The Impact of COVID-19 on Mortality and Clinical Characteristics in Hospitalized Patients With Peripheral Artery Disease in the Year 2020 in Germany.

BACKGROUND: The COVID-19 pandemic developed its full destructive capacity in 2020. This retrospective study aimed to examine the effects of COVID-19 on the mortality and the clinical characteristics in PAD patients with COVID-19 compared to PAD patients without COVID-19. METHODS AND RESULTS: Data derived from a German nationwide register of the year 2020 which encompassed all hospitalized patients with PAD (n = 173.075); N = 2553 also suffered from a COVID-19 infection and had significantly higher mortality rates of 11.2%. PAD + COVID-19 patients presented more clinical complications like major amputations (11.59%), myocardial infarction (2.08%), cardiogenic shock (2.98%), chronic kidney failure with GFR<= 15 mL/min (5.33%) and prolonged ventilation time >48 h (3.37%). Rates of pulmonary thromboembolism (0.24%), myocardial infarction (2.08%), and stroke (1.02%) were low in patients with PAD + COVID-19. Adjusted regression analyses for risk differences revealed possible causes of higher mortality rates, such as prolonged ventilation time, pneumonia, major amputations, multiple organ system failure, and length of hospital stay in patients with severe PAD (Rutherford 5-6) + COVID-19. CONCLUSION: Pneumonia and major amputations were associated with high mortality rates in PAD + COVID-19 in 2020. However, we could not detect a relevant influence of pulmonary thromboembolism, myocardial infarction or stroke on higher death rates of PAD + COVID-19.

Muscle ultrasound shear wave elastography for detection of early onset lower limb ischemia in patients with veno-arterial extracorporeal membrane oxygenation.

BACKGROUND AND OBJECTIVES: Limb ischemia or compartment syndrome, requiring surgery, are some of the frequent cannula-related complications in patients supported with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). The purpose of this exploratory study is to depict and evaluate the dynamic changes in the lower limb muscles with ultrasound shear wave elastography as marker for early lower limb ischemia. METHODS: Eleven patients with VA-ECMO after cardiac arrest were included in this study. Seven patients received distal perfusion cannula (DPC) after implantation of the VA-ECMO, whereas 4 had no DPC after VA-ECMO. Compartment syndrome was clinically excluded in all patients. Both lower limbs, e.g., with and without arterial cannula, were monitored with near-infrared spectroscopy (NIRS) for the oxygen saturation of the local tissue. We performed ultrasound shear wave elastrography (SWE) to assess dynamic changes of the medial gastrocnemius muscle at maximum passive muscle stretch (exercise) of both legs. Color-coded duplexsonography was conducted to examine the blood flow velocity of the popliteal artery of the lower limb. RESULTS: We found no difference between DPC and no DPC (p = 0.115) during use of VA-ECMO. However, we detected marked lower limb muscle perfusion deficits of cannulated (58.9 ± 13.5 kPa) vs. cannula-free limb (95.7 ± 27.9 kPa: p < 0.001), applying SWE. No relationship was detected between NIRS measurements and SWE values (kPa) of both lower limbs. The mean peak systolic velocity of the popliteal artery at the cannulated side (30.0 ± 11.7 cm/s) was reduced compared to the non-cannulated side (39.3 ± 18.6 cm/s; p = 0.054). CONCLUSIONS: Regardless of DPC after implantation of VA-ECMO, the gastrocnemius muscles seem to lose function due to cannula-related microcirculatory deficits. Muscle function analysis via SWE combined with NIRS might offer a sensitive indicator for early onset leg ischemia during VA-ECMO-related arterial cannulation.

Weakness of lower limb muscle in symptomatic peripheral artery disease with media sclerosis detected by ultrasound shear wave elastography.

Background: Symptomatic peripheral arterial disease (PAD) is difficult to non-invasively diagnose in the presence of calcified, media sclerotic arteries that are incompressible by blood pressure cuffs. Standard ankle-brachial index (ABI) measurements in these PAD patients are very often not helpful. Shear wave elastography (SWE) is a modern ultrasound technique to detect peripheral muscle stiffness changes i.e. muscle weakness during exercise. In a pilot study, we examined whether SWE could be a reproducible tool for diagnosing ischemic loss of muscle stiffness in patients with PAD and concomitant arterial media sclerosis. Patients and methods: N=13 consecutive patients with peripheral artery disease and media sclerosis were enrolled in the pilot study. All 13 patients were symptomatic in different stages of their PAD due to hemodynamically relevant arterial stenosis or occlusions of limb arteries as confirmed by oscillography, color-coded duplex sonography or angiography. Results: ABI measurements were invalid in all 13 patients. Mean SWE measurements of medial gastrocnemius muscles showed a significant transient muscle stiffness loss (weakness) at maximum exercise (active dorsal flexion of the foot, 103.4±25.9 kPa on the asymptomatic vs. 62.5±21.9 kPa on the symptomatic limb (p<0.001). Conclusions: SWE can reproducibly detect peripheral muscle weakness during exercise in the symptomatic leg of media sclerotic PAD patients. SWE of lower limb muscles may help to identify symptomatic PAD in patients presenting with invalid ABI measurements and unclear vascular status.

Bioresorbable zinc stent with ultra-thin center struts attenuates stent jail in porcine femoral artery bifurcations.

INTRODUCTION: An ultra-thin, fracture-resistant and bioresorbable stent may be advantageous for provisional stenting in vessel bifurcations, if catheter passage and side-branch post-dilatation is facilitated to prevent a 'stent jail' by struts obstructing the orifice of a major side branch. MATERIAL AND METHODS: We studied a highly radiopaque, slowly bioresorbable zinc alloy stent characterized by a novel design of a radiopaque-marked region of ultra-thin struts in the center of the stent. The stent is characterized by an extended range flexibility and high fracture resistance. Zn-stents and Zn-drug eluting stents (DES) were implanted opposite to rigid Nitinol stents into both femoral artery bifurcations of 21 juvenile pigs, followed for one and three months and studied by angiography and histomorphometry.Results and conclusion: Bare Zn-stents with thinner stent struts showed less neointimal hyperplasia compared to Zn-stents with thicker struts. Neointimal formation was further reduced by 12% in Zn-alloy DES. Both, bare Zn-stents and Zn-DES, can be precisely positioned into the femoral artery bifurcation, allowing easy balloon catheter passage through the very thin strut mesh. Side branch orifices remained open after Zn-stent deployment without stent jailing. No stent fractures or particles emboli occurred after the deployment. A Zn-stent with ultra-thin center struts may be useful for provisional stenting in vessel bifurcations.

Gender-related differences in patients undergoing transcatheter mitral valve interventions in clinical practice: 1-year results from the German TRAMI registry.

OBJECTIVES: Information on gender-related differences in terms of baseline characteristics and clinical outcome of patients undergoing MitraClip® implantation in daily clinical practice have been studied in smaller populations previously. This study sought to additionally evaluate gender-related differences in a larger German real-world patient population. METHODS AND RESULTS: We analyzed data from the prospective and multicenter German TRAMI Registry. Between 08/2010 and 07/2013 327 women and 501 men underwent MitraClip® implantation for significant mitral valve regurgitation. Female patients were significantly older and showed higher rates of frailty compared to men. In contrast, men had significantly higher rates of comorbidities compared to women. The majority of patients underwent MitraClip® implantation for secondary mitral regurgitation, with no significant gender-related differences. MitraClip® treatment was equally effective in terms of procedural results and residual mitral regurgitation in women and men and complication rates were low. However, in this real-world analysis severe bleeding complications were significantly higher in women (p = .02) and re-intervention rates were significantly higher in men after MitraClip® treatment (p = .02). Women showed less improvement in functional NYHA class after MitraClip® treatment compared to men at 1-year follow-up (FU; p < .001). No significant differences between female and male patients were found in 1-year mortality and in re-hospitalization rates. CONCLUSION: In this analysis from a large prospective, multicenter real-world registry MitraClip® implantation is safe and effective for treatment of significant mitral regurgitation with equal postprocedural results and mortality rates during 1-year follow-up. Men and women showed a persisting and significant clinical benefit at 1-year FU after treatment. Complication and re-intervention rates were low. Additional studies are needed to further evaluate our findings on increased bleeding complications and decreased functional improvement in women at 1-year follow-up after MitraClip® therapy.

Publisher Correction: Real-time magnetic resonance imaging - guided coronary intervention in a porcine model.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Real-time magnetic resonance imaging - guided coronary intervention in a porcine model.

X-ray fluoroscopy is the gold standard for coronary diagnostics and intervention. Magnetic resonance imaging is a radiation-free alternative to x-ray with excellent soft tissue contrast in arbitrary slice orientation. Here, we assessed real-time MRI-guided coronary interventions from femoral access using newly designed MRI technologies. Six Goettingen minipigs were used to investigate coronary intervention using real-time MRI. Catheters were custom-designed and equipped with an active receive tip-coil to improve visibility and navigation capabilities. Using modified standard clinical 5 F catheters, intubation of the left coronary ostium was successful in all animals. For the purpose of MR-guided coronary interventions, a custom-designed 8 F catheter was used. In spite of the large catheter size, and therefore limited steerability, intubation of the left coronary ostium was successful in 3 of 6 animals within seconds. Thereafter, real-time guided implantation of a non-metallic vascular scaffold into coronary arteries was possible. This study demonstrates that real-time MRI-guided coronary catheterization and intervention via femoral access is possible without the use of any contrast agents or radiation, including placement of non-metallic vascular scaffolds into coronary arteries. Further development, especially in catheter and guidewire technology, will be required to drive forward routine MR-guided coronary interventions as an alternative to x-ray fluoroscopy.

Zn-alloy provides a novel platform for mechanically stable bioresorbable vascular stents.

Metallic Zn alloys have recently gained interest as potential candidates for developing platforms of bioresorbable vascular stents (BVS). Previous studies revealed that Mg alloys used for BVS can degrade too early, whereas PLLA materials may fail to provide effective scaffolding properties. Here we report on results of a new bioresorbable, metallic stent made from a Zn-Ag alloy studied in a porcine animal model of thrombosis and restenosis. While the tensile strength (MPa) of Zn-3Ag was higher than that of PLLA and resembled Mg's (WE43), fracture elongation (%) of Zn-3Ag was much greater (18-fold) than the PLLA's or Mg alloy's (WE43). Zn-3Ag exposed to HAoSMC culture medium for 30 days revealed degradation elements consisting of Zn, O, N, C, P, and Na at a 6 nm surface depth. Platelet adhesion rates and blood biocompatibility did not differ between Zn-3Ag, PLLA, Mg (WE43), and non-resorbable Nitinol (NiTi) stent materials. Balloon-expandable Zn-3Ag alloy BVS implanted into iliofemoral arteries of 15 juvenile domestic pigs were easily visible fluoroscopically at implantation, and their bioresorption was readily detectable via X-ray over time. Histologically, arteries with Zn-3Ag BVS were completely endothelialized, covered with neointima, and were patent at 1, 3, and 6 months follow-up with no signs of stent thrombosis. Zn-3Ag alloy appears to be a promising material platform for the fabrication of a new generation of bioresorbable vascular stents.

Expression of the oxygen-sensitive transcription factor subunit HIF-1α in patients suffering from secondary Raynaud syndrome.

Anti-ischemic therapy remains a challenge due to the complexity of hypoxia response pathways. Hypoxia-inducible factor (HIF)-1 is a heterodimer transcription factor consisting of 2 subunits, HIF-1α and HIF-1ß. Hypoxia-dependent activation of HIF-1α regulates cellular O2 homeostasis. Raynaud syndrome (RS), as a comorbidity of the autoimmune disease systemic sclerosis (SS), is characterized by vasospasms that limit blood flow to the limbs, resulting in hypoxia. A single-center randomized study was conducted to compare prostaglandin E1 (PgE1) therapy with a treatment combining PgE1 and an endothelin-1 blocker, bosentan. A total of 30 patients suffering from SS with RS were enrolled. We examined the regulation of HIF-1α, its target heme oxygenase-1 (HMOX-1), and the serum levels of the HIF-1α protein in a subset of patients as well as in ten healthy individuals. The expression of HIF-1α and HMOX-1 in monocytes was measured using absolute plasmid-based quantitative real-time PCR, whereas serum HIF-1α levels were measured with ELISA. Samples were taken at the time of randomization and after 24 weeks. We found that HIF-1α and HMOX-1 mRNA expression in monocytes and serum HIF-1α protein levels were significantly higher in the SS/RS patients compared to the healthy control group. Single-drug therapy significantly increased HIF-1α and HMOX-1 mRNA expression in monocytes and serum HIF-1α protein levels in the SS/RS patients compared to those at the time of randomization, whereas combining PgE1 with an endothelin-1 blocker prevented the further increases in HIF-1α and HMOX-1 expression. We propose HIF-1α and HMOX-1 as novel markers for anti-ischemic therapy in RS.

Shear Wave Elastography of Peripheral Muscle Weakness in Patients with Chronic Congestive Heart Failure.

Forty-five study participants (28 chronic heart failure [CHF] patients and 17 control participants) were prospectively enrolled in this study to investigate the clinical potential of ultrasound shear wave elastography (SWE) in identifying peripheral muscle weaknesses in chronic heart failure patients. Muscle stiffness in the gastrocnemius muscle during extension (stretch) and the lower arm flexor muscles during flexion was assessed via shear wave elastography, measuring the shear modulus (kPa) for the resting and contractile states in a range of 0-300 kPa. Resting kPa revealed no significant difference between CHF and CP, but exercise kPa for extension and flexion was significantly lower in CHF than CP. The area under the receiver operating characteristic curve of the denominator kPa-Exercise stretch was 0.916, associated with a sensitivity of 89%, a specificity of 71% and a corresponding cutoff value of 81.1 kPa. Shear wave elastography is thus a reproducible and sensitive ultrasound method for evaluating peripheral muscle deficits in patients with CHF.

Urine proteome analysis as a discovery tool in patients with deep vein thrombosis and pulmonary embolism.

PURPOSE: Early and accurate detection of deep vein thrombosis (DVT) is an important clinical need. Based on the hypothesis that urinary peptides may hold information on DVT in conjunction with pulmonary embolism (PE), the study was aimed at identifying such peptide biomarkers using capillary electrophoresis coupled mass spectrometry. EXPERIMENTAL DESIGN: Patients with symptoms of unprovoked/idiopathic DVT and/or PE were examined by doppler-sonography or angio-computed tomography. Urinary proteome analysis allowed for identification of respective peptide biomarkers. To confirm their biological relevance, we induced PE in mice and assessed human ex vivo thrombi. RESULTS: We identified 62 urinary peptides as DVT-specific biomarkers, i.e. fragments of collagen type I and a fragment of fibrinogen ß-chain. The presence of fibrinogen α/ß in the acute thrombus, and collagen type I and osteopontin in the older, organized thrombus was demonstrated. The classifier DVT62 established through support vector machine (SVM) modeling based on the 62 identified peptides was validated in an independent cohort of 47 subjects (six cases and 41 controls) with a sensitivity of 100% and specificity of 83%. CONCLUSIONS AND CLINICAL RELEVANCE: Urine proteome analysis enabled the detection of DVT-specific peptides, which were validated in human and mouse tissue. Furthermore, it allowed for the establishment of an urinary-proteome based classifier that is relatively specific for DVT. The data provide the basis for assessment of these biomarkers in a prospective clinical study.

Predictors for short-term outcomes of patients undergoing transcatheter mitral valve interventions: analysis of 778 prospective patients from the German TRAMI registry focusing on baseline renal function.

AIMS: Factors predicting outcomes after MitraClip implantation are not well defined. We aimed to report the influence of baseline renal function on short-term outcomes of patients enrolled in the investigator-initiated German transcatheter mitral valve interventions (TRAMI) registry. METHODS AND RESULTS: Twenty participating German centres prospectively included 778 patients (mean age 76.0 years [71-81], 38.8% female gender) at high surgical risk (mean logistic EuroSCORE 20% [12-32%]) undergoing TMVR with the MitraClip for the treatment of symptomatic functional (70%) or degenerative (30%) mitral valve regurgitation (FMR, DMR). The patients were stratified according to renal function before clip implantation. The prevalence of moderate to severe renal impairment (glomerular filtration rate [GFR] <60 ml/min) was 62.7% (37.3%, normal renal function [GFR >60 ml/min]; 49.6%, moderate renal impairment [GFR 30-60 ml/min]; 13.1%, severe renal impairment [GFR <30 ml/min]). TMVR was successfully completed in 98.2% of cases; acute procedural failure, in-hospital and 30-day mortality rates were 1.8%, 2.3% and 4.4%, respectively. Acute procedural failure and mortality rates (in-hospital, 30-day) were significantly higher in patients with severe renal impairment (5.9%, 7.8%, 14.1%), as compared to patients with moderately (1%, 1.3%, 3.0%) or mildly impaired to normal (1.4%, 1.7%, 2.9%) renal function (p<0.0001). Following Cox regression analysis, the prevalence of severe renal impairment at the time of TMVR was the only predictor for increased 30-day mortality rates (hazard ratio 3.42, 95% confidence interval 1.88-6.2; p<0.0001). CONCLUSIONS: Renal function at the time of interventional mitral valve repair with the MitraClip system is a strong predictor for procedural outcomes. Patients with severe renal impairment have a more than threefold increased risk for acute procedural failure, in-hospital death and 30-day mortality.

Triple Antithrombotic Therapy after Percutaneous Coronary Intervention (PCI) in Patients with Indication for Oral Anticoagulation: Data from a Single Center Registry.

Antithrombotic therapy consisting of a dual anti-platelet therapy (DAPT) and oral anti-coagulation (OAC) with a vitamin k antagonist is often referred to as triple therapy. This combined anticoagulation is applied in patients undergoing coronary artery stent implantation while also having an indication for OAC. Triple therapy increases the risk for bleeding events compared to either DAPT or OAC alone and thereby might be associated with adverse outcomes. Clinical data on the frequency of bleeding events in patients on triple therapy from clinical trials derives from pre-selected patients and may differ from the real world patients. We report data on patient characteristics and bleeding incidence of patients dismissed on triple therapy from a single university hospital. Within the time span from January 2000 to December 2012, we identified a total of 213 patients undergoing PCI who were prescribed a triple therapy for at least 4 weeks (representing 0.86% of all patients treated). The usage of triple therapy significantly increased over the observed time period. The average CHA2DS2-VASc Score was 3.1 ± 1.1 with an average HAS-BLED score of 2.5 ± 0.86 representing a high-risk group for thromboembolic events as well as considerable risk for bleeding events. An on-treatment bleeding incidence of 9.4% was detected, with gastrointestinal and airway bleeding being the most frequent (5.1% and 1.4%, respectively). This is consistent with data from clinical trials and confirms the high risk of bleeding in patients on DAPT plus OAC. 29.0% of all patients receiving triple therapy had an indication for OAC other than non-valvular atrial fibrillation. This substantial patient group is underrepresented by clinical trials and needs further attention.

Drug-coated balloons--the importance of packing and dosing antiproliferative drugs.

Several balloon catheters coated with paclitaxel have been shown to reduce restenosis rates in the superficial femoral artery (SFA) revealing a relatively wide therapeutic window of effective doses ranging from 2 to 3 µg/mm(2) balloon surface area. Delivering lower antiproliferative drug doses to the vessel wall may not be inferior to higher drug doses provided that effective drug-excipient formulations have been chosen. Leaving non-flow limiting dissection in the SFA non-stented might be an option after use of drug-coated balloons.

A novel hollow and perforated flexible wire allows the safe and effective local application of thrombolytic therapy in a mouse model of deep vein thrombosis.

We tested the feasibility of local thrombolytic therapy via a novel hollow flexible and perforated wire in a mouse model of deep vein thrombosis. Inferior vena cava (IVC) thrombosis was induced by vessel wall exposure to ferric chloride after laparotomy in anesthetized C57Bl/6 mice. Thrombus formation was visualized by intravital microscopy of rhodamine-labeled platelets and leukocytes. A nitinol hypotube coronary wire with perforated tip was inserted via a 0.8 × 40 mm canula into the IVC lumen distal to the site of ferric chloride exposure. Either tissue plasminogen activator (tPA, alteplase) or saline (control) was administered via the platinum wire distal to the thrombus, avoiding mechanical fragmentation. Thrombus size was assessed by immunohistochemistry (platelet CD41 staining). Intravital microscopy of the IVC demonstrated platelet-containing thrombus growth starting 1 min after ferric chloride exposure. Alteplase administration resulted in significant thrombus size reduction within 10-20 min observed by intravital microscopy and confirmed by histological assessment of IVC cross-sections. Saline-treated mice (n = 4) demonstrated near total IVC occlusion with thrombotic material (84 ± 8% of cross-sectional area in serial sections), whereas alteplase-treated mice showed a dose-dependent decrease of thrombotic area [56 ± 5% with 1.5, 39 ± 4 % with 15 and 21 ± 6% with 150 mg/kg, respectively (n = 4)]. We demonstrate that a flexible hollow and perforated wire enables the successful application of thrombolytic therapy to IVC thrombi in mice without vessel wall perforation. Flexible wire-based thrombolytic therapy appears to be a safe and reliable method for thrombus dissolution even in fragile small veins and may become a promising strategy for targeted therapy of small vessel thrombosis.

Coronary artery treatment with paclitaxel-coated balloon using a BTHC excipient: clinical results of the international real-world DELUX registry.

AIMS: Safety and efficacy of percutaneous coronary interventions using the Pantera Lux paclitaxel-coated balloon have been demonstrated in the PEPPER first-in-man trial. This prospective, multicentre, clinical registry aims to evaluate its safety and efficacy in an international real-world setting in a larger cohort of patients. METHODS AND RESULTS: Between April 2010 and April 2011, 1,064 patients were treated for predominantly diffuse and proliferative in-stent restenosis of bare metal stents (BMS-ISR) and drug-eluting stents (DES-ISR), or for de novo lesions. Clinical device success was obtained in 98.2% of the patients. The study endpoint was major adverse cardiac events (MACE), defined as a composite of all-cause mortality, non-fatal myocardial infarction and clinically driven target vessel revascularisation, and was 8.5% in the overall, 6.0% in the BMS-ISR, 11.5% in the DES-ISR and 7.0% in the de novo population at six months, and 15.1%, 11.6%, 20.6% and 9.4% at 12 months, respectively. Definitive stent thrombosis occurred in 0.4% of the patients within 12 months. CONCLUSIONS: Safety and efficacy of the Pantera Lux paclitaxel-coated balloon was confirmed in a real-world setting with low major adverse cardiac event rates in patients with in-stent restenosis or de novo lesions. (ClinicalTrials.gov: NCT01081366).

Treatment of functional mitral valve regurgitation with the permanent percutaneous transvenous mitral annuloplasty system: results of the multicenter international Percutaneous Transvenous Mitral Annuloplasty System to Reduce Mitral Valve Regurgitation in Patients with Heart Failure trial.

OBJECTIVES: PTOLEMY-2 was a prospective multicenter phase I single-arm feasibility trial to evaluate the second-generation permanent percutaneous transvenous mitral annuloplasty (PTMA) device in reducing functional mitral regurgitation (MR). BACKGROUND: Percutaneous MR reduction has been performed through a direct method of clipping and securing the mitral leaflets together or an indirect approach of reducing mitral annular dimension via the coronary sinus. The PTMA device is the only coronary sinus mitral repair device without a static fixation element. METHODS: Patients with at least moderate functional MR, New York Heart Association functional class II to IV, and left ventricular ejection fraction of 20% to 50% were enrolled at 14 centers in 5 countries. Device effects on patients were assessed by serial echocardiography, quality of life (QOL), and exercise capacity metrics. RESULTS: A total of 43 patients were recruited, and 30 patients (70%) were implanted with a permanent PTMA device with a mean follow-up of 5.8 ± 3.8 months. The primary safety end point (freedom from death, myocardial infarction, stroke, or emergency surgery) at 30 days was met in 28 patients, whereas 2 patients died of device-related complications. The primary efficacy end point (MR reduction of at least 1.0 grade or reduction of regurgitant orifice area by 0.1 cm(2) or regurgitant volume by 15 mL or regurgitant fraction by 10% compared with baseline) was obtained in 13 patients. No significant changes were noted in MR parameters, ventricular volumes, or QOL. Distance walked on 6 minutes testing at 6-month follow-up increased from 331 ± 167 m to 417 ± 132 m (P = .65). Compared with nonresponders, responders had a higher baseline regurgitant orifice area >0.2 cm(2) (P = .001) and less prior history of myocardial infarction (P = .02), coronary artery bypass surgery (P = .03), and ischemic MR (P = .04). CONCLUSIONS: Overall, PTMA had mild impact on MR reduction, left ventricular remodeling, QOL, and exercise capacity. During follow-up, the risk/benefit ratio remained suboptimal.

Twelve-month results of a paclitaxel releasing balloon in patients presenting with in-stent restenosis First-in-Man (PEPPER) trial.

BACKGROUND: Coronary in-stent restenosis (ISR) continues to be a therapeutic challenge especially after drug eluting stent (DES) implantation. We studied patients with ISR to investigate safety and efficacy of a novel drug coated balloon (DCB) incorporating paclitaxel into a microcrystalline structure by applying the inert excipient butyryltri-n-hexyl citrate (BTHC) in a prospective First-in-Man trial. METHODS AND MATERIALS: Eighty-one patients were enrolled at 9 European sites, thereof 43 (53.1%) presenting with bare metal stent (BMS)-ISR and 38 (46.9%) with DES-ISR. The primary study endpoint was in-stent late lumen loss (LLL) independently assessed by a quantitative coronary angiography laboratory at 6 months. A secondary endpoint was major adverse cardiac events (MACE), a composite of cardiac death, non-fatal myocardial infarction, clinically driven target vessel revascularization after 6 and 12 months. RESULTS: At 6 months, overall LLL was 0.07±0.31 mm showing differences in BMS-ISR and DES-ISR treatment (-0.05±0.28 mm vs. 0.19±0.29 mm, respectively, P=.001). Overall MACE rates at 6 and 12 months were 6.5% and 11.8%. At the 12-month follow-up, one myocardial infarction, and no cardiac death nor stent thrombosis had occurred. CONCLUSION: Application of a novel paclitaxel coated balloon using BTHC as an excipient in patients with ISR is safe and results in very low LLL, revascularization- and MACE-rates at follow-up. (ClinicalTrials.gov: NCT00961181).

Impact of chronic kidney disease on long-term clinical outcomes after percutaneous coronary intervention with drug-eluting or bare-metal stents.

Chronic kidney disease (CKD) is associated with adverse outcomes after coronary bare-metal stent (BMS) and drug-eluting stent (DES) implantation, but it is unclear which stent type is associated with lower risk for morbidity and mortality in this population. Uniform treatment standards during coronary stent implantation and a median follow-up period of 2.8 years characterize the FReIburg STent (FRIST) registry, designed as a long-term outcome evaluation of a single tertiary referral cardiovascular center. CKD, defined as creatinine clearance <60 mL/min, was present at baseline in 180 (12%) of 1502 consecutive patients undergoing coronary stent intervention. Patients received first-generation DES (n = 117) or BMS (n = 63). Kaplan-Meier and multivariate Cox model analyses were applied to compare survival rates and adjust for existing clinical, procedural, and angiographic differences between the patients. The primary end point was mortality (cardiac and noncardiac death) and secondary end points were recurrent myocardial infarction, stent thrombosis, target vessel revascularization, sepsis, and major bleeding. Patients with a glomerular filtration rate <60 mL/min had a higher mortality rate (28.3% vs. 10.1%, P < 0.001) than patients with a good renal function. In patients with CKD, there was no difference in mortality rates in the BMS vs. the DES group (hazard ratio, 0.971; 95% confidence interval, 0.48-1.954). In summary, patients with CKD have significantly higher rates of death, but there appears to be no difference in long-term clinical outcomes of first-generation DES compared with BMS implantation during primary percutaneous coronary intervention.

MitraClip therapy in daily clinical practice: initial results from the German transcatheter mitral valve interventions (TRAMI) registry.

AIMS: A substantial percentage of patients with mitral regurgitation (MR) in need of mitral valve repair are currently considered not suitable for conventional surgery. In Germany, the largest cohort of patients studied to date has been treated using a percutaneous, catheter-based approach. We report the acute outcomes of patients enrolled in the investigator-initiated German transcatheter mitral valve interventions (TRAMI) registry. METHODS AND RESULTS: Between January 2009 and August 2011, 486 patients [median age 75 (interquartile range 70-80) years; 200 women (41%)] were enrolled in the registry (309 retrospectively and 177 prospectively), with 481 patients (99%) having undergone percutaneous edge-to-edge therapy for MR using the MitraClip. At baseline, 93% of patients were in New York Heart Association (NYHA) functional class III or IV and 71% of patients had a left ventricular ejection fraction (LVEF) ≤50%. Two-thirds of patients presented with functional MR. Procedural success was achieved in 94% of patients, with grade III present in 93% of patients at baseline yet only 6% post-intervention. Retrospective patients were followed for a median of 183 days, prospective patients for a median of 44 days. The periprocedural complication rate was low, with only minor bleedings as the most significant event. In-hospital and post-discharge mortality was 2.5% and 12.5%, respectively. CONCLUSIONS: Data from the German TRAMI registry suggest that MitraClip therapy is a viable treatment option in daily clinical routine for high surgical risk patients with significant MR.