[Show abstract][Hide abstract] ABSTRACT: Background/Aims: Adenosine 5'-monophosphate (AMP)-activated protein kinase (Ampk) modulates a wide array of cellular functions and regulates various ion channels and transporters. In failing human hearts an increased Ampkα1 activity was observed. The present study aimed to uncover the impact of Ampkα1 on cardiac electrical remodeling. Methods: Gene-targeted mice lacking functional Ampkα1 (Ampkα1-/-) and corresponding wild-type mice were exposed to pressure overload by “transverse aortic constriction” (TAC). In vivo electrophysiology was performed with a single catheter technique, myocardial conduction velocities and conduction characteristics investigated in isolated hearts, transcript levels quantified by RT-PCR and protein abundance determined by Western blotting. Moreover, connexin 43 (Cx43) was expressed in Xenopus oocytes with or without coexpression of wild-type or mutant AMPK and Cx43 protein abundance quantified utilizing confocal microscopy. Results: TAC treatment increased Ampkα1 protein expression in cardiac tissue from wild-type mice. TAC further increased left ventricular conduction inhomogeneity and triggered conduction blocks, effects blunted in the Ampkα1-/- mice. TAC treatment decreased Cx43 protein abundance in cardiac tissue, an effect again significantly blunted in the Ampkα1-/- mice. TAC treatment did not modify Cx43 mRNA levels but increased ubiquitination of Cx43 protein, an effect mitigated by Ampkα1 deficiency. As shown in Xenopus oocytes, Cx43 cell membrane protein abundance was significantly downregulated by wild-type AMPKWT and constitutively active AMPKγR70Q, but not by catalytically inactive AMPKαK45R. Conclusion: Ampkα1 stimulates ubiquitination of the gap junction protein Cx43, thereby contributing to gap junction remodeling following pressure overload.
Cellular Physiology and Biochemistry 01/2015; 35(1):406-418. · 3.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mutations of the human desmin gene on chromosome 2q35 cause autosomal dominant, autosomal recessive and sporadic forms of protein aggregation myopathies and cardiomyopathies. We generated R349P desmin knock-in mice, which harbor the ortholog of the most frequently occurring human desmin missense mutation R350P. These mice develop age-dependent desmin-positive protein aggregation pathology, skeletal muscle weakness, dilated cardiomyopathy, as well as cardiac arrhythmias and conduction defects. For the first time, we report the expression level and subcellular distribution of mutant versus wild-type desmin in our mouse model as well as in skeletal muscle specimens derived from human R350P desminopathies. Furthermore, we demonstrate that the missense-mutant desmin inflicts changes of the subcellular localization and turnover of desmin itself and of direct desmin-binding partners. Our findings unveil a novel principle of pathogenesis, in which not the presence of protein aggregates, but disruption of the extrasarcomeric intermediate filament network leads to increased mechanical vulnerability of muscle fibers. These structural defects elicited at the myofiber level finally impact the entire organ and subsequently cause myopathy and cardiomyopathy.
[Show abstract][Hide abstract] ABSTRACT: IntroductionRight phrenic nerve palsy (PNP) is a typical complication of cryoballoon ablation of the right-sided pulmonary veins (PV). Phrenic nerve function can be monitored by palpating the abdomen during phrenic nerve pacing from the superior vena cava (SVC pacing) or by fluoroscopy of spontaneous breathing. We sought to compare the sensitivity of these two techniques during cryoballoon ablation for detection of PNP.Methods and Results133 patients undergoing cryoballoon ablation were monitored with both SVC pacing and fluoroscopy of spontaneous breathing during ablation of the right superior PV. PNP occurred in 27/133 patients (20.0%). Most patients (89%) had spontaneous recovery of phrenic nerve function at the end of the procedure or on the following day. Three patients were discharged with persistent PNP. All PNP were detected first by fluoroscopic observation of diaphragm movement during spontaneous breathing, while diaphragm could still be stimulated by SVC pacing. In patients with no recovery until discharge, PNP occurred at a significantly earlier time (86±34s vs. 296±159s, p<0.001). No recovery occurred in 2/4 patients who were ablated with a 23mm cryoballoon as opposed to 1/23 patients with a 28mm cryoballoon (p = 0.049).Conclusion
Fluoroscopic assessment of diaphragm movement during spontaneous breathing is more sensitive for detection PNP as compared to SVC pacing. PNP as assessed by fluoroscopy is frequent (20.0%) and carries a high rate of recovery (89%) until discharge. Early onset of PNP and use of 23mm cryoballoon are associated with PNP persisting beyond hospital discharge.This article is protected by copyright. All rights reserved.
Journal of Cardiovascular Electrophysiology 04/2014; · 3.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Heart rate turbulence (HRT) is a prognostic parameter for risk stratification in patients suffering from coronary artery disease. The aims of this study were to demonstrate the feasibility of quantifying HRT in mice, both in long-term electrocardiograms (ECGs) as well as after extrastimulus pacing, and to analyse its characteristics.METHODS AND RESULTS: We performed long-term ECG recordings using implanted telemetric chips and electrophysiological (EP) investigations, using transvenously inserted EP catheters, in healthy mice. Heart rate turbulence was calculated using the established turbulence onset (TO) and slope (TS) algorithm. After spontaneous ventricular premature complexes (VPCs), we found a negative TO (-2.2 ± 7.5%) and positive TS (15.5 ± 18.3 ms/RR interval). Electrophysiological investigations revealed positive values for TO (0.6 ± 1.1%) and TS (6.5 ± 2.9 ms/RR interval) after extrastimulus pacing maneuvers. The shortening of the extrastimuli coupling intervals delivered during EP investigations significantly influenced TO (r = 0.57; P = 0.01): shorter coupling intervals provoked more positive TO values.CONCLUSION: Mice display both spontaneous and induced HRT. In terms of TO, VPCs generated by extrastimulus pacing are significantly dependent on the coupling interval. Determining HRT in mice is feasible and provides insight into basic mechanisms of blood pressure regulation, which is realized by the baroreflex.
[Show abstract][Hide abstract] ABSTRACT: Recent observational clinical and ex-vivo studies suggest that inflammation and in particular leukocyte activation predisposes to atrial fibrillation (AF). However, whether local binding and extravasation of leukocytes into atrial myocardium is an essential prerequisite for the initiation and propagation of AF remains elusive. Here we investigated the role of atrial CD11b/CD18 mediated infiltration of polymorphonuclear neutrophils (PMN) for the susceptibility to AF.
C57bl/6J wildtype (WT) and CD11b/CD18 knock-out (CD11b(-/-)) mice were treated for 14 days with subcutaneous infusion of angiotensin II (Ang II), a known stimulus for PMN activation. Atria of Ang II-treated WT mice were characterized by increased PMN infiltration assessed in immunohistochemically stained sections. In contrast, atrial sections of CD11b(-/-) mice lacked a significant increase in PMN infiltration upon Ang II infusion. PMN infiltration was accompanied by profoundly enhanced atrial fibrosis in Ang II treated WT as compared to CD11b(-/-) mice. Upon in-vivo electrophysiological investigation, Ang II treatment significantly elevated the susceptibility for AF in WT mice if compared to vehicle treated animals given an increased number and increased duration of AF episodes. In contrast, animals deficient of CD11b/CD18 were entirely protected from AF induction. Likewise, epicardial activation mapping revealed decreased electrical conduction velocity in atria of Ang II treated WT mice, which was preserved in CD11b(-/-) mice. In addition, atrial PMN infiltration was enhanced in atrial appendage sections of patients with persistent AF as compared to patients without AF.
The current data critically link CD11b-integrin mediated atrial PMN infiltration to the formation of fibrosis, which promotes the initiation and propagation of AF. These findings not only reveal a mechanistic role of leukocytes in AF but also point towards a potential novel avenue of treatment in AF.
PLoS ONE 02/2014; 9(2):e89307. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and a major cause of stroke. In the mammalian heart the gap junction proteins Connexin40 (Cx40) and Connexin43 (Cx43) are strongly expressed in the atrial myocardium mediating effective propagation of electrical impulses. Different heterozygous mutations in the coding region for Cx40 were identified in patients with AF. We have generated transgenic Cx40A96S mice harboring one of these mutations, the loss-of-function Cx40A96S mutation, as a model for atrial fibrillation. Cx40A96S mice were characterized by immunochemical and electrophysiological analyses. Significantly reduced atrial conduction velocities and strongly prolonged episodes of atrial fibrillation were found after induction in Cx40A96S mice. Analyses of the gating properties of Cx40A96S channels in cultured HeLa cells also revealed significantly lower junctional conductance and enhanced sensitivity voltage gating of Cx40A96S in comparison to Cx40 wild-type gap junctions. This is caused by reduced open probabilities of Cx40A96S gap junction channels, while single channel conductance remained the same. Similar to the corresponding patient, heterozygous Cx40A96S mice revealed normal expression levels and localization of the Cx40 protein. We conclude that heterozygous Cx40A96S mice exhibit prolonged episodes of induced atrial fibrillation and severely reduced atrial conduction velocities similar to the corresponding human patient.
Journal of Molecular and Cellular Cardiology 09/2013; · 5.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Identification of reliable risk factors for recurrence of atrial fibrillation (AF) after pulmonary vein isolation (PVI) has important implications. Left atrial (LA) pressure is a largely observator-independent parameter that can easily be determined after transseptal puncture. The purpose of this study was to investigate the predictive value of LA pressure for AF recurrence after PVI.
Two hundred five consecutive patients with paroxysmal or persistent AF scheduled for first PVI were included. Baseline clinical data were collected. During PVI, LA pressure was determined invasively after transseptal puncture. PVI was performed with radiofrequency or cryoenergy, and patients were followed for 25 ± 7 months.
One hundred five (51 %) patients had AF recurrence. Patients with persistent AF prior to ablation had significantly more recurrences than patients with paroxysmal AF (70.1 vs. 42.0 %, p < 0.001). Mean LA pressure was significantly higher in patients with recurrence of AF (13.4 ± 7.1 vs. 11.0 ± 5.2 mmHg, p = 0.007), as was mean LA volume index (40.1 ± 18.5 vs. 33.0 ± 11.2 mL/m(2), p < 0.001). In the multivariate analysis, mean LA pressure was predictive in patients with normal or mildly enlarged LA, while AF type was not predictive. For each 1-mmHg increase in LA pressure, the risk of AF recurrence increased by 11 % in this subgroup. In patients with moderately or severely enlarged LA, AF type was predictive whereas LA pressure was not.
LA pressure, AF type, and LA volume index are independent predictors for recurrence of AF after PVI. LA pressure may be helpful especially in patients with small atria, where AF type is not predictive.
Journal of Interventional Cardiac Electrophysiology 06/2013; · 1.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The cardiac intercalated disc harbors mechanical and electrical junctions as well as ion channel complexes mediating propagation of electrical impulses. Cardiac connexin43 (Cx43) co-localizes and interacts with several of the proteins located at intercalated discs in the ventricular myocardium. We have generated conditional Cx43D378stop mice lacking the last five C-terminal amino acid residues, representing a binding motif for zonula occludens protein-1 (ZO-1), and investigated the functional consequences of this mutation on cardiac physiology and morphology. Newborn and adult homozygous Cx43D378stop mice displayed markedly impaired and heterogeneous cardiac electrical activation properties and died from severe ventricular arrhythmias. Cx43 and ZO-1 were co-localized at intercalated discs in Cx43D378stop hearts, and the Cx43D378stop gap junction channels showed normal coupling properties. Patch clamp analyses of isolated adult Cx43D378stop cardiomyocytes revealed a significant decrease in sodium and potassium current densities. Furthermore, we also observed a significant loss of Nav1.5 protein from intercalated discs in Cx43D378stop hearts. The phenotypic lethality of the Cx43D378stop mutation was very similar to the one previously reported for adult Cx43 deficient (Cx43KO) mice. Yet, in contrast to Cx43KO mice, the Cx43 gap junction channel was still functional in the Cx43D378stop mutant. We conclude that the lethality of Cx43D378stop mice is independent of the loss of gap junctional intercellular communication, but most likely results from impaired cardiac sodium and potassium currents. The Cx43D378stop mice reveal for the first time that Cx43 dependent arrhythmias can develop by mechanisms other than impairment of gap junction channel function.
Archiv für Kreislaufforschung 05/2013; 108(3):348. · 5.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Advanced heart failure (HF) is associated with severe sleep-disordered breathing (SDB). In addition, most patients with HF are treated with an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death. The incidence of ICD therapy in such a patient cohort with SDB has never been investigated. The present study sought to determine the effect of SDB on the incidence of appropriate and inappropriate ICD therapy in patients with a categorical primary prevention ICD indication. A total of 133 consecutive ICD patients with New York Heart Association class II-III HF and depressed left ventricular function (≤35%) with no history of ventricular arrhythmia underwent a sleep study before ICD implantation and were followed for 24 ± 8 months, prospectively. A relevant SDB was defined as an apnea-hypopnea index of ≥10 events/hour. Of these 133 patients, 82 (62%) had SDB. Overweight (body mass index >29.1 vs 24.7 kg/m(2); p <0.001) was identified as the only independent risk factor for SDB. Appropriate ICD therapy intervention was significantly greater among patients with SDB than among patients without SDB (54% vs 34%, p = 0.03). Inappropriate ICD therapy intervention was documented more often in patients with SDB (n = 24 [29%] vs 7 [14%]; p = 0.04). An apnea-hypopnea index >10 events/hour was an independent predictor of appropriate ICD therapy on multivariate analysis (odds ratio 2.5, 95% confidence interval 1.8 to 4.04; p = 0.01). In conclusion, the present study is the first trial exploring the effect of SDB on the incidence of appropriate and inappropriate ICD therapy in patients with HF with a primary prevention indication. These results indicate that a preimplantation sleep study will identify patients with HF prone to receive appropriate and inappropriate ICD therapy.
The American journal of cardiology 02/2013; · 3.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Beta-adrenoceptors (β-AR) play an important role in the neurohumoral regulation of cardiac function. Three β-AR subtypes (β(1), β(2), β(3)) have been described so far. Total deficiency of these adrenoceptors (TKO) results in cardiac hypotrophy and negative inotropy. TKO represents a unique mouse model mimicking total unselective medical β-blocker therapy in men. Electrophysiological characteristics of TKO have not yet been investigated in an animal model.
In vivo electrophysiological studies using right heart catheterisation were performed in 10 TKO mice and 10 129SV wild type control mice (WT) at the age of 15 weeks. Standard surface ECG, intracardiac and electrophysiological parameters, and arrhythmia inducibility were analyzed.
The surface ECG of TKO mice revealed a reduced heart rate (359.2±20.9 bpm vs. 461.1±33.3 bpm; p<0.001), prolonged P wave (17.5±3.0 ms vs. 15.1±1.2 ms; p = 0.019) and PQ time (40.8±2.4 ms vs. 37.3±3.0 ms; p = 0.013) compared to WT. Intracardiac ECG showed a significantly prolonged infra-Hisian conductance (HV-interval: 12.9±1.4 ms vs. 6.8±1.0 ms; p<0.001). Functional testing showed prolonged atrial and ventricular refractory periods in TKO (40.5±15.5 ms vs. 21.3±5.8 ms; p = 0.004; and 41.0±9.7 ms vs. 28.3±6.6 ms; p = 0.004, respectively). In TKO both the probability of induction of atrial fibrillation (12% vs. 24%; p<0.001) and of ventricular tachycardias (0% vs. 26%; p<0.001) were significantly reduced.
TKO results in significant prolongations of cardiac conduction times and refractory periods. This was accompanied by a highly significant reduction of atrial and ventricular arrhythmias. Our finding confirms the importance of β-AR in arrhythmogenesis and the potential role of unspecific beta-receptor-blockade as therapeutic target.
PLoS ONE 11/2012; 7(11):e49203. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Survivin (Surv) belongs to the inhibitor of apoptosis protein family. Its cardiac-specific deletion results in reduced cardiomyocyte number, increased cardiomyocyte size and ploidy, and development of heart failure. Its impact on cardiac electrophysiology is unknown. In vivo transvenous electrophysiological studies were carried out in adult male mice with a cardiac-specific deletion of survivin (Surv(-/-); n = 12) and wild-type controls (Surv(+/+); n = 12). Epicardial activation mapping (EAM) was performed in Langendorff-perfused hearts of 16 Surv(-/-) and 6 Surv(+/+) mice. Surface-ECG showed lower heart rates in Surv(-/-) mice (326 ± 66 bpm vs. 440.6 ± 39 ms; P = 0.0001), accompanied by significantly prolonged P waves (20.3 ± 5.8 vs. 14.6 ± 2.0 ms; P = 0.009), PQ-(47.4 ± 8.6 vs. 41.1 ± 3.7 ms; P = 0.043), QRS- (19.5 ± 4.8 vs. 14.0 ± 1.0 ms; P = 0.002) and QT-intervals (41.6 ± 4.4 vs. 36.2 ± 3.4 ms; P = 0.003). The HV-interval was prolonged in Surv(-/-) mice (12.1 ± 2.4 vs. 9.3 ± 1.4 ms; P = 0.0045). We found impaired sinus-nodal function (sinus node recovery times: 310.2 ± 76.6 vs. 207.8 ± 68.6 ms; P = 0.003) and AV-nodal conduction (Wenckebach-periodicity: 105.9 ± 15.9 vs. 79.6 ± 8.1 ms; P = 0.0002). EAM showed significant slowing and heterogeneity of conduction in the myocardium of Surv(-/-) mice. All Surv(-/-) mice showed spontaneous supraventricular and ventricular ectopic beats (P < 0.0001 vs. wildtype). Quantitative immunofluorescence staining for connexin43 (Cx43) revealed a decrease in both per cardiomyocyte and single gap junction. Surv(-/-) mice exhibit severe global conduction attenuations in atrial and ventricular myocardium as well as the specific conduction system, accompanied by lower connexin43 levels. Lack of susceptibility to AF and VT suggests that reduced cardiomyocyte number and increased size constitute determinants of electrical stableness in the heart and counteract potentially proarrhythmogenic connexin43 loss in Surv(-/-).
Archiv für Kreislaufforschung 11/2012; 107(6):299. · 5.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rationale: The gap junctional protein Connexin45 (Cx45) is strongly expressed in the early embryonic myocardium. In the adult heart of mouse and man the expression is mainly restricted to the cardiac conduction system. Cx45 plays an essential role for development and function of the embryonic heart because general and cardiomyocyte-directed deficiencies of Cx45 in mice lead to embryonic lethality due to morphological and functional cardiovascular defects. The function of Cx45 in the adult mouse has not yet been cleared. Objective: To clarify the function of Cx45 in the adult mouse heart. Methods and Results: In order to circumvent the embryonic lethality resulting from Cx45 deficiency, mice were generated in which deletion of Cx45 was specifically induced in cardiomyocytes of adult mice. These Cx45-deficient mice were viable but showed a decrease in atrioventricular (AV)-nodal conductivity. In addition, the Connexin30.2 (Cx30.2) protein which is coexpressed with Cx45 in the cardiac conduction system was posttranscriptionally reduced by 70% in mutant hearts. Furthermore, deletion of both Cx45 and Cx30.2 resulted in viable mice that, however, showed stronger impairment of AV-nodal conduction than the single Cx45-deficient mice. Conclusions: Cx45 is required for optimal impulse propagation in the AV node and stabilizes the level of the coexpressed Cx30.2 protein in the adult mouse heart. In contrast to the embryo, Cx45 is not essential for viability of adult mice.
Circulation Research 09/2012; · 11.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cyclase-associated proteins are highly conserved proteins that have a role in the regulation of actin dynamics. Higher eukaryotes have two isoforms, CAP1 and CAP2. To study the in vivo function of CAP2, we generated mice in which the CAP2 gene was inactivated by a gene-trap approach. Mutant mice showed a decrease in body weight and had a decreased survival rate. Further, they developed a severe cardiac defect marked by dilated cardiomyopathy (DCM) associated with drastic reduction in basal heart rate and prolongations in atrial and ventricular conduction times. Moreover, CAP2-deficient myofibrils exhibited reduced cooperativity of calcium-regulated force development. At the microscopic level, we observed disarrayed sarcomeres with development of fibrosis. We analyzed CAP2's role in actin assembly and found that it sequesters G-actin and efficiently fragments filaments. This activity resides completely in its WASP homology domain. Thus CAP2 is an essential component of the myocardial sarcomere and is essential for physiological functioning of the cardiac system, and a deficiency leads to DCM and various cardiac defects.
Cellular and Molecular Life Sciences CMLS 09/2012; · 5.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: Cardiogenic shock (CS) remains the leading cause of death in patients hospitalized for myocardial infarction (MI). Systemic inflammation with inappropriate vasodilatation is observed in many patients with CS and may contribute to an excess mortality rate. The purpose of this study was to determine the predictive role of serial measurements of Nt-proBNP, interleukin-6 (IL-6) and procalcitonin (PCT) for 30-day mortality in patients with CS due to MI. METHODS: The present study is a prospective single-center-study including 87 patients with MI complicated by CS treated with acute revascularization and intra-aortic-balloon-counterpulsation (IABP) support. Predictive values of plasma levels at admission (T0), after 24 hours (T1), and after 72 hours (T2) were examined according to 30-day mortality. RESULTS: Significant differences between survivors (n=59) and non-survivors (n=28) were seen for Nt-proBNP at T0, for IL-6 at T0 and T1, and for PCT at T1 and T2. According to ROC analyses, highest accuracy predicting 30-day mortality was seen at T0 for IL-6, at T1 for PCT, and at T2 for PCT. In univariate analysis significant values were found for Nt-proBNP at T1, for IL-6 and PCT at all points of time. Within the multivariate analysis, age, creatinine and IL-6 were significant determinants of 30-day mortality in which IL-6 showed the highest level of significance. CONCLUSIONS: In patients with MI complicated by CS, IL-6 represented a reliable independent early prognostic marker of 30-day mortality. PCT revealed a significant value at later points of time whereas Nt-proBNP seemed to be of lower relevance.
Critical care (London, England) 08/2012; 16(4):R152. · 5.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Transcatheter ablation of the pulmonary veins (PVs) has been established as a therapeutic option for patients with symptomatic atrial fibrillation. Cryothermal energy is an alternative energy source that has been developed to overcome some of the disadvantages of radiofrequency ablation. The major complication of the cryoballoon technique seems to be right-sided phrenic nerve injury (PNI) following ablation of the right superior PV. This case report describes a left-sided PNI after cryoballoon ablation of the left superior PV. (PACE 2012; XX:1-3).
Pacing and Clinical Electrophysiology 07/2012; · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A growing number of patients with advanced heart failure fulfill a primary-prevention indication for an implantable cardioverter-defibrillator (ICD). This study seeks to identify new predictors of overall mortality in a Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)-like collective to enhance risk stratification.
An impaired renal function and severely depressed left ventricular ejection fraction pose relevant risk factors for mortality in primary prevention ICD recipients.
Ninety-four consecutive ICD patients with New York Heart Association class II-III heart failure and depressed left ventricular function (left ventricular ejection fraction [LVEF] ≤35%) with no history of malignant ventricular arrhythmias were followed for 34 ± 20 months.
During this period, 30 patients died (32%). Deceased patients revealed a significantly worse renal function before ICD implantation (1.55 ± 0.7 mg/dL vs 1.1 ± 0.4 mg/dL; P = 0.007), suffered more often from coronary artery disease (53 vs 29; P = 0.006), and were older (69.5 ± 8 y vs 67 ± 12 y; P = 0.0002) than surviving patients. Furthermore, increased serum creatinine at baseline (2 mg/dL vs 1 mg/dL; odds ratio [OR]: 3.96, 95% confidence interval [CI]: 1.2-13.04, P = 0.02), presence of coronary artery disease (OR: 8.6, 95% CI: 1.1-65, P = 0.036), and low LVEF (OR per 5% baseline LVEF deterioration: 1.4, 95% CI: 1-1.8, P = 0.034) represented strong and independent predictors for overall mortality.
Impaired renal function, the presence of coronary artery disease, and reduced LVEF before implantation represent independent predictors for mortality in a cohort of patients with advanced systolic heart failure. These conditions still bear a high mortality risk, even if ICD implantation effectively prevents sudden arrhythmic death. Indeed, in patients suffering from several of the identified "high-risk" comorbidities, primary-prevention ICD implantation might have a limited survival benefit. The possible adverse effects of these comorbidities should be openly discussed with the potential ICD recipient and his or her close relatives. Clin. Cardiol. 2012 doi: 10.1002/clc.22018 The authors have no funding, financial relationships, or conflicts of interest to disclose.
[Show abstract][Hide abstract] ABSTRACT: AIMS: The current study includes all consecutive patients with advanced heart failure and cardiac resynchronization therapy (CRT) with an implantable cardioverter defibrillator (ICD) over a 10-year period in a tertiary referral centre. It aims at identifying independent risk factors for mortality during CRT-defibrillator (CRT-D) treatment.METHODS AND RESULTS: This study includes 239 consecutive patients who had undergone implantation of a CRT-D system (ejection fraction 25.9 ± 8%; 139 patients with ischaemic, 100 patients with non-ischaemic cardiomyopathy). Enrolment took place between 2001 and 2010, resulting in a median follow-up of 43 ± 30 months. During follow-up, 59 patients (25%) died. An impaired baseline kidney function [hazard ratio (HR) 1.98; 95% confidence interval (CI) 1.7-3; P< 0.0001], appropriate ICD therapy during follow-up (HR 2.1; CI 1.1-3.4; P= 0.001), lack of beta-blocker therapy (HR 2.3; CI 1.6-3.8; P= 0.004), and intake of amiodarone (HR 2; CI 1.8-4.1; P< 0.0001) were identified as predictors of overall mortality.CONCLUSION: This study demonstrates the benefit of beta-blocker therapy also in patients on long-term CRT-D treatment. It confirms the prognostic significance of impaired renal function and the occurrence of appropriate ICD therapies also in CRT-D patients. It argues for an intensified follow-up regimen and adjustment of heart failure treatment whenever these prognostic markers are identified in a patient treated with CRT-D.
[Show abstract][Hide abstract] ABSTRACT: Atrioesophageal Fistula After Cryoballoon PV Isolation. The risk of atrioesophageal fistula after cryoballoon pulmonary vein isolation is thought to be much lower than after radiofrequency ablation, seeing that no data exist on this complication so far. We report for the first time on the occurrence of an atrioesophageal fistula 4 weeks after cryoballoon ablation at the site of the left inferior pulmonary vein. We suggest that even when using cryothermal ablation technique, an imaging modality to assess the proximity of esophagus and left atrium should be routinely performed to avoid this fatal complication. (J Cardiovasc Electrophysiol, Vol. pp. 1-4).
Journal of Cardiovascular Electrophysiology 04/2012; · 3.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In order to optimize power delivery into the myocardium during radiofrequency ablation (RFA) without overheating the electrode tip, active cooling of the tip electrode as well as electrode tips made of gold have evolved. Recently, an externally irrigated gold tip electrode ablation catheter has been developed to combine the advantages of these 2 technologies. We sought to investigate the procedural parameters tip temperature, delivered power and cooling flow requirements of the irrigated gold tip catheter in comparison to the conventional irrigated platinum iridium (Pt) tip catheter in pulmonary vein isolation (PVI) and cavotricuspid isthmus (CTI) ablation.
Sixty patients referred for first PVI were randomized into ablation with irrigated gold tip catheter versus irrigated Pt tip catheter. Forty-nine patients received ablation of CTI following PVI. Mean and standard deviation from all measurements were calculated for each patient. During RFA of pulmonary veins, mean catheter tip temperature was significantly lower in the gold group (35.4 ± 0.9 °C vs 38.2 ± 0.8 °C, P < 0.001), and total amount of delivered energy was higher (1303.1 ± 81.1 W vs 1223.7 ± 115.6 W, P = 0.004). During CTI ablation, necessary saline flow was almost 2.5-fold lower in the gold group (22.5 ± 5.9 mL/min vs 52.5 ± 9.7 mL/min, P < 0.001), accompanied by significantly lower tip temperature (39.1 ± 0.6 °C vs 40.5 ± 1.4 °C, P < 0.001).
The irrigated gold tip electrode allows to deliver significantly more energy at a lower electrode tip temperature in RFA of PV and CTI in comparison to the irrigated Pt tip electrode. The required saline flow during CTI ablation is much lower than in Pt.
Journal of Cardiovascular Electrophysiology 03/2012; 23(7):717-21. · 3.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Since predictors of recurrence of atrial fibrillation (AF) after ablation procedures are poorly defined, this prospective study was conducted to assess the value of left atrial (LA) deformation imaging with two-dimensional speckle-tracking (2D-ST) to predict AF recurrences after successful ablation procedures.
One hundred and three consecutive patients (age 58.1 ± 16.6 years, 72.8% male) with AF (76 paroxysmal, 27 persistent) and 30 matched controls underwent transthoracic echocardiography and 2D-ST-LA-deformation analysis with assessment of LA-radial and LA-longitudinal strain (Sr, Sl), and velocities derived from the apical 4- and 2-chamber views (4CV, 2CV). AF recurrence was assessed during 6 months of follow-up. For determination of AF-related LA changes, AF patients were compared to controls and patients with AF recurrences after ablation procedures (n = 30, 29.1%) were compared with patients who maintained sinus rhythm (n = 73, 70.9%). Atrial deformation capabilities were significantly reduced (P < 0.0005) in patients with AF (4CVSl 17.8 ± 13.5%; 4CVSr 22.3 ± 14.9%; 4CV-velocities 2.53 ± 0.97 seconds) when compared with controls (4CVSl 31.3 ± 12.4%; 4CVSr 30.3 ± 9.1%; 4CV-velocities 3.48 ± 1.01 cm/s). Independent predictors for AF recurrence after ablation procedures were 2CV-LA-global-strain (Sr, P = 0.03; Sl, P = 0.003), 4CV-LA-gobal-strain (Sr, P = 0.03; Sl, P = 0.02), and regional LA-septal wall-Sl (P = 0.008). LA-global-strain parameters were superior to regional LA function analysis for the prediction of AF recurrences, with cutoff values (cov), hazard ratios (HR), positive and negative predictive values (PPV, NPV) were: 4CVSl cov, 10.79% (HR 27.8, P < 0.0005; PPV 78.8%, NPV 93.9%), 4CVSr cov, -16.65% (HR 24.8, P < 0.0005; PPV 69.4%, NPV 96.6%), 2CVSl cov, 12.31% (HR 22.7, P < 0.0005; PPV 75.8%, NPV 95.3%), and 2CVSr cov, -14.9% (HR 12.9, P < 0.0005; PPV 64.3%, NPV 93.2%).
Compared with controls, AF itself seems to decrease LA deformation capabilities. The assessment of global LA strain with 2D-ST identifies patients with high risk for AF recurrence after ablation procedures. This imaging technique may help to improve therapeutic guiding for patients with AF.
Journal of Cardiovascular Electrophysiology 09/2011; 23(3):247-55. · 3.48 Impact Factor