Right-Sided Minimally Invasive Direct Coronary Artery Bypass: Clinical Experience and Perspectives.

Objective: Minimally invasive direct coronary artery bypass grafting (MIDCAB) using the left internal thoracic artery to the left descending artery is a clinical routine in the treatment of coronary artery disease. Far less is known on right-sided MIDCAB (r-MIDCAB) using the right internal thoracic artery (RITA) to the right coronary artery (RCA). We aimed to present our experience in patients with complex coronary artery disease who underwent r-MIDCAB. Materials and Methods: Between October 2019 and January 2023, 11 patients received r-MIDCAB using RITA to RCA bypass in a minimally invasive technique via right anterior minithoracotomy without using a cardiopulmonary bypass. Underlying coronary disease was complex right coronary artery stenosis (n = 7) and anomalous right coronary artery (ARCA; n = 4). All procedure-related and outcome data were evaluated prospectively. Results: Successful minimally invasive revascularization was achieved in all patients (n = 11). There were no conversions to sternotomy and no re-explorations for bleeding. Furthermore, no myocardial infarction, no strokes, and, most importantly, no deaths were observed. During the follow-up period (median 24 months), all patients were alive and 90% were completely angina free. Two patients received a repeated revascularization after surgery but independently from the RITA-RCA bypass, which was fully competent in both patients. Conclusion: Right-sided MIDCAB can be performed safely and effectively in patients with expected technically challenging percutaneous coronary intervention of the RCA and in patients with ARCA. Mid-term results showed high freedom from angina in nearly all patients. Further studies with larger patient cohorts and more evidence are needed to provide the best revascularization strategy for patients suffering from isolated complex RCA stenosis and ARCA.

Outcomes After Early Postoperative Myocardial Infarction Due to Graft Failure in Patients Undergoing Coronary Artery Bypass Grafting.

BACKGROUND: Early graft failure (EGF) after coronary artery bypass grafting (CABG) occurs in up to 12% of grafts, but is often clinically unapparent. EGF may result in perioperative myocardial infarction with consequently increased mortality. The aim of the present study was to analyze the incidence of clinically apparent EGF in patients undergoing CABG and the influence on mortality. METHODS: We analyzed outcomes of consecutive patients undergoing CABG from January 2015 to December 2018 with respect to postoperative emergency coronary angiography (CAG) due to suspected EGF and 30-day mortality. Patients with CAG-documented EGF were matched to patients without EGF to examine predictors of mortality. RESULTS: The analysis included 5638 patients undergoing CABG. Eighty-six patients (1.5%) underwent emergency CAG due to suspected EGF. Clinically apparent EGF was observed in 61 of these patients (70.9%), whereas 14 (16.3%) had a culprit lesion in a native coronary artery. The majority of patients (n = 45; 52.3%) were treated with percutaneous coronary intervention and 31 (36%) underwent re-do CABG. The remaining patients were treated conservatively. The 30-day mortality rate of suspected EGF patients undergoing CAG was 22.4% (n = 19), which was higher than the mortality rate of 2.8% overall (P<.001); this remained higher after matching the EGF patients with the control group (11 [20.4%] vs 2 [4.0%]; P=.02). CONCLUSION: Emergency CAG after CABG is rare and is primarily carried out in patients with EGF. The 30-day mortality rate of these patients is high, and EGF is an independent predictor of mortality. Perioperative CAG with subsequent treatment is mandatory in these patients.

Endothelial dysfunction and atherosclerosis related miRNA-expression in patients with haemophilia.

INTRODUCTION: Elevated markers of endothelial dysfunction and inflammation indicate worse endothelial function in the aging haemophilia population. MicroRNAs (miRNAs) regulate gene expression post-transcriptionally. Several miRNAs have been shown to be involved in the process of endothelial dysfunction and atherosclerosis. AIM: The aim of this study was to determine the underlying molecular pathways of endothelial dysfunction and inflammation in haemophilia patients. METHODS: A total of 25 patients with severe or moderate haemophilia A (20 patients) or B (5 patients), 14 controls and 18 patients with coronary artery disease (CAD) after myocardial infarction were included in this study. Expression of miRNA-126, -155, -222, -1, -let7a, -21 and -197 were analysed using a real time polymerase chain reaction. Network-based visualisation and analysis of the miRNA-target interactions were performed using the MicroRNA ENrichment TURned NETwork (MIENTURNET). RESULTS: Expression of miRNA-126 (p < .05) and miRNA-let7a (p < .05) were significantly higher in CAD patients compared to haemophilia patients and controls. MiRNA-21 (p < .05) was significantly elevated in CAD patients compared to controls. MiRNA-155 (p < .05), miRNA-1 (p < .05) and miRNA-197 (p < .05) were significantly higher expressed in CAD and haemophilia patients compared to controls and showed a strong correlation with increased levels of interleukin-6 (IL-6) and soluble intercellular adhesion molecule-1 (sICAM-1). The network analysis revealed interactions in the cytokine signalling, focal adhesion and VEGFA-VEGFR2 pathway (Vascular endothelial growth factor, -receptor). CONCLUSION: This study characterises miRNA expression in haemophilia patients in comparison to CAD patients and healthy controls. The results imply comparable biological processes in CAD and haemophilia patients.

Risk of graft loss in kidney transplant recipients after aortic valve replacement.

Surgical aortic valve replacement (SAVR) in kidney transplant recipients (KTR) is associated with high morbidity and mortality, and an increased risk of postoperative graft failure potentially leading to graft loss. Transcatheter aortic valve implantation (TAVI) emerged as an alternative in high-risk patients. However, data on TAVI in kidney transplant recipients are limited. We performed a retrospective analysis of 40 KTR in which aortic valve replacement was performed at our center between 2005 and 2015. The outcomes and follow-up of TAVI (n=20; 2010-2015) and SAVR (n=20; 2005-2015) were analyzed with respect to patient and graft survival. Baseline characteristics in both groups were comparable. Hospital stay after TAVI was significantly shorter compared to SAVR (19 [11.5-21.75] days vs. 33 [21-62] days, p=0.001). Acute graft failure occurred more frequently after SAVR (45% vs. 89.5%; p=0.006). Thirty-day mortality was 10% in both groups. However, in-hospital mortality reached 25% in the SAVR group (TAVI 10%), indicating a more complicated course after surgery. Moreover, during a median follow-up time of 1928 days in TAVI patients and 2717 days in patients after SAVR, graft loss occurred only in the surgically treated group (n=7). While one-year survival after TAVR was 90% compared to 69% after SAVR, long-term follow-up showed comparable results (at 5 years: TAVI 58% vs. 52% SAVR; log-rank-test: p=0.86). In KTR, TAVI can be performed with good mid- to long-term results. Compared to SAVR, renal outcomes seem to be improved after TAVI, suggesting better graft survival.

Propensity matched comparison of TAVI and SAVR in intermediate-risk patients with severe aortic stenosis and moderate-to-severe chronic kidney disease: a subgroup analysis from the German Aortic Valve Registry.

OBJECTIVE: We compared TAVI vs. SAVR in patients with moderate-to-severe chronic kidney disease (eGFR 15-60 ml/min/1.73 m2) for whom both procedures could possibly be considered (age ≤ 80 years, STS-score 4-8). BACKGROUND: According to both ACC/AHA and ESC/EACTS recent guidelines, aortic stenosis may be treated with either transcatheter (TAVI) or surgical (SAVR) aortic valve replacement in a subgroup of patients. A shared therapeutic decision is made by a heart team based on individual factors, including chronic kidney disease (CKD). METHODS: Data from the large nationwide German Aortic Valve Registry were used. A propensity score method was used to select 704 TAVI and 374 SAVR matched patients. Primary endpoint was 1-year survival. Secondary endpoints were clinical complications, including pacemaker implantation, vascular complications, myocardial infarction, bleeding, and the need for new-onset dialysis. RESULTS: One-year survival was similar (HR [95% CI] for TAVI 1.271 [0.795, 2.031], p = 0.316), with no divergence in Kaplan-Meier curves. In spite of post-procedural short-term survival being numerically higher for TAVI patients and 1-year survival being numerically higher for SAVR patients, such differences did not reach statistical significance (96.4% vs. 94.2%, p = 0.199, and 86.2% vs. 81.2%, p = 0.316, respectively). In weighted analyses, pacemaker implantation, vascular complications, and were significantly more common with TAVI; whereas myocardial infarction, bleeding requiring transfusion, and longer ICU-stay and overall hospitalization were higher with SAVR. Temporary dialysis was more common with SAVR (p < 0.0001); however, a probable need for chronic dialysis was rare and similar in both groups. CONCLUSION: Both TAVI and SAVR led to comparable and excellent results in patients with moderate-to-severe CKD in an intermediate-risk population of patients with symptomatic severe aortic stenosis for whom both therapies could possibly be considered.

Transcatheter Aortic Valve Implantation with ACURATE neo: Results from the PROGRESS PVL Registry.

Objectives: The PROGRESS PVL registry evaluated transcatheter aortic valve implantation (TAVI) in patients treated with ACURATE neo, a supra-annular self-expanding bioprosthetic aortic valve. Background: While clinical outcomes with TAVI are comparable with those achieved with surgery, residual aortic regurgitation (AR) and paravalvular leak (PVL) are common complications. The ACURATE neo valve has a pericardial sealing skirt designed to minimize PVL. Methods: The primary endpoint was the rate of total AR over time, as assessed by a core echocardiographic laboratory. The study enrolled 500 patients (mean age: 81.8 ± 5.1 years; 61% female; mean baseline STS score: 6.0 ± 4.5%) from 22 centers in Europe and Canada; 498 patients were treated with ACURATE neo. Results: The rate of ≥ moderate AR was 4.6% at discharge and 3.1% at 12 months; the rate of ≥ moderate PVL was 4.6% at discharge and 2.6% at 12 months. Paired analyses showed significant improvement in overall PVL between discharge and 12 months (P < 0.001); 64.6% of patients had no change in PVL grade, 24.9% improved, and 10.5% worsened. Patients also exhibited significant improvement in transvalvular gradient (P < 0.001) and effective orifice area (P=0.01). The mortality rate was 2.2% at 30 days and 11.3% at 12 months. The permanent pacemaker implantation (PPI) rate was 10.2% at 30 days and 12.2% at 12 months. Conclusions: Results from PROGRESS PVL support the sustained safety and performance of TAVI with the ACURATE neo valve, showing excellent valve hemodynamics, good clinical outcomes, and significant interindividual improvement in PVL from discharge to 12-month follow-up.

Acute kidney injury after in-hospital cardiac arrest in a predominant internal medicine and cardiology patient population: incidence, risk factors, and impact on survival.

INTRODUCTION: Prognosis of survivors from cardiac arrest is generally poor. Acute kidney injury (AKI) is a common finding in these patients. In general, AKI is well characterized as a marker of adverse outcome. In-hospital cardiac arrest (IHCA) represents a special subset of cardiac arrest scenarios with differential predisposing factors and courses after the event, compared to out-of-hospital resuscitations. Data about AKI in survivors after in-hospital cardiac arrest are scarce. METHODS: In this study, we retrospectively analyzed patients after IHCA for incidence and risk factors of AKI and its prognostic impact on mortality. For inclusion in the analysis, patients had to survive at least 48 h after IHCA. RESULTS: A total of 238 IHCA events with successful resuscitation and survival beyond 48 h after the initial event were recorded. Of those, 89.9% were patients of internal medicine, and 10.1% of patients from surgery, neurology or other departments. In 120/238 patients (50.4%), AKI was diagnosed. In 28 patients (23.3%), transient or permanent renal replacement therapy had to be initiated. Male gender, preexisting chronic kidney disease and a non-shockable first ECG rhythm during resuscitation were significantly associated with a higher incidence of AKI in IHCA-survivors. In-hospital mortality in survivors from IHCA without AKI was 29.7%, and 60.8% in patients after IHCA who developed AKI (p < 0.01 between groups).By multivariate analysis, AKI after IHCA persisted as an independent predictor of in-hospital mortality (HR 3.7 (95% CI 2.14-6.33, p ≤ 0.01)). CONCLUSION: In this cohort of survivors from IHCA, AKI is a frequent finding, with adverse impact on outcome. Therefore, therapeutic strategies to prevent AKI in post-IHCA patients are warranted.

Endothelial Function in Patients With Von Willebrand Disease.

In patients with von Willebrand disease (vWD) the interest in age-related comorbidities has grown, because the life expectancy of these patients has increased. The research question of this study was whether patients with vWD show a different endothelial function compared to the general population. A total of 37 patients with type 1 (n = 23), type 2 (n = 10) and type 3 (n = 4) vWD, 14 controls and 38 patients with coronary artery disease (CAD) were included in this study. Five markers of endothelial dysfunction (MOED) were determined. Moreover, the endothelial function was examined using the Itamar Endo-PAT. The reactive hyperemia index (RHI) was calculated from the results. The markers soluble intercellular adhesion molecule-1 (p = 0.171), P-Selectin (p = 0.512), interleukin-6 (p = 0.734) and monocyte chemoattractant protein-1 (p = 0.761) showed higher levels in patients with vWD, but were not significantly different compared to the control group. RHI was impaired in CAD-patients (1.855), whereas vWD patients had mean results of 1.870 and controls 2.112 (p = 0.367). In this study, the endothelial function measurements of patients with von Willebrand disease were not significantly different compared to healthy controls.

Impact of chronic kidney disease in 29 893 patients undergoing transcatheter or surgical aortic valve replacement from the German Aortic Valve Registry.

OBJECTIVES: Chronic kidney disease (CKD) is a key risk factor in patients undergoing transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR). We analysed the impact of estimated glomerular filtration rate (eGFR) and CKD stages on their mid-term survival. METHODS: Data from 29 893 patients enrolled in the German Aortic Valve registry from January 2011 to December 2015 receiving TAVI (n = 12 834) or SAVR (n = 17 059) at 88 sites were included. The impact of renal impairment, as measured by eGFR and CKD stages, was investigated. The primary end-point was 1-year cumulative all-cause mortality. RESULTS: Higher CKD stages were significantly associated to lower in-hospital, 30-day- and 1-year survival rates. Both TAVI- and SAVR-treated patients in CKD 3a, 3b, 4 and 5 stages showed significant and gradually increasing HR values for 1-year all-cause mortality. The same trend persisted in multivariable analysis, although HR values for CKD 3a and 5 did not reach significance in TAVI patients, whereas CKD 4 + 5 did not reach statistical significance in SAVR. Likewise, eGFR as a continuous variable was a significant predictor for 1-year mortality, with the best cut-off points being 47.4 ml/min/1.73 m2 for TAVI and 59.8 ml/min/1.73 m2 for SAVR. Significant 8.6% and 9.0% increases in 1-year mortality were observed for every 5-ml reduction in eGFR for TAVI and SAVR, respectively. CONCLUSIONS: CKD ≥3b and CKD ≥3a are the independent major risk factors for mortality in patients undergoing TAVI and SAVR, respectively. In the overall population of patients with severe aortic stenosis, an appropriate stratification based on CKD substage may contribute to a better selection of patients suitable for such therapies.

Transcatheter or surgical aortic valve implantation in chronic dialysis patients: a German Aortic Valve Registry analysis.

OBJECTIVES: The aim of this study was to compare outcomes of transcatheter and surgical aortic valve implantation in chronic dialysis patients with aortic valve stenosis (AS). BACKGROUND: Chronic dialysis patients undergoing heart valve surgery are at higher risk for morbidity and mortality. Whether interventional techniques can reduce this risk is unclear because dialysis patients have thus far been excluded from randomized trials. METHODS: Chronic dialysis patients with AS enrolled in the German Aortic Valve Registry (GARY) between 2012 and 2015 were analyzed to compare transcatheter aortic valve implantation (TAVI n = 661) with surgical aortic valve replacement (SAVR n = 457). Propensity scores for inverse probability of treatment weighting (IPTW) were used to adjust the comparison of the two treatment groups for potential confounders. RESULTS: TAVI patients were older (78 ± 7.3 vs. 69 ± 10.2 years, p < 0.01, unadjusted) and had more comorbidities. Mortality at 1 year was the same (TAVI: 33.4% vs. SAVR 35.0%, p = 0.72, IPTW-adjusted) while it was lower with TAVI at 30 days (8.6% vs. 15.0%, p = 0.02, IPTW-adjusted). TAVI patients required more pacemaker implantation and showed more aortic regurgitation. SAVR patients required more blood transfusions and had longer hospital stay. Diabetes mellitus, atrial fibrillation, previous PCI, urgent procedure and EuroSCORE were associated with elevated 30-day mortality. Atrial fibrillation and older age were independent risk factor of 1-year mortality in both groups. CONCLUSIONS: Chronic dialysis patients with AS undergoing TAVI or SAVR had the same 1-year mortality, although survival at 30 days was better with TAVI. These results suggest that TAVI may improve peri-procedural outcomes.

Value of prognostic nutritional index for survival prediction in trans-catheter aortic valve replacement compared to other common nutritional indexes.

BACKGROUND: Nutritional status predicts outcomes after TAVR. Predictive value of Prognostic Nutritional Index (PNI) was investigated in patients undergoing TAVR, and compared to other nutritional indexes. METHODS: A cohort of 114 patients undergoing TAVR in a high-volume centre was studied. A prospective 1-year follow-up was completed. PNI was estimated as follows: (10 × serum albumin[g/dl])+(0.005 × total lymphocytes [1000/µl]). One-year survival was compared in patients with PNI above vs below median; Kaplan-Meier curves were created. A multivariate analysis was used to assess predictive value of PNI for 1-year mortality. ROC curves were used to assess discrimination by PNI, and to compare it with Geriatric Nutritional Risk Index (GNRI) and Body Mass Index (BMI). RESULTS: Mean age was 82.2 years, 59.6% were male. Mean PNI was 46 ± 5. Pre-procedurally, no differences were found between patients with high vs. low PNI. One-year mortality was significantly higher in patients with low PNI values (19/57 vs. 4/57; p < .001). Complications did not differ. A higher PNI predicted 1-year survival, even after adjusting for clinical factors (model 1: HR 0.8, 95% CI 0.7-0.9, p < .0001) and laboratory parameters (NT-proBNP, IL-6, CRP, eGFR, cystatin C, haemoglobin) (model 2: HR 0.8, 95% CI 0.7-0.9, p < .05). ROC curves revealed a stronger predictive value for PNI (AUC 0.80) compared to GNRI (0.77) and BMI (0.6). The optimal cut-off for PNI was 45. CONCLUSION: PNI is a useful and practical nutritional marker reflecting malnutrition and inflammation prior to the intervention, and strongly predicts 1-year survival. PNI seems to be a better prognostic marker than BMI or GNRI after TAVR.

New developments in transcatheter therapy of mitral valve disease.

Mitral valve regurgitation (MR) belongs to one of the most common acquired valve diseases in western countries with increasing prevalence in older age. For patients with high perioperative risk and older age prohibitive for valve surgery, the development of transcatheter mitral valve therapies offers new options. Assessment of the severity and etiology of MR and thorough imaging of the mitral valve anatomy and pathology are necessary prerequisites for appropriate decision making in the field of transcatheter mitral valve therapies. Different transcatheter repair and replacement techniques are on the market, most of them mimicking surgical techniques. With some techniques (e.g., the MitraClip device), there is good clinical experience (>80,000 devices implanted worldwide), and evidence (three randomized studies), whereas for newer procedures, safety and efficacy data are still very limited. Transcatheter mitral repair and replacement techniques have to be considered as complementary treatment options for high-risk patients indicated by the Heart Teams. The different techniques and devices will be introduced and discussed in the following paper.

Percutaneous Pulmonary Valve Implantation Based on Minimally Invasive Direct Coronary Bypass Surgery.

Approximately 5% of percutaneous pulmonary valve implantations (PPVIs) are at risk for coronary compression. Therefore, PPVI is contraindicated if coronary anomalies and tested coronary flow impairment are observed. Simultaneous right ventricular outflow tract ballooning and coronary angiography are mandatory elucidating contraindications for PPVI. We present the case of a 22-year-old woman who had Rastelli repair with chronic right heart failure. Weighing the risk of several offered surgical options, she underwent successful PPVI after minimally invasive direct coronary artery bypass procedure.

Clonal haematopoiesis in patients with degenerative aortic valve stenosis undergoing transcatheter aortic valve implantation.

AIMS: Clonal haematopoiesis of indeterminate potential (CHIP), defined as the presence of an expanded somatic blood cell clone without other haematological abnormalities, was recently shown to increase with age and is associated with coronary artery disease and calcification. The most commonly mutated CHIP genes, DNMT3A and TET2, were shown to regulate inflammatory potential of circulating leucocytes. The incidence of degenerative calcified aortic valve (AV) stenosis increases with age and correlates with chronic inflammation. We assessed the incidence of CHIP and its association with inflammatory blood cell phenotypes in patients with AV stenosis undergoing transfemoral aortic valve implantation (TAVI). METHODS AND RESULTS: Targeted amplicon sequencing for DNMT3A and TET2 was performed in 279 patients with severe AV stenosis undergoing TAVI. Somatic DNMT3A- or TET2-CHIP-driver mutations with a VAF ≥ 2% were detected in 93 out of 279 patients (33.3%), with an age-dependent increase in the incidence from 25% (55-69 years) to 52.9% (90-100 years). Patients with DNMT3A- or TET2-CHIP-driver mutations did not differ from patients without such mutations in clinical parameters, concomitant atherosclerotic disease, blood cell counts, inflammatory markers, or procedural characteristics. However, patients with DNMT3A- or TET2-CHIP-driver mutations had a profoundly increased medium-term all-cause mortality following successful TAVI. Differential myeloid and T-cell distributions revealed pro-inflammatory T-cell polarization in DNMT3A-mutation carriers and increased pro-inflammatory non-classical monocytes in TET2-mutation carriers. CONCLUSION: This is the first study to show that acquired somatic mutations in the most commonly mutated CHIP-driver genes occur frequently in patients with severe degenerative AV stenosis, are associated with increased pro-inflammatory leucocyte subsets, and confer a profound increase in mortality following successful TAVI.

Percutaneous pulmonary valve implantation (PPVI) in non-obstructive right ventricular outflow tract: limitations and mid-term outcomes.

BACKGROUND: Percutaneous pulmonary valve implantation (PPVI) has been established as a safe and effective alternative to surgery treating patients with a failing pulmonary valve conduit. Nevertheless, the majority of patients in need of a valve have a native, non-obstructive right ventricular outflow tract (RVOT). The current approved stent-valves have a balloon-expandable design. Pre-stenting of the RVOT to create a landing zone and also protect the valve stability is usually mandatory; large, non-obstructive RVOTs need pre-stenting to reduce the RVOT-diameter for a balloon-expandable valve implantation. METHODS: A retrospective study design was used to analyze the medium-term outcome after PPVI in a series of 26 patients with native or reconstructed RVOT. RESULTS: PPVI was successfully performed in all, but 1 (96%). Within the follow-up of a minimum of 2 years, the percutaneous implanted valves remained competent; a significant pressure gradient was not detected. Furthermore, no PPVI-related complications such as endocarditis, migration or stent fractures were observed. The electrocardiogram at rest, in particular the QRS duration remained unchanged immediate post-PPVI as well as at medium-term follow-up of 24 months. However, ventricular arrhythmias were documented in 3 patients (11.5%); all patients were successfully treated with antiarrhythmic drugs, utilizing metoprolol. A trial of an invasive catheter based RVOT-ablation in one remained unsuccessful; pre-stented RVOT did not allow a successful intervention. CONCLUSIONS: Medium-term follow-up showed excellent results of the mechanical valve function. PPVI utilizing balloon-expandable stent-valves in a native RVOT remains an off-label use. Despite our encouraging results, advanced manipulations of the patched or native RVOT might be associated with significant ventricular arrhythmias. There is a need for less invasive RVOT reduction devices.

Bone marrow and plasma FGF-23 in heart failure patients: novel insights into the heart-bone axis.

AIMS: Fibroblast growth factor 23 (FGF-23) is known to be elevated in patients with congestive heart failure (CHF). As FGF-23 is expressed in the bone but can also be expressed in the myocardium, the origin of serum FGF-23 in CHF remains unclear. It is also unclear if FGF-23 expressed in the bone is associated with outcome in CHF. The aim of the present study was to investigate FGF-23 levels measured in bone marrow plasma (FGF-23-BM) and in peripheral blood (FGF-23-P) in CHF patients to gain further insights into the heart-bone axis of FGF-23 expression. We also investigated possible associations between FGF-23-BM as well as FGF-23-P and outcome in CHF patients. METHODS AND RESULTS: We determined FGF-23-P and FGF-23-BM levels in 203 CHF patients (85% male, mean age 61.3 years) with a left ventricular ejection fraction (LVEF) ≤45% and compared them with those of 48 healthy controls (48% male, mean age 39.2 years). We investigated the association between FGF-23-BM and FGF-23-P with all-cause mortality in CHF patients, 32 events, median follow-up 1673 days, interquartile range [923, 1828]. FGF-23-P (median 60.3 vs. 22.0 RU/mL, P < 0.001) and FGF-23-BM (median 130.7 vs. 93.1 RU/mL, P < 0.001) levels were higher in CHF patients compared with healthy controls. FGF-23-BM levels were significantly higher than FGF-23-P levels in both CHF patients and in healthy controls (P < 0.001). FGF-23-P and FGF-23-BM correlated significantly with LVEF (r = -0.37 and r = -0.33, respectively), N terminal pro brain natriuretic peptide levels (r = 0.57 and r = 0.6, respectively), New York Heart Association status (r = 0.28 and r = 0.25, respectively), and estimated glomerular filtration rate (r = -0.43 and r = -0.41, respectively) (P for all <0.001) and were independently associated with all-cause mortality in CHF patients after adjustment for LVEF, estimated glomerular filtration rate, New York Heart Association status, and N terminal pro brain natriuretic peptide, hazard ratio 2.71 [confidence interval: 1.18-6.20], P = 0.018, and hazard ratio 2.80 [confidence interval: 1.19-6.57], P = 0.018, respectively. CONCLUSIONS: In CHF patients, FGF-23 is elevated in bone marrow plasma and is independently associated with heart failure severity and all-cause mortality. The failing heart seems to interact via FGF-23 within a heart-bone axis.

Transcatheter valve-in-valve implantation (VinV-TAVR) for failed surgical aortic bioprosthetic valves.

OBJECTIVE: We sought to investigate the procedural and hemodynamic outcome after valve-in-valve transcatheter aortic valve replacement (VinV-TAVR) for different surgical (SBV) and transcatheter (TAVR) bioprosthetic valves. METHODS AND RESULTS: 223 patients (76 ± 11years, STS-Score 8.3 ± 10.1) suffering from SBV failure treated with VinV-TAVR were enrolled at 6 centers across Germany. At time of the intervention, the majority of patients were in NYHA-class ≥ III (88%, n = 180). Failure mode of the SBVs was either stenosis, regurgitation (AR) or a combination of both in 85 (38%), 76 (34%) and 62 (28%) patients, respectively. 138 (62%) patients were treated with first generation TAVR valves (Edwards Sapien XT or CoreValve). Second generation valves were implanted in 85 (38%) patients (Sapien 3, Medtronic CoreValve Evolut, SJM-Portico, JenaValve). VinV-TAVR was associated with high procedural success rate, conversion to surgery was necessary in 3 (2%) patients. After VinV-TAVR procedure, 4 (2%) patients suffered from ≥ moderate AR. In 6 (3%) patients a second valve was implanted due to mispositioning of the first valve and subsequent severe paravalvular AR. Coronary obstruction was observed in 4 (2%) patients. Major bleeding and cerebrovascular complications (according to VARC) were reported in 3 (1%) and 4 (2%) patients at 30 days. Post-interventionally, 44/178 (25%) patients evidenced a mean pressure gradient (mPG) ≥ 20 mmHg. Residual stenosis was not associated with increased mortality (HR 0.39; 95% CI 0.13-1.22; p = 0.11). CONCLUSION: In VinV-TAVR for SBV-failure is a safe procedure resulting in hemodynamic improvement in the majority of patients. Residual stenosis is a common finding which can be observed in 1/4 of patients undergoing VinV-TAVR. However, this condition is not associated with increased 1-year-mortality.

Daily non-invasive haemodynamic telemonitoring for efficacy evaluation of MitraClip® implantation in patients with advanced systolic heart failure.

AIM: Patients with advanced systolic chronic heart failure frequently suffer from progressive functional mitral regurgitation. We report our initial experience in patients with an implanted pulmonary artery pressure (PAP) sensor, who developed severe mitral regurgitation, which was treated with the MitraClip system. We non-invasively compared changes in PAP values in patients after MitraClip with PAP changes in patients without MitraClip. METHODS AND RESULTS: Among 28 patients with New York Heart Association III heart failure with implanted PAP sensor for haemodynamic telemonitoring from a single centre, four patients (age 66 ± 6 years, left ventricular ejection fraction 21 ± 3%, and cardiac index 1.8 ± 0.3) received a MitraClip procedure and were compared with 24 patients (age 72 ± 8 years, left ventricular ejection fraction 26 ± 9.9%, and cardiac index 2.0 ± 1.0) without MitraClip procedure in a descriptive manner. Ambulatory PAP values were followed for 90 days in both groups. In comparison with the PAP values 4 weeks before MitraClip procedure, PAP was profoundly reduced in all four patients after 30 days (ΔPAPmean -11 ± 5, ΔPAPdiast -7 ± 3 mmHg, P < 0.02) as well as after 90 days (ΔPAPmean -6.3 ± 6, ΔPAPdiast -1 ± 3 mmHg). Reductions in PAP were accompanied by a profound reduction in N terminal pro brain natriuretic peptide as well as clinical and echocardiographic improvement. When analysing the dynamics with a regression model, reductions in all PAP values were significantly greater after MitraClip compared with conservative haemodynamic monitoring (P < 0.001). CONCLUSIONS: The efficacy of the interventional MitraClip procedure on clinical symptoms can be confirmed by haemodynamic telemonitoring. Thus, daily non-invasive haemodynamic telemonitoring allows, for the first time, for a continuous assessment of the haemodynamic efficacy of novel therapies in patients with chronic heart failure.

Therapeutic options for functional mitral regurgitation in chronic heart failure.

INTRODUCTION: Mitral regurgitation is a common finding in patients with chronic heart failure and is associated with a progressive worsening of symptoms, reduced survival and increased cost of care. However, the use of mitral valve surgery for these patients remains controversial and has not been shown to improve survival. Consequently, research has been increasingly directed towards the nonsurgical management of this important co-morbidity of heart failure. AREAS COVERED: The present review will describe the relevance of mitral regurgitation in people with chronic heart failure, the current options for percutaneous treatment and the evidence base for each of these. EXPERT COMMENTARY: Although at present there are few solid data to guide heart teams in deciding what degree of mitral regurgitation to treat, in which patients, and with what, this situation is likely to change over the next two years with the release of the first large randomised trials of percutaneous interventions.