Justus T. Strauch

Impact of preoperative statin therapy on adverse postoperative outcomes in patients undergoing cardiac surgery: a meta-analysis of over 30 000 patients

AIMSnTo determine the strength of evidence for preoperative statin use for prevention of adverse postoperative outcomes in patients undergoing cardiac surgery.nnnMETHODS AND RESULTSnAfter literature search in major databases, 19 studies were identified [three RCT (randomized prospective clinical trials), 16 observational] that reported outcomes of 31 725 cardiac surgery patients with (n = 17 201; 54%) or without (n = 14 524; 46%) preoperative statin therapy. Outcomes that were analysed included early all-cause mortality (30-day mortality), myocardial infarction (MI), atrial fibrillation (AF), stroke and renal failure. Odds ratio (OR) with 95% confidence intervals (95%CI) were reported using fixed or random effect models and publication bias was assessed. Preoperative statin therapy resulted in a 1.5% absolute risk reduction (2.2 vs. 3.7%; P < 0.0001) and 43% odds reduction for early all-cause mortality (OR 0.57; 95%CI: 0.49-0.67). A significant reduction (P < 0.01) in statin pretreated patients was also observed for AF (24.9 vs. 29.3%; OR 0.67, 95%CI: 0.51-0.88), stroke (2.1 vs. 2.9%, OR 0.74, 95%CI: 0.60-0.91), but not for MI (OR 1.11; 95%CI: 0.93-1.33) or renal failure (OR 0.78, 95%CI: 0.46-1.31). Funnel plot and Eggers regression analysis (P = 0.60) excluded relevant publication bias.nnnCONCLUSIONnOur meta-analysis provides evidence that preoperative statin therapy exerts substantial clinical benefit on early postoperative adverse outcomes in cardiac surgery patients, but underscores the need for RCT trials.

Is the bentall procedure for ascending aorta or aortic valve replacement the best approach for long-term event-free survival?

BACKGROUNDnThis retrospective analysis of a selected series of Bentall procedures may be useful in evaluating the results of valve-sparing operations, an increasingly popular alternative for replacement of the ascending aorta and aortic valve.nnnMETHODSnOne hundred forty-two elective patients younger than 65 years without concomitant procedures who underwent replacement of the thoracic aorta and aortic valve between 1989 and 2000 were studied; 85% were men, and the median age was 46 years (range, 13 to 64 years). Degenerative disease of the aorta was the most common cause requiring operation (86%, including 46% with a bicuspid aortic valve); 8% had chronic dissection, and 6% had atherosclerotic aneurysms. The ascending aorta was replaced in 94 patients (66%); 45 patients (32%) underwent hemiarch replacement, and in 3 patients (2%) the total arch was replaced. A mechanical valve was used in 88%, and a biologic valve, in 12%.nnnRESULTSnThere were no intraoperative deaths. Two patients had a stroke postoperatively, one of which was fatal. Complications during follow-up included 2 cases of endocarditis, 1 peripheral thromboembolic event, and 10 instances of significant bleeding (requiring hospitalization or transfusion). Surgery for distal aortic segments was performed in 4 patients, but no patient required reoperation in the proximal aorta. Kaplan-Meier curves show overall survival is 0.95 (95% confidence intervals, 0.9 to 0.99) at 5 years and 0.93 (95% confidence intervals, 0.86 to 0.99) at 8 years, and event-free survival is 0.85 (95% confidence intervals, 0.78 to 0.92) at 5 years and 0.78 (95% confidence intervals, 0.68 to 0.88) at 8 years.nnnCONCLUSIONSnThe button Bentall procedure can be performed with excellent short-term and long-term results in relatively uncomplicated elective patients in whom aortic valve disease is combined with dilatation of the ascending aorta. Results of this traditional operation are the standard against which the long-term outcome of newer approaches, such as valve-sparing operations, should be compared.

Technical advances in total aortic arch replacement

BACKGROUNDnWe compared the effects of using hypothermic circulatory arrest (HCA) alone, HCA combined with selective cerebral perfusion (SCP), and use of SCP with a trifurcated graft (T) on outcome after aortic arch repair.nnnMETHODSnOne hundred fifty patients, median age 66 years (range, 27 to 85), underwent total arch replacement between 1988 and 2002; 75 were female. We retrospectively compared the results of three patient groups roughly comparable with regard to preoperative risk factors: 45 patients using HCA beginning in 1988; 67 patients using HCA/SCP beginning in 1994; and 38 patients utilizing a trifurcated arch graft in conjunction with SCP through the axillary artery (HCA/SCP/T) since 2000. The groups were well matched with regard to median age (66, 68, and 66 years), urgency (emergent 11%, 13%, 5%; urgent 24%, 9%, 18%; and elective 64%, 78%, 76%), and several other known risk factors (p = not significant).nnnRESULTSnAn adverse outcome-hospital death or permanent stroke-occurred in 14%: in 16% with HCA, in 16% with HCA/SCP, and in 8% with HCA/SCP/T. Transient neurologic dysfunction among patients surviving without stroke was lower with HCA/SCP/T (11%) than with HCA (33%) or HCA/SCP (17%). Mean duration of HCA was 52 +/- 16 minutes with HCA alone versus 45 +/- 10 minutes with HCA/SCP and 31 +/- 7 minutes with HCA/SCP/T (p < 0.0001 for groups HCA and HCA/SCP combined versus HCA/SCP/T). Mean duration of SCP was 57 +/- 25 minutes with HCA/SCP versus 62 +/- 24 minutes with HCA/SCP/T (p = not significant). Comparison of the groups of patients who had comparable preoperative risk factors for adverse outcome showed a trend toward lower adverse outcome and transient neurologic dysfunction rates using HCA/SCP/T; a significant reduction in respiratory (p < 0.001), infectious (p = 0.015) and cardiac (p = 0.005) complications in HCA/SCP/T compared with the earlier groups; and significantly shorter durations of intensive care (p < 0.0001) and hospitalization (p = 0.004).nnnCONCLUSIONSnOur results suggest that HCA/SCP is superior to HCA alone for preventing cerebral injury during operations on the aortic arch. By further reducing embolic risk as well as duration of HCA, HCA/SCP/T with axillary artery cannulation may be the optimal technique for averting adverse outcomes, reducing complications, and shortening hospital stay after aortic arch repair.

Improvement of impaired renal function in heart transplant recipients treated with mycophenolate mofetil and low-dose cyclosporine.

BACKGROUNDnCyclosporine (CsA) nephrotoxicity is a common problem after cardiac transplantation. We have studied the impact of CsA dose reduction in association with mycophenolate mofetil (MMF) treatment on renal function in heart transplant recipients with suspected CsA nephrotoxicity (serum creatinine level >2 mg/dl).nnnMETHODSnTwelve heart transplant recipients (11 men, 1 woman; 111 to 1813 days after transplantation) with CsA-based immunosuppression (plus azathioprine and/or steroids) and a serum creatinine level >2.0 mg/dl were started on a daily dose of 2000 mg of MMF. Dilated cardiomyopathy was the underlying disease in nine patients, ischemic cardiomyopathy in three patients. Mean patient age was 57 years (range 44-69 years). Azathioprine was discontinued and CsA slowly tapered. Creatinine clearance, serum creatinine level, urea nitrogen, and uric acid were monitored. CsA levels were measured, and CsA dose was adjusted for whole blood levels of 70-120 microg/L. Ten patients still had endomyocardial biopsies, whereas one had echocardiographic controls only.nnnRESULTSnOne grade 1B rejection episode according to ISHLT (International Society for Heart and Lung Transplantation) was observed until 1 year after the switch to MMF. One patient was excluded due to gastrointestinal side effects.nnnCONCLUSIONSnConversion from azathioprine to MMF with consecutive reduction of CsA in heart transplant recipients with CsA-impaired renal function improves renal function as evidenced by lower serum creatinine, urea nitrogen, uric acid, and higher creatinine clearance.

Importance of extrasegmental vessels for spinal cord blood supply in a chronic porcine model

UNLABELLEDnIObjective: Our purpose was to investigate the interaction of the important components of spinal cord blood supply in the pig model to enable its use for future studies of spinal cord protection.nnnMETHODSn25 juvenile pigs (20-22 Kg) underwent serial intercostal (IC) or lumbar artery (LA) ligation until disappearance of motor evoked potentials (MEPs). Pigs underwent sequential craniocaudal (IC/LA ligation alone (n=5); following clamping of both subclavian arteries (n=4)m, or clamping of the median sacral artery (MSA, n=4); preceded by clamping of the subclavian arteries (n=4), or of the MSA (n=4). RESULTS were verified by Tarlovs scores and perioperative angiography.nnnRESULTSnAll animals with MEP loss suffered postoperative paraplegia. Groups were equivalent with regard to stable arterial pressures throughout the experiment, temperature and other physiological parameters. Mean number of clamped IC/LA before MEP loss for cranio-caudal clamping direction was 12.8 +/-0.8 for segmental arteries isolated, 9 +/-0.8 if both subclavian arteries were ligated previously and only 4.3 +/- 0.5 IC if the median sacral artery was clamped before. Mean number of clamped LA for caudo-cranial clamping direction was 5.8 +/-0.9 for segmental lumbar arteries, 5.5 +/-0.6 LA if both subclavian arteries were ligated previously and 3.5 +/-0.6 if the median sacral artery was clamped before.nnnCONCLUSIONnThis study confirms the importance of lumbar and MSA arteries to cord viability. It documents the interaction of the subclavian and MSA (roughly equivalent to the hypogastric arteries in humans) with segmental vessels in providing spinal cord blood supply. It also provides the physiologic basis for use of the pig model for studies of spinal cord protection in aortic surgery.

Aortic arch replacement using a trifurcated graft and selective cerebral antegrade perfusion

BACKGROUNDnAortic arch aneurysm repair remains associated with considerable mortality and risk of cerebral complications. We present results of a technique utilizing a three-branched graft for arch replacement, deep hypothermic circulatory arrest (HCA), and selective antegrade cerebral perfusion (SCP).nnnMETHODSnBetween March 2000 and November 2001, 22 patients (11 female) aged 40 to 77 years (mean 64 +/- 11.2) underwent arch replacement utilizing the trifurcated-graft technique. Serial anastomosis of the branched graft to individual cerebral vessels was carried out during HCA, followed by arch reconstruction during SCP through the graft. All 22 patients had surgery electively. Eight patients (36%) had undergone previous aortic surgery. In 19 patients, arch replacement was part of an elephant trunk procedure; 2 patients had Bentall operations and 1 had isolated arch replacement. Concomitant coronary artery bypass grafting was performed in 6 patients (27%). Mean HCA duration was 30 +/- 6 minutes at a mean temperature of 11.4 +/- 0.8 degrees C. Mean duration of SCP was 52 +/- 18 minutes.nnnRESULTSnAdverse outcome--death before hospital discharge or permanent stroke or both--occurred in 2 patients (9%). Two patients experienced transient neurologic dysfunction (9%). Two patients (9%) developed renal failure requiring short-term hemodialysis and pulmonary complications occurred in 2 patients.nnnCONCLUSIONSnCerebral protection and prevention of atheroembolism remain challenges in aortic arch reconstruction. To reduce neurologic complications we developed an aortic arch reconstruction technique in which a trifurcated graft is anastomosed to the brachiocephalic vessels during HCA, reducing the risk of embolization while minimizing cerebral ischemia by permitting antegrade cerebral perfusion as arch repair is completed.

Minimally invasive transapical aortic valve implantation and the risk of acute kidney injury.

BACKGROUNDnThe new technique of minimally invasive transapical aortic valve implantation (TAP-AVI) deals with high-risk patients and despite the absence of cardiopulmonary bypass it might lead to renal impairment. The aim of this study was to estimate the risk of the development of acute kidney injury (AKI) after TAP-AVI and to identify possible risk factors with regard to the morbidity and mortality of the patients.nnnMETHODSnData of 30 consecutive patients undergoing TAP-AVI were recorded and followed up for 8 weeks. Postoperative AKI has been defined according to RIFLE criteria. Two patients on chronic hemodialysis have been followed up.nnnRESULTSnOf 28 patients, AKI occurred in 16 patients (57%). Statistical analysis revealed no influence on the risk of developing AKI caused by the dose of applicated contrast medium (p = 0.09), the patients age (p = 0.5), or the existence of diabetes (p = 0. 16). Analysis concerning the relationship between a preexisting coronary heart disease and AKI showed a tendency to be associated with a higher risk of the development of AKI (70% preexisting congenital heart disease in the AKI group versus 50%; p = 0.28). Only a preoperative serum creatinine greater than 1.1 mg/dL was a strong predictor for developing AKI (p < 0.01). Length of stay in the intensive care unit and the complete length of hospital stay revealed no difference with regard to postoperative development of AKI though statistical analysis showed a trend to a higher mortality in the AKI group (27% vs 6%); univariate analysis did not reach statistical significance (p = 0.13).nnnCONCLUSIONSnThe TAP-AVI seems to be a feasible procedure for high-risk patients with a clear risk of developing AKI. Patients at risk should be identified and, if indicated, already preoperatively treated in collaboration with the attending nephrologists.

Impact of hypothermic selective cerebral perfusion compared with hypothermic cardiopulmonary bypass on cerebral hemodynamics and metabolism

OBJECTIVEnHypothermic selective cerebral perfusion (SCP) is widely used for cerebral protection during aortic arch surgery, but the effect of the absence of systemic perfusion on cerebrovascular dynamics it has never been established. This study explored the physiology of prolonged SCP compared to hypothermic cardiopulmonary bypass (HCPB) in pigs.nnnMETHODSnIn this blinded protocol, 29 juvenile pigs (20-23 kg) were randomized after cooling on cardiopulmonary bypass (CPB) to 20 degrees C. Group I pigs (n=14) underwent 90 min of SCP, while group II (HCPB, n=15) underwent total body perfusion. Fluorescent microspheres were injected during perfusion and recovery, enabling calculation of total and regional cerebral blood flow (CBF). Cerebrovascular resistance (CVR), oxygen consumption and intracranial pressure (ICP) were also monitored.nnnRESULTSnCBF decreased significantly (P=0.0001) during cooling, but remained at significantly higher levels with SCP than with HCPB throughout perfusion and recovery (P<0.0001). CVR was significantly lower with SCP than with HCPB throughout perfusion (P=0.04). Oxygen consumption fell significantly with cooling (P=0.0001), remained low during perfusion, and rebounded promptly with rewarming; with SCP it was significantly higher than with HCPB throughout the perfusion interval (P=0.03), and remained higher thereafter. ICP rose significantly less with SCP than with HCPB (P=0.02).nnnCONCLUSIONnWe conclude that, compared with HCPB, SCP results in beneficial cerebral vasodilatation, as evidenced by significantly higher CBF and oxygen consumption during SCP, by prompt recovery of oxygen consumption after rewarming, and by significantly lower ICP during perfusion and in the post-bypass period.

Recent improvements in outcome with the Novacor left ventricular assist device.

BACKGROUNDnThe Novacor implantable, electrically powered, wearable, left ventricular assist device (LVAD) has been used as a bridge to transplantation at our institution since 1994. Recent changes in protocol have resulted in a decreased incidence of infections, thromboembolism, and mortality.nnnMETHODSnWe reviewed the medical records of all 43 patients who received implantable LVADs at the Mount Sinai Medical Center. After 1998, a number of protocol modifications were instituted. Vascular grafts were changed from a low-porosity, woven polyester (Cooley) to a gelatin-sealed, knitted polyester graft (Vascutek), the devices were implanted pre-peritoneally rather than in the posterior rectus sheath, and extensive drainage of the chest and pre-peritoneal pocket was used. The following anti-coagulation regimen was used: low-molecular-weight Dextran for 1 day, initiated after chest tube drainage <50 cc/hour; then IV heparin for 10 to 14 days, beginning at 500 U/hour, slowly increasing partial thromboplastin time to 1.5 to 2 x control; and finally Coumadin, maintaining the international normalized ratio at 2.5 to 3.5. Daily aspirin, 325 mg, was begun on post-operative Day 7. We compared 22 patients who electively underwent surgery before the changes, Group I, with 18 patients treated thereafter, Group II.nnnRESULTSnGroups I and II were well matched with regard to age (47 vs 44 years); cause of heart failure (idiopathic, 50% vs 44%; ischemic, 50% vs 56%), and duration of support (79 vs 76 days). The incidence of thromboembolic cerebrovascular events was significantly less in Group II (6%) than in Group I (23%), p = 0.025. The incidence of bleeding increased mildly in Group I. Pocket infections occurred in 27% of Group I patients vs 11% of Group II patients, p = 0.018. Only 2 patients (11%) in Group II died while receiving device support, vs 7 (32%) in Group I, p = 0.019.nnnCONCLUSIONSnOur results indicate that pre-peritoneal implantation, use of a new generation of vascular grafts, extensive drainage, and a more restricted anti-coagulation regimen improve outcome after Novacor LVAD implantation for advanced heart failure.

Conversion to sirolimus and mycophenolate can attenuate the progression of bronchiolitis obliterans syndrome and improves renal function after lung transplantation.

Background. Bronchiolitis obliterans syndrome (BOS) is the major problem after lung and heart-lung transplantation (LTx/HLTx). Sirolimus (Sir) and Mycophenolate (MMF) showed a promising efficacy in the treatment of BOS in animal models. The first clinical experience in converting LTx/HLTx-recipients with BOS from calcineurin inhibitor-(CNI)-based immunosuppression to a Sir-MMF based immunosuppression is reported herein. Methods. Six LTx- and five HLTx-recipients (eight men; 0.9 to 8 years after transplantation) with CNI-based immunosuppression (plus MMF) in whom BOS was diagnosed were included in the study. Mean patient age was 37±13 years (range 17–62 years). Sir was started with 6 mg and continued adjusted to according target trough levels (8-14 ng/ml). Subsequently, the CNIs were tapered down and finally stopped. Follow up included self determined pulmonary function tests, microbiological screening, chest radiographs, and laboratory studies Results. Two acute rejection episodes occurred during the study period. The incidence of infection was 2.2±1.3 infections/patient-year after conversion. Mean FEV1 decreased after a mean follow up of 14.8±1.4months: from 2.1±0.7l prior conversion to 1.3±0.6l after conversion (P=0.03). However, graft function remained stable in three patients and progression of BOS slowed down in three patients. Overall, 2 of 10 patients died due to ongoing BOS while awaiting retransplantation Conclusions. After BOS was diagnosed, conversion to MMF and Sir stabilized graft function only in some of the converted patients. Therefore, earlier administration of Sir-based immunosuppression might be a more promising approach. Whether conversion to CNI-free immunosuppression can actually ameliorate the extent or progression of BOS has to be investigated in randomized trials.