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.).

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.

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.

The effect of a smaller spacer in the PASCAL Ace on residual mitral valve orifice area.

BACKGROUND: Mitral transcatheter edge-to-edge repair (M-TEER) is an established treatment for functional mitral regurgitation (FMR) associated with a risk of creating iatrogenic stenosis. OBJECTIVES: To investigate the impact of the P10 and its larger spacer compared to the narrower Ace and its smaller spacer on reduction of mitral valve orifice area (MVOA) during M-TEER. METHODS: Consecutive patients undergoing M-TEER for treatment of severe FMR were screened retrospectively. Patients with a single PASCAL device implantation within the central segments of the MV leaflets, non-complex anatomy, and baseline MVOA ≥ 3.5cm2 were selected. Intraprocedural transesophageal echocardiography was used to compare MVOA reduction with 3D multiplanar reconstruction and direct planimetry. Device selection did not follow a prespecified MVOA threshold. RESULTS: Seventy-two patients (81.0 years, IQR {74.3-85.0}) were included. In 32 patients, the P10 was implanted (44.4%). MR severity (p = 0.66), MR reduction (p = 0.73), and body surface area (p = 0.56) were comparable. Baseline MVOA tended to be smaller in P10 patients with the larger spacer (5.0 ± 1.1 vs. 5.4 ± 1.3cm2, p = 0.18), however, residual MVOA was larger in these patients (2.7 ± 0.7 vs. 2.3 ± 0.6cm2, p = 0.03). Accordingly, relative MVOA reduction was significantly less in P10 patients (- 45.9 ± 7.6 vs. - 56.3 ± 7.0%, p < 0.01). Indirect annuloplasty was more pronounced in Ace patients whereas mean transmitral gradients were similar. CONCLUSION: In FMR patients with non-complex anatomy, the larger spacer of the P10 maintains greater MVOA with similar MR reduction. Hence, the use of the PASCAL Ace device in patients with small MVOAs might correlate with a risk of both clinically relevant orifice reduction and even iatrogenic stenosis.

Long-Term Mortality after Transcatheter Edge-to-Edge Mitral Valve Repair Significantly Decreased over the Last Decade: Comparison between Initial and Current Experience from the MiTra Ulm Registry.

(1) Objective: We aimed to assess whether the candidate profile, the long-term outcomes and the predictors for long-term mortality after transcatheter edge-to-edge mitral valve repair (M-TEER) have changed over the last decade; (2) Methods: Long-term follow-up data (median time of 1202 days) including mortality, MACCE and functional status were available for 677 consecutive patients enrolled in the prospective MiTra Ulm registry from January 2010 to April 2019. The initial 340 patients treated in our institution before January 2016 were compared with the following 337 patients; (3) Results: Patients treated after 2016 showed significantly less ventricular dilatation (left ventricular end-systolic diameter of 43 ± 13 mm vs. 49 ± 16 mm, p < 0.007), lower systolic pulmonary pressures (50 ± 15 mmHg vs. 57 ± 21 mmHg, p = 0.01) and a lower prevalence of severe tricuspid regurgitation (27.2% vs. 47.3%, p < 0.001) at baseline than patients treated before 2016. Compared to the cohort treated before 2016, patients treated afterwards showed a significantly lower all-cause 3-year mortality (29.4% vs. 43.8%, p < 0.001) and lower MACCE (38.6% vs. 54.1%, p < 0.001), without differences for MR etiology. While severe tricuspid regurgitation and NYHA class IV remained independently associated with an increased long-term mortality over the last decade, severe left ventricular dilatation (hazard ratio, HR 2.12, p = 0.047) and severe pulmonary hypertension (HR 2.18, p = 0.047) were predictors of long-term mortality only in patients treated before 2016. (4) Conclusions: The M-TEER candidates are currently treated earlier in the course of disease and benefit significantly in terms of a better long-term survival than patients treated at the beginning of the M-TEER era.

Impact of heart failure hospitalizations on clinical outcomes after mitral transcatheter edge-to-edge repair: Results from the EXPAND study.

AIM: This analysis aimed to compare the clinical outcomes associated with heart failure (HF) readmissions and to identify associations with HF hospitalizations (HFH) in patients treated with the MitraClip™ NTR/XTR System in the EXPAND study. METHODS AND RESULTS: The global, real-world EXPAND study enrolled 1041 patients with primary or secondary mitral regurgitation (MR) treated with the MitraClip NTR/XTR System. Echocardiograms were analysed by an independent echocardiographic core laboratory. The study population was stratified into HFH and No-HFH groups based on the occurrence of HFH 1 year post-index procedure. Clinical outcomes including MR severity, New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, and all-cause mortality were compared (HFH: n = 181; No-HFH: n = 860). Both groups achieved consistent 1-year MR reduction to ≤1+ (HFH vs. No-HFH: 87.3% vs. 89.5%, p = 0.6) and significant 1-year improvement in KCCQ scores (+16.5 vs. +22.3, p = 0.09) and NYHA functional class. However, more patients in the No-HFH group had 1-year NYHA class ≤II (HFH vs. No-HFH: 67.9% vs. 81.9%, p < 0.01). All-cause mortality at 1 year was 36.8% in the HFH group versus 10.4% in the No-HFH group (p < 0.001). The HFH rate decreased by 63% at 1 year post-M-TEER versus 1 year pre-treatment (relative risk 0.4, p < 0.001). Independent HFH associations were MR ≥2+ at discharge, HFH 1 year prior to treatment, baseline NYHA class ≥III, baseline tricuspid regurgitation ≥2+, and baseline left ventricular ejection fraction ≤40%. CONCLUSIONS: This study reports the impact of HFH on clinical outcomes post-treatment in the EXPAND study. Results demonstrate that the occurrence of HFH was associated with worse 1-year survival, and treatment with the MitraClip system substantially reduced HFH and improved patient symptoms and quality of life.