Thierry Caus

Comprehensive Diagnostic Strategy for Blood Culture-Negative Endocarditis: A Prospective Study of 819 New Cases

BACKGROUND. Blood culture-negative endocarditis (BCNE) may account for up to 31% of all cases of endocarditis. METHODS. We used a prospective, multimodal strategy incorporating serological, molecular, and histopathological assays to investigate specimens from 819 patients suspected of having BCNE. RESULTS. Diagnosis of endocarditis was first ruled out for 60 patients. Among 759 patients with BCNE, a causative microorganism was identified in 62.7%, and a noninfective etiology in 2.5%. Blood was the most useful specimen, providing a diagnosis for 47.7% of patients by serological analysis (mainly Q fever and Bartonella infections). Broad-range polymerase chain reaction (PCR) of blood and Bartonella-specific Western blot methods diagnosed 7 additional cases. PCR of valvular biopsies identified 109 more etiologies, mostly streptococci, Tropheryma whipplei, Bartonella species, and fungi. Primer extension enrichment reaction and autoimmunohistochemistry identified a microorganism in 5 additional patients. No virus or Chlamydia species were detected. A noninfective cause of endocarditis, particularly neoplasic or autoimmune disease, was determined by histological analysis or by searching for antinuclear antibodies in 19 (2.5%) of the patients. Our diagnostic strategy proved useful and sensitive for BCNE workup. CONCLUSIONS. We highlight the major role of zoonotic agents and the underestimated role of noninfective diseases in BCNE. We propose serological analysis for Coxiella burnetii and Bartonella species, detection of antinuclear antibodies and rheumatoid factor as first-line tests, followed by specific PCR assays for T. whipplei, Bartonella species, and fungi in blood. Broad-spectrum 16S and 18S ribosomal RNA PCR may be performed on valvular biopsies, when available.

Outcomes After Surgical Treatment for Type A Acute Aortic Dissection in Octogenarians: A Multicenter Study

BACKGROUND Management of octogenarian patients with acute type A acute aortic dissection is controversial. This study analyzed the surgical outcomes to identify patients who should undergo operations. METHODS Beginning January 2000, we established a registry including all octogenarian patients operated on for type A acute aortic dissection. We evaluated 57 consecutive patients enrolled up to December 2006. Their median age was 82 (range, 80 to 89 years). Compassionate indication operations were attempted in 2 moribund patients and in 5 presenting with shock associated with neurologic symptoms or renal failure, or both. Operations followed the standard procedure recommended in younger patients. Follow-up was 100% complete (mean, 3.9 +/- 2 years; range, 5 months to 8 years). RESULTS There were 26 (45.6%) in-hospital and 6 late deaths. Multivariate analysis identified compassionate indication (p < or = 0.0001) and total arch replacement (p = 0.0060) as risk factors for in-hospital mortality. Postoperative complications occurred in 36 patients (69.2%) and were associated with a higher mortality (p = 0.0001). Overall survival was 51% at 1 year and 44% at 5 years. Excluding patients with compassionate indication and those who underwent total arch replacement, or both, overall survival was 66% at 1 year and 57% at 5 years. CONCLUSIONS Surgical treatment for type A acute aortic dissection in octogenarians shows satisfactory midterm results among survivors. However, the high mortality rate imposes a requirement for better perioperative management. Compassionate cases should be managed medically. A less aggressive approach should improve outcomes of surgical treatment.

Late complications after prosthetic replacement of the ascending aorta: what did we learn from routine magnetic resonance imaging follow-up?

OBJECTIVE Advances in surgical technique have improved early survival after surgery of the ascending aorta. However, follow-up data document serious late complications, mainly evolutive peri-prosthetic false aneurysms. Magnetic resonance imaging (MRI) has proved to be highly effective for monitoring these complications. This study evaluates 10 years of experience with routine MRI for follow-up. METHODS Since January 1988, 114 patients with replacement of the ascending aorta either for type A acute dissection (group I, 45 patients) or aneurysms (group II, 69 patients) were followed up with annual MRI. Prosthetic replacement was either limited to supra-coronary ascending aorta (45%, 51/114) or extended to the aortic root and/or the aortic arch (55%). Biological glue was always utilized. MRI focused on peri-prosthetic haematoma, analyzing signal intensity changes and volume augmentation for early detection of false aneurysms, and on persistent residual dissection with or without evolutive aortic aneurysm distant to the prosthesis. RESULTS Peri-prosthetic hematomas were almost equally found in both groups (26 (58%) in group I and 42 (61%) in group II) and were detected within the first year. Peri-prosthetic false aneurysms developed in 15 patients (group I, seven; group II, eight) as a complication of pre-existing hematomas and were indicated for elective reoperation. Forty-three (96%) of patients in group I had persistent residual dissection. Five patients in group I and two in group II needed reoperation for evolutive aortic aneurysm. In total, 22 of 114 (19%) patients were reoperated on during follow-up (12 (27%) in group I and ten (15%) in group II). Operative mortality was 13% (3/22). Freedom from reoperation at 1 year/5 years was: group I, 93%/84%; group II, 98%/88%. CONCLUSION Peri-prosthetic haematoma occurs equally after aneurysm or dissection repairs and is a pre-existing condition for peri-prosthetic false aneurysm; biological glue or extended repair do not prevent late complications. Long-term MRI follow-up allows successful elective reoperation for life-threatened but asymptomatic patients.

Clinical outcome after repair of acute type A dissection in patients over 70 years-old

BACKGROUND Despite current aging of patients proposed for cardiac surgery, published results of type A dissection repair in the elderly are sparse and controversial though an increased operative risk when compared to younger patients is well-documented. Whether any patient of an advanced aged suffering from acute dissection of the proximal aorta should be referred for surgery deserves specific clinical studies. OBJECTIVE To define factors of poor outcome after repair of type A dissection in the elderly by focusing on both early and late results. METHOD A retrospective study including a consecutive series of 83 patients operated on in two neighboring French university centers between 1988 and 1999 with similar outstanding methods. Complete follow-up was achieved in March 2000. Results were compared according to: (i) the presence or the absence of complications at admission; and (ii) the use of hypothermic circulatory arrest (HCA) for completion of the distal suture. RESULTS Mean age was 75.2+/-3.6 years (70-85). Overall operative mortality (OM) was 37.3%. OM was significantly higher (51.2 versus 23.8%, P=0.01) for patients who presented at admission any one of the following complications: tamponade, shock, endotracheal intubation upon arrival or evidence of brain, myocardial, mesenteric, renal or limb malperfusion. OM was not significantly affected by age or by the use of HCA during repair. Overall Kaplan-Meier survival was 50% at 1 year, 30% at 5 years and 13% at 10 years and was significantly lower (P=0.004) for patients who presented at least one complication at admission. Kaplan-Meier survival (excluding OM) was respectively 81, 48 and 21% and was significantly lower in case of prolonged stay in ICU (P=0.014) and for patients operated on without HCA (P=0.02). CONCLUSIONS Results of repair of acute type A dissections in the elderly are acceptable for uncomplicated cases at admission. Using HCA in elderly patients whenever required for appropriate repair does not worsen early or late survival.

Thrombocytopenia After Aortic Valve Replacement With Freedom Solo Bioprosthesis: A Propensity Study

BACKGROUND The incidence of postoperative thrombocytopenia after aortic valve replacement with the Freedom Solo bioprosthesis remains unclear. This propensity-matched study was carried out to evaluate the incidence and clinical impact of thrombocytopenia in patients receiving the Freedom Solo bioprosthesis. METHODS Patients who underwent aortic valve replacement with a Freedom Solo or Carpentier-Edwards Perimount pericardial prosthesis at our institution between 2006 and 2008 were screened retrospectively. Exclusion criteria included double valve replacement, redo surgery, and active endocarditis. Two hundred six patients were considered eligible for this analysis. Using propensity scores 36 matched pairs of patients with a Freedom Solo or Perimount bioprosthesis were obtained. The primary end point was the occurrence of postoperative thrombocytopenia. Secondary end points were postoperative thromboembolic or hemorrhagic events and 30-day mortality. RESULTS Before matching, severe thrombocytopenia (<30 x 10(9) platelets/L) occurred in 22% of patients with a Freedom Solo bioprosthesis and 1% with a Perimount bioprosthesis (p < 0.0001), thromboembolic or hemorrhagic events occurred in 3% and 2%, respectively (p = 0.37), and 30-day mortality was 4% and 6%, respectively (p = 0.48). Multivariate analysis identified preoperative platelet count (p = 0.01) and Freedom Solo (p < 0.0001) as independent risk factors for severe postoperative thrombocytopenia. After matching, severe thrombocytopenia occurred in 25% and 3% of patients with Freedom Solo and Perimount bioprostheses, respectively (p < 0.0001), thromboembolic or hemorrhagic events occurred in 0%, and 30-day mortality was 3% and 6%, respectively (p = 0.99). CONCLUSIONS The risk of thrombocytopenia was high after Freedom Solo implantation. However, this complication was not related to any deleterious events in our study population.

Octogenarians With Uncomplicated Acute Type A Aortic Dissection Benefit From Emergency Operation

BACKGROUND The management of acute type A aortic dissection (aTAAD) in octogenarian patients is controversial. This study analyzed the surgical outcomes to identify patients who should undergo operations. METHODS Beginning in January 2000, we established a registry including all octogenarian patients operated on for type A acute aortic dissection. We evaluated 79 consecutive patients enrolled up to December 2010. Their median age was 81.6 years (range, 80 to 89 years). Sixteen patients (20%) presented a complicated type because of a neurologic deficit, mesenteric ischemia, a requirement for cardiopulmonary resuscitation, or some combination of those features. Operations followed the standard procedure recommended for younger patients. Follow-up was 95% complete (mean, 4.6±2.8 years). RESULTS The overall in-hospital mortality was 44.3%. The in-hospital mortality among patients with uncomplicated aTAAD was 33.3%. Multivariate analysis identified complicated aTAAD as the only risk factors for in-hospital mortality (p<0.0001). Postoperative complications occurred in 50 patients (68.5%) and were associated with a higher mortality (p<0.0001). The overall survival was 53% at 1 year and 32% at 5 years. In uncomplicated aTAAD, the overall survival was 63% at 1 year and 38% at 5 years. CONCLUSIONS Octogenarians with uncomplicated aTAAD benefit from emergency surgical repair. In those patients, early and midterm outcomes are good and are similar to those in published series of younger patients. Complicated aTAAD should be medically managed.

Anticoagulation monitoring during extracorporeal circulation with the Hepcon/HMS device

Objective: The objective of our study was to compare the standard protocol of anticoagulation to the Hepcon/HMS. Method: This study included forty-four patients who underwent coronary bypass grafting surgery (CABG), or biological aortic valve replacement (AVR). Unfractionated heparin (UH) was used for patients who underwent operations in the control group (n = 22) (300U/Kg of UH with a goal of an ACT of 400s). The heparin was antagonized dose/dose by protamine. For the patients who underwent operations in the HMS group (n = 22), the heparin and protamine doses were assessed by the Hepcon/HMS device. Results: The sex ratio amounted to 1.93 (29 men and 15 women) and the mean age was 70 ± 11 years. The patients in the HMS group had a chest closure time that was significantly shorter than patients in the control group. The times were, respectively, 42 ± 15 minutes and 68 ± 27 minutes (p = 0.001). The protamine/heparin ratio was significantly lower in the HMS group (0.62 ± 0.13 vs. 1 ± 0.11) (p = 0.0001). The postoperative bleeding amounted to 804 ± 729 ml in the HMS group versus 1416 ± 1103 in the control group (p = 0.016). In multivariate linear regression analysis, only two independent factors were significantly associated with bleeding: the Hepcon/HMS (OR = 0.1-p = 0.03) and the preoperative hemoglobin rate (OR = 1.4 - p = 0.05). Postoperatively, within 72 hours, the red blood cell transfusion was 1.04 ± 1.5 units for the HMS group and 2.1 ± 1.87 units for the control group (p = 0.05). Conclusion: During cardiac surgery under CPB, heparin and protamine titration with the Hepcon/HMS device could predict a lower protamine dose and lower postoperative bleeding without higher thromboembolic events, and lower perioperative red blood cell transfusion with a shorter chest closure time.

Optimized cardiac graft preservation: a comparative experimental study using P-31 magnetic resonance spectroscopy and biochemical analyses ☆

BACKGROUND The University of Wisconsin (UW), St. Thomas (ST) and Broussais (B) solutions were compared to the CRMBM solution, that we developed for long term heart preservation. METHODS Isolated isovolumic rat hearts were arrested with each cardioplegic solution (n = 5) to 8 hearts in each group), submitted to 12 hours of cold storage (4 degrees C) in the same solution and then reperfused for 60 minutes at 37 degrees C. Function was measured during control and reflow. High energy phosphates and intracellular pH were monitored by P-31 magnetic resonance spectroscopy. Analyses were performed by biochemical assays and HPLC in coronary effluents (CK, Pi, lactate, purines) and in freeze-clamped hearts (amino acids, nucleotides, CK, LDH) at the end of reperfusion. RESULTS Functional recovery was significantly improved with the new cardioplegic solution (50+/-12% recovery for the rate pressure product at the end of reflow vs 8+/-3% with UW, 0% with B and with ST). This result was correlated with the best metabolic and cellular protection as assessed in particular by higher PCr levels during reflow (30+/-3% vs 10+/-3% with UW, 8+/-4% with B, and 7+/-1% with ST) as well as reduced creatine kinase leakage during reflow (110+/-15 IU/60 minute vs 270 +/- 57 IU/60 minute with UW, 323+/-36 IU/60 minute with Broussais solution and 237+/-18 IU/60 minute with ST). CONCLUSION This new solution is more effective in prolonged myocardial protection than the three most widely used solutions.

NOS substrate during cardioplegic arrest and cold storage decreases stunning after heart transplantation in a rat model

BACKGROUND In this study, we evaluated how adding L-arginine to Centre de Résonance Magnétique Biologique et Médicale (CRMBM) solution affected myocardial performance during post-ischemic in vivo reperfusion. METHODS Experiments were conducted using a modified Lewis-Lewis heterotopic heart transplantation model, with a total ischemic time of 3 hours followed by 1 or 24 hours of blood reperfusion. Heart grafts were arrested using intra-aortic injection of CRMBM solution, either supplemented or not supplemented with 2 mmol/liter L-arginine (n = 12 in each group). We measured systolic indexes and simultaneously performed phosphorus magnetic resonance spectroscopy ((31)P MRS). We quantified total endothelial nitric oxide synthase (eNOS) protein using the Western blot test of freeze-clamped hearts. RESULTS Contractility during early reperfusion was significantly better in grafts arrested with CRMBM solution enriched with L-arginine: mean rate pressure product, 11249 +/- 1548 vs 5637 +/- 1118 mm Hg/min (p = 0.05), and maximal first derivative of the pressure signal (dP/dt(max)), 1721 +/- 177 vs 1214 +/- 321 mm Hg/sec (p = 0.013). Conversely, during late reperfusion, contractility did not relate to the nature of the preservation solution. The presence of L-arginine in the CRMBM solution did not alter time-related variations of high-energy phosphate ratios measured using in vivo (31)P MRS. The eNOS protein level decreased significantly during early compared with late reperfusion, with no effect caused by L-arginine. CONCLUSIONS During early reperfusion, the limited myocardial stunning observed with CRMBM solution containing L-arginine does not relate to energy metabolism but to better preservation of the NO pathway.

Transdiaphragmatic hernia 1 year after heart transplantation following implantable LVAD

Complications after ventricular assist devices placement most frequently consist of bleeding, infection, and thromboembolic events. We describe a late complication after transplantation caused by transdiaphragmatic connection of the device placed in the abdominal position that presented as an acute pulmonary syndrome, misleading initial diagnosis.