Caval Valve Implantation.

Transcathetertherapy has expanded the treatment options for patients with heart valve disease. Interventional therapy for aortic, mitral, and pulmonic valve disease is well established; however, catheter-based approaches to tricuspid regurgitation (TR) are still in early stages of development. For some of the interventional concepts to TR, including the edge-to-edge-repair, transcatheter annuloplasty, the tricuspid spacer, and caval valves, procedural feasibility and favorable early clinical outcome have been demonstrated in small compassionate case series. This article reviews the pathophysiological background and current evidence for caval valve implantation and examines the potential role of this approach for the treatment of severe TR.

Percutaneous Coronary Intervention in Stable Coronary Heart Disease -Is Less More?

BACKGROUND: This review concerns the putative benefit of percutaneous coronary intervention (PCI) over optimal medical therapy (OMT) for symptomatic patients with stable angina pectoris, or for asymptomatic persons in whom screening tests have revealed coronary heart disease (CHD; this entity has been newly designated chronic coronary syndrome, or CCS). Moreover, it addresses the question whether the indications for which PCI is now performed in Germany on patients with CCS are consistent with current scientific knowledge. METHODS: The pathophysiological concept of CHD and ischemia induction is discussed in the light of the scientific literature. This concept implies that PCI might be beneficial in the treatment of CCS. The benefit of PCI over OMT has now been evaluated in seven randomized trials (the so-called milestone trials). The current situation in Germany is presented here as well, on the basis of the available data. RESULTS: The pathophysiological concept of CHD implies that the particular coronary artery stenoses that are likely to give rise to a myocardial infarction (the so-called vulnerable plaques) cannot be identified prospectively with current methods. Moreover, a coronary artery stenosis will not necessarily cause myocardial ischemia. All of the randomized trials carried out to date that have compared OMT to PCI-plus-OMT in patients with CCS have led to the conclusion that PCI, because it focuses on individual coronary artery stenoses, cannot prolong survival or lower the incidence of myocardial infarction over the long term. This remains the case even if a single coronary artery stenosis is known to be causing moderate or severe myocardial ischemia (a conclusion of the ISCHEMIA trial). A PCI performed only because the coronary stenosis or stenoses meet certain morphological criteria, without any demonstration of a resulting functional disturbance, is generally detrimental to the health of the patient, with rare exceptions, and is inconsistent with the recommendations of current guidelines. The number of PCIs being performed in Germany at present is high compared to other countries; this arouses concern that the indications for it may be dubious in many cases. CONCLUSION: Current data imply that PCI for CCS does not improve outcomes in a large percentage of cases. A symptomatic benefit exists only in patients with frequent angina pectoris. The selection of CCS patients for PCI needs to be more strictly bound to the recommendations of current guidelines, particularly in Germany.

The History of Transcatheter Aortic Valve Implantation (TAVI)-A Personal View Over 25 Years of development.

In the early 1990s, the idea of Transcatheter Aortic Valve Implantation (TAVI) emerged from clinicians by the insight that the long-term hemodynamic and clinical results of aortic balloon valvuloplasty to treat aortic stenonosis were not satisfying. Thus, Anderson and Cribier developed the balloon-expandable and Figulla and Laborde the self-expendable TAVI systems. Sceptical views by the surgical colleagues and the industry delayed the rapid development of this disruptive new therapy until 2002, when Alain Cribier demonstrated for the first time the proof of his concept. Bulky devices and paravalvular leakages in patients treated in terms of compassionate care resulted in high mortality rates. From 2005 onwards, the treatment of patients not at highest risk using smoother devices in clinical trials could demonstrate that the technology was equivalent to surgical aortic valve replacement. The transapical access route initiated the heart team approach with the surgical colleagues, however, this access route is presently expiring due to its greater trauma. The need to treat also aortic regurgitation is addressed by the "clipping technology" of JenaValve™. Ongoing clinical trials investigate an extended indication for TAVI at an earlier stage of aortic stenosis, or in reduced ejection fraction, and just demonstrated the safety and efficiency even in low surgical risk patients.

Pulmonary Hypertension in Patients With Severe Aortic Stenosis: Prognostic Impact After Transcatheter Aortic Valve Replacement: Pulmonary Hypertension in Patients Undergoing TAVR.

OBJECTIVES: The authors investigated the development of pulmonary hypertension (PH), predictors of PH regression, and its prognostic impact on short, mid-, and long-term outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS). BACKGROUND: PH represents a common finding in patients with AS. Although TAVR is frequently associated with regression of PH, the predictors of reversible PH and its prognostic significance remain uncertain. METHODS: In this study, 617 consecutive patients undergoing TAVR between 2009 and 2015 were stratified per baseline tertiles of pulmonary artery systolic pressure (PASP) as follows: normal (PASP <34 mm Hg), mild-to-moderate (PASP ≥34 mm Hg and <46 mm Hg), and severe PASP elevation (PASP ≥46 mm Hg). After TAVR, 520 patients with PH at discharge were stratified according to the presence or absence of PASP reduction. Primary outcome was all-cause mortality at 30 days, 1 year, and long-term follow-up at a maximum of 5.9 years. RESULTS: In patients with both mild-to-moderate and severe PH at baseline, PASP decreased significantly at discharge (ΔPASP 3.0 ± 9.3 mm Hg and 12.0 ± 10.0 mm Hg, respectively) and 1 year (ΔPASP 5.0 ± 9.7 mm Hg and 18.0 ± 14.0 mm Hg, respectively). At a median follow-up of 370 days (interquartile range [IQR]: 84 to 500 days), the risk of all-cause mortality was similar among baseline PASP groups at all time intervals evaluated. After TAVR, a significant regression of PH was observed in 46% of patients. Contrarily, patients with residual PH had a higher risk of all-cause mortality at 30 days (hazard ratio [HR]: 3.49, 95% confidence interval [CI]: 1.74 to 6.99; p < 0.001), 1 year (HR: 3.12, 95% CI: 2.06 to 4.72; p < 0.001), and long-term (HR: 2.47, 95% CI: 1.74 to 3.49; p < 0.001). Left ventricular ejection fraction (LVEF) >40% (odds ratio [OR]: 3.56, 95% CI: 2.24 to 5.65; p < 0.001), baseline PASP ≥46 mm Hg (OR: 3.26, 95% CI: 2.07 to 5.12; p < 0.001), absence of concomitant tricuspid regurgitation (TR) ≥ moderate (OR: 0.53, 95% CI: 0.34 to 0.84; p < 0.001), and logistic EuroSCORE <25% (OR: 1.59, 95% CI: 1.04 to 2.45; p = 0.03) were independent predictors of PASP reduction. CONCLUSIONS: In most patients with PH and AS, TAVR is associated with a significant early and late reduction of PASP. Patients with reversible PH after TAVR are at lower risk of all-cause mortality at early, mid-, and long-term follow-up. Therefore, the presence of PH should not preclude treatment with TAVR.

Insulin like growth factor binding protein 2 (IGFBP-2) for risk prediction in patients with severe aortic stenosis undergoing Transcatheter Aortic Valve Implantation (TAVI).

INTRODUCTION: Severe aortic stenosis (AS) caused by degenerative calcification is the most frequent acquired valvular heart disease worldwide and mortality rates are considerably high. Transcatheter Aortic Valve Implantation (TAVI) is a well-established method for valve replacement in high risk patients with AS. However, there is a lack of reliable predictors for patients undergoing TAVI since commonly used scores were developed for surgical populations. MATERIALS AND METHODS: 208 patients subjected to TAVI were included in this study. Plasma samples were obtained before TAVI and were evaluated for IGFBP-2 using commercially available ELISA kits. IGFBP-2 levels were analyzed for their ability for risk prediction after TAVI. RESULTS: IGFBP-2 levels measured before TAVI correlated significantly with left ventricular ejection fraction, EUROSCORE and other functional and prognostic parameters like the 6-minute walking test. When patients were retrospectively divided in two groups with a cut-off of serum IGFBP-2 levels of 275 ng/ml, IGFBP-2 was a strong predictor for 30-day and one-year mortality (3% vs. 11%, p = 0.05 and 18.2% vs. 46.2%; p < 0.001 respectively). Compared to an EUROSCORE above 20 or an STS score cut-off above 8, IGFBP-2 plasma levels above 275 ng/ml outperformed the established risk score for prediction of one-year mortality as assessed by NRI (0.65 95% CI 0.37-0.94; p < 0.001 and 0.54 95% CI 0.25-0.82; p < 0.001, respectively). CONCLUSIONS: Our results indicate that IGFBP-2 could serve as new outcome predictor for patients undergoing TAVI procedure. By providing additional information to the commonly used EUROSCORE, IGFPB-2 analysis could further assist Heart Team decision making.

Efficacy of temperature-guided cryoballoon ablation without using real-time recordings - 12-Month follow-up.

BACKGROUND: We sought to evaluate a temperature-guided approach of cryoballoon (CB) ablation without visualization of real-time recordings. METHODS AND RESULTS: We analysed 166 patients (34.9% female, 60 ±â€¯11 years) with paroxysmal or short-term persistent atrial fibrillation (AF). Comorbidities included diabetes mellitus (n = 28), coronary artery disease (n = 24), hypertension (n = 122), previous stroke or TIA > 3 months (n = 12). Cryoablation of the pulmonary veins (PV) was performed using first-generation (n = 78) and second-generation CB (n = 88). Two 5-minute freezes were performed for the first-generation and two 4-minute freezes for the second-generation CB with the intention to achieve a temperature drop below -40 °C. At 12-month follow-up, we observed overall freedom from AF in 92 patients (56.6%, mean time to AF recurrence 3.4 ±â€¯2.9 months). There was a significant difference in freedom from AF between first-generation CB (45%) and second-generation CB (67%; p < 0.005). Complications were groin hematoma (4.8%) and phrenic nerve palsy (PVP) (2.4%). PVP disappeared after 12 months in all patients. Three patients developed cardiac tamponade (1.8%) that resolved without further sequelae after pericardiocentesis. Multivariate analysis revealed that only the achieved temperature in the right inferior PV (RIPV) was a predictor of long-term freedom from AF (OR 0.9; p = 0.014). Female gender was a predictor of AF recurrence (OR 6.1; p = 0.022). CONCLUSION: Temperature-guided CB ablation without real-time recordings is feasible and safe without reducing the efficacy if second-generation CB is used. Deep nadir temperatures especially in the RIPV are necessary for long term-success.

Multi-biomarker analysis in patients after transcatheter aortic valve implantation (TAVI).

BACKGROUND: In this study we sought to examine whether transcatheter aortic valve implantation (TAVI) is followed by a change in the plasma levels of novel cardiovascular biomarkers. METHODS: We collected blood samples of 79 patients with severe aortic valve stenosis undergoing TAVI before and at 7 days, 1 month, 3 months and 6 months post TAVI and analyzed the plasma concentrations of GDF-15, H-FABP, fetuin-A, galectin 3, sST2 and suPAR by means of ELISA. RESULTS: There was a significant increase in the concentration of fetuin-A (median: 52.44 mg/ml to 113.2 mg/ml, p < 0.001) and a significant decrease of H-FABP after TAVI (median: 4.835 ng/ml to 2.534 ng/ml, p < 0.001). The concentrations of suPAR and sST2 showed an initial increase (suPAR median: 2755 pg/ml 3489 pg/ml, p < 0.001; sST2 median: 5832 pg/ml to 7137 pq/ml, p < 0.001) and subsequently decreased significantly. CONCLUSION: We hypothesize that the decrease of H-FABP and the increase of fetuin-A could be due to a hemodynamic improvement after valve replacement. The initial increase of suPAR could indicate an inflammatory stimulus and the significant increase in sST2 could be due to the mechanical strain caused by implantation of the valve.

Interventional Treatment of Severe Tricuspid Regurgitation: Early Clinical Experience in a Multicenter, Observational, First-in-Man Study.

BACKGROUND: Transcatheter caval valve implantation is under evaluation as a treatment option for inoperable patients with severe tricuspid regurgitation (TR). The procedure involves the catheter-based implantation of bioprosthetic valves in the inferior vena cava and superior vena cava to treat symptoms associated with TR. This study is the first to evaluate the feasibility, safety, and efficacy of this interventional concept. METHODS AND RESULTS: Twenty-five patients (mean age, 73.9±7.6 years; women, 52.0%) with severe symptomatic TR despite optimal medical treatment deemed unsuitable for surgery were treated with caval valve implantation under a compassionate clinical use program. Technical feasibility defined as procedural success, hemodynamic effect defined as venous pressure reduction, and safety defined as periprocedural adverse events were evaluated, with clinical follow-up at discharge and up to 12 months. The functional impact was evaluated by assessment of New York Heart Association class at the time of hospital discharge. The total number of valves implanted in the caval position was 31. Patients were treated with single (inferior vena cava-only; n=19; 76.0%) or bicaval valve implantation (inferior vena cava+superior vena cava; n=6; 24.0%). Either balloon-expandable valves (Sapien XT/3: n=18; 72.0%) or self-expandable valves (TricValve: n=6; 24.0%; Directflow: n=1; 4.0%) were used. Procedural success was achieved in 96% (n=24). Early and late valve migration requiring surgical intervention occurred in 1 patient each. Thirty-day and in-hospital mortality were 8% (2 of 25) and 16% (4 of 25). Causes of in-hospital mortality included respiratory (n=1) or multiple organ failure (n=3) and were not linked to the procedure. Mean overall survival in the study cohort was 316±453 days (14-1540 days). CONCLUSIONS: Caval valve implantation for the treatment of severe TR and advanced right ventricular failure is associated with a high procedural success rate and seems safe and feasible in an excessive-risk cohort. The study demonstrates hemodynamic efficacy with consistent elimination of TR-associated venous backflow and initial clinical improvement. These results encourage further trials to determine which patients benefit most from this interventional approach.

Vena contracta area for severity grading in functional and degenerative mitral regurgitation: a transoesophageal 3D colour Doppler analysis in 500 patients.

Aims: Vena contracta area (VCA3D), derived by 3D colour Doppler echocardiography, has already been validated against cardiac magnetic resonance imaging, but the number of clinical studies to define cut-off values for grading of mitral regurgitation (MR) is limited. Aim of the study was to assess VCA3D in a large population of patients with functional (FMR) and degenerative MR (DMR). Methods and results: Transoesophageal echocardiography was performed in 500 patients with MR. The following 2D parameters were assessed for grading of MR: vena contracta width, effective regurgitant orifice area (EROAPISA), and regurgitation volume (RVPISA). VCA3D and the corresponding regurgitation volume (RVVCA) were quantified using 3D colour Doppler loop and CW Doppler tracing of the regurgitant jet. In 104 patients a 3D dataset of the left ventricle (LV) and the left ventricular outflow tract (LVOT) was acquired. As a reference method, regurgitation volume (RV3D) was calculated as difference between LV overall and LVOT stroke volumes. For prediction of severe MR, VCA3D yielded higher values of area under the ROC curve compared to EROAPISA (overall patient group 0.98 for VCA3D vs. 0.90 for EROAPISA, P < 0.001; FMR group 0.97 for VCA3D vs. 0.92 for EROAPISA, P = 0.002). RVVCA correlated closer with RV3D compared to RVPISA (r = 0.96 for RVPISA, r = 0.79 for RVPISA). Conclusion: This study delivers cut-off values for VCA3D in patients with different types of MR. VCA3D is a robust parameter for quantification of MR, showing a good correlation with the reference method using 3D datasets of LV.

Caval Valve Implantation.

Recently, transcatheter therapy has expanded the treatment options for patients with heart valve disease. With the growing understanding of tricuspid regurgitation and its natural history, it becomes increasingly obvious that this patient population is a heterogeneous cohort presenting for treatment in different stages of a continuous disease process. It is still unclear which interventional approach will result in functional and clinical success and in which subtype of patient population. This article reviews the pathophysiologic background and current evidence for caval valve implantation and examines the potential role of this approach for the treatment of severe tricuspid regurgitation.

Impact of concomitant mitral regurgitation on transvalvular gradient and flow in severe aortic stenosis: a systematic ex vivo analysis of a subentity of low-flow low-gradient aortic stenosis.

AIMS: Evaluation of aortic stenosis (AS) is based on echocardiographic measurement of mean pressure gradient (MPG), flow velocity (Vmax) and aortic valve area (AVA). The objective of the present study was to analyse the impact of systemic haemodynamic variables and concomitant mitral regurgitation (MR) on aortic MPG, Vmax and AVA in severe AS. METHODS AND RESULTS: A pulsatile circulatory model was designed to study function and interdependence of stenotic aortic (AVA: 1.0 cm², 0.8 cm² and 0.6 cm²) and insufficient mitral prosthetic valves (n=8; effective regurgitant orifice area [EROA] <0.2 cm² vs. >0.4 cm²) using Doppler ultrasound. In the absence of severe MR, a stepwise increase of stroke volume (SV) and a decrease of AVA was associated with a proportional increase of aortic MPG. When MR with EROA <0.2 cm² vs. >0.4 cm² was introduced, forward SV decreased significantly (70.9±1.1 ml vs. 60.8±1.6 ml vs. 47.4±1.1 ml; p=0.02) while MR volume increased proportionally. This was associated with a subsequent reduction of aortic MPG (57.1±9.4 mmHg vs. 48.6±13.8 mmHg vs. 33.64±9.5 mmHg; p=0.035) and Vmax (5.09±0.4 m/s vs. 4.91±0.73 m/s vs. 3.75±0.57 m/s; p=0.007). Calculated AVA remained unchanged (without MR: AVA=0.53±0.04 cm² vs. with MR: AVA=0.52±0.05 cm²; p=ns). In the setting of severe AS without MR, changes of vascular resistance (SVR) and compliance (C) did not impact on aortic MPG (low SVR and C: 66±13.8 mmHg and 61.1±20 mmHg vs. high SVR and C: 60.9±9.2 mmHg and 71.5±13.5 mmHg; p=ns) In concomitant severe MR, aortic MPG and Vmax were not significantly reduced by increased SVR (36.6±2.2 mmHg vs. 34.9±5.6 mmHg, p=0.608; 3.89±0.18 m/s vs. 3.96±0.28 m/s; p=ns). CONCLUSIONS: Systemic haemodynamic variables and concomitant MR may potentially affect diagnostic accuracy of echocardiographic AS evaluation. As demonstrated in the present study, MPG and Vmax are flow-dependent and significantly reduced by a reduction of forward SV from concomitant severe MR, resulting in another entity of low-flow low-gradient aortic stenosis. In contrast, calculated AVA appears to be a robust parameter of AS evaluation if severe MR is present. Changes of SVR and C did not affect the diagnostic accuracy of AS evaluation.

Elevated plasma levels of interleukin-16 in patients with acute myocardial infarction.

Interleukin (IL)-16, a polypeptide cytokine, plays a crucial role in the inflammatory process, acting as a chemoattractant for peripheral immune cells and has been linked to various inflammatory diseases. However, its role in patients with acute myocardial infarction (AMI) is unclear.We retrospectively analyzed serum levels of IL-16 in blood of patients with (STEMI, n = 45) and without ST-segment elevation myocardial infarction (NSTEMI, n = 42) compared with controls with excluded coronary artery disease (n = 55). Furthermore, correlation analysis with inflammatory cells, C-reactive protein (CRP) levels, dendritic cell precursors (DCPs), and other clinical and biochemical markers was performed.Compared with controls, patients with STEMI and NSTEMI evidenced higher levels of IL-16 in pg/mL (STEMI: 759.38 ±â€Š471.54, NSTEMI: 677.77 ±â€Š438.8, control: 500.45 ±â€Š432.21; P = .002). IL-16 correlated with CRP (r = 0.26, P = .001), leucocytes (r = 0.38, P < .001), NT-proBNP (r = 0.20, P = .02) and hsTnT (r = 0.25, P = .004). Circulating myeloid DCPs, plasmacytoid DCPs, and total DCPs showed a significant inverse correlation to IL-16 levels (r = -0.21, P = .01; r = -0.23, P = .005; r = -0.26, P = .002, respectively).Interleukin-16 might play an important role in the inflammatory process of patients suffering from AMI and correlates with inflammatory cell activation and clinical and biochemical markers. The cytokine IL-16 might upregulate the proinflammatory response and recruitment of inflammatory cells into infarcted myocardium.

Impact of Moderate Altitude on Pro-Inflammatory Cytokines in Healthy Volunteers.

BACKGROUND: The induction of microvascular inflammation and the effects on cytokine production in blood due to hypoxia has been shown in the past. We have previously reported a statistically significant increase of the pro-inflammatory cytokine interleukin-8 (IL-8) in normobaric hypoxia in the setting of a hypoxia-chamber. In the present study, we sought to analyze plasma levels of inflammatory cytokines in a real-life stetting in order to foster our knowledge on hypoxia induced microvascular inflammation at moderate altitude. METHODS: Pro-inflammatory cytokines (IL-8, IL-6, TNF-α) were measured in an experimental field study, exposing 18 healthy volunteers to moderate hypoxia while staying at a mountain lodge in Diavolezza, Switzerland (2978 meters above sea level). Plasma cytokine levels were measured by ELISA. RESULTS: In contradiction to our results in a normobaric hypoxia-chamber, exposure to moderate hypoxia led to a significant decrease of plasma IL-8 levels in a real-life setting (from 2.902 (1.046 - 4.984) pg/mL to 1.395 (0.698 - 3.712) pg/mL, p = 0.034). Concentrations of IL-6 and TNF-α did not show statistically significant changes in comparison to baseline measurements. CONCLUSIONS: The results of this study show a decrease of proinflammatory cytokine IL-8 in a real life setting of moderate altitude in healthy individuals. Initiation of angiogenesis or subliminal stimulus for an altitude-induced inflammatory reaction may be explanations for this unexpected finding.

Multibiomarker analysis in patients with acute myocardial infarction.

BACKGROUND: Novel biomarkers representing different pathobiological pathways and their role in patients with acute myocardial infarction (AMI) were studied. METHODS: We retrospectively analysed serum levels of soluble suppression of tumorigenicity (sST2), growth-differentiation factor-15 (GDF-15), soluble urokinase plasminogen activator receptor (suPAR), heart-type fatty acid-binding protein (H-FABP) and plasma fetuin A in blood of patients with AMI (STEMI, n = 61; NSTEMI, n = 57) compared to controls with excluded coronary artery disease (n = 76). Furthermore, detailed correlation analysis was performed. RESULTS: Compared with controls, in patients with STEMI and NSTEMI higher levels expressed as median of sST2 in pg/mL (STEMI: 13210·9, NSTEMI: 11989·1, control: 5248; P < 0·001), GDF-15 in pg/mL (STEMI: 818·8, NSTEMI 677·5, control 548·6; P < 0·001), suPAR in pg/mL (STEMI: 3461·1, NSTEMI: 3466·7, control: 2463·6; P < 0·001), H-FABP in ng/mL (STEMI: 5·8, NSTEMI: 5·4, control: 0·0; P < 0·001) and lower plasma fetuin A levels in µg/mL (STEMI: 95, NSTEMI: 54, control: 116·6; P < 0·001) were detected. Correlation analysis found clinical and biochemical parameters such as ejection fraction, length of hospital stay, creatine kinase, NT-proBNP and hs Troponin T levels as well as inflammatory markers (CRP, leucocytes) to be significantly correlated with novel biomarkers. CONCLUSION: Plasma levels of novel biomarkers were significantly elevated (sST2, GDF-15, H-FABP, suPAR) or inversely downregulated (fetuin A) in patients with AMI compared to a control group with excluded coronary artery disease. Significant correlations with various clinical parameters and standard biochemical markers were found.

Acute effects of moderate altitude on biomarkers of cardiovascular inflammation and endothelial function and their differential modulation by dual endothelin receptor blockade.

BACKGROUND: Endothelial dysfunction is accompanied by the release of microparticles (MP). OBJECTIVE: We sought to investigate the effect of moderate hypoxia on circulatory levels of microparticles, biomarkers of cardiovascular function and inflammation and on echocardiographic parameters in healthy volunteers staying at an altitude of 2978 m. METHODS: Eighteen healthy volunteers were subjected to moderate hypoxia by staying at 2978 m above sea level for three days. Blood samples were evaluated for MP using flow cytometry. ELISA analysis was performed for sST2, H-FABP, suPAR and GDF-15. Moreover, the effect of dual endothelin-receptor blockade was investigated. RESULTS: Oxygen saturation decreased to 93%. A significant decrease of endothelial and platelet MP levels was found. These results were corroborated by a similar response in sST2 and suPAR plasma concentration. Endothelin-receptor blockade by macitentan only had a marginal influence on MP, sST2, H-FABP, suPAR and GDF-15 levels, though it led to a significant amelioration of echocardiographic parameters of right heart function. CONCLUSIONS: These experimental results show that moderate hypoxia due to altitude exposition led to a reduction in parameters of endothelial dysfunction as shown by a decrease in endothelial and platelet MP, sST2 and suPAR levels. A slight increase in pulmonary pressure at moderate altitude was decreased by dual endothelin receptor blockade.

Endothelial progenitor cells and plaque burden in stented coronary artery segments: an optical coherence tomography study six months after elective PCI.

BACKGROUND: Endothelial progenitor cells (EPC) are involved in neovascularization and endothelial integrity. They might be protective in atherosclerosis. Optical coherence tomography (OCT) is a precise intracoronary imaging modality that allows assessment of subintimal plaque development. We evaluated the influence of EPC on coronary plaque burden in stable disease and implemented a novel computational plaque analysis algorithm using OCT. METHODS: Forty-three patients (69.8% males, 69.6 ± 7.7 years) were investigated by OCT during re-angiography 6 months after elective stent implantation. Different subpopulations of EPCs were identified by flow cytometry according to their co-expression of antigens (CD34+, CD133+, kinase domain receptor, KDR+). An algorithm was applied to calculate the underlying total plaque burden of the stented segments from OCT images. Plaque morphology was assessed according to international consensus in OCT imaging. RESULTS: A cumulative sub-strut plaque volume of 10.87 ± 12.7 mm3 and a sub-stent plaque area of 16.23 ± 17.0 mm2 were found within the stented vessel segments with no significant differences between different stent types. All EPC subpopulations (mean of EPC levels: CD34+/CD133+: 2.66 ± 2.0%; CD34+/KDR+: 7.50 ± 5.0%; CD34+/CD133+/KDR+: 1.12 ± 1.0%) inversely correlated with the identified underlying total plaque volume and plaque area (p ≤ 0.012). CONCLUSIONS: This novel analysis algorithm allows for the first time comprehensive quantification of coronary plaque burden by OCT and illustration as spread out vessel charts. Increased EPC levels are associated with less sub-stent coronary plaque burden which adds to previous findings of their protective role in atherosclerosis.