Miriam Puls

One-year outcomes and predictors of mortality after MitraClip therapy in contemporary clinical practice: results from the German transcatheter mitral valve interventions registry

Abstract Aims The transcatheter mitral valve interventions (TRAMI) registry was established in order to assess safety and efficacy of catheter-based mitral valve interventional techniques in Germany, and prospectively enrolled 828 MitraClip patients (median age 76 years, median log. EuroSCORE I 20.0%) between August 2010 and July 2013. We present the 1-year outcome in this MitraClip cohort—which is the largest published to date. Methods and results Seven forty-nine patients (90.5%) were available for 1-year follow-up and included in the following analyses. Mortality, major adverse cardiovascular event rates, and New York Heart Association (NYHA) classes were recorded. Predictors of 1-year mortality were identified by multivariate analysis using a Cox regression model with stepwise forward selection. The 1-year mortality was 20.3%. At 1 year, 63.3% of TRAMI patients pertained to NYHA functional classes I or II (compared with 11.0% at baseline), and self-rated health status (on EuroQuol visual analogue scale) also improved significantly by 10 points. Importantly, a significant proportion of patients regained the complete independence in self-care after MitraClip implantation (independence in 74.0 vs. 58.6% at baseline, P = 0.005). Predictors of 1-year mortality were NYHA class IV (hazard ratio, HR 1.62, P = 0.02), anaemia (HR 2.44, P = 0.02), previous aortic valve intervention (HR 2.12, P = 0.002), serum creatinine ≥1.5 mg/dL (HR 1.77, P = 0.002), peripheral artery disease (HR 2.12, P = 0.0003), left ventricular ejection fraction <30% (HR 1.58, P = 0.01), severe tricuspid regurgitation (HR 1.84, P = 0.003), and procedural failure (defined as operator-reported failure, conversion to surgery, failure of clip placement, or residual post-procedural severe mitral regurgitation) (HR 4.36, P < 0.0001). Conclusions Treatment of significant MR with MitraClip resulted in significant clinical improvements in a high proportion of TRAMI patients after 12 months. In the TRAMI cohort, the failure of procedural success exhibited the highest hazard ratio concerning the prediction of 1-year mortality.

Elevated heart-type fatty acid-binding protein levels on admission predict an adverse outcome in normotensive patients with acute pulmonary embolism.

OBJECTIVES We assessed the predictive value of heart-type fatty acid-binding protein (H-FABP) in normotensive patients with acute pulmonary embolism (PE). BACKGROUND Risk stratification of initially normotensive patients with PE on the basis of right ventricular dysfunction or injury remains controversial. Previous studies investigating biomarkers or imaging modalities included unselected patients, some of whom presented with cardiogenic shock. METHODS We included 126 consecutive normotensive patients with confirmed PE. Complicated 30-day outcome was defined as death, resuscitation, intubation, or use of catecholamines. Long-term survival was assessed by follow-up clinical examination. RESULTS During the first 30 days, 9 (7%) patients suffered complications. These patients had higher baseline H-FABP values (median, 11.2 ng/ml [interquartile range: 8.0 to 36.8 ng/ml]) compared with patients with an uncomplicated course (3.4 ng/ml [2.1 to 4.9 ng/ml]; p < 0.001). H-FABP values were above the calculated (by receiver operating characteristic curve analysis) cutoff value of 6 ng/ml in 29 patients. Eight (28%) of them suffered complications versus 1 of 97 patients with low H-FABP (negative predictive value, 99%; p < 0.001). By logistic regression, elevated (> or =6 ng/ml) H-FABP was associated with a 36.6-fold increase in the death or complication risk. The combination of H-FABP with tachycardia was a particularly useful prognostic indicator. H-FABP also predicted long-term mortality over 499 (interquartile range: 204 to 1,166) days (hazard ratio: 3.6; 95% confidence interval: 1.6 to 8.2; p = 0.003). CONCLUSIONS The H-FABP might be a useful biomarker for risk stratification of normotensive patients with acute PE.

Impact of the learning curve on outcomes after percutaneous mitral valve repair with MitraClip® and lessons learned after the first 75 consecutive patients

Mitral valve regurgitation plays a significant role in the aetiology and course of heart failure. We investigated the impact of the learning curve on outcomes after percutaneous mitral valve repair with MitraClip.

Impact of frailty on short- and long-term morbidity and mortality after transcatheter aortic valve implantation: risk assessment by Katz Index of activities of daily living.

AIMS Transcatheter aortic valve implantation (TAVI) represents a less invasive treatment option for elderly patients. Therefore, we aimed to determine the impact of frailty measured by the Katz Index of activities of daily living (ADL) on short- and long-term mortality after TAVI. METHODS AND RESULTS Our study included 300 consecutive patients (mean age, 82±5 years) who had undergone TAVI at our institution (158 transapical, 142 transfemoral procedures). At baseline, 144 patients were impaired in at least one ADL and therefore defined as frail (Katz Index <6). Regarding in-hospital outcome, all serious complications except for stage 3 acute kidney injury were equally distributed in both groups, but early mortality was significantly higher in frail persons (5.5% vs. 1.3%, p=0.04 for immediate procedural mortality; 17% vs. 5.8%, p=0.002 for 30-day mortality; and 23% vs. 6.4%, p<0.0001 for procedural mortality). The risk-score-based 30-day mortality estimates (29% vs. 24% for log. EuroSCORE I, 9.5% vs. 7.5% for EuroSCORE II, and 8.8% vs. 5.9% for STS score) reflected neither the observed 30-day mortality in both groups nor the threefold risk elevation in frail patients. In contrast, the Katz Index <6 was identified as a significant independent predictor of long-term all-cause mortality by multivariate analysis (HR 2.67 [95% CI: 1.7-4.3], p<0.0001). During follow-up (median observation period 537 days) 56% of frail vs. 24% of non-frail patients died. CONCLUSIONS Frailty status measured by the Katz Index represents a powerful predictor of adverse early and late outcome after TAVI, whereas commonly used risk scores lack calibration and discrimination in a TAVI-specific patient cohort. Therefore, we propose the incorporation of this simple and reproducible measure into pre-TAVI risk assessment.

Heart-type fatty acid-binding protein for risk assessment of chronic thromboembolic pulmonary hypertension

Heart-type fatty acid-binding protein (H-FABP) is a reliable marker of myocardial injury and was recently identified as a predictor of outcome in acute pulmonary embolism. The aim of the present study was to investigate the prognostic value of H-FABP in chronic thromboembolic pulmonary hypertension (CTEPH). In total, 93 consecutive patients with CTEPH were studied. During long-term follow-up (median duration 1,260 days, interquartile range (IQR) 708–2,460 days), 46 (49%) patients had an adverse outcome, defined as CTEPH-related death, lung transplantation or persistent pulmonary hypertension after pulmonary endarterectomy (PEA). Baseline H-FABP levels in plasma ranged from 0.69–24.3 ng·mL−1 (median (IQR) 3.41 (2.28–4.86) ng·mL−1). Cox regression analysis revealed a hazard ratio of 1.10 (95% confidence interval 1.04–1.18) for each increase of H-FABP by 1 ng·mL−1, and continuous elevations of H-FABP emerged as an independent predictor of adverse outcome by multivariable analysis. PEA was performed in 52 patients and favourably affected the long-term outcome. Kaplan–Meier analysis revealed that patients with baseline H-FABP concentrations >2.7 ng·mL−1, the median value of the biomarker in the surgically treated population, had a lower probability of event-free survival after PEA. Heart-type fatty acid-binding protein is a promising novel biomarker for risk stratification of patients with chronic thromboembolic pulmonary hypertension.

Detection of left atrial thrombus during routine diagnostic work-up prior to pulmonary vein isolation for atrial fibrillation: Role of transesophageal echocardiography and multidetector computed tomography☆

BACKGROUND Transesophageal echocardiography (TEE) and multidetector computed tomography (MDCT) are frequently used imaging modalities prior to pulmonary vein isolation (PVI) in order to exclude left atrial (LA) and left atrial appendage (LAA) thrombus and to visualize the anatomy of LA and pulmonary veins. This study aimed to identify predictors of LA/LAA thrombus and to analyze the diagnostic yield of routine pre-procedural TEE and MDCT. METHODS 329 patients with drug-refractory atrial fibrillation (AF) (age 62 ± 10 years; 65% males; 247 paroxysmal AF) referred for pulmonary PVI were included. Prior to the procedure, all patients underwent 64-slice MDCT and TEE, which was used as the gold standard. Risk parameters for thrombus formation were determined, including the CHADS(2) and CHA(2)DS(2)-VASc scores. RESULTS MDCT identified 10 LA/LAA thrombi (3.0%) (8 false positive, 2 true positive), whereas 7 actual thrombi (2.1%) were detected by TEE (5 false negative by MDCT). Sensitivity and specificity of MDCT was 29% and 98%, respectively, with a negative predictive value of 98% and a positive predictive value of 20%. All patients with thrombus were on effective anticoagulation. In multivariate analysis, diabetes mellitus, CHADS(2) score ≥3, and CHA(2)DS(2)-VASc score ≥4 were significantly associated with LA/LAA thrombus. No thrombus was seen in patients without risk factors. CONCLUSIONS In patients presenting for PVI, MDCT does not reliably exclude LA/LAA thrombus. Our study revealed a small but significant prevalence of thrombus despite effective anticoagulation. Diabetes mellitus, CHADS(2) score ≥3, and CHA(2)DS(2)-VASc score ≥4 were independent risk predictors of LA/LAA thrombus.

Risk and outcomes of complications during and after MitraClip implantation: Experience in 828 patients from the German TRAnscatheter mitral valve interventions (TRAMI) registry

To analyze risk and outcomes of complications during and after MitraClip implantation using multicenter data from the prospective German Transcatheter Mitral Valve Interventions (TRAMI) registry.

Plasminogen Activator Inhibitor-1 From Bone Marrow–Derived Cells Suppresses Neointimal Formation After Vascular Injury in Mice

Objective—To investigate the ability of bone marrow (BM)–derived cells to modulate neointimal growth after injury by expressing plasminogen activator inhibitor-1 (PAI-1). Methods and Results—We performed BM transplantation (BMT) in lethally irradiated wild-type (WT) and PAI-1−/− mice. Three weeks after carotid injury with ferric chloride, analysis of Y-chromosome DNA expression in the vessel wall of female hosts revealed that 20.8±6.0% of the cells in the neointima and 37.6±5.7% of those in the media were of BM origin. Lack of PAI-1 in either the host or the donor cells did not affect recruitment of BM-derived cells into sites of vascular injury. The neointima consisted predominantly of smooth muscle cells, and a proportion of these cells expressed PAI-1. Overall, lack of PAI-1 was associated with enhanced neointimal formation. However, importantly, BMTWT→PAI-1−/− mice exhibited reduced neointimal area (P=0.05) and luminal stenosis (P=0.04) compared with BMTPAI-1−/−→PAI-1−/− mice. Although PAI-1–expressing cells were shown to be present in BMTWT→PAI-1−/− lesions, these mice did not exhibit detectable levels of the inhibitor in the circulation, suggesting that local production of PAI-1 by cells in the neointima and media was sufficient to reduce luminal stenosis. Conclusions—PAI-1 from BM-derived cells appears capable of suppressing neointimal growth after vascular injury.

Effect of smoking cessation on the number and adhesive properties of early outgrowth endothelial progenitor cells

BACKGROUND Endothelial progenitor cells participate in angiogenesis and vascular repair, and cardiovascular risk factors may reduce their numbers or impair their functional properties. Cigarette smoking is a leading cause of preventable cardiovascular death, however, the functional properties of these cells before and after discontinuation of tobacco use have not been systematically analyzed. METHODS We examined changes in the number and function of early outgrowth endothelial progenitor cells (EPC), isolated from individuals (n=144; mean age, 47.8 ± 12.0 years; 43% males; more than 50% with additional cardiovascular risk factors or disease) who successfully completed a 5-week smoking cessation (SC) programme. RESULTS SC significantly reduced total white blood cell count (WBC; P<0.0001), plasma LDL cholesterol (P=0.0002) and fibrinogen (P<0.0001) levels, but did not alter the number of circulating CD34(+), VEGFR2(+) or CD34(+), CD133(+) cells (P=0.14 and 0.57, respectively). Fewer acLDL(+), lectin(+) cells could be expanded from peripheral blood mononuclear cells in comparison to baseline (P<0.001). Furthermore, SC was associated with reduced EPC adhesion to fibronectin (P<0.001) or TNFα-activated endothelial cells (P=0.003), and a diminished incorporation of EPC into endothelial cell networks (P=0.035). Mechanistically, significantly reduced β1- and β2-integrin expression (P<0.001 and 0.007) and lower contents of intracellular reactive oxygen species (P<0.007) were detected in EPC following SC, in addition to reduced plasma asymmetric dimethyl-L-arginine (ADMA) levels (P=0.0003). CONCLUSIONS Our findings suggest that the oxidative and inflammatory stress reduction associated with smoking cessation impair the adhesiveness of monocyte-derived EPC.

Safety and efficacy of MitraClip™ therapy in patients with severely impaired left ventricular ejection fraction: results from the German transcatheter mitral valve interventions (TRAMI) registry

The aim of the present study was to assess the safety and efficacy of percutaneous mitral valve repair using the MitraClip™ device in patients with severely reduced systolic left ventricular (LV) function.