Extracorporeal life support after failure of thrombolysis in pulmonary embolism

Introduction: Fulminant pulmonary embolism (PE) may lead to cardiogenic shock or cardiac arrest with high mortality rates (65%) despite treatment with thrombolysis. Patients not responding to this therapy might benefit from extracorporeal life support (ECLS). Only occasional case reports of ECLS in PE patients are available. We studied the use of ECLS after thrombolysis in patients suffering from refractory cardiogenic shock due to PE. Material and methods: Patients who were admitted to our university intensive care unit (ICU) with PE, not responding to throm-bolysis, and who received subsequent ECLS treatment were studied. Results: 12 patients with severe PE were included. 6 patients were admitted by emergency medical services, 5 patients were transferred to the ICU from other hospitals and one patient presented at the emergency department by herself. 11 of 12 patients suffered from cardiac arrest and needed cardiopulmonary resuscitation (CPR) before ECLS implantation. Three ECLS were im-planted during CPR and nine ECLS were implanted during emergency conditions in patients with cardiogenic shock. All patients received thrombolysis before implementation of ECLS. Mean duration of ICU treatment was 22.4 ± 23.0 days. Mean duration of ECLS therapy was 5.6 ± 6.5 days. Bleeding complications occurred in four patients. Complications directly related to the ECLS system occurred in two patients (overall complication rate 42%). Overall, 6 of 12 patients (50%) survived.Conclusions: ECLS may be considered as a bailout therapy in PE patients not responding to prior definitive treatment such as thrombolysis. ECLS therapy seems to be feasible with an acceptable complication rate even after thrombolysis

Connexin diversity in the heart: insights from transgenic mouse models

Cardiac conduction is mediated by gap junction channels that are formed by connexin (Cx) protein subunits. The connexin family of proteins consists of 24 members, varying in their biophysical properties and ability to combine with other connexins into heteromeric gap junction channels. The mammalian heart shows regional differences both in connexin expression profile and in degree of electrical coupling. The latter reflects functional requirements for conduction velocity, which needs to be low in the sinoatrial and atrioventricular nodes and high in the ventricular conduction system. Over the past 20 years, knowledge of the biology of gap junction channels and their role in the genesis of cardiac arrhythmias has increased enormously. This review focuses on the insights gained from transgenic mouse models. The mouse heart expresses Cx30, 30.2, 37, 40, 43, 45 and 46. For these connexins, a variety of knock-outs, heart-specific knock-outs, conditional knock-outs, double knock-outs, knock-ins and overexpressers has been studied. We discuss the cardiac phenotype in these models and compare Cx expression between mice and men. Mouse models have enhanced our understanding of (patho)-physiological implications of Cx diversity in the heart. In principle, connexin-specific modulation of electrical coupling in the heart represents an interesting treatment strategy for cardiac arrhythmias and conduction disorders

The ECG in cardiovascular-relevant animal models of electrophysiology

The most frequently used animal species in experimental cardiac electrophysiology are mice, rabbits, and dogs. Murine and human electrocardiograms (ECGs) show salient differences, including the occurrence of a pronounced J-wave and a less distinctive T-wave in the murine ECG. Mouse models can resemble human cardiac arrhythmias, although mice differ from human in cardiac electrophysiology. Thus, arrhythmia mechanisms in mice may differ from those in humans and should be transferred to the human situation with caution. Further relevant cardiovascular animal models are rabbits, dogs, and minipigs, as they show similarities of cardiac ion channel distribution with the human heart and are suitable to study ventricular repolarization or pro- and antiarrhythmic drug effects. ECG recordings in large animals like goats and horses are feasible. Both goats and horses are a suitable animal model to study atrial fibrillation (AF) mechanisms. Horses frequently show spontaneous AF due to their high vagal tone and large atria. The zebrafish has become an important animal model. Models in "exotic" animals such as kangaroos may be suitable for particular studies

Recording of bipolar multichannel ECGs by a smartwatch

$\it Aims:$ Feasibility study of accurate three lead ECG recording (Einthoven I, II and III) using an Apple Watch Series 4. $\it Methods:$ In 50 healthy subjects (18 male; age: 40 $\pm$ 12 years) without known cardiac disorders, a 12-lead ECG and three bipolar ECGs, corresponding to Einthoven leads I, II and III were recorded using an Apple Watch Series 4. Einthoven I was recorded with the watch on the left wrist and the right index finger on the crown, Einthoven II with the watch on the left lower abdomen and the right index finger on the crown, Einthoven III with the watch on the left lower abdomen and the left index finger on the crown. Four experienced cardiologists were independently asked to assign the watch ECGs to Einthoven leads from 12-lead ECG for each subject. $\it Results:$ All watch ECGs showed an adequate signal quality with 134 ECGs of good (89%) and 16 of moderate signal quality (11%). Ninety-one percent of all watch ECGs were assigned correctly to corresponding leads from 12-lead ECG. Thirty-nine subjects (78%) were assigned correctly by all cardiologists. All assignment errors occurred in patients with similar morphologies and amplitudes in at least two of the three recorded leads. Erroneous assignment of all watch ECGs to leads from standard ECG occurred in no patient. $\it Conclusion:$ Recording of Einthoven leads I-III by a smartwatch is accurate and highly comparable to standard ECG. This might contribute to an earlier detection of cardiac disorders, which are associated with repolarization abnormalities or arrhythmias

Single-lead ECG recordings including Einthoven and Wilson leads by a Smartwatch

Background: Smartwatches that are able to record a bipolar ECG and Einthoven leads were recently described. Nevertheless, for detection of ischemia or other cardiac diseases more leads are required, especially Wilson's chest leads. Objectives: Feasibility study of six single-lead smartwatch (Apple Watch Series 4) ECG recordings including Einthoven (I, II, III) and Wilson-like pseudo-unipolar chest leads (Wr, Wm, Wl). Methods: In 50 healthy subjects (16 males; age: 36 $\pm$ 11 years, mean $\pm$ SD) without known cardiac disorders, a standard 12-lead ECG and a six single-lead ECG using an Apple Watch Series 4 were performed under resting conditions. Recording of Einthoven I was performed with the watch on the left wrist and the right index finger on the crown, Einthoven II was recorded with the watch on the left lower abdomen and the right index finger on the crown, Einthoven III was recorded with the watch on the left lower abdomen and the left index finger on the crown. Wilson-like chest leads were recorded corresponding to the locations of V1 (Wr), V4 (Wm) and V6 (Wl) in the standard 12-lead ECG. Wr was recorded in the fourth intercostal space right parasternal, Wm was recorded in the fifth intercostal space on the midclavicular line, and Wl was recorded in the fifth intercostal space in left midaxillary line. For all Wilson-like chest lead recordings, the smartwatch was placed on the described three locations on the chest, the right index finger was placed on the crown and the left hand encompassed the right wrist. Both hands and forearms also had contact to the chest. Three experienced cardiologists were independently asked to allocate three bipolar limb smartwatch ECGs to Einthoven I–III leads, and three smartwatch Wilson-like chest ECGs (Wr, Wm, Wl) to V1, V4 and V6 in the standard 12-lead ECG for each subject. Results: All 300 smartwatch ECGs showed a signal quality useable for diagnostics with 281 ECGs of good signal quality (143 limb lead ECGs (95%), 138 chest lead ECGs (92%). Nineteen ECGs had a moderate signal quality (7 limb lead ECGs (5%), 12 chest lead ECGs (8%)). One-hundred percent of all Einthoven and 92% of all Wilson-like smartwatch ECGs were allocated correctly to corresponding leads from 12-lead ECG. Forty-six subjects (92%) were assigned correctly by all cardiologists. Allocation errors were due to similar morphologies and amplitudes in at least two of the three recorded Wilson-like leads. Despite recording with a bipolar smartwatch device, morphology of all six leads was identical to standard 12-lead ECG. In two patients with acute anterior myocardial infarction, all three cardiologists recognized the ST-elevations in Wilson-like leads and assumed an occluded left anterior descending coronary artery correctly. Conclusion: Consecutive recording of six single-lead ECGs including Einthoven and Wilson-like leads by a smartwatch is feasible with good ECG signal quality. Thus, this simulated six-lead smartwatch ECG may be useable for the detection of cardiac diseases necessitating more than one ECG lead like myocardial ischemia or more complex cardia arrhythmias

Catheter navigation by intracardiac echocardiography enables zero-fluoroscopy linear lesion formation and bidirectional cavotricuspid isthmus block in patients with typical atrial flutter

Abstract Introduction One of the most helpful aspects of intracardiac echocardiography (ICE) implementation in electrophysiological studies (EPS) is the real-time visualisation of catheters and cardiac structures. In this prospective study, we investigated ICE-guided zero-fluoroscopy catheter navigation during radiofrequency (RF) ablation of the cavotricuspid isthmus (CTI) in patients with typical atrial flutter (AFL). Methods and results Thirty consecutive patients (mean age 72.9 ± 11.4 years, 23 male) with ongoing (n = 23) or recent CTI-dependent AFL underwent an EPS, solely utilizing ICE for catheter navigation. Zero-fluoroscopy EPS could be successfully accomplished in all patients. Mean EPS duration was 41.4 ± 19.9 min, and mean ablation procedure duration was 20.8 ± 17.1 min. RF ablation was applied for 6.0 ± 3.1 min (50W, irrigated RF ablation). Echocardiographic parameters, such as CTI length, prominence of the Eustachian ridge (ER), and depth of the CTI pouch on the ablation plane, were assessed to analyse their correlation with EPS- or ablation procedure duration. The CTI pouch was shallower in patients with an ablation procedure duration above the median (4.8 ± 1.1 mm vs. 6.4 ± 0.9 mm, p = 0.04), suggesting a more lateral ablation plane in these patients, where the CTI musculature is stronger. CTI length or ER prominence above the respective median did not correlate with longer EPS duration. Conclusions Zero-fluoroscopy CTI ablation guided solely by intracardiac echocardiography in patients with CTI-dependent AFL is feasible and safe. ICE visualisation may help to localise the optimal ablation plane, detect and correct poor tissue contact of the catheter tip, and recognise early potential complications during the ablation procedure. Graphical Abstrac

The Effects of SEA0400 on Ca2+ Transient Amplitude and Proarrhythmia Depend on the Na+/Ca2+ Exchanger Expression Level in Murine Models.

Background/Objective: The cardiac Na+/Ca2+ exchanger (NCX) has been identified as a promising target to counter arrhythmia in previous studies investigating the benefit of NCX inhibition. However, the consequences of NCX inhibition have not been investigated in the setting of altered NCX expression and function, which is essential, since major cardiac diseases (heart failure/atrial fibrillation) exhibit NCX upregulation. Thus, we here investigated the effects of the NCX inhibitor SEA0400 on the Ca2+ transient amplitude and on proarrhythmia in homozygous NCX overexpressor (OE) and heterozygous NCX knockout (hetKO) mice compared to corresponding wild-types (WTOE/WThetKO). Methods/Results: Ca2+ transients of field-stimulated isolated ventricular cardiomyocytes were recorded with fluo-4-AM or indo-1-AM. SEA0400 (1 μM) significantly reduced NCX forward mode function in all mouse lines. SEA0400 (1 μM) significantly increased the amplitude of field-stimulated Ca2+ transients in WTOE, WThetKO, and hetKO, but not in OE (% of basal; OE = 98.7 ± 5.0; WTOE = 137.8 ± 5.2*; WThetKO = 126.3 ± 6.0*; hetKO = 140.6 ± 12.8*; *p < 0.05 vs. basal). SEA0400 (1 μM) significantly reduced the number of proarrhythmic spontaneous Ca2+ transients (sCR) in OE, but increased it in WTOE, WThetKO and hetKO (sCR per cell; basal/+SEA0400; OE = 12.5/3.7; WTOE = 0.2/2.4; WThetKO = 1.3/8.8; hetKO = 0.2/5.5) and induced Ca2+ overload with subsequent cell death in hetKO. Conclusion: The effects of SEA0400 on Ca2+ transient amplitude and the occurrence of spontaneous Ca2+ transients as a proxy measure for inotropy and cellular proarrhythmia depend on the NCX expression level. The antiarrhythmic effect of SEA0400 in conditions of increased NCX expression promotes the therapeutic concept of NCX inhibition in heart failure/atrial fibrillation. Conversely, in conditions of reduced NCX expression, SEA0400 suppressed the NCX function below a critical level leading to adverse Ca2+ accumulation as reflected by an increase in Ca2+ transient amplitude, proarrhythmia and cell death. Thus, the remaining NCX function under inhibition may be a critical factor determining the inotropic and antiarrhythmic efficacy of SEA0400