Multicenter comparison of transcatheter aortic valve implantation with the self-expanding ACURATE neo2 versus Evolut PRO transcatheter heart valves.

BACKGROUND: New-generation self-expanding transcatheter aortic heart valves (THV) were designed to overcome technical constraints of their preceding generations. We sought to compare the efficacy and safety of the self-expanding ACURATE neo2 (Neo2) versus Evolut PRO (PRO) devices. METHODS: Seven hundred nine patients undergoing transfemoral transcatheter aortic valve implantation (TAVI) with either Neo2 (n = 496) or PRO (n = 213) were included. Propensity score matching (PSM) was performed to account for differences in baseline characteristics. In-hospital and 30-day clinical outcomes were evaluated according to Valve Academic Research Consortium-3 criteria. RESULTS: Baseline characteristics were comparable between both groups after PSM (Neo2: n = 155, Evolut Pro: n = 155). Technical success rates were high in both groups (Neo2: 94.8% vs PRO: 97.4%; p = 0.239). Need for permanent pacemaker implantation was less frequent with Neo2 compared with PRO (7.5% vs 20.6%; p = 0.002), whereas major vascular complications were more frequent with Neo2 (Neo2: 11.6% vs PRO: 4.5%; p = 0.022). Intended valve performance at discharge was high in both groups without relevant differences among groups (Neo2: 97.4% vs. 95.3%; p = 0.328). CONCLUSIONS: Short-term outcomes after TAVI using latest-generation self-expanding THV were excellent, with overall low rates of adverse events. However, Neo2 was associated with lower pacemaker rates and reduced the prevalence of moderate-severe paravalvular leakage. Transprosthetic gradients after TAVI were higher with Neo2 compared with PRO.

Molecular Imaging of Myocardial Fibroblast Activation in Patients with Advanced Aortic Stenosis Before Transcatheter Aortic Valve Replacement: A Pilot Study.

Using multimodal imaging, we investigated the extent and functional correlates of myocardial fibroblast activation in patients with aortic stenosis (AS) scheduled for transcatheter aortic valve replacement (TAVR). AS may cause myocardial fibrosis, which is associated with disease progression and may limit response to TAVR. Novel radiopharmaceuticals identify upregulation of fibroblast activation protein (FAP) as a cellular substrate of cardiac profibrotic activity. Methods: Twenty-three AS patients underwent 68Ga-FAP inhibitor 46 (68Ga-FAPI) PET, cardiac MRI, and echocardiography within 1-3 d before TAVR. Imaging parameters were correlated and then were integrated with clinical and blood biomarkers. Control cohorts of subjects without a history of cardiac disease and with (n = 5) and without (n = 9) arterial hypertension were compared with matched AS subgroups. Results: Myocardial FAP volume varied significantly among AS subjects (range, 1.54-138 cm3, mean ± SD, 42.2 ± 35.6 cm3) and was significantly higher than in controls with (7.42 ± 8.56 cm3, P = 0.007) and without (2.90 ± 6.67 cm3; P < 0.001) hypertension. FAP volume correlated with N-terminal prohormone of brain natriuretic peptide (r = 0.58, P = 0.005), left ventricular ejection fraction (r = -0.58, P = 0.02), mass (r = 0.47, P = 0.03), and global longitudinal strain (r = 0.55, P = 0.01) but not with cardiac MRI T1 (spin-lattice relaxation time) and extracellular volume (P = not statistically significant). In-hospital improvement in left ventricular ejection fraction after TAVR correlated with pre-TAVR FAP volume (r = 0.440, P = 0.035), N-terminal prohormone of brain natriuretic peptide, and strain but not with other imaging parameters. Conclusion: FAP-targeted PET identifies varying degrees of left ventricular fibroblast activation in TAVR candidates with advanced AS. 68Ga-FAPI signal does not match other imaging parameters, generating the hypothesis that it may become useful as a tool for personalized selection of optimal TAVR candidates.

Impact of coronary artery disease on clinical outcomes after TAVR: Insights from the BRAVO-3 randomized trial.

OBJECTIVE: To determine the prognostic impact of coronary artery disease (CAD) in patients randomized to bivalirudin or unfractionated heparin (UFH) during transcatheter aortic valve replacement (TAVR). BACKGROUND: CAD is a common comorbidity among patients undergoing TAVR and studies provide conflicting data on its prognostic impact. METHODS: The Bivalirudin on Aortic Valve Intervention Outcomes-3 (BRAVO-3) randomized trial compared the use of bivalirudin versus UFH in 802 high-surgical risk patients undergoing transfemoral TAVR for severe symptomatic aortic stenosis. Patients were stratified according to the presence or absence of history of CAD as well as periprocedural anticoagulation. The coprimary endpoints were net adverse cardiac events (NACE; a composite of all-cause mortality, myocardial infarction, stroke, or major bleeding) and major Bleeding Academic Research Consortium (BARC) bleeding ≥3b at 30 days postprocedure. RESULTS: Among 801 patients, 437 (54.6%) had history of CAD of whom 223 (51.0%) received bivalirudin. There were no significant differences in NACE (adjusted odds ratio [OR]: 1.04; 95% confidence interval [CI]: 0.69-1.58) or BARC ≥ 3b bleeding (adjusted OR: 0.84; 95% CI: 0.51-1.39) in patients with vs without CAD at 30 days. Among CAD patients, periprocedural use of bivalirudin was associated with similar NACE (OR: 0.80; 95% CI: 0.47-1.35) and BARC ≥ 3b bleeding (OR: 0.64; 95% CI: 0.33-1.25) compared with UFH, irrespective of history of CAD (p-interaction = 0.959 for NACE; p-interaction = 0.479 for major bleeding). CONCLUSION: CAD was not associated with a higher short-term risk of NACE or major bleeding after TAVR. Periprocedural anticoagulation with bivalirudin did not show any advantage over UFH in patients with and without CAD.

Valve-Related Complications in TAVI Leading to Emergent Cardiac Surgery.

Transcatheter aortic valve implantation (TAVI) is now a standard procedure for the treatment of symptomatic aortic valve stenosis in many patients. In Germany, according to the annual reports from the German Institute for Quality Assurance and Transparency in Healthcare (Institut für Qualitätssicherung und Transparenz im Gesundheitswesen), the rate of serious intraprocedural complications, such as valve malpositioning or embolization, coronary obstruction, aortic dissection, annular rupture, pericardial tamponade, or severe aortic regurgitation requiring emergency cardiac surgery has decreased markedly in recent years from more than 5.5% in 2012 to 2.0% in 2019. However, with increased use, the total number of adverse events remains about 500 per year, about 100 of which require conversion to sternotomy. These, sometimes, fatal events can occur at any time and are still challenging. Therefore, the interdisciplinary TAVI heart team should be prepared and aware of possible rescue strategies.

Right Ventricular Function Improves Early After Percutaneous Mitral Valve Repair in Patients Suffering From Severe Mitral Regurgitation.

Background: Percutaneous mitral valve edge-to-edge procedure (PMVR) using the MitraClip® system (Abbot Vascular, CA) is an established therapy for severe mitral regurgitation (MR) in patients judged inoperable or at high surgical risk. Besides determining exercise capacity, right ventricular (RV) function has prognostic value in heart failure and after cardiac surgery. We therefore investigated the impact of PMVR on RV function in patients with severe MR. Methods and Results: Sixty-three patients undergoing PMVR at our department were prospectively enrolled. Transthoracic echocardiography was performed before, early (2-12d) after PMVR and after 3 months, including advanced echocardiographic analyses such as 3D imaging and strain analyses. At baseline, all patients presented with advanced heart failure symptoms. Etiology of MR was more often secondary and, if present, left ventricular (LV) dysfunction was predominantly caused by ischemic cardiomyopathy. PMVR substantially reduced MR to a grade ≤ 2 in most patients. Echocardiographic assessment revealed a largely unchanged LV systolic function early after PMVR, while in contrast RV function substantially improved after PMVR [3D RV EF (%): pre 33.7% [27.4; 39.6], post 40.0% [34.5; 46.0] (p < 0.01 vs. pre), 3 months 42.8% [38.3; 48.1] (p < 0.01 vs. pre); 2D RV GLS (%): pre -12.9% [-14.5; -10.5], post -16.0% [-17.9; -12.6] (p < 0.01 vs. pre), 3 months -17.2% [-21.7; -14.9] (p < 0.01 vs. pre)]. Factors that attenuated RV improvement were larger ventricular volumes, lower LV function, secondary MR, and a higher STS score (all p < 0.05). Conclusion: By using advanced echocardiographic parameters, we discovered an early improvement of RV function after PMVR that is preserved for months, independent from changes in LV function. Improvement of RV function was less pronounced in patients presenting with an advanced stage of heart failure and a higher burden of comorbidities reflected by the STS score.

Multicenter comparison of latest-generation balloon-expandable versus self-expanding transcatheter heart valves: Ultra versus Evolut.

BACKGROUND: Direct comparisons of latest-generation balloon-expandable versus self-expanding transcatheter heart valves (THV) are scarce. To compare outcomes after transcatheter aortic valve replacement (TAVR) with SAPIEN 3 Ultra (Ultra) versus Evolut R or Pro (Evolut) THVs. METHODS: 1612 consecutive patients undergoing TAVR with either Ultra (n = 616) or Evolut (n = 996) were included. After propensity score matching (PSM), 467 and 205 matched pairs were identified in the entire cohort and with latest-generation THVs, respectively. Outcomes were investigated up to 30 days after TAVR. RESULTS: After PSM, baseline characteristics were comparable in the entire cohort (n = 934). Device success (92.7% vs. 87.6%; p = 0.011) and need for permanent pacemaker implantation (PPI) (15.2% vs. 8.4%; p = 0.002) were higher for Evolut compared with Ultra. Elevated gradients (≥20 mm Hg) were less frequent (1.6% vs. 10.4%; p < 0.001), whereas rates of ≥ moderate paravalvular leakage (PVL II+) were more frequent for Evolut compared with Ultra (3.7% vs. 1.3%; p = 0.019). With latest-generation THVs (n = 410), device success was comparable (93.2% vs. 89.8%; p = 0.216), whereas the need for PPI was higher for Evolut Pro compared with Ultra (15.6% vs. 9.8%; p = 0.075). Elevated gradients were less frequent (0% vs. 8%; p < 0.001), whereas rates of PVL II+ were more frequent for Evolut compared with Ultra (5.4% vs. 1.5%; p = 0.028). CONCLUSIONS: Device success rates were high with both THV platforms with low rates of adverse events up to 30 days after TAVR. Compared with Ultra, Evolut was associated with higher pacemaker rates as well as PVL II+, but with less elevated gradients.

Novel self-expanding ALLEGRA transcatheter aortic valve for native aortic stenosis and degenerated bioprosthesis.

OBJECTIVES: To investigate the safety and efficacy of the ALLEGRA valve in routine use. BACKGROUND: The ALLEGRA aortic valve is a self-expanding transcatheter heart valve (THV) with bovine pericardial tissue and was CE approved in March 2017. Its unique design was developed to provide low prosthesis gradients. METHODS: We analyzed patients receiving an ALLEGRA THV between May 2017 and March 2021 at our center for treatment of aortic valve stenosis or degenerated valve prosthesis. Hemodynamic results and clinical outcome according to the Valve Academic Research Consortium-2 consensus criteria were evaluated at discharge and three months post transcatheter aortic valve replacement (TAVR) procedure. 93 patients with a mean age of 82.5 ± 4.8 years and a median EuroScore II of 4.7 ± 3.4 were treated, 15 of them were valve-in-valve procedures. RESULTS: Implantation was successful in 97.8% (91/93) and VARC-2 defined device success was achieved in 94.6% (88/93). In-hospital all-cause mortality was 2.2% (2/93). Life-threatening bleeding, major vascular complications and strokes were 3.2% (3/93), 2.2% (2/93) and 3.2% (3/93), respectively. Paravalvular leakage was none to trace in 60.4%, mild in 38.5% and moderate in 1.1%. Permanent pacemaker implantation in pacemaker naive patients was necessary in 9.5% (8/84). Mean gradient at discharge was 8.2 ± 4.3 mmHg for all patients; 7.1 ± 2.6 mmHg in patients treated for stenosis of the native aortic valve and 13.8 ± 6.3 mmHg in patients treated valve-in-valve. CONCLUSIONS: The ALLEGRA THV provides excellent hemodynamic results and a good safety profile with a low complication rate.

ADAMTS-13 activity in stroke of known and unknown cause: Relation to vascular risk factor burden.

Background: The identification of the underlying mechanism in ischemic stroke has important implications for secondary prevention. A disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS-13) has antithrombotic properties and was repeatedly implicated in the pathophysiology of stroke. In this study, we, therefore, aimed to investigate whether ADAMTS-13 is associated with stroke etiology and the burden of vascular risk factors. Methods: We determined ADAMTS-13 activity in two prospectively recruited stroke cohorts in the long-term course after the event. Cohort 1 (n = 88) consisted of patients who suffered a stroke due to embolic stroke of undetermined source (ESUS), cardioembolic stroke due to atrial fibrillation (AF), large-artery atherosclerosis, or small vessel disease. In cohort 2, patients with cryptogenic stroke and patent foramen ovale (PFO) scheduled for PFO closure (n = 38) were enrolled. As measures of vascular risk factor burden, the CHA2DS2VASC score, the Essen Stroke Risk Score (ESRS), and the Risk of Paradoxical Embolism (RoPE) score were calculated, as appropriate. Results: ADAMTS-13 activity was lower in patients with AF-related stroke compared to patients with ESUS (p = 0.0227), which was, however, due to confounding by vascular risk factors. ADAMTS-13 activity inversely correlated with the ESRS (r = -0.452, p < 0.001) and CHA2DS2VASC (r = -0.375, p < 0.001) in cohort 1. In accordance with these findings, we found a positive correlation between ADAMTS-13 activity and the RoPE score in cohort 2 (r = 0.413, p = 0.010). Conclusion: ADAMTS-13 activity is inversely correlated with the number of vascular risk factors across different stroke etiologies. Further study is warranted to establish ADAMTS-13 as a mediator of cerebrovascular risk.

Myeloid-Derived Growth Factor Protects Against Pressure Overload-Induced Heart Failure by Preserving Sarco/Endoplasmic Reticulum Ca2+-ATPase Expression in Cardiomyocytes.

BACKGROUND: Inflammation contributes to the pathogenesis of heart failure, but there is limited understanding of inflammation's potential benefits. Inflammatory cells secrete MYDGF (myeloid-derived growth factor) to promote tissue repair after acute myocardial infarction. We hypothesized that MYDGF has a role in cardiac adaptation to persistent pressure overload. METHODS: We defined the cellular sources and function of MYDGF in wild-type (WT), Mydgf-deficient (Mydgf-/-), and Mydgf bone marrow-chimeric or bone marrow-conditional transgenic mice with pressure overload-induced heart failure after transverse aortic constriction surgery. We measured MYDGF plasma concentrations by targeted liquid chromatography-mass spectrometry. We identified MYDGF signaling targets by phosphoproteomics and substrate-based kinase activity inference. We recorded Ca2+ transients and sarcomere contractions in isolated cardiomyocytes. Additionally, we explored the therapeutic potential of recombinant MYDGF. RESULTS: MYDGF protein abundance increased in the left ventricular myocardium and in blood plasma of pressure-overloaded mice. Patients with severe aortic stenosis also had elevated MYDGF plasma concentrations, which declined after transcatheter aortic valve implantation. Monocytes and macrophages emerged as the main MYDGF sources in the pressure-overloaded murine heart. While Mydgf-/- mice had no apparent phenotype at baseline, they developed more severe left ventricular hypertrophy and contractile dysfunction during pressure overload than WT mice. Conversely, conditional transgenic overexpression of MYDGF in bone marrow-derived inflammatory cells attenuated pressure overload-induced hypertrophy and dysfunction. Mechanistically, MYDGF inhibited G protein-coupled receptor agonist-induced hypertrophy and augmented SERCA2a (sarco/endoplasmic reticulum Ca2+-ATPase 2a) expression in cultured neonatal rat ventricular cardiomyocytes by enhancing PIM1 (Pim-1 proto-oncogene, serine/threonine kinase) expression and activity. Along this line, cardiomyocytes from pressure-overloaded Mydgf-/- mice displayed reduced PIM1 and SERCA2a expression, greater hypertrophy, and impaired Ca2+ cycling and sarcomere function compared with cardiomyocytes from pressure-overloaded WT mice. Transplanting Mydgf-/- mice with WT bone marrow cells augmented cardiac PIM1 and SERCA2a levels and ameliorated pressure overload-induced hypertrophy and dysfunction. Pressure-overloaded Mydgf-/- mice were similarly rescued by adenoviral Serca2a gene transfer. Treating pressure-overloaded WT mice subcutaneously with recombinant MYDGF enhanced SERCA2a expression, attenuated left ventricular hypertrophy and dysfunction, and improved survival. CONCLUSIONS: These findings establish a MYDGF-based adaptive crosstalk between inflammatory cells and cardiomyocytes that protects against pressure overload-induced heart failure.

Impact of anemia on short-term outcomes after TAVR: A subgroup analysis from the BRAVO-3 randomized trial.

OBJECTIVES: To determine the prognostic impact of anemia in patients randomized to bivalirudin or unfractionated heparin (UFH) during transcatheter aortic valve replacement (TAVR). BACKGROUND: Whether the periprocedural use of bivalirudin as compared with UFH in anemic patients undergoing TAVR has an impact on outcomes remains unknown. METHODS: The BRAVO-3 trial compared the use of bivalirudin versus UFH in 802 high risk patients undergoing transfemoral TAVR for severe symptomatic aortic stenosis. Patients were stratified according to the presence (defined as hemoglobin levels <13 g/dl in men and <12 g/dl in women) or absence of anemia. The primary outcomes were net adverse cardiac events (NACE; a composite of all-cause mortality, myocardial infarction, stroke, or bleeding) and major bleeding (Bleeding Academic Research Consortium ≥3b) at 30 days. RESULTS: Among 798 patients with available baseline hemoglobin levels, 427 (54%) were anemic of whom 221 (52%) received bivalirudin. There were no significant differences in NACE and major bleeding at 30 days between patients with and without anemia, irrespective of the type of anticoagulant used (pinteraction  = 0.71 for NACE, pinteraction  = 1.0 for major bleeding). However, anemic patients had a higher risk of major vascular complications (adjusted OR 2.43, 95% CI 1.42-4.16, p = 0.001), and acute kidney injury (adjusted OR 1.74, 95% CI 1.16-2.59, p = 0.007) compared to non-anemic patients at 30 days. CONCLUSIONS: Anemia was not associated with a higher risk of NACE or major bleeding at 30 days after TAVR without modification of the treatment effects of periprocedural anticoagulation with bivalirudin versus UFH.

Cardiac iron concentration in relation to systemic iron status and disease severity in non-ischaemic heart failure with reduced ejection fraction.

AIMS: Low cardiac iron levels promote heart failure in experimental models. While cardiac iron concentration (CI) is decreased in patients with advanced heart failure with reduced ejection fraction (HFrEF), CI has never been measured in non-advanced HFrEF. We measured CI in left ventricular (LV) endomyocardial biopsies (EMB) from patients with non-advanced HFrEF and explored CI association with systemic iron status and disease severity. METHODS AND RESULTS: We enrolled 80 consecutive patients with non-ischaemic HFrEF with New York Heart Association class II or III symptoms and a median (interquartile range) LV ejection fraction of 25 (18-33)%. CI was 304 (262-373) µg/g dry tissue. CI was not related to immunohistological findings or the presence of cardiotropic viral genomes in EMBs and was not related to biomarkers of systemic iron status or anaemia. Patients with CI in the lowest quartile (CIQ1 ) had lower body mass indices and more often presented with heart failure histories longer than 6 months than patients in the upper three quartiles (CIQ2-4 ). CIQ1 patients had higher serum N-terminal pro-B-type natriuretic peptide levels than CIQ2-4 patients [3566 (1513-6412) vs. 1542 (526-2811) ng/L; P = 0.005]. CIQ1 patients also had greater LV end-diastolic (P = 0.001) and end-systolic diameter indices (P = 0.003) and higher LV end-diastolic pressures (P = 0.046) than CIQ2-4 patients. CONCLUSION: Low CI is associated with greater disease severity in patients with non-advanced non-ischaemic HFrEF. CI is unrelated to systemic iron homeostasis. The prognostic and therapeutic implications of CI measurements in EMBs should be further explored.

Impact of diabetes mellitus on short term vascular complications after TAVR: Results from the BRAVO-3 randomized trial.

AIMS: The impact of diabetes mellitus (DM) on clinical outcomes after transcatheter aortic valve replacement (TAVR) remains unclear. The aim of this study was to investigate the impact of DM on short-term clinical outcomes after TAVR in a large randomized trial population. METHODS AND RESULTS: BRAVO-3 trial randomized 802 patients undergoing trans-femoral TAVR to procedural anticoagulation with bivalirudin or unfractionated heparin. The study population was divided according to the presence of DM, and further stratified according to the use of insulin. Net adverse cardiovascular outcomes (NACE - death, myocardial infarction (MI), stroke or major bleeding by Bleeding Academic Research Consortium (BARC) type 3b or above) was the primary outcome in-hospital and at 30-days. Of the total 802 randomized patients, 239 (30%) had DM at baseline, with 87 (36%) being treated with insulin. At 30-days, DM patients experienced numerically higher rates of net adverse cardiovascular events (16.3% vs. 14.4%, p=0.48) and acute kidney injury (19.7% vs. 15.1%, p=0.11), while non-DM (NDM) patients had numerically higher rates of cerebrovascular accidents (3.6% vs. 1.7%, p=0.22). After multivariable adjustment, DM patients had higher odds of vascular complications at 30-days (OR 1.57, p=0.03) and life-threatening bleeding both in-hospital (OR 1.50, p=0.046) and at 30-days (OR 1.50, p=0.03) with the excess overall risk primarily attributed to the higher rates observed among non-insulin dependent DM patients. CONCLUSIONS: Patients with DM had higher adjusted odds of vascular and bleeding complications up to 30-days post-TAVR. Overall, there was no significant association between DM and early mortality following TAVR.

Coronary artery treatment with a urea-based paclitaxel-coated balloon: the European-wide FALCON all-comers DCB Registry (FALCON Registry).

AIMS: The aim of this study was to investigate the use of a drug-coated balloon (DCB) in daily clinical practice and provide further evidence on the safety and efficacy of paclitaxel-coated balloon treatment using urea as an inert excipient. METHODS AND RESULTS: Between December 2013 and December 2015, 757 patients treated for coronary lesions with the IN.PACT Falcon balloon were enrolled in this prospective real-world all-comers registry. The primary outcome was the clinically driven target lesion revascularisation (TLR) rate at 12 months. The secondary outcome was major adverse cardiac events (MACE) defined as cardiac death, myocardial infarction, TLR and target vessel revascularisation (TVR). Out of 805 lesions, 43.1% were de novo, and 53.2% drug-eluting stent (DES) or bare metal stent (BMS) in-stent restenosis (ISR). TLR at 12 months was 6.2% and TVR 8.3%. MACE occurred in 9.7% of patients with a composite of cardiac death in 0.8% and myocardial infarction in 2.7% plus TLR/TVR. Subgroup analysis confirmed a TLR rate of 7.5% for ISR (2.1% BMS and 9.5% DES) and 4.9% for de novo lesions. CONCLUSIONS: The IN.PACT Falcon urea-based paclitaxel-coated balloon is safe and efficient in de novo and ISR lesions with low rates of TLR/TVR. The high proportion of treatment of de novo lesions indicates that a DCB-only strategy is nowadays common.

Intermediate CD14++CD16+ monocytes decline after transcatheter aortic valve replacement and correlate with functional capacity and left ventricular systolic function.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is the method of choice for patients with severe aortic valve stenosis, who are ineligible or at high risk for surgery. Though TAVR leads to a significant reduction in mortality, a notable amount of patients are re-hospitalized early after TAVR. Parameters or biomarkers predicting outcome are therefore needed to identify patients who benefit most. Specific monocyte subsets have been associated with cardiovascular diseases and were shown to possess prognostic value. METHODS: Peripheral blood was drawn before and after transfemoral TAVR with the self-expanding CoreValve, Boston Lotus or the balloon-expanding Edwards Sapien prosthesis. Classical (CD14++CD16-), intermediate (CD14++CD16+) and non-classical (CD14+CD16++) monocyte subsets were determined by flow cytometry. Transthoracic echocardiography was performed before, early after as well as 3 months after the TAVR procedure. RESULTS: No significant differences in the absolute monocyte counts were found after TAVR. A significant decline in the intermediate monocyte population was though observed early after TAVR (pre 4.01±0.38%, post 2.803±0.34%, p≤0.05). Creatinine levels stayed stable after TAVR procedure and intermediate monocytes were associated with worse renal function. Monocyte decline was not related to changes in CRP-, noradrenaline, cortisol or aldosterone-levels. The amount of intermediate monocytes correlated with worse cardiac function and predicted the possibility to reach an improvement in NYHA functional class at 3 months after TAVR. CONCLUSIONS: A significant decline of intermediate monocytes occurs shortly after TAVR. High levels of intermediate monocytes were associated with worse cardiac function and predicted poor functional capacity, hinting at a possible prognostic value.

Impact of pre-existing or new-onset atrial fibrillation on 30-day clinical outcomes following transcatheter aortic valve replacement: Results from the BRAVO 3 randomized trial.

BACKGROUND: Prior studies have suggested that patients with atrial fibrillation (AF) undergoing transcatheter aortic valve replacement (TAVR) are at higher risk for adverse cardiovascular events. Whether procedural bivalirudin compared with unfractionated heparin (UFH) has a beneficial effect on early outcomes in these patients is unknown. We examined for the effect of baseline or new-onset AF within 30 days of TAVR and explored for the effect of bivalirudin versus UFH by AF status, on 30-day outcomes from the BRAVO 3 trial. METHODS: The BRAVO-3 trial multicenter randomized trial included 802 patients undergoing transfemoral TAVR randomized to bivalirudin or UFH. We compared AF and no-AF groups and examined for 30-day Bleeding Academic Research Consortium type ≥3b bleeding, major vascular complications and all ischemic endpoints. Adjusted outcomes were analyzed using logistic regression methods. RESULTS: Of the study population, 41.4% (n = 332) patients had baseline or new-onset AF within 30 days of TAVR, whereas 58.6% (n = 470) had no AF. Patients with AF had greater prevalence of renal dysfunction, lower left ventricular ejection fraction, and higher euroSCORE I compared with their counterparts without AF. Among AF and no-AF patients, there were no significant baseline differences between bivalirudin and UFH groups. At 30 days the incidence of death (6.0 vs. 4.5%, P = 0.324) and stroke (3.9 vs. 2.6%, P = 0.274) was similar in AF vs. no-AF patients. However, new-onset AF (n = 38) was associated with significantly greater crude risk of 30-day stroke compared with no AF (HR 4.49, 95% CI 1.37-14.67). Regardless of AF status, there were no differences in 30-day death (P-int = 0.652) or stroke (P-int = 0.066) by anticoagulation type. CONCLUSIONS: Prior or new-onset AF is noted in more than one-third of patients undergoing transfemoral TAVR. Despite greater baseline comorbidities than non-AF patients, AF was not associated with significantly higher risk of adjusted 30-day outcomes. In the BRAVO 3 trial, early outcomes were similar regardless of anticoagulant strategy in each group.

Mid-term results of interventional closure of patent foramen ovale with the Occlutech Figulla® Flex II Occluder.

BACKGROUND: Patients with a patent foramen ovale (PFO) who suffered from stroke, TIA or peripheral paradoxical embolism are at substantial risk for recurrent neurologic events and in need for secondary prevention. Interventional closure of PFO has been performed for over 20 years. Numerous devices have been developed and used for treatment. We investigated PFO closure with the third generation Occlutech Figulla® Flex II Occluder device. METHODS: Between 2012 and 2015 57 patients (mean age 47.3 ± 1.5 years) who had suffered from a thromboembolic event of unknown cause underwent transcatheter PFO closure with the Occlutech Figulla® Flex II Occluder at our department. 68.4 % of all patients had suffered from cryptogenic stroke, while TIA had occurred in 28.1 %. Almost all patients were diagnosed with an atrial septum aneurysm (90.9 %) and a severe right-to-left shunt grade 3: >20 microbubbles (92.0 %). Follow-up was done 6 months post intervention by clinical examination and transesophageal contrast echocardiography. RESULTS: No major periprocedural or in-hospital complication occurred. Closure was sufficient with no residual right-to-left shunt in 94.4 % of all patients at 6 months post implantation and only minimal residual shunt in three cases. There were no thrombotic formations associated to the occluder device. Atrial fibrillation occurred in one patient and a recurrent cerebral ischemic event was seen in one patient, who suffered from another TIA. CONCLUSIONS: The Occlutech Figulla® Flex II Occluder device and its delivery system is safe and provides sufficient closure of PFO in patients who suffered from cryptogenic stroke, TIA or paradoxical peripheral embolism.

Impact of Preprocedural Left Ventricular Ejection Fraction on 1-Year Outcomes After MitraClip Implantation (from the ACCESS-EU Phase I, a Prospective, Multicenter, Nonrandomized Postapproval Study of the MitraClip Therapy in Europe).

This report describes the 12-month outcomes of the a prospective, multicenter, nonrandomized post-approval study of the MitraClip therapy in Europe (ACCESS-EU postapproval study of MitraClip therapy) with respect to preprocedural left ventricular ejection fraction (LVEF). Transcatheter deployment of the MitraClip device may be considered for patients who are not suitable for conventional surgery. A total of 567 patients with significant mitral regurgitation (MR) underwent MitraClip therapy. Of those, 393 had functional MR (FMR) and were subdivided by preprocedural LVEF (A: 10% to 20%, B: >20% to 30%, C: >30% to 40%, D: >40%). Procedural safety and efficacy and treatment outcomes including MR grade, New York Heart Association (NYHA) functional class, 6-minute walk test, and the Minnesota Living with Heart Failure Questionnaire were analyzed at baseline, 30 days, and 12 months. Baseline mean logistic EuroSCORE was 25 ± 19; 87% of patients were in NYHA classes III or IV (A: 96%, B: 83%, C: 90%, D: 86%). There was no incidence of death or stroke intraprocedurally. Eleven patients died within 30 days with no differences among subgroups. Kaplan-Meier survival at 12 months was 81.8% (A: 71%, B: 79%, C: 87%, D: 86%). There was a significant improvement in MR severity at 30 days and 12 months (p <0.0001). At 12 months, all subgroups experienced similar improvements in NYHA class, 6-minute walk test, and Minnesota Living with Heart Failure Questionnaire. This real-world registry reports promising results of MitraClip therapy in patients with FMR. In conclusion, the low rates of hospital mortality and adverse events in patients with FMR-even in patients with severely reduced LVEF-provide additional evidence of substantial benefits after MitraClip implantation.

Gender in the ACCESS-EU registry: a prospective, multicentre, non-randomised post-market approval study of MitraClip® therapy in Europe.

AIMS: Gender has been an important factor in outcomes after mitral valve surgery; however, its effect on percutaneous mitral valve repair is not well known. We aimed to report the effect of gender on outcomes in a large European prospective, multicentre, non-randomised post-approval study of percutaneous mitral valve repair. METHODS AND RESULTS: Two hundred and five female and 362 male patients with significant mitral regurgitation underwent percutaneous repair at 14 European sites from October 2008 to April 2011. Women and men had similar baseline risk scores, but women had a higher rate of degenerative disease (32% vs. 18%). Women were more likely to have one clip implanted (72% vs. 54%), but had a similar length of stay in the intensive care unit (2.6±4.1 days) and overall length of stay (8.0±6.9 days) compared to men. They were also less likely to be discharged home: more women than men went to skilled nursing facilities (25% vs. 15%) and fewer women went home compared to men (71.9% vs. 83.9%). Thirty-day and 12-month safety results were similar between genders, as was 12-month efficacy (echocardiographic and clinical). Multivariate analysis showed no effect of gender on 12-month survival. CONCLUSIONS: In a real-world, post-approval experience in Europe, female patients who underwent percutaneous mitral valve repair experienced safety and efficacy results similar to those of males. However, the discharge rates to skilled nursing facilities rather than home may indicate a need for better optimisation of the female patient's physical and social comorbidities prior to intervention and during the hospitalisation period.

NT-proBNP Indicates Left Ventricular Impairment and Adverse Clinical Outcome in Patients With Tetralogy of Fallot and Pulmonary Regurgitation.

BACKGROUND: The goal of this study was to interrelate N-terminal B-type natriuretic peptide (NT-proBNP) levels and cardiac magnetic resonance imaging-derived ventricular function, mass, and volumes in adults with pulmonary regurgitation after Fallot repair and to evaluate the prognostic relevance of these parameters regarding adverse clinical outcome. METHODS: Eighty-one patients (aged 26.3 ± 7.4 years; male sex, 45.7%; New York Heart Association class I, 72.8%; pulmonary valve velocity, < 3 m/s) were included. At baseline cardiac magnetic resonance imaging and NT-proBNP measurements were performed. RESULTS: During a mean observation time of 6.9 ± 2.6 years, 13 patients (16.1%) had sustained supraventricular arrhythmias or heart failure (2.4 per 100 patient-years). Multivariate Cox analysis identified NT-proBNP, left ventricular (LV) end-systolic volume index and LV ejection fraction, right ventricular (RV) end-diastolic volume index, and tricuspid regurgitation as independent predictors of adverse events. NT-proBNP correlated with LV but not with RV parameters. In receiver operating characteristic curve analysis using significant variables of the multivariate analysis, NT-proBNP was superior to all other parameters to detect patients at risk (area under the curve [AUC], 0.873; 95% confidence interval, 0.772-0.974). LV end-systolic volume index (AUC, 0.734), RV end-diastolic volume index (AUC, 0.645) und tricuspid regurgitation (AUC, 0.747) showed lower diagnostic accuracy. CONCLUSIONS: Even in mildly symptomatic patients with pulmonary regurgitation after Fallot repair NT-proBNP is a strong predictor of adverse outcome. It is rather associated with LV but not with RV impairment. In severe pulmonary regurgitation an increase in the level of NT-proBNP and LV impairment seem to provide additional useful information for the timing of pulmonary valve replacement.