Impact of Rescue-Thrombolysis during Cardiopulmonary Resuscitation in Patients with Pulmonary Embolism

Background: Cardiac arrest in patients with pulmonary embolism (PE) is associated with high morbidity and mortality. Thrombolysis is expected to improve the outcome in these patients. However studies evaluating rescue-thrombolysis in patients with PE are missing, mainly due to the difficulties of clinical diagnosis of PE. We aimed to determine the success influencing factors of thrombolysis during resuscitation in patients with PE. Methodology/Principal Findings: We analyzed retrospectively the outcome of 104 consecutive patients with confirmed (n = 63) or highly suspected (n = 41) PE and monitored cardiac arrest. In all patients rtPA was administrated for thrombolysis during cardiopulmonary resuscitation. In 40 of the 104 patients (38.5%) a return of spontaneous circulation (ROSC) could be achieved successfully. Patients with ROSC received thrombolysis significantly earlier after CPR onset compared to patients without ROSC (13.661.2 min versus 24.660.8 min; p,0.001). 19 patients (47.5%) out of the 40 patients with initially successful resuscitation survived to hospital discharge. In patients with hospital discharge thrombolysis therapy was begun with a significantly shorter delay after cardiac arrest compared to all other patients (11.061.3 vs. 22.560.9 min; p,0.001). Conclusion: Rescue-thrombolysis should be considered and started in patients with PE and cardiac arrest, as soon a

Profilin-1 Is Expressed in Human Atherosclerotic Plaques and Induces Atherogenic Effects on Vascular Smooth Muscle Cells

.Here we monitored profilin-1 expression in human atherosclerotic plaques by immunofluorescent staining. The effects of recombinant profilin-1 on atherogenic signaling pathways and cellular responses such as DNA synthesis (BrdU-incorporation) and chemotaxis (modified Boyden-chamber) were evaluated in cultured rat aortic and human coronary vascular smooth muscle cells (VSMCs). Furthermore, the correlation between profilin-1 serum levels and the degree of atherosclerosis was assessed in humans.<0.001 vs. no atherosclerosis or control group).Profilin-1 expression is significantly enhanced in human atherosclerotic plaques compared to the normal vessel wall, and the serum levels of profilin-1 correlate with the degree of atherosclerosis in humans. The atherogenic effects exerted by profilin-1 on VSMCs suggest an auto-/paracrine role within the plaque. These data indicate that profilin-1 might critically contribute to atherogenesis and may represent a novel therapeutic target

Local Thrombolysis for Successful Treatment of Acute Stroke in an Adolescent with Cardiac Myxoma

Intracardiac myxomas are the most common benign cardiac tumors in adults. They are a rare source of cardiogenic embolisms and sudden death, especially in young patients. This report describes the case of a male adolescent who presented with right-sided paresis and aphasia. Magnetic resonance imaging of the brain revealed an ischemic stroke without evidence of acute bleeding. Intra-arterial local thrombolysis was immediately started. An echocardiographic screening after successful thrombolysis with a remarkable recovery of symptoms detected a thrombotic-like mass in the left atrium. The mass was excised surgically, confirmed as a benign atrial myxoma, and the patient was discharged with restitution ad integrum. Thus, contrary to some critical reports, thrombolytic therapy for acute ischemic strokes due to atrial myxomas may be safe and highly effective

Transforming Growth Factor β1 Oppositely Regulates the Hypertrophic and Contractile Response to β-Adrenergic Stimulation in the Heart

BACKGROUND: Neuroendocrine activation and local mediators such as transforming growth factor-β₁ (TGF-β₁) contribute to the pathobiology of cardiac hypertrophy and failure, but the underlying mechanisms are incompletely understood. We aimed to characterize the functional network involving TGF-β₁, the renin-angiotensin system, and the β-adrenergic system in the heart. METHODS: Transgenic mice overexpressing TGF-β₁ (TGF-β₁-Tg) were treated with a β-blocker, an AT₁-receptor antagonist, or a TGF-β-antagonist (sTGFβR-Fc), were morphologically characterized. Contractile function was assessed by dobutamine stress echocardiography in vivo and isolated myocytes in vitro. Functional alterations were related to regulators of cardiac energy metabolism. RESULTS: Compared to wild-type controls, TGF-β₁-Tg mice displayed an increased heart-to-body-weight ratio involving both fibrosis and myocyte hypertrophy. TGF-β₁ overexpression increased the hypertrophic responsiveness to β-adrenergic stimulation. In contrast, the inotropic response to β-adrenergic stimulation was diminished in TGF-β₁-Tg mice, albeit unchanged basal contractility. Treatment with sTGF-βR-Fc completely prevented the cardiac phenotype in transgenic mice. Chronic β-blocker treatment also prevented hypertrophy and ANF induction by isoprenaline, and restored the inotropic response to β-adrenergic stimulation without affecting TGF-β₁ levels, whereas AT₁-receptor blockade had no effect. The impaired contractile reserve in TGF-β₁-Tg mice was accompanied by an upregulation of mitochondrial uncoupling proteins (UCPs) which was reversed by β-adrenoceptor blockade. UCP-inhibition restored the contractile response to β-adrenoceptor stimulation in vitro and in vivo. Finally, cardiac TGF-β₁ and UCP expression were elevated in heart failure in humans, and UCP--but not TGF-β₁--was downregulated by β-blocker treatment. CONCLUSIONS: Our data support the concept that TGF-β₁ acts downstream of angiotensin II in cardiomyocytes, and furthermore, highlight the critical role of the β-adrenergic system in TGF-β₁-induced cardiac phenotype. Our data indicate for the first time, that TGF-β₁ directly influences mitochondrial energy metabolism by regulating UCP3 expression. β-blockers may act beneficially by normalizing regulatory mechanisms of cellular hypertrophy and energy metabolism

Accuracy of Doppler-Echocardiographic Mean Pulmonary Artery Pressure for Diagnosis of Pulmonary Hypertension

Background: The validity of Doppler echocardiographic (DE) measurement of systolic pulmonary artery pressure (sPAP) has been questioned. Recent studies suggest that mean pulmonary artery pressure (mPAP) might reflect more accurately the invasive pressures. Methodology/Principal Findings: 241 patients were prospectively studied to evaluate the diagnostic accuracy of mPAP for the diagnosis of PH. Right heart catheterization (RHC) and DE were performed in 164 patients mainly for preoperative evaluation of heart valve dysfunction. The correlation between DE and RHC was better when mPAP (r = 0.93) and not sPAP (r = 0.81) was assessed. Bland-Altman analysis revealed a smaller variation of mPAP than sPAP. The following ROC analysis identified that a mPAP$25.5 mmHg is useful for the diagnosis of PH. This value was validated in an independent cohort of patients (n = 50) with the suspicion of chronic-thromboembolic pulmonary hypertension. The calculated diagnostic accuracy was 98%, based on excellent sensitivity of 98 % and specificity of 100%. The corresponding positive and negative predictive values were 100%, respectively 88%. Conclusion: mPAP has been found to be highly accurate for the initial diagnosis of PH. A cut-off value of 25.5 mmHg might be helpful to avoid unnecessary RHC and select patients in whom RHC might be beneficial

Beta1-Adrenoceptor Polymorphism Predicts Flecainide Action in Patients with Atrial Fibrillation

BACKGROUND: Antiarrhythmic action of flecainide is based on sodium channel blockade. Beta(1)-adrenoceptor (beta(1)AR) activation induces sodium channel inhibition, too. The aim of the present study was to evaluate the impact of different beta(1)AR genotypes on antiarrhythmic action of flecainide in patients with structural heart disease and atrial fibrillation. METHODOLOGY/PRINCIPAL FINDINGS: In 145 subjects, 87 with atrial fibrillation, genotyping was performed to identify the individual beta(1)AR Arg389Gly and Ser49Gly polymorphism. Resting heart rate during atrial fibrillation and success of flecainide-induced cardioversion were correlated with beta(1)AR genotype. The overall cardioversion rate with flecainide was 39%. The Arg389Arg genotype was associated with the highest cardioversion rate (55.5%; OR 3.30; 95% CI; 1.34-8.13; p = 0.003) compared to patients with Arg389Gly (29.5%; OR 0.44; 95% CI; 0.18-1.06; p = 0.066) and Gly389Gly (14%; OR 0.24; 95% CI 0.03-2.07; p = 0.17) variants. The single Ser49Gly polymorphism did not influence the conversion rate. In combination, patients with Arg389Gly-Ser49Gly genotype displayed the lowest conversion rate with 20.8% (OR 0.31; 95% CI; 0.10-0.93; p = 0.03). In patients with Arg389Arg variants the heart rate during atrial fibrillation was significantly higher (110+/-2.7 bpm; p = 0.03 vs. other variants) compared to Arg389Gly (104.8+/-2.4 bpm) and Gly389Gly (96.9+/-5.8 bpm) carriers. The Arg389Gly-Ser49Gly genotype was more common in patients with atrial fibrillation compared to patients without atrial fibrillation (27.6% vs. 5.2%; HR 6.98; 95% CI; 1.99-24.46; p<0.001). CONCLUSIONS: The beta(1)AR Arg389Arg genotype is associated with increased flecainide potency and higher heart rate during atrial fibrillation. The Arg389Gly-Ser49Gly genotype might be of predictive value for atrial fibrillation

Remote Ischemic Preconditioning and Renoprotection: From Myth to a Novel Therapeutic Option?

There is currently no effective prophylactic regimen available to prevent contrast-induced AKI (CI-AKI), a frequent and life-threatening complication after cardiac catheterization. Therefore, novel treatment strategies are required to decrease CI-AKI incidence and to improve clinical outcomes in these patients. Remote ischemic preconditioning (rIPC), defined as transient brief episodes of ischemia at a remote site before a subsequent prolonged ischemia/reperfusion injury of the target organ, is an adaptational response that protects against ischemic and reperfusion insult. Indeed, several studies demonstrated the tissue-protective effects of rIPC in various target organs, including the kidneys. In this regard, rIPC may offer a novel noninvasive and virtually cost-free treatment strategy for decreasing CI-AKI incidence. This review evaluates the current experimental and clinical evidence for rIPC as a potential renoprotective strategy, and discusses the underlying mechanisms and key areas for future research

Novel ECG-based scoring tool for prediction of takotsubo syndrome

BackgroundTakotsubo syndrome (TS) usually involves ECG changes mimicking acute myocardial infarction (AMI). The differentiation of both disorders is crucial for selection of appropriate treatment. The aim of this study was to assess ECG parameters in patients with TS and AMI, and try to establish a scoring tool for TS prediction.MethodsThe study consisted of two study parts: evaluation and validation cohorts. Overall, the study included 82 patients with TS and 141 subjects with AMI. In addition to the major demographic characteristics and comorbidities, the following ECG parameters were analyzed: heart rate, QRS duration, QTc, QRS amplitudes in frontal and precordial leads, frequencies for ST-segment elevation, combined sign of positive ST-segment elevation in -aVR and absent in V-1, negative T-wave in lead I and positive in III, inverted or biphasic T-waves in V-2-V-5, T-wave inversions in frontal and precordial leads. All significant variables were identified in univariate regression analysis and further included for multivariate logistic regression analysis predicting TS.ResultsTS was frequently diagnosed in women and in elderly patients. Presence of ST-segment elevation, inverted/biphasic T-waves in V-2-V-5, QRS amplitudes in frontal and precordial leads were significantly different in evaluation group. By multivariate regression analysis sex, QRS amplitudes in frontal, inverted or biphasic T-waves in septal leads and QTc were identified as powerful variables to calculate TS probability. The diagnostic accuracy of the developed 6-points-TS-score was then evaluated in the validation group. Thus, no subject with a TS-score of 5 had AMI (specificity 99%, sensitivity >92%).ConclusionThe developed ECG-based TS-score model may be a useful complimentary tool for TS prediction in acute clinical setting

ECG as a risk stratification tool in patients with wearable cardioverter-defibrillator

Background: The wearable cardioverter defibrillator (WCD) is increasingly used in patients at elevated risk for ventricular arrhythmias but not fulfilling the indications for an implantable cardioverter defibrillator (ICD). Cur-rently, there is an insufficient risk prediction of fatal arrhythmias in patients at risk. In this study, we assessed the prognostic role of baseline electrocardiogram (ECG) in WCD patients.Methods: WCD patients from diverse clinical institutions in Germany (n = 227) were retrospectively enrolled and investigated for the incidences of death or ventricular arrhythmias during WCD wearing. In addition, the widely accepted ECG predictors of adverse outcome were analyzed in patients with arrhythmic events.Results: Life-threatening arrhythmias occurred in 22 (9.7 %) patients, mostly in subjects with ischemic heart dis-ease (15 of 22). There was no difference in baseline left ventricular ejection fraction (LVEF) in subjects with and without arrhythmic events (31.3 +/- 7.9 % vs. 32.6 +/- 8.3 %; p = 0,24). Patients with arrhythmia exhibited signif-icantly longer QRS duration (109.5 +/- 23.1 ms vs. 100.6 +/- 22.3 ms, p = 0,04), Tpeak-Tend (Tp-e) (103.1 +/- 15.6 ms vs. 93.2 +/- 19.2 ms, p = 0,01) and QTc (475.0 +/- 60.0 ms vs. 429.6 +/- 59.4 ms, p < 0,001) intervals. In contrast, no significant differences were found for incidences of fragmented QRS (27.3 % vs. 24 %, p = 0.79) and inverted/ biphasic T-waves (16.6 % vs. 22.7 %, p = 0,55). In multivariate regression analysis both Tp-e (HR 1.03; 95 % CI 1.001-1.057; p = 0.02) and QTc (HR 1.02; 95 % CI 1.006-1.026; p < 0.001) were identified as independent pre-dictors of ventricular arrhythmias. After WCD use, the prophylactic ICD was indicated in 76 patients (33 %) with uneventful clinical course but per-sistent LVEF <= 35 %. The ECG analysis in these subjects did not reveal any relevant changes in arrhythmogenesis markers. Conclusions: ECG repolarization markers Tp-e and QTc are associated with malignant arrhythmias in WCD pa-tients and may be used -in addition to other established risk markers -to identify appropriate patients for ICD implantation.(c) 2022 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved