Abnormal thyroid function is common in takotsubo syndrome and depends on two distinct mechanisms: results of a multicentre observational study.

BACKGROUND: Several reports have described Takotsubo syndrome (TTS) secondary to thyrotoxicosis. A complex interaction of central and peripheral catecholamines with thyroid homeostasis has been suggested. In this study, we analysed sequential thyroid hormone profiles during the acute phase of TTS. METHODS: Thyrotropin (TSH), free T4 (FT4) and free T3 (FT3) concentrations were analysed at predefined time points in 32 patients presenting with TTS or acute coronary syndrome (ACS, n = 16 in each group) in a 2-year period in two German university hospitals. Data were compared to age- and sex-matched controls (10 samples, each of 16 subjects), and an unsupervised machine learning (ML) algorithm identified patterns in the hormone signature. Subjects with thyroid disease and patients receiving amiodarone were excluded from follow-up. RESULTS: Among patients with TTS, FT4 concentrations were significantly higher when compared to controls or ACS. Four subjects (25%) suffered from subclinical or overt thyrotoxicosis. Two additional patients developed subclinical or overt thyrotoxicosis during stay in hospital. In four subjects (25%), FT4 concentrations were increased, despite nonsuppressed TSH concentration, representing an elevated set point of thyroid homeostasis. The thyroid hormone profile was normal in only six patients (38%) presenting with TTS. CONCLUSION: Abnormal thyroid function is frequent in patients with TTS. Primary hyperthyroidism and an elevated set point of thyroid homeostasis are common in TTS, suggesting a stress-dependent endocrine response or type 2 thyroid allostasis. Thyroid function may be a worthwhile target in treating or preventing TTS.

Use of automated external defibrillators for in-hospital cardiac arrest : Any time, any place?

BACKGROUND: Acute treatment of in-hospital cardiac arrest (IHCA) is challenging and overall survival rates are low. However, data on the use of public-access automated external defibrillators (AEDs) for IHCA remain controversial. The aim of our study was to evaluate characteristics of patients experiencing IHCA and feasibility of public-access AED use for resuscitation in a university hospital. METHODS: IHCA events outside the intensive care unit were analysed over a period of 21 months. Patients' characteristics, AED performance, return of spontaneous circulation (ROSC) and 24 h survival were evaluated. Outcomes following adequate and inadequate AED use were compared. RESULTS: During the study period, 59 IHCAs occurred. AED was used in 28 (47.5%) of the cases. However, AED was adequately used in only 42.8% of total AED cases. AED use was not associated with an increased survival rate (12.9 vs. 10.7%, p = 0.8) compared to non-AED use. However, adequate AED use was associated with a higher survival rate (25 vs. 0%, p = 0.034) compared to inadequate AED use. Time from emergency call to application of AED >3 min was the most important factor of inadequate AED use. Adequate AED use was more often observed between 7:30 and 13:30 and in the internal medicine department. CONCLUSION: AEDs were applied in less than 50% of the IHCA events. Furthermore, AED use was inadequate in the majority of the cases. Since adequate AED use is associated with improved survival, AEDs should be available in hospital areas with patients at high risk of shockable rhythm.

[Prevalence of acetylsalicylic acid (ASA) - low response in vascular surgery]. / Prävalenz der ASS-Low-Response in der Gefäßchirurgie.

BACKGROUND: Research has revealed that a decreased antiplatelet effect (low response [LR]/high on-treatment platelet reactivity [HPR]) of acetylsalicylic acid (ASA) and clopidogrel is associated with an increased risk of thromboembolic events. There are extensive ASA low response (ALR) and clopidogrel low response (CLR) prevalence data in the literature, but there are only a few studies concerning vascular surgical patients. The aim of this study was to examine the prevalence and risk factors of ALR and CLR in vascular surgical patients. MATERIALS AND METHODS: We examined n = 154 patients with an antiplatelet long-term therapy, who were treated due to peripheral artery occlusive disease (PAD) and/or arteria carotis interna stenosis (CVD). To detect an ALR or CLR, we examined full blood probes with impedance aggregometry (ChronoLog® Aggregometer model 590). Risk factors were examined by acquisition of concomitant disease, severity of vascular disease, laboratory test results and medication. RESULTS: We found a prevalence of 19.3 % in the ALR group and of 21.1 % in the CLR group. Risk factors for ALR were an increased platelet and leucocyte count and co-medication with pantoprazole. We found no significant risk factors for a decreased antiplatelet effect of clopidogrel treatment. CONCLUSION: The investigated prevalence for ALR and CLR are in the range of other studies, particularly based on cardiological patients. More investigations are needed to gain a better evaluation of the risk factors for HPR and to develop an effective antiplatelet therapy regime to prevent cardiovascular complications.

[Ten years of early defibrillation: "Bochum against sudden cardiac death". Acceptance and critical analysis of using automated external defibrillators]. / Zehn Jahre Frühdefibrillation: "Bochum gegen den plötzlichen Herztod". Akzeptanz und kritische Betrachtung des Einsatzes von automatisierten externen Defibrillatoren.

BACKGROUND: There is a comprehensive early defibrillation program in Bochum (Germany); since 2003 a total of 175 automated external defibrillators (AEDs) have been installed in urban areas by the city of Bochum and private companies. These were preferably installed in places with high foot traffic, e.g., public buildings, companies, and event/shopping centers. Approximately 15,000 laypeople who work in the vicinity of the AED locations were trained in the use of defibrillators and in basic resuscitation. In addition, rescue workers on fire trucks and medically trained personnel in physicians' medical practices were equipped as "first responders" with AEDs. RESULTS: After an initiation phase, all available information after each AED use since August 2004 has been collected by the project coordinator. During the period of data collection (August 2004 to August 2013), an AED was used in a total of 17 patients who had suffered sudden cardiac death (SCD) under the project in Bochum. Eleven patients had primary ventricular fibrillation (VF). Six of these survived without neurological deficit. In another 6 patients, a nondefibrillatable rhythm disorder was diagnosed. The AEDs are reliable and showed impeccable rhythm analysis before the instructions to provide any necessary shock. DISCUSSION: Compared to the number of existing units and an estimated number of 37-100 SCD/100,000, the use of the AEDs only 17 times appears relatively small. To improve the effectiveness of the AED program in Bochum, an analysis of the emergency service responses, which were necessary because of sudden circulatory collapse, is currently being performed. This will allow areas with an increased incidence of SCD to be identified and a plan for the strategic placement of AED and emergency services can be made.

[Indications for catheter ablation of ventricular tachycardia]. / Indikationen zur Katheterablation bei ventrikulärer Tachykardie.

Ventricular tachyarrhythmias (VT) can cause sudden cardiac death. This can be prevented by an implantable cardioverter-defibrillator (ICD) but approximately 25% of patients with an ICD develop electrical storm (≥ 3 VTs within 24 hours) during the course of 4-5 years. This is a life-threatening event even in the presence of an ICD, particularly if incessant VT is present, and may significantly deteriorate the patient's psychological state if multiple shocks are discharged. Catheter ablation of VT has developed into a standard procedure in many specialized electrophysiology centers. Patients with hemodynamically stable and unstable VT are amendable to substrate-based ablation strategies. Catheter ablation can be performed as emergency procedure in patients with electrical storm as well as electively in patients with monomorphic VT stored in ICD memory. In patients with ischemic or non-ischemic cardiomyopathy, VT ablation is complementary to ICD implantation and can reduce the number of ventricular arrhythmia episodes and shocks and should be performed early. In patients with electrical storm, catheter ablation can acutely achieve rhythm stabilization and may improve prognosis in the long term. Further indications for catheter ablation exist in patients with idiopathic VT where catheter ablation represents a curative therapy, and in patients with symptomatic or asymptomatic frequent premature ventricular beats which may improve prognosis in patients with heart failure and cardiac resynchronization therapy.

The number of regulatory T cells correlates with hemodynamic improvement in patients with inflammatory dilated cardiomyopathy after immunoadsorption therapy.

Inflammatory DCM (iDCM) may be related to autoimmune processes. An immunoadsorption (IA) has been reported to improve cardiac hemodynamics. The benefit of IA is probably related to the removal of autoantibodies. A recent study suggests additional effects of IA on the T cell-mediated immune reactions, especially on regulatory T cells (Tregs). In this prospective study, the correlation between the level of Tregs and improvement of myocardial contractility in response to IA in patients with iDCM was investigated. Patients (n = 18) with iDCM, reduced left ventricular (LV) ejection fraction (<35%), were enrolled for IA. Before and 6 months after IA, LV systolic function was assessed by echocardiography, and blood levels of Tregs were quantified by FACS analysis. Patients (n = 12) with chronic ischaemic heart failure and comparable reduced LV-EF served as controls. IA improved LV-EF in 12 of 18 patients at 6-month follow-up. These patients were classified as 'IA responder'. In 6 patients, LV-EF remained unchanged. At baseline, IA responder and non-responder subgroups showed similar values for C-reactive protein, white blood cells, lymphocytes and T helper cells, but they differ for the number of circulating Tregs (responder: 2.32 ± 1.38% versus non-responder: 4.86 ± 0.28%; P < 0.01). Tregs increased significantly in the IA responders, but remained unchanged in the IA non-responders. In patients with ischaemic cardiomyopathy, none of these values changed over time. A low level of Tregs in patients with chronic iDCM may characterize a subset of patients who do best respond to IA therapy.

Predictors of sustained ventricular arrhythmia episodes in patients with primary ICD indication: male gender and AF in primary ICD prophylaxis.

AIMS: Implantable cardioverter-defibrillators (ICD) reduce mortality in patients with severely impaired left ventricular function. In randomized studies, female patients are underrepresented and data on ICD therapy is limited. Atrial fibrillation (AF) is a determinant of poor prognosis but has not been consistently evaluated. We evaluated the risk factors for the occurrence of ventricular arrhythmia episodes in patients with primary ICD prophylaxis. METHODS: Consecutive patients after ICD implantation for primary prophylaxis were followed. During follow-up, detected sustained episodes of ventricular arrhythmia were documented. Multivariate analysis controlled for propensity score was used to evaluate the correlation between gender, history of AF, and the occurrence of ventricular arrhythmia episodes. RESULTS: A total of 400 patients (19.8% female; n = 79) were included. During follow-up, 64 patients (16%) had appropriate ICD therapy episodes. Men (18%) had significantly more often episodes than women (8%; p = 0.025). Patients with a history of AF (102, 25.5%) had significantly more often episodes (30%) compared to patients without a history of AF (11%; p < 0.001). In a multivariate model, only gender (p = 0.02) and history of AF (p < 0.001) were significantly associated predictors of the occurrence of appropriate ICD therapies during follow-up. Based on the propensity score model, the adjusted hazard ratio for male gender was 2.7 (p = 0.02) and 2.6 (p = 0.0004) for history of AF. CONCLUSION: Male gender and history of AF are independent predictors for the occurrence of sustained ventricular arrhythmia in primary ICD prophylaxis. Further studies need to evaluate whether history of AF in female patients might be an indicator for higher risk of sudden cardiac arrhythmic death.

Myocardial fractional flow reserve. Its role in guiding PCI in stable coronary artery disease.

Revascularization of coronary artery lesions should be based on objective evidence of ischemia, as recommended by the guidelines of the European Society of Cardiology. However, even in the case of stable coronary artery disease and elective percutaneous coronary intervention (PCI), pre-procedural noninvasive stress test results are available in a minority of patients only. It is common practice for physicians to make decisions on revascularization in the catheterization laboratory after a cursory review of the angiogram, despite the well-recognized inaccuracy of such an approach. Myocardial fractional flow reserve (FFR) measured by a coronary pressure wire is a specific index of the functional significance of a coronary lesion, with superior diagnostic accuracy for the detection of ischemia than any noninvasive stress test. FFR trials on patients with single and multivessel disease, such as the DEFER and FAME studies, have demonstrated that the clinical benefit of PCI with respect to patient outcome is greatest when revascularization is limited to lesions inducing ischemia, whereas lesions not inducing ischemia should be treated medically.

Influence of glycaemic control on platelet bound CD40-CD40L system, P-selectin and soluble CD40 ligand in Type 2 diabetes.

AIMS: Type 2 diabetes is a potent cardiovascular risk factor, associated with proinflammatory and prothrombotic processes. The purpose of this study was to investigate whether platelet-bound CD40-CD40L signalling, P-selectin expression and soluble CD40L were increased in patients with diabetes mellitus and can be normalized by improving glycaemic control. METHODS: Soluble (s) CD40L, platelet surface expression of CD40L, CD40 and P-selectin (CD62P) on platelets were measured by flow cytometry in 71 patients with Type 2 diabetes mellitus and 37 healthy volunteers. In addition, the relationship of HbA1c to CD40-CD40L and P-selectin expression was determined in a longitudinal follow-up. RESULTS: In patients with Type 2 diabetes, platelet membrane CD40 expression (Type 2 diabetes 3.1+/-0.61 vs. controls 2.5+/-0.85 mean fluorescence intensity; P=0.001), platelet-bound CD40L (1.2+/-0.32 vs. 1.1+/-0.14; P=0.034) as well as surface expression of CD62P (0.66+/-0.19 vs. 0.57+/-0.12; P=0.007) were higher than in control subjects. Plasma sCD40L values (3.2+/-1.70 vs. 1.8+/-0.50 ng/ml; P<0.001) were also significantly increased in Type 2 diabetes. After improving glycaemic control in patients with initial HbA1c>8.5% (n=15), platelet P-selectin and CD40-CD40L expression decreased significantly by 54.0%, 36.22% and 16.26%, respectively 1 year later. CONCLUSIONS: Type 2 diabetes is associated with up-regulation of the platelet-bound CD40-CD40L system, platelet hyperactivity (enhanced P-selectin expression) and increased sCD40L levels. Improved glycaemic control, however, does help to correct abnormal platelet activation via down-regulation of CD40-CD40L system and P-selectin expression.

Gender differences in onset of symptoms in AV nodal re-entrant and accessory pathway-mediated re-entrant tachycardia.

PURPOSE: Is onset of symptoms in AV nodal re-entrant tachycardia (AVNRT) and accessory pathway-mediated re-entrant tachycardia (AVRT) patients gender-specific? METHODS: Intra- and inter-gender differences in onset of symptoms and mechanism of supraventricular tachycardia in adult patients undergoing catheter ablation for AVNRT or AVRT (N=230) were documented. RESULTS: Women with AVNRT were significantly younger at onset of symptoms compared to men (38+/-18, 51+/-18 years, p=0.01). Male AVNRT patients were significantly older at onset of symptoms compared to male AVRT patients (51+/-18, 25+/-11 years, p=0.04) but there was no difference in women. Symptoms beginning <30 years in men predicted AVRT in 73%, and beginning >or=30 years the predominant mechanism was AVNRT (85%). In women AVNRT was the most likely mechanism independent of symptom onset (>75%). CONCLUSIONS: Symptoms beginning in patients with AVNRT and AVRT prior to age 30 correlates with a 70% incidence of AVRT in men and a 80% incidence of AVNRT in women. Onset of palpitations >or= age 30 relates to AVNRT in 85% of patients.

CD31+/Annexin V+ microparticles in healthy offsprings of patients with coronary artery disease.

BACKGROUND: First-degree relatives of patients with premature coronary artery disease (CAD) develop endothelial dysfunction even in the case they are apparently healthy. In this study we wanted to clarify whether reduced blood levels of circulating endothelial progenitor cells (EPCs), an endogenous repair mechanism to replace dysfunctional endothelium, or elevated endothelial-derived microparticles (EMPs), an indicator and a mediator of increased endothelial cell damage/apoptosis, are an initial step in the pathogenesis of endothelial dysfunction in genetically predisposed subjects. MATERIALS AND METHODS: Fifty-six healthy young men (aged 23 to 31 years) from a fire brigade were enrolled, of which 20 subjects had a positive family history (FH) for premature CAD. Subjects with or without a positive FH did not differ with respect to age, body mass index, risk factors and C-reactive protein. Endothelial function was assessed by hyperaemia-mediated relaxation of the brachial artery, blood levels of EPCs (VEGFR2(+)CD34(+) cells) and number of EMPs (CD31(+(bright))/Annexin V(+) particles) were analysed by flow cytometry. RESULTS: Hyperaemia-mediated relaxation of the brachial artery was similar in both groups, and the blood levels of EPCs were comparable. However, the number of EMPs were significantly increased in subjects with a positive FH compared to those with a negative FH (neg. FH: 55.31 +/- 4.88 vs. pos. FH: 70.37 +/- 6.32 particles microL(-1 )platelet poor plasma; P < 0.05). Number of EMPs correlate inversely with the FMD response. CONCLUSIONS: These results suggest that increased plasma levels of EMPs may be an initial step in the development of endothelial dysfunction in genetically predisposed subjects.

Echocardiographic findings in patients with acute coronary syndrome and normal angiogram.

Coronary angiograms performed at the time of an acute coronary syndrome typically present vessel occlusions, ruptured plaques or thrombotic lesions that require reperfusion therapy. However, occasionally, no coronary artery stenoses are detected. Myocardial ischemia frequently causes left ventricular wall motion abnormalities that can be seen easily by echocardiography. In our study we aimed to analyze echocardiographic findings in patients with acute coronary syndrome and normal angiogram. After standardized risk stratification, a total of 897 patients were classified as an acute coronary syndrome and underwent a coronary angiography immediately. In 76/897 patients angiography excluded coronary macroangiopathy. Routine echocardiographic assessment in patients with normal angiogram showed in 21.1% a reduced left ventricular systolic function and 32.9% presented with segmental wall motion abnormalities. In summary, by detection of segmental wall motion abnormalities in 1/3 of patients with suspected acute coronary syndrome and normal angiogram, obviously, an echocardiographic evaluation in this patient population is of clinical relevance. Recommendations for performing echocardiography in patients with suspected acute coronary syndromes independent of angiographic findings are strongly supported. Further analyses should implement echocardiographic techniques as contrast and tissue doppler imaging.

Patient-prosthesis mismatch and left ventricular remodelling after implantation of Shelhigh SuperStentless aortic valve prostheses.

AIM: Aortic valve replacement is a standard procedure for the treatment of severe aortic valve stenosis. Due to lower flow velocities stentless valves are associated with a more effective regression of left ventricular hypertrophy in comparison to stented valves. However, mismatch between body surface area and valve size supports unfavourable hemodynamic results. The aim of the study was to analyze hemodynamic parameters by echocardiography after implantation of the Shelhigh SuperStentless bioprosthesis and to analyze the occurrence of patient-prosthesis mismatch and left ventricular remodelling in this specific valve type. METHODS: A total of 20 patients with severe aortic stenosis underwent implantation of a Shelhigh Super Stentless prosthesis. Clinical and echocardiographic assessment was done prior to, immediate after and six months after surgery. RESULTS: All surgical procedures were successful, no surgery-related complication was documented perioperatively. One patient died after development of multiorgan failure. Echocardiography during the first eight days after surgery showed mean gradients of 16 mmHg, mean valve orifice areas of 1.8 cm(2) and indexed effective orifice areas at 0.95 cm(2)/m(2). Six-months follow-up data were obtained in 19/20 patients. There were no relevant changes in echocardiographic hemodynamic findings at the time of follow-up measurements. Significant regression of left ventricular hypertrophy was shown (P=0.0088). A patient-prosthesis mismatch occurred in one patient (0.54 cm(2)/m(2)). No recurrent symptoms were documented. CONCLUSION: Patient-prosthesis mismatch after implantation of SuperStentless Shelhigh prosthesis is rare. A significant regression of left ventricular hypertrophy could be shown after six months. Hemodynamic valve function assessed by echocardiography may be predicted early after surgery.

[Optimized programming during cardiac resynchronization therapy]. / Optimierte Programmierung der atrio-ventrikulären und ventrikulo-ventrikulären Verzögerungszeiten bei Patienten unter biventrikulärer Stimulation - ein pragmatischer Ansatz.

Cardiac resynchronization (CRT) has evolved as a therapeutic add-on tool in patients with refractory heart failure. Additional pacing of the left ventricle leads to relevant clinical and hemodynamic improvement. Optimized programming of these pacing systems may modulate therapeutic efficacy. Optimal atrio-ventricular (AV) and ventriculo-ventricular (VV) delay programming is documented to increase invasively and non-invasively determined parameters of cardiac hemodynamics. In this manuscript different options for determining optimal AV and VV delay are discussed and a pragmatic approach to optimize CRT programming is detailed. VV delay needs to be optimized as a first step of programming. Different techniques may estimate the individual need for sequential ventricular pacing. Especially electrocardiographic criteria during right and left ventricular pacing may approximate the time-delay for pre-excitation. Delay between aortic and pulmonic valve ejection can be determined using Doppler echocardiography may identify patients who benefit from sequential pacing. Optimizing AV delay is a domain of Doppler echocardiography where using a simple formula the AV delay that produces the best diastolic resynchronization of left atrial contraction and left ventricular ejection can be calculated.Using the above mentioned techniques a pragmatic, easy and fast method for increasing CRT performance can be established. In cases of worsening heart failure or relevant changes of left ventricular dimensions adaptions (re-optimization) of VV and AV delay may be needed.

[Angiographic assessment of functionally insignificant left main coronary artery stenoses: reliability compared to intracoronary pressure measurement]. / Angiographische Beurteilung funktionell nicht signifikanter Hauptstammstenosen--Zuverlässigkeit im Vergleich zur intrakoronaren Druckmessung.

BACKGROUND AND OBJECTIVE: Left main coronary artery disease (LMCA) is still a widely accepted indication for coronary artery bypass surgery. Intermediate LMCA disease, however, often cannot be evaluated reliably on the basis of clinical and angiographic information alone. The deferral of surgical revascularization based on fractional flow reserve (FFR) measurements has been shown to be safe and feasible when taking an FFR value of (3) 0.75 as cutoff. This study was performed to compare the accuracy of visual angiographic assessment of intermediate LMCA stenoses by experienced interventional cardiologists with functional assessment by FFR in a patient population with excellent long-term outcome after deferral of surgery on the basis of FFR measurements. PATIENTS AND METHODS: 24 of 51 consecutive patients with intermediate LMCA disease were deferred from surgery based on an FFR value of > or = 0.75. Each angiogram was retrospectively reviewed independently by three experienced interventional cardiologists. Reviewers were blinded to initial FFR results, clinical data, and clinical outcome and asked to classify each lesion as SIGNIFICANT (FFR < 0.75), NOT SIGNIFICANT (FFR > or = 0.75), or UNSURE if the observer was unable to make a decision based on the angiogram. RESULTS: Mean follow-up was 29 +/- 13.6 months. No death or myocardial infarction was observed, event-free survival was 69 %. When taking the "unsure" classifications into consideration the individual reviewers achieved correct lesion classification with respect to FFR results on average in 58 % to 82 % of cases. Interobserver variability resulted in only 46 % of cases in concordant lesion classification (3 agreements or 2 agreements and 1 "unsure" evaluation). The number of concordant agreements between the individual pairs of reviewers did not exceed the rate of coincidental agreements that could be expected to result from simple guessing (mean KAPPA coefficient 0.04). More than 50 % of patients with excellent long-term outcome after deferral of surgery would potentially have undergone operative revascularization if consensual decision making had been solely based on angiographic lesion assessment. CONCLUSION: The functional significance of intermediate or equivocal LMCA lesions should not be based on visual assessment alone, even when performed by experienced interventional cardiologists.