The impact of transoesophageal echocardiography in elderly patients with infective endocarditis.

BACKGROUND: Infective endocarditis (IE) increasingly involves older patients. Geriatric status may influence diagnostic and therapeutic decisions. AIM: To describe transoesophageal echocardiography (TEE) use in elderly IE patients, and its impact on therapeutic management and mortality. METHODS: A multicentre prospective observational study (ELDERL-IE) included 120 patients aged ≥75 years with definite or possible IE: mean age 83.1±5.0; range 75-101 years; 56 females (46.7%). Patients had an initial comprehensive geriatric assessment, and 3-month and 1-year follow-up. Comparisons were made between patients who did or did not undergo TEE. RESULTS: Transthoracic echocardiography revealed IE-related abnormalities in 85 patients (70.8%). Only 77 patients (64.2%) had TEE. Patients without TEE were older (85.4±6.0 vs. 81.9±3.9 years; P=0.0011), had more comorbidities (Cumulative Illness Rating Scale-Geriatric score 17.9±7.8 vs. 12.8±6.7; P=0.0005), more often had no history of valvular disease (60.5% vs. 37.7%; P=0.0363), had a trend toward a higher Staphylococcus aureus infection rate (34.9% vs. 22.1%; P=0.13) and less often an abscess (4.7% vs. 22.1%; P=0.0122). Regarding the comprehensive geriatric assessment, patients without TEE had poorer functional, nutritional and cognitive statuses. Surgery was performed in 19 (15.8%) patients, all with TEE, was theoretically indicated but not performed in 15 (19.5%) patients with and 6 (14.0%) without TEE, and was not indicated in 43 (55.8%) patients with and 37 (86.0%) without TEE (P=0.0006). Mortality was significantly higher in patients without TEE. CONCLUSIONS: Despite similar IE features, surgical indication was less frequently recognized in patients without TEE, who less often had surgery and had a poorer prognosis. Cardiac lesions might have been underdiagnosed in the absence of TEE, hampering optimal therapeutic management. Advice of geriatricians should help cardiologists to better use TEE in elderly patients with suspected IE.

A fatal case of Human Herpesvirus 6 chronic myocarditis in an immunocompetent adult.

BACKGROUND: Human Herpesvirus 6 (HHV-6) is an important cause of fulminant or acute viral myocarditis in immunocompromised or immunocompetent patients. However the physiopathological mechanisms of HHV-6 related acute myocarditis and the involvement of subsequent HHV-6 reactivation phases in the development of chronic cardiomyopathies remain to be assessed. OBJECTIVES: To describe a case of fatal HHV-6 chronic myocarditis in an immunocompetent adult. STUDY DESIGN: Case report and detailed histological and viral diagnoses by combination of histology/immunohistochemistry and polymerase chain reaction techniques on cardiac tissues. RESULTS: Histopathological analysis of ventricular tissues showed large interstitial and scarring fibrotic areas with a moderate mononuclear cell infiltrate compatible with histological aspect of chronic myocarditis. Detection of both HHV-6 by real-time PCR and viral glycoproteins in mononuclear and endothelial cells by immunohistochemistry evidenced an ongoing cardiac HHV-6 replication with viral late protein synthesis activity. CONCLUSIONS: This case report indicates that HHV-6 can establish a chronic active myocarditis leading to heart failure in immunocompetent subjects.

Viral causes of human myocarditis.

The diagnosis of acute myocarditis is complex and challenging. The use of the Dallas criteria in the diagnosis of myocarditis is associated with poor sensitivity and specificity because of the sampling error related to the often focal distribution of the specific histological lesions in cardiac tissue and the variability in pathological interpretation. To improve histological diagnosis, additional virological evaluation of cardiac tissues is required, with immunohistochemical and polymerase chain reaction (PCR) techniques allowing identification and quantification of viral infection markers. The diagnostic gold standard is endomyocardial biopsy (EMB) with the histological Dallas criteria, in association with new immunohistochemical and PCR analyses of cardiac tissues. Using real-time PCR and reverse transcription PCR assays, parvovirus B19, Coxsackie B virus, human herpesvirus 6 (HHV-6) type B and adenovirus have been detected in 37, 33, 11 and 8% of EMB, respectively, from young adults (aged<35 years) with histologically proven acute myocarditis. Viral co-infections have also been found in 12% of acute myocarditis cases, generally parvovirus B19 plus HHV-6. Moreover, herpesviruses such as the Epstein-Barr virus or cytomegalovirus can also be associated with myocarditis after heart transplantation. During the clinical course of myocarditis, the immunohistochemical detection of enterovirus, adenovirus or parvovirus B19 capsid proteins or herpesvirus late proteins is necessary to differentiate a viral cardiac infection with replication activities from a persistent or latent cardiac infection. These new viral diagnostic approaches can lead to better identification of the aetiology of myocarditis and may therefore enable the development and evaluation of specific aetiology-directed treatment strategies.

Gingival fibroblast inhibits MMP-7: evaluation in an ex vivo aorta model.

Matrix metalloproteinases (MMP) play a deleterious role in numerous vascular diseases. In contrast, gingival matrix remodelling is adequately regulated by the gingival fibroblast (GF). Here, we aimed to evaluate the GF activity on MMP-7 expression and secretion in coculture with aorta rings. We evaluated MMP-7 transcription and secretion in rabbit aorta rings cultured or not with gingival fibroblasts in collagen gels. GF induced an increase of TIMP-1 transcription and secretion, followed, similarly to other MMPs, by the formation of TIMP-1/MMP-7 complexes. There was also a decrease of MMP-7 mRNA by RT-PCR in aorta rings cocultured with gingival fibroblasts. Interestingly, in contrast with other MMPs (which were not influenced at a transcription level), GF stimulated the release of TGF-beta1, which in turn inhibited the transcription and synthesis of MMP-7, as shown by neutralizing MMP-7 inhibition due to gingival fibroblast by overexpressing decorin (a TGF beta 1 inhibitor) or by silencing TGF beta 1 using siRNA. We showed that healing properties of the GF could be transposed to another organ, i.e., ex vivo aneurism model, implicating a down-regulation of MMP-7.

Comparison of operator radiation exposure with optimized radiation protection devices during coronary angiograms and ad hoc percutaneous coronary interventions by radial and femoral routes.

AIMS: Although underestimated by interventional cardiologists for a long time, radiation exposure of operators and patients is currently a major concern. The objective of the present operator-blinded registry was to compare related-peripheral arterial route radiation exposure of operators. METHODS AND RESULTS: During 420 consecutive coronary angiograms (CAs) and percutaneous coronary interventions (PCIs), four interventional cardiologists were blindly screened. Radiation exposures were assessed using electronic personal dosimeters. Protection of operator was ensured using a lead apron, low leaded flaps, and leaded glass. Radiation exposure of operators was significantly higher using the radial route when compared with the femoral route for both CAs and CAs followed by ad hoc PCIs: 29.0 [1.0-195.0] microSv vs. 13.0 [1.0-164.0] microSv; P < 0.0001 and 69.5 [4.0-531.0] microSv vs. 41.0 [2.0-360.0] microSv; P = 0.018, respectively. Similarly, radiation exposure of patients was significantly higher using the radial route when compared with the femoral route for both CAs and CAs followed by ad hoc PCIs. Moreover, procedural durations and fluoroscopy times were significantly higher throughout the radial route. CONCLUSIONS: Although the radial route decreases peripheral arterial complication rates, increased radiation exposure of operators despite extensive use of specific protection devices is currently a growing problem for the interventional cardiologist health. Radial route indication should be promptly reconsidered in the light of the present findings.

Infected multiple fibroelastomas in hypertrophic cardiomyopathy.

Cardiac papillary fibroelastomas are rare benign tumors of the heart with potential for life-threatening complications. The incidence of multiple lesions is less than 10% of all reported cases. Preoperative transesophageal echocardiography is important for detecting all cardiac sites involving this tumor, because excision of all such tumors must be performed to prevent serious complications. Here, the first ever case is reported of multiple infected papillary fibroelastoma of the mitral valve, aortic valve and left ventricular outflow tract with massive mitral insufficiency in a patient with hypertrophic cardiomyopathy.

Transplantation of cardiac-committed mouse embryonic stem cells to infarcted sheep myocardium: a preclinical study.

BACKGROUND: Heart failure develops after myocardial infarction and is a major cause of morbidity and mortality. The ability to direct differentiation of embryonic stem cells (ESC) towards a cardiomyogenic phenotype makes them an attractive therapeutic option for cardiac repair, but species-specific and individual-specific immunological imprinting remains a hurdle. Our aim was to ascertain whether the purported immune privilege of ESC allows for their cross-species engraftment in a clinically relevant large-animal model. METHODS: We studied engraftment and differentiation of cardiac-committed mouse ESC in 18 sheep in which a myocardial infarction had been induced; nine controls received medium and nine sheep (five of which were immunosuppressed) received ESC. The gain in myocardial function was measured by echocardiography 1 month after cell transplantation. FINDINGS: Cardiac-committed murine ESC engrafted in infarcted myocardium of immunosuppressed and immunocompetent sheep, and differentiated into mature cardiomyocytes that expressed connexins. Colonisation of the scar area by ESC was accompanied by a functional benefit of the damaged myocardium. Left-ventricular ejection fraction deteriorated in the control group by a median of 9.9% (range -20 to 0.3) relative to baseline (p=0.011) whereas in the treated group it improved by 6.6% (-5.7 to 50.8; comparison between groups p=0.002). INTERPRETATION: These findings obtained in a clinically relevant large-animal model of heart failure strengthen the potential therapeutic use of ESC to regenerate the severely dysfunctional myocardium and bring additional evidence for an immune privilege of these cells.

Adenovirus-mediated gene transfer of superoxide dismutase and catalase decreases restenosis after balloon angioplasty.

BACKGROUND: Reactive oxygen species (ROS) production increases after injury and potentially contributes to restenosis after angioplasty. We therefore evaluated the effect of adenovirus-mediated gene transfer (Ad) of superoxide dismutase (SOD) and catalase (CAT) on ROS production and restenosis after balloon angioplasty. METHODS: O(2)(-) and H(2)O(2 )production was quantified in cultured cells after incubation with either LPS or CuSO(4). Angioplasty and gene transfer were performed in rabbit atherosclerotic iliac arteries. One artery was injected with AdSOD and AdCAT, while the contralateral artery was injected with an adenovirus carrying no transgene, and served as control. RESULTS: ROS production was significantly decreased after adenovirus-mediated gene transfer of SOD and CAT as compared with control. Treated arteries showed less restenosis (32 +/- 27 vs. 63 +/- 19%, p = 0.003) and less constrictive remodeling (1.2 +/- 0.3 vs. 0.9 +/- 0.2, p = 0.02) than control arteries. Arteries injected with AdSOD and AdCAT showed better vasoreactivity to acetylcholine (11 +/- 4 vs. -1 +/- 6%, p < 0.05), lower collagen density (43 +/- 16 vs. 53 +/- 23%, p = 0.03), and lower inflammatory cell infiltration (22 +/- 6 vs. 36 +/- 11%, p = 0.04) than control arteries. CONCLUSIONS: Our data suggest that adenovirus-mediated gene transfer of SOD and CAT reduced oxidative stress, restenosis, collagen accumulation, and inflammation and improved endothelial function after angioplasty.

Skeletal myoblast transplantation through a catheter-based coronary sinus approach: an effective means of improving function of infarcted myocardium.

AIMS: This study was designed to assess the functional effects of a transvenous coronary sinus technique of skeletal myoblast delivery in infarcted myocardium. METHODS AND RESULTS: An anterior myocardial infarction was created percutaneously in 14 sheep. Simultaneously, a muscle biopsy was harvested and expanded. Two weeks later, sheep were instrumented percutaneously with a dedicated catheter incorporating an extendable needle for puncture of the venous wall and, under endovascular ultrasound guidance, a microcatheter was advanced through the needle into the target scar for cell delivery. Following the baseline echocardiographic assessment of left ventricular (LV) function, sheep were randomly allocated to receive four-staged in-scar injections of either autologous cells (n=7) or culture medium (n=7). Two months later, LV function was reassessed blindly and hearts were explanted for subsequent histological and immunohistochemical analysis. There were no acute procedural complications. Baseline LV ejection fraction (EF) was significantly lower in transplanted sheep than in controls [38% (35-48) vs. 51% (38-55), respectively, P=0.03; median (range)]. Two months later, LVEF was significantly higher in the transplanted group than in controls [50% (47-56) vs. 39% (36-47), respectively, P=0.002]. Clusters of myoblasts were identified by histology and immunohistochemistry in three of the seven transplanted sheep. CONCLUSION: These data suggest the functional efficacy of the transvenous coronary sinus technique as a less invasive means of cell delivery to infarcted myocardium.

Direct stent implantation without predilatation through 5 French guiding catheter following transfemoral coronary angiogram: a feasibility study.

Direct stenting (DS) is accepted as reducing procedural cost and duration and 5 Fr guiding catheters as lowering peripheral vascular complications. We aimed to evaluate the feasibility and safety of both strategies. We retrospectively studied 150 consecutive patients treated with DS strategy using a 5 Fr femoral approach. A need for 6 Fr devices or balloon predilatation defined 5 Fr DS failure. Procedural success was defined as good angiographic result (residual stenosis < 30% and TIMI flow 3) without ischemic complications. A total of 161 out of 174 lesions were elected as suitable for DS. The success rate of 5 Fr DS was 87.6% (141/161 lesions). The procedural success rate was 92% (138/150 patients). The angiographic success rate was 96.3% (155/161 lesions). Other complications were six non-Q-wave MI and one repeat angioplasty for acute in-stent thrombosis. Only one major peripheral vascular complication occurred. Direct stenting through 5 Fr guiding catheters in selected lesions is safe and effective with a low incidence of peripheral arterial complications.

Effect of adenovirus-mediated overexpression of decorin on metalloproteinases, tissue inhibitors of metalloproteinases and cytokines secretion by human gingival fibroblasts.

Decorin is a small leucine-rich proteoglycan that plays a role in control of cell proliferation, cell migration, collagen fibrillogenesis and modulation of the activity of TGF-beta. In the present study, we investigated the effects of decorin on the production of metalloproteinases (MMP-1, -2, -3, -9 and -13), tissue inhibitors of metalloproteinases (TIMP-1, -2) and cytokines (TGF-beta, IL-1beta, IL-4 and TNF-alpha). Decorin was overexpressed in cultured human gingival fibroblasts using adenovirus-mediated gene transfer. Decorin infection resulted in decreased protein levels of MMP-1 and MMP-3 whereas MMP-2 and TIMP-2 secretion was increased. MMP-9, MMP-13 and TIMP-1 were not affected by decorin infection. Cytokine measurements by ELISA showed that decorin overexpression reduced TGF-beta and IL-1beta. In contrast, IL-4 and TNF-alpha levels were markedly increased in decorin-infected cells. These results suggest that decorin could modulate the expression of certain metalloproteinases and their inhibitors, as well as the production of cytokines. Altogether, our data suggest that decorin might play a pivotal role in tissue remodeling by acting on the balance between extracellular matrix synthesis and degradation.