The antegrade reperfusion test avoids the risk of mitral regurgitation recurrence optimizing valve repair.

Saline injection into the left ventricle trough mitral valve (saline test) is the most commonly used intraoperative assessment method in mitral valve repair. However, potential discrepancies between the saline test findings and intraoperative transesophageal echocardiography results after the weaning of cardiopulmonary by-pass, remain significant. Here, we describe a new antegrade reperfusion test, reproducing intraoperatively, the physiologic conditions of loaded and beating heart for direct transatrial evaluation of valve tightness. The proposed test is performed by perfusing warm oxygenated blood into the aortic root under cross-clamping. From February 2016 to December 2018, 91 patients (mean age: 63 ± 11 years) underwent mitral valve repair for mitral regurgitation. In all of them, the classic saline test was completed with the newly proposed antegrade test. We report our results with this combined approach. Data were obtained from the medical records and our mitral valve repair database. In 32 (35.1%) patients, evident or undetectable minor regurgitation at the saline test were respectively unconfirmed or detected by the antegrade reperfusion test leading to their complete correction. In only three patients (3.2%) major discrepancies was present between the intraoperative evaluation and the post-pump transesophageal echocardiography. Two of them (2.1%) required a second cardiopulmonary bypass run to fix the residual regurgitation. The antegrade reperfusion test is a simple dynamic intraoperative approach mimicking the physiological conditions of ventricular systole for mitral valve repair evaluation. Combined with the classic saline test, it seems to be a valuable additional intraoperative tool, enabling a more predictable repair result.

Basic pathophysiology and options of treatment for surgical management of functional tricuspid regurgitation: a systematic review.

Background: Functional tricuspid regurgitation (TR) appears frequently in the presence of left-sided heart valve diseases, combined with symptoms of heart failure, worsens if left untreated, and is associated with poor patient survival. Correct indications for surgery and the choice of suitable technique, which should be based on pathophysiology of disease are of utmost importance to ensure longevity and durability of repair; particularly given the risky nature of reoperations due to residual/recurrent TR. Methods: A systematic review was performed using Embase, Ovid Medline, Cochrane, Web of Science, and Google to deepen knowledge of major and controversial aspects of the subject. Results: A total of 1,579 studies were reviewed, and 32 of these were enclosed in the final review: 13 studies were primarily focused on pathophysiology and preoperative assessment of functional TR; 19 studies on surgical treatment of functional TR. A total of 15,509 patients were included. Conclusions: Indications for treatment of TR are based on the severity of regurgitation (grading), as well as on the presence of signs and symtoms of right-sided heart failure and on the extent of tricuspid annular dilation, leaflet tethering, and pulmonary hypertension (staging of disease). Despite improved knowledge of the underlying pathophysiology of TR, issues regarding indications for treatment and options of repair remain present. There is no consensus within the scientific community, for the preferred method to quantify the severity of TR; the recently introduced 5-grade TR classification based on objective quantitative parameters has not yet become common practice. The assessment of TR during stress exercise is rarely performed, though it takes into account the changes in severity of regurgitation that occur under different physiological conditions. Magnetic resonance imaging, which is the gold standard for the right heart evaluation is occasionally carried out before surgery. The threshold beyond which the tricuspid annular dilation should be repaired is unclear and recent studies put forward the idea that it may be lower than current recommendations. Tricuspid valve annuloplasty is the most adopted surgical option today. However, the ideal annuloplasty device remains elusive. In addition, as severe leaflet tethering cannot be addressed by annuloplasty alone, the addition of new techniques further increasing leaflet coaptation might optimize long-term valve continence. Further investigations are needed to address all these issues, alongside the potential of percutaneous options.

Endothelium-Derived Relaxing Factors and Endothelial Function: A Systematic Review.

BACKGROUND: The endothelium plays a pivotal role in homeostatic mechanisms. It specifically modulates vascular tone by releasing vasodilatory mediators, which act on the vascular smooth muscle. Large amounts of work have been dedicated towards identifying mediators of vasodilation and vasoconstriction alongside the deleterious effects of reactive oxygen species on the endothelium. We conducted a systematic review to study the role of the factors released by the endothelium and the effects on the vessels alongside its role in atherosclerosis. METHODS: A search was conducted with appropriate search terms. Specific attention was offered to the effects of emerging modulators of endothelial functions focusing the analysis on studies that investigated the role of reactive oxygen species (ROS), perivascular adipose tissue, shear stress, AMP-activated protein kinase, potassium channels, bone morphogenic protein 4, and P2Y2 receptor. RESULTS: 530 citations were reviewed, with 35 studies included in the final systematic review. The endpoints were evaluated in these studies which offered an extensive discussion on emerging modulators of endothelial functions. Specific factors such as reactive oxygen species had deleterious effects, especially in the obese and elderly. Another important finding included the shear stress-induced endothelial nitric oxide (NO), which may delay development of atherosclerosis. Perivascular Adipose Tissue (PVAT) also contributes to reparative measures against atherosclerosis, although this may turn pathological in obese subjects. Some of these factors may be targets for pharmaceutical agents in the near future. CONCLUSION: The complex role and function of the endothelium is vital for regular homeostasis. Dysregulation may drive atherogenesis; thus, efforts should be placed at considering therapeutic options by targeting some of the factors noted.

Heart Transplantation, Either Alone or Combined With Liver and Kidney, a Viable Treatment Option for Selected Patients With Severe Cardiac Amyloidosis.

Heart transplantation in cardiac amyloidosis (CA) patients is possible and generally considered for transplantation if other organs are not affected. In this study, we aimed to describe and assess outcome in patients following heart transplantations at our CA referral center. Methods: We assessed all CA patients that had heart transplantations at our center between 2005 and 2018. Patients with New York Heart Association status 3 out of 4, with poor short-term prognosis due to heart failure, despite treatment, and without multiple myeloma, systemic disease, severe neuropathic/digestive comorbidities, cancer, or worsening infections were eligible for transplantation. Hearts were transplanted by bicaval technique. Standard induction and immunosuppressive therapies were used. Survival outcome of CA patients after transplantation was compared with recipients with nonamyloid pathologies in France. Results: Between 2005 and 2018, 23 CA patients had heart transplants: 17 (74%) had light chain (light chain amyloidosis [AL]) and 6 (26%) had hereditary transthyretin (hereditary transthyretin amyloidosis [ATTRv]) CA. Also, 13 (57%) were male, and the mean age at diagnosis was 56.5 y (range, 47.7-62.8). Among AL patients, 13 had heart-only and 5 had heart-kidney transplantations. Among ATTRv patients, 1 had heart-only and 5 had heart-liver transplantations. The 1-y survival rate after transplantation was 78%, 70% with AL, and 100% with ATTRv. At 2 y, 74% were alive: 65% with AL and 100% with ATTRv. Conclusion: After heart transplantation, French CA and nonamyloid patients have similar survival outcomes. Among CA patients, ATTRv patients have better prognosis than those with AL, possibly due to the combined heart-liver transplantation. Selected CA patients should be considered for heart transplantations.

Valvular surgery in donor hearts before orthotopic heart transplantation.

BACKGROUND: Donor heart shortage has extended the waiting time and increased the mortality of patients on the transplant waiting list. Widening old standard donor criteria has successfully increased the number of heart transplantations, but for many years, a valve disease in a donor heart has been considered a primary contraindication for organ donation. AIMS: To analyse the results of aortic and mitral valvular surgery in marginal donor hearts with valvulopathy before orthotopic heart transplantation. METHODS: Between January 2012 and November 2015, we performed 53 heart transplantations in our department. In four donors, echocardiography performed at the time of organ procurement showed a valvular disease: three had moderate-to-severe mitral regurgitation; and one had moderately severe aortic valve stenosis. RESULTS: The mean bench mitral repair and aortic replacement time, aortic cross-clamp time and total ischaemic time were: 18 (range 7-25) minutes, 78.7 (range 57-98) minutes and 184 (range 89-255) minutes, respectively. Intraoperative transoesophageal echocardiography showed good mitral repair or aortic prosthetic valve function, and good right and left ventricular function. One patient died of infectious pneumonia after 1 month. The mean duration of follow-up for the patients discharged home was 75±13 months, and all have returned to an active unrestricted lifestyle. CONCLUSIONS: Our limited series demonstrates that conventional valvular procedures performed on otherwise healthy donor hearts with mitral and aortic valve pathology can efficaciously expand the donor pool for orthotopic cardiac transplantation and decrease the mortality rate on the waiting list.

Mitral annuloplasty ring with selective flexibility for septal-lateral contraction and remodelling properties.

OBJECTIVES: To develop and evaluate a novel mitral annuloplasty ring with selective flexibility for septal-lateral contraction and rigidity for septal-lateral dilatation in an acute porcine model. METHODS: The novel mitral annuloplasty ring was designed with slits in the luminal posterior segment and annular lateral segments. The slits were designed to allow inward motion during contraction and to block outward motion during dilation. The novel mitral annuloplasty ring was tested in vitro with a dedicated mechanical test bench, followed by in vivo characterization, using sonomicrometry and echocardiography for annular and leaflet geometry, in an acute porcine model. RESULTS: From the in vitro characterization, we verified that the ring could easily contract (0.7 mm/N) in the septal-lateral dimension, while dilatation was restrained (0.4 mm/N). In vivo characterization showed a cyclic range of 2.8 ± 0.0 mm for septal-lateral contraction. CONCLUSIONS: A novel saddle-shaped remodelling mitral annuloplasty ring was developed with selective flexibility for septal-lateral contraction and rigidity for septal-lateral dilatation. The advantages of this specific ring is that it re-establishes the coaptation plane, ensures leaflet mobility and septal-lateral flexibility and at the same time improves tissue adaptation and thereby decreases the risk of ring dehiscence and redilatation of the mitral annulus. This concept may prove beneficial for patients with ischaemic mitral valve regurgitation or degenerative valve disease.

Spontaneous mechanical rupture of a papillary muscle effectively resolved by mitral valve repair.

We report a case of spontaneous mechanical papillary muscle rupture. In theory, the papillary muscle works as a shock absorber that compensates for geometric changes of left ventricular wall. We believe that the aetiology of papillary muscle rupture, in this case, is linked to the physical and mechanical strains exerted on the papillary. We performed a mitral valve repair with excellent short- and long-term results.

A New Three-Dimensional Echocardiography Method to Quantify Aortic Valve Calcification.

BACKGROUND: Aortic valve calcification (AVC) quantification is computed from multidetector computed tomography (MDCT). The aim of this study was to test the hypothesis that three-dimensional (3D) transthoracic echocardiography can be used to provide a bedside method to assess AVC. METHODS: The study included 94 patients (mean age, 78 ± 12 years; mean aortic valve [AV] area, 1.0 ± 0.6 cm2) referred for MDCT and echocardiography for AV assessment. Apical 3D full-volume data sets focused on the AV region were acquired during transthoracic echocardiography, and a region-growing algorithm was applied offline to compute 3D transthoracic echocardiographic AVC (AVC-3DEcho). AVC-3DEcho was compared with AVC by MDCT and with calcium weight in the subgroup of patients referred for surgery, with explanted AVs analyzed by a pathologist (n = 22). RESULTS: In the explanted valve group, AVC-3DEcho score exhibited fair correlations with MDCT score (r = 0.85, P < .001), calcium load (r = 0.81, P < .001), and peak AV velocity (r = 0.64, P < .001). In the overall population, AVC-3DEcho score correlated modestly with MDCT score (r = 0.61, P < .001) but had similar accuracy to identify severe aortic stenosis (area under the curve = 0.94). AVC-3DEcho > 1,054 mm3 identified severe aortic stenosis with specificity of 100% and sensitivity of 76%. In addition, AVC-3DEcho was associated with the presence of significant paravalvular regurgitation after transcatheter aortic valve implantation. Finally, intraobserver and interobserver variability for AVC-3DEcho score was 4.2% and 8.9%, respectively. CONCLUSIONS: AVC-3DEcho correlated with calcium weight obtained from pathologic analysis and MDCT. These data suggest that a bedside method for quantifying AV calcification with ultrasound is feasible.

Pulmonary Artery Dissection: A Case Treated by Homograft Replacement.

Pulmonary artery dissection was diagnosed in a 32-year-old man who was admitted to the emergency department with intense chest pain. He had a history of pulmonary balloon valvuloplasty for congenital pulmonary stenosis at the age of 7 and no pulmonary hypertension. The operation was performed with cardiopulmonary bypass. The dissected pulmonary arterial trunk was removed with the distorted valve, and replaced with a pulmonary artery homograft. The postoperative course was uneventful. Histologic examination revealed medionecrosis. Pulmonary artery dissection is a rare but highly lethal pathology. In the absence of pulmonary hypertension, surgical treatment with homograft replacement can lead to excellent results.

Is bilateral internal thoracic artery grafting a safe option for chronic dialysis patients?

BACKGROUND: The use of bilateral internal thoracic artery (BITA) grafting has been proposed for dialysis patients with multivessel coronary artery disease, primarily because of hypothetical long-term survival benefits. AIMS: To investigate the outcome of BITA grafting in dialysis patients. METHODS: This was a retrospective analysis of the use of BITA grafting in 105 consecutive patients with end-stage renal failure on chronic dialysis in three European centres with extensive experience in BITA. Baseline patient characteristics, operative data, early postoperative complications and late survival were reviewed. Outcomes of patients from one of the three centres who underwent either BITA (n=40) or single internal thoracic artery (SITA) grafting (n=19) were also analysed; a one-to-one propensity score (PS)-matched analysis was performed. RESULTS: There were 19 (18.1%) hospital deaths. Despite differences in preoperative patient characteristics and surgical features, in each centre, hospital mortality was greater than the 75th percentile of expected operative risk (EuroSCORE II). Diseased ascending aorta and extracardiac arteriopathy were found to be predictors of hospital death (odds ratio 9.7; P=0.006) and complicated hospital course (odds ratio 2.54; P=0.035), respectively. The 7-year non-parametric estimates of freedom from all-cause death and cardiac or cerebrovascular death were 59% (95% confidence interval: 52.3-65.7%) and 75.6% (95% confidence interval: 71.2-80%), respectively. There were no significant differences in early and late outcomes between BITA and SITA PS-matched groups. CONCLUSIONS: BITA grafting remains a risky operation for chronic dialysis patients, even when performed routinely. No long-term survival benefits for the use of BITA versus SITA were proven.

Surgical management of penetrating thoracic injuries during the Paris attacks on 13 November 2015.

OBJECTIVES: The Paris terrorist attacks on 13 November 2015 caused 482 casualties, including 130 deaths and 352 wounded. Facing these multisite terrorist attacks, Parisian public and military hospitals simultaneously managed numerous patients with penetrating thoracic injuries. The aim of this study was to analyse this cohort, the injury patterns, and assess the results of this mobilization. METHODS: The clinical records of all patients admitted to Parisian public and military hospitals with a penetrating thoracic injury related to the Paris 13 November terrorist attacks were reviewed. RESULTS: The study group included 25 patients (7% of the casualties) with a mean age of 34 ± 8 years and a majority of gunshot wounds ( n = 20, 80%). Most patients presented with severe thoracic injury (Abbreviated Injury Score Thorax 3.3 ± 1.2), and also associated non-thoracic injuries in 21 cases (84%). The mean Injury Severity Score was 26.8 ± 9.4. Eight patients (32%) were managed with chest tube insertion and 17 (68%) required thoracic surgery. Lung resection, diaphragmatic repair, and lung suture were performed in 6 (36%), 6 (35%), and 5 cases (29%), respectively. Extra-thoracic surgical procedures were performed in 16 patients, mostly for injuries to the extremities. Postoperative mortality was 12% ( n = 3) and postoperative morbidity was 60% ( n = 15). CONCLUSIONS: The coordination of Parisian military and civilian hospitals allowed the surgical management of 25 patients. The mortality is high but consistent with what has been reported in previous series. The current times expose us to the threat of new terrorist attacks and require that the medical community be prepared.

Prognostic value of right ventricular systolic function in cardiac amyloidosis.

BACKGROUND: Right ventricular (RV) dysfunction is a strong predictor of poor outcomes in heart failure. Its prognostic meaning in cardiac amyloidosis (CA) is under-investigated. METHODS: Hundred and twenty nine patients with suspected CA and an interventricular septum thickness (IVST) ≥ 12 mm underwent echocardiography with measurement of left ventricular (LV) and RV longitudinal strain (LS), late gadolinium-enhancement (LGE) cardiac MRI, and standard evaluation. RESULTS: Among 82 confirmed CA, types were immunoglobulin light chain (AL, n = 26), hereditary transthyretin (m-TTR, n = 37) and senile (WT-TTR, n = 19). Compared to those without, CA patients had significantly lower RV fractional shortening (RV-FS), tricuspid annular plane systolic excursion (TAPSE), tissue Doppler systolic velocity, and global RV-LS, without any difference among the CA types. RV-LGE, observed in 62% of CA patients, was associated with lower global and basal RV-FS. Median follow-up was 8(2; 16) months. Using multivariate analysis, NYHA-class and low TAPSE independently predicted major adverse cardiac event (MACE) defined as death, heart transplantation and acute heart failure. Independent determinants of TAPSE < 14 mm, the best cut-off value, were LV ejection fraction (LVEF), estimated filling pressure (E/E'), NT-proBNP and pulmonary artery pressure, but not RV-LGE. CONCLUSIONS: RV dysfunction is common in CA. Its routine evaluation by a simple TAPSE may be an aid in assessing the prognosis of CA patients.

Myocardial Gene Expression Profiling to Predict and Identify Cardiac Allograft Acute Cellular Rejection: The GET-Study.

AIMS: Serial invasive endomyocardial biopsies (EMB) remain the gold standard for acute cellular rejection (ACR) diagnosis. However histological grading has several limitations. We aimed to explore the value of myocardial Gene Expression Profiling (GEP) for diagnosing and identifying predictive biomarkers of ACR. METHODS: A case-control study nested within a retrospective heart transplant patients cohort included 126 patients with median (IQR) age 50 (41-57) years and 111 (88%) males. Among 1157 EMB performed, 467 were eligible (i.e, corresponding to either ISHLT grade 0 or ≥3A), among which 36 were selected for GEP according to the grading: 0 (CISHLT, n = 13); rejection ≥3A (RISHLT, n = 13); 0 one month before ACR (BRISHLT, n = 10). RESULTS: We found 294 genes differentially expressed between CISHLT and RISHLT, mainly involved in immune activation, and inflammation. Hierarchical clustering showed a clear segregation of CISHLT and RISHLT groups and heterogeneity of GEP within RISHLT. All EMB presented immune activation, but some RISHLT EMB were strongly subject to inflammation, whereas others, closer to CISHLT, were characterized by structural modifications with lower inflammation level. We identified 15 probes significantly different between BRISHLT and CISHLT, including the gene of the muscular protein TTN. This result suggests that structural alterations precede inflammation in ACR. Linear Discriminant Analysis based on these 15 probes was able to identify the histological status of every 36 samples. CONCLUSION: Myocardial GEP is a helpful method to accurately diagnose ACR, and predicts rejection one month before its histological occurrence. These results should be considered in cardiac allograft recipients' care.

Causes and Consequences of Longitudinal LV Dysfunction Assessed by 2D Strain Echocardiography in Cardiac Amyloidosis.

OBJECTIVES: The aim of this study was to compare left ventricular longitudinal strain (LS) evaluated by 2-dimensional echocardiography with cardiac magnetic resonance (CMR) in cardiac amyloidosis (CA), establish correlations between histological and imaging findings, and assess the prognostic usefulness of LS measurement and CMR. BACKGROUND: CA is a condition with a poor prognosis due chiefly to 3 forms of amyloidosis: light-chain amyloidosis (AL), hereditary transthyretin (M-TTR), and wild-type transthyretin (WT-TTR). Two-dimensional echocardiography measurement of LS has been reported to detect early left ventricular systolic dysfunction. The pathophysiological underpinnings, regional distribution, and prognostic significance of LS in CA are unclear. METHODS: All patients underwent echocardiography, and 53 underwent CMR. The native hearts of the 3 patients who received heart transplants were subjected to histological examination. For each of the 17 left ventricular segments in the American Heart Association model, we evaluated LS, late gadolinium enhancement (LGE) by CMR, and cardiac amyloid deposition. Univariate and multivariate analyses were performed at 6 months to identify variables associated with major adverse cardiac events (MACE). RESULTS: We studied 79 patients with CA; 26 had AL, 36 M-TTR, and 17 WT-TTR. Mean LS was -10 ± 4%. Both LS and amyloid deposits showed a basal-to-apical gradient. The mean LS and number of segments with LGE were similar across the 3 CA types. LS correlated with LGE and amyloid burden (r = 0.72). LGE was seen in the 6 basal segments in all WT-TTR patients. During the median follow-up of 11 months (range 4 to 17 months), 36 (46%) patients experienced MACE. Independent predictors of MACE were apical LS (cutoff, -14.5%), N-terminal pro-B-type natriuretic peptide (cutoff, 4,000 ng/l), and New York Heart Association functional class III to IV heart failure. CONCLUSIONS: Basal-to-apical LS abnormalities are similar across CA types and reflect the amyloid burden. Apical LS independently predicts MACE.

Inhibition by eicosapentaenoic acid of IL-1beta-induced PGHS-2 expression in human microvascular endothelial cells: involvement of lipoxygenase-derived metabolites and p38 MAPK pathway.

Prostaglandin H synthase 2 (PGHS-2), a highly inducible isoenzyme, is responsible for overproduction of the prostaglandins (PGs) in inflammatory sites. We established that among fish oil polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA), but not docosahexaenoic acid (DHA), greatly decreased interleukin-1beta (IL-1beta)-induced PGHS-2 expression in human pulmonary microvascular endothelial cells (HPMECs). Lipoxygenase products 12 (S)-hydroperoxyeicosapentaenoic acid ((S)-HpEPE), 15 (S)-HpEPE and leukotriene (LT) D5 reproduced similar inhibitory effect, suggesting that they may be the intermediate metabolites responsible for PGHS-2 down-regulation by EPA. Accordingly, the EPA effect is prevented by nordihydroguaiaretic acid (NDGA) and by REV 5901, nonspecific and specific 5-lipoxygenase inhibitors, respectively. Besides, inhibition of cyclooxygenase activity by ibuprofen, indomethacin or aspirin was not able to prevent this effect. Moreover, cyclooxygenase metabolites of EPA (PGs D3, E3 and I3) markedly potentiate IL-1beta-induced PGHS-2 expression, probably by increasing intracellular cAMP levels. Peroxisome proliferator-activated receptors (PPARs) are known to be activated by fatty acids (FAs) such as EPA. We found here that HPMECs express only weak amounts of PPARalpha and PPARgamma whose activation by synthetic agonists, Wy-14,643 and ciglitazone, does not cause any inhibition of IL-1beta-induced PGHS-2 expression. This finding ruled out the involvement of PPARs in the EPA inhibitory effect. In addition, we established that EPA, which failed to inhibit nuclear factor-kappaB (NF-kappaB) activation, suppressed p38 mitogen-activated protein kinase (MAPK) phosphorylation in stimulated HPMECs. Our data demonstrate that EPA, unlike DHA, down-regulates PGHS-2 expression in HPMECs probably through its 5-lipoxygenase-dependent metabolites and advocates a beneficial role for this FA in limiting inflammatory response.

Physiological genomics of human arteries: quantitative relationship between gene expression and arterial stiffness.

BACKGROUND: Previous genomic studies with human tissues have compared differential gene expression between 2 conditions (ie, normal versus diseased) to identify altered gene expression in a binary manner; however, a potentially more informative approach is to correlate the levels of gene expression with quantitative physiological parameters. METHODS AND RESULTS: In this study, we have used this approach to examine genes whose expression correlates with arterial stiffness in human aortic specimens. Our data identify 2 distinct groups of genes, those associated with cell signaling and those associated with the mechanical regulation of vascular structure (cytoskeletal-cell membrane-extracellular matrix). Although previous studies have concentrated on the contribution of the latter group toward arterial stiffness, our data suggest that changes in expression of signaling molecules play an equally important role. Alterations in the profiles of signaling molecules could be involved in the regulation of cell cytoskeletal organization, cell-matrix interactions, or the contractile state of the cell. CONCLUSIONS: Although the influence of smooth muscle contraction/relaxation on arterial stiffness could be controversial, our provocative data would suggest that further studies on this subject are indicated.

Contemporary results of mitral valve repair for infective endocarditis.

OBJECTIVES: We sought to evaluate the feasibility and immediate and late results of mitral valve repair (MVRep) for acute and healed endocarditis. BACKGROUND: Improvements in techniques of MVRep have extended its feasibility in complex lesions, but experience with endocarditis is limited. METHODS: Among 78 patients operated on for mitral endocarditis between 1990 and 1999, 63 underwent MVRep. The repair was performed for acute endocarditis in 25 patients (40%) at a median of 20 days after the onset of treatment and in 38 patients (60%) for healed endocarditis after a median of 11 months. RESULTS: Repair of the mitral valve was feasible in 63 patients (81%). This repair involved annuloplasty in 61 patients (97%), valve resection in 49 (78%), shortening or transposition of chordae in 29 (46%), suture of perforation in 18 (29%), a pericardial patch in 12 (19%), and a partial mitral homograft in 7 (11%). Associated procedures were aortic valve replacement in 11 patients, bypass grafting in 3, and tricuspid repair in 2. Early complications were two deaths (3.2%), one re-operation for severe mitral regurgitation and one re-operation for subsequent aortic endocarditis. The seven-year rate of event-free survival was 78 +/- 6% in the global series. Multivariate predictors of event-free survival were hypertension (p < 0.006) and intervention for acute endocarditis (p < 0.026). Five-year survival rates were 96 +/- 4% after MVRep for acute endocarditis and 91 +/- 5% for healed endocarditis. CONCLUSIONS: Mitral valve repair is frequently feasible and gives good results in patients with infective endocarditis. Patients operated on for acute endocarditis experience more events during follow-up than those operated on after healed endocarditis but have excellent late survival.

Expression, regulation and role of the MAGUK protein SAP-97 in human atrial myocardium.

OBJECTIVE: In various cell types, membrane-associated guanylate kinases proteins called MAGUK play a major role in the spatial localization and clustering of ion channels. Here, we studied the expression and role of these anchoring proteins in human right atrial myocardium by means of various molecular, biochemical and physiological methods. METHODS AND RESULTS: SAP-97, PSD-95, Chapsyn and SAP-102 messengers were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) on mRNA extracted from both whole myocardium and isolated myocytes. Western blot revealed that the MAGUK protein SAP-97 and, to a lesser extent, PSD-95, is abundantly expressed in human atrial myocardium, while Chapsyn are almost undetectable. Confocal microscopic visualization of cryosection of atrial myocardium stained with the anti-PSD-95 family antibody showed positive staining at the plasma membrane level and cell extremity. Calpain-I cleaved both SAP-97 and PSD-95 proteins, resulting in an accumulation of short bands, including an 80-kDa band that was also detected in the cytosolic protein fraction. Immunoprecipitation of SAP-97 co-precipitated hKv1.5 channels, and vice versa. Co-expression of cloned SAP-97 and hKv1.5 channels in Chinese hamster ovarian (CHO) cells increased the K(+) current (157.00+/-19.45 pA/pF vs. 344.50+/-58.58 pA/pF at +50 mV). CONCLUSIONS: The protein SAP-97 is abundantly expressed in human atrial myocardium in association with hKv1.5 channels, and probably contributes to regulating the functional expression of the latter.