-
[show abstract]
[hide abstract]
ABSTRACT: AIMS: Implantable cardioverter defibrillators (ICDs) have shown to reduce all-cause mortality in heart failure patients. In SCD-HeFT study, ICDs were programmed with a detection zone of ≥187 b.p.m. Thus, the incidence and clinical significance of slower ventricular tachycardias (VTs) in these patients remains largely unknown, though clinically important for device selection, programming, and follow-up.METHODS AND RESULTS: We prospectively studied symptomatic heart failure patients with an indication for a primary prophylactic ICD with or without concomitant resynchronization therapy according to SCD-HeFT inclusion criteria. Devices were programmed to an additional monitor zone for slow VTs at heart rates 130-186 b.p.m. Two hundred consecutive patients (86% male) were followed for a mean of 509 ± 308 days. One hundred and thirty-seven patients (68.5%) were New York Heart Association class III, 75 patients (37.5%) were on cardiac resynchronization therapy, and 124 (62%) had ischaemic cardiomyopathy. We observed 473 VT episodes in 36 patients (18%) and 131 ventricular fibrillation episodes in 30 patients (15%). Ventricular tachycardia overall occurred in 40 patients (20%). The incidence of slow VTs was low in only 12 patients (6%). No patient with slow VT suffered from syncope, palpitation, or decompensation leading to hospitalization. We did not find any reliable predictor for increased long-term risk of slow VTs.CONCLUSION: Incidence of slow VTs in a typical heart failure population with primary prophylactic ICD-implantation ± resynchronization therapy is very low. Slow VTs detected in the ICD monitor zone remained clinically asymptomatic. Thus, single chamber and atriobiventricular ICDs with a VT/ventricular fibrillation zone of ≥187 b.p.m. and one burst before shock delivery might be sufficient and pragmatic for the vast majority of these patients.
Europace 01/2013; · 1.98 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Asymptomatic bacterial colonisation of medical implants is increasingly recognised. The role of the often unusual bacteria is usually unknown however.
During a three-year period, patients presenting with clinically evident CIED lead endocarditis and/or pocket infections were included in a prospective database. Using 16s DNA analysis and sequencing, devices and pockets of consecutive patients with evident CIED infection were examined for the presence of bacterial species in addition to the ones grown in conventional culture in order to characterise their clinical role.
During the study 77 of a total of 409 consecutive operations involving the explantation of a CIED were performed for clinically evident infection. 71 were included in the study and conventional extended culture and 16s DNA analysis performed and compared. In 42.3% of the patients bacteria were identified by DNA analysis in addition to the culture of the supposedly causative organisms.
DNA analysis is more sensitive than conventional culture of swabs in detecting any, or indeed multiple bacterial strains in CIED infection. This may in future influence treatment strategies as e.g. the cohabitation of different strains seems common and is not reflected by classical culture results. Spread of infection along the leads was clearly demonstrated and this strongly supports the recommendation of complete removal of all CIED components in every form of CIED infection. The more unusual bacteria demonstrated here do not appear to play a significant clinical role as suspected earlier.
Technology and health care: official journal of the European Society for Engineering and Medicine 01/2013; 21(1):87-96.
-
[show abstract]
[hide abstract]
ABSTRACT: Restenosis after PCI and/or stent implantation is still one of the challenging problems in the field of interventional cardiology. Different approaches to prevent and to treat restenosis include the use of drug-eluting stents, which have shown to reduce restenosis. Another approach is the treatment with drug-coated balloons. This approach has been proven for different indications, e.g., in-stent restenosis and treatment of peripheral artery disease.
Patients from the PEPCAD III multicentre randomised trial in two study centres (Homburg and Hannover, Germany) were asked to participate in this intravascular ultrasound (IVUS) study at nine-month follow-up. At baseline (nine months before), patients were randomly assigned to receive either a paclitaxel-coated balloon (drug-coated balloon [DCB]) plus a premounted bare metal stent (DCB/BMS) or a sirolimus-eluting stent (drug-eluting stent [DES]) to treat de novo lesions. IVUS at follow-up was performed in order to analyse the restenosis for potential understanding of the mechanism leading to restenosis. IVUS data is available for 55 patients; 26 patients were treated with Cypher(®) DES (Cordis, Miami Lakes, FL, USA) and 29 patients with DCB/BMS. A focal malapposition of the stent was seen in six patients; four after DES and two after DCB/BMS. Stent expansion, calculated as symmetric expansion index, was equal for both groups (0.89 and 0.90). Mean stent area was also equal for both groups (6.25 ± 1.7 vs. 5.65 ± 1.5 mm(2), p=n.s.). The neointimal hyperplasia (calculated as stent area minus lumen area) was significantly different between both groups (0.69 ± 0.49 [DES] vs. 1.08 ± 0.53 mm(2) [DCB/BMS], p<0.01). This resulted in a significantly higher in-stent restenosis in the DCB/BMS group (19.7 vs. 11 %, p<0.01). There is no evidence of geographical mismatch.
First IVUS insights for the DCB/BMS showed a comparable, low incidence of malapposition for the combination of drug-coated balloon and premounted bare metal stent compared to the DES, and stent expansion was good and comparable to DES. However, at nine-month follow-up, the combination of drug-coated balloon and premounted bare metal stent showed higher in-stent restenosis compared to sirolimus DES. Geographical mismatch can be excluded as a reason for this result.
EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 08/2012; 8(4):450-5. · 3.29 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Dronedarone is a new antiarrhythmic drug for patients with nonpermanent atrial fibrillation (AF). A relatively consistent finding in all trials studying dronedarone was a moderate but significant elevation of serum creatinine. Since dronedarone competes for the same organic cation transporter in the distal renal tubule with creatinine, serum creatinine and its derived estimated glomerular filtration rate might not reflect true renal function in patients on dronedarone. We therefore investigated alternative markers for renal function in these patients. We prospectively included 20 patients with nonpermanent AF in whom dronedarone 400 mg twice daily was started. Patients had normal renal function and serum creatinine; serum cystatin C and creatinine clearance were measured before treatment and 10 and 90 days after treatment started. Mean serum creatinine level for all 20 patients at baseline (day 0) was 84.55 ± 12.14 and 87.8 ± 17.59 µmol/L on day 10. This slight increase in all patients was not significant. Patients were now divided into the predefined groups of "increased creatinine" (increase in serum creatinine level > 1 standard deviation) and "not increased creatinine." Patients with increased creatinine levels (n = 5) showed a significant elevation of serum creatinine levels from day 0 to day 10 (82.4 ± 9.18 to 104.4 ± 12.74 µmol/L; P = .003), whereas change in serum creatinine levels in the not increased creatinine group (n = 15) was not significant. Serum cystatin C levels remained stable in both of these groups (increased creatinine group: 0.76 ± 0.08 to 0.78 ± 0.08 mg/L; P = .65; not increased creatinine group: 0.77 ± 0.108 to 0.77 ± 0.107 mg/L; P = .906). In conclusion, cystatin C represents an easily available and reliable biomarker for estimation of true renal function in patients on dronedarone treatment.
Journal of Cardiovascular Pharmacology and Therapeutics 07/2012; · 1.75 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: RF ablation for cavotricuspid isthmus (CTI) dependent flutter is an established therapy. Right atrial hypertrophy and enlargement are associated with the occurrence of cavotricuspid isthmus dependent flutter. Therefore, patients with pulmonary hypertension (PAH) are prone to atrial arrhythmias like cavotricuspid isthmus dependent flutter. However, the influence of PAH on typical atrial flutter ablation procedure has not been systematically examined. METHODS: In a retrospective single-centre analysis data of patients undergoing an ablation procedure for cavotricuspid isthmus dependent flutter between January 2007 and October 2009 at Hannover Medical School, Germany were analysed. Only procedures performed by experienced electrophysiologists with an 8mm RF-ablation catheter were included. Data for 196 patients were analysed. Thirty-eight patients were identified with PAH and were compared to 158 patients without PAH for procedural ablation parameters, procedure time, ablation time, ablation points and fluoroscopy time. RESULTS: A bidirectional block of the CTI was achieved in all patients. Patients with severe PAH had a significantly longer procedure time (78±40min vs. 62±29min; p=0.033), total ablation time (20±11min vs. 15±9min; p=0.02) and more ablation lesions (26±16 vs. 19±12; p=0.018) as compared to patients without PAH. CONCLUSION: Cavotricuspid isthmus dependent flutter ablation in patients with PAH is associated with longer procedure duration and a greater amount of cumulative tissue ablation needed to achieve bidirectional block of the CTI compared to patients without pulmonary hypertension.
Heart Lung & Circulation 07/2012; · 1.20 Impact Factor
-
Sören Laurisch,
Maren Jaedtke,
Reyhan Demir,
Sajoscha A. Sorrentino,
Jan T. Kielstein,
Hans-Oliver Rennekampff,
Peter M. Vogt,
Gerd P. Meyer,
Martin Fuchs, Gunnar Klein,
Hartmut Drexler †,
Bernhard Schieffer,
L. Christian Napp
[show abstract]
[hide abstract]
ABSTRACT: Die vorliegende Kasuistik schildert den Fall eines 67-jährigen Patienten, der ein allopurinolinduziertes Hypersensitivitätssyndrom
(AHS) mit toxisch- epidermaler Nekrolyse entwickelte und in der Folge an einem septischen Multiorganversagen verstarb. Mit
dieser Falldarstellung soll in Anbetracht der zunehmenden Verschreibungshäufigkeit von Allopurinol die unterschätzte Gefahr
eines AHS demonstriert werden.
The present report describes the case of a 67-year-old patient who developed an allopurinol-induced hypersensitivity syndrome
(AHS) with toxic epidermal necrolysis and subsequently died of septic multiorgan failure. Considering the increasing prescription
rate of allopurinol, the present case report intends to demonstrate the underestimated threat of AHS.
Schlüsselwörter:
Allopurinol-Hyperurikämie-Niereninsuffizienz-Hypersensitivitätssyndrom-Toxisch-epidermale Nekrolyse-Stevens-Johnson- Syndrom
Key Words:
Allopurinol-Hyperuricemia-Chronic kidney disease-Hypersensitivity syndrome-Toxic epidermal necrolysis-Stevens-Johnson syndrome
04/2012; 105(4):262-266.
-
[show abstract]
[hide abstract]
ABSTRACT: Patients with patent foramen ovale (PFO) and cryptogenic stroke are at risk of recurrence. Therapeutic regimens range from no treatment to anticoagulation treatment to surgical or interventional closure. However, long-term follow-up is only available for up to 4 years.
Among ~5,000 transesophageal echocardiographies in stroke/TIA-patients between 1988 and 1997, a PFO was found and considered a possible mediator for the neurological event in 97 patients. In these patients, the PFO was judged to be responsible for the neurological event. Patients with cardiac or other reasons for embolism were excluded. The therapy for stroke was chosen by the attending physician. Follow-up information was obtained through telephone interviews.
Follow-up was available for 86 patients (89%) with a mean period of 15.4 years (range, 11.2-25.9 years). Thirteen patients (15%) suffered from recurrent ischemic events (7 TIAs, 5 strokes, 1 peripheral embolism) after a mean period of 4.9 years. Four patients died, not associated with recurrent thromboembolism. The risk of recurrence was increased over the entire length of the mean follow-up period. The occurrence of recurrent events was not associated with differences in baseline data, the presence of ASA, PFO size or the chosen treatment.
In patients with paradoxical embolism, recurrent ischemic events are frequent despite medical therapy. These events are not limited to the early years after the index event; this long-term follow-up revealed a risk of occurrence over the entire follow-up. These patients have a sustained risk of recurrence, requiring lifetime protection, which should be considered in tailoring individual therapeutic strategies.
Clinical Research in Cardiology 12/2011; 101(4):297-303. · 2.95 Impact Factor
-
International journal of cardiology 07/2011; 155(1):e13. · 7.08 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Pacemaker and implantable cardioverter defibrillator lead endocarditis mandates removal of all foreign material. In supposedly limited (pocket) infections, such a radical approach is still controversial. Thus, some patients are potentially exposed to persistent and recurrent infection because of retained material. Procedural risks and the success of eradicating infection were examined if involvement of the complete system was assumed in any cardiovascular implantable electronic device infection and complete removal was thus mandatory.
A 12-year experience with 192 consecutive cases of bacterial pacemaker (152) or defibrillator (40) infections is presented. Complete removal of all prosthetic material was always aimed for. This was followed by antibiotic treatment for 4 to 6 weeks under temporary pacing if required, and then the new system was implanted. A total of 104 parameters concerning patient characteristics and operative and postoperative treatment were examined for their influence on outcome.
Infection was eradicated in 92.8% of patients. Recurrence was predominantly caused by failure to remove all prosthetic material (P < .001). If the protocol was strictly followed, infection was eradicated in 97.4% of patients. Conversely, 71.4% of patients with retained material showed recurrence. Further risk factors were poor dental hygiene and evidence of chronic subclinical infection. Morbidity and mortality of the interventional and open procedures were low. Open lead extraction was performed primarily in 34 patients (17.7%) and secondarily in 3 patients (1.9%). Temporary pacing and long-term antibiotic treatment were well tolerated.
Complete removal of prosthetic material in any cardiovascular implantable electronic device infection is safe and associated with low morbidity and mortality. Success of eradicating infection is high if all system components are removed. Temporary pacing in dependent patients may be performed safely on an outpatient basis.
The Journal of thoracic and cardiovascular surgery 05/2011; 142(6):1482-90. · 3.41 Impact Factor
-
Johannes Brachmann,
Michael Böhm,
Karin Rybak, Gunnar Klein,
Christian Butter,
Hanno Klemm,
Rolf Schomburg,
Johannes Siebermair,
Carsten Israel,
Anil-Martin Sinha,
Helmut Drexler
[show abstract]
[hide abstract]
ABSTRACT: AIMS: The Optimization of Heart Failure Management using OptiVol Fluid Status Monitoring and CareLink (OptiLink HF) study is designed to investigate whether OptiVol fluid status monitoring with an automatically generated wireless CareAlert notification via the CareLink Network can reduce all-cause death and cardiovascular hospitalizations in an HF population, compared with standard clinical assessment. Methods Patients with newly implanted or replacement cardioverter-defibrillator devices with or without cardiac resynchronization therapy, who have chronic HF in New York Heart Association class II or III and a left ventricular ejection fraction ≤35% will be eligible to participate. Following device implantation, patients are randomized to either OptiVol fluid status monitoring through CareAlert notification or regular care (OptiLink 'on' vs. 'off'). The primary endpoint is a composite of all-cause death or cardiovascular hospitalization. It is estimated that 1000 patients will be required to demonstrate superiority of the intervention group to reduce the primary outcome by 30% with 80% power. CONCLUSION: The OptiLink HF study is designed to investigate whether early detection of congestion reduces mortality and cardiovascular hospitalization in patients with chronic HF. The study is expected to close recruitment in September 2012 and to report first results in May 2014.
European Journal of Heart Failure 05/2011; 13(7):796-804. · 4.90 Impact Factor
-
Circulation 04/2011; 123(13):1451-3. · 14.74 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Prevalence of patent foramen ovale (PFO) with detectable right-to-left shunt is higher in young adults with transient ischemic attack (TIA) and stroke compared to the general population. So far, published series included different occluder systems, various indications and regimens of postprocedural anticoagulation. In our experience, occluder systems may be associated with an increased prevalence of thrombus formation, which has also reported by other groups. The aim of the present study was to evaluate the follow-up results after implantation of the Amplatzer® occluder in patients with PFO using a consistent anticoagulation regimen.
One-hundred and fourteen patients with PFO (60 men; age: 47 ± 13 years) and ≥1 thromboembolic event were included. Other causes for embolism were excluded. PFO-closure was successful in all patients. All patients were treated with aspirin (100 mg/day) and clopidogrel (75 mg/day) for 6 months. TEE was repeated at a mean of 10.3 months. Mean clinical follow-up period was 18 ± 9 months. After a mean of 10 months, no patient had either a significant residual shunt nor a suspected thrombus formation on the occluder. During follow-up, 5 patients suffered from neurological events (1 stroke, 2 TIAs, 2 epileptic seizures), though complete closure of the PFO was documented by TEE. One patient suffered from bleeding complications (upper GI-bleeding).
Percutaneous closure of PFO in symptomatic patients by Amplatzer® occluder represents an effective therapy with a low incidence of peri-interventional complications and recurrent thromboembolism. Thrombus formations on the occluder system were not detected in this cohort.
Journal of Interventional Cardiology 02/2011; 24(1):85-91. · 1.18 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Background: Prevalence of patent foramen ovale (PFO) with detectable right-to-left shunt is higher in young adults with transient ischemic attack (TIA) and stroke compared to the general population. So far, published series included different occluder systems, various indications and regimens of postprocedural anticoagulation. In our experience, occluder systems may be associated with an increased prevalence of thrombus formation, which has also reported by other groups. The aim of the present study was to evaluate the follow-up results after implantation of the Amplatzer® occluder in patients with PFO using a consistent anticoagulation regimen.Methods and Results: One-hundred and fourteen patients with PFO (60 men; age: 47 ± 13 years) and ≥1 thromboembolic event were included. Other causes for embolism were excluded. PFO-closure was successful in all patients. All patients were treated with aspirin (100 mg/day) and clopidogrel (75 mg/day) for 6 months. TEE was repeated at a mean of 10.3 months. Mean clinical follow-up period was 18 ± 9 months. After a mean of 10 months, no patient had either a significant residual shunt nor a suspected thrombus formation on the occluder. During follow-up, 5 patients suffered from neurological events (1 stroke, 2 TIAs, 2 epileptic seizures), though complete closure of the PFO was documented by TEE. One patient suffered from bleeding complications (upper GI-bleeding).Conclusion: Percutaneous closure of PFO in symptomatic patients by Amplatzer® occluder represents an effective therapy with a low incidence of peri-interventional complications and recurrent thromboembolism. Thrombus formations on the occluder system were not detected in this cohort. (J Interven Cardiol 2011;24:85–91)
Journal of Interventional Cardiology 01/2011; 24(1):85 - 91. · 1.18 Impact Factor
-
European Heart Journal 01/2011; 32(9):1076. · 10.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Left ventricular assist devices (LVAD) are an effective therapeutic option for end-stage heart failure (HF). Reduced heart rate variability (HRV) as a result of autonomic derangement is evident in chronic heart failure and several studies have established the independent prognostic value of HRV in chronic heart failure.
In the present study we investigated whether autonomic function is restored in patients after LVAD implantation with persistent, severely depressed left ventricular function.
Ambulatory Holter ECG recordings were collected in heart failure patients with an LVAD (n=8) und age-matched heart failure patients without an LVAD (n=7) both on optimal medical therapy. Cardiac dimensions and function were assessed by echocardiography or angiography.
Analysis for heart rate variability revealed reduced SDNN (67±4 ms), SDANN (56±4 ms) and triangular index (18±1) in heart failure patients on optimal medical therapy. However patients with LVAD demonstrated a restoration in heart rate variability with normal SDNN (108±9 ms), SDANN (103±8 ms) and triangular index (29±2). Compared to patients without LVAD this difference was statistically significant (p<0.01).
In end-stage heart failure patients autonomic imbalance indicated by severely reduced heart rate variability is restored after LVAD implantation with unloading of the failing heart.
The International journal of artificial organs 12/2010; 33(12):851-5. · 1.86 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the relation of echocardiographic parameters of diastolic function, exercise capacity (expressed as peakVO(2)) and NT-proBNP in patients with transposition of the great arteries (TGA) and Mustard procedure.
Diastolic function was determined by measuring tricuspid flow velocities (Ea/Aa ratio), isovolumic relaxation time (IVRT), and deceleration time (DT). E/Ea ratios were calculated. For assessment of systolic function, CMR was applied.
E/A (r = 0.07, p = 0.66), E/Ea medial (r = 0.03, p = 0.84), E/Ea lateral (r = -0.01, p = 0.92), IVRT (r = -0.13, p = 0.44), and DT (r = -0.05, p = 0.76) were not correlated with peakVO(2). NT-proBNP showed a significant correlation with IVRT (r = 0.44, p = 0.004) and Ea/Aa medial (r = -0.34, p = 0.025). No correlation was found between RV systolic function and peakVO(2) (r = 0.07, p = 0.63).
Exercise capacity in patients with TGA and Mustard procedure is not related to echocardiographic parameters of diastolic function. NT-proBNP is associated with selected echocardiographic parameters of diastolic function.
Cardiology 10/2010; 117(2):112-7. · 1.71 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Modulation of the intrinsic cardiac autonomic nervous system (ICANS) has been described to occur during radiofrequency pulmonary vein (PV) isolation for paroxysmal atrial fibrillation (AF) and has been controversially proposed to increase clinical success. Energy source used for PV isolation might influence ICANS modulation. The effect of balloon-delivered cryoenergy on the ICANS is unknown. We conducted a study investigating acute periprocedural effect on ICAN as well as changes in heart rate variability (HRV) for standard deviation of normal-to-normal intervals (SDNN) and triangular index (TI) as surrogates for ICANS modulation after cryoballoon PV isolation.
Fourteen consecutive patients without structural heart disease underwent cryoballoon PV isolation for paroxysmal atrial fibrillation. Acute changes in heart rate requiring pacing during the procedure were recorded. HRV was tested by Holter ECG for SDNN and TI before ablation and after 1 week, 1 month, and 3 months following ablation.
Fifty-five out of 56 PV were isolated (98%) with short-term 6-month freedom from paroxysmal AF of 64% by one single procedure. Five patients (36%) showed significant bradycardia during balloon thawing requiring temporary pacing. HRV decreased significantly immediately after PV isolation for both SDNN and TI until 1 month, gradually normalizing toward 3 months follow-up. HRV modulation was not different between patients with or without AF recurrences.
Cryoballoon PV isolation significantly modulates the ICANS, but only temporarily for up to 3 months, measured by HRV changes after ablation.
Journal of Interventional Cardiac Electrophysiology 10/2010; 29(1):57-62. · 1.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Increasing rates of bacterial infections in device therapy of cardiac rhythm disturbances pose a clinical problem. Radical surgical treatment yields the best long-term results but is frequently preceded by conservative treatment or limited surgical procedures leading to an unnecessary long treatment course. Recurrence/persistence of infection then potentially poses an even more serious clinical problem.
A total of 192 consecutive explantation procedures were performed for cardiac implantable electronic device (CIED) infections over a 10 year period. Forty-nine cases followed recurrence of infection subsequent to prior surgical treatment for device infection. Differences in patient/disease characteristics and outcome were looked for in recurrent as compared to primary infections (referral mode) to identify a potential requirement for adjusting treatment in recurrence. With a minimum follow-up of 24 months, 98% eradication of infection was observed independent of referral mode. Differences between primary and recurrent infection essentially reflected the primary presenting clinical picture-chronic smouldering vs. acute systemic infection. Various parameters that follow from this differentiation are significantly different between the groups. There was however no difference in outcome in terms of mortality and rate of recurrence. In addition, the parameters of the extraction procedure did not differ considerably.
Despite significant differences in baseline and disease characteristics between primary and recurrent CIED infection, a standardized radical protocol results in an equally high success rate in eradicating infection in both groups. Nevertheless, direct and un-delayed referral of patients with suspected CIED infection to specialized centres is recommended as it saves time for the patient.
Europace 09/2010; 12(9):1275-81. · 1.98 Impact Factor
-
Denise Hilfiker-Kleiner,
Praphulla Shukla, Gunnar Klein,
Arnd Schaefer,
Britta Stapel,
Melanie Hoch,
Werner Müller,
Michaela Scherr,
Gregor Theilmeier,
Matthias Ernst,
Andres Hilfiker,
Helmut Drexler
[show abstract]
[hide abstract]
ABSTRACT: In patients with myocardial infarction, high serum levels of interleukin-6 cytokines predict a poor outcome. The common receptor of interleukin-6 cytokines, glycoprotein-130 (gp130), signals via janus kinase/signal transducer and activator of transcription (STAT), cytoplasmic protein tyrosine phosphatase/extracellular signal-regulated kinase, and phosphoinositide-3-kinase/Akt pathways, and the regulation of these pathways depends at least in part on the gp130 tyrosine-757 residue. By analyzing cardiomyocyte-specific gp130(Y757F) mutant mice, we investigated the effect of disturbed gp130 signaling after myocardial infarction.
The cardiomyocyte-restricted alpha-myosin heavy chain-Cre-recombinase-loxP system was used to generate mice with gp130(Y757F) mutant cardiomyocytes (alphaMHC-Cre(tg/-);gp130(fl/Y757F) [Y(757)F]); all other cells carried at least 1 functional gp130 gene, ensuring normal gp130 signaling. Y(757)F mice displayed normal cardiac function and morphology at 3 months of age comparable to their nonmutant littermates. In response to myocardial infarction, Y(757)F mice displayed higher mortality associated with increased left ventricular rupture rate, sustained cardiac inflammation, and heart failure. These adverse effects were associated with prolonged and enhanced STAT3 activation and increased expression of interleukin-6 and of the complement-activating mannose-binding lectin C. Pharmacological inhibition of the complement system by cobra venom factor attenuated inflammation, prevented left ventricular rupture, and improved cardiac function in Y(757)F mice. Stronger effects were observed with a genetic reduction of STAT3 (STAT3(flox/+)) restricted to cardiomyocytes in Y(757)F mice, which prevented extensive upregulation of interleukin-6, complement activation, and sustained inflammation and lowered left ventricular rupture rate, heart failure, and mortality in subacute myocardial infarction.
Impaired downregulation of gp130-mediated STAT3 activation in subacute infarction promotes cardiac inflammation, adverse remodeling, and heart failure, suggesting a potential causative role of high interleukin-6 serum levels after myocardial infarction.
Circulation 07/2010; 122(2):145-55. · 14.74 Impact Factor
-
Pacing and Clinical Electrophysiology 07/2010; 33(7):909; author reply 910. · 1.35 Impact Factor
