Differential immunological signature at the culprit site distinguishes acute coronary syndrome with intact from acute coronary syndrome with ruptured fibrous cap: results from the prospective translational OPTICO-ACS study.

AIMS: Acute coronary syndromes with intact fibrous cap (IFC-ACS), i.e. caused by coronary plaque erosion, account for approximately one-third of ACS. However, the underlying pathophysiological mechanisms as compared with ACS caused by plaque rupture (RFC-ACS) remain largely undefined. The prospective translational OPTICO-ACS study programme investigates for the first time the microenvironment of ACS-causing culprit lesions (CL) with intact fibrous cap by molecular high-resolution intracoronary imaging and simultaneous local immunological phenotyping. METHODS AND RESULTS: The CL of 170 consecutive ACS patients were investigated by optical coherence tomography (OCT) and simultaneous immunophenotyping by flow cytometric analysis as well as by effector molecule concentration measurements across the culprit lesion gradient (ratio local/systemic levels). Within the study cohort, IFC caused 24.6% of ACS while RFC-ACS caused 75.4% as determined and validated by two independent OCT core laboratories. The IFC-CL were characterized by lower lipid content, less calcification, a thicker overlying fibrous cap, and largely localized near a coronary bifurcation as compared with RFC-CL. The microenvironment of IFC-ACS lesions demonstrated selective enrichment in both CD4+ and CD8+ T-lymphocytes (+8.1% and +11.2%, respectively, both P < 0.05) as compared with RFC-ACS lesions. T-cell-associated extracellular circulating microvesicles (MV) were more pronounced in IFC-ACS lesions and a significantly higher amount of CD8+ T-lymphocytes was detectable in thrombi aspirated from IFC-culprit sites. Furthermore, IFC-ACS lesions showed increased levels of the T-cell effector molecules granzyme A (+22.4%), perforin (+58.8%), and granulysin (+75.4%) as compared with RFC plaques (P < 0.005). Endothelial cells subjected to culture in disturbed laminar flow conditions, i.e. to simulate coronary flow near a bifurcation, demonstrated an enhanced adhesion of CD8+T cells. Finally, both CD8+T cells and their cytotoxic effector molecules caused endothelial cell death, a key potential pathophysiological mechanism in IFC-ACS. CONCLUSIONS: The OPTICO-ACS study emphasizes a novel mechanism in the pathogenesis of IFC-ACS, favouring participation of the adaptive immune system, particularly CD4+ and CD8+ T-cells and their effector molecules. The different immune signatures identified in this study advance the understanding of coronary plaque progression and may provide a basis for future development of personalized therapeutic approaches to ACS with IFC. TRIAL REGISTRATION: The study was registered at clinicalTrials.gov (NCT03129503).

Real-time optical coherence tomography coregistration with angiography in percutaneous coronary intervention-impact on physician decision-making: The OPTICO-integration study.

AIMS: Intracoronary optical coherence tomography (OCT) imaging allows for high-resolution characterization of coronary lesions. Difficulties in matching cross-sectional OCT-images with angiographic lesion localization may limit optimal clinical utilization. We sought to prospectively assess the impact of a novel system of real-time OCT coregistration with angiography (ACR) on physician decision-making during percutaneous coronary interventions (PCI). METHODS AND RESULTS: Strategy for PCI (stent - length, - diameter, - strategy, landing zone) and PCI-optimization (stent-malappostion, -underexpansion, edge-dissections, geographical mismatch) was prospectively assessed in 50 patients with 58 coronary lesions after (I) angiography, (II) OCT imaging, and (III) ACR. Preprocedural OCT imaging altered stent-length (58.9%), diameter (33.9%), and PCI-strategy (12.5%) in 40 (71.4%) lesions. The use of ACR resulted in additional changes in PCI strategy in 40.7% of mostly complex lesions in comparison to OCT imaging alone and involved mainly device landing zone (24.1%) and stent length (22.2%). Postprocedural OCT imaging revealed the need for PCI optimization in 52.2% of the lesions, whereas post-procedural ACR had no further impact. CONCLUSIONS: Real-time OCT ACR had significant impact on PCI strategy, favoring mainly complete lesion coverage especially in complex lesions.

Coronary Angiographic Findings in Acute Ischemic Stroke Patients With Elevated Cardiac Troponin: The Troponin Elevation in Acute Ischemic Stroke (TRELAS) Study.

BACKGROUND: A relevant proportion of patients with acute ischemic stroke (AIS) have elevated levels of cardiac troponins (cTn). However, the frequency of coronary ischemia as the cause of elevated cTn is unknown. The aim of our study was to analyze coronary vessel status in AIS patients with elevated cTn compared with patients presenting with non-ST-segment-elevation acute coronary syndrome (NSTE-ACS). METHODS AND RESULTS: Among 2123 consecutive patients with AIS prospectively screened at 2 tertiary hospitals, 13.7% had cTn elevation (>50 ng/L). According to a prespecified sample size estimation, 29 patients with AIS (median age, 76 years [first-third quartiles, 70-82 years]; 52% male) underwent conventional coronary angiography and were compared with age- and sex-matched patients with NSTE-ACS. The primary end point was presence of coronary culprit lesions on coronary angiograms as analyzed by independent interventional cardiologists blinded for clinical data. Median cTn on presentation did not differ between patients with AIS or NSTE-ACS (95 versus 94 ng/L; P=0.70). Compared with patients with NSTE-ACS, patients with AIS were less likely to have coronary culprit lesions (7 of 29 versus 23 of 29; P<0.001) or any obstructive coronary artery disease (15 of 29 versus 25 of 29; P=0.02; median number of vessels with >50% stenosis, 1 [first-third quartiles, 0-2] versus 2 [first-third quartiles, 1-3]; P<0.01). CONCLUSIONS: Coronary culprit lesions are significantly less frequent in AIS patients compared with age- and sex-matched patients with NSTE-ACS despite similar baseline cTn levels. Half of all AIS patients had no angiographic evidence of coronary artery disease. Further studies are needed to clinically identify the minority of patients with AIS and angiographic evidence of a culprit lesion. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01263964.

Acute Thrombotic Occlusion of the Left Brachial Artery After Intra-Arterial Administration of Amiodarone.

OBJECTIVE: To report a case of intra-arterial amiodarone injection in a hemodynamically unstable patient leading to acute vessel occlusion and a subsequent compartment syndrome. DESIGN: Case report. SETTING: Prehospital setting, emergency department and ICU of a university hospital. PATIENT: A 58-year-old woman presenting with a ventricular tachycardia of 190 beats/min was administered amiodarone through an accidently placed arterial access in the left cubital fossa. Quickly, the woman developed clinical signs of an acute arterial occlusion. INTERVENTIONS: Immediate left brachial artery angiography with subsequent thrombectomy was performed. MEASUREMENTS AND MAIN RESULTS: A thrombotic occlusion at the injection side was found, which was immediately recanalized by thrombus aspiration. In addition to anticoagulation and an adenosine diphosphate-antagonist an adjunct therapy with vasodilators and gpIIb/IIIa inhibitors was given and repetitive duplex sonography confirmed arterial flow. However, despite restoration of blood flow the patient developed a severe compartment syndrome of the arm and had to receive multistep surgical interventions. CONCLUSIONS: This is the first report of an acute thrombotic vessel occlusion leading to a compartment syndrome upon accidental intra-arterial injection of amiodarone in an emergency setting. In the hemodynamically unstable patient healthcare providers should be aware of arterial miscanulation and its consequences. Upon intra-arterial injection, a direct antithrombotic and vasodilative therapy should be administered via the initially misplaced arterial access, which may include a gpIIb/IIIa inhibitor.

Exploring cardiac arrest in 'at-home' settings: Concepts derived from a qualitative interview study with layperson bystanders.

BACKGROUND: Two thirds of Out-of-Hospital Cardiac Arrests (OHCAs) occur at the patient's home ('at-home-CA'), where bystander CPR (B-CPR) rates are significantly lower than in public locations. Knowledge about the circumstances of this specific setting has mainly been limited to quantitative data. To develop a more conceptual understanding of the circumstances and dynamics of 'at-home CA', we conducted a qualitative interview study. METHODS: Twenty-one semi-structured in-depth interviews were performed with laypersons who had witnessed 'at-home CA'. The interviews were audio recorded, transcribed, and analysed by qualitative content analysis (QCA). A category system was developed to classify facilitating and impeding factors and to finally derive overarching concepts of 'at-home CA'. RESULTS: Qualitative Content Analysis yielded 1'347 relevant interview segments. Of these, 398 related to factors facilitating B-CPR, 328 to factors impeding, and 621 were classified neutral. Some of these factors were specific to 'at-home CA'. The privacy context was found to be a particularly supportive factor, as it enhanced the commitment to act and facilitated the detection of symptoms. Impeding factors, aggravated in 'at-home CA' settings, included limited support from other bystanders, acute stress response and impaired situational judgement, as well as physical challenges when positioning the patient. We derived six overarching concepts defining the 'at-home CA' situation: (a) unexpectedness of the event, (b) acute stress response, (c) situational judgement, (d) awareness of the necessity to perform B-CPR, (e) initial position of the patient, (f) automaticity of actions. CONCLUSION: Integrating these concepts into dispatch protocols and layperson training may improve dispatcher-bystander interaction and the outcomes of 'at-home CA'.

Gender-Specific Performance of One- Compared to Two-Catheter Concepts in Transradial Coronary Angiography - Insights From the Randomized UDDC-Radial-Trial.

OBJECTIVES: The present sub-analysis from the randomized UDDC-Radial-Trial sought to compare one-catheter concepts (OCC) with two-catheter concepts (TCC) in different patient subgroups, particularly in those depending on gender and age. BACKGROUND: There is an ongoing debate regarding potential performance differences of OCC compared to TCC for transradial coronary angiography in specific patient subgroups. METHODS: The randomized UDDC-Radial-Trial enrolled a total of 300 patients planed for coronary angiography in a 2:1 ratio to either OCC by Tiger II (n = 100) and BLK (n = 100) or TCC by Judkins (n = 100) catheters. Predefined patient subgroups stratified for age, gender and patient constitution were analyzed with regard to the primary outcome measure of time required for a complete coronary angiography. RESULTS: In male patients time for coronary angiography was significantly shorter in the TCC group compared to the OCC group (510 ± 37 s vs. 615 ± 35 s; p = 0.046). No difference between the catheter concepts was observed in the subset of female patients (525 ± 34 s vs. 583 ± 54 s; p = 0.43). TCC was associated with shorter coronary angiography time in patients aged <71 years compared to OCC (462 ± 23 s vs. 570 ± 38 s; p = 0.018). In patients ≥72 years of age no difference was detected (573 ± 41 s vs. 636 ± 45 s; p = 0.31). Other subgroups showed no relevant differences in angiography time among OCC and TCC. CONCLUSIONS: The present subgroup analysis from the UDDC-radial trial demonstrates the use of OCC in transradial diagnostic angiography to be inferior compared to TCC in terms of angiography time in younger and male patients.

Troponin elevation in acute ischemic stroke (TRELAS)--protocol of a prospective observational trial.

BACKGROUND: Levels of the cardiac muscle regulatory protein troponin T (cTnT) are frequently elevated in patients with acute ischemic stroke and elevated cTnT predicts poor outcome and mortality. The pathomechanism of troponin release may relate to co-morbid coronary artery disease and myocardial ischemia or, alternatively, to neurogenic cardiac damage due to autonomic activation after acute ischemic stroke. Therefore, there is uncertainty about how acute ischemic stroke patients with increased cTnT levels should be managed regarding diagnostic and therapeutic workup. METHODS/DESIGN: The primary objective of the prospective observational trial TRELAS (TRoponin ELevation in Acute ischemic Stroke) is to investigate the frequency and underlying pathomechanism of cTnT elevation in acute ischemic stroke patients in order to give guidance for clinical practice. All consecutive patients with acute ischemic stroke admitted within 72 hours after symptom onset to the Department of Neurology at the Campus Benjamin Franklin of the University Hospital Charité will be screened for cTnT elevations (i.e. ≥ 0.05 µg/l) on admission and again on the following day. Patients with increased cTnT will undergo coronary angiography within 72 hours. Diagnostic findings of coronary angiograms will be compared with age- and gender-matched patients presenting with Non-ST-Elevation myocardial infarction to the Department of Cardiology. The primary endpoint of the study will be the occurrence of culprit lesions in the coronary angiogram indicating underlying co-morbid obstructive coronary artery disease. Secondary endpoints will be the localization of stroke in the cerebral imaging and left ventriculographic findings of wall motion abnormalities suggestive of stroke-induced global cardiac dysfunction. DISCUSSION: TRELAS will prospectively determine the frequency and possible etiology of troponin elevation in a large cohort of ischemic stroke patients. The findings are expected to contribute to clarify pathophysiologic concepts of co-morbid cardiac damage in ischemic stroke patients and also to provide a basis for clinical recommendations for cardiac workup of such patients. TRIAL REGISTRATION: clinicaltrials.gov NCT01263964.

Impact of real-time angiographic co-registered optical coherence tomography on percutaneous coronary intervention: the OPTICO-integration II trial.

AIMS: Longitudinal geographic mismatch (LGM) as well as edge dissections are associated with an increased risk of adverse events after percutaneous coronary intervention (PCI). Recently, a novel system of real-time optical coherence tomography (OCT) with angiographic co-registration (ACR) became available and allows matched integration of cross-sectional OCT images to angiography. The OPTICO-integration II trial sought to assess the impact of ACR for PCI planning on the risk of LGM and edge dissections. METHODS: A total of 84 patients were prospectively randomized to ACR-guided PCI, OCT-guided PCI (without co-registration), and angiography-guided PCI. Primary endpoint was a composite of major edge dissection and/or LGM as assessed by post-PCI OCT. RESULTS: The primary endpoint was significantly reduced in ACR-guided PCI (4.2%) as compared to OCT-guided PCI (19.1%; p = 0.03) and angiography-guided PCI (25.5%; p < 0.01). Rates of LGM were 4.2%, 17.0%, and 22.9% in the ACR-guided PCI, in the OCT-guided PCI, and the angiography-guided PCI groups, respectively (ACR vs. OCT p = 0.04; ACR vs. angiography p = 0.04). The number of major edge dissections was low and without significant differences among the study groups (0% vs. 2.1% vs. 4.3%). CONCLUSION: This study for the first time demonstrates superiority of ACR-guided PCI over OCT- and angiography-guided PCI in reducing the composite endpoint of major edge dissection and LGM, which was meanly driven by a reduction of LGM.

A randomised comparison of monoplane versus biplane fluoroscopy in patients undergoing percutaneous coronary intervention: the RAMBO trial.

AIMS: Interventional cardiologists are exposed to substantial occupational ionising radiation. This study sought to investigate differences in radiation exposure in biplane versus monoplane coronary angiography and percutaneous coronary interventions (PCI). METHODS AND RESULTS: RAMBO (RAdiation exposure in Monoplane versus Biplane cOronary angiography and interventions) was a prospective, randomised, two-arm, single-centre, open-label trial, enrolling a total of 430 patients undergoing coronary angiography. Patients were randomly assigned to biplane or monoplane imaging. The primary efficacy measure, the operator radiation dose at the level of the left arm as measured by a wearable electronic dosimeter, was significantly higher in the biplane as compared to the monoplane group (4 [1-13] µSv vs 2 [0-6.8] µSv, p<0.001). The dose area product was 11,955 (7,095-18,246) mGy*cm2 and 8,349 (5,851-14,159) mGy*cm2 in the biplane and the monoplane groups, respectively (p<0.001). While fluoroscopy time did not differ between the groups (p=0.89), the amount of contrast medium was lower with biplane as compared with monoplane imaging (p<0.001). CONCLUSIONS: Biplane imaging for coronary angiography and PCI is related to an increased radiation exposure for the interventional cardiologist as compared with monoplane imaging. Monoplane imaging should be considered for advanced radioprotection in cardiac catheterisation, with biplane imaging used for selected cases only.

Familial Recurrent Myocarditis Triggered by Exercise in Patients With a Truncating Variant of the Desmoplakin Gene.

Background Variants of the desmosomal protein desmoplakin are associated with arrhythmogenic cardiomyopathy, an important cause of ventricular arrhythmias in children and young adults. Disease penetrance of desmoplakin variants is incomplete and variant carriers may display noncardiac, dermatologic phenotypes. We describe a novel cardiac phenotype associated with a truncating desmoplakin variant, likely causing mechanical instability of myocardial desmosomes. Methods and Results In 2 young brothers with recurrent myocarditis triggered by physical exercise, screening of 218 cardiomyopathy-related genes identified the heterozygous truncating variant p.Arg1458Ter in desmoplakin. Screening for infections yielded no evidence of viral or nonviral infections. Myosin and troponin I autoantibodies were detected at high titers. Immunohistology failed to detect any residual DSP protein in endomyocardial biopsies, and none of the histologic criteria of arrhythmogenic cardiomyopathy were fulfilled. Cardiac magnetic resonance imaging revealed no features associated with right ventricular arrhythmogenic cardiomyopathy, but multifocal subepicardial late gadolinium enhancement was present in the left ventricles of both brothers. Screening of adult cardiomyopathy cohorts for truncating variants identified the rare genetic variants p.Gln307Ter, p.Tyr1391Ter, and p.Tyr1512Ter, suggesting that over subsequent decades critical genetic/exogenous modifiers drive pathogenesis from desmoplakin truncations toward different end points. Conclusions The described novel phenotype of familial recurrent myocarditis associated with a desmoplakin truncation in adolescents likely represents a serendipitously revealed subtype of arrhythmogenic cardiomyopathy. It may be caused by a distinctive adverse effect of the variant desmoplakin upon the mechanical stability of myocardial desmosomes. Variant screening is advisable to allow early detection of patients with similar phenotypes.

Impella versus IABP in acute myocardial infarction complicated by cardiogenic shock.

Objective: We investigated the benefit of Impella, a modern percutaneous mechanical support (pMCS) device, versus former standard intra-aortic balloon pump (IABP) in acute myocardial infarction complicated by cardiogenic shock (AMICS). Methods: This single-centre, retrospective study included patients with AMICS receiving pMCS with either Impella or IABP. Disease severity at baseline was assessed with the IABP-SHOCK II score. The primary outcome was all-cause mortality at 30 days. Secondary outcomes were parameters of shock severity at the early postimplantation phase. Adjusted Cox proportional hazards models identified independent predictors of the primary outcome. Results: Of 116 included patients, 62 (53%) received Impella and 54 (47%) IABP. Despite similar baseline mortality risk (IABP-SHOCK II high-risk score of 18 % vs 20 %; p = 0.76), Impella significantly reduced the inotropic score (p < 0.001), lactate levels (p < 0.001) and SAPS II (p =0.02) and improved left ventricular ejection fraction (p = 0.01). All-cause mortality at 30 days was similar with Impella and IABP (52 % and 67 %, respectively; p = 0.13), but bleeding complications were more frequent in the Impella group (3 vs 4 units of transfused erythrocytes concentrates due to bleeding complications, p = 0.03). Previous cardiopulmonary resuscitation (HR 3.22, 95% CI 1.76 to 5.89; p < 0.01) and an estimated intermediate (HR 2.77, 95% CI 1.42 to 5.40; p < 0.01) and high (HR 4.32 95% CI 2.03 to 9.24; p = 0.01) IABP-SHOCK II score were independent predictors of all-cause mortality. Conclusions: In patients with AMICS, haemodynamic support with the Impella device had no significant effect on 30-day mortality as compared with IABP. In these patients, large randomised trials are warranted to ascertain the effect of Impella on the outcome.

Cardiac Magnetic Resonance Imaging in Patients with Acute Ischemic Stroke and Elevated Troponin: A TRoponin ELevation in Acute Ischemic Stroke (TRELAS) Sub-Study.

BACKGROUND: Elevated high-sensitive cardiac troponin (hs-cTn) can be found in more than 50% of the patients with acute ischemic stroke. The observational TRoponin ELevation in Acute ischemic Stroke (TRELAS) study revealed that about 25% of all stroke patients with elevated troponin had a coronary angiography-detected culprit lesion affording immediate intervention, and about 50% of all patients did not have any obstructive coronary artery disease. Given the risk of procedure-related complications, the identification of stroke patients in urgent need of invasive coronary angiography is desirable. METHODS: TRELAS patients were prospectively enrolled into this sub-study. In addition to conventional coronary angiography, a cardiac magnetic resonance imaging (MRI) at 3T was performed during the in-hospital stay after acute ischemic stroke to compare the diagnostic value of both imaging modalities. RESULTS: Nine stroke patients (median age 73 years [range 58-87]; four females; median NIH Stroke Severity score on admission 4 [range 0-6] with elevated hs-cTnT [median 74 ng/L, interquartile range 41-247] on admission) completed cardiac MRI and underwent coronary angiography. The absence of MRI-detected wall motion abnormalities and/or late gadolinium enhancement in 5 stroke patients corresponded with the exclusion of culprit lesions or significant coronary artery disease by coronary angiography. Four patients had abnormal MRI findings, whereof 2 showed evidence of myocardial infarction and in whom coronary angiography demonstrated a >70% stenosis of a coronary artery. CONCLUSIONS: The TRELAS sub-study indicates that noninvasive cardiac MRI may provide helpful information to identify stroke patients with or without acute coronary syndrome. Our findings might help to select stroke patients in urgent need of coronary angiography.

Comparison of resting distal to aortic coronary pressure with angiography-based quantitative flow ratio.

BACKGROUND: Quantitative flow ratio (QFR) is a novel, adenosine-free method for functional coronary lesion interrogation, which is based on 3-dimensional quantitative coronary angiography and computational algorithms. Data on QFR in all-comer patients with intermediate coronary lesions are scarce, and the diagnostic performance in comparison to resting distal to aortic coronary pressure (Pd/Pa) ratio unknown. METHODS: A total of 436 patients with 516 vessels undergoing FFR measurements were included in the analysis. Diagnostic performance of QFR, distal to aortic coronary pressure (Pd/Pa) ratio, and anatomic indices versus FFR was assessed. RESULTS: FFR ≤0.80 was measured in 19.4% of interrogated vessels. QFR significantly correlated with FFR (r = 0.82, p < 0.001) with good agreement between QFR and FFR (mean difference 0.011, 95% CI 0.008-0.015). The AUC for an FFR ≤0.80 was 0.86 (95% CI 0.83-0.89, p < 0.001) for QFR, 0.76 (0.72-0.80, p < 0.001) for resting Pd/Pa ratio, and 0.63 (0.59-0.67, p < 0.001) for diameter stenosis. The diagnostic accuracy for identifying an FFR ≤0.80 was 93.4% for QFR, 84.3% for resting Pd/Pa ratio, and 80.4% for diameter stenosis. CONCLUSIONS: QFR provides a novel diagnostic tool for functional coronary lesion assessment with superior diagnostic accuracy as compared with resting Pd/Pa ratio and anatomic indices. Future studies are needed to determine the non-inferiority of QFR analysis to FFR assessment with respect to clinical outcomes.

Performance of One- Compared With Two-Catheter Concepts in Transradial Coronary Angiography (from the Randomized Use of Different Diagnostic Catheters-Radial-Trial).

The Use of Different Diagnostic Catheters-Radial-Trial sought to compare the safety and efficacy of one-catheter concepts (OCC) using Tiger II or BLK catheters with two-catheter concepts (TCC) using standard Judkins catheters for transradial coronary angiography. A total of 300 patients planed for coronary angiography were enrolled into this single-center, single-blinded trial. Patients were randomized in a 2:1 ratio to either OCC by Tiger II (n = 100) and BLK (n = 100) or TCC by Judkins (n = 100) catheters. Primary end point was time required to perform a complete coronary angiography. Coronary angiography duration was 603 ± 29 seconds and 552 ± 26 sec in the OCC and the TCC groups (p = 0.052). Fluoroscopy time was longer in the OCC (408 ± 28 sec) as compared with the TCC group (258 ± 28 sec, p = 0.009) and the amount of contrast volume used significantly higher (98 ± 5 ml vs 67 ± 4 ml, p < 0.001). Crossover rates were increased in the OCC as compared with the TCC group (37% vs 4%, p < 0.001). These effects were observed irrespective of OCC catheter type. In conclusion, this study demonstrates that OCC do not reduce angiography time, but are associated with an increased amount of contrast volume and longer fluoroscopy time as compared with TCC.

Effect of Physical Disability on Mortality in Elderly Patients of ≥80 Years of Age Undergoing Percutaneous Coronary Intervention.

Functional decrease has been linked with adverse events in different clinical contexts. The predictive role of activity of daily living status as assessed by the Barthel index (BI) in elderly patients who underwent percutaneous coronary intervention (PCI) has not been investigated, yet. In this study, a total of 616 patients (≥80 years) who underwent PCI between January 2009 and December 2014 and with available activity of daily living data on admission were stratified according to BI (low BI <85, intermediate BI 85 to 95, high BI 100). The primary end point was all-cause mortality at a total follow-up of 442 days (interquartile range 47 to 1243). Of the 616 patients, 178 (29%), 128 (21%), and 310 (50%) were in the low, the intermediate, and the high BI groups, respectively. All-cause mortality was 10%, 13%, and 5% in the low, the intermediate, and the high BI groups, respectively (log-rank p <0.001). Belonging to the high BI group was associated with a reduced risk of all-cause mortality (hazard ratio 0.35, 95% confidence interval 0.18 to 0.69, p = 0.002), and associations remained significant after multivariable adjustments (adjusted hazard ratio 0.34, 95% confidence interval 0.13 to 0.93, p = 0.04). Functional capacity was identified as independent predictor of survival in a large cohort of patients who underwent PCI. In conclusion, activities of daily living should be incorporated into the risk stratification of elderly patients with coronary artery disease.

Pulmonary fibrosis after chemotherapy with oxaliplatin and 5-fluorouracil for colorectal cancer.

BACKGROUND: Chemotherapy with oxaliplatin and 5-fluorouracil (5-FU)/folinic acid is the standard first-line therapy of metastatic colorectal carcinoma and has shown activity in several other malignancies. This regimen is mostly well tolerated. Known side effects include myelosuppression, nausea/vomiting and neuropathies; acute pulmonary toxicity has only been described in very few reports. CASE REPORT: A 66-year-old male with metastatic rectal adenocarcinoma treated with 12 cycles of oxaliplatin and 5-FU/folinic acid developed bilateral pulmonary infiltrates and respiratory failure. Broad-spectrum antibiotic therapy did not improve his condition and extended microbiological diagnostics did not show an infectious etiology. Therapy with corticosteroids led to a short improvement, however the patient died 1 week after the initiation of corticosteroid treatment due to respiratory insufficiency. The clinical and histopathological data as well as the lack of an infectious cause indicate that pulmonary fibrosis was induced by oxaliplatin and 5-FU/folinic acid. CONCLUSION: This case demonstrates that treatment with oxaliplatin and 5-FU/folinic acid can cause acute pulmonary fibrosis. Even though pulmonary toxicity is rare in patients treated with this chemotherapy regimen compared to infectious pulmonary complications, it should be considered early in the clinical course of otherwise unexplained pulmonary infiltrates hopefully leading to a better outcome.

[Role of coronary intervention after successful cardiopulmonary resuscitation]. / Die Rolle der Koronarintervention nach erfolgreicher kardiopulmonaler Reanimation.

Immediate coronary angiography and intervention in suitable stenoses in patients resuscitated from cardiac arrest of presumed coronary origin and return of spontaneous circulation is widely established in interventional centers. The procedure is based on the analogy of positive results achieved with coronary intervention in many forms of acute coronary syndromes on the one hand and otherwise from registries showing promising data from coronary intervention of resuscitated patients. Results from randomized controlled studies, however, are not yet available. With respect to ST-elevation myocardial infarction, the diagnostic reliability of an ECG registered shortly after cardiopulmonary resuscitation is sufficient. The results of the registries are specifically promising for patients with ST-elevation myocardial infarction but less favorable for other forms of acute coronary syndromes. Moreover, insight into the results of the registries reveals that patients with the best prognostic conditions were preferentially selected for coronary intervention (e.g., younger patients, those with an initially shockable arrhythmia, bystander resuscitation), whereas those, for example, with cardiac or renal failure were excluded. For better definition of the actual benefit of coronary intervention after resuscitation from cardiac arrest and the optimal target groups, randomized controlled studies on patients with ST-elevation myocardial infarction are desirable, while for other forms of acute coronary syndromes these studies are essential.

Double-blind, randomized, prospective comparison of loading doses of 600 mg clopidogrel versus 60 mg prasugrel in patients with acute ST-segment elevation myocardial infarction scheduled for primary percutaneous intervention: the ETAMI trial (early thienopyridine treatment to improve primary PCI in patients with acute myocardial infarction).

OBJECTIVES: This study compared the timing of onset of antiplatelet action after treatment with clopidogrel and prasugrel at first medical contact in patients with ST-segment elevation myocardial infarction (STEMI) scheduled for primary percutaneous coronary intervention (PPCI). BACKGROUND: Little is known about the timing of onset of antiplatelet action after a pre-percutaneous coronary intervention (PCI) loading dose of clopidogrel or prasugrel in patients with STEMI. METHODS: This double-blind, prospective study randomized 62 patients with STEMI scheduled for PPCI in the ambulance or the emergency department to 60 mg prasugrel (n = 31) or 600 mg clopidogrel (n = 31). The primary endpoint was the platelet reactivity index (PRI) measured with the vasodilator-stimulated phosphoprotein assay 2 h after intake of the study medication. Secondary endpoints were PRI after 4 h, TIMI (Thrombolysis In Myocardial Infarction) patency of the infarct-related artery before and after PCI, and clinical events until day 30. RESULTS: The PRI after 2 h (50.4 ± 32.7% vs. 66.3 ± 22.2%; p = 0.035) and after 4 h (39.1 ± 27.5% vs. 54.5 ± 49.3%; p = 0.038) were significantly lower with prasugrel compared with clopidogrel. In addition, the rate of patients with a PRI <50% tended to be higher with prasugrel compared with clopidogrel after 2 h (46.7% vs. 28.6%; p = 0.15) and after 4 h (63.0% vs. 38.9%; p = 0.06). There were no significant differences in TIMI 2/3 patency before PCI (39.2% vs. 31.0%; p = 0.43) and TIMI 3 patency after PCI (88.5% vs. 89.3%; p = 0.92). CONCLUSIONS: The pre-PCI administration of prasugrel in patients with STEMI undergoing PPCI was associated with a significant faster platelet inhibition compared with clopidogrel. Therefore, prasugrel should be preferred to clopidogrel in this setting. (ETAMI-Study: Early Thienopyridine Treatment to Improve Primary PCI in Patients With Acute Myocardial Infarction; NCT01327534).