Mechthild Westhoff-Bleck

Increased thrombin levels during thrombolytic therapy in acute myocardial infarction : relevance for the success of therapy

BackgroundIt has been suggested that thrombolysis in a feedback reaction may generate pro-coagulant activities. Methods and ResultsFifty-five patients were treated with urokinase-preactivated pro-urokinase (n = 35) or tissue-type plasminogen activator (n =20) for acute myocardial infarction and underwent coronary angiography at 90 minutes and at 24-36 hours into thrombolysis, and fibrinogen (Ratnoff-Menzie), D-dimer (ELISA) and thrombin-antithrombin III complex levels (ELISA) were measured. Primary patency was achieved in 39 patients (70.9%), 13 of whom (33.3%) suffered early reocclusion. Nonsignificant decreases in fibrinogen levels were observed while D-dimer levels increased +3,008±4,047 gg/l (p<0.01), differences not being significant in respect to the thrombolytic agents or to the clinical course. In contrast, while thrombin-antithrombin III complex levels decreased −4.4 ± 13.0, ug/l in patients with persistent patency, they increased +7.5±13.6 pg/l in case of nonsuccessful thrombolysis (p<0.02) and + 11.9±23.8, g/l in case of early reocclusion (p <0.001). For patients with thrombin-antithrombin III complex levels greater than 6 ng/l 120 minutes into thrombolysis, the unfavorable clinical course was predicted with 96.2% sensitivity and 93.1% specificity. ConclusionGeneration of thrombin, occurring during thrombolysis, is a major determinant for the success of therapy and thrombin-antithrombin III levels may serve as predictors for the short-term prognosis. (Circulation 1991;83:937–944)

Decellularized fresh homografts for pulmonary valve replacement: a decade of clinical experience

OBJECTIVES Decellularized homografts have shown auspicious early results when used for pulmonary valve replacement (PVR) in congenital heart disease. The first clinical application in children was performed in 2002, initially using pre-seeding with endogenous progenitor cells. Since 2005, only non-seeded, fresh decellularized allografts have been implanted after spontaneous recellularization was observed by several groups. METHODS A matched comparison of decellularized fresh pulmonary homografts (DPHs) implanted for PVR with cryopreserved pulmonary homografts (CHs) and bovine jugular vein conduits (BJVs) was conducted. Patients’ age at implantation, the type of congenital malformation, number of previous cardiac operations and number of previous PVRs were considered for matching purposes, using an updated contemporary registry of right ventricular outflow tract conduits (2300 included conduits, >12 000 patient-years). RESULTS A total of 131 DPHs were implanted for PVR in the period from January 2005 to September 2015. Of the 131, 38 were implanted within prospective trials on DPH from October 2014 onwards and were therefore not analysed within this study. A total of 93 DPH patients (58 males, 35 females) formed the study cohort and were matched to 93 CH and 93 BJV patients. The mean age at DPH implantation was 15.8 ± 10.21 years (CH 15.9 ± 10.4, BJV 15.6 ± 9.9) and the mean DPH diameter was 23.9 mm (CH 23.3 ± 3.6, BJV 19.9 ± 2.9). There was 100% follow-up for DPH, including 905 examinations with a mean follow-up of 4.59 ± 2.76 years (CH 7.4 ± 5.8, BJV 6.4 ± 3.8), amounting to 427.27 patient-years in total (CH 678.3, BJV 553.0). Tetralogy-of-Fallot was the most frequent malformation (DPH 50.5%, CH 54.8%, BJV 68.8%). At 10 years, the rate of freedom of explantation was 100% for DPH, 84.2% for CH (P = 0.01) and 84.3% for BJV (P= 0.01); the rate of freedom from explantation and peak trans-conduit gradient ≥50 mmHg was 86% for DPH, 64% for CH (n.s.) and 49% for BJV (P < 0.001); the rate of freedom from infective endocarditis (IE) was 100% for DPH, 97.3 ± 1.9% within the matched CH patients (P = 0.2) and 94.3 ± 2.8% for BJV patients (P = 0.06). DPH valve annulus diameters converged towards normal Z-values throughout the observation period, in contrast to other valve prostheses (BJV). CONCLUSIONS Mid-term results of DPH for PVR confirm earlier results of reduced re-operation rates compared with CH and BJV.

Circulating miR-423_5p fails as a biomarker for systemic ventricular function in adults after atrial repair for transposition of the great arteries.

BACKGROUND Recently, the microRNA miR-423_5p was identified as a biomarker for left ventricular heart failure. Its role in patients with a systemic right ventricle and reduced ejection fraction after atrial repair for transposition of the great arteries has not been evaluated. METHODS In 41 patients and 10 age- and sex-matched healthy controls circulating miR-423_5p concentration was measured and correlated to clinical parameters, cardiac functional parameters assessed by magnetic resonance imaging, and cardiopulmonary exercise testing. RESULTS Levels of circulating miR-423_5p showed no difference between patients and controls. Further, there was no correlation between miR-423_5p and parameters of cardiopulmonary exercise testing or imaging findings. CONCLUSIONS In patients with a systemic right ventricle and reduced ejection fraction miR-423_5p levels are not elevated. Therefore, circulating miR-423_5p is not a useful biomarker for heart failure in this patient group.

Symmetrical dimethylarginine outperforms CKD-EPI and MDRD-derived eGFR for the assessment of renal function in patients with adult congenital heart disease.

Background/Aims: Adults with congenital heart disease exhibit a 3-fold higher mortality in the presence of chronic kidney disease, hence assessment of renal function is crucial in this patient population. Formulas for the estimation of glomerular filtration rate (GFR) have not been evaluated in this patient population. Therefore, this study compares different markers and equations for the estimation of renal function in adults with congenital heart disease. Methods: Renal function was assessed in 102 patients using the Modification of Diet in Renal Disease (MDRD) equation, the simplified MDRD equation, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the Cockcroft-Gault formula. Additionally, symmetrical dimethylarginine (SDMA) was measured. Those parameters were compared to cystatin C-derived GFR using the Larsson equation. Results: GFR estimates using the original MDRD (r = 0.465, p < 0.001) and the CKD-EPI equation (r = 0.462, p < 0.001) showed a similar strong correlation with the cystatin C-based eGFR equation, while eGFR using the simplified MDRD equation showed a slightly weaker correlation (r = 0.439, p < 0.001). The Cockcroft-Gault formula showed no correlation at all to the cystatin C-based eGFR (r = 0.144, p = 0.17). The strongest correlation was observed for SDMA and cystatin C-based eGFR (r = –0.552, p < 0.001). Conclusion: GFR in adults with congenital heart disease should be estimated using the original MDRD or the CKD-EPI formula. SDMA seems to be a promising marker of renal function for this patient group.

Long-term morbidity and quality of life after surgical repair of transposition of the great arteries: atrial versus arterial switch operation

Since a growing number of patients after surgical repair of transposition of the great arteries (TGA) survive until adulthood the focus of attention has shifted to the management of associated long-term morbidity and quality of life (QoL). Therefore, we reviewed all patients that underwent surgical repair of TGA at our institution and compared long-term results after atrial and arterial switch operation. Between 1973 and 2000, a total of 302 patients underwent either atrial switch operation (n=222) or arterial switch operation (n=80). Mean follow-up was 14.5±10.1 years. The arterial switch repair was associated with a higher early mortality whereas long-term survival was comparable between both groups. Postoperative arrhythmias including loss of sinus rhythm and pacemaker implantation occurred significantly more often after atrial switch repair. There was a trend towards a more favourable outcome of the arterial switch group concerning freedom from re-interventions, severe systemic ventricular dysfunction and need for heart failure medication. However, also the arterial switch operation was associated with an increased incidence of loss of sinus rhythm and neo-aortic valve regurgitation during late follow-up. Health related QoL according to the SF-36 questionnaire was not significantly different between both groups and comparable to a healthy population.

Aerobic training in adults after atrial switch procedure for transposition of the great arteries improves exercise capacity without impairing systemic right ventricular function.

BACKGROUND Exercise training safely and efficiently improves symptoms in patients with heart failure due to left ventricular dysfunction. However, studies in congenital heart disease with systemic right ventricle are scarce and results are controversial. In a randomised controlled study we investigated the effect of aerobic exercise training on exercise capacity and systemic right ventricular function in adults with d-transposition of the great arteries after atrial redirection surgery (28.2 ± 3.0 years after Mustard procedure). METHODS 48 patients (31 male, age 29.3 ± 3.4 years) were randomly allocated to 24 weeks of structured exercise training or usual care. Primary endpoint was the change in maximum oxygen uptake (peak VO2). Secondary endpoints were systemic right ventricular diameters determined by cardiac magnetic resonance imaging (CMR). Data were analysed per intention to treat analysis. RESULTS At baseline peak VO2 was 25.5 ± 4.7 ml/kg/min in control and 24.0 ± 5 ml/kg/min in the training group (p=0.3). Training significantly improved exercise capacity (treatment effect for peak VO2 3.8 ml/kg/min, 95% CI: 1.8 to 5.7; p=0.001), work load (p=0.002), maximum exercise time (p=0.002), and NYHA class (p=0.046). Systemic ventricular function and volumes determined by CMR remained unchanged. None of the patients developed signs of cardiac decompensation or arrhythmias while on exercise training. CONCLUSIONS Aerobic exercise training did not detrimentally affect systemic right ventricular function, but significantly improved exercise capacity and heart failure symptoms. Aerobic exercise training can be recommended for patients following atrial redirection surgery to improve exercise capacity and to lessen or prevent heart failure symptoms. ( CLINICAL TRIAL REGISTRATION ClinicalTrials.gov #NCT00837603).

Safety and efficiency of chronic ACE inhibition in symptomatic heart failure patients with a systemic right ventricle

BACKGROUND ACE inhibition is an established treatment regimen in patients with congestive heart failure due to left ventricular dysfunction which improves morbidity and mortality. However, little is known about the beneficial effects of ACE inhibition in adult patients after Mustard procedure for transposition of the great arteries with heart failure symptoms. Therefore, we investigated the effects of ACE inhibition in these patients on heart failure symptoms, echocardiographic diameters, NT-proBNP and exercise capacity. METHODS In 14 patients (age 25.2 ± 3.5 years), after Mustard procedure for transposition of the great arteries (age at operation 1.1 ± 1.3 years) with heart failure NYHA II (New York Heart Association class), an ACE inhibition was initiated. At baseline and 13.3 ± 4.0 months after treatment with enalapril (10mg twice a day), echocardiography, exercise test and NT-proBNP measurements were performed and compared to an age- and sex-matched control group. RESULTS Maximum oxygen uptake and echocardiographic parameters did not change significantly in both groups. However, NT-proBNP showed a significant decrease in the treatment group (242 ± 105 vs. 151 ± 93 ng/l, p=0.004), while in the control group a significant increase (120 ± 89 vs. 173 ± 149 ng/l, p<0.05) was observed. Furthermore, ACE inhibitor treatment did not result in a deterioration of heart failure symptoms or renal function. CONCLUSIONS Thus, ACE inhibitor treatment of heart failure symptoms in patients with a systemic right ventricle is safe and reduces NT-proBNP levels significantly as a marker for ventricular overload. Nevertheless, larger scale trials are warranted to show effects on morbidity and mortality in this highly selected patient group.

Relation of diastolic and systolic function, exercise capacity and brain natriuretic peptide in adults after Mustard procedure for transposition of the great arteries.

Objectives: To evaluate the relation of echocardiographic parameters of diastolic function, exercise capacity (expressed as peakVO2) and NT-proBNP in patients with transposition of the great arteries (TGA) and Mustard procedure. Methods: Diastolic function was determined by measuring tricuspid flow velocities (Ea/Aa ratio), isovolumic relaxation time (IVRT), and deceleration time (DT). E/Ea ratios were calculated. For assessment of systolic function, CMR was applied. Results: E/A (r = 0.07, p = 0.66), E/Ea medial (r = 0.03, p = 0.84), E/Ea lateral (r = –0.01, p = 0.92), IVRT (r = –0.13, p = 0.44), and DT (r = –0.05, p = 0.76) were not correlated with peakVO2. NT-proBNP showed a significant correlation with IVRT (r = 0.44, p = 0.004) and Ea/Aa medial (r = –0.34, p = 0.025). No correlation was found between RV systolic function and peakVO2 (r = 0.07, p = 0.63). Conclusions: Exercise capacity in patients with TGA and Mustard procedure is not related to echocardiographic parameters of diastolic function. NT-proBNP is associated with selected echocardiographic parameters of diastolic function.

The Adverse Effects of Angiographic Radiocontrast Media

SummaryRadiographic procedures which require the intravascular administration of water-soluble radiocontrast media are performed with increasing frequency. Each examination carries risks that are related either to the technique itself or to the opaque medium chosen. The pathogenesis of radiocontrast media-related adverse effects cannot be explained by a unique theory. The major factors implicated are direct chemotoxic effects and the physicochemical properties of contrast media, the latter being the basis for development of new contrast agents. With non-ionic opaque media cardiovascular adverse effects, heat sensation and local pain are observed less frequently. However, it remains unclear whether the incidence of organ dysfunction or anaphylactic reactions with nonionic contrast media currently used can be reduced. This review compares ionic and nonionic contrast media, and current thoughts on the pathophysiology and treatment of adverse reactions are presented.

Decellularized aortic homografts for aortic valve and aorta ascendens replacement

OBJECTIVES The choice of valve prosthesis for aortic valve replacement (AVR) in young patients is challenging. Decellularized pulmonary homografts (DPHs) have shown excellent results in pulmonary position. Here, we report our early clinical results using decellularized aortic valve homografts (DAHs) for AVR in children and mainly young adults. METHODS This prospective observational study included all 69 patients (44 males) operated from February 2008 to September 2015, with a mean age of 19.7 ± 14.6 years (range 0.2–65.3 years). In 18 patients, a long DAH was used for simultaneous replacement of a dilated ascending aorta as an extended aortic root replacement (EARR). Four patients received simultaneous pulmonary valve replacement with DPH. RESULTS Thirty-nine patients (57%) had a total of 62 previous operations. The mean aortic cross-clamp time in isolated cases was 129 ± 41 min. There was 1 conduit-unrelated death. The mean DAH diameter was 22.4 ± 3.7 mm (range, 10–29 mm), the average peak gradient was 14 ± 15 mmHg and the mean aortic regurgitation grade (0.5 = trace, 1 = mild) was 0.6 ± 0.5. The mean effective orifice area (EOA) of 25 mm diameter DAH was 3.07 ± 0.7 cm2. DAH annulus z-values were 1.1 ± 1.1 at implantation and 0.7 ± 1.3 at the last follow-up. The last mean left ventricle ejection fraction and left ventricle end diastolic volume index was 63 ± 7% and 78 ± 16 ml/m2 body surface area, respectively. To date, no dilatation has been observed at any level of the graft during follow-up; however, the observational time is short (140.4 years in total, mean 2.0 ± 1.8 years, maximum 7.6 years). One small DAH (10 mm at implantation) had to be explanted due to subvalvular stenosis and developing regurgitation after 4.5 years and was replaced with a 17 mm DAH without complication. No calcification of the explanted graft was noticed intraoperatively and after histological analysis, which revealed extensive recellularization without inflammation. CONCLUSIONS DAHs withstand systemic circulation, provide outstanding EOA and appear as an alternative to conventional grafts for AVR in young patients. EARR using DAH is a further option in aortic valve disease associated with aorta ascendens dilatation as it avoids the use of any prosthetic material.