Use of Pre- and Intensified Postprocedural Physiotherapy in Patients with Symptomatic Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement Study (the 4P-TAVR Study).

BACKGROUND: Physiotherapy prior to open-heart surgery lowers the rate of pneumonia and length of the hospital stay. Pneumonia is a major contributor to short-term mortality following transcatheter aortic valve replacement (TAVR). Hence, we hypothesized that pre- and intensified postprocedural physiotherapy in patients undergoing TAVR might impact the net functional and clinical outcome. METHODS AND RESULTS: The 4P-TAVR study was a prospective, monocentric, randomized trial. The study was designed to compare the efficacy and safety of intensified periprocedural physiotherapy including inspiratory muscle training versus standard postprocedural physiotherapy. Patients were randomized in a 1 : 1 fashion. 108 patients were included and followed up for 90 days after TAVR. While patients in group A (control group: 50 patients, age: 81.7 ± 5.0 years, 52% male) did not receive physiotherapy prior to TAVR, group B (intervention group: 58 patients, age: 82.2 ± 5.82 years, 47% male) participated in intensive physiotherapy. Compared to the control group, patients in the interventional group showed a lower incidence of postinterventional pneumonia (10 [20.0%] vs. 3 [5.1%], p=0.016) and had a 3-day shorter mean hospital stay (13.5 ± 6.1 days vs. 10.1 ± 4.7 days, p=0.02). The primary composite endpoint of mortality and rehospitalization was not different between the groups. CONCLUSION: Intensified physiotherapy is safe and has positive effects on clinical outcomes up to 90 days after TAVR but has no impact on the primary combined endpoint of mortality and rehospitalization. Longer follow-up, a multicenter design, and a higher number of subjects are needed to confirm these preliminary results. This trial is registered with DRKS00017239.

Innovations and novel technologies in TAVI. Second generation transcatheter heart valves.

Transcatheter aortic valve implantation (TAVI) is the new standard-of-care for inoperable patients with superior outcome compared to conservative management including balloon valvuloplasty. In high-risk patients, TAVI has shown non-inferiority compared with surgical aortic valve replacement. Although data from national multi-centre registries are very encouraging and use of TAVI in intermediate risk patients has been discussed, it is of note that the commercially available and currently used transcatheter heart valves (THV) have not yet been assessed by randomized clinical trials in those patients. New technology advances promise to simplify TAVI and to improve outcome by reducing the rate of TAVI-specific issues such as paravalvular aortic regurgitation (PAR), annular rupture, and conduction disturbances. A reduction in the incidence and severity of PAR represents an obvious target for technical improvements in the design of upcoming "next generation" THVs and of implantation techniques including repositioning/recapturing features, paravalvular sealing techniques, and precise peri-interventional imaging modalities.

Impact of coronary artery disease on in-hospital mortality in patients with aortic valve disease. Results from the German ALKK registry.

OBJECTIVE: Although aortic valve disease (AVD) is frequently associated with coronary artery disease (CAD), little is known about the impact of significant coronary artery disease on mortality after diagnostic cardiac catheterization in patients with AVD. METHODS: We analyzed data of the coronary angiography registry of the "Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte" (ALKK) in Germany. The primary endpoint was in-hospital mortality. RESULTS: A total of 1427 consecutive patients with AVD (438 patients with CAD versus 989 patients without CAD) underwent diagnostic catheterization in 2006 in 42 hospitals. All cause in-hospital mortality was more than threefold higher in patients with CAD (16/438; 3.7%) as compared to patients without CAD (12/989; 1.2%; p < 0.01; OR 3.09, 95% CI 1.45-6.58). Even after adjustment for age, sex, presence of diabetes mellitus and renal insufficiency, in-hospital all cause mortality remained statistically significant different between the two groups (OR 2.4; 95% CI 1.09-5.28; p < 0.01). Several factors, such as transient ischemic attack/stroke, volume of contrast agent, and left heart catheter-associated complications could not be identified as possible causes for the increase in mortality. CONCLUSION: This analysis in patients with the leading diagnosis of AVD shows a significantly higher in-hospital mortality after diagnostic cardiac catheterization in case of an accompanying CAD. However, further studies are necessary to identify the driving force for the increase in mortality.

De novo coronary lesions treated with the novel polymer-freeBiolimus-A9 coated stents: four- and twelve-month angiographicresults from the prospective, randomised, multicentreBIOFREEDOM clinical trial

Aims: We report the results of the first-in-man evaluation of the BioFreedom (BF)Biolimus A9 (BA9) coated stent (Biosensors Int., Singapore), available in 2different formulations: standard dose (SD: 15.6 μg/mm) and low dose (LD: 7.8μg/mm).Methods and results: A total of 182 pts w/ single lesion were included in theprospective, multicenter (4 sites in Germany), randomised (1:1:1 ratio)BIOFREEDOM trial. Pts were treated with the BF-SD (n=60), BF-LD (n=62) vs.Taxus paclitaxel-eluting stents (PES) (n=60). Lesion criteria were native vessels2.25-3.0 mm in diameter, and <14 mm in length. Overall, pts were divided into 2cohorts w/ similar randomisation ratio: 1st cohort (n=75), enrolled Sep/08-Jan/09(angiographic FU at 4-month); and 2 cohort (n=107), enrolled Jan-Jun/09(angiographic FU at 12-month). Primary endpoint was in-stent late lumen loss(LLL) (non-inferiority, margin=0.24 mm) at 12-month FU (2nd cohort). Baselineclinical/angiographic characteristics were comparable among the 3 groups; 38% oflesions were located in LAD, and all pts achieved angiographic success. At4-month FU (1 cohort), QCA results showed significant decrease in in-stent LLL w/BF-SD and BF-LD vs. PES: 0.08 and 0.12 vs. 0.37mm (p<0.0001 for BF-SD vs.PES; p=0.002 for BF-LD vs. PES); at 12-month, similar results were foundincluding in-stent LLL of 0.17 and 0.22 vs. 0.35 mm for BF-SD and BF-LD vs. PES(p=0.001 for BF-SD vs. PES; p=0.21 for BF-LD vs. PES – p values fornon-inferiority). In addition, the rates of major adverse cardiac events at 12-monthfollow-up were 6.1% in BF-SD, 11.6% in BF-LD, and 5.5% in PES, including targetlesion revascularisation rates of 1.8%, 10% and 5.5% for BF-SD, BF-LD andPES, respectively. Importantly, there were neither death nor stent thrombosis(ARC) up to 12 months.Conclusions: The novel BF polymer-free BA9-coated stents showed excellentacute results, and sustained safety and efficacy through 12-month FU.

Advances in percutaneous treatment for adult valvular heart disease.

Valvular heart disease occurs in 2-3% of the general population with an increase in prevalence with advancing age. The aetiology of valvular heart disease has evolved in recent decades with degenerative aortic and mitral valve disease supplanting rheumatic heart disease as a primary cause. The common valve lesions to be discussed in this article are aortic stenosis and mitral regurgitation. The traditional approach to calcific aortic stenosis when either symptoms or left ventricular impairment develops is surgical aortic valve replacement and it remains a treatment with excellent outcomes. In recent years there has been interest in less invasive approaches, including percutaneous and transapical aortic valve implantation. With refinements in technology these approaches are becoming a potential treatment option, primarily for high-risk patients who may otherwise be unsuitable for traditional open surgical treatment. Catheter-based approaches for mitral valve disease are also evolving. Mitral regurgitation may often be the result of mitral annular dilatation seen in patients with an enlarged left ventricle or left atrium. Percutaneous implantation of a constricting device in the coronary sinus, which lies in close proximity to the mitral annulus, results in a change to the geometry of the mitral valve and reduced regurgitation. Another technique in patients with degenerative mitral regurgitation is the endovascular edge-to-edge repair in which coaptation of the mitral valve leaflets can be improved with a percutaneously deployed clip. Small patient series indicate that these new techniques are promising. As such, advances in percutaneous interventional and surgical approaches have the potential to further improve outcomes for selected patients with valvular heart disease.

Volume-outcome relation for contemporary percutaneous coronary interventions (PCI) in daily clinical practice: is it limited to high-risk patients? Results from the Registry of Percutaneous Coronary Interventions of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausarzte (ALKK).

OBJECTIVE: The formerly observed volume-outcome relation for percutaneous coronary interventions (PCIs) has recently been questioned. DESIGN: We analysed data of the PCI registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte. PATIENTS: In 2003 a total of 27 965 patients at 67 hospitals were included. RESULTS: The median PCI volume per hospital was 327. In-hospital mortality was 1.85% in hospitals belonging to the lowest PCI volume quartile and 1.21% in the highest quartile (p for trend <0.001). Two groups of patients were then compared according to their treatment at hospitals with either <325 PCIs (n = 5754) or >325 PCIs (n = 22 211) per year. Logistic regression analysis showed that a PCI performed at hospitals with a volume of >325 PCI/year was independently associated with a lower hospital mortality (OR = 0.67, 95% CI: 0.52 to 0.87; p = 0.002). If PCI was performed in patients with acute myocardial infarction there was a significant decline in mortality with increasing volume (p for trend = 0.004); however, there was no association in patients without a myocardial infarction. CONCLUSIONS: This analysis of contemporary PCI in clinical practice shows a small but significant volume-outcome relation for in-hospital mortality. However, this relation was only apparent in high-risk subgroups, such as patients presenting with acute myocardial infarction.

The safety and efficacy of an extravascular, water-soluble sealant for vascular closure: initial clinical results for Mynx.

OBJECTIVE: The purpose of this study was to evaluate the hemostatic efficacy and safety of the Mynx extravascular sealant for femoral artery closure. BACKGROUND: The Mynx device is an extra-arterial vascular closure technology utilizing a water-soluble, porous, polyethylene glycol matrix that immediately seals the arteriotomy by rapidly absorbing subcutaneous fluids and expanding in the tissue tract and then, resorbs within 30 days. METHODS: The Mynx study was a prospective, multicenter, single-arm clinical investigation conducted at five European centers. The safety and effectiveness of the Mynx device was evaluated in patients following diagnostic or interventional endovascular procedures performed through 5 Fr, 6 Fr, or 7 Fr introducer sheaths in the common femoral artery. The primary safety endpoint was the combined rate of major complications within 30 days (+/-7 days). The primary efficacy endpoints were time to hemostasis and time to ambulation. RESULTS: Patient enrollment included 190 patients with 50% having undergone diagnostic catheterization and 50% interventional procedures with a mean activated clotting time of 221 sec. One (0.5%) major vascular complication (transfusion) occurred in one patient. No device-precipitated complications associated with serious clinical sequelae were reported. Mean (+/- standard deviation) times to hemostasis and ambulation were 1.3 +/- 2.3 min and 2.6 +/- 2.6 hr, respectively. There was no significant difference in median times to hemostasis between diagnostic and interventional patients (0.5 vs. 0.6 min). CONCLUSIONS: The initial experience with the extra-arterial Mynx closure technology supports hemostatic safety and efficacy in patients undergoing diagnostic and interventional catheterization procedures.

First-In-Man application of a miniature self-contained intracoronary magnetic resonance probe. A multi-centre safety and feasibility trial.

AIMS: To assess safety and feasibility of intracoronary Magnetic Resonance (MR) Spectroscopy in living patients, using a self-contained MR catheter. METHODS AND RESULTS: Prospective, multi-centre study in patients with stable or unstable angina that were scheduled for percutaneous coronary diagnostic or therapeutic catheterization. We assessed the feasibility of an intravascular MR catheter, capable of analysing the arterial wall without external magnets or coils, by differentiating lipid rich, intermediate and fibrotic areas of the atherosclerotic plaque on the basis of differential water diffusion.Twenty-nine patients were included at 4 centres. The intracoronary MR-spectroscopy procedure was well tolerated; no MACE and no device related serious adverse event was observed. The MR catheter was successfully advanced into the lesion in 28 patients. Introduction of the MR catheter was not possible in one patient with a tortuous proximal right coronary artery. MR data were obtained in 22 patients. According to the predominant MR pattern, lesions were classified as fibrous plaque in 4 patients, as intermediate plaque in 4 patients and as lipid-rich plaque in 8 patients. Six patients were excluded from analysis because artifacts impeded the quality of the MR signal. Plaque type did not show a correlation with angina status (p=0.552; all groups) or angiographic parameters, such as minimal lumen diameter and diameter stenosis. CONCLUSIONS: This prospective, multi-centre study demonstrates for the first time that coronary artery assessment of potentially vulnerable, non-flow limiting lesions using a dedicated intravascular MR catheter, free of external magnets or coils, is feasible in clinical practice. Assessment of the coronary wall may provide important data regarding the composition of the atherosclerotic lesion, which then could contribute to predicting the likelihood of eventual rupture and clinical instability.

First experience with the Impella Recover(R) LP 2.5 micro axial pump in patients with cardiogenic shock or undergoing high-risk revascularisation.

AIM: To study the feasibility, safety and efficacy of the Recover(R) LP 2.5 assist device in patients scheduled for high risk off-pump coronary bypass surgery, percutaneous coronary intervention or patients in cardiogenic shock. METHODS AND RESULTS: 40 patients presenting with cardiogenic shock (n=13) or scheduled for a high risk revascularisation (n=27) were included.36 were selected for safety and feasibility analysis. In 3 patients the pump could not be placed in an adequate position. 5 patients had access related complications. In 9 patients free Hb rose above 80 mg/dl. 3 malfunctions and early device-removal occurred. After device modifications these problems did not recur. CO in the shock group increased significantly: 4.4 l/min+/-1.9 to 4.8 l/min+/-1.2 (p=0.0178).The left ventricular filling pressures decreased in both groups (22 mmHg+/-7.5 to 16 mmHg+/-6 in the shock group, [p=0.0008] and over 6 hours from 14.3 mmHg+/-5.8 to 10 mmHg+/-2.9 in the high-risk revascularisation group,[p=0.0327]). CONCLUSIONS: The Recover(R) LP 2.5 micro axial pump allows, via percutaneous approach, partial unloading of the left ventricle. The technique is, after design modifications, feasible and safe and results in haemodynamic improvement.

Comparative endoluminal visualization of TAXUS crush-stenting at 9 months follow-up by intravascular ultrasound and optical coherence tomography.

We report a case of crush-stenting with Paclitaxel-eluting TAXUS stents in a left anterior descending artery (LAD) bifurcation lesion. In order to obtain precise information on the mid-term neointimal response of the main vessel to this approach, we evaluated the patient angiographically 9 months later, including intravascular visualization with optical coherence tomography (OCT), a new high resolution imaging technique, and IVUS. The evaluation revealed that there was a homogeneous neointimal coverage of the main vessel stents without evidence of significant recurrent lumen renarrowing or malappositions. Compared to IVUS, OCT proved the coverage of the stent struts adjacent to the vessel wall with a superior imaging quality and, in addition, provided new insights into the stent performance at the open bifurcation site.

Incidental finding of a papillary fibroelastoma on the aortic valve in 16 slice multi-detector row computed tomography.

Papillary fibroelastoma (PFE) is a benign, rare, gelatinous tumour derived from the endocardium, primarily the cardiac valves, which is usually diagnosed by high resolution echocardiography. Although rarely clinically symptomatic, PFEs have a potential for coronary ischaemia, systemic embolisation with neurologic symptoms, and sometimes valvar dysfunction. There are reports of coronary occlusion and even sudden cardiac death due to a ball valve phenomenon on the coronary ostia. This report describes the characteristics of a PFE with multidetector 16 slice computed tomography and 1.5 Tesla cardiac magnetic resonance imaging.

Long-term evaluation of paclitaxel-coated stents for treatment of native coronary lesions. First results of both the clinical and angiographic 18 month follow-up of TAXUS I.

The development of restenoses due to tissue proliferation within the stented segment is a major limitation of conventional stent implantations. Recently published studies have shown that drug-eluting stents effectively decrease the incidence of stent restenosis at 6 month follow-up as compared to bare metal stents. However, a persistent efficacy of this stent design beyond the 6 month period still needs to be proven. Therefore, in this study, we are demonstrating the first 18 month follow-up results of a Paclitaxel-coated coronary stent, based on the patient population of the TAXUS I study, a multicenter randomized study to evaluate both safety and efficacy of the Paclitaxel-coated NIRx stent as compared to an uncoated, bare metal stent. In this study we evaluated the long-term outcome of NIRx patients of our center, in which 20 out of 31 patients of the TAXUS I study with NIRx stent implantation have been enrolled. A clinical follow-up was available in 20 out of 20 patients (100%) 535 +/- 82 days post stent implantation (17.8 months). An angiographic follow-up was available in 14 out of 20 patients (70%) 580 +/- 77 days post stent implantation (19.1 months). The MACE rate at 18 month follow-up was 0.0%. There was no stent restenosis in the study group up to 18 month post drug-eluting stent implantation. There was one non-clinically driven target vessel revascularization due to a stent edge lumen renarrowing, which was subsequently calculated as a 43% diameter stenosis. Accordingly, this event was not regarded as MACE. The IVUS analysis of the study population has shown a decrease of the mean minimum lumen area from 8.45 mm(2) postinterventional to 6.87 mm(2) at 6 month follow-up with a relative mean maximum plaque area of 16%. At 18 month follow-up, there were no additional significant changes with a mean minimum lumen area of 7.16 mm(2) and a relative mean maximum plaque area of 13.4%. The reported results of the 18 month follow-up of TAXUS I are the first experiences demonstrating a persistent benefit of the Paclitaxel-coated NIRx stent. Therefore, this stent design seems to be safe and effective, even in long-term follow-up.

Drug-eluting stents: clinical experiences and perspectives.

Drug-eluting stents (DES) have entered the arena and are about to changed the landscape of Interventional Cardiology. Today, the number of agents under preclinical and clinical investigation has increased considerably, including drugs such as Paclitaxel, Sirolimus, Tacrolimus, Everolimus, Dexamethasone, etc. Several studies have recently been published or are still ongoing evaluating different stent designs with respect to their safety and efficacy in treatment of coronary lesions. The SCORE trial (Paclitaxel) revealed a significant reduction in restenosis at follow-up (FU) in the drug-eluting stent group (6.4% vs 36.9% control group), attributable to decreased intimal proliferation. However, stentthromboses and myocardial infarctions, due to both stent design and high drug dosages, were observed causing a MACE rate of 10.2% in the DES group. Confirming the beneficial reduction of stent renarrowing using a local drug-eluting device, the rate of restenosis in the TAXUS-I trial (Paclitaxel) was 0% at follow-up in patients with DES vs 10% in patients with bare stents. Differences in MACE were not observed, which underlined the potential impact of an optimal stent design. First clinical experiences with a Sirolimus-coated stent (FIM trial) demonstrated again a profound inhibition of neointimal ingrowth at 4-month follow-up. The RAVEL trial, the first multicenter trial evaluating the Sirolimus stent and the largest DES study published so far, confirmed the FIM findings with a rate of restenosis in the DES group of 0% at 6 month FU. At 12 month FU, the beneficial impact on neointimal growth inhibition was persistent. The pivotal study SIRIUS is addressed to evaluate this stent design more extensively. However, given all the results being available today, local application of anti-proliferative agents delivered by coronary stents is one of the most promising techniques in treatment of coronary lesions. Nevertheless, we need more trials and an agreement of definitions in order to evaluate this treatment concept and eliminate unwanted side-effects.

[Brugada syndrome or ARVD (arrhythmogenic right ventricular dysplasia) or both? Significance and value of right precordial ECG changes]. / Brugada-Syndrom oder ARVD oder beides? Bedeutung und Wertigkeit rechtspräkordialer EKG-Veränderungen.

We report about a 20-year old patient suffering cardiopulmonary resuscitation due to ventricular fibrillation. We diagnosed Brugada syndrome after exclusion structural heart disease and a positive Ajmalin test and implanted an ICD. In that there is a 20-30% familiar disposition, it was necessary that all family members undergo a cardiac examination. It was found that one brother and one sister presented the beginning of a right ventricular dilatation and a fibrolipomatous area in the anterior wall segment of the right ventricle. This result is compatible with a "concealed" arrhythmogenic right ventricular dysplasia (ARVD). As a prognostic indication we decided to implant an ICD prophylactically. The case report demonstrates the value of familiar examination of patients with an unclear ventricular arrhythmogenic event.

Drug eluting stents: initial experiences.

Local delivery of immunosuppressive or antiproliferative agents using a drug-eluting stent is a new technology meant to inhibit in-stent restenosis providing both a biological and mechanical solution and has recently emerged as a very promising approach. Up to now several agents have been in use: Paclitaxel, Rapamycin, Actinomycin D or Tacrolimus. Evaluating these drugs regarding their release kinetics, effective dosage, safety in clinical practice and benefit, several studies have been published or are still ongoing: SCORE (Paclitaxel-derivative), TAXUS I, II, III, IV (Paclitaxel), ELUTE, ASPECT (Paclitaxel), RAVEL, SIRIUS (Sirolimus), ACTION (Actinomycin), EVIDENT, PRESENT (Tacrolimus). Paclitaxel was the first stent-based antiproliferative agent under clinical investigation providing profound inhibition of neointimal thickening, depending on delivery duration and drug dosage. The randomized multicenter SCORE trail (Quanam stent, Paclitaxel coated) enrolled 266 patients at 17 sites. At 6 month follow-up, a drop of 83% in stent restenosis using the drug-eluting stent could be achieved (6.4% drug-eluting stent vs. 36.9% control group) attributable to a remarkable decrease in intimal proliferation. Unfortunately, due to both frequent stent thrombosis and side-branch occlusions the reported 30-day MACE rate was 10.2%. The randomized TAXUS I safety trail (NIRx, Paclitaxel coated) also demonstrated beneficial reduction of restenotic lesions at 6-month FU (0% vs. 11%) but, this time, associated with the absence of thrombotic events presumably due to the lower drug dosage. The ongoing TAXUS II, III and IV trails are aimed at providing additional insight regarding the efficacy of the TAXUS Paclitaxel-eluting stent. Both the RAVEL and the SIRIUS trial have been conducted to evaluate a Sirolimus-coated stent (Bx VELOCITY stent). From the results available, the beneficial findings regarding reduction of renarrowing using a drug-eluting stent have been confirmed without any adverse effects. Although parameters like drug toxicity, optimal drug dosage or delayed endothelial healing need to be further evaluated, summarizing the today's clinical experience the strategy of drug-coated stents promises a striking benefit in interventional treatment of coronary lesions.

Balloon-protected carotid artery stenting: relationship of periprocedural neurological complications with the size of particulate debris.

BACKGROUND: Carotid artery stenting (CAS) has been advocated as an alternative to endarterectomy. To prevent cerebral atheroembolism during CAS, distal balloon occlusion of the target artery increasingly is employed during the procedure. A correlation of the size of captured particles with the incidence of periprocedural neurological complications (PNCs) has not been attempted. METHODS AND RESULTS: In a 4-center, phase-1 trial, 54 patients (46 men; age, 69+/-8 years) underwent 58 CAS procedures using the PercuSurge GuardWire system for distal protection. Aspirated debris was sent for histological/cytological analysis. Stent placement was successful in all cases. Mean balloon occlusion time was 10.4+/-4.0 minutes (range, 3.0 to 22.0 minutes). Three patients (5.2%) experienced PNCs: 1 prolonged reversible ischemic neurological deficit that resolved in /=10 000 micrometer(2)) were found in 48 aspirates (83%). The median number of particles, their maximum diameter, and their maximum area were all significantly higher in the aspirates obtained during procedures associated with PNCs than in aspirates obtained during procedures not associated with PNCs. However, pronounced overlap in the distributions (PNCs versus no PNCs) of the number and maximum diameter of particles precluded any predictive inferences. In contrast, a maximum particle area >800 000 micrometer(2) (>0.8 mm(2)) was associated with a 60% chance of having a PNC. CONCLUSIONS: Despite balloon protection, PNCs occurred in 5.2% of patients who underwent CAS procedures. The maximum area of aspirated particles seems to be an indicator of increased risk for PNCs.