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

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.

Confusion in a patient with premature ventricular complexes originating in the left ventricular summit.

Background: Premature ventricular complexes (PVCs) originating in the ventricular outflow tracts are mostly of benign character. Case Summary: We describe a rare case of pulmonary hypertension with severe hypoxaemia and confusion caused by a significant mitral regurgitation (MR) during PVC originating in the left ventricle summit. After successful PVC ablation, all above-mentioned clinical parameters had normalized. Discussion: Premature ventricular complexes originating in the outflow tracts should be considered as a potential though rare cause of severe MR and pulmonary hypertension.

Predictors and prognosis of right ventricular function in pulmonary hypertension due to heart failure with reduced ejection fraction.

AIMS: Failure of right ventricular (RV) function worsens outcome in pulmonary hypertension (PH). The adaptation of RV contractility to afterload, the RV-pulmonary artery (PA) coupling, is defined by the ratio of RV end-systolic to PA elastances (Ees/Ea). Using pressure-volume loop (PV-L) technique we aimed to identify an Ees/Ea cut-off predictive for overall survival and to assess hemodynamic and morphologic conditions for adapted RV function in secondary PH due to heart failure with reduced ejection fraction (HFREF). METHODS AND RESULTS: This post hoc analysis is based on 112 patients of the prospective Magdeburger Resynchronization Responder Trial. All patients underwent right and left heart echocardiography and a baseline PV-L and RV catheter measurement. A subgroup of patients (n = 50) without a pre-implanted cardiac device underwent magnetic resonance imaging at baseline. The analysis revealed that 0.68 is an optimal Ees/Ea cut-off (area under the curve: 0.697, P < 0.001) predictive for overall survival (median follow up = 4.7 years, Ees/Ea ≥ 0.68 vs. <0.68, log-rank 8.9, P = 0.003). In patients with PH (n = 76, 68%) multivariate Cox regression demonstrated the independent prognostic value of RV-Ees/Ea in PH patients (hazard ratio 0.2, P < 0.038). Patients without PH (n = 36, 32%) and those with PH but RV-Ees/Ea ≥ 0.68 showed comparable RV-Ees/Ea ratios (0.88 vs. 0.9, P = 0.39), RV size/function, and survival. In contrast, secondary PH with RV-PA coupling ratio Ees/Ea < 0.68 corresponded extremely close to cut-off values that define RV dilatation/remodelling (RV end-diastolic volume >160 mL, RV-mass/volume-ratio ≤0.37 g/mL) and dysfunction (right ventricular ejection fraction <38%, tricuspid annular plane systolic excursion <16 mm, fractional area change <42%, and stroke-volume/end-systolic volume ratio <0.59) and is associated with a dramatically increased short and medium-term all-cause mortality. Independent predictors of prognostically unfavourable RV-PA coupling (Ees/Ea < 0.68) in secondary PH were a pre-existent dilated RV [end-diastolic volume >171 mL, odds ratio (OR) 0.96, P = 0.021], high pulsatile load (PA compliance <2.3 mL/mmHg, OR 8.6, P = 0.003), and advanced systolic left heart failure (left ventricular ejection fraction <30%, OR 1.23, P = 0.028). CONCLUSIONS: The RV-PA coupling ratio Ees/Ea predicts overall survival in PH due to HFREF and is mainly affected by pulsatile load, RV remodelling, and left ventricular dysfunction. Prognostically favourable coupling (RV-Ees/Ea ≥ 0.68) in PH was associated with preserved RV size/function and mid-term survival, comparable with HFREF without PH.

Pressure-volume loop validation of TAPSE/PASP for right ventricular arterial coupling in heart failure with pulmonary hypertension.

AIMS: The aim of this study was to validate the tricuspid annular plane systolic excursion/systolic pulmonary artery (PA) pressure (TAPSE/PASP) ratio with the invasive pressure-volume (PV) loop-derived end-systolic right ventricular (RV) elastance/PA elastance (Ees/Ea) ratio in patients with heart failure with reduced ejection fraction (HFREF) and secondary pulmonary hypertension (PH). METHODS AND RESULTS: The relationship of TAPSE and TAPSE/PASP with RV-PV loop (single-beat)-derived contractility Ees, afterload Ea, and Ees/Ea was assessed in 110 patients with HFREF with and without secondary PH. The results were compared with other surrogate parameters such as the fractional area change/PASP ratio. The association of the surrogates with all-cause mortality was evaluated. In patients with PH (n = 74, 67%), TAPSE significantly correlated with Ees (r = 0.356), inverse with Ea (r = -0.514) but was most closely associated with Ees/Ea (r = 0.77). Placing TAPSE in a ratio with PASP slightly reduced the relationship to Ees/Ea (r = 0.71) but was more closely related to the parameters of PA vascular load, diastolic RV function, and RV energetics. The area under the curve of TAPSE/PASP and TAPSE for discriminating overall survival in receiver operating characteristic analysis was not different (P = 0.78. Prognostic relevant cut-offs were 17 mm for TAPSE and 0.38 mm/mmHg for TAPSE/PASP. Both parameters in multivariate cox regression remained independently prognostically relevant. CONCLUSION: TAPSE is an easily and reliably obtainable and valid surrogate parameter for RV-PA coupling in PH due to HFREF. Putting TAPSE into a ratio with PASP did not further improve the coupling information or prognostic assessment. TRIAL IDENTIFIER: DRKS-German Clinical Trials Register (DRKS00011133; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011133).

DNA-PK: gatekeeper for IKKγ/NEMO nucleocytoplasmic shuttling in genotoxic stress-induced NF-kappaB activation.

The transcription factors of the nuclear factor κB (NF-κB) family play a pivotal role in the cellular response to DNA damage. Genotoxic stress-induced activation of NF-κB differs from the classical canonical pathway by shuttling of the NF-κB Essential Modifier (IKKγ/NEMO) subunit through the nucleus. Here, we show that DNA-dependent protein kinase (DNA-PK), an enzyme involved in DNA double-strand break (DSB) repair, triggers the phosphorylation of NEMO by genotoxic stress, thereby enabling shuttling of NEMO through the nucleus with subsequent NF-κB activation. We identified serine 43 of NEMO as a DNA-PK phosphorylation site and point mutation of this serine to alanine led to a complete block of NF-κB activation by ionizing radiation (IR). Blockade of DNA-PK by a specific shRNA or by DNA-PKcs-deficient cells abrogated NEMO entry into the nucleus, as well. Accordingly, SUMOylation of NEMO, a prerequisite of nuclear NEMO, was abolished. Based on these observations, we propose a model in which NEMO phosphorylation by DNA-PK provides the first step in the nucleocytoplasmic trafficking of NEMO.

Patient Directed Recording of a Bipolar Three-Lead Electrocardiogram using a Smartwatch with ECG Function.

Cardiac arrhythmias and cardiovascular diseases are a major public health problem in developed countries. A major goal in preventive medicine is the reduction of cardiovascular death by early detection of atrial fibrillation (AF), which may cause stroke, or early detection of life-threatening myocardial ischemia in acute coronary syndrome. Detection of arrhythmia is often challenging if symptoms occur when patients have no chance for immediate electrocardiogram (ECG) diagnostic testing, or if the observation time period is short or an immediate visit to their doctor is not possible. Smartwatches and other wearable devices are able to record a single lead ECG recording, but a single lead ECG is often not sufficient for diagnosis of cardiovascular disorders. Even diagnosis of AF can be difficult with only information from a single lead bipolar ECG. Some smart devices use photoplethysmography for detection of cardiac rhythm, but this technique can only give indirect hints of the underlying cardiac rhythm, is prone to interferences, and cannot be used for detection of myocardial ischemia. A three-lead bipolar ECG like the Einthoven leads used in regular ECGs can add useful information concerning arrhythmia detection or even diagnosis of other cardiovascular diseases like ischemia. Therefore, we describe a protocol for the patient-directed recording of an Einthoven three-lead ECG using a smartwatch.

High-risk PCI under support of a pulsatile left ventricular assist device - First German experience with the iVAC2L system.

BACKGROUND: During high-risk percutaneous coronary intervention (PCI) complications may occur, leading to unstable hemodynamic conditions. Circulatory support devices might help to intercept these conditions by supporting cardiac output. We investigated in a prospective trial the performance of the pulsatile iVAC2L system in the setting of high-risk PCI. METHODS: Circulatory support by the iVAC2L device was attempted in 20 consecutive patients (three females, mean age 72 ±â€¯9 years, LVEF 44 ±â€¯12%) undergoing high-risk PCI. Aortic pressure data were collected after device placement and immediately after PCI. RESULTS: Successful device placement was achieved in 17 (85%) patients; kinking of iliac artery and device length limited correct device placement in the remaining three patients. PCI success was 100%. With ongoing support (overall support time 122 ±â€¯32min) systolic, diastolic and mean blood pressure increased significantly and kept the higher level until device removal. Critical events occurred in three patients (massive vasospasm, coronary perforation, no-flow in LCA after wire placement), but the iVAC2L device helped to maintain stable hemodynamic conditions with no need for cardiopulmonary resuscitation. Serial controls of hemolysis related parameters in a subgroup of ten patients revealed no significant device related hemolysis after the performance of the iVAC2l system. CONCLUSIONS: High-risk PCI under hemodynamic support by the iVAC2L device is feasible and safe. Aortic pressure increases with ongoing support. The device helps to stabilize hemodynamic situations if complications occur.

Single-Lead ECG Recordings Including Einthoven and Wilson Leads by a Smartwatch: A New Era of Patient Directed Early ECG Differential Diagnosis of Cardiac Diseases?

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 ± 11 years, mean ± 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.

Out-of-hospital cardiac arrest due to idiopathic ventricular fibrillation in patients with normal electrocardiograms: results from a multicentre long-term registry.

AIMS: To define the clinical characteristics and long-term clinical outcomes of a large cohort of patients with idiopathic ventricular fibrillation (IVF) and normal 12-lead electrocardiograms (ECGs). METHODS AND RESULTS: Patients with ventricular fibrillation as the presenting rhythm, normal baseline, and follow-up ECGs with no signs of cardiac channelopathy including early repolarization or atrioventricular conduction abnormalities, and without structural heart disease were included in a registry. A total of 245 patients (median age: 38 years; males 59%) were recruited from 25 centres. An implantable cardioverter-defibrillator (ICD) was implanted in 226 patients (92%), while 18 patients (8%) were treated with drug therapy only. Over a median follow-up of 63 months (interquartile range: 25-110 months), 12 patients died (5%); in four of them (1.6%) the lethal event was of cardiac origin. Patients treated with antiarrhythmic drugs only had a higher rate of cardiovascular death compared to patients who received an ICD (16% vs. 0.4%, P = 0.001). Fifty-two patients (21%) experienced an arrhythmic recurrence. Age ≤16 years at the time of the first ventricular arrhythmia was the only predictor of arrhythmic recurrence on multivariable analysis [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.18-0.92; P = 0.03]. CONCLUSION: Patients with IVF and persistently normal ECGs frequently have arrhythmic recurrences, but a good prognosis when treated with an ICD. Children are a category of IVF patients at higher risk of arrhythmic recurrences.

Clinical improvement and enhanced collateral vessel growth after xenogenic monocyte transplantation.

Background: Monocytes (Mo) are the most important mediators in arteriogenesis. Previous results from our group demonstrated the great potential of allogenic Mo transplantation for improving collateral vessel growth, which appeared to be due to a considerable host vs. graft reaction. To prove this hypothesis and introduce this new method in clinical practice, we performed transplantation of human Mo (HuMo) in a mouse model. Methods and results: We ligated the femoral artery of BALB/c mice and transplanted Mo via the tail vein. Perfusion was measured by laser Doppler perfusion imaging (LDPI). We also performed clinical scoring based on behavior, wound healing, signs of inflammation and mobility of the ligated extremity. Finally, arteriogenesis and angiogenesis were examined histologically and by quantitative RT-PCR of the hind limb musculature. LDPI increased within one week after ligation when HuMo were transplanted and increased further up to day 21 (0.63±0.12 (n=12) in HuMo vs. 0.50±0.12 (n=17) in the control group (P<0.01)). A histological evaluation showed significantly more collateral arteries within the adductor muscles after HuMo transplantation. The promotion of collateral vessel growth after HuMo transplantation resulted in better clinical scores (0.33±0.26 (n=12) vs. 3.3 (n=9), SEM; P<0.01). Conclusions: Transplantation of HuMo improves collateral vessel growth and clinical outcomes in mice. These results verify our hypothesis that controlled triggering of the inflammatory mechanism resulted in collateral vessel growth by a local host vs. a graft reaction in the ischemic hind limbs and could represent a further step in the development of a clinical strategy for promoting arteriogenesis.

Recording of Bipolar Multichannel ECGs by a Smartwatch: Modern ECG Diagnostic 100 Years after Einthoven.

Aims: Feasibility study of accurate three lead ECG recording (Einthoven I, II and III) using an Apple Watch Series 4. Methods: In 50 healthy subjects (18 male; age: 40 ± 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. 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. 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.

Intracardiac echocardiography versus fluoroscopy for endovascular and endocardial catheter navigation during cryo-ablation of the slow pathway in AVNRT patients.

BACKGROUND: A new zero-fluoroscopy technique for electrophysiology catheter navigation relying on intracardiac echocardiography (ICE) has been recently reported (Ice&ICE trial). We investigated potential differences in efficacy, safety or procedural performance between conventional fluoroscopy- and ICE-guided cryothermal ablation (CA) in symptomatic AVNRT patients. METHODS: Clinical and electrophysiological data of AVNRT patients included in the Ice&ICE trial (22 patients, 16 females; =zero-fluoroscopy group) were compared to those of consecutive AVNRT patients, who underwent fluoroscopy-guided CA (25 patients, 17 females; = fluoroscopy group) during the last 2 years in our institution. RESULTS: Slow pathway ablation or modulation was successful in all patients. Fluoroscopy time and radiation dose in the fluoroscopy group were 11.2 ± 9.0 min and 20.3 ± 16.2Gycm2, whereas no fluoroscopy was used in the opposite group (p <  0.001, respectively). EPS duration was not different between the groups (zero-fluoroscopy:101.6 ± 40.2 min, fluoroscopy:99.4 ± 37.2 min, p = n.s.). Catheter placement time was significantly shorter in the fluoroscopy group (2.2 ± 1.6 min vs. 12.0 ± 7.5 min, p <  0.05), whereas cryo-application duration (from the first cryo-mapping to the last CA) was significantly shorter in the zero-fluoroscopy group (27.5 ± 37.0 min vs. 38.1 ± 33.9 min, p <  0.05). Mean cryo-mapping and CA applications were numerically lower in the zero-fluoroscopy group (CM:7.5 ± 5.7 vs. 8.8 ± 6.2; CA:3.1 ± 1.7 vs. 3.2 ± 2.0, p = n.s.). No major adverse events occurred in both groups. After 15.0 ± 4.2 months, arrhythmia recurrence was not different between the groups (4.5% vs. 8.0%, p = n.s.). CONCLUSIONS: Zero-fluoroscopy ICE-guided EP catheter navigation shows comparable efficacy and safety to fluoroscopic guidance during CA in AVNRT patients. ICE visualization of catheters and endocardial structures within the triangle of Koch shortens the cryo-application duration, though time needed for catheter placement is longer, when compared with conventional fluoroscopic guidance, which results in similar mean EPS duration with both navigation techniques. TRIAL REGISTRATION: (German Clinical Trials Register ID: DRKS00011360 ; Registration Date 14.12.2016).

Cerebrovascular events, bleeding complications and device related thrombi in atrial fibrillation patients with chronic kidney disease and left atrial appendage closure with the WATCHMAN™ device.

BACKGROUND: Impaired renal function increases the bleeding risk, leading to a conservative prescription and frequent discontinuation of oral anticoagulation in atrial fibrillation patients with chronic kidney disease (CKD). Interventional left atrial appendage closure (LAAC) might be an alternative therapeutic strategy for these patients. METHODS: We aimed to prospectively assess cerebrovascular (CE) and bleeding events, as well as peri-procedural and long-term complications in a cohort of consecutive patients undergoing interventional LAAC using the WATCHMAN™ device, with focus on CKD patients. RESULTS: One hundred and eighty-nine consecutive patients undergoing interventional LAAC were included in this analysis; 171 (90.5%) patients had a reduced estimated glomerular filtration rate (eGFR; patients for each CKD stage: II = 66; IIIa = 32; IIIb = 43; IV = 18; V = 12). During a follow-up of 310 patient years three (1.0%) patients suffered a CE (two strokes, one transitory ischemic attack) and five (1.6%) other ones a bleeding complication. The observed stroke rate was more than two-thirds and the bleeding risk more than half lower than expected. Device related thrombi (DRT) were detected in twelve (6.5%) patients; women had significantly more DRT than men (12.5% vs. 2.6%; p = 0.009). Patients with an eGFR< 30 ml/min/1.73m2 showed a trend to a higher DRT rate as compared to the opposite group (13.3% vs. 5.1%; p = 0.10). Thrombus resolved with temporary oral anticoagulation therapy in ten patients without sequelae; thrombus consolidation was confirmed by serial TEE controls in the remaining two patients. CONCLUSIONS: Atrial fibrillation patients with CKD have low CE and bleeding rates after LAAC with the WATCHMAN™ device. DRT risk is higher in female and patients with severe CKD. More frequent post-interventional TEE controls might be justified for early DRT detection and safe management of patients at high DRT risk. TRIAL REGISTRATION: (German Clinical Trials Register ID: DRKS00 010768 ; Registration Date 07.07.2016).

Right heart function interacts with left ventricular remodeling after CRT: A pressure volume loop study.

BACKGROUND: Right ventricular (RV) dysfunction is recognized as a cardinal prognostic marker in systolic heart failure patients. Conflicting data exist on the interaction of RV function and left ventricular (LV) reverse remodeling after cardiac resynchronization therapy (CRT). This prospective monocentric trial was set up to assess the predictive value of baseline RV function and corresponding RV-pulmonary artery (PA) coupling on LV reverse remodeling after CRT. METHODS: 110 patients with a CRT indication were prospectively enrolled. RV function and RV-PA interaction were analyzed at baseline using echocardiographic and invasive pressure-volume loop catheter approach. The primary endpoint was reverse LV remodeling (CRT-responder) defined as a reduction in LV end-systolic volume of ≥15% at 6 months. RESULTS: Responders had higher RV-PA coupling ratios (single-beat end-systolic elastance/PA elastance: Ees/Ea) at baseline, which corresponded to smaller RVs with better ejection fraction and lower afterload. After multivariate adjustment, the baseline Ees/Ea remained an independent predictor for LV response (OR 14.0 [1.5-130.8], p = 0.021). Normal coupling (Ees/Ea ≥ 1) was associated with higher responder rates (RR) (86%). Progressive uncoupling was associated with lower LV-RR (Ees/Ea ≤ 1-0.5: 57%, and Ees/Ea < 0.5: 32%, p < 0.001), corresponded with higher degrees of LV impairment and severity of mitral regurgitation, and was independently associated with an adverse outcome. CONCLUSIONS: A higher baseline RV-PA coupling, reflecting a lower degree of LV-induced pulmonary hypertension and secondary RV-dysfunction, is associated with an improved LV-reverse remodeling and is independently associated with better prognosis. The value of RV-PA ratio as potential guide for CRT patient selection warrants further investigation. Clinical Trial Registration - URL: http://www.drks.de. Unique Identifier: DRKS00011133.

Zero-fluoroscopy cryothermal ablation of atrioventricular nodal re-entry tachycardia guided by endovascular and endocardial catheter visualization using intracardiac echocardiography (Ice&ICE Trial).

INTRODUCTION: Stochastic damage of the ionizing radiation to both patients and medical staff is a drawback of fluoroscopic guidance during catheter ablation of cardiac arrhythmias. Therefore, emerging zero-fluoroscopy catheter-guidance techniques are of great interest. METHODS AND RESULTS: We investigated, in a prospective pilot study, the feasibility and safety of the cryothermal (CA) slow-pathway ablation in patients with symptomatic atrioventricular-nodal-re-entry-tachycardia (AVNRT) using solely intracardiac echocardiography (ICE) for endovascular and endocardial catheter visualization. Twenty-five consecutive patients (mean age 55.6 ± 12.0 years, 17 female) with ECG-documentation or symptoms suggesting AVNRT underwent an electrophysiology study (EPS) in our laboratory utilizing ICE for catheter navigation. Supraventricular tachycardia was inducible in 23 (92%) patients; AVNRT was confirmed by appropriate stimulation maneuvers in 20 (80%) patients. All EPS in the AVNRT subgroup could be accomplished without need for fluoroscopy, relying solely on ICE-guidance. CA guided by anatomical location and slow-pathway potentials was successful in all patients, median cryo-mappings = 6 (IQR:3-10), median cryo-ablations = 2 (IQR:1-3). Fluoroscopy was used to facilitate the trans-septal puncture and localization of the ablation substrate in the remaining 3 patients (one focal atrial tachycardia and two atrioventricular-re-entry-tachycardias). Mean EPS duration in the AVNRT subgroup was 99.8 ± 39.6 minutes, ICE guided catheter placement 11.9 ± 5.8 minutes, time needed for diagnostic evaluation 27.1 ± 10.8 minutes, and cryo-application duration 26.3 ± 30.8 minutes. CONCLUSIONS: ICE-guided zero-fluoroscopy CA in AVNRT patients is feasible and safe. Real-time visualization of the true endovascular borders and cardiac structures allow for safe catheter navigation during the ICE-guided EPS and might be an alternative to visualization technologies using geometry reconstructions.

Serial Assessment of Natriuretic Peptides in Patients Undergoing Interventional Closure of the Left Atrial Appendage.

BACKGROUND: Closure of the left atrial appendage (LAA) to prevent cardioembolic events is an alternative therapy to oral anticoagulation in patients with non-valvular atrial fibrillation. The LAA is an important source of natriuretic peptides and its exclusion from the circulation may alter the blood level of these hormones, thereby influencing their diagnostic value and clinical effects. METHODS: We aimed to prospectively assess potential changes in mid-regional pro A-type natriuretic peptide (MR-proANP) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels 6 weeks and 6 months after interventional LAA closure using the WATCHMAN device. RESULTS: In 29 consecutive patients with successful LAA closure baseline MR-proANP level was 274±208pmol/l and decreased by -24.5±68 (p=0.07) and -15.0±44pmol/l (p=0.10) after 6 weeks and 6 months, respectively. The drop in the MR-proANP level after 6 weeks and 6 months was significant in patients with elevated (≥214pmol/l) baseline MR-proANP level (n=15: -54.3±78.0, p<0.01 and -31.8±45.4pmol/l, p=0.03, respectively) and those with reduced left ventricular ejection fraction (LVEF<45%, n=7: -87.4±97.3, p=0.02 and -60.3±42.6pmol/l, p=0.01, respectively). Baseline NT-proBNP level (median 1054pg/ml; IQR 621-1977pg/ml), sodium, potassium, mean systolic or diastolic blood pressure did not change significantly in the mentioned patient groups. CONCLUSIONS: After LAA closure, MR-proANP level decreased significantly in patients with elevated baseline MR-proANP level or reduced LVEF, whereas NT-proBNP level remained unchanged, thereby altering the correlation coefficient between the two biomarkers. Our findings should be considered when using these biomarkers for diagnostic or prognostic evaluation in patients with interventional LAA closure.

Left atrial enlargement and clinical considerations in patients with or without a residual interatrial shunt after closure of the left atrial appendage with the WATCHMAN™-device.

BACKGROUND: Interventional closure of the left atrial appendage (LAA) in patients with non-valvular atrial fibrillation, high thromboembolic and bleeding risk or bleeding history is an alternative therapeutic strategy to oral anticoagulation. It is not known if the exclusion of the LAA from the blood circulation affects the left atrial volume (LAV) and consequently its prognostic value or the circulatory performance of the heart in humans. METHODS: We aimed to prospectively assess potential changes in baseline LAV, left ventricular ejection fraction (LVEF), NT-proBNP-level and the covered distance in the 6-min walk-test 6 weeks and 6 months after LAA closure with the WATCHMAN™ device. We used serial 3-dimensional transthoracic and transesophageal echocardiography to assess LAV, residual interatrial shunt and device performance in 58 consecutive patients with successful LAA closure. RESULTS: Accurate 3D-echocardiographic data for LAV measurements were evaluable for 51 (91%) patients. Maximum LAV (LAVmax) at baseline was 102.8 ± 30.8 ml and increased significantly to 107.7 ± 32.8 ml after 6 weeks (p < 0.01) and 113.5 ± 34.2 ml after 6 months (p < 0.01). Minimal LAV (LAVmin) increased from 76.9 ± 29.5 ml at baseline to 81.8 ± 30.2 ml after 45 days (p < 0.01) and 82.1 ± 33.3 ml after 6 months (p < 0.01). Similarly, their indexes to BSA (LAVImax and LAVImin) increased significantly, as well. Patients without a residual left-to-right interatrial shunt showed a significantly higher increase in LAVmax or LAVmin. Baseline LVEF, NT-proBNP-level or the distance covered at the 6-min walk test did not significantly change 6 weeks or 6 months after LAA closure. CONCLUSIONS: LAVmax and LAVmin increase significantly after interventional LAA closure. LA enlargement does not correlate with clinical progression of heart failure. Persistent left-to-right interatrial shunt counteracts the LA enlargement. A reduced LA compliance after exclusion of the LAA from the blood circulation with consecutive increase in LA pressure may be a potential cause of LA enlargement and warrants further investigation. TRIAL REGISTRATION: German Clinical Trials Register ID: DRKS00010768 ; Registration Date 07.07.2016.

Analysis of cardiovascular mortality, bleeding, vascular and cerebrovascular events in patients with atrial fibrillation vs. sinus rhythm undergoing transfemoral Transcatheter Aortic Valve Implantation (TAVR).

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has been demonstrated to be an established therapy for high-risk, inoperable patients with severe symptomatic aortic valve stenosis. For patients with moderate surgical risk, TAVR is equivalent to conventional aortic valve surgery. However, atrial fibrillation (AF) is also present in many of these patients, thus requiring post-implantation oral anticoagulation therapy in addition to the inhibition of thrombocyte aggregation, which poses the risk of bleeding complications. The aim of our work was to investigate the influence of AF on mortality and the occurrence of bleeding, vascular and cerebrovascular complications related to TAVR according to the VARC-2 criteria. METHODS: Two hundred eighty-three patients who underwent TAVR between March 2010 and April 2016 were retrospectively examined. In total, 257 patients who underwent transfemoral access were included in this study. The mean patient age was 81 ± 6 years, 54.1% of the patients were women, and 42.4% had pre-interventional AF. RESULTS: Compared to patients with sinus rhythm (SR, n = 148), patients with AF (n = 109) had an almost three-fold higher incidence of major vascular complications (AF 14.7% vs. SR 5.4%, p = 0.016) and life-threatening bleeding (AF 11.9% vs. SR 4.1%, p = 0.028) during the first 30 post-procedural days. However, the rate of cerebrovascular complications (AF 3.7% vs. SR 2.7%, p = 0.726) did not significantly differ between the two groups. Overall mortality was significantly higher in patients with AF during the first month (AF 8.3% vs. SR 2.0%, p = 0.032) and the first year (AF 28.4% vs. SR 15.3%; p = 0.020) following TAVR. CONCLUSION: Patients with AF had significantly more severe bleeding complications after TAVR, which were significantly related to mortality. Future prospective randomized studies must clarify the optimal anticoagulation therapy for patients with AF after TAVR. TRIAL REGISTRATION: DRKS00011798 on DRKS (Date 17.03.2017).

[Unclear Abdominal Pain - Not Always a Gastroenterological Emergency]. / Der unklare Bauchschmerz ­ nicht immer ein gastroenterologischer Notfall.

History and admission findings An 84-year old patient with persistent atrial fibrillation and chronic renal failure received a subcutaneous injection with low molecular weight heparin (LMWH) during a hospital stay. Over the course of her hospitalization, the patient developed abdominal pain. There was a marked hematoma at the injection site. A large tumor was palpable in the right abdominal quadrant. Examinations Due to the significant reduction in hemoglobin, we performed a CT-angiogram of the abdomen. Diagnosis We were able to visualize an intramuscular hematoma within the rectus abdominis muscle. Therapy and clinical course After visualization with digital subtraction angiography and application of microcoils and histoacryl-glue, we were able to stop bleeding. After implantation of left atrial appendage occluder, oral anticoagulation therapy could be stopped. Conclusion LMWH-treated patients with nonspecific abdominal pain should be meticulously examined to exclude iatrogenic abdominal muscle hematoma.