Role of proinflammatory markers and NT-proBNP in patients with an implantable cardioverter-defibrillator and an electrical storm.

BACKGROUND: Several studies have attempted to identify risk factors for the development of an electrical storm (ES), which is defined as 3 separate ventricular tachyarrhythmic (VT/VF) events, but in the majority of studies no triggers have been found. However, little is known about the role of inflammation and NT-proBNP in patients with ES. The aim of this study was therefore to assess the relationship of Interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) and NT-proBNP serum concentrations in ICD-patients with or without single spontaneous ventricular tachyarrhythmic events (VT/VF) and in ES. METHODS: Markers were determined in 51 patients without ICD-intervention, in 15 ICD-patients with single VT/VF-episodes during 9-months follow-up and in 20 ICD-patients with ES (blood sampling performed within 60min after fulfilling ES criteria). VT/VF-episodes were analysed by stored ICD-electrograms. RESULTS: All patients had idiopathic dilated cardiomyopathy (n=23) or coronary artery disease (n=63). Patients with ES revealed significantly higher mean serum concentrations of all markers (IL-6 15.19+/-10.34 pg/mL, hs-CRP 20.12+/-14.4 mg/L, NT-proBNP 4799+/-4596 pg/mL) compared to baseline values of patients with single VT/VF-events during follow-up (IL-6 8.37+/-5.8 pg/mL (p=0.03), hs-CRP 4.7+/-5.3 mg/dL (p<0.001), NT-proBNP 1913+/-2665pg/mL (p=0.04)) and compared to baseline values of ICD-patients without device intervention (IL-6 4.62+/-3.66 pg/mL (p<0.001), hs-CRP 4.1+/-3.4 mg/L (p<0.001), NT-proBNP 1461+/-2281pg/mL (p<0.001)). In 9/20 patients presenting with ES (45%) baseline values were available. All markers were significantly higher during ES compared to event-free determination (IL-6 14.54+/-10.43 vs. 7.03+/-2.83 pg/mL (p=0.04), hs-CRP 19.07+/-16.07 vs. 6.5+/-3.9 mg/L (p=0.02), NT-proBNP 4218+/-2561 vs. 2099+/-1279 pg/mL (p=0.03)). CONCLUSIONS: Electrical storm is associated with significantly elevated IL-6, hs-CRP and NT-proBNP serum concentrations in ICD-patients with structural heart disease. Thus, ES may be triggered by proinflammatory activity. Combined intraindividual elevation of determined markers might help to identify patients at risk of impending electrical storm.

Effects of xanthine oxidase inhibition with allopurinol on endothelial function and peripheral blood flow in hyperuricemic patients with chronic heart failure: results from 2 placebo-controlled studies.

BACKGROUND: In patients with chronic heart failure (CHF), hyperuricemia is a common finding and is associated with reduced vasodilator capacity and impaired peripheral blood flow. It has been suggested that the causal link of this association is increased xanthine oxidase (XO)-derived oxygen free radical production and endothelial dysfunction. We therefore studied the effects of XO inhibition with allopurinol on endothelial function and peripheral blood flow in CHF patients after intra-arterial infusion and after oral administration in 2 independent placebo-controlled studies. METHODS AND RESULTS: In 10 CHF patients with normal serum uric acid (UA) levels (315+/-42 micromol/L) and 9 patients with elevated UA (535+/-54 micromol/L), endothelium-dependent (acetylcholine infusion) and endothelium-independent (nitroglycerin infusion) vasodilation of the radial artery was determined. Coinfusion of allopurinol (600 microg/min) improved endothelium-dependent but not endothelium-independent vasodilation in hyperuricemic patients (P<0.05). In a double-blind, crossover design, hyperuricemic CHF patients were randomly allocated to allopurinol 300 mg/d or placebo for 1 week. In 14 patients (UA 558+/-21 micromol/L, range 455 to 743 micromol/L), treatment reduced UA by >120 micromol/L in all patients (mean reduction 217+/-15 micromol/L, P<0.0001). Compared with placebo, allopurinol improved peak blood flow (venous occlusion plethysmography) in arms (+24%, P=0.027) and legs (+23%, P=0.029). Flow-dependent flow improved by 58% in arms (P=0.011). Allantoin, a marker of oxygen free radical generation, decreased by 20% after allopurinol treatment (P<0.001). There was a direct relation between change of UA and improvement of flow-dependent flow after allopurinol treatment (r=0.63, P<0.05). CONCLUSIONS: In hyperuricemic CHF patients, XO inhibition with allopurinol improves peripheral vasodilator capacity and blood flow both locally and systemically.

Elevated serum levels of leptin and soluble leptin receptor in patients with advanced chronic heart failure.

Patients with chronic heart failure (CHF) have metabolic abnormalities, leading to a catabolic syndrome, with progressive loss of skeletal muscle in advanced stages of the disease. Leptin, the product of an obesity gene, has been associated with energy expenditure and weight regulation. The aim of this study was to assess serum levels of leptin and its soluble receptor in relation to exercise intolerance and neurohumoral activation in patients with CHF. We investigated 53 patients with CHF left ventricular ejection fraction (LVEF) 25+/-1%, age 56.6+/-1.3 years, Maximal oxygen uptake (VO(2) max) 16.3+/-0.6 ml/min.kg) sub-classified according to peak oxygen consumption of > or 14 ml/min.kg and controls). Elevated levels of leptin correlated with an increased serum concentration of TNFalpha (r=0.749, P<0.01) in this subgroup of patients with CHF. We conclude that patients with advanced CHF show elevated serum levels of leptin and its soluble receptor. This finding indicates that leptin may participate in the catabolic state leading to the development of cardiac cachexia in the course of CHF.

Capsule Endoscopy in a Patient with an Implanted CCM System and an Implantable Defibrillator.

Wireless video capsule endoscopy (CE) is a modern diagnostic tool. Because of its use of digital radiofrequency, it is still relatively contraindicated in patients with implanted cardiac devices. We report the case of a patient with an Optimizer III system delivering cardiac contractility modulating signals (CCM) for heart failure therapy and an implantable cardioverter defibrillator (ICD) who underwent CE. No interferences between the devices were found.

Prevention of inappropriate ICD shocks in patients with Brugada syndrome.

BACKGROUND: In Brugada syndrome implantable cardioverter defibrillator (ICD) therapy is associated with a high rate of inappropriate therapies, mainly due to supraventricular tachyarrhythmias (SVT) (2.7-14.1%/year). Aim of the present study was to evaluate a single ventricular fibrillation (VF) detection zone with a high cut-off rate with respect to prevention of inappropriate ICD shock due to SVT and safety of this programming. METHODS: Sixty-one consecutive patients (mean age 42.6 +/- 12.9 years; 41 males) diagnosed with Brugada syndrome and implanted with an ICD were included. ICDs were prospectively programmed with a single VF detection zone and a cut-off rate of 222 beats/minute (bpm). A maximum of six shocks with the maximal shock energy were programmed. The minimal follow-up was 1 year. RESULTS: During a follow-up of 47.6 +/- 23.1 months seven patients (2.91%/year) received appropriate ICD shocks. No patient suffered from syncope or died. Five patients (2.07%/year) received inappropriate ICD shocks: four patients due to T-wave oversensing and only one patient (0.4%/year) due to SVT (atrial fibrillation with a ventricular rate of >222 bpm). CONCLUSIONS: Programming of a single, high-rate VF zone in patients with Brugada syndrome and an implanted defibrillator is safe. Such programming may be associated with reduced inappropriate defibrillator discharges. A single detection zone with a high VF cut-off rate can be recommended in patients with Brugada syndrome.

Functional and morphological skeletal muscle abnormalities correlate with reduced electromyographic activity in chronic heart failure.

BACKGROUND: Exercise intolerance and early muscle fatigue are key symptoms in patients with chronic heart failure (CHF). In advanced stages of the disease, profound metabolic abnormalities have been described finally leading to a catabolic state with progressive loss of muscle bulk. The aim of this study was to investigate morphological, functional and electromyographical parameters of the skeletal muscle in CHF. METHODS: We included 17 patients with CHF and 12 age-matched healthy controls (left ventricular ejection fraction 25+/-2 versus 68+/-1%, body mass index 26.6+/-0.8 versus 28.0+/-1.0 kg/m2; P=NS) in this study. Cross-sectional area (CSA) of the thigh was assessed by computed tomography. Under electromyographical control, maximal and submaximal (30%) isometric strength as well as the relative decrease of muscle strength of the quadriceps muscle over a period of 20 s were determined. RESULTS: Patients with CHF showed a significant reduction of muscle CSA (134.8+/-5.3 versus 165.2+/-7.4 cm2, P=0.002) as compared with healthy controls. The maximal quadriceps muscle strength was found to be significantly reduced in patients with CHF (226.7+/-22.3 versus 286.9+/-17.1 N, P<0.05) who also exhibited a higher extent of muscular fatigability (-2.18+/-0.33 versus -0.54+/-0.20 N/s, P<0.01). Electromyographic activity at 30% submaximal contraction showed a lower increase in patients with CHF (66+/-22 versus 114+/-36%; P<0.05) indicating impaired muscle fibre recruitment. Furthermore, a significant correlation between muscular fatigability and reduced electromyographic activity was found in CHF (r=0.84; P<0.001). CONCLUSIONS: Our findings demonstrate an impaired electromyographic activity and muscular function in patients with CHF suggesting a new pathomechanism contributing to functional abnormalities of the skeletal muscle in advanced stages of this disease.