cardiopulmonary bypass (nasopharyngeal temperature >35.5 degrees C) and 12 had hypothermic cardiopulmonary bypass (28-34 degrees C). In the intensive care unit, urinary bladder temperature and skin surface temperature gradient (forearm temperature minus fingertip temperature: >0 degrees C = vasoconstriction, < or =0 degrees C = vasodilatation) were measured at 30-min intervals for 10 h postoperatively. At the same intervals, the patients were evaluated for extubation according to common extubation criteria. RESULTS: On arrival in the intensive care unit the mean urinary bladder temperature was 36.8 +/- 0.5 degrees C in the normothermic group and 36.4+/-0.3 degrees C in the hypothermic group (P = 0.014). The skin surface temperature gradient indicated severe vasoconstriction in the both groups. The shift from vasoconstriction to vasodilatation was faster in normothermic cardiopulmonary bypass patients (138+/-65 min) than in patients after hypothermic cardiopulmonary bypass (186+/-61 min, P = 0.034). There was a linear relation between the time to reach a skin surface temperature gradient = 0 degrees C and extubation time (r2 = 0.56, normothermic group; r2 = 0.82, hypothermic group). CONCLUSIONS: The transition from peripheral vasoconstriction to vasodilatation is related to extubation time in patients following cardiac surgery under normothermic as well as hypothermic cardiopulmonary bypass.

Prolonged asystole provoked by head-up tilt testing.

We describe a patient with a history of neurocardiogenic syncopes who had a positive headup tilt test that resulted in an lasting asystole lasting 34 seconds. However, the previously carried out Schellong test with a 30-min phase of standing showed a normal result. The patient showed typical orthostatic symptoms while tilted at the angle of 75 degrees. Shortly before asystole occurred, heart rate variability showed high frequency bands, indicating vagal stimulation. The pathophysiology of neurocardiogenic syncope (NCS) in context with heart rate variability is discussed. This patient was successfully treated with propranolol. This case shows the utility of a provocative head-up tilt test in establishing the diagnosis of NCS. If the Schellong test is normal, still further examination by tilt-table test is indispensable.

Unexplained syncope in patients with structural heart disease and no documented ventricular arrhythmias: value of electrophysiologically guided implantable cardioverter defibrillator therapy.

AIMS: To evaluate electrophysiologically guided implantable cardioverter defibrillator (ICD) therapy in patients with syncope, structural heart disease and no documented sustained ventricular tachycardia (sVT). METHODS AND RESULTS: Programmed ventricular stimulation (PVS) was performed in 52 patients (age 62+/-10 years): 40 patients had ischaemic and 12 patients had idiopathic dilated cardiomyopathy. On PVS sVT and ventricular fibrillation were induced in seven and four patients, respectively, and two patients spontaneously experienced symptomatic sVT. These patients received an ICD (ICD group, n=13). Non-inducible patients were left on conventional therapy (non-ICD group, n=39). During 5+/-2.8 years five ICD patients received therapies, all appropriate. There were seven non-sudden deaths and overall survival analysis revealed no significant difference. Recurrent syncope occurred in five ICD and four non-ICD patients and did not correlate well with sVT. The positive and negative predictive values of PVS for tachyarrhythmias or sudden death were 36 and 98%, respectively. CONCLUSION: Syncope per se does not necessarily herald a bad prognosis. PVS identifies high-risk patients. Induction of ventricular fibrillation with double or triple extrastimuli is of limited value. Patients with poor left ventricular function and bad clinical condition benefit most from an ICD. Syncope and sVT are not necessarily correlated during follow-up, which may merit consideration.

Can hypocapnia reduce cerebral embolization during cardiopulmonary bypass?

BACKGROUND: Cerebral embolization is a major cause of central nervous dysfunction after cardiopulmonary bypass. Experimental studies demonstrate that reductions in arterial carbon dioxide tension (PaCO2) can reduce cerebral embolization during cardiopulmonary bypass. This study examined the effects of brief PaCO2 manipulations on cerebral embolization in patients undergoing cardiac valve procedures. METHODS: Patients were prospectively randomized to either hypocapnia (PaCO2 = 30 to 32 mm Hg, n = 30) or normocapnia (PaCO2 = 40 to 42 mm Hg, n = 31) before aortic cross-clamp removal. With removal of the aortic cross-clamp embolic signals were recorded by transcranial Doppler ultrasonography for the next 15 minutes. RESULTS: Despite significant differences in PaCO2, groups did not differ statistically in total cerebral emboli counts. The mean number of embolic events was 107 +/- 100 (median, 80) in the hypocapnic group and 135 +/- 115 (median, 96) in the normocapnic group, respectively (p = 0.315). CONCLUSIONS: Due to the high between-patient variability in embolization, reductions in PaCO2 did not result in a statistically significant decrease in cerebral emboli. In contrast to experimental studies, the beneficial effect of hypocapnia on cerebral embolization could not be demonstrated in humans.

The use of the antioxidant tirilazad mesylate in human liver transplantation: is there a therapeutic benefit?

OBJECTIVES: To test the hypothesis whether in patients undergoing liver transplantation the antioxidant tirilazad mesylate can reduce hepatic ischaemia-reperfusion injury and improve postoperative outcome. DESIGN: Prospective, randomised, placebo controlled trial. SETTING: University hospital. PATIENTS: 20 patients were randomised to receive either tirilazad mesylate or placebo (saline). INTERVENTIONS: Patients in the tirilazad group (n = 10) received four intravenous infusions of tirilazad at 6-h intervals (men 3 mg/kg, women 3.75 mg/kg) after the induction of anaesthesia. The other patients (n = 10) served as controls. MEASUREMENTS AND RESULTS: Plasma levels of malonaldehyde (MDA) were determined after the induction of anaesthesia prior to the infusion of tirilazad (baseline), during the anhepatic period, and 5 min and 24 h after reperfusion. Postoperatively, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and serum cholinesterase were determined daily for 1 week. Compared to baseline, plasma MDA levels did not significantly change during the anhepatic period and after reperfusion and they did not differ between groups. Postoperative liver enzymes and prothrombin time did not differ between groups, but on the first (p = 0.03) and second (p = 0.01) postoperative day cholinesterase levels were significantly higher in tirilazad-treated patients than in control patients. For neither length of stay in the intensive care unit nor hospital stay were any differences observed between groups. CONCLUSIONS: In patients undergoing liver transplantation, tirilazad does not improve overall outcome. Whether the higher cholinesterase levels on the first 2 postoperative days in tirilazad treated patients indicates an earlier recovery of liver function remains to be tested.

[Protein catabolism after lung transplantation and heart transplantation]. / Eiweisskatabolismus nach Lungentransplantation und Herztransplantation.

Any surgical intervention is associated with an activation of protein catabolism, the extent of which is dependent on the severity of surgical trauma. There is a paucity of reports on protein catabolism after transplantation of chest organs (lung transplantation (LTX) and heart transplantation (HTX)). The aim of the present study was to quantify and compare the extent of postoperative protein catabolism and associated metabolic perturbations in patients after LTX and HTX. Eighteen consecutive patients after LTX and 15 consecutive patients after HTX who required postoperative intensive care for more than 4 days, constituted the study population. The nitrogen balance (assessed on the basis of the urea nitrogen production rate and nitrogen intake) was assessed retrospectively and correlated with insulin requirements, immunosuppression and the clinical course. Within the first 5 days the nitrogen balance became progressively negative in both groups, reaching a maximum on the 5th day. Thereafter the nitrogen balance of patients following LTX remained negative, whereas the nitrogen balance of patients following HTX tended to improve. The evolution of nitrogen balance significantly differed between both groups (p < 0.01). The mean nitrogen loss was -0.29 +/- 0.17g/kg BW/day after LTX versus -0.22 +/- 0.12g/kg BW/day after HTX. Smaller amounts of glucocorticoids were used for immunosuppression in patients after HTX than in patients after LTX; nevertheless, heart transplant recipients required higher doses of insulin to maintain normoglycemia. A regression analysis revealed that the duration of stay at the intensive care unit (p < 0.001) and the amount of glucocorticoids (p < 0.01) negatively affected the nitrogen balance, whereas an increased protein intake (p < 0.001) exerted a positive effect. Compared to other major surgical procedures, protein catabolism is excessively elevated in patients after thoracic transplantation. Immunosuppressive therapy with glucocorticoids contributes to protein degradation; the nitrogen balance after LTX is more negative than that after HTX because of higher glucocorticoid requirements following LTX. More aggressive nutritional intervention and especially an increased nitrogen intake might help to reduce protein losses in these patients.

Nitric oxide concentration in the gas phase of the gastrointestinal tract in man.

Nitric oxide (NO) has been implicated in various aspects of physiological regulation in the gastrointestinal tract. Hence, measurement of luminal NO concentrations is of interest for studying physiological and pathophysiological alterations in NO generation; however, at present, no reliable measurement techniques are available. Here we describe novel approaches for measurement of NO concentrations directly in the gas phase of the stomach and colon in healthy subjects and patients. Studies were conducted in young healthy volunteers (n = 13), intensive care patients (n = 8) and patients undergoing gastroscopy (n = 8) or colonoscopy (n = 8). NO concentrations were measured by chemolumininescence detection in air obtained through a nasogastric tube, after inflation into the stomach of a defined volume of air, or directly in the air suctioned from the endoscope. The mean NO concentration obtained from the stomach of healthy volunteers studied under baseline conditions was 18.0 +/- 2.8 (SEM) p.p.m. Day-to-day reproducibility of NO measurements was high. Tube feeding with a nitrite- and nitrate-free feeding solution left gastric NO concentrations unchanged, but standardized bicycle exercise caused an approximately 30% decrease in NO levels. NO concentrations in intensive care patients were approximately 2 log cycles lower than in healthy volunteers. NO levels in the colon were similar to those in the stomach. We have described two readily applicable techniques for direct, uncontaminated measurement of NO concentrations in the lumen of the gastrointestinal tract. Our finding of a striking reduction in gastric NO concentrations in intensive care patients requires further study.