Steffen Schoen

Transcatheter closure of patent foramen ovale in patients with cerebral ischemia

OBJECTIVES The present study was conducted to determine the safety of the transcatheter closure of a patent foramen ovale (PFO) in patients with cryptogenic cerebral ischemia and the midterm follow-up of recurrent thromboembolic events after interventional PFO closure. BACKGROUND Current therapeutic options for stroke prevention in patients with PFO and a history of thromboembolic events include chronic antithrombotics and more invasive treatments such as surgical closure or minor invasive transcatheter permanent closure of the PFO. Promising preliminary and pilot data with the Amplatzer Septal Occluder or the PFO-Star Occluder have been reported. Systematic and long-term data are still missing. METHODS A total of 276 consecutive patients with a PFO and a history of at least one thromboembolic event were recruited in four medical centers and underwent percutaneous PFO closure with the PFO-Star device. Follow-up data were analyzed over an average of 15.1 months, equivalent to 345 patient-years. RESULTS The implantation was successful in all 276 patients. Peri-interventional reversible complications included transient ST-segment elevations (1.8%) and transient ischemic attack (TIA) (0.8%). Two devices have been removed surgically. During follow-up the annual recurrence rate of thromboembolic events was 1.7% for TIA, 0% for stroke and 0% for peripheral emboli. CONCLUSIONS Interventional PFO closure with the PFO-Star device appears to be a reliable and promising technique resulting in a low recurrence rate of thromboembolic events, especially stroke in patients with a history of cryptogenic ischemia presumably due to paradoxical embolization. To our knowledge, this is the largest coherent and prospective study for interventional PFO closure.

Levosimendan is superior to enoximone in refractory cardiogenic shock complicating acute myocardial infarction.

Objective:Cardiogenic shock is the leading cause of death in patients hospitalized for acute myocardial infarction. The objectives were to investigate the effects of levosimendan, a novel inodilator, compared with the phosphodiesterase-III inhibitor enoximone in refractory cardiogenic shock complicating acute myocardial infarction, on top of current therapy. Design:Prospective, randomized, controlled single-center clinical trial. Setting:Medical and coronary intensive care unit in a university hospital. Patients:Thirty-two patients with refractory cardiogenic shock for at least 2 hrs requiring additional therapy. Interventions:Infusion of either levosimendan (12 &mgr;g/kg over 10 min, followed by 0.1 &mgr;g/kg/min over 50 min, and of 0.2 &mgr;g/kg/min for the next 23 hrs) or enoximone (fractional loading dose of 0.5 mg/kg, followed by 2–10 &mgr;g/kg/min continuously) after initiation of current therapy, always including revascularization, intra-aortic balloon pump counterpulsation, and inotropes. Measurements and main results:Survival rate at 30 days was significantly higher in the levosimendan-treated group (69%, 11 of 16) compared with the enoximone group (37%, 6 of 16, p = 0.023). Invasive hemodynamic parameters during the first 48 hrs were comparable in both groups. Levosimendan induced a trend toward higher cardiac index, cardiac power index, left ventricular stroke work index, and mixed venous oxygen saturation. In addition, lower cumulative values for catecholamines at 72 hrs and for clinical signs of inflammation were seen in the levosimendan-treated patients. Multiple organ failure leading to death occurred exclusively in the enoximone group (4 of 16 patients). Conclusions:In severe and refractory cardiogenic shock complicating acute myocardial infarction, levosimendan, added to current therapy, may contribute to improved survival compared with enoximone.

Protein kinase C in the human heart: differential regulation of the isoforms in aortic stenosis or dilated cardiomyopathy

ObjectivesProtein kinase C (PKC) is a central enzyme in the regulation of growth and hypertrophy. Little was known on PKC isoform regulation in human heart. Goal of this study was to characterize the isoforms of protein kinase C in human heart, their changes during ontogenesis, and their regulation in myocardial hypertrophy and heart failure.MethodsIn left ventricular and atrial samples from adults with end-stage dilated cardiomyopathy (DCM), from adults with severe aortic stenosis (AS), from small infants undergoing repair of ventricular septal defects, and from healthy organ donors (CO), activity of protein kinase C and the expression of its isozymes were examined.ResultsIn the adult human heart, the isoforms PKC-α, PCK-β, PKC-δ, PKC-ε, PKC-λ/-ι, and PKC-ζ were detected both on protein and on mRNA level. All isozymes are subjected to downregulation during ontogenesis. No evidence, however, exists for an isoform shift from infancy to adulthood. DCM leads to a pronounced upregulation of PKC-β. Severe left ventricular hypertrophy in AS, however, recruits a distinct isoform pattern, i.e., isoforms PKC-α, PKC-δ, PKC-ε, PKC-λ/-ι, and PKC-ζ are upregulated, whereas PKC-β is not changed under this condition.ConclusionThis work gives evidence for a differential recruitment of human PKC isoforms in various forms of myocardial hypertrophy and heart failure.

Transcatheter closure of atrial septal defects improves right ventricular volume, mass, function, pulmonary pressure, and functional class: a magnetic resonance imaging study

Objective: To characterise prospectively by magnetic resonance imaging (MRI) changes in right ventricular (RV) volume, function, and mass after transcatheter closure of atrial septal defects (ASDs) and to evaluate the course of pulmonary pressure and functional class criteria. Methods: In 20 patients with secundum-type ASD and dilated RV diameter, MRI was performed to quantify RV end diastolic (RVEDV) and end systolic volumes (RVESV), RV mass, tricuspid annular diameter, and RV ejection fraction before and 6 and 12 months after transcatheter closure of the ASD. RV systolic pressure was measured during follow up by transthoracic echocardiography. Results: Functional class improved in the majority of patients after ASD closure. RVESV (from 81 (18) ml/m2 to 53 (15) ml/m2, p < 0.001), RVEDV (from 127 (17) ml/m2 to 99 (18) ml/m2, p < 0.001), and RV mass (from 79 (10) g to 63 (8) g, p < 0.01) decreased significantly during follow up, although tricuspid annular diameter did not. RV ejection fraction improved (by 9% compared with baseline, p < 0.05) and RV systolic pressure decreased significantly (from 33 (8) mm Hg to 24 (6) mm Hg, p < 0.001) after closure. Conclusion: MRI studies showed significant improvement of RV volumes, mass, and function after transcatheter closure of ASDs. Restoration of the RV leads to decreased pulmonary pressure resulting in a better functional class in the majority of patients.

Correlation of heart-type fatty acid–binding protein with mortality and echocardiographic data in patients with pulmonary embolism at intermediate risk

BACKGROUND The management strategy in patients presenting with pulmonary embolism at intermediate risk still remains controversial. Our aim was to determine the role of heart-type fatty acid-binding protein (H-FABP) in this patient population. METHODS One hundred one consecutive patients with confirmed pulmonary embolism and echocardiographic signs of right ventricular overload but without evidence for hypotension or shock, referred to as pulmonary embolism at intermediate risk, were included in the study. Heart-type fatty acid-binding protein and other biomarkers were measured in all patients upon arrival in the emergency department. RESULTS Of the included 101 patients, 14 had positive H-FABP tests. Ten patients with positive H-FABP (71%) had clinical deterioration during the hospital course and required inotropic support and 8 of these patients died. None of the 87 patients with a negative test worsened or needed inotropic support or died during hospital stay (P < .005). In the H-FABP-positive group, right ventricular function on echocardiography was more impaired (tricuspid annular plane systolic excursion 13 +/- 4 vs 18 +/- 4 mm, RV/LV ratio 1.1 +/- 0.2 vs 0.9 +/- 0.2, presence of paradoxical septal movement 79% vs 46%, presence of McConnell sign 100% vs 60%, respectively, all P < .05) compared to the H-FABP-negative group. After adjusting for potential confounding parameters, in multivariate analysis, H-FABP was the only independent predictor of mortality. CONCLUSIONS Heart-type fatty acid-binding protein significantly predicts mortality in patients with pulmonary embolism at intermediate risk. Furthermore, it is significantly associated with impaired right ventricular function and shows better correlation with mortality than troponin I. It may be a novel prognostic parameter enabling the optimization of management strategy in the very difficult population of pulmonary embolism at intermediate risk.

Incidence of aortic valve regurgitation and outcome after percutaneous closure of atrial septal defects and patent foramen ovale.

Background: In recent years percutaneous, transcatheter closure of atrial septal defects (ASD) or patent foramen ovale (PFO) was introduced into clinical practice. Objective: To investigate the functional effects on heart valves caused by an interatrial closure device. Methods and results: Between 2001 and 2006, 240 consecutive patients underwent percutaneous closure of an ASD or a PFO. Heart valve functions were defined by transoesophageal echocardiography before implantation and 3, 6 and 12 months after defect closure. A successful implantation procedure was performed in 98% of patients. Sufficient closure without residual shunt was achieved in 89% of patients with ASD and in 92% of patients with PFO. An overall major complication rate of 0.8% was apparent during the observation time (mean (SD) 27 (15) months). Long-term follow-up disclosed newly developed or worsened aortic valve regurgitation (AR) in 9% of patients with ASD and in 10% of patients with PFO. A potential cause for developing AR may be overgrowth of the device by tissue, leading to changes in interatrial septal geometry and traction on the root of the non-coronary aortic cusp. Conclusion: AR occurred in 9% of patients with closed ASD and in 10% of patients with closed PFO. Indication for closure should consider this potential complication despite an otherwise safe interventional procedure.

Nitric oxide synthases are crucially involved in the development of the severe cardiomyopathy of caveolin-1 knockout mice.

Targeted ablation of caveolin-1 (cav-1) results in a severe cardiomyopathy. How the loss of cav-1 mediates these abnormalities is currently under investigation. Mounting evidence indicates that cav-1 acts as a negative regulator of endothelial nitric oxide synthase resulting in a constitutive hyperactivation of the nitric oxide (NO)-pathway in cav-1 knockout mice (cav-1 ko). In this context we hypothesized that disturbed NO signalling is implicated in these changes. To explore this question cav-1 ko were compared with knockout counterparts experiencing 2 month postnatal NO synthase inhibition by N(G)-nitro-l-arginine methyl ester (l-NAME) treatment. Chronic l-NAME treatment resulted in significant improvements in heart function and exercise capacity in cav-1 ko. Furthermore, we found evidence for an enhanced radical stress in hearts of cav-1 ko which was markedly reduced by l-NAME treatment. Collectively, these findings suggest that NO synthases play a crucial role in the evolution of heart failure evident in cav-1 ko.

Right Ventricular Reduction as an Adjunct Procedure in Tricuspid Valve Repair

Functional tricuspid regurgitation secondary to mitral valve disease can not be attributed to the dilatation of the tricuspid annulus alone. Furthermore, geometrical changes of the right ventricle lead to tethering of the tricuspid valve leaflets and thereby to an incomplete leaflet coaptation. With this pathologic entity, conventional isolated tricuspid valve annuloplasty will presumably result in significant residual tricuspid regurgitation. The surgical goal should be the reduction of tricuspid annulus dilatation and annihilation of tethering forces on the tricuspid leaflets. In combination with conventional tricuspid valve annuloplasty, right ventricular reduction surgery, as demonstrated, may be effective in reaching these goals and hereby avoiding residual tricuspid regurgitation in this patient population.

Intra-aortic balloon pump (IABP) counterpulsation improves cerebral perfusion in patients with decreased left ventricular function

Background: The current goal of treatment after acute ischemic stroke is the increase of cerebral blood flow (CBF) in ischemic brain tissue. Intra-aortic balloon pump (IABP) counterpulsation in the setting of cardiogenic shock is able to reduce left ventricular afterload and increase coronary blood flow. The effects of an IABP on CBF have not been sufficiently examined. We hypothesize that the use of an IABP especially enhances cerebral blood flow in patients with pre-existing heart failure. Methods: In this pilot study, 36 subjects were examined to investigate the effect of an IABP on middle cerebral artery (MCA) transcranial Doppler (TCD) flow velocity change and relative CBF augmentation by determining velocity time integral changes (ΔVTI) in a constant caliber of the MCA compared to a baseline measurement without an IABP. Subjects were divided into two groups according to their left ventricular ejection fraction (LVEF): Group 1 LVEF >30% and Group 2 LVEF ≤30%. Results: Both groups showed an increase in CBF using an IABP. Patients with a LVEF ≤30% showed a significantly higher increase of ΔVTI in the MCA under IABP augmentation compared to patients with a LVEF >30% (20.9% ± 3.9% Group 2 vs.10.5% ± 2.2% Group 1, p<0,05). The mean arterial pressure (MAP) increased only marginally in both groups under IABP augmentation. Conclusions: IABP improves cerebral blood flow, particularly in patients with pre-existing heart failure and highly impaired LVEF. Hence, an IABP might be a treatment option to improve cerebral perfusion in selected patients with cerebral misperfusion and simultaneously existing severe heart failure.

Influence of the trigger technique on ventricular function measurements using 3-Tesla magnetic resonance imaging: comparison of ECG versus pulse wave triggering

Background Three Tesla cardiovascular magnetic resonance imaging (3T-CMR) is increasingly used in clinical practice. Despite many advantages one drawback is that ECG signal disturbances and artifacts increase with higher magnetic field strength resulting in trigger problems and false gating. This particularly affects cardiac imaging because most pulse sequences require ECG triggering. Pulse wave (PW) triggering is robust and might have advantages over ECG triggering. Purpose To evaluate differences in left ventricular (LV) function as an integral part of most CMR studies between ECG- and PW-triggered short-axis imaging using 3T-CMR. Material and Methods Forty-three patients underwent multiple short-axis cine imaging for LV-function assessment with ECG and PW triggering using standard multibreath hold steady-state free precession. LV-volumes (EDV, ESV), ejection fraction (EF), and mass were determined by slice summation. LV-wall motion was assessed by using a 4-point scoring scale. Bland Altman statistics for inter-observer variability were performed. Results ECG triggering failed in 15 patients (34.8%). Thus, analysis was performed in 28 patients (13 with impaired LV function). Difference in volumes (EDV 0.13 ± 1.8 mL, ESV 0.59 ± 1.1 mL), EF (–0.32 ± 0.6%) and mass (0.01 ± 1.1 g) between ECG and PW triggering were very small and significant only for ESV and EF (p ≤ 0.011). In patients with impaired LV function (n = 19) differences were not significant (p ≥ 0.128). Wall motion scores did not differ between ECG and PW triggering (p ≥ 0.295). Inter-observer variability for function measurements was low. Conclusion Short-axis cine imaging for LV-function assessment can accurately be performed using PW triggering on 3T magnets, and may be used in clinical practice when ECG triggering is disturbed.