Takotsubo cardiomyopathy (TTC), initially defined as a benign disease, is associated with several complications. One of them is a thromboembolism, which is clinically presented by events such as ...stroke, ventricular thrombi, and peripheral embolization, and can be present at index event of TCC as well as at any time in disease course. Patients with elevated C-reactive protein levels, markedly elevated D-dimers and severely impaired left ventricular function seem to be at higher risk of developing thrombemboli. Treatment strategies prescribed in the management of thombembolic complications in patients with acute myocardial infarction includes a short course of anticoagulation. A similar analogy could also be considered for patients with TTC presenting with this complications. Nevertheless, an individualized close-follow-up is of utmost importance to avoid any relapse and not to oversee any impeding complications in light of dynamic processes in myocardial stunning.
The aim of this study was to evaluate the extent of epicardial adipose tissue (EAT) and its relationship with left ventricular (LV) parameters assessed by cardiovascular magnetic resonance (CMR) in ...patients with congestive heart failure (CHF) and healthy controls.
EAT is the true visceral fat deposited around the heart which generates various bioactive molecules. Previous studies found that EAT is related to left ventricular mass (LVM) in healthy subjects. Further studies showed a constant EAT to myocardial mass ratio in normal, ischemic and hypertrophied hearts.
CMR was performed in 66 patients with CHF due to ischemic cardiomyopathy (ICM), or dilated cardiomyopathy (DCM) and 32 healthy controls. Ventricular volumes, dimensions and LV function were assessed. The amount of EAT was determined volumetrically and expressed as mass indexed to body surface area. Additionally, the EAT/LVM and the EAT/left ventricular remodelling index (LVRI) ratios were calculated.
Patients with CHF had less indexed EAT mass than controls (22 +/- 5 g/m2 versus 34 +/- 4 g/m2, p < 0.0001). In the subgroup analysis there were no significant differences in indexed EAT mass between patients with ICM and DCM (21 +/- 4 g/m2 versus 23 +/- 6 g/m2, p = 0.14). Linear regression analysis showed that with increasing LV end-diastolic diameter (LV-EDD) (r = 0.42, p = 0.0004) and LV end-diastolic mass (LV-EDM) (r = 0.59, p < 0.0001), there was a significantly increased amount of EAT in patients with CHF. However, the ratio of EAT mass/LV-EDM was significantly reduced in patients with CHF compared to healthy controls (0.54 +/- 0.1 versus 0.21 +/- 0.1, p < 0.0001). In CHF patients higher indexed EAT/LVRI-ratios in CHF patients correlated best with a reduced LV-EF (r = 0.49, p < 0.0001).
Patients with CHF revealed significantly reduced amounts of EAT. An increase in LVM is significantly related to an increase in EAT in both patients with CHF and controls. However, different from previous reports the EAT/LVEDM-ratio in patients with CHF was significantly reduced compared to healthy controls. Furthermore, the LV function correlated best with the indexed EAT/LVRI ratio in CHF patients. Metabolic abnormalities and/or anatomic alterations due to disturbed cardiac function and geometry seem to play a key role and are a possible explanation for these findings.
Full text
Available for:
DOBA, GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, UILJ, UKNU, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
For years early repolarization (ER) has been considered as a benign electrocardiographic finding. However, recent reports show that ER is associated with a higher incidence of ventricular ...fibrillation (VF) and sudden cardiac death in patients without structural heart disease. Sporadic case studies have pointed out that ER might be related to an adverse outcome in patients with stable coronary artery disease.
To evaluate the incidence of ER in patients with acute myocardial infarction complicated by VF.
The study population consisted of 60 patients (80% men; mean age 61.8 ± 13.1 years) with acute myocardial infarction. Thirty consecutive patients (80% men; mean age 63.3 ± 12 years) admitted to our hospital had documented VF during myocardial infarction and were successfully resuscitated before hospital admission. A matched control group consisted of 30 patients (80% men; mean age 60.2 ± 14.2 years) with myocardial infarction without ventricular tachyarrhythmias. Twelve-lead electrocardiograms were analyzed for ER defined as J-point elevation ≥ 0.1 mV and "notching" and "slurring" of the terminal part of the QRS complex in at least 2 lateral or inferior leads.
The ER pattern was observed in 18 of the 60 patients with acute myocardial infarction. Mean elevation of the J point was 0.151 ± 0.46 mV. Notching of the J wave was observed in 14 of the 18 patients and slurring in 4 of the 18 patients. ER was more common in patients with myocardial infarction complicated by VF than in patients with myocardial infarction without ventricular tachyarrhythmias (47% vs 13%; P = .005). There have been no statistical differences in the distribution of ER in the 12-lead electrocardiogram (inferior 39% vs lateral 33% vs inferolateral 28%; P >.05).
Early repolarization pattern seems to be associated with ventricular tachyarrhythmias in the setting of acute myocardial infarction.
Cardiomyopathies are a major cause of heart diseases in all age groups leading to heart failure and arrhythmias. Additionally, they are an important cause of sudden cardiac death (SCD) in young ...people. Major advances have been made in the understanding of the complex and manifold underlying pathomechanisms and their correlating blood measured biomarkers. The aim of this review is to outline the role of such biomarkers in non-ischemic cardiomyopathies and their role in the prediction of SCD.
A search in bibliographic databases was conducted. Most relevant references focusing on blood measured biomarkers in non-ischemic cardiomyopathies and biomarkers in SCD were reviewed regarding their role in pathophysiology and clinical practice. The references contain prospective and retrospective studies as well as meta-analyses. Current guidelines were analyzed concerning the implementation of biomarkers.
Most research on the role of biomarkers in cardiomyopathies is focused on myocardial stress (natriuretic peptides), injury (troponins), inflammation, and remodelling (fibrosis marker). Various studies suggest a potential application of biomarkers in diagnostics, prognosis and treatment response. Further approaches include microRNAs or multimarker approaches. Biomarkers to delineate patients being at risk for SCD have demonstrated predictive ability and could improve risk stratification strategies.
To improve the prognosis of cardiomyopathies an early onset of treatment is needed. This necessitates further research and a better integration of biomarkers in the diagnostic work-up of cardiomyopathies. Identification of patients being at risk for SCD is mandatory, however, reliable data of biomarkers are still lacking.
Background The tandem of P domains in a weak inward rectifying K+ channel (TWIK)-related acid-sensitive K
channel (TASK-1; hK
3.1) two-pore-domain potassium channel was recently shown to regulate the ...atrial action potential duration. In the human heart, TASK-1 channels are specifically expressed in the atria. Furthermore, upregulation of atrial TASK-1 currents was described in patients suffering from atrial fibrillation (AF). We therefore hypothesized that TASK-1 channels represent an ideal target for antiarrhythmic therapy of AF. In the present study, we tested the antiarrhythmic effects of the high-affinity TASK-1 inhibitor A293 on cardioversion in a porcine model of paroxysmal AF. Methods and Results Heterologously expressed human and porcine TASK-1 channels are blocked by A293 to a similar extent. Patch clamp measurements from isolated human and porcine atrial cardiomyocytes showed comparable TASK-1 currents. Computational modeling was used to investigate the conditions under which A293 would be antiarrhythmic. German landrace pigs underwent electrophysiological studies under general anesthesia. Paroxysmal AF was induced by right atrial burst stimulation. After induction of AF episodes, intravenous administration of A293 restored sinus rhythm within cardioversion times of 177±63 seconds. Intravenous administration of A293 resulted in significant prolongation of the atrial effective refractory period, measured at cycle lengths of 300, 400 and 500 ms, whereas the surface ECG parameters and the ventricular effective refractory period lengths remained unchanged. Conclusions Pharmacological inhibition of atrial TASK-1 currents exerts antiarrhythmic effects in vivo as well as in silico
resulting in acute cardioversion of paroxysmal AF. Taken together, these experiments indicate the therapeutic potential of A293 for AF treatment.
Takotsubo syndrome (TTS) and acute coronary syndrome (ACS) patients have a similar mortality rate. In this study, we sought to determine the short- and long-term outcome of TTS patients as compared ...to ACS patients both treated with beta-blockers.
In the present study we described the data of 5 years of follow up of 103 TTS and 422 ACS patients both treated with beta-blockers.
Data from TTS patients were included retrospectively and prospectively, ACS patients were included retrospectively. All retrospectively included patients have been followed up for 5 years. The end point in this study was the occurrence of death.
TTS affected significantly more women (87.4%) than ACS (34.6%) (p < 0.01). TTS patients suffered significantly more often from thromboembolic events (14.6% versus 2.1%; p < 0.01) and cardiogenic shock (11.9% versus 3.6%; p < 0.01) than the ACS group. TTS patients had a significantly higher long-term mortality (within 5 years) as compared to ACS patients (17.5% versus 3.6%) (p < 0.01). Patients of the TTS group compared to the ACS group did not benefit from combination of beta-blockers and ACE-inhibitors in terms of long-term mortality (p < 0.01). As we compare TTS patients who were treated with beta-blockers and ACE-inhibitors versus single use of beta-blockers there was no difference in long-term mortality (p = 0.918).
TTS patients had a significantly higher long-term mortality (within 5 years) than patients with an ACS.
Acute Heart Failure (AHF), owing to the difficulties in diagnosis, prognostic stratification and patient-related management, is still associated with unusually high morbidity and mortality. The ...advent of novel biomarkers apart from natriuretic peptides involved in myocardial injury, neuro-hormonal activation, and ventricular remodeling augurs immense hope in redefining the biomarker-based approach towards AHF.
A thorough review of the available literature including latest review articles from distinguished experts, textbook references and guidelines from leading cardiological societies worldwide as well as the latest trials, encompassing various biomarkers known in AHF was conducted. The most relevant ones were chosen as references for the current review article.
Biomarkers such as midregional proatrial natriuretic peptide, soluble ST2, highly-sensitive troponin, and midregional proadrenomedullin are some such examples that have passed various stages of substantiation while there is an array of potential biomarkers innascent stages like osteopontin, CTGF, GDF-15 and TGF beta-1 awaiting further reiteration. Not only the diagnosis of AHF itself but the evaluation of co-morbidities using markers like PCT, hematologic markers or acute kidney injury markers like NGAL present a new perspective to the management of AHF.
This review article outlines the current status of the most relevant cardiac biomarkers related to AHF.
Background Short QT syndrome ( SQTS ) is a rare inheritable disease associated with sudden cardiac death. Data on long-term outcomes of families with SQTS are limited. Methods and Results Seventeen ...patients with SQTS in 7 independent families (48% men; median age, 42.4 years; corrected QT interval, 324.9±40.8 ms) were followed up for 13.5±2.5 years. A history of sudden cardiac death was documented in 71% of families. A large number of them showed sudden cardiac deaths at a younger age, with a predominance of men (67%). Five patients had syncope (29%) and 9 (53%) had atrial fibrillation or atrial flutter. An SQTS -related gene was found in 76% of the patients as follows: KCNH 2 ( SQTS 1) in 4, CACNA 1C ( SQTS 4) in 3, and CACN b2 ( SQTS 5) in 6. Five patients (29%) received an implantable cardioverter-defibrillator and 5 patients received long-term prophylaxis with hydroquinidine. During follow-up, 1 patient received an appropriate implantable cardioverter-defibrillator shock attributable to ventricular fibrillation. The patient received no further implantable cardioverter-defibrillator shocks after treatment with hydroquinidine. Conclusions The risk of sudden cardiac death in SQTS families is high. However, after appropriate risk assessment and individualized treatment options (hydroquinidine and/or implantable cardioverter-defibrillator), the long-term outcome is relatively benign when patients are seen at a reference center.
The adipokine leptin regulates energy expenditure, vascular function, bone and cartilage growth as well as the immune system and systemic inflammatory response. Several activating effects towards T ...cells, monocytes, endothelium cells and cytokine production have been reported suggesting a protective role of leptin in the setting of an acute systemic inflammation. However, the pathophysiological role of leptin during severe sepsis is currently not elucidated in detail. This study aims to investigate leptin expression in cultured human adipocytes within an inflammatory model and in patients suffering from severe sepsis and evaluates treatment effects of drotrecogin alpha (activated) (DAA), the recombinant form of human activated protein C.
In an in-vitro inflammatory model of adipocyte cell-culture the effect of DAA on leptin mRNA expression was evaluated. Synthesis of mRNA was measured by quantitative polymerase chain reaction (qPCR). Additionally, supernatants of these adipocytes as well as serum levels of adiponectin were measured in blood of 104 severe septic patients by ELISA-method. 26 patients were treated with DAA (DAA+), 78 patients were not treated with DAA (DAA-).
Stimulation of human adipocytes with TNF alpha over 6 and 24 hours resulted in a significant decrease by 46% and 59% of leptin mRNA transcripts compared to un-stimulated controls (p < 0.05). Leptin levels of supernatants of adipocyte culture decreased by 25% and 23% (p < 0.05) after incubation with TNF alpha after 6 and 24 hours. Incubation with DAA at 50 ng/ml DAA and 5 μg/ml doubled mRNA expression significantly at 24 hours (p < 0.05) but not at 6 hours. From day 1 to day 3 of sepsis, leptin levels increased in DAA+ compared to DAA- patients (p<0.10).
Leptin appears to be involved in the pathogenesis of a systemic inflammatory response during sepsis. Administration of DAA significantly increased leptin expression. The specific mechanism or even benefit of DAA towards leptin needs further ongoing research.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Short QT syndrome (SQTS) is associated with sudden cardiac arrest. There are limited data on the impact of antiarrhythmic drugs on the outcome of SQTS.
We studied data that describe the clinical ...outcome of 62 SQTS patients treated with antiarrhythmic drugs, who were recruited from a pool of patients diagnosed in our institution and also from known databases after a systematic search of the published literature.
Sixty-two SQTS patients treated with antiarrhythmic drugs were followed up over a median timeframe of 5.6 years (interquartile range 1.6-7.7 years). Six patients, in particular, received multiple drugs as a combination. Of the 55 patients treated with hydroquinidine (HQ), long-term prophylaxis was documented in 41 patients. Fourteen patients stopped treatment due to the following reasons: gastrointestinal intolerance (n = 4), poor compliance (n = 8), and no QTc prolongation (n = 2). Of the 41 patients treated with HQ, the QTc interval increased from 313.5 ± 17.2 to 380.1 ± 21.2 ms. Thirteen of the 41 patients suffered from at least one or more ventricular tachyarrhythmias (VAs) before HQ initiation. VAs are reduced in incidence after HQ treatment (13/41: 31% versus 3/41: 7.3%, p < 0.001).
HQ increases the corrected QT interval and prevents VAs in the majority of the patients in this cohort. HQ is safe for use in SQTS patients, particularly due to its low rate of side effects. Other antiarrhythmic drugs might be useful, but the data justifying their use are sparse.
PDF
