Re-do MitraClip in patients with functional mitral valve regurgitation and advanced heart failure.

AIM: Percutaneous mitral valve repair (PMVR) via MitraClip implantation is a therapeutic option for severe mitral regurgitation (MR) in advanced stages of heart failure (HF). However, progressive left ventricular dilation in these patients may lead to recurrent MR after PMVR and consequent re-do MitraClip implantation. Here, we describe the characteristics and outcomes of this clinical scenario. METHODS AND RESULTS: Patients with systolic HF and functional MR undergoing a re-do MitraClip procedure were retrospectively analysed. Inclusion criteria were age ≥18 years, technical, device and procedural success at first MitraClip procedure, functional MR and systolic HF with an ejection fraction (EF) of <45%. Seventeen out of 684 patients undergoing PMVR with the MitraClip device at our institution between September 2009 and July 2019 were included. All patients displayed advanced HF with an EF of 20% (±9.9) and highly elevated N-terminal pro-brain natriuretic peptide. Technical success of the re-do MitraClip procedure was 100%, whereas procedural and device success were only achieved in 11 patients (65%). Unsuccessful re-do procedures were related to lower EF and implantation of more than one clip at initial procedure. However, despite reduction in MR grade and no occurrence of significant mitral stenosis after the procedure, the mortality during 12 months follow-up remained high (8 of 17; 47%). CONCLUSIONS: In a cohort of patients with advanced HF undergoing PMVR, re-do MitraClip procedure was feasible, but procedural success was unsatisfactory and morbidity and mortality remained high, possibly reflecting the advanced stage of HF in these patients.

Are Sutureless and Rapid-Deployment Aortic Valves a Serious Alternative to TA-TAVI? A Matched-Pairs Analysis.

BACKGROUND: Transcatheter aortic valve implantation is a feasible alternative to conventional aortic valve replacement with expanding indication extending to low-risk patients. Sutureless and rapid-deployment aortic valves were developed to decrease procedural risks in conventional treatment. This paired-match analysis aims to compare patients undergoing surgical transcatheter aortic valve implantation to sutureless and rapid-deployment aortic valve implantation. METHODS: Retrospective database analysis between 2010 and 2016 revealed 214 patients undergoing transcatheter aortic valve implantation procedures through surgical access (predominantly transapical) and 62 sutureless and rapid-deployment aortic valve procedures including 26 patients in need of concomitant coronary artery bypass surgery. After matching, 52 pairs of patients were included and analyzed. RESULTS: In-hospital death (5.8% vs. 3.8%; p = 0.308) was comparable between transcatheter aortic valve implantation (mean age 77 ± 4.3 years) and sutureless and rapid-deployment aortic valve implantation groups (mean age 75 ± 4.0 years), including 32 females in each group. The logistic EuroSCORE was similar (19 ± 12 vs. 17 ± 10; p = 0.257). Postoperative renal failure (p = 0.087) and cerebrovascular accidents (p = 0.315) were without significant difference. The incidence of complete heart block requiring permanent pacemaker treatment was relatively low for both groups (1.9% vs. 7.7%; p = 0.169) for TAVI and sutureless and rapid-deployment valves respectively. Intraoperative use of blood transfusion was higher in the sutureless and rapid-deployment aortic valve implantation group (0.72 U vs. 1.46 U, p = 0.014). Estimated survival calculated no significant difference between both groups after 6 months (transcatheter aortic valve implantation: 74 ± 8% vs. sutureless and rapid-deployment aortic valve implantation: 92 ± 5%; log rank p = 0.097). CONCLUSION: Since sutureless and rapid-deployment aortic valve implantation is as safe and effective as transapical transcatheter aortic valve implantation, combining the advantage of standard diseased-valve removal with shorter procedural times, sutureless and rapid-deployment aortic valve replacement may be considered as an alternative for patients with elevated operative risk considered to be in the "gray zone" between transcatheter aortic valve implantation and conventional surgery, especially if concomitant myocardial revascularization is required.

Percutaneous mitral valve repair in recurrent severe mitral valve regurgitation after mitral annuloplasty : MitraClip-in-the-ring as a complementary strategy.

BACKGROUND: Patients with reduced left ventricular (LV) function undergoing coronary artery bypass graft surgery or/and aortic valve replacement occasionally show severe mitral valve (MV) regurgitation and thus also undergo surgical mitral annuloplasty. Over time, further deterioration of LV function and additional ischemic events cause recurrence of severe MV regurgitation due to the Carpentier IIIb morphology of the MV that is not adequately addressed by the previously implanted annuloplasty ring. METHODS: Seven patients (Society of Thoracic Surgeons score: 7.5 ± 1.5%) with Carpentier type-IIIb recurrent severe MV regurgitation, having undergone prior cardiothoracic surgery (median: 40 months) including mitral annuloplasty, were treated with the MitraClip device. RESULTS: MitraClip implantation resulted in significantly reduced MV regurgitation and improved New York Heart Association functional state, translating into an increased exercise capability and improved cardiac biomarkers. The morphology of the MV was adequately addressed without causing relevant MV stenosis, while the MV annulus area remained unaltered. The procedure was safe with a 30-day mortality rate of 0%. CONCLUSION: MitraClip-in-the-ring is feasible and in principle safe for treating Carpentier type IIIb severe MV regurgitation after surgical MV repair using mitral annuloplasty. MitraClip-in-the-ring resulted in immediate amelioration of clinical symptoms and increased physical exercise capacity.

Initial experience with percutaneous mitral valve repair in patients with cardiac amyloidosis.

BACKGROUND: Percutaneous mitral valve repair (PMVR) is a therapeutic option for severe mitral regurgitation (MR) in patients with heart failure due to differential aetiologies. However, only little is known about the safety and efficacy of this procedure in patients with amyloid cardiomyopathy. METHODS: Five patients with cardiac amyloidosis and moderate to severe or severe MR undergoing PMVR were analysed retrospectively and compared to seven patients with cardiac amyloidosis and severe MR without intervention. Clinical and functional data, renal function and cardiac biomarkers as well as established risk scores for cardiac amyloidosis were assessed. Primary endpoint was the reduction in MR one year after PMVR. Secondary endpoints were safety, overall mortality after 12 months compared with the control group, as well as changes in clinical and functional parameters. RESULTS: Amyloidosis risk assessment documented amyloid cardiomyopathy at an advanced stage in all patients. Procedural, technical and device success of PMVR were all 100% and residual MR remained mild to moderate at 12 months follow-up (P = .038 vs before PMVR). Differences in survival compared with the control (no PMVR) group pointed to a possible survival benefit in the PMVR group (P = .02). CONCLUSION: PMVR is a feasible and safe procedure in patients with cardiac amyloidosis and might carry a possible survival benefit in this patient group.

Left atrial appendage closure in patients with chronic kidney disease: results from the German multicentre LAARGE registry.

OBJECTIVES: Chronic kidney disease (CKD) is associated with an increased complication rate after cardiac interventions. Although CKD has a high prevalence among atrial fibrillation patients, the impact of CKD on periprocedural complications and the outcome after an interventional left atrial appendage closure (LAAC) is unclear. The present study, therefore, aimed to investigate whether CKD influences the procedure's effectiveness and safety. METHODS: LAARGE is a prospective, non-randomised registry. LAAC was conducted with different standard commercial devices, and the follow-up period was one year. CKD was defined by an eGFR < 60 mL/min/1.73 m2, and subgroups were further analysed (i.e. eGFR < 15, 15-29, and 30-59 mL/min/1.73 m2, respectively). RESULTS: Two hundred ninety-nine of 623 patients (48.0%) revealed a CKD. The prevalence of cardiovascular comorbidity, CHA2DS2-VASc score (4.9 vs. 4.2), and HAS-BLED score (4.3 vs. 3.5) was significantly higher in CKD patients (each p < 0.001). Implantation success was similarly high across all GFR groups (97.9%). Periprocedural MACCE (0.7 vs. 0.3%), and other major complications (4.7 vs. 3.7%) were comparably infrequent. Survival free of stroke was significantly lower among CKD patients within 1 year (82.0 vs. 93.0%; p < 0.001; consistent after adjustment for confounding factors), without significant accentuation in advanced CKD (i.e. eGFR < 30 mL/min/1.73 m2; p > 0.05 vs. eGFR 30-59 mL/min/1.73 m2). Non-fatal strokes were absolutely infrequent during follow-up (0 vs. 1.1%). Severe non-fatal bleedings were observed only among CKD patients (1.4 vs. 0%; p = 0.021). CONCLUSIONS: Despite an increased cardiovascular risk profile of CKD patients, device implantation was safe, and LAAC was associated with effective stroke prevention across all CKD stages.

Broken Heartstrings-Post-Traumatic Stress Disorder and Psychological Burden after Acute Mitral Regurgitation Due to Chordae Tendineae Rupture.

Chordae tendineae rupture (CTR) is a potentially life-threatening cardiac event often resulting in Acute mitral regurgitation (AMR). We assessed Post-traumatic stress disorder (PTSD), depression, and anxiety symptoms in n=21 CTR patients with AMR (age 82.3 ± 4.2 years; 66.7% men) and compared them to n=23 CTR patients with Chronic mitral regurgitation (CMR) and n=35 Myocardial infraction (MI) patients. Regression analyses revealed that PTSD scores were significantly higher in CTR patients with AMR than in CTR patients with CMR or MI patients. CTR patients with CMR had the lowest levels of PTSD-symptoms. Depression and anxiety scores were elevated across all three groups. Our results suggest that psychosocial factors need to be considered in CTR patients' care.

MitraClip implantation followed by insertion of a left ventricular assist device in patients with advanced heart failure.

AIMS: Mitral valve regurgitation (MR) is common in patients with advanced heart failure (HF). Percutaneous mitral valve repair (PMVR) via MitraClip (MC) has emerged as a feasible treatment strategy for these high-risk patients. However, as HF often further progresses, there is a frequent need for left ventricular assist device (LVAD) implantation in these patients. We aimed to investigate whether prior MC implantation affects the subsequent LVAD implantation and outcome. METHODS AND RESULTS: Thirty-seven patients with advanced HF and significant MR who underwent LVAD implantation were retrospectively analysed. Follow-up data were collected at 1 year after LVAD implantation. Primary endpoint was all-cause mortality. Secondary endpoint included peri-operative parameters and clinical development depicted as New York Heart Association (NYHA) class and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) level. Seventeen patients initially received a MC device (MC group), resulting in a significant reduction in MR grade. After MC, NYHA class and INTERMACS level further worsened, leading to subsequent LVAD implantation after a median time of 475 days in the MC group. At LVAD implantation, overall characteristics were comparable with those of the patients undergoing LVAD implantation without prior MC placement (no-MC group). Procedural data revealed a higher incidence of right ventricular (RV) failure needing mechanical RV assistance and a longer need for nitric oxide ventilation in the MC group after LVAD implantation. One-year survival was slightly better in the no-MC group compared with the MC group [41% (n = 7/17) vs. 65% (n = 13/20); P = 0.15], albeit event-free survival was comparable between both groups, MC and no-MC. CONCLUSIONS: LVAD implantation after MC is feasible and safe. However, in patients with advanced HF and severe MR, PMVR may only delay a needed LVAD implantation and thereby lead to poorer peri-operative RV function and impaired outcome. Arguably, these patients might benefit from the timely management of advanced HF by the means of early LVAD implantation or heart transplantation.

Comparison in Patients < 75 Years of Age - Versus - Those > 75 Years on One-year-Events With Atrial Fibrillation and Left Atrial Appendage Occluder (From the Prospective Multicenter German LAARGE Registry).

Left atrial appendage closure (LAAC) is an alternative to oral anticoagulation therapy in patients with non-valvular atrial fibrillation for the prevention of embolic stroke and systemic embolism. Although elderly patients (>75 years) have both higher ischemic and bleeding risk as compared with younger patients, they benefit from optimal anticoagulation. The subanalysis aimed to assess the indications, the safety, efficacy, and 1-year outcomes of interventional LAAC in elderly patients (≥ 75 years) compared with younger (< 75 years) patients in clinical practice. We analyzed data from the prospective Left-Atrium-Appendage Occluder Registry Germany. A total of 638 patients were included in the registry, 402 (63%) were aged ≥ 75 years. Compared with younger subjects, patients aged ≥75 were more likely to have higher CHA2DS2-VASC and HAS-BLED scores. Procedural success rate was high und similar in both groups (97.6%). Periprocedural adverse events were not statistically significant in groups (11.9% in <75 years vs 12.9% in ≥75 years; p = 0.80). At 1 year follow-up, all-cause mortality was higher in patients aged ≥75 compared withwith younger group (13.0% vs 7.8 %,p = 0.04), mainly due to non-cardiovascular causes (10.6% vs 6.0%). No significant differences in major bleeding, stroke, systemic embolism were observed. In conclusion, LAAC is feasible and safe in patients with AF at high stroke risk and with contraindications for OAC and should be considered as candidates for LAA closure. Elderly patients often present these characteristics and could benefit from this novel therapy.

Identification of patients at higher risk for myocardial injury following elective coronary artery intervention.

OBJECTIVES: To evaluate myocardial injury and infarction (MI) following elective percutaneous coronary intervention (PCI). BACKGROUND: The substantially higher analytical power of high-sensitivity troponin (hsTn) assays allows detection of minor cardiac troponin (cTn) levels, which may be useful in monitoring myocardial injury and guiding therapies. METHODS: Serial hsTnT measurements were conducted in patients undergoing elective PCI and were related to the extent of coronary artery disease (CAD) as reflected by the SYNTAX score risk categories and American College of Cardiology/American Heart Association classification of coronary lesions. Myocardial injury and MI were diagnosed according to the second and third versions of universal MI definition. RESULTS: The study population consisted of 530 patients, who were grouped into low (41.3%), intermediate (35.4%), and high (23.3%) SYNTAX risk categories. The treated coronary lesions were classified into A 7.8%, B1 24.1%, B2 21.1%, C1 24.6%, and C2 22.4%. Postprocedural hsTnT increases correlated significantly with the complexity of treated coronary lesions (p < .05) and CAD magnitude (p < .05). Rates of MI type 4a according to the second and third MI definition criteria were 98 (27.5%) and 15 (4.2%) cases in patients with normal baseline hsTnT values (N = 357, 67.4%), as well as 137 (79.2%) and 27 (15.6%) cases in those with elevated baseline hsTnT values (N = 173, 32.6%), respectively. CONCLUSIONS: After elective PCI, cTn releases correlate significantly with lesion complexity and CAD extent. Use of hsTnT assay enables precise monitoring of PCI-related myocardial injury and may identify patients at higher risk for ischemic events, who may benefit from potent platelet inhibition, which needs to be investigated in randomized trials.

Temporary oral anticoagulation after MitraClip - a strategy to lower the incidence of post-procedural stroke?

Background: Incidence of stroke within 30 days after percutaneous mitral valve repair using the MitraClip varies from 0.7% and 2.6% between registries. Standard medical treatment after the MitraClip procedure, in the absence of risk factors requiring antithrombotic therapy such as atrial fibrillation, is dual antiplatelet therapy using aspirin and clopidogrel. ESC/EACTS and ACC/AHA surgical guidelines show a Class IIa indication for temporary antithrombotic therapy after mitral valve repair/bioprosthetic valve replacement within the first three months even in patients with no additional risk factors.Methods: 470 patients were treated with the MitraClip receiving oral anticoagulation (Coumadin: INR 2.0-3.0) instead of dual antiplatelet therapy for at least 30 days after the procedure. The incidence of stroke, as well as major adverse events such as bleeding, were analysed in comparison to large registries and multi-centre studies.Results: Incidence of stroke within 30 days was significantly reduced as compared to comparative cohorts (0.2% vs. Median 1.3% [0.7-2.6%]; p < .05). Cardiovascular risk factors such as age, atrial fibrillation, hypertension, diabetes, STS score and prior stroke did not differ significantly between cohorts (ns). Bleeding complications were not increased due to 30 days oral anticoagulation treatment (4.6% vs. Median 7.4% [3.4-13.6%]; ns).Conclusions: Temporary oral anticoagulation might be a strategy to reduce the incidence of stroke within the first 30 days after the MitraClip procedure. Bleeding events were not significantly altered due to temporary oral anticoagulation.

Comprehensive cardiac phenotyping in large animals: comparison of pressure-volume analysis and cardiac magnetic resonance imaging in pig post-myocardial infarction systolic heart failure.

Large animal ischemic cardiomyopathy models are widely used for preclinical testing of promising novel therapeutic approaches. Pressure volume (PV) loop analysis and cardiac magnetic resonance imaging (CMRI) allow functional and morphological phenotyping. In this study we performed a comparative analysis of both methods highlighting the strength of each and their synergistic potential. Myocardial infarction (MI) was created in German farm pigs (German Landrace) by 2 h LCX occlusion (n = 11) and subsequent reperfusion. Cardiac function was assessed by PV-loops and CMRI 56 and 112 days post-MI. Two hours occlusion of the LCX led to mid-size left ventricular (LV) MI represented by high-sensitive troponin T (hsTnT) 3 days post-MI, correlating well with cardiac CMRI late enhancement. CMRI determined end-diastolic and end-systolic volumes significantly increased post-MI, while ejection fraction was reduced in infarcted animals compared to the sham group (n = 6). PV-loop derived preload-insensitive parameters of systolic and diastolic function were diminished post-MI compared to sham animals while preload-dependent parameters only deteriorated in advanced HF. PV-loop analysis significantly correlates with CMRI analysis of cardiac function in pig post-MI ischemic cardiomyopathy. PV-Loop analysis accurately quantifies LV volumetry and function in post-MI HF, and thus eccentric LV morphology. PV-loop analysis correlates well to cardiac MRI. Preload-insensitive parameters show high sensitivity to quantify HF while preload-sensitive parameters are not able to quantify early-stages of LV HF.

Effects of MitraClip on cognitive and psychological function in heart failure patients: the sicker the better.

PURPOSE: Cognitive impairment and reduced quality of life is a common condition in patients with heart failure (HF). Percutaneous mitral valve repair using (PMVR) MitraClip (MC) has emerged as a promising interventional tool, reducing all-cause mortality and hospitalization as well as increasing cognitive functioning and quality of life. However, the benefit of HF patients with severely depressed cognitive functioning remains unknown. METHODS: We assessed cognitive functioning (figural memory-FGT, executive function-TOL, TMT B), psychosocial functioning (depression-PHQ-9, quality of life-SF36), and clinical parameters (echocardiography, 6-min walk test distance, and cardiac biomarkers) 1 day before (t0) and 6 weeks after (t1) MC intervention in HF patients (n = 40). First, paired sample t tests were conducted to uncover improvements in cognitive functioning post-MC intervention. Second, the COGBAT Norm-sample, a representative age-matched healthy sample, was used to compare participants' individual scores. Third, bivariate linear regressions were calculated for all key predictors of the detected improvements in cognitive functioning post-MC intervention (t1-t0). RESULTS: Following the MC intervention, we found significant improvements in figural memory, executive functioning, and psychosocial functioning. Most of the patients with depressed executive functioning before the MC intervention showed post-intervention test scores within the normal range (> 50th percentile; t0 22.5% vs. t1 60%) as compared to the normative COGBAT sample. Regression analyses revealed that lower baseline scores in planning ability before the MC intervention (t0) were associated with greater planning ability (TOL; B = - 0.78, 95% CI - 1.04 to - 0.53), figural memory (FGT; B = - 0.26, 95% CI - 0.44 to - 0.07), and cognitive flexibility (TMT B; B = - 0.36, 95% CI - 0.50 to - 0.23) improvement post-MC intervention (t1-t0). Psychosocial functioning and age were not associated with these improvements. CONCLUSIONS: Patients with depressed executive functioning showed the greatest benefit from the MC intervention regarding cognitive functioning. Age and psychological functioning seem less important for cognitive performance improvements post-MC intervention. Hence, severely depressed cognitive functioning in patients is not a contraindication for PMVR using MitraClip.

Invasive hemodynamics and cardiac biomarkers to predict outcomes after percutaneous edge-to-edge mitral valve repair in patients with severe heart failure.

BACKGROUND: Percutaneous mitral valve repair (PMVR) via MitraClip implantation is a therapeutic option for high-risk or non-surgical candidates with severe mitral regurgitation (MR) and advanced stages of heart failure (HF). However, these patients have a high mortality despite PMVR, and predictors for outcomes are not well established. Here, we evaluated invasive hemodynamics, echocardiography parameters, and biomarkers to predict outcomes after PMVR in severe HF patients. METHODS: Patients with reduced ejection fraction (EF) and severe and moderate-to-severe MR undergoing PMVR at our centre between September 2009 and January 2016 were analysed retrospectively. Inclusion criteria were: left ventricular EF < 45%, preoperative right heart catheterization, successful MitraClip deployment ("technical success"), and follow-up for at least 1 year after the procedure. Data from preoperative right heart catheterization, echocardiography, and biomarkers were assessed. Primary endpoint was all-cause mortality at 1 year after PMVR. We performed univariate and multivariate Cox regression analyses and generated a risk score to predict outcomes. RESULTS: Of 174 patients with PMVR and severe HF, 79.9% had functional MR. Mean EF was 25% (17.2; 30.7) and advanced New York Heart Association functional class was prevalent (class II: 13%; class III: 70%; and class IV: 17%). The cumulative incidences of all-cause death were 6.9% and 17.8% at 30 days and 1 year, respectively. In the Cox multivariate model, high-sensitive troponin T [hsTnT; hazard ratio (HR) 1.01; confidence interval (CI) 1.01-1.02; p < 0.0001] and mixed venous O2-saturation (HR 0.92; CI 0.89-0.96; p < 0.0001) were found to significantly and independently predict outcomes. A simple risk score including these two parameters was sufficient to discriminate between low- and high-risk patients (HR 7.22; CI 3.4-15.5; p < 0.001). CONCLUSION: In a cohort of patients with severe HF undergoing PMVR, patients with elevated hsTnT and reduced mixed venous O2-saturation carried the worst prognosis. A simple risk score including these two parameters may improve patient selection and outcomes after PMVR.

The need for dedicated advanced heart failure units to optimize heart failure care: impact of optimized advanced heart failure unit care on heart transplant outcome in high-risk patients.

AIM: With an increasing prevalence of heart failure (HF), more patients with advanced disease have to be treated in cardiology units by sophisticated medical and interventional strategies. We therefore developed a dedicated advanced heart failure unit (AHFU) to target the specific needs of the many patients with advanced HF. We here present our concept and its impact on outcome in high-risk high-urgency (HU) heart transplant candidates. METHODS AND RESULTS: The eight-bed unit was established as an extension of the cardiologic intensive care and coronary care units in an intermediate care setting. Each bed was equipped with 24 h haemodynamic, respiratory, and arrhythmia monitoring. The unit is served 24/7 by five residents in cardiology, one staff cardiologist specializing in medical and interventional HF care, and 10 intensive care nurses. The cardiology team is supported by colleagues from cardiac surgery, sports medicine, psychosomatics, and the internal medicine departments. As an example of the intensified care on the AHFU, data from the cohorts of patients undergoing heart transplantation from HU status before (pre-AHFU 2008-11) and after establishment of the AHFU (AHFU 2012-15) were analysed. Interestingly, mortality on HU waiting list and post-heart transplant survival was comparable in both cohorts, despite significant increase in morbidity and co-morbidity as assessed by the Index for Mortality Prediction After Cardiac Transplantation model in the AHFU group. CONCLUSIONS: Our AHFU provides a unique and novel setting for the integration of modern pharmacological, interventional, surgical, and supportive HF therapy embedded in an academic heart centre. This may be a major step forward in the care of critical patients with advanced HF.

Haemodynamic effects of percutaneous mitral valve edge-to-edge repair in patients with end-stage heart failure awaiting heart transplantation.

AIMS: Functional mitral regurgitation is complicating end-stage heart failure and potential heart transplantation by increasing pulmonary artery pressures. The aim of the present study was to investigate feasibility and haemodynamic effects of percutaneous mitral valve edge-to-edge repair using the MitraClip™ device in patients with end-stage heart failure awaiting heart transplantation. METHODS AND RESULTS: In this retrospective study, we identified nine patients suffering from end-stage heart failure listed for heart transplantation in whom moderate-severe or severe functional mitral regurgitation was recognized and treated with percutaneous mitral valve edge-to-edge repair. Twenty-two patients listed for heart transplantation and presenting with moderate-severe or severe functional mitral regurgitation treated in the pre-MitraClip™ era served as controls. Patients were analysed at two separate time points: MitraClip™ group: pre-procedure and post-procedure (follow-up: 215 ± 53 days) and control group: study entry with recognition of moderate-severe or severe functional mitral regurgitation (follow-up: 197 ± 47 days). Percutaneous mitral valve edge-to-edge repair with the MitraClip™ was feasible and safe in our high-risk end-stage heart failure population. The intervention resulted in significant reduction of mitral regurgitation (grade 3.0 [0.5] to 1.5 [0.5]; P = 0.009), left atrial diameter (51 mm [16] to 49 mm [4]; follow-up MitraClip™ vs. control group P = 0.0497), pulmonary artery pressures (sPA 50 mmHg [15] to 45 mmHg [10]; P = 0.02; mPA 34 mmHg [8] to 30 mmHg [10]; P = 0.02), and New York Heart Association class (3.5 [1.0] to 3.0 [0.5]; P = 0.01) and improved mixed-venous oxygen saturation (57% [11] to 55% [7]; follow-up MitraClip™ vs. control group P = 0.02). No changes in the control group were observed. CONCLUSIONS: MitraClip™ implantation as 'bridge-to-transplant' strategy in patients with end-stage heart failure and severe functional mitral regurgitation awaiting heart transplantation is feasible and appears to result in favourable haemodynamic effects.

Percutaneous repair of mitral valve regurgitation in patients with severe heart failure: comparison with optimal medical treatment.

BACKGROUND: Occurrence of severe mitral valve (MV) regurgitation (MR) is an independent negative predictor of mortality in patients with severe systolic heart failure (HF). This study examines clinical effects and cardiac reverse remodelling in patients with severe systolic HF receiving percutaneous mitral valve repair (PMVR) using MitraClip in comparison to patients receiving optimal medical therapy only. METHODS: Between 2010 and 2014, 86 patients (Society of Thoracic Surgeons score: 10.5% ± 1.2%) with severe HF (left ventricular [LV] ejection fraction; LVEF: 25% ± 2%; LV endsystolic diameter [LVESD]: 55 ± 3 mm) and severe MR received PMVR using MitraClip. Cardiac reverse remodelling and clinical parameters were compared to HF patients with severe MR (from our HF outpatient clinic; n = 69; LVEF: 26% ± 1.4%; LVESD: 53 ± 2 mm) receiving optimal medical therapy (OMT) only. All patients received stable OMT and were characterised by echocardiography, 6-minwalk-distance test and cardiac biomarkers within a 24 months observation period. RESULTS: PMVR in patients with end-stage HF and severe MR resulted in reduction of MR and significant additional cardiac reverse remodelling (LVEF: 26 ± 1.4 vs. 33% ± 2%, p < .05; LVESD: 53 ± 2 vs. 47 ± 2 mm, p < .05) over the 24 months observation period as compared to pharmacologically-only managed comparators. CONCLUSIONS: Both OMT and PMVR cause cardiac reverse remodelling and relief of symptoms in patients with HF and severe MR. PMVR results in significant additional cardiac reverse remodelling compared to pharmacologically-only managed patients.

Percutaneous repair of severe mitral valve regurgitation secondary to chordae rupture in octogenarians using MitraClip.

OBJECTIVES: The aim of this study was to assess feasibility and clinical effectiveness of the MitraClip device in octogenarians suffering from severe mitral valve regurgitation due to chordae rupture. BACKGROUND: The MitraClip procedure is a suitable technique in high-risk surgical patients to achieve safe and effective percutaneous repair of mitral valve regurgitation. Octogenarians show cumulative risk and social aspects hindering mitral valve surgery. No data exists regarding the use of the MitraClip device in high-risk octogenarians suffering from mitral valve chordae rupture. METHODS: Between October 2009 and March 2017 98 high-risk octogenarians (society of thoracic surgeons score [STS]: 9.7% ± 0.8) with mitral valve prolapse and consecutively chordae rupture were treated with the MitraClip after interdisciplinary discussion. RESULTS: Successful mitral valve repair was achieved in 91% of the octogenarians. Repair of the mitral valve caused immediate and significant reduction of dyspnoea (NYHA class: 3.5 ± 0.4 vs 2.0 ± 0.3; P < 0.001), cardiac reverse remodeling (LVESD: 39 ± 0.8 vs 35 ± 0.8; P < 0.01) and amelioration of cardiac biomarkers (NTproBNP (4884 ± 52 ng/L vs 2473 ± 210 ng/L; P < 0.05,). Effects were stable over the 12 months observation period. None of our patients died intraprocedurally. CONCLUSIONS: Percutaneous repair of chordae rupture is feasible and safe in high-risk octogenarians. The MitraClip should be considered to repair severe mitral valve regurgitation due to mitral valve chordae rupture in high-risk octogenarians after interdisciplinary discussion even facing a challenging anatomy.

Feasibility and safety of vitamin K antagonist monotherapy in atrial fibrillation patients undergoing transcatheter aortic valve implantation.

AIMS: We aimed to assess the efficacy and safety of vitamin K antagonist (VKA) monotherapy in atrial fibrillation (AF) patients undergoing transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: In 735 TAVIs since 2008 we identified 167 patients suffering from concomitant AF who received either VKA monotherapy (n=77), VKA plus single antiplatelet therapy (SAPT, n=41) or a triple anticoagulation regimen (n=49). Thromboembolic as well as bleeding complications were analysed for six months after TAVI. Only one minor bleeding and no thromboembolic events occurred after VKA therapy had been initiated post TAVI. Compared to patients being treated with additional either single or dual antiplatelet therapy, the incidence of major/life-threatening bleeding complications was significantly lower in the VKA mono group (0/77 [VKA mono] vs. 3/41 [VKA+SAPT; p=0.04] vs. 4/49 [triple anticoagulation; p=0.02]). Analysis of a combined endpoint of post-procedural death, stroke, embolism and major bleeding revealed a significant superiority of VKA monotherapy compared to VKA plus SAPT or DAPT, respectively (5/77 vs. 9/41 [p=0.02] vs. 14/49 [p=0.002]). CONCLUSIONS: VKA therapy without additional antiplatelet treatment is effective and safe in AF patients undergoing TAVI.

The Effects of Mitral Valve Repair on Memory Performance, Executive Function, and Psychological Measures in Patients With Heart Failure.

OBJECTIVES: Heart failure (HF) is a prevalent disease that remains costly and associated with a high mortality rate. HF is also associated with poor neurocognitive functioning. For the treatment for HF patients with severe mitral regurgitation, the MitraClip device has emerged as a promising interventional tool that reduces the mitral valve leakage and thus increases cardiac output. Currently, there is only limited knowledge on changes in cognitive and psychosocial functioning before and after the MitraClip intervention. METHODS: Cognitive function (memory and executive function) and psychosocial measures (depression, anxiety, and quality of life) were assessed before and after the MitraClip intervention in 24 HF patients and 23 healthy participants (comparison group). RESULTS: MitraClip intervention in HF patients was followed by improvements in figural long-term memory (p = .003) and executive function (planning ability, p < .001) relative to the comparison group. In addition, the intervention resulted in a significant improvement in depression (p = .002), anxiety (p = .003) and quality of life scores (physical p = .017, mental p = .013) as well as improved 6-minute walk test results over time (p = .002). CONCLUSIONS: The presented data provide evidence of a significant improvement in memory and executive function as well as in depression, anxiety, and quality of life scores in patients with chronic HF after MitraClip intervention. Further research is needed to shed light on the long-term development of cognitive function, psychosocial well-being, and clinical parameters after MitraClip intervention and how these factors depend on one another.

S100A1 DNA-based Inotropic Therapy Protects Against Proarrhythmogenic Ryanodine Receptor 2 Dysfunction.

Restoring expression levels of the EF-hand calcium (Ca(2+)) sensor protein S100A1 has emerged as a key factor in reconstituting normal Ca(2+) handling in failing myocardium. Improved sarcoplasmic reticulum (SR) function with enhanced Ca(2+) resequestration appears critical for S100A1's cyclic adenosine monophosphate-independent inotropic effects but raises concerns about potential diastolic SR Ca(2+) leakage that might trigger fatal arrhythmias. This study shows for the first time a diminished interaction between S100A1 and ryanodine receptors (RyR2s) in experimental HF. Restoring this link in failing cardiomyocytes, engineered heart tissue and mouse hearts, respectively, by means of adenoviral and adeno-associated viral S100A1 cDNA delivery normalizes diastolic RyR2 function and protects against Ca(2+)- and ß-adrenergic receptor-triggered proarrhythmogenic SR Ca(2+) leakage in vitro and in vivo. S100A1 inhibits diastolic SR Ca(2+) leakage despite aberrant RyR2 phosphorylation via protein kinase A and calmodulin-dependent kinase II and stoichiometry with accessory modulators such as calmodulin, FKBP12.6 or sorcin. Our findings demonstrate that S100A1 is a regulator of diastolic RyR2 activity and beneficially modulates diastolic RyR2 dysfunction. S100A1 interaction with the RyR2 is sufficient to protect against basal and catecholamine-triggered arrhythmic SR Ca(2+) leak in HF, combining antiarrhythmic potency with chronic inotropic actions.