Diagnostic and prognostic value of miR-1 and miR-29b on adverse ventricular remodeling after acute myocardial infarction - The SITAGRAMI-miR analysis.

BACKGROUND: MicroRNAs (miRs) have shown to exert fibrotic and anti-fibrotic effects in preclinical models of acute myocardial infarction (AMI). The aim of this study was to evaluate miR-1, miR-21, miR-29b and miR-92a as circulating biomarkers for adverse ventricular remodeling (AVR) in post-AMI patients. METHODS: Plasma levels of miR-1, miR-21, miR-29b and miR-92a were measured in 44 patients of the SITAGRAMI trial population at day 4, day 9 and 6month after AMI and in 18 matched controls (CTL). MiR expression patterns were correlated with magnetic resonance imaging (MRI) parameters for AVR (absolute change (Δ) in infarct volume (IV), left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume (LVEDV) between day 4 and 6months after AMI) and a combined cardiovascular endpoint. RESULTS: Expression of miR-1, miR-21 and miR-29b but not miR-92a was increased in AMI vs. CTL cohort showing highest miR levels at d9. However, only miR-1 and miR-29b levels significantly correlated with ΔIV and showed a trend for correlation with ΔLVEF. Only miR-29b levels at day 9 correlated with ΔLVEDV at 6-month follow-up. There was no correlation of miR levels with an adverse outcome. CONCLUSION: Mir-1 and miR-29b plasma levels post-AMI correlate with IV changes. In addition, miR-29b levels are associated with changes of LVEDV over time. These results provide insights into the role of miRs as diagnostic AVR surrogate markers. Further large scale clinical trials will be needed to evaluate the real prognostic relevance of these miRs with respect to a clinical implication in the future.

Safety and efficacy in ablation of premature ventricular contraction: data from the German ablation registry.

BACKGROUND: Patients with frequent premature ventricular contractions (PVCs) are often highly symptomatic with significantly reduced quality-of-life. We evaluated the outcome and success of PVC ablation in patients in the German Ablation Registry. METHODS: The German Ablation Registry is a nationwide prospective multicenter database of patients who underwent an ablation procedure, initiated by the "Stiftung Institut für Herzinfarktforschung" (IHF), Ludwigshafen, Germany. Data were acquired from March 2007 to May 2011. Patients underwent PVC ablation in the enrolling ablation centers. RESULTS: A total of 408 patients (age 53.5 ± 15 years, 55 % female) undergoing ablation for PVCs were included. 32 % of patients showed a co-existing structural heart disease. Acute ablation success of the procedure was 82 % in the overall patient group. In patients without structural heart disease, acute success was significantly higher compared with patients with structural heart disease (86 vs. 74 %, p = 0.002). All patients were discharged alive after a median of 3 days. No patient suffered an acute myocardial infarction, stroke, or major bleeding. After 12 months' follow-up, 99 % of patients were still alive showing a significant different mortality between patients with structural heart disease compared with those without (2.3 vs. 0 %, p = 0.012). In addition, 76 % of patients showed significantly improved symptoms after 12 months of follow-up. CONCLUSION: Based on the data from this registry, ablation of PVCs is a safe and efficient procedure with an excellent outcome and improved symptoms after 12 months.

[Clinical development of the automatic implantable defibrillator over 35 years: A success story]. / Klinische Entwicklung des implantierbaren Kardioverter-Defibrillators über 35 Jahre : Eine Erfolgsgeschichte.

After 12 years of development and experimental evaluation, the first automatic implantable cardioverter-defibrillator (ICD) was implanted in man on February 4, 1980. This overview describes the technical and functional developments over 35 years from a simple shock-box, weighing 292 g, to the sophisticated 80 g device of today, delivering graded therapy to sustained ventricular arrhythmias and biventricular stimulation to treat heart failure. Finally, a special tribute is given to Michel Mirowski, one of the inventors of the ICD, as scientist and physician dedicated to patient care.

A single German center experience with intermittent inotropes for patients on the high-urgent heart transplant waiting list.

AIM: Currently, more than 900 patients with end-stage heart failure are listed for heart transplantation in Germany. All patients on the Eurotransplant high-urgent status (HU) have to be treated in intensive care units and have to be relisted every 8 weeks. Long-term continuous inotropes are associated with tachyphylaxia, arrhythmias and even increased mortality. In this retrospective analysis, we report our single center experience with HU patients treated with intermittent inotropes as a bridging therapy. METHODS AND RESULTS: 117 consecutive adult HU candidates were treated at our intensive care heart failure unit between 2008 and 2013, of whom 14 patients (12 %) were stabilized and delisted during follow-up. In the remaining 103 patients (age 42 ± 15 years), different inotropes (dobutamine, milrinone, adrenaline, noradrenaline, levosimendan) were administered based on the patient's specific characteristics. After initial recompensation, patients were weaned from inotropes as soon as possible. Thereafter, intermittent inotropes (over 3-4 days) were given as a predefined weekly (until 2011) or 8 weekly regimen (from 2011 to 2013). In 57 % of these patients, additional regimen-independent inotropic support was necessary due to hemodynamic instabilities. Fourteen patients (14 %) needed a left- or biventricular assist device; 14 patients (14 %) died while waiting and 87 (84 %) received heart transplants after 87 ± 91 days. Cumulative 3 and 12 months survival of all 103 patients was 75 and 67 %, respectively. CONCLUSION: Intermittent inotropes in HU patients are an adequate strategy as a bridge to transplant; the necessity for assist devices was low. These data provide the basis for a prospective multicenter trial of intermittent inotropes in patients on the HU waiting list.

Direct thermography-a new in vitro method to characterize temperature kinetics of ablation catheters.

PURPOSE: For the treatment of increasingly complex cardiac arrhythmias, new catheter designs as well as alternative energy sources are constantly being developed. However, there is presently no in vitro method available for assessment of the temperature changes induced at various myocardial levels during energy delivery. Therefore, our study was aimed at developing an in vitro model to record and display the temperature kinetics during ablation in the entire muscle cross section. METHODS AND RESULTS: A sapphire glass pane was inserted into one wall of the in vitro experimental set-up. Due to its thermodynamic properties, the temperature distribution in an adjacent cross section of the cardiac muscle can be measured exactly ( 1 °C) through this pane by means of a thermography camera. Computer-supported image processing enables the colour-coded and two-dimensional display of the temperature kinetics during the energy application at any location of the myocardial cross section (± 0.5 mm). This new measuring methodology was validated by direct temperature measurements utilizing several intramyocardial thermo elements. CONCLUSION: This new method allows a temporal and spatial analysis of the temperature phenomena during ablation without the interference and spatial limitation of intramyocardial temperature probes. New ablation technologies can thus be evaluated, independent of the catheter configuration or source of energy used.

[A rest or arrest--asystolic episodes of 7 seconds in a 22-year-old athlete]. / 22-jähriger Sportler mit Sinusarrest und Pausen bis 7 Sekunden.

A 22-year-old athlete with nocturnal asymptomatic episodes of transient sinus arrest/sinoatrial block up to 7.3 s and recurrent inappropriate sinus tachycardias which had been incidentally found during Holter electrocardiography diagnostics is presented. In spite of extensive diagnostic work-up including invasive procedures like coronary angiography and electrophysiological study, no causal etiology was found. Based on the normal findings and the lack of symptoms, we decided not to implant a permanent pacemaker. After 14 months, the patient is still asymptomatic. Howerver, the 24-h Holter electrocardiography shows unchanged frequency of nocturnal transient sinus arrest episodes.

Impact of the type of centre on management of AF patients: surprising evidence for differences in antithrombotic therapy decisions.

Atrial fibrillation (AF) patients may receive treatment from specialists or from general medicine physicians representing different levels of care within a structured health care system. This "choice" is influenced by patient flow within a health care system, patient preference, and individual access to health care resources. We analysed how the postgraduate training and work environment of treating physicians affects management decisions in AF patients. Patient characteristics and treatment decisions were analysed at the time of enrolment into the registry of the German Atrial Fibrillation NETwork (AFNET). A total of 9,577 patients were enrolled from 2004 to 2006 in 191 German centres that belonged to the following four levels of care: 13 tertiary care centres (TCC) enrolled 3,795 patients (39.6%), 58 district hospitals (DH) enrolled 2,339 patients (24.4%), 62 office-based cardiologists (OC) enrolled 2,640 patients (27.6%), and 58 general practitioners or internists (GP) enrolled 803 patients (8.4%). Patients with new-onset AF were often treated in DH. TCC treated younger patients who more often presented with paroxysmal AF. Older patients and patients in permanent AF more often received outpatient care. Consistent with recommendations, younger patients and patients with non-permanent AF received rhythm control therapy more often. In addition, the type of centre affected the decision for rhythm control. Stroke risk was similar between centre types (mean CHADS2 scores 1.6 -1.9). TCC (68.8%) and OC (73.6%) administered adequate antithrombotic therapy more often than DH (55.1%) or GP (52.0%, p<0.001 between groups). Upon multivariate analysis, enrolment by TCC or OC was associated with a 1.60 (1.20-2.12, p=0.001) fold chance for adequate antithrombotic treatment. This difference between centre types was consistent irrespective of the type of stroke risk estimation (ESC 2001 guidelines, CHADS2 score), and also consistent when the recently suggested CHA2DS2-VASc score was used to estimate stroke risk. In conclusion, management decisions in AF are influenced by the education and clinical background of treating physicians in Germany. Inpatients receive more rhythm control therapy. Adequate antithrombotic therapy is more often administered in specialist (cardiologist) centres.

Mortality due to myocardial infarction in the Bavarian population during World Cup Soccer 2006.

BACKGROUND: Previously, we had demonstrated that the World Cup Soccer 2006 provoked levels of emotional stress sufficient to increase the incidence of acute cardiovascular events. We sought to assess whether mortality was also increased as a result. METHOD: We analyzed daily data on mortality due to myocardial infarction (MI) and total mortality using data from the Bavarian State Office for Statistics. We retrospectively assessed study periods from 2006, 2005 and 2003. Quasi-Poisson regression with a log link to model the number of daily deaths was used. To be able to account for a possible delay, we also fitted a cubic distributed lag quasi-Poisson model for both 1 and 2 weeks post-exposure. RESULTS: A total of 6,699 deaths due to MI were investigated. No increase in death was found on days of World Cup matches either with or without German participation compared to the matched control periods. In addition, none of the analyses showed a significant effect of the (lagged) exposure to the risk period. Likewise, total mortality rates remained unchanged over the entire period of our analysis. CONCLUSION: During World Cup Soccer, the number of deaths due to myocardial infarction was not measurably increased compared to a matched control period. Thus, we could not demonstrate a translation of a stress-induced increase of cardiac morbidity into a noticeable increase in mortality. However, our findings are based on a public mortality registry, which may be flawed in many ways, regarding ascertainment of causes of death, in particular.

[Registry and studies of the German Competence Network on Atrial Fibrillation (AFNET)]. / Register und Studien des Deutschen Kompetenznetzes Vorhofflimmern (AFNET).

The German Competence Network on Atrial Fibrillation (AFNET) is a national interdisciplinary research network funded by the Federal Ministry of Education and Research (BMBF). AFNET was initiated in 2003 and aims at improving treatment of atrial fibrillation (AF), the most frequent sustained cardiac arrhythmia. AFNET has established a nationwide patient registry on diagnostics, therapy, course and complications of AF in Germany. The data analyzed to date demonstrate that patients with AF are likely to have multiple co-morbidities, such as hypertension, valvular heart disease, coronary artery disease, diabetes mellitus and advanced age. Oral anticoagulation is provided to the majority of patients in accordance with the recommendations given by guidelines. Further areas of research deal with the optimal duration of antiarrhythmic therapy following electrical cardioversion of atrial fibrillation and the value of strategies to prevent arrhythmogenic changes, such as fibrosis in the atria, for prevention of further episodes of atrial fibrillation. Additional registry projects were established for patients with catheter-based interventional therapy of atrial fibrillation and surgical ablation to define success, complications and long term results of these recently developed procedures more clearly. Data and insights gathered from these projects were used to further develop standards of care in two international conferences.

[ICD therapy for primary prevention. The patient in the early post-infarct phase]. / ICD-Therapie zur Primärprävention. Der Patient in der frühen Postinfarktphase.

There is high mortality during the first few weeks after an acute myocardial infarction. However, according to the guidelines, the prophylactic implantation of an ICD, given the corresponding risk constellation, is recommended not earlier than 1 month after acute myocardial infarction. This article analyzes available data and highlights that the recently published IRIS study supports current clinical practise.

Proton pump inhibitors reduce mycophenolate exposure in heart transplant recipients-a prospective case-controlled study.

This prospective study investigates the impact of proton pump inhibitors (PPI) on mycophenolic acid (MPA) pharmacokinetics in heart transplant recipients receiving mycophenolate mofetil (MMF) and tacrolimus. MPA plasma concentrations at baseline (C(0 h)), 30 min (C(0.5 h)), 1(C(1 h)) and 2 h (C(2 h)) were obtained by high-performance liquid chromatography (HPLC) in 22 patients treated with pantoprazole 40 mg and MMF 2000 mg. Measurements were repeated 1 month after pantoprazole withdrawal. A four-point limited-sampling strategy was applied to calculate the MPA area under the curve (MPA-AUC). Predose MPA concentrations with PPI were 2.6 +/- 1.6 mg/L versus 3.4 +/- 2.7 mg/L without PPI (p = ns). Postdose MPA concentrations were lower with PPI at C(0.5 h) (8.3 +/- 5.7 mg/L vs. 18.3 +/- 11.3 mg/L, p = 0.001) and C(1 h) (10.0 +/- 5.6 mg/L vs. 15.8 +/- 8.4 mg/L, p = 0.004), without significant differences at C(2 h) (8.3 +/- 6.5 mg/L vs. 7.6 +/- 3.9 mg/L). The MPA-AUC was significantly lower with PPI medication (51.2 +/- 26.6 mg x h/L vs. 68.7 +/- 30.3 mg x h/L; p = 0.003). The maximum concentration of MPA (MPA-C(max)) was lower (12.2 +/- 7.5 mg/L vs. 20.6 +/- 9.3 mg/L; p = 0.001) and the time to reach MPA-C(max) (t(max)) was longer with PPI (60.0 +/- 27.8 min vs. 46.4 +/- 22.2 min; p = 0.05). This is the first study to document an important drug interaction between a widely used immunosuppressive agent and a class of drugs frequently used in transplant patients. This interaction results in a decreased MMF drug exposure which may lead to patients having a higher risk for acute rejection and transplant vasculopathy.

CD36 mRNA expression is increased in CD14+ monocytes of patients with coronary heart disease.

1. Blood-derived monocytes/macrophages within the intima of the arterial wall are the main source of inflammatory cytokines and factors contributing to lesion growth, plaque instability and thrombotic events. In the present study, we assessed the hypothesis that mRNA expression levels of candidate genes of atherosclerosis in circulating CD14(+) blood monocytes are associated with coronary heart disease (CHD). 2. We investigated mRNA expression levels using reverse transcription-polymerase chain reaction of genes involved in cholesterol uptake (macrophage scavenger receptor (MSR1), scavenger receptor class B member 1 (SRB1), lectin-like oxidized low-density lipoprotein (LDL) receptor 1 (LOX1), CD36, LDL receptor (LDLR)), reverse cholesterol transport (apolipoprotein E (ApoE), ATP-binding cassette sub-family A member 1 (ABCA1)) and inflammation (tumour necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-1alpha (MIP-1alpha), interleukin-6 (IL-6), tissue factor) in CD14(+) monocytes from 119 consecutively recruited patients and found that median CD36 mRNA expression levels were significantly increased in patients with CHD compared with controls (111 x 10(3) vs 96 x 10(3) copies/10(6) copies beta-actin, respectively; n = 79 and 40, respectively; P < 0.05), despite a high interindividual variability in gene expression. 3. A common T --> C polymorphism (rs2151916) located only 14 bp upstream of the upstream transcriptional start site did not influence CD36 expression. 4. Expression levels of the other candidate genes investigated in the present study did not show any statistically significant differences between patients with CHD and controls. 5. We conclude that CD36 mRNA expression is significantly increased in patients with CHD and may serve as an indicator of CHD burden.

[Invasive electrophysiology: complications, nightmares and their management]. / Invasive Elektrophysiologie: Komplikationen, Alpträume und deren Management--Rechtskardiale Katheterablationen.

Most minor side effects of ablation in the right atrium and right ventricle relate to femoral venous catheterization but there is a small risk of severe complications including atrioventricular (AV) block, damage of surrounding structures and thromboembolic events. Impairment of AV conduction can occur during ablation of atrioventricular re-entrant tachycardia, ablation of anteroseptal, mid-septal and parahisian accessory pathways, ablation of ectopic atrial tachycardia originating from the vicinity of the atrioventricular node and when ablating the septal isthmus for typical atrial flutter. Damage of the right coronary artery is a very rare complication after inferior isthmus ablation with high energy. The thromboembolic risk during and after cardioversion and ablation of atrial flutter is higher than previously recognized and anticoagulation therapy decreases this risk. The risk of perforation and tamponade during ablation in the right atrium and right ventricle is very low but particular caution is necessary in thin-walled structures such as the coronary sinus and the upper right ventricular outflow tract. Phrenic nerve injury can be avoided by pacing from the mapping electrode before application of radiofrequency energy at the right atrial free wall. Limitation of power output depending on the site of ablation and titration of energy application with continuous control of temperature and impedance should be considered to minimize the risk of complications.

Alternatives to heart transplantation. Symposium of the "Treatment of End-stage Heart and Lung Failure" working group on October 22, 2005 in Munich.

Heart transplantation is currently the treatment of first choice in patients with end-stage refractory heart failure. But already the demand for donor organs cannot be met, and patients face long waiting times for transplantation. In the future waiting times will become even longer as life expectancy increases and the number of heart-failure patients requiring transplantation grows. Consequently, in view of the poor prognosis of the disease in its advanced stages, alternatives to heart transplantation are increasingly gaining importance. In recent years new innovative treatment methods and techniques have been developed which have already proved clinically successful in patients with end-stage heart failure, especially as bridging measures. Some of these techniques appear suitable for long-term use and could therefore serve as an alternative to heart transplantation in some patients. Interesting new avenues of research may even lead to cardiac cell replacement therapies in the future. These approaches are currently undergoing initial clinical trials. This report presents surgical and cardiologic treatments for end-stage heart failure that have already been clinically investigated as well as techniques that are still in the preclinical stage and discusses their potential as alternatives to heart transplantation.

The delay of contrast arrival in magnetic resonance first-pass perfusion imaging: a novel non-invasive parameter detecting collateral-dependent myocardium.

AIM: To establish the regional delay of contrast arrival in magnetic resonance perfusion imaging (MRPI) for the detection of collateral-dependent myocardium in patients with coronary artery disease. DESIGN AND SETTING: Observational study, case series; single centre, university hospital. PATIENTS: 30 patients with coronary artery disease and collateral-dependent myocardium and 17 healthy volunteers. METHODS: Resting and hyperaemic (adenosine) MRPI was used to determine the delay time (Deltat(d)) of contrast arrival between the left ventricle and collateral-dependent or antegradely perfused myocardium, and myocardial perfusion (MP, ml/min/g). RESULTS: In healthy volunteers, mean (SD) Deltat(d) at rest and during hyperaemia were 0.8 (0.4) and 0.3 (0.3) s, and MP was 1.14 (0.21) and 4.23 (1.12) ml/min/g. In patients Deltat(d) in antegradely perfused vs collateral-dependent myocardium was 0.9 (0.7) vs 1.7 (1.0) s at rest (p<0.001), and 0.4 (0.3) vs 1.1 (0.6) s (p<0.001) during hyperaemia. MP was 1.12 (0.11) and 0.98 (0.28) ml/min/g (p = NS) at rest and 2.46 (0.85) vs 1.86 (0.91) ml/min/g (p<0.01) during hyperaemia. Receiver operating characteristics analysis showed the best sensitivity and specificity of 90% and 83% for hyperaemic Deltat(d) of >0.6 s (area under the curve (AUC) = 0.89) to detect collateral-dependent myocardium, while resting Deltat(d) (AUC = 0.77) and perfusion (AUC = 0.69 at rest or 0.70 during hyperaemia) were less accurate. CONCLUSIONS: MRPI-derived hyperaemic delay of contrast arrival detects collateral-dependent myocardium with high sensitivity and specificity. Perfusion was less sensitive, emphasising the clinical role of Deltat(d) in non-invasive detection of collateral-dependent myocardium.

Acute respiratory distress syndrome with transiently impaired left ventricular function and Torsades de Pointes arrhythmia unmasking congenital long QT syndrome in a 25-yr-old woman.

We report a case of recurrent episodes of Torsades de Pointes arrhythmia in the setting of transiently impaired left ventricular ejection fraction, acute respiratory distress syndrome, transient hypokalaemia and QT-prolonging drugs, in a previously healthy 25-yr-old female patient. In the course of the clinical and genetic work-up this patient was newly diagnosed with a mutation in KCNH2 encoding the alpha-subunit of the human repolarizing potassium channel I(Kr). This case report illustrates the multivariate nature of long-QT syndrome, and emphasizes the usefulness of a pharmacological test for repolarization abnormalities.