Ulrich Lotze

Diagnostic accuracy of combined cardiac troponin and copeptin assessment for early rule-out of myocardial infarction: : a systematic review and meta-analysis

Aims: This systematic review aimed to investigate the diagnostic accuracy of combined cardiac troponin (cTn) and copeptin assessment in comparison to cTn alone for early rule-out of acute myocardial infarction (AMI). Methods: Primary studies were eligible if they evaluated diagnostic accuracy for cTn with and without copeptin in patients with symptoms suggestive of AMI. AMI was defined according to the universal definition, using detection of cTn as a marker for myocardial necrosis. Eligible studies were identified by searching electronic databases (Medline, EMBASE, Science Citation Index Expanded, CINAHL, Pascal, and Cochrane) from inception to March 2013, reviewing conference proceedings and contacting field experts and the copeptin manufacturer. Results: In 15 studies totalling 8740 patients (prevalence of AMI 16%), adding copeptin improved the sensitivity of cTn assays (from 0.87 to 0.96, p=0.003) at the expense of lower specificity (from 0.84 to 0.56, p<0.001). In 12 studies providing data for 6988 patients without ST-segment elevation, the summary sensitivity and specificity estimates were 0.95 (95% CI 0.89 to 0.98) and 0.57 (95% CI 0.49 to 0.65) for the combined assessment of cTn and copeptin. When a high-sensitivity cTnT assay was used in combination with copeptin, the summary sensitivity and specificity estimates were 0.98 (95% CI 0.96 to 1.00) and 0.50 (95% CI 0.42 to 0.58). Conclusion: Despite substantial between-study heterogeneity, this meta-analysis demonstrates that copeptin significantly improves baseline cTn sensitivity. Management studies are needed to establish the effectiveness and safety of measuring copeptin in combination with high-sensitivity cTnT for early rule-out of AMI without serial testing.

Comparison of conventional and high-sensitivity troponin in patients with chest pain: A collaborative meta-analysis

BACKGROUND Multiple studies have evaluated the diagnostic and prognostic performance of conventional troponin (cTn) and high-sensitivity troponin (hs-cTn). We performed a collaborative meta-analysis comparing cTn and hs-cTn for diagnosis of acute myocardial infarction (AMI) and assessment of prognosis in patients with chest pain. METHODS MEDLINE/PubMed, Cochrane CENTRAL, and EMBASE were searched for studies assessing both cTn and hs-cTn in patients with chest pain. Study authors were contacted and many provided previously unpublished data. RESULTS From 17 included studies, there were 8,644 patients. Compared with baseline cTn, baseline hs-cTn had significantly greater sensitivity (0.884 vs 0.749, P < .001) and negative predictive value (NPV; 0.964 vs 0.935, P < .001), whereas specificity (0.816 vs 0.938, P < .001) and positive predictive value (0.558 vs 0.759, P < .001) were significantly reduced. Based on summary receiver operating characteristic curves, test performance for the diagnosis of AMI was not significantly different between baseline cTn and hs-cTn (0.90 [95% CI 0.85-0.95] vs 0.92 [95% CI 0.90-0.94]). In a subanalysis of 6 studies that alternatively defined AMI based on hs-cTn, cTn had lower sensitivity (0.666, P < .001) and NPV (0.906, P < .001). Elevation of baseline hs-cTn, but negative baseline cTn, was associated with increased risk of death or nonfatal myocardial infarction during follow-up (P < .001) compared with both negative. CONCLUSION High-sensitivity troponin has significantly greater early sensitivity and NPV for the diagnosis of AMI at the cost of specificity and positive predictive value, which may enable early rule in/out of AMI in patients with chest pain. Baseline hs-cTn elevation in the setting of negative cTn is also associated with increased nonfatal myocardial infarction or death during follow-up.

Tako-Tsubo-Like Cardiomyopathy: Specific ECG Findings, Characterization and Clinical Findings in a European Single Center

Objectives: A newly discovered heart syndrome mimicking acute coronary syndrome has been termed ‘Tako-Tsubo cardiomyopathy’ (TTC). Differentiation from acute myocardial infarction using the ECG is an important issue in clinical practice. Methods: We retrospectively analyzed patients admitted for cardiac catheterization between September 2003 and September 2006. Results: From 26,593 cardiac catheterization procedures, we identified 21 patients with suggested TTC (0.08%). Trigger mechanisms were present in 38.1%; all patients had elevated troponin levels (mean 3.9 ng/ml). Median age was 68.4 years; 90.5% were female. Hypertension was seen in 85.7% and atrial fibrillation in 19.1%. Specific ECG findings related to a TTC are: a mild elevation of the ST segment arising from the S curve of the QRS complex, where the maximum ST segment elevation at the basis of the T wave is <1.5 mm, T-wave inversion, absence of ST segment depression and a summated amplitude of the S curve in V1 plus R in V6 <1.5 mV. An intraventricular gradient was seen in 9.5%; coronary atherosclerosis was detected in 57.1%. Follow-Up Data: Mean follow-up was 13.2 months. 47.6% were free from angina or dyspnea, most of the patients received β-blockers/ACE inhibitors (76.2%). One patient had a sudden cardiac death (4.8%), 1 patient became an implantable cardioverter-defibrillator primarily due to resuscitation. Conclusion: TTC is a rare syndrome mimicking acute coronary syndrome that shows a specific ECG pattern and does not appear to be an unambiguously benign disease.

Carvedilol inhibits platelet-derived growth factor-induced signal transduction in human cardiac fibroblasts.

In the current study, first the platelet-derived growth factor (PDGF)-induced stimulation of the PDGF-&bgr; receptor kinase in human cardiac fibroblasts was examined, and then the possibility of counterbalancing this signal transduction by carvedilol, a &bgr;-blocker with &agr;1-blocking properties, was investigated. Human cardiac fibroblasts were cultured from myocardial biopsy samples taken from patients with idiopathic dilated cardiomyopathy. The stimulation of the PDGF-&bgr; receptor kinase by recombinant human PDGF (BB) in the cells and the inhibitory effect of carvedilol (1, 5, 10, and 20 &mgr;M) were investigated by analyzing PDGF-induced PDGF receptor tyrosine phosphorylation using Western blotting and by measuring DNA synthesis with a colorimetric assay. In human cardiac fibroblasts, the PDGF receptor kinase could be stimulated with PDGF (100 ng/ml) and inhibited with carvedilol (5 &mgr;M). In addition, carvedilol at a concentration of 5 &mgr;M significantly decreased DNA synthesis by approximately 50%. The inhibition of PDGF-stimulated mitogenesis by carvedilol at concentrations of 10 and 20 &mgr;M was 64 or 75%, respectively. Other &bgr;-adrenoceptor antagonists such as propranolol (10 &mgr;M) and metoprolol (10 &mgr;M) did not significantly affect the PDGF-induced &bgr;-receptor autophosphorylation. These findings provide novel experimental support for the known beneficial clinical effects of carvedilol in the treatment of chronic heart failure associated with myocardial fibrosis.

Cardiac sympathetic activity as measured by myocardial 123-I-metaiodobenzylguanidine uptake and heart rate variability in idiopathic dilated cardiomyopathy

In patients with idiopathic dilated cardiomyopathy (IDC) the increased sympathetic activity owing to chronic congestive heart failure leads to an imbalance of cardiac autonomic tone, as reflected by decreased heart rate variability (HRV). Iodine-123-metaiodobenzylguanidine (123-I-MIBG), which has the same affinity for sympathetic nerve endings as norepinephrine, can be used to assess the integrity and function of the cardiac sympathetic nervous system. The aim of the present study was to measure cardiac sympathetic activity by assessing 123-I-MIBG uptake compared with HRV in patients with IDC. In 12 patients with IDC and mild to moderate heart failure, myocardial MIBG uptake was calculated from the myocardial (M) to left ventricular cavity (C) voxel values density ratio and the 123-I activity in a blood sample as a reference (= M/C ratio) using a double radionuclide study with 123-I-MIBG and technetium-99m-MIBI. To investigate the relation between myocardial MIBG uptake and HRV in time domain, the linear regression between the M/C ratio, a new scintigraphic parameter, and the mean RR interval or the HRV triangular index, respectively, was determined. A significant correlation between the M/C ratio and mean RR interval (r = 0.52; p = 0.016) or M/C ratio and HRV triangular index (r = 0.76; p = 0.003), respectively, was found. Thus, the significant correlation between the M/C ratio and HRV indicate that they are both suitable noninvasive methods for evaluating cardiac sympathetic activity in patients with IDC and, furthermore, favor the view that there is evidence of a relation between HRV and the disorder of the cardiac presynaptic sympathetic nerve endings as demonstrated by a reduced M/C ratio.

Leptin: ein Parameter für metabolische Veränderungen der Herzinsuffizienz

Objective Advanced chronic heart failure is a hypercatabolic state with an imbalance between anabolic and catabolic metabolism and finally progressive loss of both muscle mass and adipose tissue. Leptin, the product of the obesity gene, is a hormone secreted by adipocytes. Therfore, we tested the hypothesis that plasma leptin concentrations are reduced in advanced chronic heart failure. Methods In 20 patients with chronic congestive heart failure (LVEF 23±6%) and 20 healthy controls (LVEF 65±8%) matched for gender, age, and body mass index, fasting plasma leptin (ELISA) and TNFα (ELISA) were measured. Follow-up examination was performed after 1 year. Results The fasting plasma leptin concentrations of patients with NYHA grade III (8.4±3.8 ng/ml*) and NYHA grade IV (4.6±2.4 ng/ml†) were significantly lower as compared with the controls (11.2±3.1 ng/ml; *p<0.05, †p<0.01). In patients with NYHA grade II plasma leptin levels were significantly elevated as compared with the healthy controls (14.9±4.2 ng/ml). TNFα was higher in heart failure patients than in healthy controls (8.6±3.6 pg/ml; 5.9±2.1 pg/ml; respectively; p<0.05), but did not correlate with the NYHA functional class. Mortality of the controls was 0%, whereas 15% (n=3) in the congestive heart failure group; one patient (5%) needs an urgent heart transplantation. All of those patients had leptin concentrations below 5 ng/ml. Conclusions Plasma leptin concentrations correlate with the NYHA functional class suggesting anabolic metabolism in NYHA class II and catabolic metabolism in advanced heart failure which might be of prognostic relevance. Hintergrund Die terminale Herzinsuffizienz ist ein hyperkataboler Status der durch ein Ungleichgewicht zwischen anabolem und katabolem Stoffwechsel gekennzeichnet ist und mit einem progredienten Verlust sowohl von Muskel- als auch Fettmasse einhergeht. Leptin, ist ein Hormon, das von dem obese-Gen kodiert und überwiegend von Adipozyten sezerniert wird. Wir stellten deshalb die Hypothese auf, dass die Plasmaleptinkonzentration bei der chronischen, fortgeschrittenen Herzinsuffizienz vermindert ist. Methoden 20 Patienten mit chronischer Herzinsuffizienz (LVEF 25±6%) wurden mit 20 Patienten ohne kardiovaskuläre Erkrankung (LVEF 65±8%) in einer „matched-pair” Analyse (Alter, Geschlecht und body mass index [BMI]) hinsichtlich ihrer Leptin- (ELISA) und TNFα- (ELISA) Plasmakonzentrationen untersucht. Eine Follow-up-Untersuchung erfolgte nach einem Jahr. Ergebnisse Die Leptinkonzentration von Patienten im NYHA-Stadium III (8,4±3,8 ng/ml*) und IV (4,6±2,4 ng/ml†) waren im Vergleich zu dem Kontrollkollektiv (11,2±3,1 pg/ml) signifikant erniedrigt (*p<0,05, †p<0,01). Patienten im NYHA-Stadium II (14,9±4,2 ng/ml) zeigten die höchsten Leptinspiegel. Die TNFα-Konzentrationen waren bei den herzinsuffizienten Patienten höher als bei dem herzgesunden Kontrollkollektiv (8,6±3,6 pg/ml vs. 5,9±2,1 pg/ml; p<0,05), korrelierten aber nicht mit dem NYHA-Stadium. Die Mortalität des Kontrollkollektives lag bei 0%, hingegen waren aus der Gruppe der herzinsuffizienten Patienten 15% (n=3) verstorben, ein Patient (5%) bedurfte einer dringlichen Herztransplantation. Alle vier Patienten zeigten Plasmaleptinspiegel unter 5 ng/ml. Schlussfolgerung Die Plasmaleptinkonzentration korreliert invers mit dem klinischen Stadium der Herzinsuffizienz und charakterisiert den anabolen Stoffwechsel im Frühstadium und den katabolen Stoffwechsel im Spätstadium der Herzinsuffizienz und besitzt möglicherweise prognostische Relevanz.

Early Time Course of Heart Rate Variability after Thrombolytic and Delayed Interventional Therapy for Acute Myocardial Infarction

In 89 of 97 consecutive patients with myocardial infarction (MI) undergoing thrombolysis and delayed early coronary angiography with PTCA, if indicated, heart rate variability (HRV) in time domain was evaluable 40 ± 11 h after the onset of chest pain using 24-hour ECG recordings. Patients with anterior MI (n = 40) had lower values for HRV and left ventricular ejection fraction (p < 0.05). The mean of all 5-min standard deviations of RR intervals (SDNNi) and the root-mean-square difference of successive RR intervals (rMSSD) decreased significantly (p < 0.001 each), whereas the standard deviation of all normal RR intervals and the percentage of absolute differences between successive RR intervals only showed a tendency to lower values 4 weeks after MI (p = 0.20 and 0.08, respectively). The decreases in SDNNi and rMSSD were more evident in inferior than in anterior MI. The time course of HRV following MI was similar in patients with and without PTCA. These results indicate an initial vagal hyperactivity in inferior MI, which is quickly predominated by sympathetic activation and a prolonged recovery of the cardiac autonomic imbalance after MI despite a successful combined reperfusion therapy.

Cardiac catheterisation in nonagenarians： Single center experience

Objective To explore the treatment, procedure related risks, and outcomes of patients older than 90 years of age undergoing cardiac catheterization. Methods We retrospectively studied 32 patients ≥ 90 years (93.0 ± 1.2 years) who underwent cardiac catheterisation in a tertiary specialist hospital (0.2% of 14,892 procedures during three years). The results were compared to a patient cohort younger than 90 years of age. Results Baseline characteristics revealed a higher prevalence of diabetes (P < 0.001), chronic obstructive pulmonary disease (P < 0.04), previous myocardial infarction (P < 0.02), and complex coronary anatomy (SYNTAX score 33 vs. 19) in nonagenarians. Patients < 90 years of age showed more hyperlipidemia (P < 0.01) and previous percutaneous coronary interventions (P < 0.015). Nonagenarians underwent coronary angiography more often for acute coronary syndrome (ACS) (P < 0.003), were presented more often in cardiogenic shock (P < 0.003), and were transferred faster to coronary angiography in cases of ACS (P < 0.0001). The observed in-hospital mortality rate (13% study group vs. 1% control group; P < 0.003) in nonagenarians was lower than the calculated rate of thrombolysis in myocardial infarction (TIMI) and global registry of acute cardiac events (GRACE) mortality and strongly influenced by the severity of clinical presentation and the presence of co-morbidities. Conclusion Despite the common scepticism that cardiac catheterisation exposes patients ≥ 90 years to an unwarranted risk, our data demonstrate an acceptable incidence of complications and mortality in this group of patients.

Unexpanded, irretrievable stent in the proximal right coronary artery: successful management with stent graft implantation.

Stent loss and failure of retrieval are rare; nevertheless, complications have to be taken into account during percutaneous coronary intervention. Here we report a case of an unexpanded, irretrievable Palmaz‐Schatz stent in the proximal right coronary artery near to the ostium and the successful management by implanting a synthetic stent graft. Cathet. Cardiovasc. Intervent. 46:344–349, 1999.

Cryptogenic transient ischemic attack after nose blowing: association of huge atrial septal aneurysm with patent foramen ovale as potential cause

Association of atrial septal aneurysm (ASA) with patent foramen ovale (PFO) is considered an important risk factor for cardioembolism frequently forwarding paradoxical embolism in patients with cryptogenic or unexplained cerebral ischemic events. We herein describe the case of a 69-year-old male patient reporting uncontrolled movements of the right arm due to a muscle weakness, slurred speech, and paresthesia in the oral region some seconds after he had blown his nose. These neurological symptoms had improved dramatically within a few minutes and were completely regressive at admission to our hospital about two hours later. On transesophageal echocardiography (TEE) a huge ASA associated with PFO was detected. Diagnosis of the large-sized ASA was also confirmed by cardiac magnetic resonance imaging. Due to the early complete recovery from his neurological symptoms, the patient was diagnosed with a transient ischemic attack (TIA). After nine days he was discharged in a good clinical condition under the treatment with oral anticoagulation. It is concluded that in cryptogenic or unexplained stroke or TIA TEE should always be performed to rule out ASA and PFO as potential sources for paradoxical embolism in those inconclusive clinical situations.