Christian Fastner

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.

Impact of concomitant atrial fibrillation on the prognosis of Takotsubo cardiomyopathy

Aims Previous studies revealed that patients with Takotsubo cardiomyopathy (TTC) have a higher mortality rate than the general population. Supraventricular tachycardia is a well-known complication of TTC. This study was performed to determine the short- and long-term prognostic impact of atrial fibrillation associated with TTC patients. Methods and results Our institutional database constituted a collective of 114 patients diagnosed with TTC from 2003 to 2015. The patients were divided into two groups according to the presence (n = 21, 18.4%) or absence (n = 93, 81.5%) of atrial fibrillation. The endpoint was a composite of in-hospital events (thromboembolic events and life-threatening arrhythmias), all-cause mortality, rehospitalization due to heart failure, stroke, and the recurrence of TTC. The in-hospital mortality, 30-day mortality, and long-term mortality were significantly higher in the atrial fibrillation group. Kaplan-Meier analysis indicated a significantly lower event-free survival rate over a mean follow-up of 3 years in the atrial fibrillation group than that in the non-atrial fibrillation group (log-rank, P < 0.01). In a multivariate cox regression analysis, atrial fibrillation (hazard ratio, HR 2.3, 95% confidence interval, CI: 1.1-4.9, P < 0.05) and EF ≤ 35% (HR 2.0, 95% CI: 1.1-3.8, P < 0.05) were the only independent predictors of a primary endpoint. Conclusion Rates of in-hospital events and short- as well as long-term mortality were significantly higher in TTC patients suffering from atrial fibrillation compared with patients without atrial fibrillation.

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.

Prevalence of malignant arrhythmia and sudden cardiac death in takotsubo syndrome and its management

Aims Recent studies have highlighted that takotsubo syndrome (TTS) is associated with a poor clinical outcome. Our study was conducted to determine the short- and long-term prevalence, recurrence rate and impact of life-threatening arrhythmias (LTA) on the clinical outcome of TTS. Methods and results Our institutional database constituted a collective of 114 patients diagnosed with TTS between 2003 and 2015. The patient groups, divided according to the presence (n = 13, 11.4%) or absence (n = 101, 88.6%) of LTAs, were followed-up over a period of 3 years so as to determine the clinical outcome. Our analyses suggest that patients comprising the LTA group suffered significantly more often from an acute cardiovascular event including cases of a newly diagnosed atrial fibrillation (38.4% vs. 2.9%), cardiogenic shock with use of inotropic agents (53.8% vs. 14.8%) and cardiopulmonary resuscitation (61.5% vs. 1%). The short-term recurrence rate of a LTA episode was 15.3%, while the long-term recurrence rate of any LTA was around 5%. Whereas, in-hospital mortality was significantly higher in TTS associated with LTAs, the overall survival rate over 3 years was similar. A multivariate Cox regression analysis suggested atrial fibrillation, EF ≤ 35%, cardiogenic shock, and glomerular filtration rate <60 mL/min. as independent predictors of adverse outcome. Conclusion The short- as well as the long-term prevalence and recurrence of LTAs in TTS patients is high. The long-term mortality rates were similar to the TTS patients presenting without any LTAs. LTAs in TTS could be triggered by a concomitant atrial fibrillation.

Triple head-to-head comparison of fibrotic biomarkers galectin-3, osteopontin and gremlin-1 for long-term prognosis in suspected and proven acute heart failure patients

BACKGROUND To comparatively evaluate long-term prognostic values of fibrotic biomarkers galectin-3, gremlin-1 and osteopontin in patients presenting to the emergency department (ED) suspected of acute heart failure (AHF). METHODS Patients with acute dyspnea or peripheral edema were enrolled in the ED. Biomarkers were measured and added to prognostic models including 11 conventional risk factors plus NT-proBNP assessing state-of-the-art statistics of discrimination, calibration, reclassification and Cox regression analyses. Prognostic outcomes were long-term all-cause mortality (ACM) and AHF-related rehospitalization (AHF-RH) at 1 and 5 years. RESULTS 401 patients including 122 AHF patients were enrolled (mean age 67 years, males 51%). During 5 years follow-up 129 patients (30%) died and 73 (18%) were re-hospitalized because of AHF. In multivariate analysis, galectin-3 (hazard ratios (HR) range 1.4–1.9; p = 0.03) and osteopontin (HR range 1.2–1.4; p = 0.001) remained associated with ACM overall and in the AHF population at 5 years, whereas gremlin-1 remained associated with AHF-RH at 1 year in AHF patients (HR 1.3; p = 0.002). ACM in whole cohort was best discriminated (AUC = 0.85, p = 0.0001), calibrated and re-classified (NRI + 0.50 to + 0.56, p = 0.0001) by galectin-3, whereas in AHF patients ACM was best discriminated by osteopontin (AUC range: 0.82–0.84, p = 0.0001; NRI + 0.34 to + 0.38, p < 0.1) and AHF-RH at 1 year by gremlin-1 (AUC range: 0.82–0.92, p = 0.0001; NRI + 0.59 to + 0.60, p = 0.006). CONCLUSIONS A panel of fibrotic biomarkers, including osteopontin, galectin-3 and gremlin-1, might be useful for long term risk-stratification of symptomatic ED patients being suspected of AHF.

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.

Impact and Management of Left Ventricular Function on the Prognosis of Takotsubo Syndrome

Early research has proposed that patients with Takotsubo syndrome (TTS) could have a higher mortality rate than the general population. Our study was conducted to determine the short‐ and long‐term outcome of TTS patients associated with a significantly compromised left ventricular function on hospital admission.

Veno-venous double lasso pull-and-push technique for transseptal retrieval of an embolized Watchman occluder

Intraprocedural device dislodgement of a 24-mm Watchman™ left atrial appendage (LAA) closure device occurred in a 83-year-old female with a wide left atrial appendage ostium (broccoli configuration) and a surgical mitral valve reconstruction. Device rested in the atrial cavity. A second stable 12French transseptal electrophysiological sheath and two snares were needed to stabilize, elongate and gently guide the device into the second sheath. One of the snares was unclamped at its proximal end and retrogradely pulled through. After successful retrieval, a 27-mm Watchman™ device could easily be implanted in the very same session via the left delivery sheath. Patient was discharged from hospital in good general health after regular turnaround time.

Combined treatment with olmesartan medoxomil and amlodipine besylate attenuates atherosclerotic lesion progression in a model of advanced atherosclerosis.

Introduction Besides their blood pressure-lowering effects, olmesartan medoxomil and amlodipine besylate exhibit additional anti-inflammatory mechanisms in atherosclerosic disease. Most of the studies investigating the effects of atherosclerosis focused on early atherosclerotic lesions, whereas lesions in human disease, at the time when medical treatment is started, are already well established. Therefore, we set up a model of advanced atherosclerosis and investigated the effects of olmesartan medoxomil, amlodipine besylate, and the combination of both on atherosclerotic lesion size and lesion composition. Materials and methods Olmesartan medoxomil (1 mg/kg/day), amlodipine besylate (1.5 mg/kg/day), and the combination of both was added to chow and was fed to apolipoprotein E-deficient (ApoE−/−) mice at 25 weeks of age. Mice were sacrificed after 25 weeks of drug administration and perfused with formalin. Innominate arteries were dissected out and paraffin embedded. Serial sections were generated, and lesion sizes and their composition – such as minimal thickness of the fibrous cap, size of the necrotic core, and presence of calcification – were analyzed. Electrophoretic mobility shift assays were used to detect DNA-binding activity of the transcription factor nuclear factor-kappa B (NF-κB) in aortic tissue. Results Treatment with the combination of olmesartan medoxomil and amlodipine besylate led to a significant reduction in atherosclerotic lesion size in ApoE−/− mice (olmesartan medoxomil/amlodipine besylate: 122,277±6,795 μm2, number [n]=14; versus control: 177,502±10,814 μm2, n=9; P<0.001). Treatment with amlodipine besylate (n=5) alone did not reach significance. However, a trend toward a decrease in lesion size in the amlodipine besylate-treated animals could be observed. In the histological analysis of atherosclerotic lesion composition, significantly thicker fibrous caps were found in treatment with amlodipine besylate (amlodipine: 5.12±0.26 μm, n=6; versus control: 3.98±0.18 μm, n=10; P<0.01). Furthermore, all sections revealed morphological signs of calcification, but no difference could be detected. Treatment with the combination of olmesartan medoxomil and amlodipine besylate showed no effect on lesion composition. Electrophoretic mobility shift assays of nuclear extracts demonstrated reduced activity of the transcription factor NF-κB when treated with olmesartan medoxomil, amlodipine besylate, or their combination, as compared to controls. Conclusion Combined treatment with olmesartan medoxomil and amlodipine besylate attenuated atherosclerotic lesion progression, possibly due to anti-inflammatory mechanisms. Our data support the hypothesis that even in advanced atherosclerosis anti-inflammatory treatment, using angiotensin II type 1 receptor blockers and calcium channel antagonists of the dihydropyridine type can attenuate atherosclerotic lesion progression.

Interventional Left Atrial Appendage Closure Affects the Metabolism of Acylcarnitines

Background: Left atrial appendage closure (LAAC) represents the interventional alternative to oral anticoagulation for stroke prevention in atrial fibrillation (AF). The metabolism of acylcarnitines was shown to affect cardiovascular diseases. This study evaluates the influence of successful LAAC on the metabolism of acylcarnitines. Methods: Patients undergoing successful LAAC were enrolled prospectively. Peripheral blood samples for metabolomics measurements were collected immediately before (i.e., index) and six months after LAAC (i.e., mid-term). A targeted metabolomics analysis based on electrospray ionization–liquid chromatography–mass spectrometry (ESI–LC–MS/MS) and MS/MS measurements was performed. Results: 44 patients with non-valvular AF (median CHA2DS2-VASc score 4, median HAS-BLED score 4) and successful LAAC were included. Significant changes in acylcarnitine levels were found in the total cohort, which were mainly attributed to patients with impaired left ventricular and renal function, elevated amino-terminal pro-brain natriuretic peptide (NT-proBNP) and diabetes mellitus. Adjusted multivariable regression models revealed significant changes of five metabolites over mid-term follow-up: C2, C14:1, C16, and C18:1 decreased significantly (each p < 0.05); short-chain C5 acylcarnitine plasma levels increased significantly (p < 0.05). Conclusion: This study demonstrates that successful LAAC affects the metabolism of acylcarnitines at mid-term follow-up. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02985463.