Deformation of Transcatheter Aortic Valve Prostheses: Implications for Hypoattenuating Leaflet Thickening and Clinical Outcomes.

BACKGROUND: Although transcatheter aortic valve replacement (TAVR) therapy continues to grow, there have been concerns about the occurrence of hypoattenuating leaflet thickening (HALT), which may affect prosthesis function or durability. This study aimed to examine prosthesis frame factors and correlate their extent to the frequency of HALT and clinical outcomes. METHODS: We prospectively examined 565 patients with cardiac computed tomography screening for HALT at 30 days after balloon-expandable SAPIEN3 and self-expanding EVOLUT TAVR. Deformation of the TAVR prostheses, asymmetric prosthesis leaflet expansion, prosthesis sinus volumes, and commissural alignment were analyzed on the postprocedural computed tomography. For descriptive purposes, an index of prosthesis deformation was calculated, with values >1.00 representing relative midsegment underexpansion. A time-to-event model was performed to evaluate the association of HALT with the clinical outcome. RESULTS: Overall, HALT was present in 21% of SAPIEN3 patients and in 16% of EVOLUT patients at 30 days after TAVR. The occurrence of HALT was directly associated with greater prosthesis frame deformation (P<0.001), worse asymmetry of the leaflets (P<0.001), and smaller TAVR neosinus volumes (P<0.001). These relations were present in both prosthetic types and in all of their size ranges (all P<0.05). In multivariable analyses that include clinical variables previously associated with HALT (eg, anticoagulant therapy), variables of TAVR prosthesis deformation remained predictive of HALT. Although HALT was not associated with changes in prosthetic hemodynamics, its presence was associated with the risk of mortality at 1 year, with respect to greater incidences of all-cause mortality (hazard ratio, 2.98 [95% CI, 1.57-5.63]; P=0.001), cardiac death (hazard ratio, 4.58 [95% CI, 1.81-11.6]; P=0.001), and a composite outcome of all-cause mortality and heart failure hospitalization (hazard ratio, 1.94 [95% CI, 1.14-3.30]; P=0.02) with adjustment for age, sex, and comorbidities. CONCLUSIONS: Nonuniform expansion of TAVR prostheses resulting in frame deformation, asymmetric leaflet, and smaller neosinus volume is related to occurrence of HALT in patients who undergo TAVR. These data may have implications for both prosthesis valve design and deployment techniques to improve clinical outcomes for these patients.

Outcomes and challenges of the provisional stenting technique: Insights from the PROGRESS-BIFURCATION registry.

BACKGROUND: Provisional stenting is the most commonly used coronary bifurcation stenting strategy. METHODS: We examined the clinical and angiographic characteristics, challenges encountered, and procedural outcomes with the provisional bifurcation stenting strategy in the Prospective Global Registry of Percutaneous Coronary Intervention (PCI) in Bifurcation Lesions (PROGRESS-BIFURCATION, NCT05100992). RESULTS: Provisional stenting was used in 334 of 430 bifurcation interventions (78%). Technical success was lower (95% vs. 100%, p = 0.017) in provisional, but procedural success (90% vs. 95%, p = 0.095) and incidence of in-hospital major adverse cardiovascular events were similar (5% vs. 5%, p = 0.945) compared with two-stent strategies. Provisional was less often preferred in left main/left anterior descending involvement (47% vs. 73%, p < 0.001). Provisional stenting cases had smaller side branch (SB) diameter (2.4 ± 0.5 vs. 2.7 ± 0.6 mm, p < 0.001), shorter SB lesion length (5 [3-8] vs. 10 [5-10] mm, p < 0.001), less SB diameter stenosis (46 ± 35 vs. 81 ± 20%, p < 0.001), and were less likely to be Medina 1,1,1 (34% vs. 73%, p < 0.001). PCI challenges were less common (30% vs. 58%, p < 0.001) with provisional stenting: (1) rewiring difficulty (43%) that was overcome with use of a different wire (74%) or microcatheter (46%); (2) inability to deliver a stent (22%) or balloon (9%) that was overcome with use of a smaller balloon (88%), rewiring (25%), or increased support/microcatheter (25%). CONCLUSIONS: Provisional bifurcation stenting was more often performed in distal lesions with less SB involvement and had lower technical success, but similar procedural success and complications compared with two-stent strategies.

Early surgery or conservative management for asymptomatic severe aortic stenosis: Meta-analysis of RECOVERY and AVATAR.

The standard practice for management for asymptomatic severe aortic stenosis with a normal left ventricular systolic function is conservative management with a few exceptions. This practice is challenged by two recent randomized controlled trials (RCT). All the prior data is observational. We performed a meta-analysis of these 2 RCTs to determine if early surgical aortic valve replacement in this patient population is beneficial compared with the standard conservative therapy.

Adoptability and accuracy of point-of-care ultrasound in screening for valvular heart disease in the primary care setting.

PURPOSE: Despite continued efforts, a majority of patients with valvular heart disease (VHD) remain undiagnosed and untreated. This study aimed to assess the adoptability and accuracy of point-of-care handheld echocardiographic assessments (POCE) in the primary care setting. METHODS: Eleven previously untrained primary care providers were trained to use the Vscan Extend (GE, WI) POCE to assess VHD, left ventricular function (LVEF), and major extra-cardiac findings. Their assessments were compared to those of three blinded expert readers. A total of 175 patients underwent POCE assessments which were evaluated using Kappa statistics (κ) together with their estimated standard error, p value, and 95% CI bounds. RESULTS: Each patient had a mean of 3.3 ± 1.1 (±SD) assessments performed. Identical or nearly identical agreement between previously untrained primary providers and expert readers was evident for the diagnosis of tricuspid regurgitation, mitral regurgitation, pericardial effusion, and volume status. These agreements were strongest in apical long axis (κ = 1, p < 0.001) and parasternal long and short axis views (κ > =0.82 p < 0.001), though agreement remained robust in apical 4-chamber views (κ ≥ 0.76). The agreements in LVEF assessment were identical in the apical long axis view (κ = 1, p < 0.001) and robust in the remaining 3 views (κ > =0.66, p < 0.001). The assessments of aortic stenosis (parasternal/long, κ = 0.42, and parasternal/short, κ = 0.47, both p < 0.001) were weak in their agreement. CONCLUSION: Compared to expert echocardiography readers, the untrained providers' use of POCE for VHD shows high user adoptability and diagnostic accuracies in the primary care setting.

Transcatheter aortic valve replacement in patients with severe comorbidities: A retrospective cohort study.

OBJECTIVE: To investigate the long-term outcomes of patients with severe comorbidities (sCM) undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: The benefit of TAVR may be limited among patients with sCM due to a lack of mortality- or quality-of-life-benefit. METHODS: All TAVR patients in the Allina Health System between January 1, 2011 and August 7, 2018 were included (n = 890, 82 ± 8 years, 55% men). sCM included: severe lung disease, severe liver disease, end-stage renal disease, severe, severe dementia, severe dilated cardiomyopathy, and frailty. Outcomes between patients with (n = 215, 24%) and without (n = 675, 76%) sCM were compared. RESULTS: At baseline, patients with sCM had worse symptoms, higher STS-PROM and a lower Kansas City Cardiomyopathy Questionnaire (KCCQ) score compared to those without. During a median follow-up of 15 months (IQR, 7-29 months), there were 208 (23%) deaths. Patients with sCM had a lower 3-year survival free from all-cause mortality (40% vs. 79%, p < .001), and lower 3-year survival free from the composite endpoint of all-cause mortality, re-hospitalization for heart failure, myocardial infarction or stroke (31% vs. 64%, p < .001) compared to those without sCM. The estimated monthly increase in KCCQ scores following TAVR was 1.5, 95%CI (1.3, 1.7), p < .001 irrespective of sCM grouping. From Cox regression analysis, severe comorbidities, with the exception of liver disease, were associated with an increased risk of all-cause mortality and any additional comorbidity was associated with a multiplicative increase in risk of mortality of 2.8 (95%CI 2.3, 3.6), p < .001. CONCLUSIONS: TAVR patients with sCM have poor 3-year outcomes but may experience improvements in their quality of life.

Temporal changes in patient characteristics and outcomes in ST-segment elevation myocardial infarction 2003-2018.

BACKGROUND: We sought to describe changes in demographic variables, process of care measures, and outcomes of patients treated in a regional ST-segment elevation myocardial infarction (STEMI) program over the last 15 years. METHODS: We describe demographic variables, process of care measures, and outcomes of patients treated in the program in various 5-year time periods: 2003-2007 (n = 1,821), 2008-2012 (n = 1,968), and 2013-2018 (n = 2,223). The primary outcome measures were in-hospital and 30-day mortality. RESULTS: Among 6,012 STEMI patients treated from 2003 to 2018 we observed a significant increase in mean age at presentation (62 ± 14 to 64 ± 13 years) and diabetes (14-22%, p < .01). The proportion of patients with cardiogenic shock (CS) and cardiac arrest (CA) pre-PCI increased significantly from 9.5% to 11.1% and 8.5% to 12.7% (p < .05), respectively. The median door-to-balloon (D2B) times decreased from 98 to 93 min and total ischemic time decreased from 202 to 185 min (all p < .05). Despite increased patient complexity, the proportion of nontransfer and transfer patients achieving D2B times consistent with guideline recommendations remained unchanged (for nontransfer patients 79-82%, p = .45 and for transfer patients 65-64%, p = .34). Among all STEMI patients, in-hospital mortality increased during the study period from 4.9 to 6.9% (p = .007) but remained stable (<2%) when CA and CS patients were excluded. CONCLUSIONS: Over the last 15 years, short-term STEMI mortality has increased despite improvements in care delivery metrics. Patients with CA and/or CS now represent 10% of STEMI patients and are responsible for 80% of deaths. Therefore, efforts to improve STEMI mortality, and metrics for assessing STEMI programs, should focus on these patients.

Natural history observations in moderate aortic stenosis.

BACKGROUND: The natural history of patients with moderate aortic stenosis (AS) is poorly understood. We aimed to determine the long-term outcomes of patients with moderate AS. METHODS: We examined patients with moderate AS defined by echocardiography in our healthcare system, and performed survival analyses for occurrence of death, heart failure (HF) hospitalization, and progression of AS, with accounting for symptoms, left ventricular dysfunction, and comorbidities. RESULTS: We examined 729 patients with moderate AS (median age, 76 years; 59.9 % men) with a median follow-up of 5.0 years (interquartile range: 2.0 to 8.1 years). The 5-year overall survival was 52.3 % (95 % confidence interval [CI]: 48.6 % to 56.0 %) and survival free of death or HF hospitalization was 43.2 % (95 % CI: 39.5 % to 46.9 %). Worse New York Heart Association (NYHA) functional class was associated with poor long-term survival, with mortality rates ranging from 7.9 % (95 % CI: 6.6-9.2 %) to 25.2 % (95 % CI: 20.2-30.3 %) per year. Among patients with minimal or no symptoms, no futility markers, and preserved left ventricular function, 5-year overall survival was 71.9 % (95 % CI: 66.4-77.4 %) and survival free of death or HF hospitalization was 61.4 % (95 % CI: 55.5-67.3 %). Risk factors associated with adverse events were age, NYHA class, low ejection fraction and high aortic valve velocity (all p < 0.05). CONCLUSIONS: Patients with moderate AS are at significant risk of death. Our findings highlight the need for more study into appropriate therapeutic interventions to improve the prognosis of these patients.

Changes in quality of life in patients with low-flow aortic stenosis undergoing transcatheter aortic valve replacement.

BACKGROUND: We sought to quantify and compare changes in quality of life measures after transcatheter aortic valve replacement (TAVR) in patients with low-flow (LF) and normal-flow (NF) aortic stenosis (AS). METHODS: We included 297 patients treated with TAVR at Abbott Northwestern Hospital from January 2015 to October 2017. Health status was assessed at baseline and 30 days post-procedure using the Kansas City Cardiomyopathy Questionnaire 12 (KCCQ-12). Overall (KCCQ-OS) and domain-specific (physical limitation, symptom frequency, quality of life, and social limitation) scores were compared in three subsets of patients as defined by stroke volume index (≤ or >35 ml/m2 ), ejection fraction (EF) (≤ or >40%), and mean gradient (≤ or >40 mmHg). RESULTS: Of the 297 patients included, 129 (43%) had NF high-gradient (NF AS group) and 168 (56%) had LF severe AS, including 25 (8%) with low EF (8%) ("Classical" low-flow low-gradient LEF [LF-LG-LEF] group) and 143 (48%) with preserved EF ("Paradoxical" LF-LG group). At baseline, patients with LF-LG-LEF AS had more severe impairment in symptoms frequency (p = .06) but similar KCCQ-OS. At 1-month after TAVR, all groups had moderate improvements in quality of life (Delta KCCQ-OS: "Classical" LF-LG-LEF 18 ± 21, paradoxical AS 14 ± 18, and NF AS 15 ± 16, p = .57). During a median follow-up time of 2.4 years, there was no difference in mortality (p = .34) but patients with paradoxical LF-LG AS had a higher risk of rehospitalization for heart failure (p = .01). CONCLUSIONS: Patients with LF severe AS derive significant improvements in quality of life measures after TAVR, indistinguishable from patients with NF AS.

Outcomes after pacemaker implantation in patients with new-onset left bundle-branch block after transcatheter aortic valve replacement.

New-onset left bundle branch block (N-LBBB) after transcatheter aortic valve replacement (TAVR) is a challenging clinical dilemma. In our single-center study, 60 out of 172 patients who underwent permanent pacemaker implantation (PPM) after TAVR had N-LBBB (34.9%). At a median follow-up duration of 357 days (IQR, 178; 560 days), two patients (3.5%) were completely pacemaker-dependent, and four others (7%) were partially dependent. Twelve patients (24%) recovered conduction in their left bundle at a median follow-up duration of 5 weeks (IQR, 4; 14 weeks). Due to the lack of clinical predictors of pacemaker dependency, active surveillance is warranted and may be an alternative to permanent pacemaker implantation.

Incidence, predictors, management and outcomes of coronary perforations.

OBJECTIVES: We examined the contemporary incidence, types, predictors, angiographic characteristics, management and outcomes of coronary perforation. BACKGROUND: Coronary perforation is a rare, but important, complication of percutaneous coronary intervention (PCI). There is lack of data on perforations stratified as large and distal vessel perforations. METHODS: Retrospective, observational cohort study of all patients who underwent PCI at a high volume, tertiary hospital between the years 2009 and 2016. Angiograms of all coronary perforation cases were reviewed to determine the mechanism, type, and management of perforation. Risk-adjusted periprocedural complication rates were compared between patients with and without coronary perforation. One-year mortality outcomes of patients with large vessel vs. distal vessel perforation were also examined. RESULTS: Coronary perforation occurred in 68 of 13,339 PCIs (0.51%) performed during the study period: 51 (75%) were large vessel perforations and 17 (25%) distal vessel perforations. Most (67%) large vessel perforations were due to balloon/stent inflation, whereas most (94%) distal vessel perforations were due to guidewire exit. Patients with coronary perforations had significantly higher risk for periprocedural complications (adjusted odds ratio 7.57; 95% CI: 4.22-13.50; P < 0.001). Only one patient with large vessel perforation required emergency cardiac surgery, yet in-hospital mortality was high with both large vessel (7.8%) and distal vessel (11.8%) perforations. CONCLUSIONS: Coronary perforation is an infrequent, but potentially severe PCI complication. Most coronary perforations are large vessel perforations. Although coronary perforations rarely lead to emergency cardiac surgery, both distal vessel and large vessel perforations are associated with high in-hospital mortality, highlighting the importance of prevention.

Maneuvers for technical success with transcatheter mitral valve repair.

Mitral valve regurgitation (MR) is common, with a prevalence that exceeds 9% for those patients >75 years of age. For symptomatic patients with prohibitive surgical risk, transcatheter mitral valve repair with the MitraClip® system (Abbott Vascular, Menlo Park, CA) is available for clinical use and is effective in reducing MR in select patients. For optimal clinical success, the procedure requires mastery of complex catheterization skills with application of an in-depth understanding of the mitral valve anatomy. We herein describe elementary and advanced maneuvers for successful transcatheter mitral valve repair with MitraClip® . © 2017 Wiley Periodicals, Inc.

Impact of sleep deprivation on the outcomes of percutaneous coronary intervention.

OBJECTIVES: This study sought to compare the clinical outcomes of percutaneous coronary interventions (PCIs) performed by sleep deprived and non-sleep deprived operators. BACKGROUND: Interventional cardiologists are at risk for sleep deprivation as they often have to perform emergent procedures at night, but the effects of sleep deprivation on clinical outcomes have received limited study. METHODS: We examined the frequency, clinical characteristics, and outcomes of daytime PCIs performed by sleep deprived and non-sleep deprived operators at a tertiary medical center. Operators were considered sleep deprived when performing a daytime (7 am-11:59 pm) procedure preceded by a nighttime (12 am-6:59 am) procedure on the same date. RESULTS: Of the 12,680 daytime PCIs performed from 6/29/09 to 12/30/2016, 367 (2.9%) were performed by sleep deprived operators. Patients undergoing PCI performed by a sleep deprived operator were more likely to be younger, white, and to present with ST-elevation acute myocardial infarction (STEMI). The incidence of in-hospital death (1.1% vs. 1.3%, P = 1.0) and bleeding within 72 hr (3.9% vs. 2.9%, P = 0.29) were similar for procedures performed by sleep-deprived and non-sleep deprived operators. When the sleep deprived group was further stratified based on degree of sleep deprivation or length of sleep interruption, differences in mortality and total bleeding remained non-significant. CONCLUSIONS: In this large single center study, operator sleep deprivation did not appear to adversely impact PCI outcomes.

Meta-analysis of the impact of successful chronic total occlusion percutaneous coronary intervention on left ventricular systolic function and reverse remodeling.

BACKGROUND: We sought to examine the impact of coronary chronic total occlusion (CTO) percutaneous coronary intervention (PCI) on left ventricular (LV) function. METHODS: We performed a systematic review and meta-analysis of studies published between January 1980 and November 2017 on the impact of successful CTO PCI on LV function. RESULTS: A total of 34 observational studies including 2735 patients were included in the meta-analysis. Over a weighted mean follow-up of 7.9 months, successful CTO PCI was associated with an increase in LV ejection fraction by 3.8% (95%CI 3.0-4.7, P < 0.0001, I2 = 45%). In secondary analysis of 15 studies (1248 patients) that defined CTOs as occlusions of at least 3-month duration and reported follow-up of at least 3-months after the procedure, successful CTO PCI was associated with improvement in LV ejection fraction by 4.3% (95%CI [3.1, 5.6], P < 0.0001). In the 10 studies (502 patients) that reported LV end-systolic volume, successful CTO PCI was associated with a decrease in LV end-systolic volume by 4 mL, (95%CI -6.0 to -2.1, P < 0.0001, I2 = 0%). LV end-diastolic volume was reported in 9 studies with 403 patients and did not significantly change after successful CTO PCI (-2.3 mL, 95%CI -5.7 to 1.2 mL, P = 0.19, I2 = 0%). CONCLUSIONS: Successful CTO PCI is associated with a statistically significant improvement in LV ejection fraction and decrease in LV end-systolic volume, that may reflect a beneficial effect of CTO recanalization on LV remodeling. The clinical implications of these findings warrant further investigation.

Current Status of Catheter-Based Treatment of Mitral Valve Regurgitation.

PURPOSE OF REVIEW: This review examines the current status of catheter-based repair and replacement for mitral valve disease, with a focus on native primary and secondary mitral valve regurgitation. RECENT FINDINGS: Transcatheter mitral valve repair with the MitraClip®, with >40,000 performed procedures worldwide, has significantly advanced the field of transcatheter therapy for mitral valve regurgitation. Transcatheter mitral valve replacement remains in the early stages of development, mainly due to the complex anatomy and physiology of the mitral valve. Early feasibility studies in high-risk patients show promising procedural success, yet the adverse events require further study. Transcatheter therapies for mitral valve disease are the next endeavor for the pioneers of percutaneous structural heart disease interventions. Early results are encouraging but also show that further rigorous study is needed to determine efficacy and safety.

Failing left ventricle to ascending aorta conduit-Hybrid implantation of a melody valve and NuMed covered stent.

We present the case of a 36-year-old woman with increasing shortness of breath, a new 3/4 diastolic murmur, and a complex history of LV outflow tract obstruction. She has undergone multiple surgeries including the replacement of her old LV apex to ascending aorta conduit with a 20-mm Gore-Tex tube graft, addition of a 24-mm homograft sutured between the conduit and the LV apex, and insertion of a 21-mm Freestyle porcine valve conduit between the Gore-Tex tube graft and allograft at age 23. The current assessment showed a failing Freestyle conduit prosthesis leading to left heart decompensation. Due to substantial surgical risk, the patient underwent successful implantation of a Melody valve into the Gore-Tex tube and exclusion of the failing Freestyle bioprosthesis with a NuMed CP stent in a hybrid procedure. The case nicely illustrates the collaborative potential of cardiovascular surgeons and interventional cardiologists in the new arena of a hybrid operating room. Complex hybrid procedures like the current one, especially those including percutaneous placements of valves, offer therapeutic options for patients that are otherwise too high risk for conventional open heart surgery.

Inflammatory and injury signals released from the post-stenotic human kidney.

AIMS: The mechanisms mediating kidney injury and repair in humans with atherosclerotic renal artery stenosis (ARAS) remain poorly understood. We hypothesized that the stenotic kidney releases inflammatory mediators and recruits progenitor cells to promote regeneration. METHODS AND RESULTS: Essential hypertensive (EH) and ARAS patients (n=24 each) were studied during controlled sodium intake and antihypertensive treatment. Inferior vena cava (IVC) and renal vein (RV) levels of CD34+/KDR+ progenitor cells, cell adhesion molecules, inflammatory biomarkers, progenitor cell homing signals, and pro-angiogenic factors were measured in EH and ARAS, and their gradient and net release compared with systemic levels in matched normotensive controls (n= 24). Blood pressure in ARAS was similar to EH, but the glomerular filtration rate was lower. Renal vein levels of soluble E-Selectin, vascular cell adhesion molecule-1, and several inflammatory markers were higher in the stenotic kidney RV vs. normal and EH RV (P < 0.05), and their net release increased. Similarly, stem-cell homing factor levels increased in the stenotic kidney RV. Systemic CD34+/KDR+ progenitor cell levels were lower in both EH and ARAS and correlated with cytokine levels. Moreover, CD34+/KDR+ progenitor cells developed a negative gradient across the ARAS kidney, suggesting progenitor cell retention. The non-stenotic kidney also showed signs of inflammatory processes, which were more subtle than in the stenotic kidney. CONCLUSION: Renal vein blood from post-stenotic human kidneys has multiple markers reflecting active inflammation that portends kidney injury and reduced function. CD34+/KDR+ progenitor cells sequestered within these kidneys may participate in reparative processes. These inflammation-related pathways and limited circulating progenitor cells may serve as novel therapeutic targets to repair the stenotic kidney.

Remote ischemic preconditioning immediately before percutaneous coronary intervention does not impact myocardial necrosis, inflammatory response, and circulating endothelial progenitor cell counts: a single center randomized sham controlled trial.

AIMS: Percutaneous coronary intervention (PCI) is frequently accompanied by myocardial injury. The present study was performed to determine whether remote ischemic preconditioning (IP) induces cardioprotection during PCI. METHODS: We enrolled 95 patients requiring nonemergency PCI for stable disease or unstable angina into this prospective clinical trial. Patients were randomized to either remote IP (induced by three 3-min cycles of blood pressure cuff inflations to 200 mm Hg around the upper arm, followed by 3-min of reperfusion n = 47) or sham control (n = 48) immediately preceding PCI. The primary outcome measure was the frequency of post-PCI myonecrosis, defined as a peak postprocedural cTnT T ≥ 0.03 ng/dL. Secondary outcome measures were the change in plasma high-sensitivity C-reactive protein (hsCRP) levels following PCI and in endothelial progenitor cells (EPC) counts following IP. RESULTS: There was no difference in the primary endpoint of the frequency of PCI related myonecrosis which occurred in 22 (47%) and 19 (40%) patients in the remote IP and control groups, respectively, P = 0.42. There was significant increase in hsCRP post-PCI in both groups (P < 0.001), but there was no difference between the groups (median %change in hsCRP 46% vs. 54%, P = 0.73). There was no significant change in circulating early (CD34 -/CD133+/KDR+), intermediate (CD34+/CD133+/KDR+), or late (CD34+/CD133-/KDR+) EPC in the two groups immediately following IP. The composite rate of death, myocardial infarction, and target lesion revascularization at 1 year was 14.1% versus 13.7% (P = 0.90). CONCLUSIONS: Our study indicates that remote IP immediately before PCI does not induce cardioprotection in low to moderate risk patients.

Polyphenol-rich cranberry juice has a neutral effect on endothelial function but decreases the fraction of osteocalcin-expressing endothelial progenitor cells.

PURPOSE: Cranberry juice (CJ) contains a remarkably high concentration of polyphenols, considered to be beneficial for cardiovascular and bone health. The current double-blind, randomized study was designed to test whether daily consumption of double-strength Ocean Spray light CJ (2 × 230 ml) over 4 months has beneficial effects on vascular function and on endothelial progenitor cells (EPCs) carrying the osteoblastic marker osteocalcin in particular. METHODS: A total of 84 participants (49.5 ± 16.2 years) with peripheral endothelial dysfunction and cardiovascular risk factors were enrolled in this double-blind, randomized, controlled trial (69 completed the 4-month protocol-32 in the CJ group and 37 in the placebo group, respectively). Vascular responses to reactive hyperemia were measured non-invasively by peripheral arterial tonometry (EndoPAT). Peripheral blood mononuclear cells were stained for EPC markers, as well as osteocalcin, and counted by flow cytometry. RESULTS: Baseline characteristics were similar in both groups. The effect of CJ on peripheral endothelial function and on circulating EPC counts (CD34(+)/CD133(+)/KDR(+)) did not change during the study. A high percentage of EPCs expressed osteocalcin (59.4 ± 35.7%). CJ, as compared to placebo, induced a decrease in the fraction of EPCs expressing osteocalcin (-8.64 ± 48.98 and 19.13 ± 46.11%, respectively, p = 0.019). Systemic levels of the adhesion marker ICAM correlated significantly with the number of EPCs expressing osteocalcin. CONCLUSIONS: The study demonstrated that long-term supplementation of polyphenol-rich CJ did not improve peripheral endothelial function. However, the decrease in the fraction of osteocalcin+ EPCs suggests a potential beneficial effect of polyphenol-rich CJ.

Percutaneous treatment of aortic and mitral valve paravalvular regurgitation.

Percutaneous paravalvular leak closure represents a small but important niche in structural interventions in the current era of interventional cardiology. It is estimated that paravalvular regurgitation affects 5-17 % of all surgically implanted prosthetic heart valves (which equates to 500 to 10,200 cases annually). Patients may present with clinical signs and evidence of heart failure, hemolysis or both. Due to the increased morbidity and mortality, reoperation is often best avoided, especially if the underlying perivalvular tissue is friable or heavily calcified. Perimitral defects are usually approached in an antegrade approach via a transeptal puncture; periaortic defects usually in a retrograde approach. Depending on the number, size and shape of the defect(s) - as determined by 2D and 3D echocardiography - one or multiple closure devices are deployed using various wiring and anchor techniques. This brief review provides a summary of the currently applied paravalvular leak closure techniques.

Osteocalcin positive CD133+/CD34-/KDR+ progenitor cells as an independent marker for unstable atherosclerosis.

AIMS: For the characterization of endothelial progenitor cells (EPCs), commonly the markers CD34 and KDR have been used. CD133+/CD34-/KDR+ cells may represent more immature 'early' progenitors. In patients with coronary artery disease (CAD), a large fraction of EPCs carry the osteoblastic marker osteocalcin (OCN), which may mediate vascular calcification and abnormal repair. The aim of this study was to evaluate the expression of OCN+ 'early' EPCs in patients with risk factors (RFs) and a history of stable (history of stenting/coronary artery bypass grafting) or unstable CAD (myocardial infarction). METHODS AND RESULTS: Medical history and blood samples from 282 patients (age 58 ± 16 years) with CAD or at least one RF (mean 2.5 ± 1.5) were analysed. For the analysis of EPC markers (CD133, CD34, KDR) and OCN, the flow cytometry of peripheral blood mononuclear cells was performed. Circulating OCN+/CD133+/CD34-/KDR+ cells (median counts [interquartile range] per 100 000 events) were 15 [4-41] in patients with RF (n = 199), 26 [1-136] in those with a history of stable (n = 57), and 246 [105-308] in those with a history of unstable CAD (n = 26; P < 0.001). The association with unstable CAD remained highly significant even after multivariate adjusting for RFs and the different characteristics of the groups. Osteocalcin positive 'early' EPCs trend to predict further events [HR for each doubling of the cell number: 1.20 (95% CI: 1.00-1.46), P = 0.06]. CONCLUSION: Circulating OCN+ 'early' EPCs are strongly associated with unstable CAD. Therefore, this particular subset of EPCs could mediate abnormal vascular repair and may help identifying patients with a more unstable phenotype of atherosclerosis.