Influence of renal sympathetic denervation on quality of life.

BACKGROUND: Therapy-resistant arterial hypertension causing psychosocial stress and is associated with cardiovascular morbidity and mortality. The aim of the study was to evaluate the effect on quality of life (QoL) in patients with resistant hypertension undergoing renal sympathetic denervation (RSD). METHODS AND RESULTS: We analyzed responses to the SF-36 Quality of Life Questionnaire provided by patients with resistant arterial hypertension after RSD. Thirty consecutive patients from 2 centers were included in this study, from October 2011 until February 2012. The phone interview was performed after the 3-month follow-up. A significant reduction (26 ± 13.5 mmHg) in systolic blood pressure (BP) was detected at the 3-month follow-up (142.0 ± 15.1 mmHg vs 168.0 ± 13.7 mmHg; P < 0.001). Seventy-five percent of the patients indicated that their health situation was a lot better (better, 21%; equal to, 4%) 3 months after RSD compared to the time before the therapeutic procedure. Furthermore, the majority of patients felt full of pep (always, 29%; mostly, 58%; quite often, 8%; sometimes, 4%), and full of energy (always, 25%; mostly, 54%; quite often, 16.7%; sometimes, 4.2%) after the procedure. Recipients of RSD indicated that they felt more light and healthy, and nearly all recipients (93%) described a loss of anxiety and indisposition. CONCLUSIONS: This investigation revealed that sufficient BP reduction by RSD and time following therapeutic success lead to significant improvements in patient QoL.

Release kinetics of circulating muscle-enriched microRNAs in patients undergoing transcoronary ablation of septal hypertrophy.

OBJECTIVES: This study sought to evaluate exact release kinetics of microRNAs (miRNAs) in acute myocardial infarction (AMI). BACKGROUND: miRNAs may be useful as novel biomarkers in patients with cardiovascular disease, although it is difficult to establish the detailed release kinetics of miRNAs in patients with AMI. METHODS: We analyzed the release kinetics of circulating cardiac-specific (miR-21, miR-208a) and muscle-enriched (miR-1, miR-133a) miRNAs using the TaqMan polymerase chain reaction in patients with hypertrophic obstructive cardiomyopathy who were undergoing transcoronary ablation of septal hypertrophy (TASH), a procedure mimicking AMI. Consecutive patients (n = 21) undergoing TASH were included. Serum samples were collected prior to and at 15, 30, 45, 60, 75, 90, and 105 min and 2, 4, 8, and 24 h after TASH. RESULTS: Circulating concentrations of miR-1 were significantly increased (>3-fold; p = 0.01) after 15 min, with a peak after 75 min (>60-fold; p < 0.001). The miR-21 concentrations were not increased at any time point. Concentrations of miR-133a were significantly increased at 15 min (2.9-fold; p < 0.001) and reached a plateau between 75 and 480 min (>50-fold change). The miR-208a concentrations were elevated at 105 min (>2-fold; p = 0.01), without a further increase. CONCLUSIONS: miR-1, miR-133a, and miR-208a were continuously increased during the first 4 h after the induction of MI. In particular, miR-1 and miR-133a were significantly increased at early time points. These results demonstrate the release kinetics of miRNAs, which are helpful for developing their potential use as biomarkers in patients with acute coronary syndromes.

Door-to-implantation time of extracorporeal life support systems predicts mortality in patients with out-of-hospital cardiac arrest.

OBJECTIVE: This study aimed to identify predictors of mortality in patients with out-of-hospital cardiac arrest (OHCA) undergoing in-hospital extracorporeal life support system (ECLS) treatment. METHODS: We retrospectively studied the characteristics and clinical outcomes of 28 patients (January 2010 and December 2011) with OHCA and veno-arterial ECLS implemented during ongoing cardiopulmonary resuscitation (CPR) upon admission to the cath lab. Baseline left ventricular ejection fraction (LVEF) was determined after ECLS implantation and then every 24 h during and after successful weaning from ECLS. RESULTS: Overall 30-day survival rate was 39.3 % (11 of 28 patients). Baseline characteristics, initial laboratory measurements, and LVEF on admission were not significantly different between survivors and non-survivors. There was no difference regarding median CPR duration [survivors 44.0 min (IQR 31.0-45.0) vs. non-survivors 53.0 min (IQR 40.0-61.3); P = 0.23]. Door-to-ECLS implantation time was significantly longer in non-survivors [42.5 min (IQR 28.0-56.5) vs. 25.0 min (IQR 21.0-30.0); P < 0.01]. ECLS treatment duration was not significantly different between the two groups [survivors: 4.0 days (IQR 1.5-7.5) vs. non-survivors 6.5 days (IQR 1.0-8.0); P = 0.69]. LVEF significantly improved in survivors during ECLS treatment (mean ± SD survivor 47.5 ± 14.7 % vs. non-survivor 23.3 ± 14.9 %; P < 0.01). The door-to-ECLS implantation time was the only significant and independent predictor of 30-day mortality in multivariate Cox regression analysis (P = 0.04). Kaplan-Meier survival analysis showed a benefit favouring patients with a door-to-ECLS implantation time <30 min (log rank 6.29; P = 0.01). CONCLUSION: A door-to-ECLS implantation time <30 min significantly improves 30-day outcomes in patients with OHCA.

Neutrophil gelatinase-associated lipocalin (NGAL) for the early detection of cardiac surgery associated acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a common complication after cardiac surgery. Neutrophil gelatinase-associated lipocalin (NGAL) may be an early biomarker for cardiac surgery-associated (CSA) AKI. We investigated whether increased urinary NGAL concentrations were predictive of AKI within 4 days after surgery and of mortality within 9 months. METHODS: Consecutive patients (n = 141) undergoing major cardiac surgery were included. Creatinine, blood urea nitrogen, cystatin C and urinary NGAL were measured before, 4 hours and 4 days after extracorporeal circulation. RESULTS: AKI was observed in 47 (33.3%) patients. The 4-hour urinary NGAL measurement was an independent predictor of stage 2 and 3 AKI (AUC 0.901; 95% CI 0.81-0.99). Patients with AKI had a higher 9-month mortality rate (19.1% vs. 3.2%; logrank 10.9; P = 0.001; HR 19.8; 95% CI 3.7-107.1). Urinary NGAL was not predictive of mortality within 9 months after surgery. CONCLUSION: Urinary NGAL is a biomarker for very early risk stratification of AKI after cardiac surgery and may be useful as a basis for early interventional strategies to prevent CSA-AKI.

Mechanisms of stress (takotsubo) cardiomyopathy.

Stress cardiomyopathy is a form of reversible systolic dysfunction of the mid and apical left ventricle with pathologic changes of the electrocardiogram in the absence of an obstructive coronary artery disease. The prevalence of stress cardiomyopathy among patients with symptoms suggestive of myocardial infarction is 0.7% to 2.5%, and it is found predominantly in postmenopausal women (90%). No large studies have confirmed the cause of stress cardiomyopathy. Published data suggest that substantially elevated plasma catecholamine levels, due to emotional or physical stress, may be relevant.

Mobile left ventricular thrombus in left ventricular dysfunction: case report and review of literature.

INTRODUCTION: Left ventricular (LV) thrombi carry a high risk of embolization. Therapeutic recommendations like treatment with low molecular heparin and intravenous unfractionated heparin (UFH), thrombolysis or surgical thrombectomy have failed to reach a consensus. CASE DESCRIPTION: A 56-year-old female patient presented in cardiogenic shock to the emergency department. Echocardiography demonstrated a dilated LV with a severely depressed global systolic function and a large LV apical thrombus. Treatment with UFH was initiated as well as a treatment with catecholamines for stabilizing the patient's hemodynamic situation. On the follow-up echocardiographic examination, extensive free-floating parts of the thrombus could be documented. Given the high risk of embolization in a now hemodynamically stable situation, emergency surgical embolectomy was performed. DISCUSSION: A conservative procedure might be useful for bridging till surgical treatment is available and/or the risk due to surgery is acceptable. CONCLUSION: In absence of evidence-based guidelines for the treatment of LV thrombi, individualized management options concerning surgical, embolization and bleeding risk must be taken into account.

Novel rat model reveals important roles of ß-adrenoreceptors in stress-induced cardiomyopathy.

BACKGROUND: Stress-induced cardiomyopathy (SIC), also known as Takotsubo cardiomyopathy, is an acute cardiac syndrome with substantial morbidity and mortality. The unique hallmark of SIC is extensive ventricular akinesia involving apical segments with preserved function in basal segments. Adrenergic overstimulation plays an important role in initiating SIC but the pathophysiological pathways and receptors involved are unknown. METHODS: Sprague Dawley rats (~300 g) were injected with a single dose of the ß-adrenergic agonist isoprenaline (ISO, i.p.) and echocardiography was used to study cardiac function. The akinetic part of the left ventricle was biopsied in six SIC patients. Amount of intracellular lipid and glycogen as well as degree of permanent cardiac damage were assessed by histology. RESULTS: In rats, ISO at doses ≥ 50 mg/kg induced severe SIC-like regional akinesia that completely resolved within seven days. Intracellular lipid content was higher in akinetic, but not in normokinetic myocardium in both SIC patients and rats. ß2-receptor blockade or Gi-pathway inhibition was associated with less widespread akinesia and low lipid accumulation but significantly increased acute mortality. CONCLUSIONS: We provide a novel rat model of SIC that supports the hypothesis of circulating catecholamines as initiators of SIC. We propose that the ß-adrenoreceptor pathway is important in the setting of severe catecholamine overstimulation and that perturbations of cardiac metabolism occur in SIC.

Release kinetics of copeptin in patients undergoing transcoronary ablation of septal hypertrophy.

BACKGROUND: The release kinetics of copeptin in patients with acute myocardial infarction (AMI) have been difficult to establish. METHODS: We analyzed the release kinetics of copeptin in patients with hypertrophic obstructive cardiomyopathy undergoing transcoronary ablation of septal hypertrophy (TASH) as a model of AMI. We included 21 consecutive patients who underwent TASH. Blood samples were collected before and at 15, 30, 45, 60, 75, 90, and 105 min, and at 2, 4, 8, and 24 h after TASH. Serum copeptin was quantified by a sandwich immunoluminometric assay. RESULTS: All patients had copeptin concentrations below the 99th percentile at baseline. The median copeptin concentration was significantly increased at 30 min [16.0 pmol/L; interquartile range (IQR), 13.4-20.2 pmol/L], compared with the median baseline concentration (6.6 pmol/L; IQR, 5.3-8.3 pmol/L; P = 0.002). The copeptin concentration peaked 90 min after induction of myocardial infarction and returned to baseline concentrations (median, 8.2 pmol/L; IQR, 6.3-10.1) after 24 h, compared with the above baseline values (P = 0.06). Serum creatine kinase (CK) activities were significantly increased above baseline values by 1 day after TASH [median maximal postprocedural CK activity, 935.0 U/L (IQR, 545.5-1115.0 U/L); median baseline CK activity, 80.0 U/L (IQR, 63.5-109.0 U/L); P < 0.001]. CONCLUSIONS: Our results provide additional evidence that early rule-out of suspected AMI is possible by using the copeptin concentration in combination with cardiac troponin T.

A mouse model reveals an important role for catecholamine-induced lipotoxicity in the pathogenesis of stress-induced cardiomyopathy.

AIM: Stress-induced cardiomyopathy (SIC), also known as takotsubo cardiomyopathy, is an acute cardiac syndrome with substantial morbidity and mortality. The unique hallmark of SIC is extensive ventricular dysfunction (akinesia) involving apical segments with preserved function in basal segments. Adrenergic overstimulation plays an important role in initiating SIC, but the pathomechanisms involved are unknown. We tested the hypothesis that excessive catecholamines cause perturbation of myocardial lipid metabolism and that cardiac lipotoxicity is responsible for the pathogenesis of SIC. METHODS AND RESULTS: A single dose injection of isoprenaline (ISO; 400 mg/kg) induced SIC-like regional akinesia in mice. Oil red O staining revealed severe lipid accumulation in the heart 2 h post-ISO. Both intramyocardial lipid accumulation and cardiac function were normalized within 1 week post-ISO and no significant amount of fibrosis was detected. We found that gene expression of lipid importers and exporters (ApoB lipoprotein) was depressed 2 h post-ISO. These results were confirmed by similar findings in SIC patients and in ISO/patient serum-stressed HL-1 cardiomyocytes. Moreover, overexpression of ApoB in the heart was found to protect against the development of ISO-induced cardiac toxicity and cardiac dysfunction. We also found that ISO-induced intramyocardial lipid accumulation caused electrophysiological disturbance and stunning in ISO/patient serum-stressed HL-1 cardiomyocytes. CONCLUSIONS: The present study demonstrates that lipotoxicity is closely associated with catecholamine-induced myocardial dysfunction, including neurogenic stunning, metabolic stunning, and electrophysiological stunning. Cardiac lipotoxicity may originate from direct inhibition of myocardial ApoB lipoprotein and subsequent decreased lipid export, caused by supraphysiological levels of catecholamines.

Multi-detector computed tomography is equivalent to trans-oesophageal echocardiography for the assessment of the aortic annulus before transcatheter aortic valve implantation.

OBJECTIVES: In transcatheter aortic valve implantation (TAVI), assessment of the aortic annulus is mandatory. We sought to investigate the correlation between trans-oesophageal echocardiography (TEE) and multi-detector computed tomography (MDCT) for annulus diameter assessment before TAVI. METHODS: A total of 122 patients (67 male, mean age 84 ± 6 years) underwent MDCT and TEE for TAVI planning. In TEE annulus diameters were obtained in a long-axis view at diastole. MDCT data were evaluated using MPR images, and corresponding projections were adjusted for MDCT and TEE. Patients were classified by the predominant localisation of aortic valve calcifications, and annulus diameters between TEE and MDCT were correlated. Additionally, the eccentricity of the aortic annulus was calculated. RESULTS: Mean eccentricity of the aortic annulus determined by MDCT was 0.34 ± 0.17, with no difference according to valve calcification. Regarding the aortic annulus diameter, the mean values measured were 24.3 ± 2.1 mm in MDCT and 24.0 ± 2.5 mm in TEE (P < 0.0001 for agreement). CONCLUSIONS: Independent of the pattern of aortic valve calcification, close correlation is found between CT and TEE measurements of the aortic annulus diameter. In addition, CT demonstrates the non-circular shape of the aortic annulus. KEY POINTS: Accurate assessment of aortic annulus before transcatheter aortic valve implantation is crucial. Trans-oesophageal echocardiography has been the preferred method for aortic annulus assessment. We demonstrated a strong correlation between TEE and CT for annulus dimensions. CT reliably demonstrates the non-circular shape of the aortic annulus. CT could therefore be generally used for aortic annulus assessment before TAVI.

Bone marrow-derived cells contribute to cell turnover in aging murine hearts.

The paradigm that cardiac myocytes are non-proliferating, terminally differentiated cells was recently challenged by studies reporting the ability of bone marrow-derived cells (BMCs) to differentiate into cardiomyocytes after myocardial damage. However, little knowledge exists about the role of BMCs in the heart during physiological aging. Twelve-week-old mice (n=36) were sublethally irradiated and bone marrow from littermates transgenic for enhanced green fluorescent protein (eGFP) was transplanted. After 4 weeks, 18 mice were sacrificed at the age of 4 months and served as controls (group A); the remaining mice were sacrificed at the age of 18 months (group B). Group A did not exhibit a significant number of eGFP+ cells, whereas 9.4±2.8 eGFP+ cells/mm2 was documented in group B. In total, only five eGFP+ cardiomyocytes were detected in 20 examined hearts, excluding a functional role of BM differentiation in cardiomyocytes. Similarly, a relevant differentiation of BMCs in endothelial or smooth muscle cells was excluded. In contrast, numerous BM-derived fibroblasts and myofibroblasts were observed in group B, but none were detected in group  A. The present study demonstrates that BMCs transdifferentiate into fibroblasts and myofibroblasts in the aging murine myocardium, suggesting their contribution to the preservation of the structural integrity of the myocardium, while they do not account for regenerative processes of the heart.

Release kinetics of cardiac biomarkers in patients undergoing transcoronary ablation of septal hypertrophy.

BACKGROUND: The release kinetics of cardiac troponin T measured with conventional vs high-sensitivity cardiac troponin T (hs-cTnT) assays in patients with acute myocardial infarction (AMI) is difficult to establish. METHODS: We analyzed the release kinetics of cTnT measured by fourth generation and high-sensitivity assays, creatine kinase-MB (CK-MB), and myoglobin in patients with hypertrophic obstructive cardiomyopathy undergoing transcoronary ablation of septal hypertrophy (TASH), a model of AMI. Consecutive patients (n = 21) undergoing TASH were included. Serum and EDTA-plasma samples were collected before and at 15, 30, 45, 60, 75, 90, and 105 min, and 2, 4, 8, and 24 h after TASH. RESULTS: cTnT concentrations measured by the hs assay were significantly increased at 15 min [21.4 ng/L, interquartile range (IQR) 13.3-39.7 ng/L vs 11.3 ng/L, IQR 6.0-18.8 ng/L at baseline; P = 0.031]. In comparison, cTnT concentrations measured by the conventional fourth generation assay increased significantly at 60 min (30.0 ng/L, IQR 20.0-30.0 ng/L vs <10.0 ng/L, IQR <10.0-10.0 ng/L; P < 0.01), CK-MB at 90 min (8.4 µg/L, IQR 6.9-14.4 µg/L vs 0.9 µg/L, IQR 0.4-1.1 µg/L; P < 0.01), and myoglobin at 30 min (188.0 µg/L, IQR 154.0-233.0 µg/L vs 38.0 µg/L, IQR 28.0-56.0; P < 0.01). CONCLUSIONS: cTnT concentrations measured by the hs assay were significantly increased after TASH at all of the time points, with a doubling at 15 min after induction of AMI, confirming earlier evidence of myocardial injury compared to the fourth generation cTnT assay and CK-MB and myoglobin.

Regression of cardiac hypertrophy by granulocyte colony-stimulating factor-stimulated interleukin-1ß synthesis.

AIMS: Aortic stenosis causes cardiac hypertrophy and fibrosis, which often persists despite pressure unloading after aortic valve replacement. The persistence of myocardial fibrosis in particular leads to impaired cardiac function and increased mortality. We investigated whether granulocyte colony-stimulating factor (G-CSF) beneficially influences cardiac remodelling after pressure unloading. METHODS AND RESULTS: Left ventricular hypertrophy was induced by transverse aortic constriction in C57bl6 mice followed by debanding after 8 weeks. This model closely mimics aortic stenosis and subsequent aortic valve replacement. After debanding, mice were treated with either G-CSF or saline injection. Granulocyte colony-stimulating factor treatment significantly improved systolic (ejection fraction 70.48 ± 1.17 vs. 58.41 ± 1.56%, P < 0.001) and diastolic (E/E' 26.0 ± 1.0 vs. 32.6 ± 0.8, P < 0.05) function. Furthermore, cardiac fibrosis was significantly reduced in G-CSF-treated mice (collagen-I area fraction 7.96 ± 0.47 vs. 11.64 ± 1.22%, P < 0.05; collagen-III area fraction 10.73 ± 0.99 vs. 18.46 ± 0.71%, P < 0.001). Direct effects of G-CSF on cardiac fibroblasts or a relevant transdifferentiation of mobilized bone marrow cells could be excluded. However, a considerable infiltration of neutrophils was observed in G-CSF-treated mice. This sterile inflammation was accompanied by a selective release of interleukin-1 ß (IL-1ß) in the absence of other proinflammatory cytokines. In vitro experiments confirmed an increased expression of IL-1ß in neutrophils after G-CSF treatment. Interleukin-1ß directly induced the expression of the gelatinases matrix metalloproteinase-2 (MMP-2) and MMP-9 in cardiac fibroblasts thereby providing the regression of cardiac fibrosis. CONCLUSION: Granulocyte colony-stimulating factor treatment improves the cardiac function and leads to the regression of myocardial fibrosis after pressure unloading. These findings reveal a previously unknown mechanism of fibrosis regression. Granulocyte colony-stimulating factor might be a potential pharmacological treatment approach for patients suffering from congestive heart failure after aortic valve replacement, although further basic research and clinical trials are required in order to prove beneficial effects of G-CSF in the human organism.

Direct admission versus transfer of AMI patients for primary PCI.

BACKGROUND: Guidelines for the treatment of patients with ST-elevation myocardial infarction (STEMI) recommend primary PCI as first choice therapy. This recommendation has been linked to defined time limits achievable in a logistic network for the treatment of ACS. In the present study we analyzed the difference in 6 months outcome between STEMI patients who were admitted directly to a PCI center and those requiring transfer for primary PCI. RESULTS: 2,034 consecutive patients were included in the Bad Nauheim ACS registry. Admission diagnosis was STEMI in 1,057 (52%) patients (71% male, aged 63 ± 13). 637 (60%) patients were directly admitted for primary PCI with a time delay from first medical contact until admission in the PCI center of 64 min (IQR 45-90) at median and door-to-balloon time (DTB) at median 29 min (IQR 20-41). 420 (40%) patients were transferred from peripheral hospitals. In this subgroup time delay was 135 min (IQR 69-285) and DTB at median 31 min (IQR 22-49). 178 (16.8%) patients were at high risk (CPR or cardiogenic shock). Patients, who were admitted directly had a better outcome as transferral patients (log rank 6.1; p = 0.013 for 6 months mortality). However, Kaplan-Meier survival analysis (log rank 4.25; p = 0.039) and Cox regression analysis (95% CI 1.08-3.17; p = 0.026) revealed that this difference in outcome was restricted to high-risk patients. CONCLUSION: A network for the treatment of STEMI provides the logistic basis for the initiation of primary PCI according to current guidelines. However, transferral patients do not meet the defined time limits. Mortality rates for high-risk transferral patients appear to be higher as those of patients taken directly to the center by the EMS.