Publications by authors named "Christian F Vahl"

34 Publications

Increased Lymphangiogenesis and Lymphangiogenic Growth Factor Expression in Perivascular Adipose Tissue of Patients with Coronary Artery Disease.

J Clin Med 2019 Jul 9;8(7). Epub 2019 Jul 9.

Center for Cardiology, Cardiology 1, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.

Experimental and human autopsy studies have associated adventitial lymphangiogenesis with atherosclerosis. An analysis of perivascular lymphangiogenesis in patients with coronary artery disease is lacking. Here, we examined lymphangiogenesis and its potential regulators in perivascular adipose tissue (PVAT) surrounding the heart (C-PVAT) and compared it with PVAT of the internal mammary artery (IMA-PVAT). Forty-six patients undergoing coronary artery bypass graft surgery were included. Perioperatively collected C-PVAT and IMA-PVAT were analyzed using histology, immunohistochemistry, real time PCR, and PVAT-conditioned medium using cytokine arrays. C-PVAT exhibited increased PECAM-1 (platelet endothelial cell adhesion molecule 1)-positive vessel density. The number of lymphatic vessels expressing lymphatic vessel endothelial hyaluronan receptor-1 or podoplanin was also elevated in C-PVAT and associated with higher inflammatory cell numbers, increased intercellular adhesion molecule 1 (ICAM1) expression, and fibrosis. Significantly higher expression of regulators of lymphangiogenesis such as vascular endothelial growth factor (VEGF)-C, VEGF-D, and VEGF receptor-3 was observed in C-PVAT compared to IMA-PVAT. Cytokine arrays identified angiopoietin-2 as more highly expressed in C-PVAT vs. IMA-PVAT. Findings were confirmed histologically and at the mRNA level. Stimulation of human lymphatic endothelial cells with recombinant angiopoietin-2 in combination with VEGF-C enhanced sprout formation. Our study shows that PVAT surrounding atherosclerotic arteries exhibits more extensive lymphangiogenesis, inflammation, and fibrosis compared to PVAT surrounding a non-diseased vessel, possibly due to local angiopoietin-2, VEGF-C, and VEGF-D overexpression.
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http://dx.doi.org/10.3390/jcm8071000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678243PMC
July 2019

A Multicenter Experience With a New Fenestrated-Branched Device for Endovascular Repair of Thoracoabdominal Aortic Aneurysms.

J Endovasc Ther 2018 Apr 9;25(2):209-219. Epub 2018 Jan 9.

6 Department of Vascular Surgery, Hospital of Diakonie-Jung-Stilling, Siegen, Germany.

Purpose: To investigate the outcomes of patients who were treated for thoracoabdominal aortic aneurysms (TAAAs) using custom-made fenestrated-branched stent-grafts.

Methods: A consecutive series of 108 patients (mean age 73.5 years; 73 men) with TAAA were treated with E-xtra Design Engineering customized fenestrated-branched stent-grafts between November 2011 and January 2017. Data on baseline characteristics, procedures, and clinical follow-up were collected from 6 regional European surgical centers for retrospective analysis of endoleaks, reinterventions, and target vessel patency. The median aneurysm diameter was 6.75 cm (range 5.5-13). The distribution of the TAAA according to the modified Crawford classification of extent was 25 (24%) type I, 19 (17%) type II, 20 (18%) type III, 29 (27%) type IV, and 15 (14%) type V.

Results: Technical success was achieved in 95% (103/108) of cases. Major early perioperative complications occurred in 40 (37%) patients. The 30-day mortality was 9.2% (10/108), and perioperative spinal cord ischemia was observed in 6 (5.5%) patients [2 (1.8%) permanent]. During the mean follow-up of 17.6 months (range 3-52), 28 (26%) patients required late reintervention. Two patients died due to aneurysm- or procedure-related causes. The estimated survival rates at 1, 2, and 4 years were 87%, 84%, and 51%, respectively. The estimated target vessel patency rates at the same time points were 95%, 91%, and 90%, respectively. The freedom from reintervention estimates were 84% and 73% at 1 and 4 years, respectively.

Conclusion: Endovascular repair of TAAA using Jotec customized fenestrated-branched stent-grafts appears to be safe and effective in the early to midterm. The considerable rate of secondary interventions indicates that further improvements, graft surveillance, and follow-up are required.
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http://dx.doi.org/10.1177/1526602817752147DOI Listing
April 2018

Adjunct Perfusion Branch for Reduction of Spinal Cord Ischemia in the Endovascular Repair of Thoracoabdominal Aortic Aneurysms.

Thorac Cardiovasc Surg 2018 04 2;66(3):233-239. Epub 2017 May 2.

Department of Cardiothoracic and Vascular Surgery, Medical Center of the Johannes Gutenberg-University Mainz, Germany.

Background: To analyze utilization of a perfusion branch for temporary sac perfusion to reduce the spinal cord ischemia (SCI) in the endovascular repair of thoracoabdominal aortic aneurysms (TAAAs).

Methods: Between January 2012 and August 2016, 30 patients (18, men; median age 72 years) were treated for TAAAs with total endovascular repair using customized branched/fenestrated endografts in our institution. The median aneurysm size was 6.6 cm. Types of TAAA were: type I, 9 (30%), type II, 5 (16.6%), type III, 4 (13.3%), type IV, 6 (20%), and type V, 6 (20%). Ten patients received a perfusion branch to create an intentional endoleak, which was occluded with vascular plugs in mean interval time of 8.2 weeks (range: 6-10). Staged procedure and automated cerebrospinal fluid drainage were used in 23 (77%) and 24 (80%) patients, respectively.

Results: The technical success was 97%; 107 renovisceral target vessels were revascularized (32 fenestrations, 75 branches). At the time of the planned reinterventions, the mean arterial pressure (MAP) gradients were measured between the temporarily perfused aneurysm sac and the aortic endografts, and they were significantly higher (mean gradients 42.5 ± 10 mm Hg; range: 30-60) within the aortic grafts. The in-hospital and 30-day mortality was 3.3%. The incidence of postoperative SCI was 3/20 (15%) in the standard group and 0% in the group of the perfusion branch ( = 0.28). The mean follow-up was 12 months (range: 2-51).

Conclusion: We experience that the use of a dedicated perfusion branch is feasible and may serve as protective adjunct to reduce the risk of SCI in endovascular treatment of TAAA. The risk of rupture in interval appears to be low. Larger series and multicenter studies are warranted to corroborate these results.
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http://dx.doi.org/10.1055/s-0037-1602376DOI Listing
April 2018

Treating iliac aneurysm using the Nellix Endovascular Sac Sealing System.

Semin Vasc Surg 2016 Sep 5;29(3):114-119. Epub 2016 Nov 5.

Department of Cardiothoracic and Vascular Surgery, Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstr. 1 55131 Mainz, Germany.

As endovascular treatment of abdominal aortic aneurysms has become established, there has been growing focus on treatment of the aneurysmal iliac artery. Isolated, large iliac aneurysms >30 mm pose a risk of rupture, but, in addition, 20% to 30% of abdominal aortic aneurysms are associated with iliac aneurysmal dilatation, which can compromise long-term outcomes. Endovascular solutions are evolving and until recently have utilized standard stent graft technology. The endovascular aortic sealing system was introduced as a new, effective method for the treatment of infrarenal aortic aneurysms. In this article, we present our recent extended use of the Nellix system, with or without a combination of adjuvant endovascular techniques, in the treatment of 84 common iliac artery aneurysms. The results support the use of endovascular aortic sealing system in endovascular therapy for aneurysmal iliac pathologies. Different endovascular sealing techniques for the treatment of common iliac artery aneurysms, re-interventions, and extended follow-up are also discussed.
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http://dx.doi.org/10.1053/j.semvascsurg.2016.11.004DOI Listing
September 2016

Three-Dimensional Analysis of Component Stability of the Nellix Endovascular Aneurysm Sealing System After Treatment of Infrarenal Abdominal Aortic Aneurysms.

J Endovasc Ther 2017 04 19;24(2):201-209. Epub 2016 Nov 19.

1 Division of Vascular Surgery, Department of Cardiothoracic and Vascular Surgery, University Medical Center, Johannes-Gutenberg University, Mainz, Germany.

Purpose: To assess short-term stability and conformational changes of the Nellix EndoVascular Aneurysm Sealing (EVAS) System using 3-dimensional (3D) analysis.

Methods: Postoperative computed tomography (CT) scans obtained at 0, 3, and 12 months in 24 patients (mean age 75±7 years; 22 men) who underwent EVAS between December 2013 and December 2014 for intact abdominal aortic aneurysm (within the instructions for use) were evaluated for stent-graft deviation in multiple planes using dedicated 3D analysis software. In addition, 2D analysis using an anatomically fixed reference landmark was performed to assess craniocaudal migration. Clinical and follow-up data of the patients were recorded and matched with results of the imaging analysis.

Results: Overall stability of the Nellix endografts was promising. Relevant conformational changes in the majority of cases were limited to the iliac graft segment and were clinically benign in all cases. Conversely, the only deviation of the proximal stent-graft segment was found in a patient with type Ia endoleak. Additional 2D analysis found relevant (≥5 mm) caudal migration of the Nellix stent-graft in 6 patients, including the one with the type Ia endoleak. In 3 patients, 3D analysis demonstrated the absence of relevant conformational changes of the endografts despite caudal migration.

Conclusion: Overall stability of the separate EVAS stent-grafts is promising in the short term. Relevant conformational changes (stent-graft deviation) in the majority of cases were benign and confined to the iliac segment.
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http://dx.doi.org/10.1177/1526602816678201DOI Listing
April 2017

Endovascular Aneurysm Sealing (EVAS) and Chimney EVAS in the Treatment of Failed Endovascular Aneurysm Repairs.

J Endovasc Ther 2017 02 26;24(1):115-120. Epub 2016 Oct 26.

1 Department of Cardiothoracic and Vascular Surgery, Medical Center of the Johannes Gutenberg-University Mainz, Germany.

Purpose: To assess the technical success and clinical outcome of reinterventions using the Nellix Endovascular Aneurysm Sealing (EVAS) System to treat complications after endovascular aneurysm repair (EVAR).

Methods: Fifteen consecutive patients (mean age 79 years; 14 men) with prior EVAR were treated with EVAS between March 2014 and December 2015 at 2 institutions. The failed prior EVARs included 13 bifurcated endografts, 1 bifurcated graft plus fenestrated cuff, and 1 tube endograft. Endoleaks were the predominant indications: type Ia in 10 and type III in 5 (3 type IIIa and 2 type IIIb). All patients presented with progressive aortic aneurysms (median 7.85-cm diameter; range 6.5-11). Eight patients were treated on an urgent or emergency basis (6 symptomatic aneurysms and 2 contained ruptures). All patients underwent Nellix relining of the failed stent-graft; 10 had chimney (Ch) procedures in combination with EVAS (chEVAS) because the proximal landing zones were inadequate.

Results: Technical success was 100%. All endoleaks were successfully sealed, and no additional intervention was required. No further endoleak after EVAS or chEVAS was recorded. Endobag protrusion occurred in 1 case without sequelae. One elderly patient with ruptured aneurysm died from multiple organ failure 2 months postoperatively. One renal artery guidewire injury led to nephrectomy because of active bleeding. No reinterventions, aneurysm-related mortalities, graft thrombosis, endoleaks, or chimney graft occlusions were observed during a median follow-up of 8 months (range 3-24).

Conclusion: The present preliminary experience demonstrates that the use of EVAS/chEVAS is feasible for treatment of failed EVAR. This technique may be used as bailout or an alternative treatment when other established methods are infeasible or not available.
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http://dx.doi.org/10.1177/1526602816675622DOI Listing
February 2017

Initial Experience in the Treatment of Extensive Iliac Artery Aneurysms With the Nellix Aneurysm Sealing System.

J Endovasc Ther 2016 Apr 23;23(2):290-6. Epub 2016 Jan 23.

Department of Cardiothoracic and Vascular Surgery, Medical Center of the Johannes Gutenberg-University Mainz, Germany.

Purpose: To assess the feasibility and effectiveness of the Nellix prosthesis in the treatment of common iliac artery aneurysms.

Methods: Between May 2013 and June 2015, 230 patients underwent implantation of the Nellix device at 2 institutions. Fifty of these patients (mean age 76 years; 35 men) were identified as having 60 common iliac artery aneurysms (CIAAs) with a median diameter of 4 cm (range 3.5-7). The majority of patients had aortoiliac aneurysms (5, 70%), 10 (20%) had isolated CIAAs, and 5 (10%) had iliac anastomotic aneurysms after aortoiliac bypass. In 20 patients, the iliac aneurysm was the indication for the intervention; in the other 30 patients, the endovascular iliac repair was an adjunct procedure to endovascular aneurysm sealing (EVAS). An iliac branch device (IBD) was used when feasible to preserve flow to the internal iliac artery.

Results: Seventeen (34%) patients underwent elective implantation of the Nellix graft in combination with an IBD, 33 (66%) patients underwent Nellix sealing of the CIAA using 1 (n=5), 2 (n=22), or 3 Nellix grafts (2 bilateral grafts and 1 graft as an extension to the external iliac artery in 6 patients). The technical success rate was 100%, and no graft-related complications were reported postoperatively. No buttock claudication, reinterventions, graft thrombosis, or endoleaks were observed during a mean follow-up of 12 months.

Conclusion: Our initial experience demonstrates that Nellix grafts are feasible and safe for the treatment of extensive iliac artery aneurysms. The long-term durability of these grafts should be validated in larger patient cohorts before this promising alternative endovascular technique can gain widespread acceptance.
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http://dx.doi.org/10.1177/1526602815627357DOI Listing
April 2016

Mortality in patients with acute aortic dissection type A: analysis of pre- and intraoperative risk factors from the German Registry for Acute Aortic Dissection Type A (GERAADA).

Eur J Cardiothorac Surg 2016 Feb 28;49(2):e44-52. Epub 2015 Oct 28.

Department of Cardiothoracic and Vascular Surgery, Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany.

Objectives: Acute aortic dissection type A (AADA) is an emergency with excessive mortality if surgery is delayed. Knowledge about independent predictors of mortality on surgically treated AADA patients is scarce. Therefore, this study was conducted to identify pre- and intraoperative risk factors for death.

Methods: Between July 2006 and June 2010, 2137 surgically treated patients with AADA were enrolled in a multicentre, prospective German Registry for Acute Aortic Dissection type A (GERAADA), presenting perioperative status, operative strategies, postoperative outcomes and AADA-related risk factors for death. Multiple logistic regression analysis was performed to identify the influence of different parameters on 30-day mortality.

Results: Overall 30-day mortality (16.9%) increased with age [adjusted odds ratio (OR) = 1.121] and among patients who were comatose (adjusted OR = 3.501) or those who underwent cardiopulmonary resuscitation (adjusted OR = 3.751; all P < 0.0001). The higher the number of organs that were malperfused, the risk for death was (adjusted OR for one organ = 1.651, two organs = 2.440, three organs or more = 3.393, P < 0.0001). Mortality increased with longer operating times (total, cardiopulmonary bypass, cardiac ischaemia and circulatory arrest; all P < 0.02). Arterial cannulation site for extracorporeal circulation, operative techniques and arch interventions had no significant impact on 30-day mortality (all P > 0.1). No significant risk factors, but relevant increases in mortality, were determined in patients suffering from hemiparesis pre- and postoperatively (each P < 0.01), and in patients experiencing paraparesis after surgery (P < 0.02).

Conclusions: GERAADA could detect significant disease- and surgery-related risk factors for death in AADA, influencing the outcome of surgically treated AADA patients. Comatose and resuscitated patients have the poorest outcome. Cannulation sites and operative techniques did not seem to affect mortality. Short operative times are associated with better outcomes.
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http://dx.doi.org/10.1093/ejcts/ezv356DOI Listing
February 2016

How should I treat a DeBakey type I acute aortic dissection four weeks after transcatheter aortic valve implantation in an old, fragile patient?

EuroIntervention 2015 Apr 22;10(12):e1-6. Epub 2015 Apr 22.

Department of Cardiothoracic and Vascular Surgery, Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany.

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http://dx.doi.org/10.4244/EIJV10I12A261DOI Listing
April 2015

Impact of previous cardiovascular surgery on postoperative morbidity and mortality after major pulmonary resection for non-small cell lung cancer.

Langenbecks Arch Surg 2013 Aug 13;398(6):903-7. Epub 2013 Jun 13.

Department of Cardiothoracic and Vascular Surgery, Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.

Purpose: The aim of this study was to evaluate the impact of previous cardiovascular surgery on the postoperative morbidity and mortality following major pulmonary resection for non-small cell lung cancer (NSCLC).

Methods: Medical records of 227 patients, who underwent major pulmonary resection for NSCLC from 2003 to 2012 at our department, were reviewed retrospectively. Thirty-one patients with a mean age of 65.8 years had previous cardiovascular surgery (group A) including coronary artery revascularization in 11 patients, peripheral arterial revascularization in 6 patients, carotis endarterectomy in 9 patients, and combined coronary artery revascularization and carotis endarterectomy in 5 patients, whereas 167 patients (mean age = 62.0 years) had no cardiovascular comorbidity (group B). Twenty-nine patients with nonsurgically treated cardiovascular comorbidity were excluded from this study.

Results: There were no significant differences in overall postoperative morbidity (22.6 % in group A vs. 19.2 % in group B) and mortality (no mortality in group A vs. 2.4 % in group B) between both groups.

Conclusions: Major pulmonary resections for NSCLC can be performed safely in patients with previous cardiovascular surgical history who are fulfilling the common cardiopulmonary criteria of operability. Operative risk in this subpopulation is comparable to that in patients without cardiovascular comorbidity.
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http://dx.doi.org/10.1007/s00423-013-1081-6DOI Listing
August 2013

How to do it: direct true lumen cannulation technique of the ascending aorta in acute aortic dissection type A.

Interact Cardiovasc Thorac Surg 2012 Jun 28;14(6):869-70. Epub 2012 Feb 28.

Department of Cardiothoracic and Vascular Surgery, Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.

In acute aortic dissection type A (AADA), direct true lumen cannulation (DTLC) of the ascending aorta is a fast and safe cannulation site providing antegrade perfusion of the supraaortic and visceral vessels. An Overholt clamp is passed around the ascending aorta to place a Mersilene tape for later securing of the arterial cannula. After draining venous blood into the cardiopulmonary bypass system (CPB), the ascending aorta is transected and the aortic lumen inspected. The true lumen is identified and an arterial cannula inserted directly. Finally, the cannula is secured with the previously placed tape and CPB is initiated. DTLC can be used as arterial cannulation standard technique in operations for AADA.
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http://dx.doi.org/10.1093/icvts/ivs042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3352716PMC
June 2012

Postoperative non-invasive assessment of pulmonary vascular resistance using Doppler echocardiography.

Interact Cardiovasc Thorac Surg 2011 Dec 5;13(6):579-84. Epub 2011 Jul 5.

Department of Cardiothoracic and Vascular Surgery, University of Mainz, Langenbeckstr 1, 55131 Mainz, Germany.

Non-invasive monitoring of pulmonary vascular resistance (PVR) in postoperative cardiac surgery patients might be useful, particularly for management of pulmonary hypertension. For this purpose, we sought to assess Doppler echocardiography in the intensive care setting. In 73 patients, hemodynamics was measured using both, invasive gold standard (pulmonary artery catheter), and non-invasively by Doppler echocardiography. Four Doppler parameters: (1) tricuspid regurgitant velocity/time-velocity-integral of right ventricular outflow tract (TRV/VTI(RVOT)), (2) tricuspid annular systolic velocity (S'), (3) tricuspid annular strain, and (4) tricuspid annular strain rate, were compared with invasive PVR, using linear regression analysis and receiver-operating-characteristics. Patients without (n = 25, group 1) and patients with elevated left ventricular filling pressure (wedge pressure ≥ 15 mmHg, group 2, n = 48) were compared. Correlations were (1) R = 0.874, P < 0.0001, (2) R = -0.765, P < 0.0001, (3) R = 0.279, P = 0.009, (4) R = 0.378, P = 0.001. TRV/VTI(RVOT) showed prediction of PVR >300 dyn*s*/cm(5) (area-under-curve 0.975, cut-off 0.245, sensitivity 100%, specificity 91%). Strain correlated with PVR in group 2 patients only. TRV/VTI(RVOT) and tricuspid annular systolic velocity (S'), are useful for non-invasive monitoring of PVR in postoperative cardiac surgery patients with or without elevated left ventricular filling pressure. Strain may be used in patients with elevated filling pressure.
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http://dx.doi.org/10.1510/icvts.2011.271619DOI Listing
December 2011

Wet-chemical approach for the cell-adhesive modification of polytetrafluoroethylene.

Biomed Mater 2011 Jun 20;6(3):035007. Epub 2011 Apr 20.

Department of Cardiothoracic and Vascular Surgery, Johannes Gutenberg-University School ofMedicine, Mainz, Germany.

Polytetrafluoroethylene (PTFE), a frequently utilized polymer for the fabrication of synthetic vascular grafts, was surface-modified by means of a wet-chemical process. The inherently non-cell-adhesive polymer does not support cellular attachment, a prerequisite for the endothelialization of luminal surface grafts in small diameter applications. To impart the material with cell-adhesive properties a treatment with sodium-naphthalene provided a basis for the subsequent immobilization of the adhesion promoting RGD-peptide using a hydroxy- and amine-reactive crosslinker. Successful conjugation was shown with cell culture experiments which demonstrated excellent endothelial cell growth on the modified surfaces.
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http://dx.doi.org/10.1088/1748-6041/6/3/035007DOI Listing
June 2011

Successful management of fulminant pulmonary embolism using a novel portable extracorporeal life support system.

Ann Thorac Surg 2011 Apr;91(4):1265-7

Department of Cardiothoracic and Vascular Surgery, Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany.

A 46-year-old man presented to the emergency room with pain in his left leg, dyspnea, and general cyanosis. During examination he collapsed and required resuscitation. Under suspicion of pulmonary embolism, a new portable "click 'n run" extracorporeal life support system (LIFEBRIDGE-B(2)T [Medizintechnik AG, Ampfing, Germany]) was implanted by the femoral vessels under resuscitation within 15 minutes of presentation. The patient was stabilized, despite severe decompensation (pH, 6.8), and could be transferred for a computed tomographic scan, which confirmed massive pulmonary embolism. Still connected to the life support system, the patient was transferred to the operating room. After a pulmonary thrombectomy was performed, the patient recovered without any organ dysfunction. A portable emergency extracorporeal life support may change clinical practice in the treatment of patients with severe hemodynamic deterioration at emergency care hospitals.
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http://dx.doi.org/10.1016/j.athoracsur.2010.09.045DOI Listing
April 2011

Successful management of fulminant pulmonary embolism using a novel portable extracorporeal life support system.

Ann Thorac Surg 2011 Apr;91(4):1265-7

Department of Cardiothoracic and Vascular Surgery, Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany.

A 46-year-old man presented to the emergency room with pain in his left leg, dyspnea, and general cyanosis. During examination he collapsed and required resuscitation. Under suspicion of pulmonary embolism, a new portable "click 'n run" extracorporeal life support system (LIFEBRIDGE-B(2)T [Medizintechnik AG, Ampfing, Germany]) was implanted by the femoral vessels under resuscitation within 15 minutes of presentation. The patient was stabilized, despite severe decompensation (pH, 6.8), and could be transferred for a computed tomographic scan, which confirmed massive pulmonary embolism. Still connected to the life support system, the patient was transferred to the operating room. After a pulmonary thrombectomy was performed, the patient recovered without any organ dysfunction. A portable emergency extracorporeal life support may change clinical practice in the treatment of patients with severe hemodynamic deterioration at emergency care hospitals.
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http://dx.doi.org/10.1016/j.athoracsur.2010.09.045DOI Listing
April 2011

A minimally invasive approach for aortobifemoral bypass procedure.

J Vasc Surg 2011 Mar 7;53(3):870-5. Epub 2011 Jan 7.

Department of Cardiac, Thoracic and Vascular Surgery, Johannes Gutenberg University Clinic, Mainz, Germany.

Surgical aortobifemoral bypass procedure for aortoiliac occlusive disease remains the gold standard treatment despite rapidly expanding range of indications for endovascular repair. Besides several disadvantages such as dysparaesthesias, hernias, and unpleasant outcome, transperitoneal exposure of the aorta is also associated with operative autonomic nerve injury. In five male patients, infrarenal aorta was exposed through a small (8 cm) supraumbilical midline incision. Incision of the posterior peritoneum above the infrarenal aorta was limited to 3 cm. A 1 cm infraumbilical incision allowed transperitoneal placement of the distal aortic clamp outside of the operative field. Four centimeters transverse incisions were made over the femoral bifurcations and implantation of the aortobifemoral graft followed. Extubation was performed after an operating time of 200 to 150 minutes with 30 to 20 minutes aortic clamping time. Nonopioids or nonsteroidal anti-inflammatory drugs were intermittently administered during 12 hours of intermediate care unit monitoring. Oral alimentation started 6 hours and complete mobilization at 48 hours postoperatively. Hospital discharge followed on the fourth to tenth postoperative day. This minimally invasive technique allows a precise and controlled open performance of all vascular anastomoses minimizing intraoperative and postoperative complications and significantly decreasing patient discomfort related to standard abdominal surgery.
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http://dx.doi.org/10.1016/j.jvs.2010.10.075DOI Listing
March 2011

Giant bronchogenic cyst within the aortic wall mimicking symptoms of acute type A aortic dissection.

J Thorac Cardiovasc Surg 2011 Jan 3;141(1):e7-8. Epub 2010 Nov 3.

Department of Cardiothoracic and Vascular Surgery, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.

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http://dx.doi.org/10.1016/j.jtcvs.2010.09.031DOI Listing
January 2011

Liver transplantation and combined liver-heart transplantation in patients with familial amyloid polyneuropathy: a single-center experience.

Liver Transpl 2010 Mar;16(3):314-23

Department of Internal Medicine I, Johannes Gutenberg University, Langenbeckstrasse 1, 55101 Mainz, Germany.

Liver transplantation (LT) is the only curative option for patients with familial amyloid polyneuropathy (FAP) at present. Twenty patients with FAP underwent LT between May 1998 and June 2007. Transthyretin mutations included predominantly the Val30Met mutation but also 10 other mutations. Seven patients received a pacemaker prior to LT, and because of impairment of mechanical cardiac function, 4 combined heart-liver transplants were performed, 1 simultaneously and 3 sequentially. The first patient, who underwent simultaneous transplantation, died. Seven patients died after LT, with 5 dying within the first year after transplantation. The causes of death were cardiac complications (4 patients), infections (2 patients), and malnutrition (1 patient). One-year survival was 75.0%, and 5-year survival was 64.2%. Gly47Glu and Leu12Pro mutations showed an aggressive clinical manifestation: 2 patients with the Gly47Glu mutation, the youngest patients of all the non-Val30Met patients, suffered from severe cardiac symptoms leading to death despite LT. Two siblings with the Leu12Pro mutation, who presented only with grand mal seizures, died after LT because of sepsis. In conclusion, the clinical course in patients with FAP is very variable. Cardiac symptoms occurred predominantly in patients with non-Val30Met mutations and prompted combined heart-liver transplantation in 4 patients. Although early LT in Val30Met is indicated in order to halt the typical symptoms of polyneuropathy, additional complications occurring predominantly with other mutations may prevail and lead to life-threatening complications or a fatal outcome. Combined heart-liver transplantation should be considered in patients with restrictive cardiomyopathy.
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http://dx.doi.org/10.1002/lt.21996DOI Listing
March 2010

True-lumen collapse of the ascending aorta in acute type A aortic dissection.

Eur J Cardiothorac Surg 2010 Apr 26;37(4):955. Epub 2009 Nov 26.

Department of Cardiothoracic and Vascular Surgery, Johannes Gutenberg-University Mainz, Germany.

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http://dx.doi.org/10.1016/j.ejcts.2009.09.046DOI Listing
April 2010

Reevaluation of direct true lumen cannulation in surgery for acute type A aortic dissection.

Ann Thorac Surg 2009 Apr;87(4):1182-6

Department of Cardiothoracic and Vascular Surgery, Johannes Gutenberg-University Mainz, Germany.

Background: The optimal mode of arterial cannulation in acute type A aortic dissection is controversial. We retrospectively investigated our experience with direct true lumen cannulation as an alternative to standard cannulation procedures.

Methods: From April 2004 to August 2007, 29 patients (20 men, 9 women; mean age of 63.2 +/- 12.6 years) underwent emergency operation for acute type A aortic dissection with direct true lumen cannulation. After venous drainage into the venous reservoir, the ascending aorta was completely transected in the region between the sinotubular junction and innominate artery. After visual and digital identification of the true lumen, the arterial cannula was directly inserted into the true lumen and secured with a ligature.

Results: Mean aortic cross-clamp time was 77.4 +/- 28.3 minutes, and hypothermic circulatory arrest for the distal anastomosis was 10.4 +/- 11.0 minutes. All patients survived the surgical procedure. No surgical problems were observed by applying this strategy. Mean intensive care unit stay was 4.0 +/- 3.5 days. Postoperative mean ventilation time was 43.3 +/- 41.3 hours. One patient had a prolonged postoperative course and required permanent ventilation. Two patients required temporary hemofiltration. Neurologic disorders occurred in 6 patients: 2 had severe cerebral hypoxia, and 4 had temporary hemiplegia under good regression. All patients were alive at discharge.

Conclusions: Direct true lumen cannulation is a promising surgical strategy for emergency operations in type A aortic dissection. It is a simple, quick, and safe method to provide antegrade flow through the true aortic lumen.
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http://dx.doi.org/10.1016/j.athoracsur.2009.01.027DOI Listing
April 2009

Oxidative inhibition of the mitochondrial aldehyde dehydrogenase promotes nitroglycerin tolerance in human blood vessels.

J Am Coll Cardiol 2007 Dec 19;50(23):2226-32. Epub 2007 Nov 19.

II Medizinische Klinik für Kardiologie und Angiologie, Johannes Gutenberg University, Mainz, Germany.

Objectives: We tested the hypothesis of whether an inhibition of the nitroglycerin (GTN) bioactivating enzyme mitochondrial aldehyde dehydrogenase (ALDH-2) contributes to GTN tolerance in human blood vessels.

Background: The hemodynamic effects of GTN are rapidly blunted by the development of tolerance, a phenomenon associated with increased formation of reactive oxygen species (ROS). Recent studies suggest that ROS-induced inhibition of ALDH-2 accounts for tolerance in animal models.

Methods: Segments of surgically removed arteria mammaria and vena saphena from patients undergoing coronary bypass surgery were used to examine the vascular responsiveness to GTN and the endothelium-dependent vasodilator acetylcholine. The ALDH-2 activity and expression in these segments were assessed by the conversion of a benzaldehyde or its derivative to the benzoic acid metabolite and by Western blotting technique.

Results: In contrast to patients not treated with nitrates (n = 36), patients treated with GTN for 48 h (n = 14) before surgery showed tolerance to GTN and endothelial dysfunction in arterial and venous vessels. In vivo GTN tolerance was mimicked in vitro by incubation of nontolerant vessels with the ALDH-2 inhibitor benomyl. In vivo GTN treatment decreased vascular aldehyde dehydrogenase activity compared with nontolerant vessels and decreased the expression of ALDH-2 in arterial tissue. Incubation of control venous vessels with GTN caused a significant attenuation of aldehyde dehydrogenase activity that was reversed by presence of the sulfhydryl group donor dithiothreitol.

Conclusions: Long-term GTN treatment induces tolerance and endothelial dysfunction in human vessels, associated with an inhibition and down-regulation of vascular ALDH-2. Thus, these findings extend results of previous animal studies to humans.
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http://dx.doi.org/10.1016/j.jacc.2007.08.031DOI Listing
December 2007

Ischemia-Reperfusion Injury : Pathophysiology and Clinical Implications.

Eur J Trauma Emerg Surg 2007 Dec 20;33(6):600-12. Epub 2007 Nov 20.

Department of Cardiothoracic and Vascular Surgery, University Hospital, Johannes-Gutenberg Medical School, Mainz, Germany.

The term ischemia-reperfusion injury describes the experimentally and clinically prevalent finding that tissue ischemia with inadequate oxygen supply followed by successful reperfusion initiates a wide and complex array of inflammatory responses that may both aggravate local injury as well as induce impairment of remote organ function. Conditions under which ischemia-reperfusion injury is encountered include the different forms of acute vascular occlusions (stroke, myocardial infarction, limb ischemia) with the respective reperfusion strategies (thrombolytic therapy, angioplasty, operative revascularization) but also routine surgical procedures (organ transplantation, free-tissue-transfer, cardiopulmonary bypass, vascular surgery) and major trauma/shock. Since the first recognition of ischemia-reperfusion injury during the 1970s, significant knowledge has accumulated and the purpose of this review is to present an overview over the current literature on the molecular and cellular basis of ischemia-reperfusion injury, to outline the clinical manifestations and to compile contemporary treatment and prevention strategies. Although the concept of reperfusion injury is still a matter of debate, it is corroborated by recent and ongoing clinical trials that demonstrated ischemic preconditioning, inhibition of sodium-hydrogen-exchange and administration of adenosine to be effective in attenuating ischemia-reperfusion injury.
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http://dx.doi.org/10.1007/s00068-007-7152-zDOI Listing
December 2007

Effects of aprotinin on gene expression and protein synthesis after ischemia and reperfusion in rats.

Circulation 2007 Sep;116(11 Suppl):I121-6

Department of Internal Medicine III, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle/Saale, Germany.

Background: Reperfusion injury of ischemic myocardium has been attributed to neutrophil infiltration, inflammatory activation and cardiac necrosis/apoptosis. Serine protease inhibition with aprotinin is cardioprotective, but the mechanism is unknown.

Methods And Results: We studied aprotinin in a rat model of myocardial ischemia for 20 minutes and reperfusion for 20 minutes, 8 hours or 24 hours. Aprotinin (20,000 IU/kg) given 5 minutes before reperfusion significantly reduced leukocyte accumulation (P<0.01), myocardial injury (determined by CK depletion, P<0.01) and myocyte apoptosis (P<0.05) compared with vehicle treated rats. Differential gene expression analysis showed myocardial ischemia plus reperfusion increased expression of proinflammatory genes like P-selectin, E-selectin, intercellular adhesion molecule, tumor necrosis factor-alpha, tumor necrosis factor-alpha receptor, interleukin-6, monocyte chemoattractant protein-1, p53, and Fas (CD59). Aprotinin before reperfusion suppressed expression of these inflammatory genes. Finally, differential protein expression analysis demonstrated increased intercellular adhesion molecule-1, tumor necrosis factor-alpha, and p53 after myocardial ischemia plus reperfusion, and this effect was diminished by aprotinin.

Conclusions: We demonstrated myocardial ischemia plus reperfusion induced leukocyte accumulation, inflammation, gene expression, protein expression and finally tissue injury and showed aprotinin limiting reperfusion injury through each of these stages, even after 24 hours of reperfusion. This effect seems partly attributable to suppression of proinflammatory genes and leukocyte accumulation. This work casts further light on the complex signaling of ischemia and reperfusion.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.106.680249DOI Listing
September 2007

Poly(ADP-ribose) polymerase inhibitor PJ-34 reduces mesenteric vascular injury induced by experimental cardiopulmonary bypass with cardiac arrest.

Am J Physiol Heart Circ Physiol 2005 Jun 28;288(6):H2972-8. Epub 2005 Jan 28.

Dept. of Visceral, Thoracic and Vascular Surgery, Carl Gustav Carus Univ. Hospital, Fetscherstrasse 74, Haus 59, 01307 Dresden, Germany.

The aim of this study was to investigate effects of poly(ADP-ribose) polymerase (PARP) inhibition on mesenteric vascular function and metabolism in an experimental model of cardiopulmonary bypass (CPB) with cardiac arrest. Twelve anesthetized dogs underwent 90-min hypothermic CPB. After 60 min of cardiac arrest, reperfusion was started for 40 min following application of either saline vehicle (control, n = 6) or a potent PARP inhibitor, PJ-34 (10 mg/kg iv bolus and 0.5 mg.kg(-1).min(-1) infusion for 20 min, n = 6). PJ-34 led to better recovery of cardiac output (2.2 +/- 0.1 vs. 1.8 +/- 0.2 l/min in control) and mesenteric blood flow (175 +/- 38 vs. 83 +/- 4 ml/min, P < 0.05 vs. control) after reperfusion. The impaired vasodilator response of the superior mesenteric artery to acetylcholine, assessed in the control group after CPB (-32.8 +/- 3.3 vs. -57.6 +/- 6.6% at baseline, P < 0.05), was improved by PJ-34 (-50.3 +/- 3.6 vs. -54.3 +/- 4.1% at baseline, P < 0.05 vs. control). Although plasma nitrate/nitrite concentrations were not significantly different between groups, mesenteric nitric oxide synthase activity was increased in the PJ-34 group (P < 0.05). Moreover, the treated group showed a marked attenuation of mesenteric venous plasma myeloperoxidase levels after CPB compared with the control group (75 +/- 1 vs. 135 +/- 9 ng/ml, P < 0.05). Pharmacological PARP inhibition protects against development of post-CPB mesenteric vascular dysfunction by improving hemodynamics, restoring nitric oxide production, and reducing neutrophil adhesion.
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http://dx.doi.org/10.1152/ajpheart.01039.2004DOI Listing
June 2005

Nitric oxide-sensitive soluble guanylyl cyclase activity is preserved in internal mammary artery of type 2 diabetic patients.

Diabetes 2004 Oct;53(10):2640-4

Faculty of Clinical Medicine Mannheim, Institute of Pharmacology and Toxicology, University of Heidelberg, Mannheim, Germany.

Vascular reactivity to nitric oxide (NO) is mediated by NO-sensitive soluble guanylyl cyclase (sGC). Since a diminished activity of vascular sGC has been reported in an animal model of type 2 diabetes, the sGC activity was assayed in vitro in internal mammary artery specimens obtained during bypass surgery from patients with and without type 2 diabetes. The sensitivity of sGC to NO, which is dependent on Fe(2+)-containing heme, was measured in vitro using stimulation with diethylamine NONOate (DEA/NO). In addition, the novel cyclic guanosine monophosphate-elevating compound HMR-1766 was used to test the stimulation of the oxidized heme-Fe(3+)-containing form of sGC. Basal activity of sGC and its sensitivity to stimulation by DEA/NO and HMR-1766 were not different between control and type 2 diabetic patients: maximum stimulation by DEA/NO amounted to 475 +/- 67 and 418 +/- 59 pmol. mg(-1). min(-1) in control and type 2 diabetic patients, respectively. The maximum effects of HMR-1766 were 95 +/- 18 (control subjects) and 83 +/- 11 pmol. mg(-1). min(-1) (type 2 diabetic patients). Hypertension, hyperlipidemia, drug treatment with statins, ACE inhibitors, or nitrates had no effect on sGC activity. In conclusion, the present findings do not support the hypothesis that desensitization of sGC contributes to the pathogenesis of diabetic vascular dysfunction in humans.
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http://dx.doi.org/10.2337/diabetes.53.10.2640DOI Listing
October 2004

Expression of bone sialoprotein and bone morphogenetic protein-2 in calcific aortic stenosis.

J Heart Valve Dis 2004 Jul;13(4):560-6

1st Department of Medicine (Cardiology, Angiology, and Pneumology), University Hospital of Mannheim, Germany.

Background And Aim Of The Study: Calcific aortic stenosis, the major heart valve disease encountered in the elderly, leads to massive calcium deposition in the valve leaflets that morphologically resembles bone formation. Recent studies have demonstrated the expression of various bone-associated proteins in stenotic valves, suggesting that valvular calcification may be an actively regulated process. Bone sialoprotein (BSP), a non-collagenous bone matrix protein, and bone morphogenetic protein-2 (BMP-2), a member of the transforming growth factor cytokine superfamily, are known to participate in the regulation of bone development and maturation. Their pathogenetic role in calcific aortic stenosis is unknown.

Methods: Using an immunoperoxidase technique and antibodies against BSP and BMP-2, the expression of BSP and BMP-2 was examined in 16 human aortic valves with calcific aortic stenosis obtained at valve replacement, and in seven normal autopsy controls without signs of aortic stenosis.

Results: By semiquantitative scoring, stenotic valves showed a significantly increased staining of BSP in cells and extracellular matrix as compared to control valves (2.7 +/- 0.1 versus 0.6 +/- 0.2 score units, p <0.001). Marked BMP-2 expression was detected in stenotic valves, mostly in cell-rich areas associated with focal calcium deposits, but no specific staining for BMP-2 was detected in control valves (1.5 +/- 0.2 versus 0.0 +/- 0.0 score units, p <0.001).

Conclusion: These results demonstrate for the first time that BSP and BMP-2 are differentially expressed in normal aortic valves and in aortic stenosis, thereby supporting the concept that valvular calcification might be based on an actively regulated process involving BSP and BMP-2.
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July 2004

Regurgitant jet evaluation using three-dimensional echocardiography and magnetic resonance.

Ann Thorac Surg 2004 Jul;78(1):96-102

Department of Cardiac Surgery, University of Heidelberg, Germany.

Background: Three-dimensional assessment of regurgitant jet volume is the prerequisite for stratifying valve insufficiency. However, systematic comparison of three-dimensional methods is lacking. Therefore, we evaluated magnetic resonance imaging and three-dimensional echocardiography experimentally.

Methods: An insufficiency chamber (22 x 18.5 x 27 cm; ostia 10, 16, and 20 mm; regurgitant volumes 2.3 to 25 mL) within experimental circulation (BioMedicus pump, tubes, pulsatile flow 0.2 to 1.9 L/min) was used for three-dimensional echocardiography (HP Sonos 2500) and magnetic resonance imaging (Siemens Magnetom Vision). Doppler flowmeter served as a gold standard. Segmentation used thresholding and surface integration of velocity vectors. Jet volume was evaluated qualitatively by polynom fitting.

Results: Jet volume calculated by magnetic resonance (r = 0.99, p < 0.0001) and by echocardiography (r = 0.99, p < 0.0001) correlated identically to the gold standard. Jet volume derived from imaging correlated with each other by r = 0.98 (p < 0.0001). Polynom fits indicated a more paraboloid shape of magnetic resonance jet volume.

Conclusions: Experimentally, three-dimensional echocardiography and magnetic resonance imaging possess identical accuracy for determining regurgitant jet volume. Magnetic resonance imaging seems to provide qualitatively better image data for three-dimensional reconstruction.
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http://dx.doi.org/10.1016/j.athoracsur.2003.11.055DOI Listing
July 2004

INO-1001 a novel poly(ADP-ribose) polymerase (PARP) inhibitor improves cardiac and pulmonary function after crystalloid cardioplegia and extracorporal circulation.

Shock 2004 May;21(5):426-32

Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany, D-69120.

Poly(ADP-ribose) polymerase (PARP) activation plays a key role in free radical-induced injury in the context of systemic inflammation and ischemia/reperfusion. In the present preclinical study, we investigated the effects of INO-1001, a novel PARP inhibitor, on cardiac and pulmonary function during reperfusion in an experimental model of cardioplegic arrest and extracorporal circulation. Twelve anesthetized dogs underwent hypothermic cardiopulmonary bypass. After 60 min of hypothermic cardiac arrest, reperfusion was started after application of either saline vehicle (control, n = 6), or INO-1001 (1 mg/kg), a potent PARP inhibitor (n = 6). Biventricular hemodynamic variables were measured by combined pressure-volume-conductance catheters. Coronary and pulmonary blood flow and vasodilative responses to acetylcholine and sodium nitroprusside as well as pulmonary gas exchange were also determined. The administration of INO-1001 led to a significantly better recovery of left and right ventricular systolic function (P < 0.05) after 60 min of reperfusion. Coronary blood flow was also significantly higher in the INO-1001 group (P < 0.05). Although the vasodilative response to sodium nitroprusside was similar in both groups, acetylcholine resulted in a significantly greater increase in coronary and pulmonary blood flow in the INO-1001 group (P < 0.05). Pulmonary function in terms of alveolar arterial oxygen difference was better preserved in the INO-1001-treated group (P < 0.05). Thus, PARP inhibition improves the recovery of myocardial and endothelial function after hypothermic cardiac arrest and reduces pulmonary injury associated with extracorporal circulation.
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http://dx.doi.org/10.1097/00024382-200405000-00005DOI Listing
May 2004

Ventricular energetics after the Fontan operation: contractility-afterload mismatch.

J Thorac Cardiovasc Surg 2003 May;125(5):1061-9

Department of Cardiac Surgery, University of Heidelberg, Germany.

Objective: Fontan-type operations offer the opportunity to create pulmonary and systemic circulation in series with a single pumping chamber. The effectiveness of such a circulatory pattern determines resting and exercise hemodynamics in these patients. The present study investigated cardiac performance after the Fontan operation by using ventricular-vascular coupling framework analysis.

Methods: In 12 anesthetized open-chest dogs, Fontan circulation was established by using a cavopulmonary anastomosis. Left ventricular hemodynamic variables were measured by using a combined pressure-volume-conductance catheter. Additionally, aortic flow and pressure were recorded continuously. Ventricular contractility was quantified by using the load-independent slope of the end-systolic pressure-volume relationship. Arterial system properties were quantified by using the end-systolic pressure/stroke volume ratio. The coupling between the left ventricle and arterial system was expressed by using the ratio of end-systolic pressure/stroke volume to slope of the end-systolic pressure-volume relationship. Additionally, external stroke work, total mechanical energy and mechanical efficiency (Mechanical efficiency = Stroke work/Total mechanical energy) were calculated. Impedance spectra were determined by means of Fourier analysis.

Results: During Fontan circulation, the slope of the end-systolic pressure-volume relationship (5.3 +/- 0.6 vs 7.5 +/- 0.6 mm Hg/mL, P <.05) decreased, and the end-systolic pressure-stroke volume relationship (4.2 +/- 0.7 vs 3.3 +/- 0.5 mm Hg/mL, P =.23) increased with parallel increased characteristic impedance. Furthermore, the end-systolic pressure-stroke volume/slope of the end-systolic pressure-volume relationship ratio increased significantly (0.76 +/- 0.04 vs 0.42 +/- 0.03, P <.005). Simultaneously, stroke work (1846 +/- 146 vs 1389 +/- 60 mm Hg/mL, P <.05) and mechanical efficiency (0.82 +/- 0.09 vs 0.56 +/- 0.05, P <.05) were significantly reduced.

Conclusions: Fontan circulation leads to contractility-afterload mismatch by means of increased impedance caused by additional connection of the pulmonary vascular bed to the systemic vasculature and by means of deterioration of myocardial contractility. The increased ventriculoarterial coupling ratio and reduced mechanical efficiency predict limited cardiac functional reserve after the Fontan operation.
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http://dx.doi.org/10.1067/mtc.2003.405DOI Listing
May 2003

In vivo validation of cardiac spiral computed tomography using retrospective gating.

Ann Thorac Surg 2003 Mar;75(3):885-9

Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany.

Background: Cardiac functional assessment represents the basis for diagnostics and cardiac operation planning. Spiral computed tomography (CT) combines the advantages of three-dimensional imaging and high temporal resolution when using gating techniques. However, in vivo validation data of this novel imaging technology are lacking. The purpose of this study was to validate in vivo the new imaging method using retrospective gating and to evaluate the clinical usefulness of the achieved temporal resolution.

Methods: In domestic pigs (n = 10, weight 35 to 40 kg) a flowmeter was placed surgically on the ascending aorta. Flow velocity integrated over systole served as the gold standard for left ventricular (LV) stroke volume (LVSV-FM). CT signal, projection data, pacemaker signal, and flow velocity were recorded simultaneously at constant heart rate (pacemaker, 90 beats per minute). End-systolic and end-diastolic frames were calculated by retrospective gating. LV volumes were traced, the difference representing CT stroke volume (LVSV-CT). Image data were three-dimensionally reconstructed using ray-tracing.

Results: Temporal resolution was 170 ms. Correlation of stroke volumes was high (r = 0.94, mean difference 1.75 mL). Intraobserver (0.49 mL for LVEDV, 0.31 for LVESV) and interobserver variability (p = 0.21 and p = 0.06, respectively) were low. Postprocessing resulted in four-dimensional beating-heart models useful for operation planning.

Conclusions: Spiral CT using retrospective gating was validated in vivo. Clinically acceptable temporal resolution and accuracy in determining cardiac stroke volumes were found. As a true volumetric imaging modality the method may now play an important role in computer-assisted diagnostics and surgery.
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http://dx.doi.org/10.1016/s0003-4975(02)04505-8DOI Listing
March 2003