Transcatheter aortic valve replacement in Germany with need for a surgical bailout.

BACKGROUND: In transcatheter aortic valve replacement (TAVR), complications may force the need for a surgical bailout, but knowledge is rare about outcomes in Germany. METHODS: Using national health records, we investigated all TAVR in German hospitals between 2007 and 2020, focusing on 2018-2020. We extracted data on those interventions with need for a surgical bailout. RESULTS: A total of 159,643 TAVR were analyzed, with an overall rate of surgical bailout of 2.30 %, an overall in-hospital mortality of 3.85 %, and in-hospital mortality in case of bailout of 16.51 %. The number of all annual TAVR procedures increased substantially (202 to 22,972), with the rate of surgical bailout declining from 27.23 to 0.61 % and overall mortality from 11.39 to 2.29 %. However, in-hospital mortality after bailout was still high (28.37 % in 2020). The standardized rates of overall mortality and surgical bailout between 2018 and 2020 were significantly lower for balloon-expandable and self-expanding transfemoral TAVR than for transapical TAVR after risk adjustment [transapical/transfemoral balloon-expandable/transfemoral self-expanding TAVR: in-hospital mortality: 5.66 % (95 % CI 4.81 %; 6.52 %)/2.30 % (2.03 %; 2.57 %)/2.32 % (2.07 %; 2.57 %); surgical bailout: 2.33 % (1.68 %; 2.97 %)/0.79 % (0.60 %; 0.98 %)/0.42 % (0.31 %; 0.53 %)]. Coronary artery disease [risk-adjusted OR = 1.50 (1.21; 1.85), p < 0.001] and atrial fibrillation [OR = 1.29 (1.07; 1.57), p = 0.009] were found to be the main risk factors for bailout. CONCLUSIONS: Rates of TAVR with need for a surgical bailout and overall in-hospital mortality have declined noticeably over the years in Germany. However, the outcomes are still unfavorable after surgical bailout, as in-hospital mortality is continuously high. We present risk factors for surgical bailout to improve preparation of subsequent measures. It must be a major goal to further reduce the rate of surgical bailouts in the future.

Comparing balloon-expandable and self-expanding transfemoral transcatheter aortic valve replacement based on subgroups in Germany 2019/2020.

BACKGROUND: Previously, overall comparable outcomes were seen for balloon-expandable (BE) or self-expanding (SE) transfemoral transcatheter aortic valve replacement (TAVR). However, subgroup analyses based on large case numbers are still needed. METHODS: German national data of all BE and SE transfemoral TAVR treating aortic valve stenosis in 2019 and 2020 were analysed. We then compared different outcomes and performed a subgroup analysis for the endpoint in-hospital mortality. RESULTS: Overall, 46,243 TAVR were analysed, 19,910 BE, and 26,333 SE. Patients in the SE group had a significantly higher logistic EuroSCORE (13.61 vs 12.66%, p < 0.001), age (81.55 vs 79.99a, p < 0.001), and proportion of women (54.82 vs 40.06%, p < 0.001). Both groups showed a similar in-hospital mortality with 2.37% in BE and 2.35% in SE (p = 0.916). In-hospital mortality also did not differ significantly after risk adjustment (OR = 0.98 [0.86, 1.13], p = 0.799). Patients in the SE group had a significantly lower risk of major bleeding (OR = 0.83 [0.73, 0.95], p = 0.006), but a significantly higher risk of stroke (OR = 1.38 [1.19, 1.59], p < 0.001), delirium (OR = 1.15 [1.06, 1.24], p = 0.001), and permanent pacemaker implantation (OR = 1.29 [1.21, 1.37], p < 0.001). In the subgroup analysis of in-hospital mortality, there were no significant differences in any of the observed subgroups (age < 75/75-79/80-84/ ≥ 85a, logistic EuroSCORE < 4/4- < 9/ ≥ 9, gender, NYHA III/IV, previous CABG, peripheral vascular disease, COPD, pulmonary hypertension, renal disease GFR < 30 ml/min, and diabetes mellitus). CONCLUSION: In the direct comparison of balloon-expandable and self-expanding TAVR, there are no differences for in-hospital mortality in subgroups.

Center Volumes Correlate with Likelihood of Stent Implantation in German Coronary Angiography.

Aims: Literature on percutaneous coronary intervention (PCI) stated an inverse relationship between hospital volume and mortality, but the effects on other characteristics are unclear. Methods: Using German national records, all coronary angiographies with coronary artery disease in 2017 were identified. We applied risk-adjustment to account for differences in population characteristics. Results: Of overall 528,188 patients, 55.22% received at least one stent, with on average 1.01 stents implanted in all patients. Based on those patients who received at least one stent, this corresponds to an average number of 1.82 stents. In-hospital mortality across all patients was 2.93%, length of hospital stay was 6.46 days, and mean reimbursement was €5,531. There were comparatively more emergency admissions in low volume centers and more complex cases (3-vessel disease, left main stenosis, and in-stent stenosis) in high volume centers. In multivariable regression analysis, volume and likelihood of stent implantation (p=0.003) as well as number of stents (p=0.020) were positively correlated. No relationship was seen for in-hospital mortality (p=0.105), length of stay (p=0.201), and reimbursement (p=0.108). Nonlinear influence of volume suggests a ceiling effect: In hospitals with ≤100 interventions, likelihood and number of implanted stents are lowest (∼34% and 0.6). After that, both rise steadily until a volume of 500 interventions. Finally, both remain stable in the categories of over 500 interventions (∼60% and 1.1). Conclusion: In PCI, lower volume centers contribute to emergency care. Higher volume centers treat more complex cases and show a higher likelihood of stent implantations, with a stable safety.

Treatment of pure aortic regurgitation using surgical or transcatheter aortic valve replacement between 2018 and 2020 in Germany.

Background: In pure aortic regurgitation, transcatheter aortic valve replacement (TAVR) is not yet used on a regular base. Due to constant development of TAVR, it is necessary to analyze current data. Methods: By use of health records, we analyzed all isolated TAVR or surgical aortic valve replacements (SAVR) for pure aortic regurgitation between 2018 and 2020 in Germany. Results: 4,861 procedures-4,025 SAVR and 836 TAVR-for aortic regurgitation were identified. Patients treated with TAVR were older, showed a higher logistic EuroSCORE, and had more pre-existing diseases. While results indicate a slightly higher unadjusted in-hospital mortality for transapical TAVR (6.00%) vs. SAVR (5.71%), transfemoral TAVR showed better outcomes, with self-expanding compared to balloon-expandable transfemoral TAVR having significantly lower in-hospital mortality (2.41% vs. 5.17%; p = 0.039). After risk adjustment, balloon-expandable as well as self-expanding transfemoral TAVR were associated with a significantly lower mortality vs. SAVR (balloon-expandable: risk adjusted OR = 0.50 [95% CI 0.27; 0.94], p = 0.031; self-expanding: OR = 0.20 [0.10; 0.41], p < 0.001). Furthermore, the observed in-hospital outcomes of stroke, major bleeding, delirium, and mechanical ventilation >48 h were significantly in favor of TAVR. In addition, TAVR showed a significantly shorter length of hospital stay compared to SAVR (transapical: risk adjusted Coefficient = -4.75d [-7.05d; -2.46d], p < 0.001; balloon-expandable: Coefficient = -6.88d [-9.06d; -4.69d], p < 0.001; self-expanding: Coefficient = -7.22 [-8.95; -5.49], p < 0.001). Conclusions: TAVR is a viable alternative to SAVR in the treatment of pure aortic regurgitation for selected patients, showing overall low in-hospital mortality and complication rates, especially with regard to self-expanding transfemoral TAVR.

Mechano-electrical interactions and heterogeneities in wild-type and drug-induced long QT syndrome rabbits.

Electromechanical reciprocity - comprising electro-mechanical (EMC) and mechano-electric coupling (MEC) - provides cardiac adaptation to changing physiological demands. Understanding electromechanical reciprocity and its impact on function and heterogeneity in pathological conditions - such as (drug-induced) acquired long QT syndrome (aLQTS) - might lead to novel insights in arrhythmogenesis. Our aim is to investigate how electrical changes impact on mechanical function (EMC) and vice versa (MEC) under physiological conditions and in aLQTS. To measure regional differences in EMC and MEC in vivo, we used tissue phase mapping cardiac MRI and a 24-lead ECG vest in healthy (control) and IKr -blocker E-4031-induced aLQTS rabbit hearts. MEC was studied in vivo by acutely increasing cardiac preload, and ex vivo by using voltage optical mapping (OM) in beating hearts at different preloads. In aLQTS, electrical repolarization (heart rate corrected RT-interval, RTn370) was prolonged compared to control (P < 0.0001) with increased spatial and temporal RT heterogeneity (P < 0.01). Changing electrical function (in aLQTS) resulted in significantly reduced diastolic mechanical function and prolonged contraction duration (EMC), causing increased apico-basal mechanical heterogeneity. Increased preload acutely prolonged RTn370 in both control and aLQTS hearts (MEC). This effect was more pronounced in aLQTS (P < 0.0001). Additionally, regional RT-dispersion increased in aLQTS. Motion-correction allowed us to determine APD-prolongation in beating aLQTS hearts, but limited motion correction accuracy upon preload-changes prevented a clear analysis of MEC ex vivo. Mechano-induced RT-prolongation and increased heterogeneity were more pronounced in aLQTS than in healthy hearts. Acute MEC effects may play an additional role in LQT-related arrhythmogenesis, warranting further mechanistic investigations. KEY POINTS: Electromechanical reciprocity comprising excitation-contraction coupling (EMC) and mechano-electric feedback loops (MEC) is essential for physiological cardiac function. Alterations in electrical and/or mechanical heterogeneity are known to have potentially pro-arrhythmic effects. In this study, we aimed to investigate how electrical changes impact on the mechanical function (EMC) and vice versa (MEC) both under physiological conditions (control) and in acquired long QT syndrome (aLQTS). We show that changing the electrical function (in aLQTS) results in significantly altered mechanical heterogeneity via EMC and, vice versa, that increasing the preload acutely prolongs repolarization duration and increases electrical heterogeneity, particularly in aLQTS as compared to control. Our results substantiate the hypothesis that LQTS is an ?electro-mechanical', rather than a 'purely electrical', disease and suggest that acute MEC effects may play an additional role in LQT-related arrhythmogenesis.

Impact of the COVID-19 pandemic on aortic valve replacement procedures in Germany.

BACKGROUND: COVID-19 has caused the deferral of millions of elective procedures, likely resulting in a backlog of cases. We estimate the number of postponed surgical aortic valve replacement (sAVR) and transcatheter aortic valve replacement (TAVR) procedures during the first two waves of the COVID-19 pandemic in Germany. METHODS: Using German national records, all isolated TAVR and sAVR procedures between 2007 and 2020 were identified. Using weekly TAVR and sAVR procedures between 2017 and 2019, we created a forecast for 2020 and compared it with the observed number of procedures in 2020. RESULTS: In Germany, a total of 225,398 isolated sAVR and 159,638 isolated TAVR procedures were conducted between 2007 and 2020 that were included in our analysis. The reduction in all AVR procedures (sAVR and TAVR) for the entire year 2020 was 19.07% (95%CI: 15.19-22.95%). During the first wave of the pandemic (week 12-21), the mean weekly reduction was 32.06% (23.44-40.68%) and during the second wave of the pandemic (week 41-52), the mean weekly reduction was 25.58% (14.19-36.97%). The number of sAVR procedures decreased more than the number of TAVR procedures (24.63% vs. 16.42% for the entire year 2020). CONCLUSION: The first year of the COVID-19 pandemic saw a substantial postponing of AVR procedures in Germany. Postponing was higher for sAVR than for TAVR procedures and less pronounced during the second wave of the COVID-19 pandemic.

Gene- and variant-specific efficacy of serum/glucocorticoid-regulated kinase 1 inhibition in long QT syndrome types 1 and 2.

AIMS: Current long QT syndrome (LQTS) therapy, largely based on beta-blockade, does not prevent arrhythmias in all patients; therefore, novel therapies are warranted. Pharmacological inhibition of the serum/glucocorticoid-regulated kinase 1 (SGK1-Inh) has been shown to shorten action potential duration (APD) in LQTS type 3. We aimed to investigate whether SGK1-Inh could similarly shorten APD in LQTS types 1 and 2. METHODS AND RESULTS: Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and hiPSC-cardiac cell sheets (CCS) were obtained from LQT1 and LQT2 patients; CMs were isolated from transgenic LQT1, LQT2, and wild-type (WT) rabbits. Serum/glucocorticoid-regulated kinase 1 inhibition effects (300 nM-10 µM) on field potential durations (FPD) were investigated in hiPSC-CMs with multielectrode arrays; optical mapping was performed in LQT2 CCS. Whole-cell and perforated patch clamp recordings were performed in isolated LQT1, LQT2, and WT rabbit CMs to investigate SGK1-Inh (3 µM) effects on APD. In all LQT2 models across different species (hiPSC-CMs, hiPSC-CCS, and rabbit CMs) and independent of the disease-causing variant (KCNH2-p.A561V/p.A614V/p.G628S/IVS9-28A/G), SGK1-Inh dose-dependently shortened FPD/APD at 0.3-10 µM (by 20-32%/25-30%/44-45%). Importantly, in LQT2 rabbit CMs, 3 µM SGK1-Inh normalized APD to its WT value. A significant FPD shortening was observed in KCNQ1-p.R594Q hiPSC-CMs at 1/3/10 µM (by 19/26/35%) and in KCNQ1-p.A341V hiPSC-CMs at 10 µM (by 29%). No SGK1-Inh-induced FPD/APD shortening effect was observed in LQT1 KCNQ1-p.A341V hiPSC-CMs or KCNQ1-p.Y315S rabbit CMs at 0.3-3 µM. CONCLUSION: A robust SGK1-Inh-induced APD shortening was observed across different LQT2 models, species, and genetic variants but less consistently in LQT1 models. This suggests a genotype- and variant-specific beneficial effect of this novel therapeutic approach in LQTS.

Survival of Patients Treated With Extracorporeal Hemoadsorption and Extracorporeal Membrane Oxygenation: Results From a Nation-Wide Registry.

Extracorporeal hemoadsorption with the CytoSorb adsorber is increasingly being used during the past years. The use in combination with extracorporeal membrane oxygenation (ECMO) is feasible, but frequency of its use and outcomes have not been assessed in larger cohorts. We analyzed all patients treated with veno-venous (VV) ECMO either with or without CytoSorb in Germany from 2017 to 2019. Data were retrieved from a nationwide claim dataset collected by the Research Data Center of the Federal Bureau of Statistics. During this three-year episode, 7,699 patients were treated with VV ECMO. Among these, the number of CytoSorb-treated patients constantly increased from 156 (6.6%) in 2017 to 299 (11.8%) in 2019. In this large cohort hemoadsorption with the CytoSorb adsorber was associated with higher mortality and increased treatment costs. Due to limited information in the dataset about the severity of disease comparison of outcomes of patients treated with and without CytoSorb has to be interpreted with caution. Further studies have to examine if this finding is due to a negative effect of hemoadsorption with the CytoSorb device or is rather to be attributed to disease severity.

The impact of transcatheter aortic valve implantation planning and procedure on acute and chronic renal failure.

BACKGROUND: Severe aortic valve stenosis inhibits renal perfusion, thereby potentially worsening renal function, in particular in elderly patients most often assigned to transcatheter aortic valve implantation (TAVI). Pre-TAVI diagnostics and the procedure itself may adversely impact renal function, however renal perfusion and function may also improve post-procedure. This study aimed to clarify the impact of TAVI planning and procedure on kidney function METHODS: In this retrospective study, kidney function of patients who underwent transfemoral TAVI at a tertiary university hospital between 2016 and 2019 was analyzed. The present study investigated kidney function at baseline, after computed tomography (CT) was performed for evaluation of TAVI, after TAVI, at discharge and at follow-up. RESULTS: Among 366 patients, the prevalence of acute kidney injury (AKI) was 14.5% after TAVI. Independent predictors of AKI were arterial hypertension, baseline creatinine, AKI post CT and coronary intervention during pre-procedural diagnostics. At discharge and follow-up, 2.1% and 3.4%, respectively had sustained relevant impairment of kidney function (defined as creatinine/baseline creatinine > 1.5 or renal replacement therapy). Patients with known chronic kidney disease showed no higher rates of short- and long-term impairment, but higher rates of improvement of renal function after TAVI. CONCLUSIONS: In most cases TAVI does not worsen renal function. A sustained impairment after TAVI was found in only a few cases. This was independent of reduced baseline kidney function. Transfemoral TAVI can thus be planned and performed even in patients with higher stages of chronic kidney disease.

COVID-19 pandemic affects STEMI numbers and in-hospital mortality: results of a nationwide analysis in Germany.

BACKGROUND: The COVID-19 pandemic led to extensive restrictions in Germany in 2020, including the postponement of elective interventions. We examined the impact on ST-elevation myocardial infarction (STEMI) as an acute and non-postponable disease. METHODS: Using German national records, all STEMI between 2017 and 2020 were identified. Using the number of STEMI cases between 2017 and 2019, we created a forecast for 2020 and compared it with the observed number of STEMI in 2020. RESULTS: From 2017 to 2020, 248,062 patients were treated for STEMI in Germany. Mean age was 65.21 years and 28.36% were female. When comparing forecasted and observed STEMI in 2020, a correlation can be seen: noticeable fewer STEMI were treated in those weeks respectively months with an increasing COVID-19 hospitalization rate (monthly percentage decrease in STEMI: March - 14.85%, April - 13.39%, November - 11.92%, December - 22.95%). At the same time, the crude in-hospital mortality after STEMI increased significantly at the peaks of the first and second waves (relative risk/RR of monthly in-hospital mortality: April RR = 1.11 [95% CI 1.02; 1.21], November RR = 1.13 [1.04; 1.24], December RR = 1.16 [1.06; 1.27]). CONCLUSION: The COVID-19 pandemic led to a noticeable decrease in the number of STEMI interventions in Germany at the peaks of the first and second waves in 2020, corresponding to an increase in COVID-19 hospitalizations. At the same time, in-hospital mortality after STEMI increased significantly in these phases. Impact of the COVID-19 pandemic on STEMI numbers and in-hospital mortality in Germany. Relative difference between forecasted and observed STEMI numbers (above figure), the relative risk of in-hospital mortality (middle figure) as well as number of new hospital admissions for COVID-19 per million inhabitants according to Roser et al.27 (bottom figure).

Hospital intervention volume affects outcomes of emergency transcatheter aortic valve implantations in Germany.

The literature has shown an inverse volume-outcome relationship for transcatheter aortic valve implantation (TAVI). However, little is known about emergency admissions in Germany. Using German national electronic health records, we identified all isolated balloon-expandable and self-expanding transfemoral TAVI in 2018. The focus was on those patients with emergency admission. 17,295 patients were treated with TAVI, including 1682 emergency cases. 49.2% of the emergency admissions were female, the mean age was 81.2 years and the logistic EuroSCORE was 23.3%. The percentage of emergency cases was higher in lower volume than in higher volume centers (p < 0.001): In detail, centers performing < 50 TAVI showed an emergency admission rate of ~ 15%, those with > 200 TAVI a rate of ~ 11%. After propensity score adjustment, analyzing the outcomes for an increase in volume per 10 emergency admissions, higher volume centers showed significantly better outcomes regarding in-hospital mortality (OR = 0.872, p = 0.043), major bleeding (OR = 0.772, p = 0.001), stroke (OR = 0.816, p = 0.044), mechanical ventilation > 48 h (OR = 0.749, p = 0.001), length of hospital stay (risk adjusted difference in days of hospitalization per 10 emergency admissions: - 1.01 days, p < 0.001), and reimbursement (risk adjusted difference in reimbursement per 10 emergency admissions: -€314.89, p < 0.001). Results were not significant for acute kidney injury (OR = 0.951, p = 0.104), postoperative delirium (OR = 0.975, p = 0.480), and permanent pacemaker implantation (OR = 1.010, p = 0.732). In conclusion, regarding transfemoral TAVI, the percentage of emergency cases was higher in lower volume centers in Germany. However, higher volume centers show significantly better outcomes for in-hospital mortality and complication rates as well as resource utilization parameters.

Impact of Procedure Volume on the Outcomes of Surgical Aortic Valve Replacement.

BACKGROUND: Literature demonstrated that procedure volumes affect outcomes of patients undergoing transcatheter aortic valve implantation. We evaluated the outcomes of surgical aortic valve replacement. METHODS: All isolated surgical aortic valve replacement procedures in Germany in 2017 were identified. Hospitals were divided into five groups from ≤25 (very low volume) until >100 (very high volume) annual procedures. RESULTS: In 2017, 5,533 patients underwent isolated surgical aortic valve replacement. All groups were of comparable risk (logistic EuroSCORE, 5.12-4.80%) and age (66.6-68.1 years). In-hospital mortality and complication rates were lowest in the very high-volume group. Multivariable logistic regression analyses showed no significant volume-outcome relationship for in-hospital mortality, stroke, postoperative delirium, and mechanical ventilation > 48 hours. Regarding acute kidney injury, patients in the very high-volume group were at lower risk than those in the very low volume group (odds ratio [OR] = 0.53, p = 0.04). Risk factors for in-hospital mortality were previous cardiac surgery (OR = 5.75, p < 0.001), high-grade renal disease (glomerular filtration rate < 15 mL/min, OR = 5.61, p = 0.002), surgery in emergency cases (OR = 2.71, p = 0.002), and higher grade heart failure (NYHA [New York Heart Association] III/IV; OR = 1.80, p = 0.02). Risk factors for all four complication rates were atrial fibrillation and diabetes mellitus. CONCLUSION: Patients treated in very low volume centers (≤25 operations/year) had a similar risk regarding in-hospital mortality and most complications compared with very high-volume centers (>100 operations/year). Only in the case of acute kidney injury, very high-volume centers showed better outcomes than very low volume centers. Therefore, surgical aortic valve replacement can be performed safely independent of case volume.

Annual hospital procedural volume and outcome in extracorporeal membrane oxygenation for respiratory failure.

BACKGROUND: The hospital mortality of patients suffering from pulmonary failure requiring venovenous extracorporeal membrane oxygenation (V-V ECMO) or extracorporeal carbon dioxide removal (ECCO2 R) is high. It is unclear whether outcome correlates with a hospital's annual procedural volume. METHODS: Data on all V-V ECMO and ECCO2 R cases treated from 2007 to 2019 were retrieved from the German Institute for Medical Documentation and Information. Comorbidities and outcomes were assessed by DRG, OPS, and ICD codes. The study population was divided into 5 groups depending on annual hospital V-V ECMO and ECCO2 R volumes (<10 cases; 10-19 cases; 20-29 cases; 30-49 cases; ≥50 cases). Primary outcome was hospital mortality. RESULTS: A total of 25 096 V-V ECMO and 3607 ECCO2 R cases were analyzed. V-V ECMO hospitals increased from 89 in 2007 to 214 in 2019. Hospitals handling <10 cases annually increased especially (64 in 2007 to 149 in 2019). V-V ECMO cases rose from 807 in 2007 to 2597 in 2019. Over 50% of cases were treated in hospitals handling ≥30 cases annually. Hospital mortality was independent of the annual hospital procedural volume (55.3%; 61.3%; 59.8%; 60.2%; 56.3%, respectively, p = 0.287). We detected no differences when comparing hospitals handling <30 cases to those with ≥30 annually (p = 0.659). The numbers of ECCO2 R hospitals and cases has dropped since 2011 (287 in 2007 to 48 in 2019). No correlation between annual hospital procedural volume and hospital mortality was identified (p = 0.914). CONCLUSION: The number of hospitals treating patients requiring V-V ECMO and V-V ECMO cases rose from 2007 to 2019, while ECCO2 R hospitals and their case numbers decreased. We detected no correlation between annual hospital V-V ECMO or ECCO2 R volume and hospital mortality.

Oxytocin exerts harmful cardiac repolarization prolonging effects in drug-induced LQTS.

Background: Oxytocin is used therapeutically in psychiatric patients. Many of these also receive anti-depressant or anti-psychotic drugs causing acquired long-QT-syndrome (LQTS) by blocking HERG/IKr. We previously identified an oxytocin-induced QT-prolongation in LQT2 rabbits, indicating potential harmful effects of combined therapy. We thus aimed to analyze the effects of dual therapy with oxytocin and fluoxetine/risperidone on cardiac repolarization. Methods: Effects of risperidone, fluoxetine and oxytocin on QT/QTc, short-term variability (STV) of QT, and APD were assessed in rabbits using in vivo ECG and ex vivo monophasic AP recordings in Langendorff-perfused hearts. Underlying mechanisms were assessed using patch clamp in isolated cardiomyocytes. Results: Oxytocin, fluoxetine and risperidone prolonged QTc and APD in whole hearts. The combination of fluoxetine + oxytocin resulted in further QTc- and APD-prolongation, risperidone + oxytocin tended to increase QTc and APD compared to monotherapy. Temporal QT instability, STVQTc was increased by oxytocin, fluoxetine / fluoxetine + oxytocin and risperidone / risperidone + oxytocin. Similar APD-prolonging effects were confirmed in isolated cardiomyocytes due to differential effects of the compounds on repolarizing ion currents: Oxytocin reduced IKs, fluoxetine and risperidone reduced IKr, resulting in additive effects on IKtotal-tail. In addition, oxytocin reduced IK1, further reducing the repolarization reserve. Conclusion: Oxytocin, risperidone and fluoxetine prolong QTc / APD. Combined treatment further prolongs QTc/APD due to differential effects on IKs and IK1 (block by oxytocin) and IKr (block by risperidone and fluoxetine), leading to pronounced impairment of repolarization reserve. Oxytocin should be used with caution in patients in the context of acquired LQTS.

Catheter ablation of short-coupled variant of torsade de pointes.

BACKGROUND: The short-coupled variant of torsade de pointes (sc-TdP) is a malignant arrhythmia that frequently presents with ventricular fibrillation (VF) electrical storm. Verapamil is considered the first-line therapy of sc-TdP while catheter ablation is not widely adopted. The aim of this study was to determine the origin of sc-TdP and to assess the outcome of catheter ablation using 3D-mapping. METHODS AND RESULTS: We retrospectively analyzed five patients with sc-TdP who underwent 3D-mapping and ablation of sc-TdP at five different institutions. Four patients initially presented with sudden cardiac arrest, one patient experienced recurrent syncope as the first manifestation. All patients demonstrated a monomorphic premature ventricular contraction (PVC) with late transition left bundle branch block pattern, superior axis, and a coupling interval of less than 300 ms. triggering recurrent TdP and VF. In four patients, the culprit PVC was mapped to the free wall insertion of the moderator band (MB) with a preceding Purkinje potential in two patients. Catheter ablation using 3D-mapping and intracardiac echocardiography eliminated sc-TdP in all patients, with no recurrence at mean 2.7 years (range 6 months to 8 years) of follow-up. CONCLUSION: 3D-mapping and intracardiac echocardiography demonstrate that sc-TdP predominantly originates from the MB free wall insertion and its Purkinje network. Catheter ablation of the culprit PVC at the MB free wall junction leads to excellent short- and long-term results and should be considered as first-line therapy in recurrent sc-TdP or electrical storm.

Docosahexaenoic acid normalizes QT interval in long QT type 2 transgenic rabbit models in a genotype-specific fashion.

AIM: Long QT syndrome (LQTS) is a cardiac channelopathy predisposing to ventricular arrhythmias and sudden cardiac death. Since current therapies often fail to prevent arrhythmic events in certain LQTS subtypes, new therapeutic strategies are needed. Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid, which enhances the repolarizing IKs current. METHODS AND RESULTS: We investigated the effects of DHA in wild type (WT) and transgenic long QT Type 1 (LQT1; loss of IKs), LQT2 (loss of IKr), LQT5 (reduction of IKs), and LQT2-5 (loss of IKr and reduction of IKs) rabbits. In vivo ECGs were recorded at baseline and after 10 µM/kg DHA to assess changes in heart-rate corrected QT (QTc) and short-term variability of QT (STVQT). Ex vivo monophasic action potentials were recorded in Langendorff-perfused rabbit hearts, and action potential duration (APD75) and triangulation were assessed. Docosahexaenoic acid significantly shortened QTc in vivo only in WT and LQT2 rabbits, in which both α- and ß-subunits of IKs-conducting channels are functionally intact. In LQT2, this led to a normalization of QTc and of its short-term variability. Docosahexaenoic acid had no effect on QTc in LQT1, LQT5, and LQT2-5. Similarly, ex vivo, DHA shortened APD75 in WT and normalized it in LQT2, and additionally decreased AP triangulation in LQT2. CONCLUSIONS: Docosahexaenoic acid exerts a genotype-specific beneficial shortening/normalizing effect on QTc and APD75 and reduces pro-arrhythmia markers STVQT and AP triangulation through activation of IKs in LQT2 rabbits but has no effects if either α- or ß-subunits to IKs are functionally impaired. Docosahexaenoic acid could represent a new genotype-specific therapy in LQT2.

Coronary artery bypass grafting versus stent implantation in patients with chronic coronary syndrome and left main disease: insights from a register throughout Germany.

BACKGROUND: Recent randomized controlled trials have sparked debate about the optimal treatment of patients suffering from left main coronary artery disease. The present study analyzes outcomes of left main stenting versus coronary bypass grafting (CABG) in a nationwide registry in patients with chronic coronary syndrome (CCS). METHODS: All cases suffering from CCS and left main coronary artery disease treated either with CABG or stent, were identified within the database of the German bureau of statistics. Logistic or linear regression models were used with 20 baseline patient characteristics as potential confounders to compare both regimens. RESULTS: In 2018, 1318 cases with left main stenosis were treated with CABG and 8,920 with stent. Patients assigned for stenting were older (72.58 ± 9.87 vs. 68.63 ± 9.40, p < 0.001) and at higher operative risk, as assessed by logistic EuroSCORE (8.77 ± 8.45 vs. 4.85 ± 4.65, p < 0.001). After risk adjustment, no marked differences in outcomes were found for in-hospital mortality and stroke (risk adjusted odds ratio (aOR) for stent instead of CABG: aOR mortality: 1.08 [95% CI 0.66; 1.78], p = 0.748; aOR stroke: 0.59 [0.27; 1.32], p = 0.199). Stent implantation was associated with a reduced risk of relevant bleeding (aOR 0.38 [0.24; 0.61], p < 0.001), reduced prolonged ventilation time (aOR 0.54 [0.37 0.79], p = 0.002), and postoperative delirium (aOR 0.16 [0.11; 0.22], p < 0.001). Furthermore, stent implantation was associated with shorter hospital stay (- 6.78 days [- 5.86; - 7.71], p < 0.001) and lower costs (- €10,035 [- €11,500; - €8570], p < 0.001). CONCLUSION: Left main stenting is a safe and effective treatment option for CCS-patients suffering from left main coronary artery disease at reasonable economic cost. Coronary artery bypass grafting versus stent implantation in patients with chronic coronary syndrome and left main disease: insights from a register throughout Germany. All cases with chronic coronary syndrome and left main stenosis treated in 2018 in Germany either with left main stenting or coronary bypass grafting were extracted from a nation-wide database. In-hospital outcomes were compared after logistic regression analysis.

In-hospital outcomes of patients undergoing concomitant aortic and mitral valve replacement in Germany.

OBJECTIVES: To evaluate in-hospital outcomes of concomitant mitral valve replacement (MVR) in patients undergoing conventional aortic valve replacement due to aortic stenosis in a nationwide cohort. METHODS: Administrative data from all patients with aortic stenosis undergoing conventional aortic and concomitant MVR (reason for MVR not specified) between 2017 and 2018 in Germany were analysed. RESULTS: A total of 2597 patients with a preoperative logistic EuroScore of 9.81 (standard deviation: 8.56) were identified. In-hospital mortality was 6.8%. An in-hospital stroke occurred in 3.4%, acute kidney injury in 16.3%, prolonged mechanical ventilation of more than 48 h in 16.3%, postoperative delirium in 15.8% and postoperative pacemaker implantation in 7.6% of the patients. Mean hospital stay was 16.5 (standard deviation: 12.1) days. Age [odds ratio (OR): 1.03; P = 0.019], New York Heart Association class III or IV (OR: 1.63; P = 0.012), previous cardiac surgery (OR: 2.85, P = 0.002), peripheral vascular disease (OR: 2.01, P = 0.031), pulmonary hypertension (OR: 1.63, P = 0.042) and impaired renal function (glomerular filtration rate <15, OR: 3.58, P = 0.001; glomerular filtration rate <30, OR: 2.51, P = 0.037) were identified as independent predictors for in-hospital mortality. CONCLUSIONS: In this nationwide analysis, concomitant aortic and MVR was associated with acceptable in-hospital mortality, morbidity and length of in-hospital stay. The regression analyses may help to identify high-risk patients and further optimize treatment strategies.

Coronary angiography following out-of-hospital cardiac arrest (OHCA): a review of outcomes and clinical considerations.

INTRODUCTION: In patients suffering a sudden out-of-hospital cardiac arrest (OHCA), the prevalence of a coronary artery lesion as the underlying cause is relatively high, but many other causes have been described. For this reason, identifying patients who would benefit from an emergency coronary angiography is important. AREAS COVERED: In the present manuscript, we reviewed the literature covering some relevant studies regarding the role of coronary angiography in patients with OHCA, including our local algorithm for the management of patients with OHCA. We particularly focused on the selection of patients who would benefit from an emergency coronary angiography, the time period until the performance of the angiography, the role of extracorporeal cardiopulmonary resuscitation (ECPR), the identification of a coronary artery lesion as the underlying cause of cardiac arrest and clinical outcomes. EXPERT OPINION: In summary, a local standard algorithm for the management of patients with OHCA appears favorable. An emergency coronary angiography should be advised in patients with a presumed cardiac cause and without obvious non-cardiac cause. A shockable initial rhythm, ST elevation in the post-resuscitation ECG, a previously known coronary artery disease, and ECPR are important predictors of cardiac cause of OHCA.