Tobias Becher

Characteristics and long-term outcome of right ventricular involvement in Takotsubo cardiomyopathy

OBJECTIVE Takotsubo cardiomyopathy, also known as stress-induced cardiomyopathy (SCM) resembles a reversible cardiomyopathy that is characterized by localized wall motion abnormalities in the absence of stenotic coronary vascular disease. Patients typically present with apical ballooning of the left ventricle (LV), however the right ventricle (RV) is also affected in up to 50.0% of patients. Long-term prognosis of classical SCM resembles that of patients after ST elevation myocardial infarction. Data on long-term prognosis of biventricular compared to classical SCM is controversial. The aim of this study was therefore to analyze patients with biventricular SCM regarding in-hospital outcome and long-term prognosis. MATERIALS AND METHODS 114 consecutive patients with SCM were retrospectively analyzed. 88 patients presented with classical SCM, 26 patients (22.8%) were diagnosed with biventricular SCM. Follow-up was conducted for a total of 4.4years. Mean age was 67.1years with 83.3% of patients being female. The primary endpoint was a composite of all-cause mortality, recurrence of SCM and re-hospitalization due to heart failure. RESULTS Although patients with biventricular SCM presented with a tendency towards an increased rate of cardiogenic shock (30.8% vs. 15.9%; p=0.09) and significantly more usage of inotropic support upon hospital admission (34.6% vs. 13.6%; p=0.01), there was no difference concerning the primary endpoint in both groups (50.0% vs. 44.3%; p=0.31). Furthermore, there was no difference in mortality both in-hospital (7.7% vs. 7.9%; p=0.66) and during long-term follow-up (27.3% vs. 23.1%; p=0.46). CONCLUSION Patients with biventricular SCM have the same in-hospital and long-term outcome compared to classical SCM.

Monitoring of plasma levels of activated protein C using a clinically applicable oligonucleotide-based enzyme capture assay

Summary.  Background: Human‐activated protein C (APC) is a serine protease with anticoagulant, anti‐inflammatory and cytoprotective functions. This feature renders APC to be a promising vascular‐inflammatory biomarker.Objective: The aim of the present study was the development and validation of a technique that allows the measurement of APC plasma levels under practical laboratory conditions.Methods/patients: Based on the APC‐binding ssDNA aptamer HS02‐52G we developed an oligonucleotide‐based enzyme capture assay (OECA) that quantifies aptamer‐captured APC through hydrolysis rates of a fluorogenic peptide substrate. After optimization of pre‐analytical conditions, plasma APC levels were measured in healthy individuals and patients undergoing hip replacement surgery.Results and conclusion: A combination of APC–OECA with an aprotinin‐based quenching strategy allowed APC analysis with a limit of detection as low as 0.022 ± 0.005 ng mL−1 (0.39 ± 0.10 pmol L−1) and a limit of quantification of 0.116 ± 0.055 ng mL−1 (2.06 ± 0.98 pmol L−1). While APC plasma levels in healthy individuals fell below the quantifiable range of the APC–OECA platform, levels substantially increased in patients undergoing hip replacement surgery reaching peak values of up to 12 ng mL−1 (214 pmol L−1). When normalized to the amount of thrombin generated, interindividual variabilities in the APC generating capacity were observed. In general, with a turn‐around time from blood sampling to generation of test results of < 7 h, the APC–OECA platform allows sensitive and rapid determination of circulating APC levels under pathological conditions.

Prevalence, Clinical Characteristics, and Predictors of Patients with Thromboembolic Events in Takotsubo Cardiomyopathy

Background Several acute complications related to takotsubo cardiomyopathy (TTC) have been documented recently. However, the incidence and clinical significance of acute thromboembolic events in TTC is not well established. Methods A detailed investigation of the clinical characteristics and in-hospital complications of 114 consecutive patients diagnosed with TTC between January 2003 and September 2015 was carried out. This study was initiated to reveal the predictors, clinical significance, and short-term and long-term outcomes of patients with TTC associated with acute thromboembolic events on index presentation. Results The incidence of acute thromboembolic events related to TTC was around 12.2%, and these included ventricular thrombi, cerebrovascular events, retinal and brachial artery pathologies, renal, splenic, and aortic involvement. The most frequent complication on initial presentation was cardiogenic shock (20%) accompanied with pulmonary congestion (20%). Interestingly, patients experiencing thromboembolic events had higher C-reactive protein (CRP) levels as compared to the non-thromboembolic group (P = 0.02). Certain thromboembolic events were characterized by the presence of ST-segment elevation in electrocardiogram (P 0.02). Chest pain was the primary symptom in these patients (P 0.09). Furthermore, there was significant right ventricular involvement (as assessed by transthoracic echocardiography) in patients presenting with an acute thromboembolic event (P 0.08). A Kaplan–Meier analysis indicated a significantly higher mortality rate over a mean follow-up of three years in the thromboembolic group than the non-thromboembolic group (log-rank, P = 0.02). Conclusions Our results confirmed the relative common occurrence of thromboembolic events in the setting of TTC. Inflammation might play an important role in the development of thromboembolic events, and a right ventricular involvement and ST-segment elevation could be positive predictors for this occurrence. In order to circumvent the risk of a negative outcome, it is recommended that an anticoagulation therapy be initiated in all high-risk patients.

Comparison of Coronary Computed Tomography Angiography-Derived vs Invasive Fractional Flow Reserve Assessment: Meta-Analysis with Subgroup Evaluation of Intermediate Stenosis

RATIONALE AND OBJECTIVES Invasive coronary angiography (ICA) with fractional flow reserve (FFR) assessment is the reference standard for the detection of hemodynamically relevant coronary lesions. We have investigated whether coronary computed tomography angiography (cCTA)-derived FFR (fractional flow reserve from coronary computed tomographic angiography [CT-FFR]) measurement improves diagnostic accuracy over cCTA. METHODS AND RESULTS A literature search was performed for studies comparing invasive FFR, cCTA, and CT-FFR. The analysis included three prospective multicenter trials and two retrospective single-center studies; a total of 765 patients and 1306 vessels were included in the meta-analysis. Compared to invasive FFR on a per-lesion basis, CT-FFR reached a pooled sensitivity, specificity, positive predictive value, and negative predictive value of 83.7% (95% confidence interval [CI]: 78.1-89.3), 74.7% (95% CI: 52.2-97.1), 64.8% (95% CI: 52.1-77.5), and 90.1% (95% CI: 80.8-99.3) compared to 84.6% (95% CI: 78.1-91.1), 49.7% (95% CI: 31.1-68.4), 39.0% (95% CI: 28.0-50.1), and 87.3% (95% CI: 72.5-100.0) for cCTA alone. In 634 vessels with intermediate stenosis (30%-70%), sensitivity, specificity, positive predictive value, and negative predictive value were 81.4% (95% CI: 70.4-92.9), 71.7% (95% CI: 54.5-89.0), 59.4% (95% CI: 35.5-83.4), and 89.9% (95% CI: 85.0-94.7) compared to 90.2% (95% CI: 80.6-99.9), 35.4% (95% CI: 23.5-47.3), 50.7% (95% CI: 30.6-70.8), and 82.5% (95% CI: 64.5-100.0) for cCTA alone. The summary area under the receiver operating characteristic curve of CT-FFR was superior to cCTA alone on a per-vessel (0.90 [95% CI: 0.82-0.98] vs 0.74 [95% CI: 0.63-0.86]; P = .0047) and for intermediate stenoses (0.76 [95% CI: 0.65-0.88] vs 0.57 [95% CI: 0.49-0.66]; P = .0027). CONCLUSION CT-FFR significantly improves specificity without noticeably altering the sensitivity of cCTA with invasive FFR as a reference standard for the detection of hemodynamically relevant stenosis.

Radiation exposure and contrast agent use related to radial versus femoral arterial access during percutaneous coronary intervention (PCI)-Results of the FERARI study.

BACKGROUND Data regarding radiation exposure related to radial versus femoral arterial access in patients undergoing percutaneous coronary intervention (PCI) remain controversial. This study aims to evaluate patients enrolled in the FERARI study regarding radiation exposure, fluoroscopy time and contrast agent use. METHODS The Femoral Closure versus Radial Compression Devices Related to Percutaneous Coronary Interventions (FERARI) study evaluated prospectively 400 patients between February 2014 and May 2015 undergoing PCI either using the radial or femoral access. In these 400 patients, baseline characteristics, procedural data such as procedural duration, fluoroscopy time, dose-area product (DAP) as well as the amount of contrast agent used were documented and analyzed. RESULTS Median fluoroscopy time was not significantly different in patients undergoing radial versus femoral access (12.2 vs. 9.8min, p=0.507). Furthermore, median DAP (54.5 vs. 52.0 Gycm2, p=0.826), procedural duration (46.0 vs. 45.0min, p=0.363) and contrast agent use (185.5 vs. 199.5ml, p=0.742) were also similar in radial and femoral PCI. CONCLUSION There was no difference regarding median fluoroscopy time, procedural duration, radiation dose or contrast agent use between radial versus femoral arterial access in PCI.

Coronary artery perforation in a patient with STEMI and a myocardial bridge: an increased risk for coronary artery perforation?

We present the case of a patient with ST-elevation myocardial infarction (STEMI) due to subtotal occlusion of the left anterior descending coronary artery caused by an atherosclerotic lesion and a myocardial bridge (MB). Stenting of the MB caused coronary artery perforation resulting in a fistula to the right ventricle that was closed by implantation of a PTFE-covered stent. Follow-up coronary angiography showed persistent shunting, which was sealed by inflation of a high-pressure balloon over the site of extravasation guided by intravascular ultrasound. Additionally, we provide a short review of cases with coronary artery perforation after stenting of an MB.

Incremental benefit of late gadolinium cardiac magnetic resonance imaging for risk stratification in patients with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) has a low risk for sudden cardiac death (SCD). The ESC clinical risk prediction model estimates the risk of SCD using clinical and echocardiographical parameters without taking into account cardiac magnetic resonance (CMR) parameters. Therefore, we compared the CMR characteristics of 149 patients with low, intermediate and high ESC risk scores. In these patients left and right ventricular ejection fraction and volumes were comparable. Patients with a high ESC risk score revealed a significantly higher extent of late gadolinium enhancement (LGE) compared to patients with intermediate or a low risk scores. During follow-up of 4 years an extent of LGE ≥20% identified patients at a higher risk for major adverse cardiac arrhythmic events in the low and intermediate ESC risk group whereas an extent of LGE <20% was associated with a low risk of major adverse cardiac arrhythmic events despite a high ESC risk score ≥6%. Hence, we hypothesize that the extent of fibrosis might be an additional risk marker.

Diagnostic Performance of Contrast Enhanced Pulmonary Computed Tomography Angiography for the Detection of Angioinvasive Pulmonary Aspergillosis in Immunocompromised Patients

Invasive pulmonary aspergillosis (IPA) is one of the major complications in immunocompromised patients. The mainstay of diagnostic imaging is non-enhanced chest-computed-tomography (CT), for which various non-specific signs for IPA have been described. However, contrast-enhanced CT pulmonary angiography (CTPA) has shown promising results, as the vessel occlusion sign (VOS) seems to be more sensitive and specific for IPA in hematologic patients. The aim of this study was to evaluate the diagnostic accuracy of CTPA in a larger cohort including non-hematologic immunocompromised patients. CTPA studies of 78 consecutive immunocompromised patients with proven/probable IPA were analyzed. 45 immunocompromised patients without IPA served as a control group. Diagnostic performance of CTPA-detected VOS and of radiological signs that do not require contrast-media were analyzed. Of 12 evaluable radiological signs, five were found to be significantly associated with IPA. The VOS showed the highest diagnostic performance with a sensitivity of 0.94, specificity of 0.71 and a diagnostic odds-ratio of 36.8. Regression analysis revealed the two strongest independent radiological predictors for IPA to be the VOS and the halo sign. The VOS is highly suggestive for IPA in immunocompromised patients in general. Thus, contrast-enhanced CTPA superior over non-contrast_enhanced chest-CT in patients with suspected IPA.

Ezetimibe inhibits platelet activation and uPAR expression on endothelial cells

PURPOSE Lipid lowering therapy constitutes the basis of cardiovascular disease therapy. The purpose of this study was to investigate effects of ezetimibe, a selective inhibitor of intestinal cholesterol absorption, on platelets and endothelial cells in an in vitro endothelial cell model. METHODS After a 24h incubation period with ezetimibe (concentrations 1, 50, 100 and 1000ng/ml), human umbilical vein endothelial cells (HUVEC) were stimulated for 1h with lipopolysaccharide (LPS) and were then incubated in direct contact with activated platelets. Following this, the expression of CD40L and CD62P on platelets, and the expression of ICAM-1, VCAM-1, uPAR, and MT1-MMP on endothelial cells were measured by flow cytometry. Supernatants were analysed by enzyme linked immunosorbent assay for soluble MCP-1, IL-6 and MMP-1. RESULTS The increased expression of uPAR on endothelial cells by proinflammatory stimulation with LPS and by direct endothelial contact with activated platelets was significantly reduced through pre-incubation with 100ng/ml and 1000ng/ml ezetimibe (p<0.05). Platelets directly incubated with ezetimibe but without endothelial cell contact showed significantly reduced CD62P and CD40L surface expression (p<0.05). Ezetimibe had no significant effects on HUVEC expression of MT1-MMP, ICAM-1 and VCAM-1 and on CD40L expression on platelets in direct contact with endothelial cells. Levels of soluble IL-6 in HUVEC supernatants were significantly lower after pre-incubation with ezetimibe. CONCLUSION In this in vitro analysis, ezetimibe directly attenuates platelet activation and has significant endothelial cell mediated effects on selected markers of atherosclerosis.

Comparison of peri and post-procedural complications in patients undergoing revascularisation of coronary artery multivessel disease by coronary artery bypass grafting or protected percutaneous coronary intervention with the Impella 2.5 device

Background: While coronary artery bypass grafting remains the standard treatment of complex multivessel coronary artery disease, the advent of peripheral ventricular assist devices has enhanced the safety of percutaneous coronary intervention. We therefore evaluated the safety in terms of inhospital outcome comparing protected high-risk percutaneous coronary intervention with the Impella 2.5 device and coronary artery bypass grafting in patients with complex multivessel coronary artery disease. Methods: This retrospective study included patients with complex multivessel coronary artery disease (SYNTAX score >22) undergoing either coronary artery bypass grafting before the implementation of a protected percutaneous coronary intervention programme with a peripheral ventricular assist device or protected percutaneous coronary intervention with the Impella 2.5 device following the start of the programme. The primary endpoint consisted of inhospital major adverse cardiac and cerebrovascular events. The combined secondary endpoint included peri and post-procedural adverse events. Results: A total of 54 patients (mean age 70.1±9.9 years, 92.6% men) were enrolled in the study with a mean SYNTAX score of 34.5±9.8. Twenty-six (48.1%) patients underwent protected percutaneous coronary intervention while 28 (51.9%) patients received coronary artery bypass grafting. The major adverse cardiac and cerebrovascular event rate was numerically higher in the coronary artery bypass grafting group (17.9 vs. 7.7%; P=0.43) but was not statistically significant. The combined secondary endpoint was not different between the groups; however, patients undergoing coronary artery bypass grafting experienced significantly more peri-procedural adverse events (28.6 vs. 3.8%; P<0.05). Conclusion: Patients with complex multivessel coronary artery disease undergoing protected percutaneous coronary intervention with the Impella 2.5 device experience similar intrahospital major adverse cardiac and cerebrovascular event rates when compared to coronary artery bypass grafting. Protected percutaneous coronary intervention represents a safe alternative to coronary artery bypass grafting in terms of inhospital adverse events.