Hartmut Gülker

Coagulation of Ventricular Myocardium Using Radiofrequency Alternating Current: Bio‐Physical Aspects and Experimental Findings

Within the last years, a variety of different energy sources has been investigated to test their feasibilty for catheter ablation of myocardial tissue. This report summarizes our experience of the use of radiofrequency alternating current (500 kHz, unipolar mode) for coagulation of ventricular myocardium in canine experiments. Under standardized in vitro conditions, we found a significant correlation between actually delivered radiofrequency energy and assesed myocardial necrosis (r = 0.87). However, this did not hold for percutaneous application of radiofrequency alternating current to the beating dog heart (r = 0.32). In the intact dog heart, the size of induced lesions paralleled catheter contact pressure which was varied until ST‐egment elevation was either 0–2 mV or 5–7 mV. However, no statistical significant differences in either calculated energy or tissue impedance were observed. Under in vivo conditions, a significant improvement in the predictability of the resulting size of lesions was observed when catheter tip temperature, measured via a built‐in Ni/CrNi thermoelement, was monitored (r = 0.07). Changes in tip temperature during coagulation also indicated the quality of catheter contact, catheter damage and the appearance of carbonization at the tip of the ablation catheter. Total perforation of the myocardial wall and proarrhythmogenic effects were only rarely observed. In conclusion, catheter coagulation of myocardial tissue using radiofrequency energy can be considered as safe and effective. Since changes in catheter tip temperature occurring during coagulation were found to predict the extent of induced tissue necrosis, the development of temperature controlled radiofrequency devices seems promising and necessary.

C/T polymorphism of the intercellular adhesion molecule-1 gene (exon 6, codon 469). A risk factor for coronary heart disease and myocardial infarction

BACKGROUND The intercellular adhesion molecule-1 (ICAM-1) mediates the interaction of activated endothelial cells with leukocytes and plays a fundamental role in the pathogenesis of coronary atherosclerosis. ICAM-1 single-base C/T polymorphism, which determines an amino acid substitution in the ICAM-1 protein in exon 6 codon 469, has been described. Our purpose was to determine whether this C/T polymorphism influences the risk of coronary heart disease (CHD) and myocardial infarction (MI) in humans. METHODS AND RESULTS We enrolled 349 patients with angiographically documented CHD, including a sub-group of 179 patients with acute or chronic MI. The control group consisted of 213 patients with normal left ventricular function and no documented evidence of CHD. All patients and controls were Germans genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for the ICAM-1 polymorphism. In the patients with CHD and MI the frequencies of the T genotype (TT+TC) were significantly higher than the CC genotype compared to the control subjects (P<0.001). With the additional use of multivariable logistic regression analysis for CHD (TT+TC versus CC; P=0.011, odds ratio 2.21, 95% CI 1.20-4.07), we found a significant association between CHD and MI and the TT and TC genotype of the ICAM-1 gene polymorphism. CONCLUSIONS These results suggest that the TT and TC genotype of the ICAM-1 gene polymorphism in codon 469 is a genetic factor that may determine an individuals susceptibility for CHD and MI.

Frequency and quantity of the parvovirus B19 genome in endomyocardial biopsies from patients with suspected myocarditis or idiopathic left ventricular dysfunction

n Zusammenfassung Parvovirus B19 (PB19) gilt als Erreger der Myokarditis und als möglicher Auslöser einer Herzinsuffizienz im Kindes- und Erwachsenenalter. In der vorliegenden Studie wurde mittels quantitativer PCR-Analyse (real time PCR) die Häufigkeit und Quantität von PB19-Genom in Endomyokardbiopsien von 80 Patienten mit Verdacht auf Myokarditis oder idiopathischer linksventrikulärer Funktionsstörung und 36 Kontrollenpersonen ermittelt. Das Vorliegen einer Entzündung des Myokards wurde durch histologische (Dallas-Klassifikation) und immunhistologische Untersuchungen der Myokardbiopsien erfasst. PB19-Virusgenom konnte bei 9 von 80 Patienten (11,2%) bioptisch nachgewiesen werden. Bei 4 von 31 (12,9%) Patienten mit immunhistologisch nachgewiesenen entzündlichen Infiltraten im Myokard und bei 5 von 49 (10,2%) Patienten mit linksventrikulärer Dysfunktion ohne Entzündungszeichen in der Myokardbiopsie. Die Menge viraler PB19-DNA in der Endomyokardbiopsie lag zwischen 30 und 3900 Kopien pro μg zellulärer DNA. Vier Patienten mit dem klinischen Verdacht auf Myokarditis hatten Kopienzahlen für PB19 DNA von 70, 740, 3400 und 3900 pro μg zellulärer DNA in der Endomyokardbiopsie. Fünf Patienten mit idiopathischer linksventrikulärer Dysfunktion ohne entzündliche Infiltrate im Myokard wiesen bioptisch Kopienzahlen für PB19-DNA von 30, 38, 52, 58 und 90 pro μg zellulärer DNA auf. Die Sequenzierung eines der neun positiven PCR-Fragmente zeigte eine identische Sequenz zu den publizierten PB19-VP1/VP2-Genen (NCBI-Genbank). Bei allen Patienten konnte eine akute Myokarditis histologisch nach den Dallas-Kriterien ausgeschlossen werden. Alle Biopsien der 36 Kontrollpersonen, die weder bioptisch eine Myokarditis noch eine positive Anamnese für eine kürzlich durchgemachte Virusinfektion aufwiesen, waren für PB19-DNA negativ. Zusammengefasst zeigen die vorliegenden Ergebnisse, dass PB19-Virusgenom in Endomyokardbiopsien von Patienten mit Verdacht auf Myokarditis und idiopathischer linksventrikulärer Funktionsstörung mittels real time PCR erfasst und quantifiziert werden kann. Parvovirus B19 (PB19) has been identified as a possible cause of myocarditis and heart failure in both children and adult patients. This study used real time PCR analysis, to determine the frequency and to quantify PB19 viral genomes in endomyocardial tissue samples from 80 adult patients with clinically suspected myocarditis or idiopathic left ventricular dysfunction and from 36 controls. Histological (Dallas classification) and immunohistological analyses were performed to detect myocardial inflammation in the endomyocardial biopsies. PB19 genomic DNA was found in nine of 80 patients (11.2%), 4 out of 31 (12.9%) patients with inflammatory infiltrates detected via immunohistological methods and 5 out of 49 (10.2%) patients with left ventricular dysfunction without myocardial inflammation. The copy numbers for PB19 DNA ranged between 30 and 3900 per μg of cellular DNA. Four patients with clinically suspected myocarditis had copy numbers for PB19 DNA of 70, 740, 3400 and 3900, respectively, per μg of cellular DNA in the endomyocardial biopsy. Five patients with idiopathic left ventricular dysfunction had copy numbers for PB19 DNA of 30, 38, 52, 58 and 90, respectively, per μg of cellular DNA in the endomyocardial biopsy. The amplicon of one of the nine positive PCR fragment was sequenced and was found to be fully identical in the highly conserved sequence of published Parvovirus B19 VP1/VP2 genes (NCBI gene bank). In all patients, acute myocarditis was excluded according to the Dallas classification. All biopsies of 36 controls with no history of myocarditis or recent viral infection were negative for myocardial inflammation and parvovirus B19 genomes. In summary, Parvovirus B19 DNA is present within the myocardium of patients with suspected myocarditis and idiopathic left ventricular dysfunction and can be detected and quantified in endomyocardial specimens via real time PCR.

Screening for undiagnosed diabetes in patients with acute myocardial infarction

BackgroundScreening for undiagnosed diabetes in patients with acute myocardial infarction is recommended (ESC and EASD Task Force 2007). Glucose tolerance testing in the peri-infarct period may not be valid because of confounding, e.g. by the acute stress reaction. The aim was to evaluate undiagnosed diabetes (DM) and impaired glucose regulation (IGR) in AMI during hospital stay and 3 months after discharge.Materials and methodsIn 96 consecutively admitted AMI patients (Heart Center Wuppertal, Germany) OGTT were performed, of whom in 62 OGTT were also carried out 3 months later.ResultsBefore discharge 32% of the patients had newly diagnosed diabetes and 47% patients had prediabetes (IGR). Glucose tolerance was normal in 20 (21%) patients only. After 3 months, 74% with newly diagnosed DM at baseline still had disturbed glucose metabolism (58% DM, 16% IGT). No patient with normal OGTT became diabetic after 3 months. In multivariate regression, the odds of having diabetes (3 months) was about sixfold higher when having diabetes before discharge (OGTT). Admission glucose, infarction size CKMAX, and inflammation (CRP) were not significantly related to OGTT results.ConclusionsThis prospective study confirms a high prevalence of undiagnosed DM in patients with AMI. In about 60% of AMI patients, newly diagnosed DM persisted after 3 months. For the first time we could show that there is no correlation between infarction size and undiagnosed diabetes. Thus, an OGTT performed before discharge may provide a reliable measure of disturbed glucose regulation but needs to be repeated.

High prevalence of undiagnosed impaired glucose regulation and diabetes mellitus in patients scheduled for an elective coronary angiography

SummaryBackgroundImpaired glucose regulation (IGR) and diabetes mellitus (DM) are amongst the main risk factors for developing coronary heart disease (CHD). The aim of this study was to investigate previously unknown glucose metabolism disorder in patients scheduled for an elective coronary angiography.MethodsA total of 141 patients scheduled for coronary angiography without signs of acute myocardial ischemia or previous history of a glucose metabolism disorder were prospectively included in the study. An oral glucose tolerance test (OGTT) was performed in each patient.ResultsIGR was diagnosed in 40.4% (95% confidence interval 32.3–49.0) and undetected DM in 22.7% (16.1–30.5) of patients undergoing an elective coronary angiography. Depending on the severity of CHD, the percentage of IGR and DM increased up to 45.3% (34.6–56.5) and 26.7% (17.8–37.4) in the subgroup with the need of percutaneous angioplasty, while the corresponding proportions in the group without CHD were 30.3% (15.6–48.7) and 12.1% (3.4–28.2). The percentage of undiagnosed DM increased with the number of epicardial vessels involved. Using the recommended fasting plasma glucose value of ≥ 126 mg/dl for the diagnosis of DM, we would have missed 71.9% of the patients with undiagnosed DM.If all patients with a fasting plasma glucose of ≥ 90 mg/dl had been subjected to OGTT, 93.8% of DM would have been identified.ConclusionsPrevalences of DM and IGR are higher than expected in patients with CHD. An OGTT should be considered for all patients with a fasting plasma glucose ≥ 90 mg/dl undergoing a coronary angiography.

Six sequence variants on chromosome 9p21.3 are associated with a positive family history of myocardial infarction: a multicenter registry

BackgroundRecent genome-wide association studies have identified several genetic loci linked to coronary artery disease (CAD) and myocardial infarction (MI). The 9p21.3 locus was verified by numerous replication studies to be the first common locus for CAD and MI. In the present study, we investigated whether six single nucleotide polymorphisms (SNP) rs1333049, rs1333040, rs10757274, rs2383206, rs10757278, and rs2383207 representing the 9p21.3 locus were associated with the incidence of an acute MI in patients with the main focus on the familial aggregation of the disease.MethodsThe overall cohort consisted of 976 unrelated male patients presenting with an acute coronary syndrome (ACS) with ST-elevated (STEMI) as well as non-ST-elevated myocardial infarction (NSTEMI). Genotyping data of the investigated SNPs were generated and statistically analyzed in comparison to previously published findings of matchable control cohorts.ResultsStatistical evaluation confirmed a highly significant association of all analyzed SNPs with the occurrence of MI (p < 0.0001; OR: 1.621-2.039). When only MI patients with a positive family disposition were comprised in the analysis a much stronger association of the accordant risk alleles with incident disease was found with odds ratios up to 2.769.ConclusionsThe findings in the present study confirmed a strong association of the 9p21.3 locus with MI particularly in patients with a positive family history thereby, emphasizing the pathogenic relevance of this locus as a common genetic cardiovascular risk factor.

Nd:YAG laser-photocoagulation: acute electrophysiological, hemodynamic, and morphological effects in large irradiated areas.

Laser‐photocoagulation (LPC) of arrhythmogenic myocardium has been reported to successfully ablate ventricular tachycardia. The purpose of this study was to investigate the acute hemodynamic and electrophysiological effect of continuous laser energy (Nd: YAG, 1060 nm) applied via a 0.4‐mm quartz fiberoptic on the epicardial surface of the heart in nine dogs. A total of 51 ± 2.3 pulses was delivered in each animal to induce homogeneous tissue necrosis. Applied energy was 12.3 ± 2.7 J/mm2, irradiated surface measured 12.6 ± 3.0 cm2, lesion depth was 6.3 ±1.2 mm (range: 5.0–8.1 mm), lesion volume was 8.1 ± 2.8 cm3 (6.8% of left ventricular [LV] mass). After LPC, epicardial stimulation threshold significantly rose from 1.0 ± 0.3 to 10.2 ± 4.9 mA in the border zone to nontreated tissue and from 0.9 ± 0.4 to 32 ± 15.7 mA in the center of the lesions. Loss of epicardial activation in the irradiated areas could be demonstrated by epicardial mapping. Ventricular extrasystoles during LPC were seen in all dogs, ventricular tachycardia in seven, and ventricular fibrillation in two dogs. After LPC, cardiac output and LV dP/dtmax significantly decreased by 14.2% and 11.2%. LPC induced predictable homogeneous tissue edema, eosinophilic staining, contraction band necrosis, and sharp demarcated hemorrhagic border zones with a sharp electrical border zone to nontreated tissue and loss of epicardial activation. During LPC, various arrhythmogenic effects could be observed. However, no persistent arrhythmic activity developed after LPC. The results confirm the feasibility of epicardial LPC of the myocardium. Although not tested in this study, LPC of arrhythmogenic tissue may also be feasible as a treatment modality of ventricular tachycardia.

Left Ventricular Malposition of a Transvenous Cardioverter Defibrillator Lead: A Case Report

A case of left ventricular endocardial malposition of a transvenous implantabie cardioverter defibrillator (ICD) lead through a patent foramen ovale is presented. Diagnostic modalities include lateral chest radiography, echocardiography, and electrocardiographic analysis during lead placement. The operative therapy consists of open lead replacement. Measures to avoid lead misplacement are suggested.

Wolff–Parkinson–White syndrome associated with persistent left superior vena cava

Priv.-Doz. Dr. med. Marc Horlitz ()) · Philipp Schley Anja Thiel · Dong-In Shin · Michael Müller · Rolf Michael Klein Hartmut Gülker HELIOS Klinikum Wuppertal Universitätsklinikum der Universität Witten/Herdecke Herzzentrum Wuppertal, Kardiologie Arrenberger Str. 20 42117 Wuppertal Tel.: 02 02/8 96-57 08 Fax: 02 02/8 96-57 07 E-Mail: mhorlitz@wuppertal.helios-kliniken.de A highly symptomatic young female patient with a Wolff-Parkinson-White (WPW) syndrome underwent radiofrequency catheter ablation. The surface ECG indicated an accessory pathway in a left posterior location. Achieving a good ablation site underneath the posterior mitral valve was not feasible by a retrograd transaortal approach. Therefore, the mapping catheter was advanced to the proximal coronary sinus (CS) via femoral vein access. Since the CS ostium appeared dilated, contrast angiography was performed, revealing a persistent left superior vena cava (PLSVC) draining into a significantly enlarged CS (Fig. 1). Recurrent episodes of atrial fibrillation with rapid preexcited ventricular rate occurred during the procedure (Fig. 2). In this anatomically challenging situation, the optimal ablation site was identified within the proximal CS. The preexcitation disappeared during successful ablation. The existence of other cardiac anomalies could be excluded by magnetic resonance imaging (Fig. 3). PLSVC is an uncommon anomaly, estimated to be present in 0.3–0.5% of the population [2]. It results from an embryological defect involving failure of the left cardinal vein to degenerate [3]. Commonly, this malformation is hemodynamically insignificant, and simultaneous complete absence of the right superior vena cava is rare [5]. However, because of the large

Effects of β-Blockade on the Incidence of Ventricular Tachyarrhythmias during Acute Myocardial Ischemia: Experimental Findings and Clinical Implications

Myocardial ischemia and infarction are the most common substrates for life-threatening ventricular tachyarrhythmias. Experimental and clinical evidence suggests that enhanced activity of the sympathetic nervous system plays an important role in the genesis of ischemia-related arrhythmias. In animal experiments, β-blockers display significant antifibrillatory effects during the acute phase of myocardial ischemia. Preconditions for their antifibrillatory effects are high serum- and tissue-concentrations, and absence of a significant partial agonist activity. During the delayed phase of ischemic arrhythmias which starts 6–8 h after coronary occlusion, β-blockers gain significance as antiarrhythmic and potentially antifibrillatory drugs, if sympathetic activity is enhanced.