Jan-Malte Sinning

Aortic regurgitation index defines severity of peri-prosthetic regurgitation and predicts outcome in patients after transcatheter aortic valve implantation.

OBJECTIVES The aim of this study was to provide a simple, reproducible, and point-of-care assessment of peri-prosthetic aortic regurgitation (periAR) during transcatheter aortic valve implantation (TAVI) and to decipher the impact of this peri-procedural parameter on outcome. BACKGROUND Because periAR after TAVI might be associated with adverse outcome, precise quantification of periAR is of paramount importance but remains technically challenging. METHODS The severity of periAR was prospectively evaluated in 146 patients treated with the Medtronic CoreValve (Minneapolis, Minnesota) prosthesis by echocardiography, angiography, and measurement of the aortic regurgitation (AR) index, which is calculated as ratio of the gradient between diastolic blood pressure (DBP) and left ventricular end-diastolic pressure (LVEDP) to systolic blood pressure (SBP): [(DBP - LVEDP)/SBP] × 100. RESULTS After TAVI, 53 patients (36.3%) showed no signs of periAR and 71 patients (48.6%) showed only mild periAR, whereas 18 patients (12.3%) and 4 patients (2.7%) suffered from moderate and severe periAR, respectively. The AR index decreased stepwise from 31.7 ± 10.4 in patients without periAR, to 28.0 ± 8.5 with mild periAR, 19.6 ± 7.6 with moderate periAR, and 7.6 ± 2.6 with severe periAR (p < 0.001), respectively. Patients with AR index <25 had a significantly increased 1-year mortality risk compared with patients with AR index ≥25 (46.0% vs. 16.7%; p < 0.001). The AR index provided additional prognostic information beyond the echocardiographically assessed severity of periAR and independently predicted 1-year mortality (hazard ratio: 2.9, 95% confidence interval: 1.3 to 6.4; p = 0.009). CONCLUSIONS The assessment of the AR index allows a precise judgment of periAR, independently predicts 1-year mortality after TAVI, and provides additional prognostic information that is complementary to the echocardiographically assessed severity of periAR.

Renal Function as Predictor of Mortality in Patients After Percutaneous Transcatheter Aortic Valve Implantation

OBJECTIVES The aim of this study was to determine the influence of baseline renal function and periprocedural acute kidney injury (AKI) on prognosis after transcatheter aortic valve implantation (TAVI). BACKGROUND Evidence is growing that renal function is a major predictor of mortality in patients after TAVI. METHODS TAVI was performed with the 18-F CoreValve prosthesis via transfemoral access. All-cause mortality was determined 30 days and 1 year after TAVI in 77 patients with a mean Society of Thoracic Surgeons mortality score of 9.3 ± 6.1% and a mean logistic European System for Cardiac Operative Risk Evaluation of 31.2 ± 17.6%. RESULTS Overall procedural success rate was 98% with 1 periprocedural death. The 30-day mortality was 10%, and 1-year mortality was 26%. The mortality risk increased stepwise across quartiles of baseline serum creatinine. An AKI occurred in 20 of 77 patients: 12 patients (60%) with AKI died during follow-up. The incidence of AKI was related to peripheral arterial disease (65% vs. 39%; p = 0.04), the occurrence of a systemic inflammatory response syndrome (60% vs. 21%, p = 0.002), and post-procedural peri-prosthetic regurgitation ≥2+ (35% vs. 9%, p = 0.02). Impaired renal function at baseline reflected by serum creatinine ≥1.58 mg/dl (hazard ratio: 3.9, 95% confidence interval: 1.6 to 9.5; p = 0.002) and the occurrence of AKI (hazard ratio: 5.9, 95% confidence interval: 2.4 to 14.5, p < 0.001) that was not related to the amount of contrast dye were strong predictors of 1-year mortality after TAVI. CONCLUSIONS Impaired renal function at baseline and the occurrence of periprocedural AKI, independent whether renal function returns to baseline or not, are strong predictors of 30-day and 1-year mortality after TAVI.

Circulating CD31+/Annexin V+ microparticles correlate with cardiovascular outcomes

AIMS CD31+/Annexin V+ microparticles (MPs) are increased in patients with cardiovascular risk factors and impaired coronary endothelial function. We evaluated whether MPs are an independent marker for cardiovascular events in patients with stable coronary artery disease (CAD). METHODS AND RESULTS The number of CD31+/Annexin V+ MP was determined by flow cytometry in 200 patients (age 66.1±10.4 years) and correlated with cardiovascular outcomes. The median follow-up time for major adverse cardiovascular and cerebral event (MACCE)-free survival was 6.1 (6.0/6.4) years. Four patients were lost to follow-up. A first MACCE occurred in 72 patients (37%). Microparticle levels were significantly higher in patients with MACCE compared with patients without event (P=0.004). The prevalence of diabetes (P=0.02) and male gender (P=0.05) was significantly related to the MP level. In multivariate analysis (cardiovascular risk factors, number of diseased vessels, use of angiotensin-converting enzyme-inhibitors and statins), high MP levels were associated with a higher risk for cardiovascular death [Hazard ratio (HR) 4.0, 95% confidence interval (CI) 1.1-14.6; P=0.04], the need for revascularization (HR 2.4, 95% CI 1.3-4.4; P=0.005), and the occurrence of a first MACCE (HR 2.3, 95% CI 1.4-3.8; P=0.001). Inclusion of the MP level into a classical risk factor model substantially increased c-statistics from 0.637 (95% CI: 0.557-0.717) to 0.702 (95% CI: 0.625-0.780) (P=0.03). CONCLUSION The level of circulating CD31+/Annexin V+ MPs is an independent predictor of cardiovascular events in stable CAD patients and may be useful for risk stratification.

Evaluation and Management of Paravalvular Aortic Regurgitation After Transcatheter Aortic Valve Replacement

Paravalvular aortic regurgitation (PAR) negatively affects the prognosis after transcatheter aortic valve replacement (TAVR) with dramatically increased morbidity and mortality in patients with more than mild PAR. Because transcatheter heart valves are implanted in a sutureless fashion using oversizing to anchor the prosthesis stent frame at the level of the virtual aortic annulus, stent frame underexpansion due to heavily calcified cusps, suboptimal placement of the prosthesis, and/or annulus-prosthesis-size mismatch due to malsizing can contribute to paravalvular leakage. In contrast to open heart surgery, TAVR does not offer the opportunity to measure the aortic annulus under direct vision during the procedure. Therefore, the dilemma before each TAVR procedure is the appropriate sizing of the dimensions of the aortic annulus and to choose not only the size but also the transcatheter heart valve type (self-expanding vs. balloon-expandable) that fits the given anatomy best. Because precise echocardiographic quantification of PAR in patients with TAVR remains challenging especially in the acute implantation situation, a multimodal approach for the evaluation of PAR with the use of hemodynamic measurements and imaging modalities is imperative to precisely quantify the severity of aortic regurgitation immediately after valve implantation and to identify patients who will benefit from corrective measures such as post-dilation or valve-in-valve implantation. Every measure has to be taken to prevent or reduce PAR to provide a satisfying long-term clinical outcome.

Transcatheter aortic valve replacement in bicuspid aortic valve disease.

BACKGROUND Limited information exists describing the results of transcatheter aortic valve (TAV) replacement in patients with bicuspid aortic valve (BAV) disease (TAV-in-BAV). OBJECTIVES This study sought to evaluate clinical outcomes of a large cohort of patients undergoing TAV-in-BAV. METHODS We retrospectively collected baseline characteristics, procedural data, and clinical follow-up findings from 12 centers in Europe and Canada that had performed TAV-in-BAV. RESULTS A total of 139 patients underwent TAV-in-BAV with the balloon-expandable transcatheter heart valve (THV) (n = 48) or self-expandable THV (n = 91) systems. Patient mean age and Society of Thoracic Surgeons predicted risk of mortality scores were 78.0 ± 8.9 years and 4.9 ± 3.4%, respectively. BAV stenosis occurred in 65.5%, regurgitation in 0.7%, and mixed disease in 33.8% of patients. Incidence of type 0 BAV was 26.7%; type 1 BAV was 68.3%; and type 2 BAV was 5.0%. Multislice computed tomography (MSCT)-based TAV sizing was used in 63.5% of patients (77.1% balloon-expandable THV vs. 56.0% self-expandable THV, p = 0.02). Procedural mortality was 3.6%, with TAV embolization in 2.2% and conversion to surgery in 2.2%. The mean aortic gradient decreased from 48.7 ± 16.5 mm Hg to 11.4 ± 9.9 mm Hg (p < 0.0001). Post-implantation aortic regurgitation (AR) grade ≥ 2 occurred in 28.4% (19.6% balloon-expandable THV vs. 32.2% self-expandable THV, p = 0.11) but was prevalent in only 17.4% when MSCT-based TAV sizing was performed (16.7% balloon-expandable THV vs. 17.6% self-expandable THV, p = 0.99). MSCT sizing was associated with reduced AR on multivariate analysis (odds ratio [OR]: 0.19, 95% confidence intervals [CI]: 0.08 to 0.45; p < 0.0001). Thirty-day device safety, success, and efficacy were noted in 79.1%, 89.9%, and 84.9% of patients, respectively. One-year mortality was 17.5%. Major vascular complications were associated with increased 1-year mortality (OR: 5.66, 95% CI: 1.21 to 26.43; p = 0.03). CONCLUSIONS TAV-in-BAV is feasible with encouraging short- and intermediate-term clinical outcomes. Importantly, a high incidence of post-implantation AR is observed, which appears to be mitigated by MSCT-based TAV sizing. Given the suboptimal echocardiographic results, further study is required to evaluate long-term efficacy.

First-in-man use of a novel embolic protection device for patients undergoing transcatheter aortic valve implantation.

AIMS We describe the first-in-human experience with a novel cerebral embolic protection device used during transcatheter aortic valve implantation (TAVI). One current challenge of TAVI is the reduction of procedural stroke. Procedural mobilisation of debris is a known source of cerebral embolisation. Mechanical protection by transient filtration of cerebral blood flow might reduce the embolic burden during TAVI. We aimed to evaluate the feasibility and safety of the Claret CE Pro™ cerebral protection device in patients undergoing TAVI. METHODS AND RESULTS Patients scheduled for TAVI were prospectively enrolled at three centres. The Claret CE Pro™ (Claret Medical, Inc. Santa Rosa, CA, USA) cerebral protection device was placed via the right radial/brachial artery prior to TAVI and was removed after the procedure. The primary endpoint was technical success rate. Secondary endpoints encompassed procedural and 30-day stroke rates, as well as device-related complications. Deployment of the Claret CE Pro™ cerebral protection device was intended for use in 40 patients, 35 devices were implanted into the aortic arch. Technical success rate with delivery of the proximal and distal filter was 60% for the first generation device and 87% for the second-generation device. Delivery times for the first-generation device were 12.4±12.1 minutes and 4.4 ± 2.5 minutes for the second-generation device (p<0.05). The quantity of contrast used related to the Claret CE Pro System was 19.6 ± 3.8 ml. Captured debris was documented in at least 19 of 35 implanted devices (54.3%). No procedural transient ischaemic attacks, minor strokes or major strokes occurred. Thirty-day follow-up showed one minor stroke occurring 30 days after the procedure, and two major strokes both occurring well after the patient had completed TAVI. CONCLUSIONS The use of the Claret CE Pro™ system is feasible and safe. Capture of debris in more than half of the patients provides evidence for the potential to reduce the procedural cerebral embolic burden utilising this dedicated filter system during TAVI.

MicroRNA Expression in Circulating Microvesicles Predicts Cardiovascular Events in Patients With Coronary Artery Disease

Background Circulating microRNAs (miRNAs) are differentially regulated and selectively packaged in microvesicles (MVs). We evaluated whether circulating vascular and endothelial miRNAs in patients with stable coronary artery disease have prognostic value for the occurrence of cardiovascular (CV) events. Methods and Results Ten miRNAs involved in the regulation of vascular performance—miR‐126, miR‐222, miR‐let7d, miR‐21, miR‐20a, miR‐27a, miR‐92a, miR‐17, miR‐130, and miR‐199a—were quantified in plasma and circulating MVs by reverse transcription polymerase chain reaction in 181 patients with stable coronary artery disease. The median duration of follow‐up for major adverse CV event–free survival was 6.1 years (range: 6.0–6.4 years). Events occurred in 55 patients (31.3%). There was no significant association between CV events and plasma level of the selected miRNAs. In contrast, increased expression of miR‐126 and miR‐199a in circulating MVs was significantly associated with a lower major adverse CV event rate. In univariate analysis, above‐median levels of miR‐126 in circulating MVs were predictors of major adverse CV event–free survival (hazard ratio: 0.485 [95% CI: 0.278 to 0.846]; P=0.007) and percutaneous coronary interventions (hazard ratio: 0.458 [95% CI: 0.222 to 0.945]; P=0.03). Likewise, an increased level of miR‐199a in circulating MVs was associated with a reduced risk of major adverse CV events (hazard ratio: 0.518 [95% CI: 0.299 to 0.898]; P=0.01) and revascularization (hazard ratio: 0.439 [95% CI: 0.232 to 0.832]; P=0.01) in univariate analysis. miRNA expression analysis in plasma compartments revealed that miR‐126 and miR‐199a are present mainly in circulating MVs. MV‐sorting experiments showed that endothelial cells and platelets were found to be the major cell sources of MVs containing miR‐126 and miR‐199a, respectively. Conclusion MVs containing miR‐126 and miR‐199a but not freely circulating miRNA expression predict the occurrence of CV events in patients with stable coronary artery disease.

Blood Transfusion and the Risk of Acute Kidney Injury After Transcatheter Aortic Valve Implantation

Background—Blood transfusion is associated with acute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI). We sought to elucidate in more detail the relation between blood transfusion and AKI and its effects on short- and long-term mortality. Methods and Results—Nine hundred ninety-five patients with aortic stenosis underwent TAVI with the Medtronic CoreValve or the Edwards Valve in 7 centers. AKI was defined by the Valve Academic Research Consortium (absolute increase in serum creatinine ≥0.3 mg/dL [≥26.4 &mgr;mol/L] or ≥50% increase <72 hours). Logistic and Cox regression was used for predictor and survival analysis. AKI occurred in 20.7% (n=206). The number of units of blood transfusion <24 hours was the strongest predictor of AKI (≥5 units, OR, 4.81 [1.45–15.95], 3–4 units, OR, 3.05 [1.24–7.53], 1–2 units, OR, 1.47 [0.98–2.22]) followed by peripheral vascular disease (OR, 1.48 [1.05–2.10]), history of heart failure (OR, 1.43 [1.01–2.03]), leucocyte count <72 hours after TAVI (OR, 1.05 [1.02–1.09]) and European System for Cardiac Operative Risk Evaluation (EuroSCORE; OR, 1.02 [1.00–1.03]). Potential triggers of blood transfusion such as baseline anemia, bleeding-vascular complications, and perioperative blood loss were not identified as predictors. AKI and life-threatening bleeding were independent predictors of 30-day mortality (OR, 3.15 [1.56–6.38], OR, 6.65 [2.28–19.44], respectively), whereas transfusion (≥3 units), baseline anemia, and AKI predicted mortality beyond 30 days. Conclusions—AKI occurred in 21% of the patients after TAVI. The number of blood transfusions but not the indication of transfusion predicted AKI. AKI was a predictor of both short- and long-term mortality, whereas blood transfusion predicted long-term mortality. These findings indicate that outcome of TAVI may be improved by more restrictive use of blood transfusions.

Impact of Paravalvular Leakage on Outcome in Patients After Transcatheter Aortic Valve Implantation

OBJECTIVES The aim of this study was to evaluate the performance of the aortic regurgitation (AR) index as a new hemodynamic parameter in an independent transcatheter aortic valve implantation (TAVI) cohort and validate its application. BACKGROUND Increasing evidence associates more-than-mild periprosthetic aortic regurgitation (periAR) with increased mortality and morbidity; therefore precise evaluation of periAR after TAVI is essential. The AR index has been proposed recently as a simple and reproducible indicator for the severity of periAR and predictor of associated mortality. METHODS The severity of periAR was evaluated by echocardiography, angiography, and periprocedural measurement of the dimensionless AR index = ([diastolic blood pressure - left ventricular end-diastolic pressure]/systolic blood pressure) × 100. A cutoff value of 25 was used to identify patients at risk. RESULTS One hundred twenty-two patients underwent TAVI by use of either the Medtronic CoreValve (Medtronic, Minneapolis, Minnesota) (79.5%) or the Edwards-SAPIEN bioprosthesis (Edwards Lifesciences, Irvine, California) (20.5%). The AR index decreased stepwise from 29.4 ± 6.3 in patients without periAR (n = 26) to 28.0 ± 8.5 with mild periAR (n = 76), 19.6 ± 7.6 with moderate periAR (n = 18), and 7.6 ± 2.6 with severe periAR (n = 2) (p < 0.001). Patients with AR index <25 had a significantly increased 1-year mortality rate compared with patients with AR index ≥ 25 (42.3% vs. 14.3%; p < 0.001). Even in patients with none/mild periAR, the 1-year mortality risk could be further stratified by an AR index <25 (31.3% vs. 14.3%; p = 0.04). CONCLUSIONS The validity of the AR index could be confirmed in this independent TAVI cohort and provided prognostic information that was complementary to the severity of AR.

Growth-Differentiation Factor-15 for Risk Stratification in Patients with Stable and Unstable Coronary Heart Disease: Results from the AtheroGene Study

Background—Growth-differentiation factor-15 (GDF-15) is a stress-responsive transforming growth factor-&bgr;-related cytokine that has emerged as a prognostic biomarker in acute coronary syndrome trial populations. Its predictive role in stable coronary heart disease (CHD) has never been assessed. Methods and Results—The circulating levels of GDF-15 were measured by immunoradiometric assay in patients with stable angina pectoris (n=1352) or acute coronary syndrome (n=877) who were followed up for a median of 3.6 years. Stable angina pectoris patients presenting with normal (<1200 ng/L), moderately elevated (1200 to 1800 ng/L), or markedly elevated (>1800 ng/L) GDF-15 levels had 3.6-year CHD mortality rates of 1.4%, 2.7%, and 15.0%, respectively (P<0.001). By backward stepwise Cox-regression analysis, which adjusted for age and gender, clinical variables, the number of diseased vessels, renal function, the levels of C-reactive protein, cardiac troponin I, and N-terminal pro–B-type natriuretic peptide, GDF-15 remained an independent predictor of CHD mortality (P<0.001). Addition of GDF-15 improved the prognostic accuracy of a clinical risk prediction model concerning CHD mortality (c-statistic, 0.84 versus 0.74; P=0.005). Analysis of the acute coronary syndrome part of the study population confirmed GDF-15 as an independent predictor of CHD mortality (P<0.001). The circulating levels of GDF-15 did not predict the future risk of nonfatal myocardial infarction in patients with stable angina pectoris or acute coronary syndrome. Conclusion—This study identifies GDF-15 as a strong and independent predictor of CHD mortality across the broad spectrum of patients with stable and unstable CHD.