A rare type of ventricular oversensing in ICD therapy--inappropriate ICD shock delivery due to triple counting.

Irregular sensing by triple counting of wide QRS complexes resulted in inappropriate shocks in a patient with a biventricular implantable cardioverter defibrillator (ICD): A 66-year-old male patient with ischemic cardiomyopathy, left bundle branch block, and impaired left ventricular function received a biventricular ICD for optimal therapy of heart failure (CHF). Two years after implantation, the patient experienced recurrent unexpected ICD shocks without clinical symptoms of malignant tachyarrhythmia, or worsened CHF. The patient's condition rapidly worsened, with progressive cardiogenic shock and electrical-mechanical dissociation. After unsuccessful resuscitation of the patient the interrogation of the ICD showed an initial triple counting of extremely wide and fragmented QRS complexes with inappropriate shocks.

Transcatheter closure of patent foramen ovale in patients with cerebral ischemia.

OBJECTIVES: The present study was conducted to determine the safety of the transcatheter closure of a patent foramen ovale (PFO) in patients with cryptogenic cerebral ischemia and the midterm follow-up of recurrent thromboembolic events after interventional PFO closure. BACKGROUND: Current therapeutic options for stroke prevention in patients with PFO and a history of thromboembolic events include chronic antithrombotics and more invasive treatments such as surgical closure or minor invasive transcatheter permanent closure of the PFO. Promising preliminary and pilot data with the Amplatzer Septal Occluder or the PFO-Star Occluder have been reported. Systematic and long-term data are still missing. METHODS: A total of 276 consecutive patients with a PFO and a history of at least one thromboembolic event were recruited in four medical centers and underwent percutaneous PFO closure with the PFO-Star device. Follow-up data were analyzed over an average of 15.1 months, equivalent to 345 patient-years. RESULTS: The implantation was successful in all 276 patients. Peri-interventional reversible complications included transient ST-segment elevations (1.8%) and transient ischemic attack (TIA) (0.8%). Two devices have been removed surgically. During follow-up the annual recurrence rate of thromboembolic events was 1.7% for TIA, 0% for stroke and 0% for peripheral emboli. CONCLUSIONS: Interventional PFO closure with the PFO-Star device appears to be a reliable and promising technique resulting in a low recurrence rate of thromboembolic events, especially stroke in patients with a history of cryptogenic ischemia presumably due to paradoxical embolization. To our knowledge, this is the largest coherent and prospective study for interventional PFO closure.

Impedance cardiography as a noninvasive technique for atrioventricular interval optimization in cardiac resynchronization therapy.

INTRODUCTION: Impedance cardiography (IC) and Doppler echocardiography (DE) are two noninvasive methods to evaluate hemodynamics in patients with dual-chamber pacemakers. The aim of the present study was to compare both techniques in respect to their ability of AV-interval optimization in cardiac resynchronization therapy (CRT) based on cardiac output (CO) measurements. METHODS AND RESULTS: Twenty-four patients (64 +/- 8 years) with congestive heart failure (EF<35%; NYHA III-IV) and LBBB (>150 ms) were evaluated at baseline and 1 month after implantation of a CRT-D. The optimal AV interval was defined by IC and subsequently by transaortic flow DE as the interval corresponding to the highest CO measured at different AV intervals, varying from 60 to 200 ms (with 20 ms increments). For standardization and comparison of both techniques, a fixed atriobiventricular pacing rate of 90 beats/min was used. Absolute values of COmax were higher by IC (5.8+/-0.9 l/min) as compared to DE (4.6 +/- 0.9 l/min, p < 0.01). The optimal AV interval as determined by IC varied interindividually from 80-180 ms (mean: 121+/-18 ms). In DE, the range was also 80-180 ms with the mean optimal AV interval of 128+/-23 ms. Thus, there was a strong correlation for AV-interval optimization in CRT between both methods (r=0.74; p<0.001). CONCLUSION: In CRT, AV-interval optimization based on CO values determined by IC correlates closely to those measured by transaortic flow DE. Impedance cardiography as an easy and cost-effective technique for AV-interval optimization is a promising alternative for routine management of heart failure patients on a beat-to-beat analysis during CRT follow-up.

Right ventricular hypertrophy and apoptosis after pulmonary artery banding: regulation of PKC isozymes.

OBJECTIVE: Pressure overload induced by pulmonary artery banding (PAB) leads to right ventricular (RV) hypertrophy and cardiomyocyte apoptosis. The present study was performed to investigate whether protein kinase C isozymes (PKC-alpha, PKC-betaI, PKC-betaII, PKC-delta and PFC- epsilon ), calcineurin and the renin-angiotensin system (RAS) contribute to PAB-induced cardiac remodeling. METHODS AND RESULTS: PAB in male Wistar rats for 3 weeks results in enhanced PKC activity (as determined by ELISA assay) in the cytosol and membrane fraction of the hypertrophied RV, which was accompanied by increased expression (as determined by Western blot analysis) of cytosolic PKC-delta (+72%), PKC-alpha (+49%), and PKC-betaI (+39%), but not PKC-betaII and PKC- epsilon. This differential regulation of cardiac PKC isozymes was limited to the strained ventricle and was not altered in response to chronic angiotensin-converting enzyme inhibition with ramiprilate. Furthermore, no significant changes in the expression of calcineurin alpha and beta subunits were observed in RV pressure overload compared to controls. PAB-induced cardiac apoptosis was determined using Western blot analysis by a significantly increased expression of Bax protein and caspase-3 in the hypertrophied RV, which was diminished to almost control levels by chronic ramiprilate treatment. The myocardial expression of Bcl-2 was not significantly altered in the experimental groups. CONCLUSION: We have shown for the first time that PAB-induced RV hypertrophy is associated with a differential regulation of cardiac PKC isozymes independent of the RAS and further provide evidence for a pivotal role of the RAS in the development of PAB-induced cardiac apoptosis.

Differential regulation of cardiac protein kinase C isozyme expression after aortic banding in rat.

OBJECTIVE: Protein kinase C (PKC) plays a key role in myocardial hypertrophy. To evaluate whether its isoforms are expressed differentially during gradual development of pressure-overload-induced cardiac hypertrophy, banding of the ascending aorta was used as an experimental model of left ventricular hypertrophy. METHODS: One, 7 and 30 days after sham operation or aortic banding in male Wistar rats, the PKC activity and the expression of the cardiac PKC isozymes (PKC-alpha, -delta, - epsilon and -zeta), both at the protein and the mRNA level, were determined in the left and right ventricle. RESULTS: Left ventricular hypertrophy developed rapidly as early as 1 day after aortic banding followed by further progression at day 7 and day 30. This was paralleled by an increased total PKC enzyme activity in the cytosol fraction and a selectively enhanced protein expression of PKC-delta (day 7, 267+/-18%; day 30, 289+/-12%) and PKC-alpha (day 7, 212+/-20%; day 30, 193+/-14%). The protein amount of PKC- epsilon was not changed in either group. This differential protein expression was associated with a significant increase of the absolute mRNA levels for PKC-delta and PKC-alpha up to 202+/-20% (day 30) and 177+/-17% (day 30), whereas significant alterations in the PKC- epsilon mRNA levels were not detected. A selective upregulation of PKC-alpha and PKC-delta, both on the protein and on the mRNA level, was also noted in the right ventricle during the development of right ventricular hypertrophy, suggesting an adaptive response following elevated left ventricular enddiastolic pressure after long-term aortic banding for 30 days. CONCLUSIONS: This study characterizes in the right and left ventricle a differential regulation of the dominant PKC isozymes in pressure-overload cardiac hypertrophy both at the protein and the mRNA level.

Dual mechanism of autoregulation of protein kinase C in myocardial ischemia.

BACKGROUND: Recently, a dual activation mechanism of protein kinase C (PKC) in ischemia has been reported, consisting of early translocation and late expressional regulation. Moreover, autophosphorylation of the enzyme has been shown in vitro during its activation. This study aimed to show modes of late activation of PKC in myocardial ischemia in intact hearts. METHODS AND RESULTS: Isolated perfused hearts of male Wistar rats were used. A: To examine if the early translocation of PKC influences the late transcriptional activation, hearts were treated with the PKC-inhibitor Bisindolylmaleimid (BIS, 0.25 microM) before the onset of ischemia and then subjected to ischemia (30 min). PKC-isoform mRNA was quantified by RT-PCR. In these experiments, ischemia leads to a selective increase of mRNA specific for the isoforms PKC-delta and PKC-epsilon (163% and 168% of control, p<0.05). This ischemia-induced upregulation could be completely blocked by BIS given before the onset of ischemia. B: To test the capacity of PKC to undergo phosphorylation during ischemia, hearts were perfused with [32P]-phosphorus and then subjected to ischemia. Ischemia (30 min) induced a significant 3-fold increase of PKC phosphorylation. Stimulation of heart with the PKC-activator tetradecanoylphorbol-13-acetate (TPA) lead to a comparable phosphorylation, suggesting that ischemia leads to autophosphorylation of PKC. CONCLUSION: Ischemia activates two distinct forms of autoregulation of PKC. The expressional upregulation of PKC-delta and PKC-epsilon is dependent on early activation of the enzyme. At the same time, processes of enzyme phosphorylation occur. Both the mechanisms may contribute to enzyme activation processes beyond the classical enzyme translocation.

Single coronary artery with anomalous origin from the right sinus Valsalva.

A single coronary artery is a rare congenital anomaly with an incidence of 0.02-0.04%. We report on a 65-year-old male presenting with atypical chest pain and a history of hypertension and hypercholesterinemia, having diagnosed a very rare variant of a single coronary artery arising from the right sinus of Valsalva continuing as circumflex coronary artery (LCX) and thereafter as left anterior descending artery (LAD). Because the patient was asymptomatic on antiischemic medication and had a proposed relative benign course, we recommended medical treatment without coronary artery bypass surgery, and the patient has been in fine condition up to now (11 months after angiography).

Percutaneous lead implantation connected to an external device in stimulation-dependent patients with systemic infection--a prospective and controlled study.

BACKGROUND: Permanent pacemaker implantation usually is contraindicated in patients with systemic infection. The aim of the present study was to compare two different techniques of transvenous temporary pacing to bridge the infectious situation until permanent pacemaker implantation under infection-free conditions is possible. METHODS AND RESULTS: Forty-nine patients with systemic infection and hemodynamic-relevant bradyarrhythmia/asystole were temporarily paced using either a conventional pacing wire/catheter (n = 26, reference group) or a permanent bipolar active pacing lead, which was placed transcutaneously in the right ventricle and connected to an external pacing generator (n = 23, external lead group). In both groups, there were no significant differences in patient characteristics. Whereas the sensing values were almost identical, the median pacing threshold was significantly higher in the reference group (1.0 V vs 0.6 V, P < 0.05). Within comparable duration of pacing (median: 8.2 vs 7.7 days), there were 24 pacing-related adverse events (including dislocation, resuscitation due to severe bradycardia, or local infection) in the reference group as compared to one event in the external lead group (P < 0.01). None of these complications resulted in cardiac death. CONCLUSION: Thus, transvenous pacing with active fixation is safe and associated with a significantly lower rate of pacing-related adverse events as compared to the standard technique of transvenous pacing using a passive external pacing catheter.

Perforation of aortic root as secondary complication after implantation of patent foramen ovale occlusion device in a 31-year-old woman.

Transesophageal echocardiography (TEE) revealed a 3-mm-large patent foramen ovale (PFO). No other reason for these neurological events could be found and the patient underwent percutaneous closure of the PFO with a CARDIA Star 03/30 device without periprocedural complications. Four weeks later, the patient underwent a routine control of device without any adverse clinical symptoms. Surprisingly, echocardiography revealed a perforation of the aortic root by an umbrella strut with a small shunt from the aortic root to the right atrium. Magnetic resonance imaging (MRI) confirmed the diagnosis of device malposition. Consecutively, the patient underwent minimal invasive surgery. After removal of the single perforating strut, the bleeding lesion was closed. The patient remained free of any additional complications during the postoperative course and up until now has had uneventful follow-ups.

Regulation of the isozymes of protein kinase C in the surviving rat myocardium after myocardial infarction: distinct modulation for PKC-alpha and for PKC-delta.

OBJECTIVE: The goal of this study was to clarify the regulation of the isozymes of protein kinase C (PKC) in the process of remodeling after myocardial infarction. METHODS: An in vivo model of regional myocardial infarction induced by ligation of the left anterior coronary artery in rats was used. Hemodynamic parameters and the heart and lung weights were determined 1 week and 1, 2 and 3 months after operation. In transmural biopsies from the non-ischemic left ventricular wall of the infarcted heart, PKC activity (ELISA) and the expression of its major isozymes, PKC-alpha, PKC-delta and PKC-epsilon (Westernblot analysis) were determined. RESULTS: As early as one week after myocardial infarction, heart weight and left ventricular enddiastolic pressures were significantly increased. Lung weights increased after 2 - 3 months, indicating progressive pulmonary congestion. The activity of PKC was significantly increased about 1.8-fold after 1 week, decreasing progressively in the later time course. Whereas the expression of PKC-epsilon did not change, PKC-alpha was increased after 1 month (157%) and then returned to baseline values. In contrast, PKC-delta expression was significantly augmented after 2 and 3 months of myocardial infarction (187%). CONCLUSIONS: These data demonstrate for the first time that in the remodeling heart after myocardial infarction, a subtype-selective regulation of the PKC isozymes occurs: The upregulation of PKC-alpha coincides with the development of hypertrophy, whereas the extensive upregulation of PKC-delta outlasts the process of developing hypertrophy and persists in the failing heart. The trigger mechanisms for this newly characterized process remains to be elucidated.

Regulation of protein kinase C isozymes in volume overload cardiac hypertrophy.

Protein kinase C (PKC) is a family of at least 11 isozymes and known to play a crucial role in myocardial growth. The present study was performed to investigate whether PKC-isozymes are differentially regulated during the development of volume-overload cardiac hypertrophy. After 2, 7 and 30 days of sham or aortocaval shunt operation in male Wistar rats, PKC-activity and the expression of cardiac PKC-isozymes (PKC-alpha, delta and epsilon) were determined at the protein and at the mRNA-level in the left and the right ventricle separately. Myocardial hypertrophy after 2, 7 and 30 days of aortocaval shunt was more pronounced in the right than in the left ventricle. Right ventricular hypertrophy was associated with an increased PKC-enzyme activity, a selectively enhanced protein expression of cytosolic PKC-delta (day 7: +83 +/- 12%, day 30: +94 +/- 14%) and PKC-alpha (day 7: +48 +/- 11%, day 30: +62 +/- 16%) and a transcriptional upregulation of the absolute mRNA-levels of these PKC-isozymes in the aortocaval shunt group as compared to controls. In contrast, the expression of PKC-epsilon was unchanged. A significant upregulation of PKC-delta both on the protein and on the mRNA-level was also noted in volume-overload induced left ventricular hypertrophy, whereas the expression of PKC-alpha and PKC-epsilon were not altered. Furthermore, the expression of calcineurin in both ventricles was not significantly changed in response to volume-overload. This study characterizes in the left and right ventricle a differential regulation of the dominant PKC-isozymes in volume-overload cardiac hypertrophy both at the protein and at the mRNA-level.

Mechanisms of myocardial remodeling: ramiprilat blocks the expressional upregulation of protein kinase C-epsilon in the surviving myocardium early after infarction.

Inhibition of angiotensin-converting enzyme (ACEI) after myocardial infarction reduces remodeling of the surviving myocardium. The cellular signaling mechanisms contributing to remodeling are not fully elucidated. Goal of the current study was to test whether protein kinase C (PKC) is regulated in the surviving myocardium shortly after infarction and whether this regulation is influenced by ACEI. Rats were subjected to anterior wall myocardial infarction in vivo or sham operation. After 15-45 min, mRNA levels and protein expression of the major cardiac PKC isoforms were measured in the ischemic and the remote myocardium. The influence of ACEI on PKC was tested by pretreating the rats with ramiprilat. In the ischemic region of the myocardium, a significant increase of the mRNA for PKC-delta and PKC-epsilon was observed in close correlation with increased isoform protein expression. In the surviving, remote myocardium, however, only PKC-epsilon expression was significantly augmented both at the mRNA level (158%) and at the protein level (149%). PKC-delta and PKC-alpha were unchanged. Treatment with ramiprilat could abolish this isoform-specific PKC regulation in both areas. These data characterize for the first time an isoform-specific transcriptional regulation process of PKC in the surviving myocardium after infarction. This induction of PKC-epsilon can be prevented by ACEI. It is speculated that PKC-epsilon plays a role in the signal transduction of early remodeling after infarction.