Outcomes following implantation of the Biolimus A9-eluting BioMatrix coronary stent: Primary analysis of the e-BioMatrix registry.

OBJECTIVES: To assess the safety and efficacy of Biolimus A9-eluting stents (BES, BioMatrix™ and BioMatrix Flex™) in routine clinical practice. BACKGROUND: The LEADERS randomized trial has documented equivalent efficacy and superior safety of the BES when compared to a first generation Sirolimus-eluting Cypher(TM) stent. METHODS: 5,472 patients from 57 centers, treated with BES, were enrolled in an international multicenter registry and followed clinically up to 2 years. RESULTS: Mean patient age was 63.2 ± 11 years, 24% of patients had diabetes, and 49.8% presented with an acute coronary syndrome. 99.3% of patients were discharged on dual antiplatelet therapy (DAPT), 83.3% remained on DAPT at 1 year and 30.6% at 2 years. The incidence of the composite primary end point [major adverse cardiac events (MACE) at 12 months] was 4.5% [cardiac death 0.9%, myocardial infarction 1.7%, clinically indicated target vessel revascularization (ci-TVR) 2.8%]. MACE incidence was 6.8% at 24 months (cardiac death 1.5%, myocardial infarction 2.4%, ci-TVR 4.3%). At 12 months, 32 patients (0.6%) had suffered at least one definite or probable stent thrombosis (ST), and 91 patients (1.7%) a major bleed (MB). Nine patients with ST (27.3%) and 7 patients with a MB (7.7%) died during the first year after the index procedure. Between 12 and 24 months after implantation, there were 18 (0.4%) additional MB and 8 (0.2%) additional ST. CONCLUSIONS: This large international cohort documents a low 12 and 24 months MACE incidence and a very low ST incidence in an unselected patient population undergoing BES implantation. The results are in keeping with those of the randomized controlled LEADERS trial. Even though ST with this stent was a rare event, it was still associated with significant mortality. MB remains a problem, and warrants improved tailoring of DAPT in recipients of drug eluting stents.

Acute and long-term results of bifurcation stenting (from the Coroflex Registry).

Angioplasty of bifurcation lesions represents a continuing challenge. A total of 421 consecutive patients were prospectively followed in a registry on bifurcation stenting with a high-end bare metal stent (Coroflex, BBraun, Berlin, Germany), allowing side branch percutaneous transluminal coronary angioplasty through the stent struts without distraction of the main vessel stent from the vessel wall or other distortions. This approach obviated the 2-wire technique and kissing balloons. Detailed data, including lesion location, stenosis morphology, procedural success, and hospital and follow-up major adverse cardiac events (MACEs; acute myocardial infarction, death, revascularization, hospitalization due to angina), were collected from 6 European centers. Of the patients, 60% had stable angina, 23% had unstable angina pectoris/non-ST-elevation myocardial infarction, and 17% had ST-elevation myocardial infarction. In 17% of patients, the main vessel alone was stented; in 71%, stenting of the main vessel was complemented by side branch percutaneous transluminal coronary angioplasty. Technical success (residual stenosis <50%) in the 2 branches was achieved in 90% (main vessel in 99%). The rate of MACEs at discharge was 2%. After 6 months, 17% of patients had undergone target lesion revascularization or coronary artery bypass grafting. The total 6-month MACE rate was 22%. In conclusion, successful bifurcation stenting with a low MACE rate is possible in most patients using a simplified approach with a dedicated high-end bare metal stent.

An update on prevention of venous thromboembolism in hospitalized acutely ill medical patients.

Both the recently updated consensus guidelines published by the American College of Chest Physicians, and the International Union of Angiology recommend thromboprophylaxis with either low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) in medical patients at risk of VTE. However, no guidance is given regarding the appropriate dosing regimens that should be used for thromboprophylaxis in this patient group. LMWH (enoxaparin and dalteparin) and UFH have been shown to be effective for thromboprophylaxis in at-risk hospitalized medical patients. Although LMWH once daily (o.d.) has been shown to be as effective as UFH three times daily (t.i.d.) for thromboprophylaxis in at-risk medical patients, there are no data to show that UFH twice daily (b.i.d) is as effective as either LMWH o.d. or UFH t.i.d. On the basis of currently available evidence, the LMWHs enoxaparin and dalteparin are more attractive alternatives to UFH for the prevention of VTE in hospitalized medical patients because of their convenient once-daily administration and better safety profile, demonstrated in terms of reduced bleeding, HIT, and other adverse events.

Transcatheter closure of interatrial communications for secondary prevention of paradoxical embolism: single-center experience.

BACKGROUND: Patients with a patent foramen ovale (PFO) after cerebral, coronary, or systemic embolic events of presumed paradoxical origin are at risk for recurrent thromboembolism. We report our single-center experience of interventional closure of interatrial communications for secondary prevention of presumed paradoxical embolism. Methods and Results- Since 1997, percutaneous closure of interatrial communications was performed at our institution in 66 patients (mean age 47.8+/-12.7 years; 31 males) with a PFO or an atrial septal defect and at least 1 documented presumed paradoxical thromboembolic event. Fifty-eight patients had cerebral embolism, 10 had coronary embolism, and 3 had peripheral embolism. Several patients experienced multilocal arterial embolism. Fifty-four patients had a PFO, 33 of them with an atrial septal aneurysm, and 12 had an atrial septal defect. The implantation procedure was successful and without complication in all patients. After 3 months, only 2 patients showed a residual shunt, which disappeared in both cases after 12 months. In 112.2 patient-years of follow-up (range, 5 weeks to 3.5 years), we have not seen any recurrent thromboembolic event. CONCLUSIONS: Interventional closure of interatrial communications is a safe and effective therapeutic option for the secondary prevention of presumed paradoxical embolism. To further evaluate this strategy, randomized trials comparing interventional closure with anticoagulation have been initiated by us and others.

The calcium sensitizer levosimendan improves the function of stunned myocardium after percutaneous transluminal coronary angioplasty in acute myocardial ischemia.

OBJECTIVES: We assessed the effects of levosimendan on left ventricular (LV) function in patients with acute myocardial ischemia and after coronary angioplasty. BACKGROUND: The calcium sensitizer levosimendan improves the function of myocardium in experimental stunning. METHODS: Twenty-four patients with an acute coronary syndrome underwent angioplasty followed by double-blinded, randomized treatment with 24 microg/kg of levosimendan (n = 16) or placebo (n = 8). Left ventricular pressures and volumes were recorded by cineventriculography and micromanometer-tipped catheters 10 min after angioplasty before drug administration (baseline) and 20 min after drug administration. Left ventricular function was assessed by the pressure-volume loop, and regional function analysis by the Slager method. RESULTS: The number of hypokinetic segments decreased with levosimendan, from 8.9 +/- 0.9 to 6.5 +/- 1.1 (mean +/- SEM), as compared with an increase from 7.8 +/- 1.0 to 8.5 +/- 1.1 with placebo (p = 0.016). A leftward and/or upward shift of the systolic part of the pressure-volume loop, indicating improved systolic function, was observed in eight of 16 of the levosimendan-treated and one of eight of the placebo patients (p = 0.178). In addition, the single-beat elastance was increased by levosimendan (p = 0.045). The pressure-volume area (p = 0.001), end-systolic pressure (p = 0.002), and volume index (p < 0.001) were decreased by levosimendan, but there was no change in the end-systolic pressure-volume ratio. End-diastolic pressure remained unchanged, whereas the end-diastolic volume index was decreased by levosimendan (p = 0.002). The time constant of isovolumic LV pressure fall decreased with levosimendan (p = 0.001). CONCLUSIONS: Levosimendan improved the function of stunned myocardium without obvious impairment of diastolic function.

Percutaneous extracorporeal life support in patients with circulatory failure: results of the German Lifebridge Registry.

OBJECTIVES: Mortality rates remain high in patients with cardiogenic shock or acute refractory circulatory failure. Extracorporeal life support (ECLS) has been recently introduced into clinical practice for treatment of refractory hypotension in selected patients in combination with rapid restoration of gas exchange. The aim of this study was to evaluate the procedural performance and safety of the automated Lifebridge ECLS system (Zoll Lifebridge GmbH). METHODS: A total of five tertiary cardiovascular centers located in Germany contributed data to this registry (n = 54 patients). Data were collected using a standardized case report form to record clinical characteristics, demographic, procedural, and follow-up data. Patients were included if they were in circulatory crisis (caused by cardiogenic shock or ongoing resuscitation) in an acute setting or in an elective setting during high-risk percutaneous intervention. RESULTS: The Lifebridge device was successfully used in all patients. During elective use, no complications occurred besides 1 minor vascular injury. All elective patients were successfully weaned from the device and alive at the primary endpoint after 30 days. In the emergency setting, 85% of the patients were successfully weaned from the device and 49% of the patients were alive after 30 days. Relevant bleeding resulting in transfusion of red blood cells occurred in 5% of patients. CONCLUSION: In this observational study, we report data from the real-world use of a novel automated ECLS system. Elective use of Lifebridge was feasible and safe without major side effects. In the emergency setting, mortality rates were high; however, stabilization of the selected patients was safe and feasible.

Randomized comparison of enoxaparin with unfractionated heparin for the prevention of venous thromboembolism in medical patients with heart failure or severe respiratory disease.

BACKGROUND: We compared the efficacy and safety of the low-molecular weight heparin enoxaparin with unfractionated heparin (UFH) for the prevention of venous thromboembolic disease in patients with heart failure or severe respiratory disease. METHODS: This was a multicenter, controlled, randomized, open study in which patients received either enoxaparin (40 mg once daily) or UFH (5000 IU 3 times daily) for 10 +/- 2 days in 64 medical departments in Germany. Patients were stratified and enrolled according to their underlying disease: severe respiratory disease or heart failure. The primary efficacy parameter was a thromboembolic event up to 1 day after the treatment period. RESULTS: Of the 665 patients enrolled, 451 patients were able to be evaluated in the primary efficacy analysis. The incidence of thromboembolic events was 8.4% with enoxaparin and 10.4% with UFH. Enoxaparin was at least as effective as UFH, with a 1-sided equivalence region of -4% (90% CI -2.5-6.5, P =.015). Enoxaparin was associated with fewer deaths, less bleeding, and significantly fewer adverse events (45.8% vs 53.8%, P =.044). CONCLUSIONS: Enoxaparin is at least as effective as UFH in the prevention of thromboembolic events in patients with heart failure or severe respiratory disease. Its beneficial safety profile and once-daily administration is advantageous for inpatient and outpatient use.

Assessment of symptoms and exercise capacity in cyanotic patients with congenital heart disease.

OBJECTIVES: Patients with cyanotic congenital heart disease are generally thought to be limited by hypoxemia. To correlate exercise tolerance to the severity of the cardiac abnormality and to further characterize dyspnea in affected patients, we examined 25 adults with uncorrected cyanotic congenital heart disease. DESIGN AND SETTING: Cohort study at a university hospital. METHODS: Symptom-limited cardiopulmonary exercise testing (CPX) was performed on a treadmill. Expiratory gas was analyzed breath by breath for evaluation of maximal exercise performance, ventilation, and ventilatory efficiency in combination with blood gas analysis during rest and exercise. Symptoms were assessed by the ability index and New York Heart Association class, and the results were compared to 101 healthy volunteers. RESULTS: PaO(2) decreased by 26 +/- 8% (mean +/- SD) with exercise (from 49 +/- 12 to 36 +/- 10 mm Hg), while PaCO(2) was only slightly decreased compared to control subjects. Peak oxygen uptake (O(2)) was significantly reduced when compared to control subjects: 16.7 +/- 6.6 mL/kg/min vs 36.1 +/- 7.7 mL/kg/min. Ventilatory efficiency was markedly impaired at rest (minute ventilation [E]/carbon dioxide output [CO(2)] ratio of 70 +/- 18; control subjects, 53 +/- 11; p < 0.005) and during exercise (E vs CO(2) slope, 58 +/- 31; control subjects, 26 +/- 4; p < 0.005). At rest, ventilatory efficiency was correlated to resting pH and PaO(2), while during exercise it was linked to PaO(2). Ventilatory efficiency during exercise had the strongest correlation with observed symptoms, while hypoxemia and peak O(2) were not significantly associated with symptomatic state. CONCLUSION: CPX in patients with cyanotic congenital heart disease provides helpful parameters that better define the symptomatic state of these patients. The summation of disease-related factors is best reflected by ventilatory efficiency. This parameter offers additional and independent information when compared to peak O(2) and the extent of cyanosis alone.

Smoking and hyperlipidemia are important risk factors for coronary artery spasm.

OBJECTIVE: To investigate the role of coronary artery spasm in the etiology of chest pain lacking significant coronary stenosis and to identify the clinical risk factors related to coronary artery spasm. METHODS: Two hundred and seventy five patients with chest pain, but without significant coronary artery stenosis underwent the intracoronary acetylcholine test. Coronary artery spasm was diagnosed while coronary artery stenosis increased to 90% and was accompanied by the usual chest pain with or without ischemic changes on electrocardiogram. Logistic regression was employed to investigate the relationships between coronary artery spasm and sex, age, hypertension, diabetes mellitus, smoking, hyperlipidemia and results of electrocardiographic treadmill stress test. Left ventricular ejection fraction and end diastolic pressure were compared between spasm group and non-spasm group. RESULTS: Coronary artery spasm was detected in 103 out of 271 patients, a rate of 38%. Logistic regression analysis showed that smoking and hyperlipidemia increased the relative risk of coronary artery spasm 4.2 times and 2.3 times, respectively. There was a significantly negative relationship between diabetes mellitus and coronary artery spasm. Furthermore, there was no significant difference of left ventricular ejection fraction and end diastolic pressure between spasm group and non-spasm group. CONCLUSIONS: Coronary artery spasm was one of the important etiological factors for patients with chest pain but no coronary artery stenosis. Smoking and hyperlipidemia were the main clinical risk factors for coronary artery spasm.

Occlusion of PFO with a dedicated adjustable device: influence on one year outcome.

AIMS: Though the association of patent foramen ovale with cryptogenic stroke in young patients has been known for 20 years, most interventional closure systems are not specifically designed for PFO closure, but instead are adapted from ASD closure systems. We describe the safety, feasibility and efficacy of transcatheter closure of PFO using a dedicated adjustable device specifically designed to overcome some of the pitfalls of PFO occlusion like erosion, left atrial thrombus formation, embolisation, maladaptation to cardiac structures and excessive foreign material deposition. METHODS AND RESULTS: Seventy-two consecutive patients, aged between 20 and 72 years, underwent PFO occlusion using the Premere® PFO occluder, for the greater part for presumed paradoxical embolism causing cryptogenic stroke or transient ischaemic attack. Forty patients received the 20 mm, while 32 received the 25 mm device. Implantation was successful in all patients. Residual shunt rate, excluding absolutely trivial shunts, was 2.8% at six months on contrast TEE study. Peri- and postprocedural adverse events with some possibility of a causal link to the procedure occurred in six patients. The postprocedural annual recurrence rate (0.99%) was lower than reported in most other series. CONCLUSIONS: PFO occlusion using the dedicated Premere® PFO occluder is effective and safe. The residual shunt rate and post-interventional recurrence rate compares favourably to the literature.

Migraine headache relief after percutaneous transcatheter closure of interatrial communications.

BACKGROUND: Migraine headache (MHA) is present in 12% of adults, but has been reported to have a higher prevalence in patients with presumed paradoxical embolism and patent foramen ovale. PFO closure in these patients has been reported to improve migraine, but follow-up periods in previous studies have been relatively short and concomitant medical therapy as well as placebo effects might have influenced the results. This study investigated the long term course of MHA in a large cohort of patients after closure of PFO well beyond the initial phase of concomitant antiplatelet medication. METHODS: 191 consecutive patients with presumed paradoxical embolism underwent percutaneous transcatheter closure of patent interatrial communications for prevention of recurrent thromboembolism. We report the course of MHA before and after closure. RESULTS: Before the procedure, MHA was present in 24% of patients. At a mean follow-up of 38 months (range 6 to 82) after the procedure MHA had disappeared completely in 24% of patients, and in another 63% symptoms had improved. At a mean duration of follow-up of 38 months a significant reduction (p < 0.000) of number, intensity, duration of episodes, and in the number of accompanying symptoms during an MHA episode was found. CONCLUSIONS: Percutaneous transcatheter closure of patent interatrial communications results in significant amelioration of MHA in 87% of patients (complete resolution in 24% and significant improvement in symptoms in 63%). Ongoing randomized trials and larger epidemiologic surveys need to further elucidate the role of device therapy for MHA.

Exclusion of patients with arteriosclerosis reduces long-term recurrence rate of presumed arterial embolism after PFO closure.

BACKGROUND: Percutaneous transcatheter closure of patent interatrial communications after presumed paradoxical embolism is used as an alternative to surgery or long-term anticoagulation for the treatment of patients who are at risk for recurrent thromboembolism. To avoid atherosclerotic events to be judged as recurrent paradoxical embolism, we prospectively excluded all patients with detectable arteriosclerosis from our series and investigated long-term results. METHODS AND RESULTS: We report the outcome of 180 patients who underwent percutaneous transcatheter closure of patent foramen ovale (PFO), PFO like atrial septal defect (ASD), or an ASD because of paradoxical embolism. One hundred four patients had cerebral embolism, 57 had transient ischemic attacks, 16 coronary embolism, and 3 had peripheral embolism. Twenty-three patients experienced multilocal arterial embolism. One hundred twenty-five patients had a PFO, 63 of them with an atrial septal aneurysm (ASA), 24 a PFO-like ASD (7 of them with an ASA), and 31 had an ASD. After 18 months, only 5 patients (2.8%) showed a trivial residual shunt. At a mean follow-up of 40 months (range 4 to 88), resulting in 602 observed patient-years, only 1 patient experienced a presumed paradoxical (coronary) embolism (calculated annual risk to suffer a recurrent thromboembolic event: 0.16%). CONCLUSIONS: Percutaneous transcatheter closure of PFO/ASD is a safe and effective therapeutic option for the secondary prevention of presumed paradoxical embolism. It is associated with a high success rate, low incidence of hospital complications, and very low frequency of recurrent systemic embolic events.

Clinical efficacy and survival with first-line inhaled iloprost therapy in patients with idiopathic pulmonary arterial hypertension.

AIMS: To describe the long-term clinical efficacy of inhaled iloprost as first-line vasodilator mono-therapy in patients with idiopathic pulmonary arterial hypertension (IPAH). METHODS AND RESULTS: Seventy-six IPAH patients were prospectively identified and treated with inhaled iloprost. Clinical, haemodynamic, and exercise parameters were obtained at baseline, after 3 and 12 months of therapy and yearly thereafter. Four endpoints were prospectively defined as follows: (i) death, (ii) transplantation, (iii) switch to intravenous (i.v.) therapy, or (iv) addition of or switch to other active oral therapy. During follow-up (535+/-61 days), 11 patients died, six were transplanted, 25 were switched to i.v. prostanoids, 16 received additional or other oral therapy, and 12 patients discontinued iloprost inhalation for other reasons. Event-free survival at 3, 12, 24, 36, 48, and 60 months was 81, 53, 29, 20, 17 and 13%, respectively. Among haemodynamic and exercise parameters, mixed venous oxygen saturation (P<0.001), right atrial pressure (P<0.001), and peak oxygen uptake (P=0.002) were associated with event-free survival. CONCLUSION: In this study, only a minority of patients could be stabilized with inhaled iloprost mono-therapy during a follow-up period of up to 5 years. In the presence of multiple treatment options, chronic iloprost inhalation as mono-therapy appears to have a limited role.

Changes in right ventricular dimensions and performance after passive cardiac containment.

BACKGROUND: Previous studies have shown that the cardiac support device (CSD) improves left ventricular structure and function in patients with heart failure by preventing further cardiac enlargement. The aim of this study was to identify effects on the right ventricle (RV). METHODS: Ten male patients with idiopathic dilated cardiomyopathy underwent electron-beam computed tomographic (CT) examination within 1 month before, and 6 to 9 months after CSD implantation. The RV end-diastolic and end-systolic volumes (EDV, ESV) and diameters (EDD, ESD), stroke volume (SV), ejection fraction (EF), total and forward RV output (RVO, fRVO), and tricuspid regurgitation fraction (TRF) were calculated. RESULTS: The EDV measurements decreased from 182.1 +/- 49.6 to 137.5 +/- 37.0 mL, ESV from 114.8 +/- 47.0 to 68.3 +/- 23.8 mL, EDD from 48.2 +/- 6.6 to 41.6 +/- 7.1 mm, and ESD from 39.6 +/- 6.9 to 32.7 +/- 6.5 mm (p < 0.05 for each). Ejection fraction increased from 38.5 +/- 8.9 to 52.0% +/- 7.7% and fRVO from 4.0 +/- 0.8 to 4.6 +/- 1.1 L/min (each with p < 0.05). TRF decreased from 18.2 +/- 14.1 to 10.4% +/- 13.5%, whereas SV and RVO remained nearly unchanged. Postoperatively, RV volumes, EF, and fRVO were not different from 15 age- and gender-matched normal control patients. CONCLUSIONS: Implantation of a CSD leads to a decrease in RV size and improved RV performance. These data together with the results of previous studies demonstrating improved left ventricular structure and function confirm the biventricular nature of recovery with the CSD.