ABSTRACT: OBJECTIVES: Oral anticoagulation in mechanical heart valve recipients remains crucial, and vitamin K antagonists (VKA) are still the gold standard. Polymorphisms of vitamin K epoxide oxidase reductase (VKORC) and cytochrome p450 (CYP2C9) were recently found to influence VKA metabolism. We retrospectively investigated the prevalence of these genotypes and associated anticoagulation-related complications in our patients. METHODS: Between August 1998 and August 2008, 563 patients received mechanical heart valve replacement in our institution. Of these, 179 completed a questionnaire on anticoagulation-related complications and consented to genetic analysis. We analysed polymorphisms of VKORC (-1639 G>A; 1173 C>T) and of CYP2C9 (*2, 144 C>T; *3, 359 A>C) by PCR and restriction analysis. RESULTS: For VKORC-1639/1173 alleles, there were 62 (35%) patients with the combination GG/CC, 91 (51%) with GA/CT, 25 (14%) with AA/TT and 1 (1%) with AA/CT. Phenprocoumon (PC) dosage was related to VKORC polymorphism (P < 0.001) with lower doses required for AA/TT patients. Overall, there were 27 severe bleedings and 11 thromboembolic events. For GG/CC, the incidence of major bleeding events and thromboembolic events was 13 and 6%, respectively, and for AA/TT, it was 27 and 12%, respectively. Variation in international normalized ratio (INR) >1.5 was associated with severe bleeding complications (P = 0.025) and GA/CT patients were predisposed to INR variations >1.5 (P = 0.028). No influence of CYP2C9 polymorphism on PC dosage and anticoagulation-related complications was found. CONCLUSIONS: VKORC polymorphism affects PC dosage and anticoagulation-related complication rates in mechanical heart valve recipients. Genotyping may help to identify patients at particular risk of anticoagulation-related complications.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 02/2013; · 2.40 Impact Factor
ABSTRACT: In Vorstudien konnten wir belegen, dass kontinuierliche antegrade Koronarperfusion mit warmen ultrakurz wirkendem Beta-Blocker
(Esmolol/ES) angereichertem Blut den funktionellen und strukturellen Schutz der Herzmuskelzellen unter aortokoronaren Bypassoperation
im Vergleich mit konventioneller Brettschneider-Kardioplegie (BKP) verbessert. Ziel unserer Studie war der Vergleich der beiden
Protektionstechniken in Bezug auf die postoperativen klinischen Ergebnisse. Hierfür analysierten wir 150 aufeinanderfolgende
Patienten retrospektiv, die mit herkömmlicher Brettschneidertechnik protektioniert worden waren und verglichen diese mit 150
Patienten, die mit kontinuierlichen warmen Blut, welches mit einem ultrakurz wirkenden Beta-Blocker angereichert war, am schlagenden
Herzen mit arteriellen und venösen koronaren Bypässen versorgt worden waren. Beide Gruppen zeigten vergleichbare Werte für
Alter, Geschlecht, präoperativer linksventrikulärer Funktion, präoperatives Vorhandensein von Niereninsuffizienz und neurologischen
Vorschädigungen. Sie wurden im gleichen Zeitraum operiert. Es ergaben sich keine signifikanten Unterschiede zwischen den Gruppen
in Bezug auf die perioperative Infarktrate, Gabe von positiv inotroper Medikation, Anwendung von kreislaufunterstützenden
Systemen, Dauer der Nachbeatmung, Dauer des postoperativen Intensivstationsaufenthaltes, des Mobilisationszeitraum, Häufigkeit
der postoperativer Niereninsuffizienz, Herzrhythmusstörungen, neurologischen Auffälligkeiten, Infektionshäufigkeit und 30-Tage-Mortalität.
Esmolol-Patienten (ES) wurden signifikant seltener auf die Intensivstation zurückverlegt (3 von 150=2,2% [95% Konfidenzinterval:
0-4-2%] gegen 13 von 150=8,7% [KI 4,2–13,2%]; p=0,010). Außerdem wiesen ES-Patienten eine kürzere Krankenhausverweildauer
auf (ES: 12,3±4,8Tage [95%-Konfidenzinterval 11,5–13,0] im Vergleich BKP-Patienten 13,5±3,8 [95%-KI 12,9–14,1] Tage; p=0,013).
Damit wurden 159 Patiententage auf Normalstation gespart. Zusätzlich lagen die Kosten für die Beta-Blockade-Behandlung bei
durchschnittlich 60 Euro im Vergleich zu 120 Euro für die Brettschneider-Kardioplegie-Technik pro Patient. Unsere Daten zeigten
keine Unterschiede im klinischen Ergebnis zwischen den Gruppen, jedoch sehr wohl einen Unterschied in den tatsächlichen Kosten.
Recently it was shown that continuous coronary perfusion with warm blood enriched with the ultra-short acting β-blocker Esmolol
(ES) improves functional and structural myocardial protection during coronary artery surgery as compared with conventional
cardioplegia (CP). The aim of the presented study was to compare both myocardial protection techniques in terms of patient
outcome. We therefore retrospectively analyzed data of 150 consecutive patients planed for coronary artery surgery using the
ES-technique; 150 patients matched for age, gender, preoperative left ventricular function, history of renal failure, and
history of neurological symptoms undergoing surgery with conventional CP during the same time period served as control group.
There were no significant differences between both groups with respect to perioperative myocardial infarction rate, need for
positive inotropic medication, need for mechanical circulatory support, duration of mechanical ventilation, duration of intensive
care unit stay, time of mobilization, postoperative renal failure, cardiac arrhythmias, neurological symptoms, infections
or in-hospital mortality. ES-patients were less frequently readmitted to the intensive care unit (ES: 3/150; 2.2% [95% confidence
interval: 0–4.2%] vs CP: 13/150; 8.7% [4.2–13.2%]; p=0.010) and total hospital stay was shorter (ES: 12.3±4.8 days [95% CI:
11.5–13.0] vs CP: 13.5±3.8 [12.9–14.1] days; p=0.0013), thus saving 159 patient days on the normal ward. Costs of myocardial
protection were less for the ES-technique (60 Euro per patient) compared to the cardioplegia technique (120 Euro per patient).
These data suggest that myocardial protection using the ES-technique does not improve clinical outcome in patients subjected
to routine coronary artery surgery, but may save costs.
Zeitschrift für Herz- Thorax- und Gefäßchirurgie 04/2012; 17(2):64-68.
The Annals of thoracic surgery 07/2011; 92(1):407-8. · 3.74 Impact Factor
ABSTRACT: Acute rejection after kidney transplantation was found to be associated with increased recipient-derived lymph angiogenesis. However, the relation of lymph angiogenesis to acute rejection in lung transplantation has not yet been investigated.
Transbronchial biopsies from 23 lung transplant recipients (47 + or - 15 years old, 15 male, 19 double lungs, 4 single lungs), taken at 14 and 90 days after transplantation were investigated. Immunohistostaining for PROX-1 (an lymphatic endothelial marker) and for vascular endothelial growth factor receptor (VEGFR) 1 and 2 (blood capillary markers) was performed. Biopsies with no sign of rejection (International Society for Heart and Lung Transplantation [ISHLT] grade A0, n = 27) were compared with biopsies with rejection grade A1/A2 (n = 19).
Biopsies with ISHLT rejection grade A1 or A2 showed a significantly higher density of PROX-1 marked lymphatics in comparison with biopsies of grade A0 at 14 days (p < 0.001) and at 90 days (p < 0.001) after transplantation, and in the collective comparison (all biopsies with ISHLT grade A1 or A2 versus all biopsies with grade A0, p < 0.001). For VEGFR-1 and VEGFR-2, no difference was found between ISHLT grade A1 or A2 compared with grade A0, neither at 14 or 90 days nor in the collective comparison.
Increased lymphatic angiogenesis after lung transplantation, demonstrated by increased density of the PROX-1 lymphatic endothelial marker, was associated with histologically evident acute organ rejection in humans. Although the exact role of lymphatic angiogenesis in acute organ rejection remains to be determined, further study of the interaction between the microvasculature and acute rejection seems warranted. Pending further investigation, analysis of PROX-1 density may develop into a new tool for rejection monitoring, supplementing conventional rejection grading.
The Annals of thoracic surgery 08/2010; 90(2):406-11. · 3.74 Impact Factor
The Annals of thoracic surgery 11/2009; 88(5):1466-7. · 3.74 Impact Factor
ABSTRACT: Surgery plays a central role in the management of acquired valvular heart disease. The optimal diagnostic evaluation, surgical treatment, and postoperative care of these patients are only possible through a cooperative effort of the primary care physician, the cardiologist, and the cardiac surgeon.
The literature was selectively searched for information on surgical indications, operative techniques, and postoperative care in acquired valvular heart disease. Evidence-based guidelines and treatment recommendations were also taken into account.
A wide variety of techniques and implants are now available for the surgical treatment of acquired valvular heart disease. If they are used in evidence-based fashion, the perioperative mortality is low and the long-term outcome is favorable.
The volume of surgery for acquired valvular heart disease in Germany has increased substantially in recent years, from 25,495 cases in 2002 (corresponding to 26.5% of all heart operations in that year) to 33,412 in 2007 (36.5% of all heart operations). The causes for this include both demographic changes and the availability of new, less invasive surgical techniques that yield better results in elderly and/or multimorbid patients. Because of these new techniques, the indications for surgery have widened, while the results have remained favorable.
04/2009; 106(13):224-33; quiz 234. · 2.92 Impact Factor
ABSTRACT: Terminal heart failure is associated with chronic myocardial edema, which in part is compensated by increased myocardial lymph flow. However, little is known about the impact of terminal heart failure on lymphangiogenesis. The purpose of the study was to investigate the morphological and quantitative changes of the initial myocardial lymphatics in terminal heart failure.
Paraffin-embedded left ventricular endomyocardial biopsies, taken during heart transplantation from 7 heart transplant recipients (failing heart) and 8 heart transplant donors (control), were investigated by immunohistostaining and triple immunofluorescence for lymphatic endothelial markers LYVE-1, PROX-1, and VEGFR-3. The vessel density was calculated and the ratio of open versus collapsed vessels was estimated by analyzing randomly selected marked vessels.
The absolute densities of lymph vessels in failing and control myocardium were not significantly different for all investigated markers. The ratio of open LYVE-1 positive lymph vessels in failing heart was significantly higher than in control (64+/-12.5 vs. 44.3+/-9.3, p<0.008). There was no difference for the ratio of open VEGFR-3 vessels between groups (69.0+/-17.5 vs. 70.7+/-17.2). Triple fluorescent immunohistostaining revealed in failing hearts LYVE-1 and PROX-1 positive open vessels, which were VEGFR-3 negative. VEGFR-3 positive, but LYVE-1 and PROX-1 negative vessels could also be seen.
Myocardial initial lymphatics in patients with terminal heart failure undergo significant morphological changes in comparison to normal hearts. The ratio of open LYVE-1 vessels was higher in failing hearts by no difference in absolute densities for all markers. These findings suggest that appositional growth of initial lymphatics, rather than "de novo" genesis from pluripotent stem cells or sprouting from preexisting venous vessels, may be the predominant mechanism of lymphangiogenesis in terminal heart failure.
Lymphatic Research and Biology 02/2009; 7(1):21-7.
ABSTRACT: Decline in renal and cognitive function may complicate early recovery after coronary-artery bypass grafting. AT(1)-receptor antagonists have been demonstrated to be neuro- and renoprotective. Aim of ARTA, a prospective, double-blind, randomised and placebo controlled study, was to detect whether preoperative treatment with candesartan influences postoperative cognitive and renal function.
One hundred and five patients eligible for coronary artery bypass graft surgery (65-85 years old, all suffering from hypertension and coronary artery disease, with stable kidney function) were randomized to candesartan (8 mg od) or placebo for between 8 and 11 days prior to surgery. Existing ACE-inhibitor/angiotensin receptor antagonist-therapy had to be stopped prior to the study. Validated cognitive function tests (trail making, Horn's perfomance III und VI, divided attention and change of reaction, memory - immediate and delayed recall, digit span) were performed preoperatively, 1 week and 3 months after surgery. Renal function was assessed by creatinine clearance on the day before, 1 week and 3 months after surgery.
Eighty-seven patients (n = 43 Candesartan, n = 44 placebo) were included in the ITT-population for analysis. Drug treatment had no adverse effect on perioperative blood pressure. Only five patients experienced a period of hypotension during introduction of anaesthesia (Candesartan 1/44, placebo 4/44). One week as well as three months after surgery, there were no differences in relevant cognitive function parameters compared to the status prior to surgery, independent from treatment. Creatinine clearance showed a clear decrease one week after surgery with a minor further reduction observed 3 months after surgery, but there was no difference between Candesartan and placebo treated patients. Between both groups, there were no significant differences in the number of adverse events and number of patients with adverse events nor in the incidence of renal failure with consecutive dialysis and cerebral strokes (candesartan 2, placebo 5) and possibly drug related severe adverse events.
This randomised placebo-controlled and prospective study in elderly patients does not support previous reports suggesting a substantial impairment of cognitive function after coronary artery bypass graft surgery. Preservation of cognitive and renal function was independent of pre-surgical administration of candesartan.
Clinical Research in Cardiology 11/2008; 98(1):33-43. · 2.95 Impact Factor
ABSTRACT: 1. The present study investigates the vasoselectivity of lercanidipine (LER), a 1,4-dihydropyridine calcium channel blocker, compared with amlodipine (AML) and nifedipine (NIF) in human cardiovascular tissue. Experiments were performed either in human left ventricular failing myocardium (orthotopic heart transplants) or in isolated right atrial trabeculae and isolated vessel preparations of arteria mammaria obtained from patients undergoing aortocoronary bypass operation. 2. The obtained rank order for the L-type Ca2+ channel affinity in human tissue was LER > NIF >or= AML. Lercanidipine had the lowest negative inotropic efficacy (1 micromol/L LER: 60.3% basal < AML: 79.1% basal < NIF: 92.4 basal) and potency (IC50 NIF: 3.5 nmol/L < AML: 48 nmol/L < Ler: 127 nmol/L) in right atrial trabeculae. 3. The vasorelaxant potency of LER (IC50 0.5 nmol/L) and AML (IC50 0.8 nmol/L) was similar and significantly increased compared with that of NIF (IC50 5.9 nmol/L) in arteria mammaria preparations of the very same patients. 4. The following rank order was obtained for vasoselectivity: LER (260) < AML (60) < NIF (0.6). 5. The pharmacological effects of LER and AML were still present 2 h after drug washout. 3. Lercanidipine is characterized by a high vasoselectivity and a prolonged interaction with the L-type calcium channel in human cardiovascular tissue This may be advantageous, especially in the treatment of patients with arterial hypertension.
Clinical and Experimental Pharmacology and Physiology 09/2005; 32(9):708-13. · 1.85 Impact Factor
ABSTRACT: Device supported beating heart surgery has been advocated to extend patient selection criteria for off-pump surgery. This article reports the initial experimental and clinical results with a novel paracardial right ventricular support device.
Preclinical experiments were performed in two pigs. Ten elective patients with triple vessel disease were subjected to beating heart coronary artery bypass grafting surgery during right ventricular support by the paracardial device. Measurements included intraoperative hemodynamics during cardiac tilting, perioperative left ventricular ejection fraction (LVEF), hemolysis parameters, mortality and major morbidity events.
A mean of 3.2 +/- 0.2 distal anastomoses per patient were performed. Mean arterial pressure and central venous oxygen saturation remained stable during cardiac tilting. Perioperative LVEF did not vary significantly. Sixty-day mortality and postoperative infarction rate were 0%. Functional Canadian Cardiovascular Society class at 6 days after surgery was 1.2 +/- 0.1 vs. 3.3 +/- 0.2 pre-operatively.
In this initial clinical experience, application of the novel paracardial right ventricular support device proved to be safe and efficient.
Artificial Organs 02/2004; 28(1):102-8. · 2.00 Impact Factor
ABSTRACT: Objective: The role of nitric oxide (NO) in myocardial ischemia/reperfusion is controversial. While some studies have shown cardioprotective effects of NO, others suggested that increased myocardial NO release secondary to ischemia may contribute to reperfusion injury. However, the impact of cardioplegia-induced myocardial ischemia/reperfusion on the activity of the NO-producing enzyme constitutive NO-synthase (cNOS or NOS-III) has not been investigated. Methods: Twenty elective CABG patients were randomized to receive myocardial protection using either intermittent cold blood cardioplegia with ‘hot-shot’ (CBC; n=10) or continuous warm blood enriched with the ultra-fast-acting β-blocker esmolol (WBE; n=10). We collected transmural LV biopsies prior to cardiopulmonary bypass (CPB), at the end of the cross-clamp period, and at the end of CPB. Specimen were subjected to immunocytochemical staining against myocardial NOS-III and cGMP using polyclonal antibodies. NOS-III activity was determined using TV-densitometry (gray units) and cGMP content using a semiquantitative score. Global myocardial metabolism was assessed by arterio-coronary sinus lactate concentration difference (a-csDLAC). For LV function determination we measured the fractional area of contraction (FAC) using TEE. Results: In CBC hearts a-csDLAC was significantly decreased following cross-clamp removal as compared to pre-CPB indicating global ischemia during cross-clamp. In contrast, a-csDLAC was unchanged in WBE hearts indicating absence of relevant ischemia in this group. In CBC hearts NOS-III activity did not change from pre-CPB (35.6±11.1 U) to the end of the cross-clamp period (38.0±8.1 U; P=0.2), but increased significantly to 48.5±12.1 U at the end of CPB following initial warm blood reperfusion (P=0.026). In WBE hearts NOS-III activity remained unchanged throughout (29.2±10.8, 35.1±11.8, and 32.2±14.7 U, respectively; P>0.3). At the end of CPB, nine CBC hearts, but only one WBE heart showed increased cGMP content (P=0.002). Compared to pre-CPB, FAC in the CBC group was 109±25% following weaning off CPB (P=0.26), but was slightly decreased to 87±22% at 4 h post-CPB (P=0.03). In the WBE group FAC remained unchanged compared to pre-CPB throughout (103±21 and 96±37%, respectively; P>0.5). Conclusions: Our data show that global myocardial ischemia and reperfusion induced by CBC is associated with myocardial NOS-III activation and increased cGMP content suggesting increased NO release. In contrast, avoidance of ischemia by use of WBE prevented NOS-III and c-GMP increase. As LV function was decreased at 4 h post-CPB in the CBC group, these data suggest that increased NO release secondary to NOS-III activation may have contributed to ischemia-reperfusion injury as has been shown experimentally.
European Journal of Cardio-Thoracic Surgery.