Stefan Frantz

Role of T-cells in myocardial infarction

Innate immunity has been studied for several decades in the context of ischaemia-reperfusion injury, myocardial remodelling, and healing. In the last years, a number of experimental and clinical studies focused on adaptive immunity in these processes. Meanwhile, there is considerable evidence especially on the role of CD4(+) T-cells in myocardial injury and healing, whereas their role in remodelling is less clear. Innate leukocytes are able to recognize a wide array of self and foreign molecular patterns, whereas the activation of adaptive immunity requires the highly specific cooperation of antigen-presenting cells and distinct antigen-specific receptors on lymphocytes. Relevant autoantigens have not yet been definitely identified but experimental evidence indicates that autoantigen recognition is necessary for T-cell activation after myocardial infarction. Non-antigen-specific modes of activation might also play a role especially during acute ischaemia and reperfusion of the myocardium. This review summarizes the current evidence from experimental studies and presents side-by-side recent clinical data on the role of T cells in the pathophysiology of myocardial reperfusion injury and post myocardial infarction healing.

Socioeconomic inequalities in access to treatment for coronary heart disease: A systematic review

Strong socioeconomic inequalities exist in cardiovascular mortality and morbidity. The current review aims to synthesize the current evidence on the association between socioeconomic status (SES) and access to treatment of coronary heart disease (CHD). We examined quantitative studies analyzing the relationship between SES and access to CHD treatment that were published between 1996 and 2015. Our data sources included Medline and Web of Science. Our search yielded a total of 2066 records, 57 of which met our inclusion criteria. Low SES was found to be associated with low access to coronary procedures and secondary prevention. Access to coronary procedures, especially coronary angiography, was mainly related to SES to the disadvantage of patients with low SES. However, access to drug treatment and cardiac rehabilitation was only associated with SES in about half of the studies. The association between SES and access to treatment for CHD was stronger when SES was measured based on individual-level compared to area level, and stronger for individuals living in countries without universal health coverage. Socioeconomic inequalities exist in access to CHD treatment, and universal health coverage shows only a minor effect on this relationship. Inequalities diminish along the treatment pathway for CHD from diagnostic procedures to secondary prevention. We therefore conclude that CHD might be underdiagnosed in patients with low SES. Our results indicate that there is an urgent need to improve access to CHD treatment, especially by increasing the supply of diagnostic angiographies, to reduce inequalities across different healthcare systems.

Cardiovascular Risk Factors Associated With Blood Metabolite Concentrations and Their Alterations During a 4-Year Period in a Population-Based Cohort.

Background—The effects of lifestyle risk factors considered collectively on the human metabolism are to date unknown. We aim to investigate the association of these risk factors with metabolites and their changes during 4 years. Methods and Results—One hundred and sixty-three metabolites were measured in serum samples with the AbsoluteIDQ kit p150 (Biocrates) following a targeted metabolomics approach, in a population-based cohort of 1030 individuals, aged 45 to 83 years at baseline. We evaluated associations between metabolite concentrations (28 acylcarnitines, 14 amino acids, 9 lysophosphocholines, 72 phosphocholines, 10 sphingomyelins and sum of hexoses) and 5 lifestyle risk factors (body mass index [BMI], alcohol consumption, smoking, diet, and exercise). Multilevel or simple linear regression modeling adjusted for relevant covariates was used for the evaluation of cross-sectional or longitudinal associations, respectively; multiple testing correction was based on false discovery rate. BMI, alcohol consumption, and smoking were associated with lipid metabolism (reduced lyso- and acyl-alkyl-phosphatidylcholines and increased diacylphosphatidylcholines concentrations). Smoking showed positive associations with acylcarnitines, and BMI correlated inversely with nonessential amino acids. Fewer metabolites showed relative changes that were associated with baseline risk factors: increases in 5 different acyl-alkyl phosphatidylcholines were associated with lower alcohol consumption and BMI and with a healthier diet. Increased levels of tyrosine were associated with BMI. Sex-specific effects of smoking and BMI were found specifically related to acylcarnitine metabolism: in women higher BMI and in men more pack-years were associated with increases in acylcarnitines. Conclusions—This study showed sex-specific effects of lifestyle risks factors on human metabolism and highlighted their long-term metabolic consequences.

Direct inhibition, but indirect sensitization of pacemaker activity to sympathetic tone by the interaction of endotoxin with HCN-channels.

In critically ill patients regulation of heart‐rate is often severely disturbed. Interaction of bacterial endotoxin (lipopolysaccharide, LPS) with hyperpolarization‐activated cyclic nucleotide‐gated cation‐(HCN)‐channels may interfere with heart‐rate regulation. This study analyzes the effect of LPS, the HCN‐channel blocker ivabradine or Ca2+‐channel blockers (nifedipine, verapamil) on pacemaking in spontaneously beating neonatal rat cardiomyocytes (CM) in vitro. In vivo, the effect of LPS on the heart‐rate of adult CD1‐mice with and without autonomic blockade is analyzed telemetrically. LPS (100 ng/mL) and ivabradine (5 μg/mL) reduced the beating‐rate of CM by 20.1% and 24.6%, respectively. Coincubation of CM with both, LPS and ivabradine, did not further reduce the beating‐rate, indicating interaction of both compounds with HCN‐channels, while coincubation with Ca2+‐channel blockers and LPS caused additive beating‐rate reduction. In CD1‐mice (containing an active autonomic‐nervous‐system), injection of LPS (0.4 mg/kg) expectedly resulted in increased heart‐rate. However, if the autonomic nervous system was blocked by propranolol and atropine, in line with the in vitro data, LPS induced a significant reduction of heart‐rate, which was not additive to ivabradine. The in vivo and in vitro results indicate that LPS interacts with HCN‐channels of cardiomyocytes. Thus, LPS indirectly sensitizes HCN‐channels for sympathetic activation (tachycardic‐effect), and in parallel directly inhibits channel activity (bradycardic‐effect). Both effects may contribute to the detrimental effects of septic cardiomyopathy and septic autonomic dysfunction.

The innate immune system in chronic cardiomyopathy: a European Society of Cardiology (ESC) scientific statement from the Working Group on Myocardial Function of the ESC

Activation of the immune system in heart failure (HF) has been recognized for over 20 years. Initially, experimental studies demonstrated a maladaptive role of the immune system. However, several phase III trials failed to show beneficial effects in HF with therapies directed against an immune activation. Preclinical studies today describe positive and negative effects of immune activation in HF. These different effects depend on timing and aetiology of HF. Therefore, herein we give a detailed review on immune mechanisms and their importance for the development of HF with a special focus on commonalities and differences between different forms of cardiomyopathies. The role of the immune system in ischaemic, hypertensive, diabetic, toxic, viral, genetic, peripartum, and autoimmune cardiomyopathy is discussed in depth. Overall, initial damage to the heart leads to disease specific activation of the immune system whereas in the chronic phase of HF overlapping mechanisms occur in different aetiologies.

Longitudinal association of short-term, metronome-paced heart rate variability and echocardiographically assessed cardiac structure at a 4-year follow-up: results from the prospective, population-based CARLA cohort

Aims To assess the value of cardiac structure/function in predicting heart rate variability (HRV) and the possibly predictive value of HRV on cardiac parameters. Methods and results Baseline and 4-year follow-up data from the population-based CARLA cohort were used (790 men, 646 women, aged 45-83 years at baseline and 50-87 years at follow-up). Echocardiographic and HRV recordings were performed at baseline and at follow-up. Linear regression models with a quadratic term were used. Crude and covariate adjusted estimates were calculated. Missing values were imputed by means of multiple imputation. Heart rate variability measures taken into account consisted of linear time and frequency domain [standard deviation of normal-to-normal intervals (SDNN), high-frequency power (HF), low-frequency power (LF), LF/HF ratio] and non-linear measures [detrended fluctuation analysis (DFA1), SD1, SD2, SD1/SD2 ratio]. Echocardiographic parameters considered were ventricular mass index, diastolic interventricular septum thickness, left ventricular diastolic dimension, left atrial dimension systolic (LADS), and ejection fraction (Teichholz). A negative quadratic relation between baseline LADS and change in SDNN and HF was observed. The maximum HF and SDNN change (an increase of roughly 0.02%) was predicted at LADS of 3.72 and 3.57 cm, respectively, while the majority of subjects experienced a decrease in HRV. There was no association between further echocardiographic parameters and change in HRV, and there was no evidence of a predictive value of HRV in the prediction of changes in cardiac structure. Conclusion In the general population, LADS predicts 4-year alteration in SDNN and HF non-linearly. Because of the novelty of the result, analyses should be replicated in other populations.

So lässt sich das Herz stärken

ZusammenfassungDas Spektrum der Therapieoptionen der chronischen Herzinsuffizienz ist in den vergangenen Jahren deutlich breiter geworden. Hierzu tragen neben neuen Behandlungsmöglichkeiten zugrundeliegender kardiovaskulärer Komorbiditäten wie koronarer Herzerkrankung oder Herzklappendysfunktionen auch Fortschritte in der medikamentösen Therapie bei.

Wire- and needle potentials facilitating transseptal puncture

BACKGROUND Transseptal puncture for left heart interventions became a routine procedure guided by fluoroscopy and echocardiography. The use of intracardiac potentials derived from the sheath-transseptal-needle/guidewire-combination may provide helpful information to increase safety of this procedure. METHODS AND RESULTS We recorded the intracardiac potentials from the sheath-transseptal-needle/guidewire-combination during the transseptal puncture procedure in 31 consecutive patients (mean age 67.2±8.2years; 21 in sinus rhythm, 10 in atrial fibrillation) designated for ablation of atrial fibrillation by the Cryo-balloon ® technique (Medtronic, Minnesota, USA). The EP-Navigator ® 3-D-image integration tool (Philips Healthcare, Hamburg, Germany) was used for visualization of the device position in relation to the cardiac structures. Typical and reproducible potentials could be derived in all patients for the different device localizations at transseptal puncture procedure. Especially the transition from the muscular interatrial septum into the fossa ovalis could be easily depicted by the changes of both morphology and magnitude of the atrial signal (6.1±2.3mV in sinus rhythm [SR]/3.5±0.9mV in atrial fibrillation [AF] at the muscular interatrial septum and 0.5±0.2mV in SR/0.5±0.1mV in AF in the fossa ovalis). CONCLUSIONS The crucial steps of a transseptal procedure can be verified by typical changes (morphology and amplitude) of the intracardiac signals derived from the sheath-transseptal-needle/guidewire-combination in patients with sinus rhythm as well as in atrial fibrillation.

Herzinsuffizienz — Diagnostik und Therapie in der Praxis

ZusammenfassungDie Herzinsuffizienz ist in Ländern westlicher Prägung eine der bedeutendsten Volkskrankheiten. Zu den Ursachen gehören Bluthochdruck, koronare Herzkrankheit und Herzinfarkt, Diabetes mellitus sowie Nikotin- und Alkoholmissbrauch. Aber auch virale Infekte, Kardiomyopathien und Herzrhythmusstörungen können die Pumpfunktion des Herzens so schwächen, dass die Versorgung des Körpers mit sauerstoffreichem Blut nicht mehr gewährleistet ist. Erfahren Sie hier, wie man die Herzinsuffizienz diagnostiziert und was man dagegen tun kann.