Transcatheter Repair versus Mitral-Valve Surgery for Secondary Mitral Regurgitation.

BACKGROUND: Current treatment recommendations for patients with heart failure and secondary mitral regurgitation include transcatheter edge-to-edge repair and mitral-valve surgery. Data from randomized trials comparing these therapies are lacking in this patient population. METHODS: In this noninferiority trial conducted in Germany, patients with heart failure and secondary mitral regurgitation who continued to have symptoms despite guideline-directed medical therapy were randomly assigned, in a 1:1 ratio, to undergo either transcatheter edge-to-edge repair (intervention group) or surgical mitral-valve repair or replacement (surgery group). The primary efficacy end point was a composite of death, hospitalization for heart failure, mitral-valve reintervention, implantation of an assist device, or stroke within 1 year after the procedure. The primary safety end point was a composite of major adverse events within 30 days after the procedure. RESULTS: A total of 210 patients underwent randomization. The mean (±SD) age of the patients was 70.5±7.9 years, 39.9% were women, and the mean left ventricular ejection fraction was 43.0±11.7%. Within 1 year, at least one of the components of the primary efficacy end point occurred in 16 of the 96 patients with available data (16.7%) in the intervention group and in 20 of the 89 with available data (22.5%) in the surgery group (estimated mean difference, -6 percentage points; 95% confidence interval [CI], -17 to 6; P<0.001 for noninferiority). A primary safety end-point event occurred in 15 of the 101 patients with available data (14.9%) in the intervention group and in 51 of the 93 patients with available data (54.8%) in the surgery group (estimated mean difference, -40 percentage points; 95% CI, -51 to -27; P<0.001). CONCLUSIONS: Among patients with heart failure and secondary mitral regurgitation, transcatheter edge-to-edge repair was noninferior to mitral-valve surgery with respect to a composite of death, rehospitalization for heart failure, stroke, reintervention, or implantation of an assist device in the left ventricle at 1 year. (Funded by Abbott Vascular; MATTERHORN ClinicalTrials.gov number, NCT02371512.).

Timing of Complete Revascularization with Multivessel PCI for Myocardial Infarction.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI) with multivessel coronary artery disease, the time at which complete revascularization of nonculprit lesions should be performed remains unknown. METHODS: We performed an international, open-label, randomized, noninferiority trial at 37 sites in Europe. Patients in a hemodynamically stable condition who had STEMI and multivessel coronary artery disease were randomly assigned to undergo immediate multivessel percutaneous coronary intervention (PCI; immediate group) or PCI of the culprit lesion followed by staged multivessel PCI of nonculprit lesions within 19 to 45 days after the index procedure (staged group). The primary end point was a composite of death from any cause, nonfatal myocardial infarction, stroke, unplanned ischemia-driven revascularization, or hospitalization for heart failure at 1 year after randomization. The percentages of patients with a primary or secondary end-point event are provided as Kaplan-Meier estimates at 6 months and at 1 year. RESULTS: We assigned 418 patients to undergo immediate multivessel PCI and 422 to undergo staged multivessel PCI. A primary end-point event occurred in 35 patients (8.5%) in the immediate group as compared with 68 patients (16.3%) in the staged group (risk ratio, 0.52; 95% confidence interval, 0.38 to 0.72; P<0.001 for noninferiority and P<0.001 for superiority). Nonfatal myocardial infarction and unplanned ischemia-driven revascularization occurred in 8 patients (2.0%) and 17 patients (4.1%), respectively, in the immediate group and in 22 patients (5.3%) and 39 patients (9.3%), respectively, in the staged group. The risk of death from any cause, the risk of stroke, and the risk of hospitalization for heart failure appeared to be similar in the two groups. A total of 104 patients in the immediate group and 145 patients in the staged group had a serious adverse event. CONCLUSIONS: Among patients in hemodynamically stable condition with STEMI and multivessel coronary artery disease, immediate multivessel PCI was noninferior to staged multivessel PCI with respect to the risk of death from any cause, nonfatal myocardial infarction, stroke, unplanned ischemia-driven revascularization, or hospitalization for heart failure at 1 year. (Supported by Boston Scientific; MULTISTARS AMI ClinicalTrials.gov number, NCT03135275.).

Kidney disease, diabetes, and diameter stenosis predict Rotablation bailout in modified balloon application for severely calcified coronary lesions.

BACKGROUND: Modified balloon (MB) treatment in severely calcified coronary artery lesions is an established technique. However, some lesions require Rotablation (RA) as bailout strategy. AIMS: This study aimed to assess predictors of switch from MB to RA and its impact on procedural and midterm outcomes. METHODS: Four hundred and eighty-three consecutive patients were included undergoing MB treatment (n = 204) with a scoring or cutting balloon, or upfront RA treatment (n = 279) serving as control cohort. Strategy switch from MB to RA was performed in 19 of 204 patients. Procedural success was defined as successful stent implantation and TIMI III flow. RESULTS: In the MB cohort, median age was 72 [63-78] years, 75.5% were male and 42.1% had acute coronary syndrome. Procedure success was achieved in 89.4% of the switch group versus 98.4% of the MB only group (p < 0.001) and in 96.4% of the RA cohort. In the switch group, periprocedural complications (31.6% vs. 8.1% vs. 11.8%, p = 0.007), radiation dose (149 [126-252] vs. 59 [30-97] vs. 102 [59-156] Gcm2; p < 0.001) and contrast volume (250 [190-250] vs. 190 [150-250] vs. 195 [190--250] mL; p < 0.001) were significantly higher. Diabetes (OR 3.8, 95% CI 1.1-13.9, p = 0.042), chronic kidney disease stage 4 or 5 (OR 19.0, 95% CI 3.3-108.6, p < 0.001) and pronounced calcification resulting in higher angiographic diameter stenosis (OR 1.13, 95% CI 1.1-1.2, p = 0.001) independently predicted strategy switch. Midterm results were not affected by strategy switch regarding 1-year target lesion revascularization rates (86% vs. 89% vs. 89%; log-rank p = 0.95). CONCLUSION: Primary RA strategy might be considered in patients with severely calcified coronary artery lesions with high angiographic diameter stenosis, diabetes or impaired renal function due to increased periprocedural complication rates, radiation dose, and contrast volume following strategy switch.

Impact of concomitant tricuspid regurgitation on outcome after edge-to-edge mitral valve repair.

AIMS: To evaluate the impact of tricuspid regurgitation (TR) on echocardiographic and functional outcome after mitral valve transcatheter edge-to-edge-repair (M-TEER). METHODS AND RESULTS: A total of 740 patients underwent M-TEER at our center from 2010 to 2021. Patients were analyzed according to severity of concomitant TR at the time of M-TEER procedure: low-grade TR (grade ≤I [trace-mild], 279 patients [37.7%]), moderate TR (grade II, 170 patients [23.0%]) and high-grade TR (grade III-V [severe-torrential], 291 patients [39.3%]). Patients with moderate to high-grade TR had higher morbidity. Procedural success of M-TEER was achieved similarly in all groups (98.2% vs. 97.6% vs. 95.9%, p = 0.22). TR severity decreased rapidly and consistently after M-TEER to only 48.0% of high-grade TR patients after 3 months (p < 0.001) and to 46.8% after 12 months (p = 0.99). High-grade TR patients had significantly higher mortality (21.5% vs. 18.2% vs. 11.1%, p = 0.003) up to 12 months after M-TEER. However, high-grade TR did not independently predict mortality (HR 1.302, 95% CI 0.937-1.810; p = 0.116). Echocardiographic and functional outcome was similar in both secondary and primary MR patients. CONCLUSIONS: High-grade concomitant TR did not independently predict adverse outcome following M-TEER. A wait-and-observe approach for these patients is reasonable.

Coronary Stent Fracture Causing Myocardial Infarction: Case Report and Review of Literature.

Coronary stent fracture (SF) is a potential cause of stent failure increasing the risk for in-stent restenosis, stent thrombosis, target lesion revascularization and major adverse cardiac events. Overall incidence of SF ranges from < 1.0% up to 18.6% and SF can be found in up to 60% of failed devices. Advanced imaging techniques have improved the detection of SF. However, defining the optimal therapeutic approach towards these complex lesions is challenging. This review summarizes the most important publications on the topic of SF and discusses current insights into pathophysiology, diagnostic tools, classification and therapeutic management. Furthermore, two illustrative cases of SF leading to myocardial infarction are presented, which demonstrate typical SF risk factors such as vessel angulation and hinge motion, stenting in the right coronary artery, use of long stents and multiple stent layers.

Implications of concomitant obstructive or restrictive pulmonary diseases on functional and clinical results after MitraClip.

OBJECTIVES: We investigated the impact of underlying pulmonary limitations (PL) on symptoms and clinical outcomes after transcatheter mitral valve repair (TMVr). BACKGROUND: Patients with pulmonary disease and patients with symptomatic mitral regurgitation (MR) suffer common symptoms like dyspnea and reduced exercise capacity. METHODS: Datasets from the TMVr Ulm registry were retrospectively analyzed by a blinded specialist in pneumology. Patients were dichotomized according to an unambiguous manifestation of concomitant pulmonary disease in a PL-group and a non-PL-group and were analyzed regarding baseline characteristics and clinical follow-up. RESULTS: Overall, 483 patients were included in the study of which 32.3% (n = 156) showed an underlying pulmonary disease. Patients in the PL-group were similar to patients in the non-PL-group, including Euro SCORE II (8.2 vs. 8.4, p = 0.39), New York Heart Association (NYHA) classification (3.2 ± 0.7 in both groups, p = 0.65) and the incidence of moderate-to-severe or severe MR after TMVr (5.8 vs. 8.3%, p = 0.32). Equal and significant symptom relief after TMVr was experienced in both cohorts according to NYHA functional class (2.24 ± 0.84 vs. 2.24 ± 0.86, p = 0.93) and rate of hospitalization during 2 years of follow-up decreased comparably from 61.1 to 19.3%. However, all-cause mortality for 2 year follow-up was significantly higher in the PL-group compared to the non-PL-group (31.4 vs. 21.4%, p = 0.018). CONCLUSION: In patients with MR and concomitant pulmonary disorders, a significant increase of exercise capacity and a significant decrease of rehospitalization rate were observed after TMVr. Nevertheless, all-cause mortality remains significantly increased within a follow-up period of 2 years compared to patients without pulmonary disorders.

Immunoadsorption for heart failure is associated with normalization of iron metabolism.

AIMS: In heart failure (HF) patients, early stages are associated with increased iron levels, whereas iron deficiency is a common feature of chronic HF. We investigated the acute and long-term changes in iron metabolism in HF patients after immunoadsorption treatment and intravenous immunoglobulin (IVIG) administration. METHODS AND RESULTS: Twenty-seven patients with HF with reduced ejection fraction (HFrEF) received a single cycle of immunoadsorption followed by IVIG administration. Left ventricular ejection fraction (LVEF) and iron biomarker (ferritin, hepcidin and interleukin-6) were evaluated at baseline, after immunoadsorption and during long-term follow-up of 29.3 months. LVEF improved significantly after immunoadsorption treatment from baseline 27% to 43% at long-term follow-up. Ferritin decreased from baseline 300.2 to 201.3 ng/mL (p < 0.0001) during immunoadsorption treatment and normalized during long-term to 207.9 ng/mL. Hepcidin showed a V-shaped course, with a significant decrease after immunoadsorption and normalization during long-term. Interleukin-6 levels showed no relevant inflammation. CONCLUSIONS: Our data suggest that initial high serum ferritin and hepcidin levels indicate elevated iron levels characteristic of early stages of HFrEF, without inflammation. Normalization of hepcidin and ferritin was paralleled by restoration of systolic cardiac function after immunoadsorption treatment, without development of iron deficiency, as usually observed in chronic HF.

Predictors of left ventricular reverse remodeling after percutaneous therapy for mitral regurgitation with the MitraClip system.

OBJECTIVES: To investigate the predictors and clinical impact of left ventricular reverse remodeling (LVRR) after MitraClip (MC) therapy for degenerative (DMR) and functional mitral regurgitation (FMR). BACKGROUND: MC therapy induces LVRR in patients with mitral regurgitation (MR) at high-risk for surgery. However, specific data on predictors of LVRR therapy are limited. METHODS: This study included 164 patients treated by MC implantation with complete clinical and echocardiographic evaluation at baseline, 6 months, and 12 months. LVRR was defined as a decrease of ≥10% of the left ventricular end-diastolic diameter after 12 months and was found in 49% of the patients. RESULTS: LVRR was associated with significantly reduced event rate 2 years after MC procedure. In the total cohort, multivariate regression analysis determined severe recurrent/residual MR after 12 months (p = .010, odds ratio [OR] = 0.26), male gender (p = .050, OR = 0.49) and left ventricular ejection fraction (LVEF) <20% (p = .046, OR = 0.24) as predictors of absence of LVRR. In the subgroup analysis according to etiology of MR, multivariate regression analysis revealed severe recurrent/residual MR after 12 months (p = .04, OR = 0.184) to inversely predict LVRR only in the DMR subgroup. In FMR, residual severe tricuspid regurgitation (TR) inversely predicts LVRR (p = .032, OR = 0.361). CONCLUSIONS: LVRR occurs in half of the patients after MC and is associated with reduced MACCE rates at follow-up. Combined information on residual/recurrent MR, baseline LVEF and gender predict LVRR after MC procedure. While residual/recurrent MR is the independent predictor for the absence of LVRR in DMR, in FMR only severe residual TR independently predict LVRR.

Stress cardiomyopathy associated with the first manifestation of multiple sclerosis: a case report.

BACKGROUND: We present a case with a close temporal association of the first diagnosis of multiple sclerosis and stress cardiomyopathy. CASE PRESENTATION: A 19-year-old man experienced severe dyspnoea. The cardiac biomarkers troponin T and NT-proBNP were elevated, and transthoracic echocardiography showed basal hypokinesia. The man was diagnosed with stress cardiomyopathy after main differential diagnoses such as acute coronary syndrome, myocarditis, and pheochromocytoma were excluded. Furthermore, the patient reported vertigo and paraesthesia. Brain and spinal MRI revealed T2-hyperintense lesions with a prominent acute lesion in the pontomedullary area. Cerebrospinal fluid findings revealed a lymphocytic pleocytosis and intrathecal IgG synthesis. Serum neurofilaments were elevated. The patient was diagnosed with MS, and treatment with intravenous Methylprednisolone was initiated. The brainstem lesion due to multiple sclerosis was assumed to be the cause of stress cardiomyopathy. The patient fully recovered. CONCLUSION: Stress cardiomyopathy may be linked with the first manifestation of multiple sclerosis in the presented case since pontomedullary lesions could affect the sympathetic nervous system. This case highlights the importance of neurological history and examination in young patients with unexplained acute cardiac complaints.

[Severe Metformin-Associated Lactic Acidosis in a 67-Year-Old Patient]. / Schwere Metformin-assoziierte Laktatazidose bei einem 67-jährigen Patienten.

Metformin-associated lactic acidosis (MALA) is a difficult to diagnose and potentially life-threatening disease. We report a rare case of severe MALA treated at our hospital's intensive care unit. Suspected diagnosis of MALA and quick initiation of an adequate therapy containing renal replacement therapy led to successful management of this complicated MALA-case.

The VAMP-associated protein VAPB is required for cardiac and neuronal pacemaker channel function.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels encode neuronal and cardiac pacemaker currents. The composition of pacemaker channel complexes in different tissues is poorly understood, and the presence of additional HCN modulating subunits was speculated. Here we show that vesicle-associated membrane protein-associated protein B (VAPB), previously associated with a familial form of amyotrophic lateral sclerosis 8, is an essential HCN1 and HCN2 modulator. VAPB significantly increases HCN2 currents and surface expression and has a major influence on the dendritic neuronal distribution of HCN2. Severe cardiac bradycardias in VAPB-deficient zebrafish and VAPB-/- mice highlight that VAPB physiologically serves to increase cardiac pacemaker currents. An altered T-wave morphology observed in the ECGs of VAPB-/- mice supports the recently proposed role of HCN channels for ventricular repolarization. The critical function of VAPB in native pacemaker channel complexes will be relevant for our understanding of cardiac arrhythmias and epilepsies, and provides an unexpected link between these diseases and amyotrophic lateral sclerosis.-Silbernagel, N., Walecki, M., Schäfer, M.-K. H., Kessler, M., Zobeiri, M., Rinné, S., Kiper, A. K., Komadowski, M. A., Vowinkel, K. S., Wemhöner, K., Fortmüller, L., Schewe, M., Dolga, A. M., Scekic-Zahirovic, J., Matschke, L. A., Culmsee, C., Baukrowitz, T., Monassier, L., Ullrich, N. D., Dupuis, L., Just, S., Budde, T., Fabritz, L., Decher, N. The VAMP-associated protein VAPB is required for cardiac and neuronal pacemaker channel function.

Long-term clinical outcome of persistent left bundle branch block after transfemoral aortic valve implantation.

OBJECTIVE: The impact of persistent left bundle-branch block (pLBBB) on long-term clinical outcome remains to be determined. BACKGROUND: New-onset of pLBBB occurs frequently after transfemoral aortic valve implantation (TAVI). METHODS: Seven hundred and seven consecutive patients who underwent TAVI were analyzed for baseline and procedural characteristics and clinical outcome in an up to 2-year follow-up. Patients were divided into either a group with pLBBB until hospital discharge or a group without LBBB. We performed propensity-score matching and analyzed baseline characteristics, procedural data and clinical outcome of both groups. Patients received balloon-expandable valves in 56.4%, mechanically expandable valves in 37.5%, and self-expandable valves in 6.3%. RESULTS: A new-onset, pLBBB was observed in 47.5% of patients after TAVI. The implantation of a mechanically expandable valve was associated with higher rate of pLBBB (54.2% vs. 20.8%, P < 0.001), whereas implantation of a balloon-expandable valve was associated with lower incidence of pLBBB (39.8% vs. 73.1%, P < 0.001). Deeper ventricular implantation at left-coronary side led to higher rates of pLBBB (7.5 ± 2.5 vs. 6.7 ± 2.6 mm, P < 0.001). The occurrence of pLBBB was associated with higher rates of permanent pacemaker implantation (40.9% vs. 15.9%, P < 0.001). By multivariate analysis, implantation of a mechanically expandable valve (Boston Scientific Lotus valve) was identified as independent predictor of occurrence of pLBBB (odds ratio 4.7, confidence interval 3.2-7.0, P < 0.001). In the 2-year follow-up, there were no significant differences between "pLBBB" and "no LBBB"-groups regarding mortality and rehospitalization due to heart failure. CONCLUSIONS: The occurrence of pLBBB is associated with the choice of valve type and implantation depth and requires significantly higher rates of permanent pacemaker implantations. Importantly, there are no differences in the 2-year follow-up regarding mortality and rehospitalization due to heart failure.

Novel spiral mapping catheter facilitates observation of the time-to-pulmonary vein isolation during cryoballoon ablation.

Observation of the time-to-pulmonary vein isolation (TTI) by a spiral mapping catheter has emerged as a valuable procedural parameter in cryoballoon pulmonary vein isolation (PVI). The 1st generation spiral mapping catheter (Achieve, SMC1) has been available as an 8-polar catheter with a distal loop diameter of 15 or 20 mm. The novel spiral mapping catheter (Achieve Advance, SMC2) was designed as a true guidewire and is available, in addition to the sizes of the SMC1, as a 10-polar mapping catheter with a distal loop diameter of 25 mm. Whether these novel features of SMC2 influence procedural characteristics of Cryo-PVI in comparison to SMC1 has not been reported. In this prospective cohort study 158 patients (age 65.1 ± 12.4 years, female 39%, paroxysmal AF 60%) undergoing PVI with the 2nd generation cryoballoon were included. SMC1 was used in 57 patients (36%), whereas 101 patients (64%) underwent Cryo-PVI with the SMC2. All PVs (623/623, 100%) were isolated successfully. Mean procedure duration was 72.0 ± 18.9 min in the SMC1 group and 74.4 ± 19.1 min in the SMC2 group (p = 0.432). Mean fluoroscopy time was also not different between both study groups (SMC1 15.7 ± 6.6 min, SMC2 15.7 ± 7.3 min, p = 0.593). TTI was observed in 68.6% of pulmonary veins in the SMC1 group, whereas TTI observation rate was 82.6% in the SMC2 group (p < 0.001). Number of freezes (5.5 ± 1.5 vs. 6.5 ± 1.9; p = 0.001) and total freeze duration (14.1 ± 4.5 vs. 17.6 ± 5.6; p < 0.001) were increased in the SMC2 group. SMC2 significantly increases TTI observation rate during Cryo-PVI. Procedure duration and fluoroscopy time are similar and number of freezes and total freeze duration are increased compared to PVI with SMC1 due to decreased stability and maneuverability of SMC2.

Mutation of the Na+/K+-ATPase Atp1a1a.1 causes QT interval prolongation and bradycardia in zebrafish.

The genetic underpinnings that orchestrate the vertebrate heart rate are not fully understood yet, but of high clinical importance, since diseases of cardiac impulse formation and propagation are common and severe human arrhythmias. To identify novel regulators of the vertebrate heart rate, we deciphered the pathogenesis of the bradycardia in the homozygous zebrafish mutant hiphop (hip) and identified a missense-mutation (N851K) in Na+/K+-ATPase α1-subunit (atp1a1a.1). N851K affects zebrafish Na+/K+-ATPase ion transport capacity, as revealed by in vitro pump current measurements. Inhibition of the Na+/K+-ATPase in vivo indicates that hip rather acts as a hypomorph than being a null allele. Consequently, reduced Na+/K+-ATPase function leads to prolonged QT interval and refractoriness in the hip mutant heart, as shown by electrocardiogram and in vivo electrical stimulation experiments. We here demonstrate for the first time that Na+/K+-ATPase plays an essential role in heart rate regulation by prolonging myocardial repolarization.

Intra-aortic balloon counterpulsation pump in heart failure patients during MitraClip implantation-A propensity-score matched analysis.

OBJECTIVES: To analyze 30-day and 6-month results after percutaneous mitral valve repair using an IABP as circulatory support. BACKGROUND: The use of intra-aortic balloon counterpulsation pump extended the spectrum of cardiovascular interventions. METHODS: Since 2014, 17 patients of 365 patients (4.7%) at our center received an IABP during MitraClip implantation procedure. We compare the periprocedural results to a control group of 17 patients treated with MitraClip without an IABP support. To adjust for differences of baseline characteristics a propensity-score matching for age, baseline blood pressure, preoperative EuroSCORE II and left ventricular ejection fraction was performed. The decision for prophylactic implantation of an IABP was at the discretion of the interventionalist. For both groups, clinical results up to 6 months were evaluated. RESULTS: The IABP group had higher NT-pro BNP levels at baseline and increased left ventricular diameters. The procedure was more often categorized as "urgent" due to refractory heart failure in the IABP group. All procedures were carried out successfully, thereby achieving a sufficient MR reduction in both groups. Length of hospital stay was significantly longer in the IABP group 11.7 ± 14 days (compared to 6.5 ± 2.9 days in the No IABP group, P < 0.01). All patients in both groups had an event-free 30-day follow-up. MACCE rate was higher in the IABP group compared to the No IABP group (47.1% vs. 23.5%, P = 0.14). CONCLUSION: Insertion of an IABP during MitraClip procedure might be a feasible option to achieve comparable results and may provide additional safety and procedural hemodynamic stability in the setting of high-risk percutaneous mitral valve repair.

Predictors of permanent pacemaker implantation after transfemoral aortic valve implantation with the Lotus valve.

BACKGROUND: Permanent pacemaker implantation (PPMI) after transcatheter aortic valve implantation is of high clinical relevance, but PPMI rates differ widely between valve types. Although the Lotus valve can be repositioned, reported rates for PPMI are high. The predictors of PPMI after Lotus valve implantation have not been defined yet. METHODS: We analyzed the impact of preexisting conduction disturbances, depth of implantation, oversizing, and amount of calcification on PPMI in 216 patients with severe symptomatic aortic stenosis underdoing Lotus valve implantation. RESULTS: PPMI was required in 39.8% of patients. Patients with need for PPMI compared with patients without need for PPMI had more often the following criteria: male gender (P=.035); preprocedural right bundle-branch block (RBBB) (16.3% vs 0, P<.001); atrioventricular (AV) block first degree (26.7% vs 10.1%, P=.004); higher calcium volume of the left coronary cusp (63.1±87.5 mm3 vs 42.8±49.3 mm3, P=.05); and deeper valve implantation at right coronary (P=.011), noncoronary (P=.026), and left coronary (P=.012) position. Oversizing in relation to annulus and left ventricular outflow tract did not have an impact on need for PPMI. By multiple regression analysis, preprocedural AV block first degree (P=.005), RBBB (P<.001), and depth of implantation (P=.006) were independent risk factors for need of PPMI. CONCLUSIONS: In patients with severe aortic stenosis receiving transfemoral Lotus valve, preexisting AV block first degree, RBBB, and implantation depth are independent predictors of PPMI, highlighting the importance of careful valve positioning.

In vivo characterization of human myofibrillar myopathy genes in zebrafish.

Myofibrillar myopathies (MFM) are progressive diseases of human heart and skeletal muscle with a severe impact on life quality and expectancy of affected patients. Although recently several disease genes for myofibrillar myopathies could be identified, today most genetic causes and particularly the associated mechanisms and signaling events that lead from the mutation to the disease phenotype are still mostly unknown. To assess whether the zebrafish is a suitable model system to validate MFM candidate genes using targeted antisense-mediated knock-down strategies, we here specifically inactivated known human MFM disease genes and evaluated the resulting muscular and cardiac phenotypes functionally and structurally. Consistently, targeted ablation of MFM genes in zebrafish led to compromised skeletal muscle function mostly due to myofibrillar degeneration as well as severe heart failure. Similar to what was shown in MFM patients, MFM gene-deficient zebrafish showed pronounced gene-specific phenotypic and structural differences. In summary, our results indicate that the zebrafish is a suitable model to functionally and structurally evaluate novel MFM disease genes in vivo.

Loss of dihydrolipoyl succinyltransferase (DLST) leads to reduced resting heart rate in the zebrafish.

The genetic underpinnings of heart rate regulation are only poorly understood. In search for genetic regulators of cardiac pacemaker activity, we isolated in a large-scale mutagenesis screen the embryonic lethal, recessive zebrafish mutant schneckentempo (ste). Homozygous ste mutants exhibit a severely reduced resting heart rate with normal atrio-ventricular conduction and contractile function. External electrical pacing reveals that defective excitation generation in cardiac pacemaker cells underlies bradycardia in ste (-/-) mutants. By positional cloning and gene knock-down analysis we find that loss of dihydrolipoyl succinyltransferase (DLST) function causes the ste phenotype. The mitochondrial enzyme DLST is an essential player in the citric acid cycle that warrants proper adenosine-tri-phosphate (ATP) production. Accordingly, ATP levels are significantly diminished in ste (-/-) mutant embryos, suggesting that limited energy supply accounts for reduced cardiac pacemaker activity in ste (-/-) mutants. We demonstrate here for the first time that the mitochondrial enzyme DLST plays an essential role in the modulation of the vertebrate heart rate by controlling ATP production in the heart.

Valve unit instead of intensive or intermediate care unit admission following transcatheter edge-to-edge mitral valve repair is safe and reduces postprocedural complications.

BACKGROUND: Transcatheter edge-to-edge mitral valve repair (M-TEER) is often performed in general anesthesia, and postprocedural monitoring is usually warranted on an intensive or intermediate care unit (ICU/IMC). We evaluated the implications of a dedicated valve unit (VU) instead of an ICU/IMC for monitoring after M-TEER. METHODS AND RESULTS: In total, 624 patients were retrospectively analyzed. A total of 312 patients were primarily transferred to either ICU or IMC following M-TEER, and 312 patients were scheduled for the VU in the absence of indications for ICU/IMC treatment. Hospital stay was significantly shorter in VU patients (median 6.0 days (interquartile range (IQR) 5.0 - 8.0) vs. 7.0 days (IQR 6.0 - 10.0), p < 0.001) and their risk for infections (2.9 vs. 7.7%, p = 0.008) and delirium (0.6 vs. 2.6%, p = 0.056) was substantially lower compared to ICU/IMC patients. In-hospital mortality was similar in both groups (0.6% vs. 1.3%, p = 0.41). Fifty patients (16.0%) in the VU group had to cross over to unplanned ICU/IMC admission. The most frequent indication was prolonged need for catecholamines (52.0%). Patients with ICU/IMC crossover had more advanced stages of heart failure (LV-EF < 30% in 36.0 vs. 16.0%, p = 0.001; severe concomitant tricuspid regurgitation in 48.0 vs. 27.8%, p = 0.005) and an LV-EF < 30% was independently associated with unplanned ICU/IMC admission. CONCLUSIONS: Following M-TEER postprocedural monitoring on a VU instead of an ICU/IMC is safe, reduces complications, and spares ICU capacities. Patients with advanced heart failure have a higher risk for unplanned ICU/IMC treatment after M-TEER.