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Jan Monti,
Judith Fischer,
Svetlana Paskas,
Matthias Heinig,
Herbert Schulz,
Claudia Gösele,
Arnd Heuser,
Robert Fischer,
Cosima Schmidt, Alexander Schirdewan, [......],
Martin Vingron,
Steven M Weldon,
Klaus Lindpaintner,
Bruce D Hammock,
Klaus Rohde,
Rainer Dietz,
Stuart A Cook,
Wolf-Hagen Schunck,
Friedrich C Luft,
Norbert Hubner
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ABSTRACT: MRI Results of the MACPAF Study. Background: Left atrial catheter ablation (LACA) is an established therapeutic approach to abolish symptomatic atrial fibrillation (AF). Objective: Based on the prospective MACPAF study (clinicaltrials.gov NCT01061931) we report the rate of ischemic brain lesions postablation and their impact on cognitive function. Methods: Patients with symptomatic paroxysmal AF were randomized to LACA using the Arctic Front® or the HD Mesh Ablator® catheter. All patients underwent brain MRI at 3 Tesla, neurological, and neuropsychological examinations within 48 hours prior and after the ablation procedure. Results: There was no clinically evident stroke in 37 patients (mean age 62.4 ± 8.4 years; 41% female; median CHADS2 score 1 [IQR 0-2]) after LACA but high-resolution diffusion-weighted imaging (DWI) detected new ischemic lesions in 15 (41%) patients after LACA. Four (27%) of the HD Mesh Ablator® patients and 11 (50%) of the Arctic Front® patients suffered a silent ischemic lesion (P = 0.19). In these 15 patients, there was a nonsignificant trend toward lower cardiac ejection fraction (P = 0.07) and AF episodes during LACA (P = 0.09), while activated clotting time levels, number of energy applications, periprocedural electrocardioversion or CHADS(2) score had no impact. Lesion volumes varied from 5 to 150 mm(3) and 1 to 5 lesions were detected per patient. However, acute brain lesions had no effect on cognitive performance immediately after LACA. Of the DWI lesions postablation 82% were not detectable on FLAIR images 6-9 months postablation. Conclusions: According to 3 Tesla high-resolution DWI, ischemic brain lesions after LACA were common but not associated with impaired cognitive function after the ablation procedure. (J Cardiovasc Electrophysiol, Vol. pp. 1-8).
Journal of Cardiovascular Electrophysiology 07/2012; · 3.06 Impact Factor
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Lydia Koch,
Karl Georg Haeusler,
Juliane Herm,
Erdal Safak,
Robert Fischer,
U Malzahn,
Thomas Werncke,
Peter U Heuschmann,
Matthias Endres,
Jochen B Fiebach,
Heinz-Peter Schultheiss, Alexander Schirdewan
[show abstract]
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ABSTRACT: Catheter ablation of the pulmonary veins (PVs) is a promising therapeutic approach for symptomatic atrial fibrillation (AF). The prospective randomized single-centre study 'Mesh Ablator versus Cryoballoon Pulmonary Vein Ablation of Symptomatic Paroxysmal Atrial Fibrillation' (MACPAF; clinicaltrials.gov NCT01061931) compared the efficacy and safety of two balloon-based PV ablation systems.
Thirty-two patients underwent PV ablation for symptomatic paroxysmal AF using the Arctic Front(®) or the HD Mesh Ablator(®) catheter according to study protocol. The primary endpoint was complete PV isolation (PVI) at the end of the ablation procedure, determined by exit block after achieving entrance block. Long-term follow-up data are not included in this publication. Patients' mean age was 61.7 ± 8.9 years, 43.2% were female, and median CHA(2)DS(2)-VASc score was 2.0. In the intention-to-treat analysis, the rate of the primary endpoint was 56.5% in patients randomized to the Arctic Front(®) and 9.5% in patients randomized to the HD Mesh Ablator(®) catheter (P = 0.001). In the per-protocol analysis, complete PVI was achieved in 13 (76.5%) of 17 Arctic Front(®) patients but in none of the 15 HD Mesh Ablator(®) patients (P < 0.0001). There were one major and two minor complications in each study arm but no clinically evident stroke. Post-procedural AF recurrence was detected within hospital stay in two (11.8%) Arctic Front(®) patients and in seven (46.7%) HD Mesh Ablator(®) patients (P = 0.049).
The MACPAF study revealed a superiority of the Arctic Front(®) catheter concerning complete PVI. Owing to the insufficient efficacy of the HD Mesh Ablator(®) catheter, the safety board decided to stop MACPAF prematurely.
Europace 04/2012; 14(10):1441-9. · 1.98 Impact Factor
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ABSTRACT: The problem of identifying idiopathic dilated cardiomyopathy (IDC) patients who are at risk of sudden death is still unsolved. The presence of autonomic imbalance in patients with IDC might predict sudden death and tachyarrhythmic events. The aim of this study was to analyze the suitability of blood pressure variability (BPV) compared to heart rate variability (HRV) for noninvasive risk stratification in IDC patients.
Continuous noninvasive blood pressure and high-resolution electrocardiogram were recorded from 91 IDC patients for 30 minutes. During a median follow-up period of 28 months (range: [17-38] months), 14 patients died due to sudden death or necessary resuscitation due to a life-threatening arrhythmia. HRV and BPV analyses were performed in time domain, frequency domain, and nonlinear dynamics. Using the Mann-Whitney U test and Cox regression, we estimated the accuracy of clinical and nonclinical parameters in discriminating high-risk from low-risk patients.
Dynamics of blood pressure regulation was significantly changed in high-risk patients, indicating an increased BPV. BPV indexes from nonlinear symbolic dynamics revealed significant univariate (sensitivity: 85.7%; specificity 77.9%; area under receiver-operator characteristics [ROC] curve: 87.8%) differences. In an optimum multivariate set consisting of two clinical indexes (left ventricular end-diastolic diameter, New York Heart Association) and one nonlinear index (symbolic dynamics), highly significant differences between low- and high-risk IDC groups were estimated (sensitivity of 92.9%, specificity of 86.5%, and area under ROC curve of 95.3%).
Diastolic BPV indexes, especially those from symbolic dynamics, appear to be useful for risk stratification of sudden death in patients with IDC.
Pacing and Clinical Electrophysiology 01/2012; 35(4):471-9. · 1.35 Impact Factor
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ABSTRACT: We hypothesized that infarct transmurality assessed with late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) predicts arrhythmic events in patients with chronic myocardial infarction.
Patients with decreased left ventricular function due to chronic myocardial infarction are at increased risk for life-threatening arrhythmias related to infarcted tissue. LGE-CMR accurately detects infarct morphology.
We prospectively enrolled 52 patients with chronic myocardial infarction referred for primary preventive implantable cardioverter-defibrillator (ICD) implantation following MADIT (Multicenter Automatic Defibrillator Implantation Trial) study criteria. Using LGE-CMR, left ventricular volumes, function, and infarct morphology were assessed including calculation of total and relative infarct mass, infarct border, infarct border zone, and infarct transmurality.
Patients were followed for 1,235 ± 341 days. The primary combined endpoint including appropriate device therapy (ICD discharge or antitachycardia pacing) or death from cardiac cause occurred in 16 individuals resulting in an annual event rate of 4.7%. Six patients received an appropriate shock, 7 patients received recurrent appropriate antitachycardia pacing for sustained ventricular tachycardia, and 3 patients died of cardiac cause. There was a significant association to relative infarct mass (38 ± 8% vs. 28 ± 14%, p = 0.02), infarct transmurality (24 ± 8 g vs. 16 ± 12 g, p = 0.02), and relative infarct transmurality (RIT) (63 ± 12% vs. 48 ± 23%, p = 0.01). In separate logistic regression models, no variable emerged as significant when combined with RIT. As a single effect, RIT emerged as a predictor of the primary endpoint (p = 0.02). A RIT cutoff at 43% resulted in a sensitivity of 88%, a specificity of 50%, a positive predictive value of 44%, and a negative predictive value of 90%.
In patients with chronic myocardial infarction scheduled for primary preventive ICD implantation, infarct transmurality as defined by LGE-CMR identifies a subgroup with increased risk for life-threatening arrhythmias and cardiac death.
JACC. Cardiovascular imaging 08/2011; 4(8):871-9. · 14.29 Impact Factor
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ABSTRACT: BACKGROUND: Treatment of heart failure patients with aldosterone antagonists has been shown to reduce the occurrence of sudden cardiac death. Therefore we aimed at determining the consequences of chronic exposure to aldosterone and the aldosterone antagonists eplerenone and spironolactone on the electrophysiological properties of the heart in a rat model. METHODS AND RESULTS: Male Wistar rats were chronically treated (4weeks) with aldosterone (ALD) via an osmotic minipump. Spironolactone (SPI) or eplerenone (EPL) was administered with the rat chow. ALD treated animals developed left ventricular hypertrophy, prolonged QT-intervals, a higher rate of ventricular premature beats and non-sustained ventricular tachycardia despite normal blood pressure values. Spironolactone and eplerenone were both able to inhibit the alterations. Left-ventricular mRNA expressions of Kv4.2 and Kv4.3 (I(to)), Kv1.5 (I(Kur)), Kir2.1 and Kir2.3 (I(K1)) and of Ca(v)1.2 (L-type Ca(2+) channel) were significantly down-regulated in ALD. Correspondingly, the protein expressions of subunits Kv1.5, Kir2.3 and Cav1.2 were significantly decreased. A diminished calcineurin activity and mRNA expression of the Aß subunit of calcineurin were found in ALD, which was insensitive to aldosterone antagonists. CONCLUSIONS: Chronic aldosterone-overload induces blood pressure independent structural and electrical remodeling of the myocardium resulting in an increased risk for malignant ventricular arrhythmias.
International journal of cardiology 07/2011; · 7.08 Impact Factor
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Karl Georg Haeusler,
Lydia Koch,
Juliane Ueberreiter,
Nalan Coban,
Erdal Safak,
Claudia Kunze,
Kersten Villringer,
Matthias Endres,
Heinz-Peter Schultheiss,
Jochen B Fiebach, Alexander Schirdewan
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ABSTRACT: Up to now there is little evidence about the safety and reliability of insertable cardiac monitors (ICMs) in patients undergoing magnetic resonance imaging (MRI).
The purpose of this prospective single-center study (MACPAF; clinicaltrials.govNCT01061931), which we are currently performing, was to evaluate these issues for the ICM Reveal XT at a 3 Tesla MRI scanner in patients undergoing serial brain MRI.
We present an interim analysis including 62 brain MRI examinations in 24 patients with paroxysmal atrial fibrillation bearing the Reveal XT. All patients were interviewed for potential ICM-associated clinical symptoms during and after MRI examination. According to the study protocol, data from the Reveal XT were transmitted before and after the MRI examination.
All patients were clinically asymptomatic during the MRI procedure. Moreover, the reliability (ability to detect signals, battery status) of the Reveal XT was unaffected, except for one MRI-induced artifact that was recorded by the ICM, mimicking a narrow complex tachycardia, as similarly recorded in a further study patient bearing the forerunner ICM Reveal DX. No loss of ICM data was observed after the MRI examination.
The 3 Tesla brain MRI scanning is safe for patients bearing the ICM Reveal XT and does not alloy reliability of the Reveal XT itself. MRI-induced artifacts occur rarely but have to be taken into account.
Heart rhythm: the official journal of the Heart Rhythm Society 11/2010; 8(3):373-6. · 4.56 Impact Factor
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ABSTRACT: Wound healing is a major determent in the post-surgical course of patients (pts) after pacemaker (PM) and implantable cardioverter defibrillator (ICD) implantation. Insufficient closure may lead to serious complications with pocket infections leading to the device's explantation as the worst case scenario. In addition to the different types of suture and suture clips, a novel topical skin adhesive containing 2-octyl-cyanoacrylate is commercially available.
Over a period of 18 months, we prospectively assigned all cases of PM, ICD, and loop recorder implants either to skin adhesive (Group 1) or to absorbable intracutaneous polydioxanon suture (Group 2). Data were analysed with respect to operation time, wound infections, and healing disorders. One hundred and eighty-three pts were randomized into Group 1 [71 PMs, 60 ICD, 15 cardiac resynchronization therapy (CRT), 11 loop recorders, and 26 generator replacements]. One hundred and eighty-five pts were assigned to Group 2 (62 PMs, 70 ICD, 30 CRT, 7 loop recorders, and 16 generator replacements). There were no differences regarding sex, diabetes, renal insufficiency, corticosteroid therapy, oral anticoagulants, and acetylsalicylic asa/clopidogrel (P = n.s.). For the significantly higher amount of CRT devices (P < 0.05) in Group 2, the procedure times are given for surgeries except CRT. It was 49.1 ± 27.7 min for Group 1 and 53.4 ± 31.9 min for Group 2 (P = n.s.). Adverse events as insufficient closure, major and minor bleeding, pocket haematoma, erythema, incrustation, dehiscence, keloid, and explantation due to infection occurred significantly more often in the adhesive group (P = 0.02). The greatest impact on this result had early adverse events as insufficient closure, wound incrustation, and inflammation (9.3 vs. 6.0%; P = 0.02). We did not find any difference in long-term adverse events, infections in particular (2.7 vs. 1.6%; P = 0.47).
This study shows no benefit using skin adhesive in comparison to absorbable intracutaneous suture regarding surgery times for the implantation of cardiac rhythm devices. The rate of early adverse events after wound closure is higher after skin adhesive but no difference in long-term adverse events occurred.
Europace 11/2010; 13(3):416-20. · 1.98 Impact Factor
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ABSTRACT: Catheter ablation of the pulmonary veins has become accepted as a standard therapeutic approach for symptomatic paroxysmal atrial fibrillation (AF). However, there is some evidence for an ablation associated (silent) stroke risk, lowering the hope to limit the stroke risk by restoration of rhythm over rate control in AF. The purpose of the prospective randomized single-center study "Mesh Ablator versus Cryoballoon Pulmonary Vein Ablation of Symptomatic Paroxysmal Atrial Fibrillation" (MACPAF) is to compare the efficacy and safety of two balloon based pulmonary vein ablation systems in patients with symptomatic paroxysmal AF.
Patients are randomized 1:1 for the Arctic Front(R) or the HD Mesh Ablator(R) catheter for left atrial catheter ablation (LACA). The predefined endpoints will be assessed by brain magnetic resonance imaging (MRI), neuro(psycho)logical tests and a subcutaneously implanted reveal recorder for AF detection. According to statistics 108 patients will be enrolled.
Findings from the MACPAF trial will help to balance the benefits and risks of LACA for symptomatic paroxysmal AF. Using serial brain MRIs might help to identify patients at risk for LACA-associated cerebral thromboembolism. Potential limitations of the study are the single-center design, the existence of a variety of LACA-catheters, the missing placebo-group and the impossibility to assess the primary endpoint in a blinded fashion.
clinicaltrials.gov NCT01061931.
BMC Neurology 01/2010; 10:63. · 2.17 Impact Factor
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ABSTRACT: Telemetric surveillance systems are part of a well-accepted and evolving field in the care of cardiac patients. Especially in patients with implanted cardioverter-defibrillators (ICD), they are well established and their usefulness and reliability have been shown in several clinical trials. Currently, three generations of Home Monitoring™ (HM, Biotronik GmbH & Co. KG, Berlin, Germany) are commercially available.
This paper presents three cases demonstrating the various limitations of the first and second generations of HM and the way they can be overcome by the third generation.
In the first case, atrial flutter was misinterpreted by the device and classified as ventricular tachycardia (VT). Thus, in the online IEGM, supraventricular tachycardia was identified, and the short IEGM strip and lack of transmitted atrial signals of the dual-chamber device necessitated an appointment for ICD interrogation, to clarify the diagnosis and propose further treatment. The second case is that of a patient in whom a VT was ineffectively treated by anti-tachycardia pacing (ATP) and continued with longer cycle length, leading to syncope. A second-generation HM device with online- IEGM misleadingly appears to indicate successful treatment. The third case demonstrates correct detection and therapy of a fast VT by an ICD of third-generation HM type. The online IEGM now gives all information needed for complete telemetric assessment.
Home Monitoring (HM) is a helpful remote surveillance tool for the early detection of both arrhythmias and technical problems. As shown, the first two generations had limitations which the patient must take into account when using the system. These limitations have been overcome in the third generation, making Home Monitoring more self-sufficient and reliable.
Aging clinical and experimental research 12/2009; 22(5-6):459-65. · 1.55 Impact Factor
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Journal of Cardiovascular Magnetic Resonance. 01/2009;
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ABSTRACT: Lead dysfunctions in implantable cardioverter-defibrillator (ICD) patients can lead to inappropriate shocks or even complete loss of function of the device. Home monitoring (HM) systems are capable of daily data transmissions regarding the device and the lead integrity as well as information concerning anti-arrhythmic therapies. We therefore analysed the data from the Biotronik HM system whether it enables physicians to react quickly on serious ICD malfunctions and to avoid inappropriate shocks.
Fifty-four patients who had to undergo resurgery due to malfunctions of the ICD lead were included. Eleven of them were on HM interrogating the device every night at 3 am. If any adverse event was detected, a fax alert was sent to the clinic and the patients were asked for in-hospital ICD interrogation. The rate of inappropriate shocks and symptomatic pacemaker inhibition due to oversensing was compared with the 43 patients without remote surveillance. HM sent alert messages in 91% of all incidents. All lead failures became obvious because of oversensing of high frequency artefacts. Only in 18%, changes in the pacing impedance were noticed, in all cases preceded by oversensing. Eighty per cent of the patients were asymptomatic at the first onset of oversensing. Only one patient suffered an inappropriate shock as first manifestation of lead failure. Compared with the patients without HM, inappropriate shocks occurred in 27.3% in the HM group vs. 46.5% (P = n.s.). This trend gains statistical significance, if the compound endpoint of symptomatic lead failure consisting of inappropriate shocks and symptomatic pacemaker inhibition due to oversensing is focused: 27.3% event in the HM group vs. 53.4% in the group without HM (P = 0.04). Event messages were despatched in a mean of 54 days after the last ICD interrogation and 56 days before next scheduled visit. Thus, 56 days of reaction time are gained to avoid adverse events.
In 91% of all lead-related ICD complications, the diagnosis could be established correctly by an alert of the HM system. Mostly, the first incident sent was oversensing of artefacts, falsely detected as ventricular fibrillation-the VF zone. The automatic HM surveillance system enables physicians to detect severe lead problems early and to react quickly; thus, it might have a potential to avoid inappropriate shocks due to lead failure and T-wave oversensing.
Europace 01/2009; 11(4):483-8. · 1.98 Impact Factor
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Ulrike Lisewski,
Yu Shi,
Uta Wrackmeyer,
Robert Fischer,
Chen Chen, Alexander Schirdewan,
Rene Jüttner,
Fritz Rathjen,
Wolfgang Poller,
Michael H. Radke,
Michael Gotthardt
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ABSTRACT: The Coxsackievirus-adenovirus receptor (CAR) is known for its role in virus uptake and as a protein of the tight junction.
It is predominantly expressed in the developing brain and heart and reinduced upon cardiac remodeling in heart disease. So
far, the physiological functions of CAR in the adult heart are largely unknown. We have generated a heart-specific inducible
CAR knockout (KO) and found impaired electrical conduction between atrium and ventricle that increased with progressive loss
of CAR. The underlying mechanism relates to the cross talk of tight and gap junctions with altered expression and localization
of connexins that affect communication between CAR KO cardiomyocytes. Our results indicate that CAR is not only relevant for
virus uptake and cardiac remodeling but also has a previously unknown function in the propagation of excitation from the atrium
to the ventricle that could explain the association of arrhythmia and Coxsackievirus infection of the heart.
Journal of Experimental Medicine 09/2008; 205(10):2369-2379. · 13.85 Impact Factor
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ABSTRACT: The objective was to determine the characteristics of heart rate variability and ventricular arrhythmias prior to the onset of ventricular tachycardia (VT) in patients with an implantable cardioverter defibrillator (ICD). Sixty-eight beat-to-beat time series from 13 patients with an ICD were analyzed to quantify heart rate variability and ventricular arrhythmias. The episodes of VT were classified in one of two groups depending on whether the sinus rate in the 1 min preceding the VT was greater or less than 90 beats per minute. In a subset of patients, increased heart rate and reduced heart rate variability was often observed up to 20 min prior to the VT. There was a non-significant trend to higher incidence of premature ventricular complexes (PVCs) before VT compared to control recordings. The patterns of the ventricular arrhythmias were highly heterogeneous among different patients and even within the same patient. Analysis of the changes of heart rate and heart rate variability may have predictive value about the onset of VT in selected patients. The patterns of ventricular arrhythmia could not be used to predict onset of VT in this group of patients.
Medical & Biological Engineering 08/2008; 46(7):715-27. · 1.76 Impact Factor
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Jan Monti,
Judith Fischer,
Svetlana Paskas,
Matthias Heinig,
Herbert Schulz,
Claudia Gösele,
Arnd Heuser,
Robert Fischer,
Cosima Schmidt, Alexander Schirdewan, [......],
Martin Vingron,
Steven M Weldon,
Klaus Lindpaintner,
Bruce D Hammock,
Klaus Rohde,
Rainer Dietz,
Stuart A Cook,
Wolf-Hagen Schunck,
Friedrich C Luft,
Norbert Hubner
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ABSTRACT: We aimed to identify genetic variants associated with heart failure by using a rat model of the human disease. We performed invasive cardiac hemodynamic measurements in F2 crosses between spontaneously hypertensive heart failure (SHHF) rats and reference strains. We combined linkage analyses with genome-wide expression profiling and identified Ephx2 as a heart failure susceptibility gene in SHHF rats. Specifically, we found that cis variation at Ephx2 segregated with heart failure and with increased transcript expression, protein expression and enzyme activity, leading to a more rapid hydrolysis of cardioprotective epoxyeicosatrienoic acids. To confirm our results, we tested the role of Ephx2 in heart failure using knockout mice. Ephx2 gene ablation protected from pressure overload-induced heart failure and cardiac arrhythmias. We further demonstrated differential regulation of EPHX2 in human heart failure, suggesting a cross-species role for Ephx2 in this complex disease.
Nature Genetics 06/2008; 40(5):529-37. · 35.53 Impact Factor
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Robert Fischer,
Ralf Dechend,
Fatimunnisa Qadri,
Marija Markovic,
Sandra Feldt,
Florian Herse,
Joon-Keun Park,
Andrej Gapelyuk,
Ines Schwarz,
Udo B Zacharzowsky,
Ralph Plehm,
Erdal Safak,
Arnd Heuser, Alexander Schirdewan,
Friedrich C Luft,
Wolf-Hagen Schunck,
Dominik N Muller
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ABSTRACT: We compared the effect n-3 polyunsaturated fatty acids (PUFAs) with direct renin inhibition on electrophysiological remodeling in angiotensin II-induced cardiac injury. We treated double-transgenic rats expressing the human renin and angiotensinogen genes (dTGRs) from week 4 to 7 with n-3 PUFA ethyl-esters (Omacor; 25-g/kg diet) or a direct renin inhibitor (aliskiren; 3 mg/kg per day). Sprague-Dawley rats were controls. We performed electrocardiographic, magnetocardiographic, and programmed electrical stimulation. Dietary n-3 PUFAs increased the cardiac content of eicosapentaenoic and docosahexaenoic acid. At week 7, mortality in dTGRs was 31%, whereas none of the n-3 PUFA- or aliskiren-treated dTGRs died. Systolic blood pressure was modestly reduced in n-3 PUFA-treated (180+/-3 mm Hg) compared with dTGRs (208+/-5 mm Hg). Aliskiren-treated dTGRs and Sprague-Dawley rats were normotensive (110+/-3 and 119+/-6 mm Hg, respectively). Both n-3 PUFA-treated and untreated dTGRs showed cardiac hypertrophy and increased atrial natriuretic peptide levels. Prolonged QRS and QT(c) intervals and increased T-wave dispersion in dTGRs were reduced by n-3 PUFAs or aliskiren. Both treatments reduced arrhythmia induction from 75% in dTGRs to 17% versus 0% in Sprague-Dawley rats. Macrophage infiltration and fibrosis were reduced by n-3 PUFAs and aliskiren. Connexin 43, a mediator of intermyocyte conduction, was redistributed to the lateral cell membranes in dTGRs. n-3 PUFAs and aliskiren restored normal localization to the intercalated disks. Thus, n-3 PUFAs and aliskiren improved electrical remodeling, arrhythmia induction, and connexin 43 expression, despite a 70-mm Hg difference in blood pressure and the development of cardiac hypertrophy.
Hypertension 03/2008; 51(2):540-6. · 6.21 Impact Factor
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Proceedings of the First International Conference on Biomedical Electronics and Devices, BIOSIGNALS 2008, Funchal, Madeira, Portugal, January 28-31, 2008, Volume 2; 01/2008
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Journal of Cardiovascular Magnetic Resonance. 01/2008;
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10/2007: pages 203 - 210; , ISBN: 9780470987483
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Robert Fischer,
Ralf Dechend,
Andrej Gapelyuk,
Erdenechimeg Shagdarsuren,
Konstanze Gruner,
Andreas Gruner,
Petra Gratze,
Fatimunnisa Qadri,
Maren Wellner,
Anette Fiebeler,
Rainer Dietz,
Friedrich C Luft,
Dominik N Muller, Alexander Schirdewan
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ABSTRACT: Rats harboring the human renin and angiotensinogen genes (dTGR) feature angiotensin (ANG) II/hypertension-induced cardiac damage and die suddenly between wk 7 and 8. We observed by electrocardiogram (ECG) telemetry that ventricular tachycardia (VT) is a common terminal event in these animals. Our aim was to investigate electrical remodeling. We used ECG telemetry, noninvasive cardiac magnetic field mapping (CMFM) at wk 5 and 7, and performed in vivo programmed electrical stimulation at wk 7. We also investigated whether or not losartan (Los; 30 mg x kg(-1) x day(-1)) would prevent electrical remodeling. Cardiac hypertrophy and systolic blood pressure progressively increased in dTGR compared with Sprague-Dawley (SD) controls. Already by wk 5, untreated dTGR showed increased perivascular and interstitial fibrosis, connective tissue growth factor expression, and monocyte infiltration compared with SD rats, differences that progressed through time. Left-ventricular mRNA expression of potassium channel subunit Kv4.3 and gap-junction protein connexin 43 were significantly reduced in dTGR compared with Los-treated dTGR and SD. CMFM showed that depolarization and repolarization were prolonged and inhomogeneous. Los ameliorated all disturbances. VT could be induced in 88% of dTGR but only in 33% of Los-treated dTGR and could not be induced in SD. Untreated dTGR show electrical remodeling and probably die from VT. Los treatment reduces myocardial remodeling and predisposition to arrhythmias. ANG II target organ damage induces VT.
AJP Heart and Circulatory Physiology 09/2007; 293(2):H1242-53. · 3.71 Impact Factor
