Corinna Heinisch

Comparison of three patent foramen ovale closure devices in a randomized trial (Amplatzer versus CardioSEAL-STARflex versus Helex occluder).

This randomized trial compared procedural complications and 30-day clinical outcomes of 3 patent foramen ovale (PFO) closure devices (Amplatzer, Helex, and CardioSEAL-STARflex). It examined 660 patients (361 men, 299 women, mean age 49.3+/-1.9 years), with 220 patients per group. All patients had a history of paradoxical embolism. All PFO closures were successful technically. Exchange of devices for others was most frequently required for the Helex occluder (7 of 220) and 2 of 220 in either of the other groups. Three device embolizations in the Helex group were retrieved and replaced successfully. One patient with a Helex occluder developed a transient ischemic attack and recovered without treatment. A hemopericardium in that group was punctured without affecting the device. One tamponade in the Amplatzer group required surgical device explantation. In 8 of 660 patients in the CardioSEAL-STARflex group, thrombi resolved after anticoagulation. Sixteen patients (11 in the CardioSEAL-STARflex group, 3 in the Amplatzer group, and 2 in the Helex group) had episodes of atrial fibrillation. PFOs were closed completely in 143 of 220 patients (65%) in the Amplatzer group, 116 of 220 patients (52.7%) in the Helex group, and 137 of 220 patients (62.3%) in the CardioSEAL-STARflex group at 30 days with significant differences between the Helex and Amplatzer occluders (p=0.0005) and the Helex and CardioSEAL-STARflex occluders (p=0.0003). PFO closure can be performed safely with each device. In conclusion, the Helex occluder embolized more frequently. Device thrombus formation and paroxysmal atrial fibrillation were more common with the CardioSEAL-STARflex occluder.

Early diagnosis of acute myocardial infarction in patients with pre-existing coronary artery disease using more sensitive cardiac troponin assays

AIMSnWe sought to examine the diagnostic and prognostic utility of sensitive cardiac troponin (cTn) assays in patients with pre-existing coronary artery disease (CAD).nnnMETHODS AND RESULTSnWe conducted a multicentre study to examine the diagnostic accuracy of one high-sensitive and two sensitive cTn assays in 1098 consecutive patients presenting with symptoms suggestive of acute myocardial infarction (AMI), of whom 401 (37%) had pre-existing CAD. Measurements of Roche high-sensitive cTnT (hs-cTnT), Siemens cTnI-Ultra, Abbott-Architect cTnI and the standard assay (Roche cTnT) were performed in a blinded fashion. The final diagnosis was adjudicated by two independent cardiologists. Acute myocardial infarction was the final diagnosis in 19% of CAD patients. Among patients with diagnoses other than AMI, baseline cTn levels were elevated above the 99th percentile with Roche hs-cTnT in 40%, with Siemens TnI-Ultra in 15%, and Abbott-Architect cTnI in 13% of them. In patients with pre-existing CAD, the diagnostic accuracy at presentation, quantified by the area under the receiver operator characteristic curve (AUC), was significantly greater for the sensitive cTn assays compared with the standard assay (AUC for Roche hs-cTnT, 0.92; Siemens cTnI-Ultra, 0.94; and Abbott-Architect cTnI, 0.93 vs. AUC for the standard assay, 0.87; P < 0.01 for all comparisons). Elevated levels of cTn measured with the sensitive assays predicted mortality irrespective of pre-existing CAD, age, sex, and cardiovascular risk factors.nnnCONCLUSIONnSensitive cTn assays have high-diagnostic accuracy also in CAD patients. Mild elevations are common in non-AMI patients and test-specific optimal cut-off levels tend to be higher in CAD patients than in patients without history of CAD. Sensitive cTn assays also retain prognostic value. (ClinicalTrials.gov number, NCT00470587).

Effect and Clinical Prediction of Worsening Renal Function in Acute Decompensated Heart Failure

We aimed to establish the prevalence and effect of worsening renal function (WRF) on survival among patients with acute decompensated heart failure. Furthermore, we sought to establish a risk score for the prediction of WRF and externally validate the previously established Forman risk score. A total of 657 consecutive patients with acute decompensated heart failure presenting to the emergency department and undergoing serial creatinine measurements were enrolled. The potential of the clinical parameters at admission to predict WRF was assessed as the primary end point. The secondary end point was all-cause mortality at 360 days. Of the 657 patients, 136 (21%) developed WRF, and 220 patients had died during the first year. WRF was more common in the nonsurvivors (30% vs 41%, p = 0.03). Multivariate regression analysis found WRF to independently predict mortality (hazard ratio 1.92, p <0.01). In a single parameter model, previously diagnosed chronic kidney disease was the only independent predictor of WRF and achieved an area under the receiver operating characteristic curve of 0.60. After the inclusion of the blood gas analysis parameters into the model history of chronic kidney disease (hazard ratio 2.13, p = 0.03), outpatient diuretics (hazard ratio 5.75, p <0.01), and bicarbonate (hazard ratio 0.91, p <0.01) were all predictive of WRF. A risk score was developed using these predictors. On receiver operating characteristic curve analysis, the Forman and Basel prediction rules achieved an area under the curve of 0.65 and 0.71, respectively. In conclusion, WRF was common in patients with acute decompensated heart failure and was linked to significantly worse outcomes. However, the clinical parameters failed to adequately predict its occurrence, making a tailored therapy approach impossible.

Direct Comparison of Three Natriuretic Peptides for Prediction of Short- and Long-term Mortality in Patients With Community-Acquired Pneumonia

BACKGROUNDnEarly and accurate risk stratification for patients with community-acquired pneumonia (CAP) is an unmet clinical need.nnnMETHODSnWe enrolled 341 unselected patients presenting to the ED with CAP in whom blinded measurements of N-terminal pro-B-type natriuretic peptide (NT-proBNP), midregional pro-atrial natriuretic peptide (MR-proANP), and B-type natriuretic peptide (BNP) were performed. The potential of these natriuretic peptides to predict short- (30-day) and long-term mortality was compared with the pneumonia severity index (PSI) and CURB-65 (confusion, urea plasma level, respiratory rate, BP, age over 65 years). The median follow-up was 942 days.nnnRESULTSnNT-proBNP, MR-proANP, and BNP levels at presentation were higher in short-term (median 4,882 pg/mL vs 1,133 pg/mL; 426 pmol/L vs 178 pmol/L; 436 pg/mL vs 155 pg/mL, all P < .001) and long-term nonsurvivors (3,515 pg/mL vs 548 pg/mL; 283 pmol/L vs 136 pmol/L; 318 pg/mL vs 103 pg/mL, all P < .001) as compared with survivors. Receiver operating characteristics analysis to quantify the prognostic accuracy showed comparable areas under the curve for the three natriuretic peptides to PSI for short-term (PSI 0.76, 95% CI, 0.71-0.81; NT-proBNP 0.73, 95% CI, 0.67-0.77; MR-proANP 0.72, 95% CI, 0.67-0.77; BNP 0.68, 95% CI, 0.63-0.73) and long-term (PSI 0.72, 95% CI, 0.66-0.77; NT-proBNP 0.75, 95% CI, 0.70-0.80; MR-proANP 0.73, 95% CI, 0.67-0.77, BNP 0.70, 95% CI, 0.65-0.75) mortality. In multivariable Cox-regression analysis, NT-proBNP remained an independent mortality predictor (hazard ratio 1.004, 95% CI, 1.00-1.01, P = .02 for short-term; hazard ratio 1.004, 95% CI, 1.00-1.01, P = .001 for long-term, increase of 300 pg/mL). A categorical approach combining PSI point values and NT-pro-BNP levels adequately identified patients at low, medium, and high short- and long-term mortality risk.nnnCONCLUSIONSnNatriuretic peptides are simple and powerful predictors of short- and long-term mortality for patients with CAP. Their prognostic accuracy is comparable to PSI.

Plasma neutrophil gelatinase-associated lipocalin for the prediction of acute kidney injury in acute heart failure

IntroductionThe accurate prediction of acute kidney injury (AKI) in patients with acute heart failure (AHF) is an unmet clinical need. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel sensitive and specific marker of AKI.MethodsA total of 207 consecutive patients presenting to the emergency department with AHF were enrolled. Plasma NGAL was measured in a blinded fashion at presentation and serially thereafter. The potential of plasma NGAL levels to predict AKI was assessed as the primary endpoint. We defined AKI according to the AKI Network classification.ResultsOverall 60 patients (29%) experienced AKI. These patients were more likely to suffer from pre-existing chronic cardiac or kidney disease. At presentation, creatinine (median 140 (interquartile range (IQR), 91 to 203) umol/L versus 97 (76 to 132) umol/L, P < 0.01) and NGAL (114.5 (IQR, 67.1 to 201.5) ng/ml versus 74.5 (60 to 113.9) ng/ml, P < 0.01) levels were significantly higher in AKI compared to non-AKI patients. The prognostic accuracy for measurements obtained at presentation, as quantified by the area under the receiver operating characteristic curve was mediocre and comparable for the two markers (creatinine 0.69; 95%CI 0.59 to 0.79 versus NGAL 0.67; 95%CI 0.57 to 0.77). Serial measurements of NGAL did not further increase the prognostic accuracy for AKI. Creatinine, but not NGAL, remained an independent predictor of AKI (hazard ratio (HR) 1.12; 95%CI 1.00 to 1.25; P = 0.04) in multivariable regression analysis.ConclusionsPlasma NGAL levels do not adequately predict AKI in patients with AHF.

Transcatheter Closure of Patent Foramen Ovale Without an Implant: Initial Clinical Experience

Background— Currently available catheter techniques for closure of a patent foramen ovale (PFO) rely on the placement of an implantable closure device. The objective of the Paradigm I study was to evaluate the safety and feasibility of transcatheter closure of PFO using radiofrequency energy without an implanted device in patients with cryptogenic stroke or transient ischemic attack. Methods and Results— Thirty patients were enrolled (15 females; mean age 48 years). Mean PFO size was 8.5±2.7 mm. Technical success (ie, successful application of radiofrequency energy) was achieved in 27 patients. The remaining 3 patients received an implantable closure device. All 30 patients were free from serious procedure-related adverse events. No recurrent strokes, deaths, or perforations occurred as a result of the procedure. The mean follow-up was 6 months, and 13 (43%) of the 30 patients experienced PFO closure after the first procedure. Nine of the patients whose PFOs remained patent after the first procedure elected to receive a second procedure using radiofrequency. The PFO was closed for 6 of those patients after the second procedure, which resulted in a secondary closure rate of 63%. Conclusions— This study demonstrates that transcatheter closure of an intracardiac defect without a permanent implant is technically feasible. Achievement of improved primary closure rates through technique and device modifications will warrant randomized clinical comparison to permanently implanted devices.

Pathophysiology of Lower Extremity Edema in Acute Heart Failure Revisited

BACKGROUNDnThe pathophysiology and key determinants of lower extremity edema in patients with acute heart failure are poorly investigated.nnnMETHODSnWe prospectively enrolled 279 unselected patients presenting to the Emergency Department with acute heart failure. Lower extremity edema was quantified at predefined locations. Left ventricular ejection fraction, central venous pressure quantifying right ventricular failure, biomarkers to quantify hemodynamic cardiac stress (B-type natriuretic peptide), and the activity of the arginine-vasopressin system (copeptin) also were recorded.nnnRESULTSnLower extremity edema was present in 218 (78%) patients and limited to the ankle in 22%, reaching the lower leg in 40%, reaching the upper leg in 11%, and was generalized (anasarca) in 3% of patients. Patients in the 4 strata according to the presence and extent of lower leg edema had comparable systolic blood pressure, left ventricular ejection fraction, central venous pressure, and B-type natriuretic peptide levels, as well as copeptin and glomerular filtration rate (P=NS for all). The duration of dyspnea preceding the presentation was longer in patients with more extensive edema (P=.006), while serum sodium (P=.02) and serum albumin (P=.03) was lower.nnnCONCLUSIONnCentral venous pressure, hemodynamic cardiac stress, left ventricular ejection fraction, and the activity of the arginine-vasopressin system do not seem to be key determinants of the presence or extent of lower extremity edema in acute heart failure.

Percutaneous closure of the patent foramen ovale using the HELEX® Septal Occluder: acute and long-term results in 405 patients.

AIMSnAlthough routinely used, limited data are available regarding the long-term outcome after patent foramen ovale (PFO) closure using the HELEX® Occluder system. The aim of this study was therefore the examination of the acute and long-term outcome after transcatheter PFO closure using this system.nnnMETHODS AND RESULTSnAll (n=407) patients included had undergone PFO closure with the HELEX® Occluder system for secondary prevention of stroke, transient ischaemic attack (TIA) or peripheral embolism at a single centre. Primary endpoints were residual shunts at six or 12 months (assessed by transoesophageal echocardiography) and the number of neurological and other adverse events during follow-up. Device implantation was successful in 99% of patients. Complete closure at six months was achieved in 81%. During follow-up of 1,695 patient-years, 10 neurologic events occurred (four TIA, six strokes). The annual incidence of stroke was 1.2%. Other adverse events were wire frame fractures requiring no further intervention in five (1%), device-associated thrombus formation in one (0.25%), and paroxysmal atrial fibrillation in nine patients (2%).nnnCONCLUSIONSnPFO closure using the HELEX® Occluder system is feasible and safe. Complications and adverse events during long-term follow-up are rare. The safety profile and efficacy in prevention of recurrent events compare well to that reported with other closure devices.

Quantifying Cardiac Hemodynamic Stress and Cardiomyocyte Damage in Ischemic and Nonischemic Acute Heart Failure

Background— The early and noninvasive differentiation of ischemic and nonischemic acute heart failure (AHF) in the emergency department (ED) is an unmet clinical need. Methods and Results— We quantified cardiac hemodynamic stress using B-type natriuretic peptide (BNP) and cardiomyocyte damage using 2 different cardiac troponin assays in 718 consecutive patients presenting to the ED with AHF (derivation cohort). The diagnosis of ischemic AHF was adjudicated using all information, including coronary angiography. Findings were validated in a second independent multicenter cohort (326 AHF patients). Among the 718 patients, 400 (56%) were adjudicated to have ischemic AHF. BNP levels were significantly higher in ischemic compared with nonischemic AHF (1097 [604–1525] pg/mL versus 800 [427–1317] pg/mL; P<0.001). Cardiac troponin T (cTnT) and sensitive cardiac troponin I (s-cTnI) were also significantly higher in ischemic compared with nonischemic AHF patients (0.040 [0.010–0.306] &mgr;g/L versus 0.018 [0.010–0.060] &mgr;g/L [P<0.001]; 0.024 [0.008–0.106] &mgr;g/L versus 0.016 [0.004–0.044 ] &mgr;g/L [P=0.002]). The diagnostic accuracy of BNP, cTnT, and s-cTnI for the diagnosis of ischemic AHF, as quantified by the area under the receiver-operating characteristic curve, was low (0.58 [95% CI, 0.54–0.63], 0.61 [95% CI, 0.57–0.66], and 0.59 [95% CI,0.54–0.65], respectively). These findings were confirmed in the validation cohort. Conclusions— At presentation to the ED, patients with ischemic AHF exhibit more extensive hemodynamic cardiac stress and cardiomyocyte damage than patients with nonischemic AHF. However, the overlap is substantial, resulting in poor diagnostic accuracy.

A suture not always the ideal solution: Problems encountered in developing a suture-based PFO closure technique†

Objectives: To summarize our experiences with the first‐in‐man suture‐based patent foramen ovale (PFO) closure technique. Background: PFO is often present with the occurrence of cryptogenic stroke and migraine with aura. Successful PFO closure can be performed percutaneously using catheter techniques with many different closure devices. The described novel closure system is intended to deliver, via endovascular access, a suture into the atrial septal wall tissue for closure of PFO. Methods: Eleven patients, between 22 and 58 years of age (mean 46.6 ± 9.6), who had a cryptogenic ischemic stroke, TIA, or a peripheral embolism and a PFO were considered for percutaneous closure with this technique. Results: The mean stretched diameter of the defect evaluated during balloon sizing was 8.8 ± 0.4 mm (range 7–12.5). Delivery of the suture was successful in all patients. No intraprocedural complications occurred. During the follow up, complete closure could be achieved in one patient. Six patients with significant residual shunting during follow‐up had successful closure using a conventional device. One patient was lost for follow‐up after the 3‐month visit. The residual shunt in the remaining three patients was very small and they declined to be treated with a conventional device. No complications occurred during the follow up. Conclusions: Transcatheter application of a suture for closure of PFO is technically feasible and safe. However, despite successful suturing of the septum primum to the septum secundum, the PFO did not close in most of the patients.