Aortic Root Thrombus Directly After Left Ventricular Assist Device Implantation.

A 70-year-old female heart failure patient could not be weaned from temporary left ventricular mechanical support with Impella CP (Abiomed Inc, Danvers, MA) after myocardial infarction; therefore, she underwent left ventricular assist device implantation (HeartMate 3; Abbott, Chicago, IL). After uneventful surgery, the patient had an early postoperative thrombus in the aortic root, and surgical thrombectomy on extracorporeal circulation was performed on the seventh postoperative day. The patient recovered well and presented in good condition with no neurologic symptoms at the 6-month follow-up visit. Surgical excision of aortic root thrombus is a feasible option even for frail patients with a left ventricular assist device.

Après un infarctus du myocarde, une patiente de 70 ans présentant une insuffisance cardiaque n'a pas pu être sevrée d'une assistance mécanique temporaire pour le ventricule gauche par dispositif Impella CP (Abiomed Inc, Danvers, MA); elle a donc subi l'implantation d'un dispositif d'assistance ventriculaire gauche (HeartMate 3; Abbott, Chicago, IL). Après une intervention sans incident, la patiente a présenté un thrombus postopératoire précoce dans l'anneau aortique, et une thrombectomie chirurgicale sous circulation extracorporelle a été réalisée le septième jour suivant l'intervention. La patiente s'est bien rétablie et semblait en bonne santé, sans symptômes neurologiques, au moment de la visite de suivi six mois plus tard. L'excision chirurgicale du thrombus de l'anneau aortique est une option réaliste même chez les patients fragiles ayant un dispositif d'assistance ventriculaire gauche.

Evaluation of calcium loss after transcatheter aortic valve implantation.

OBJECTIVES: Aortic valve calcification and changes after transcatheter aortic valve implantation (TAVI) were specifically assessed by computed tomography (CT). The main difference between TAVI and the conventional technique is the compression of the cusps of the calcified native valve against the aortic wall before implantation. The objective of this study was to quantify the segmented calcification in the area of the basal annular plane before and after TAVI. METHODS: The CT scans of 20 patients (13 male and 7 female; mean age: 82.9 ± 8.1 years) were assessed. The aortic valve calcification was segmented; derived from this segmentation volume, mass and Hounsfield units (HU)/density of the calcifications on the annulus and cusps before and after TAVI were evaluated. Pre- and postoperative data were compared regarding potential calcification loss and calcification distances to the left and right coronary ostia. RESULTS: Significantly lower postprocedural mean volumes and masses for all cusps (P < 0.001) were found. The mean differences in the volume for the non-coronary, right-coronary and left-coronary cusp were -156.8 ± 53.73, -155.5 ± 62.54 and -115 ± 57.53 mm(3), respectively, and differences in mass were -88.78 ± 29.48, -95.2 ± 39.27 and -71.56 ± 35.62 mg, respectively. Over all cusps, mean HU increased after intervention [784.41 ± 92.5 HU (pre) and 818.63 ± 78.71 HU (post); P < 0.004]. In 80.03% of all cusps, calcification loss was found; all patients were affected. Significantly lower (P < 0.047) postprocedural mean distances were found from the left and right coronary ostia to the next calcification point. CONCLUSIONS: Our results show a significant loss of calcification in all patients after TAVI, with a reduction in the calcification distances to the coronary ostia and the compression of calcification in the area of the device landing zone. The clinical implications of this finding need to be investigated further.

Assessment of inflammatory response to transfemoral transcatheter aortic valve implantation compared to transapical and surgical procedures: a pilot study.

AIMS: Surgical aortic valve replacement (AVR) has been associated with systemic inflammatory reactions. Yet, the role of inflammation following transcatheter aortic valve implantation (TAVI) has not been fully elucidated. METHODS AND RESULTS: In a total of 40 patients evaluated by the 'heart team,' this retrospective study assessed levels of high-sensitive C-reactive protein (hs-CRP) and leukocyte counts following 'uneventful' AVR and TAVI. Four groups of matched patients were compared (AVR; transapical and transfemoral Edwards SAPIEN [TA ES and TF ES, respectively]; and transfemoral Medtronic CoreValve [TF CV]). A postprocedural increase of both hs-CRP levels and leukocyte counts was observed (P<.001) with peak levels 48 hours after the procedures. Comparing treatment groups, hs-CRP levels at 48 hours were significantly higher following AVR and TA ES compared to TF ES and TF CV (P<.04). Leukocyte counts at 48 hours were higher following TA ES compared to TF ES and TF CV (P<.03). Multivariate analysis incorporating both hs-CRP levels and leukocyte counts confirmed significant differences for all measurements over time (P<.001). Furthermore, the treatment group significantly influenced postprocedural hs-CRP levels and leukocyte counts (P<.001). CONCLUSION: Both AVR and TAVI evoke a postprocedural inflammatory response. Higher hs-CRP levels and leukocyte counts following AVR and apical TAVI suggest less inflammation following femoral procedures.

Myeloid related proteins activate Toll-like receptor 4 in human acute coronary syndromes.

INTRODUCTION: We previously reported increased expression of TLR4 on monocytes in thrombi from patients with acute coronary syndromes (ACS). In mice, myeloid related protein (MRP) 8 and MRP14, cytoplasmic proteins of neutrophils and monocytes, activate Toll-like receptor (TLR) 4 during sepsis. In human ACS, we investigated now whether the pro-inflammatory action of MRPs occurs through TLR4 in monocytes derived from thrombi. METHODS: Coronary thrombi and peripheral blood of 27 ACS patients were analyzed. CD14(+) monocytes were isolated and incubated with TLR2 ligand PM3SKA, TLR4 ligand lipopolysaccharide (LPS), MRP8, MRP14, or MRP8/14 heterocomplex. Anti-TLR4 antibodies (HTA125) were used to block TLR4 and polymyxin B (PMB) was employed to inhibit endotoxins. Before and after stimulation, the release of TNFα was measured by ELISA and the expression of TLR4 on CD14(+) monocytes was determined by flow cytometry. Further, selected pathways of downstream signaling were analyzed. RESULTS: MRP8 and MRP8/14 increased release of TNFα in cultures of CD14(+) monocytes, more in cells derived from thrombi compared with matched peripheral blood cells (p<0.001). LPS, MRP8, and MRP8/14, but much less PM3SKA and MRP14 alone, stimulated TNFα release, which can be inhibited by HTA125. MRP8/14 enhanced TLR4 expression on monocytes from thrombi (p<0.001), but not on monocytes from peripheral blood of the same patients. CONCLUSION: In ACS, MRP8 and MRP8/14 complex are specific ligands of TLR4, which induce the release of TNFα and probably other pro-inflammatory agents from monocytes. This specific MRP8/14-dependent pathway with striking similarities to sepsis increasing expression of TLR4 in thrombi appears to be involved in the pathogenesis of coronary occlusion and may represent a novel therapeutic target in ACS.

Transcatheter aortic valve implantation: impact on clinical and valve-related outcomes.

BACKGROUND: Transcatheter aortic valve implantation is an alternative to open heart surgery in patients with aortic stenosis. However, long-term data on a programmatic approach to aortic valve implantation remain sparse. METHODS AND RESULTS: Transcatheter aortic valve implantation was performed in 168 patients (median age, 84 years) in the setting of severe aortic stenosis and high surgical risk. Access was transarterial (n=113) or, in the presence of small iliofemoral artery diameter, transapical (n=55). The overall success rate was 94.1% in this early experience. Intraprocedural mortality was 1.2%. Operative (30-day) mortality was 11.3%, lower in the transarterial group than the transapical group (8.0% versus 18.2%; P=0.07). Overall mortality fell from 14.3% in the initial half to 8.3% in the second half of the experience, from 12.3% to 3.6% (P=0.16) in transarterial patients and from 25% to 11.1% (P=0.30) in transapical patients. Functional class improved over the 1-year postprocedure period (P<0.001). Survival at 1 year was 74%. The bulk of late readmission and mortality was not procedure or valve related but rather was due to comorbidities. Paravalvular regurgitation was common but generally mild and remained stable at late follow-up. At a maximum of >3 years and a median of 221 days, structural valve failure was not observed. CONCLUSIONS: Transcatheter aortic valve implantation can result in early and sustained functional improvement in high-risk aortic stenosis patients. Late outcome is determined primarily by comorbidities unrelated to aortic valve disease.

Transapical transcatheter aortic valve implantation: 1-year outcome in 26 patients.

BACKGROUND: We reported the first case of successful transapical transcatheter aortic valve implantation in a human subject in 2005 and have now completed a 12-month follow-up on our first 26 patients. This is, to date, the longest follow-up of patients undergoing transapical aortic valve implantation. METHODS: Between October 2005 and January 2007, 26 patients (13 female) underwent transcatheter transapical aortic valve implantation with either 23- or 26-mm Edwards Lifesciences transcatheter bioprostheses. All patients with symptomatic aortic stenosis were declined for conventional aortic valve replacement because of unacceptable operative risks and were not candidates for transfemoral aortic valve implantation because of poor arterial access. Clinical and echocardiographic follow-up was performed before discharge and at 1, 6, and 12 months. Data from the 17 patients who survived over 12 months were used for comparisons of the baseline and follow-up results. RESULTS: The mean age was 80 +/- 9 years, and the predicted operative mortality was 37% +/- 20% by using logistic EuroSCORE and 11% +/- 6% by using the Society of Thoracic Surgeons Risk Calculator. Valves were successfully implanted in all patients. Six patients died within 30 days (30-day mortality, 23%), and 3 patients died from noncardiovascular causes after 30 days (late mortality, 12%). Among patients who survived at least 30 days, 12-month survival was 85%. There were no late valve-related complications. New York Heart Association functional class improved significantly. The aortic valve area and mean gradient remained stable at 12 months (1.6 +/- 0.3 cm(2) and 9.6 +/- 4.8 mm Hg, respectively). CONCLUSION: Our 1-year clinical and echocardiographic outcomes suggest that transapical transcatheter aortic valve implantation is a viable alternative to conventional aortic valve replacement in selected high-risk patients.

Atrioventricular block after transcatheter balloon expandable aortic valve implantation.

OBJECTIVES: Transcatheter aortic valve replacement (AVR) is a promising approach to aortic valve disease. The implications of this new therapy are not entirely known. We describe the potential for the development of new atrioventricular (AV) block. BACKGROUND: Atrioventricular block is a known complication of conventional surgical AVR. Block is presumed to occur as a consequence of surgical trauma to the cardiac conduction tissue during excision of the diseased aortic valve and débridement of the calcified annulus. Whether AV block might occur as a consequence of nonsurgical implantation of an aortic stent valve is unknown. METHODS: We reviewed our experience with patients undergoing transcatheter AVR using both the percutaneous transarterial and the open-chest direct left ventricular apical ventriculotomy approaches. Patients were considered at high risk for conventional surgery because of comorbidities. Continuous arrhythmia monitoring was performed for at least 48 h after the valve implantation procedure. Patients who developed apparently new, clinically significant AV block were identified. RESULTS: Transcatheter AVR was successfully performed in 123 patients. Seventeen of these patients (13.8%) had pre-existing permanent pacemakers. Two patients (1.6%) required pacemaker implantation because of pre-existing intermittent bradycardia. Seven patients (5.7%) developed new and sustained complete AV block requiring pacemaker implantation. An additional 4 patients (3.3%) developed new and sustained left bundle branch block but did not require pacemaker implantation. CONCLUSIONS: As with conventional AVR surgery, transcatheter AVR may result in impaired atrioventricular conduction. Physicians and patients should be aware of the potential for AV block and pacemaker dependence.

Percutaneous transarterial aortic valve replacement in selected high-risk patients with aortic stenosis.

BACKGROUND: Percutaneous aortic valve replacement represents an endovascular alternative to conventional open heart surgery without the need for sternotomy, aortotomy, or cardiopulmonary bypass. METHODS AND RESULTS: Transcatheter implantation of a balloon-expandable stent valve using a femoral arterial approach was attempted in 50 symptomatic patients with severe aortic stenosis in whom there was a consensus that the risks of conventional open heart surgery were very high. Valve implantation was successful in 86% of patients. Intraprocedural mortality was 2%. Discharge home occurred at a median of 5 days (interquartile range, 4 to 13). Mortality at 30 days was 12% in patients in whom the logistic European System for Cardiac Operative Risk Evaluation risk score was 28%. With experience, procedural success increased from 76% in the first 25 patients to 96% in the second 25 (P=0.10), and 30-day mortality fell from 16% to 8% (P=0.67). Successful valve replacement was associated with an increase in echocardiographic valve area from 0.6+/-0.2 to 1.7+/-0.4 cm2. Mild paravalvular regurgitation was common but was well tolerated. After valve insertion, there was a significant improvement in left ventricular ejection fraction (P<0.0001), mitral regurgitation (P=0.01), and functional class (P<0.0001). Improvement was maintained at 1 year. Structural valve deterioration was not observed with a median follow-up of 359 days. CONCLUSIONS: Percutaneous valve replacement may be an alternative to conventional open heart surgery in selected high-risk patients with severe symptomatic aortic stenosis.

Myeloid-related protein 8/14 complex is released by monocytes and granulocytes at the site of coronary occlusion: a novel, early, and sensitive marker of acute coronary syndromes.

AIMS: We investigated whether myeloid-related protein 8/14 complex (MRP8/14) expressed by infiltrating monocytes and granulocytes may represent a mediator and early biomarker of acute coronary syndromes (ACS). METHODS AND RESULTS: Immunohistochemistry of coronary thrombi was done in 41 ACS patients. Subsequently, levels of MRP8/14 were assessed systemically in 75 patients with ACS and culprit lesions, with stable coronary artery disease (CAD), or with normal coronary arteries. In a subset of patients, MRP8/14 was measured systemically and at the site of coronary occlusion. Macrophages and granulocytes, but not platelets stained positive for MRP8/14 in 76% of 41 thrombi patients. In ACS, local MRP8/14 levels [22.0 (16.2-41.5) mg/L] were increased when compared with systemic levels [13.4 (8.1-14.7) mg/L, P = 0.03]. Systemic levels of MRP8/14 were markedly elevated [15.1 (12.1-21.8) mg/L, P = 0.001] in ACS when compared with stable CAD [4.6 (3.5-7.1) mg/L] or normals [4.8 (4.0-6.3) mg/L]. Using a cut-off level of 8 mg/L, MRP8/14 but not myoglobin or troponin, identified ACS presenting within 3 h from symptom onset. CONCLUSION: In ACS, MRP8/14 is markedly expressed at the site of coronary occlusion by invading phagocytes. The occurrence of elevated MRP8/14 in the systemic circulation prior to markers of myocardial necrosis makes it a prime candidate for the detection of unstable plaques and management of ACS.

Inflammatory markers at the site of ruptured plaque in acute myocardial infarction: locally increased interleukin-6 and serum amyloid A but decreased C-reactive protein.

BACKGROUND: Acute myocardial infarction (AMI) is associated with inflammation. However, it remains unclear whether it originates from the ruptured plaque or represents a systemic process. METHODS AND RESULTS: In 42 patients with AMI, a balloon-based embolization protection device and aspiration catheter (PercuSurge) were used during acute coronary interventions. Samples from the site of the ruptured plaque were taken under distal balloon occlusion. Systemic samples were taken from the aorta. Sera, plaques, and thrombi were analyzed for inflammatory markers and lipoproteins. Systemic levels of C-reactive protein (CRP), interleukin-6 (IL-6), and serum amyloid A (SAA) in the aorta amounted to 3.0 mg/L, 5.0 ng/L, and 22.1 mg/L, respectively (interquartile ranges [IQRs], 1.1 to 7.4 mg/L, 5.0 to 6.5 ng/L, and 13.9 to 27.0 mg/L, respectively). In blood surrounding ruptured plaques, local levels of IL-6 (8.9 ng/L; IQR, 5.0 to 16.9 ng/L) and SAA (24.3 mg/L; IQR, 16.3 to 44.0 mg/L) were significantly higher, whereas CRP levels (2.5 mg/L; IQR, 0.9 to 7.7 mg/L) were decreased compared with the aorta (all P<0.0001). The coronary levels of IL-6 determined in vivo showed biological activity in vitro. Harvested thrombus contained CD68-positive monocytes expressing IL-6 and showed extracellularly and intracellularly positive staining for SAA, whereas CRP was found exclusively in the cytoplasm of phagocyting white blood cells. CONCLUSIONS: Coronary levels of IL-6 and SAA at the site of plaque rupture were increased relative to the systemic circulation, indicating local production of biologically active inflammatory mediators. In contrast, CRP was locally decreased, at least in part by uptake by the phagocyting cells, suggesting a systemic origin of the protein.

Age-related changes of vitamin A status.

Ageing is an independent risk factor for the development of cardiovascular disease. The ageing process is known to be associated with increased oxidative stress and an increased risk for cardiovascular and other diseases, such as cancer. To delay this process, therapeutic strategies involving the use of naturally occurring antioxidants, such as vitamin A, have gained considerable interest. Therefore, we wanted to investigate in a model of mammalian ageing whether changes in tissue and plasma levels of vitamin A occur with increasing age. This would constitute a prime rationale for its dietary supplementation. Experiments were performed in three different age groups (4-6 months old, 19 months old, 32-35 months old) of F1 (F344 x BN) healthy male rats that were fed a normal diet without any additional supplementation. Vitamin A and carotenoids in plasma and major organs were measured by reverse-phase high-performance liquid chromatography. In 3-year-old rats, vitamin A levels were found to be decreased in plasma (P < 0.0001) as compared with young and middle-aged animals. However, they were markedly increased in the main storage organ (ie, the liver) (P < 0.01-0.0001), and also in the aortic vessel wall. They were undetectable in the heart, irrespective of age. Increased tissue levels of vitamin A, especially in the vasculature, may be part of an age-associated self-regulatory process of adaptation, possibly as a counter-regulation against oxidative tissue damage. Based upon the assumption that in elderly humans, as in our animal model, a similar demand-regulated mechanism may work independently of additional dietary vitamin A supplementation, one may question the strategy of large clinical interventional trials using vitamin A or its derivatives beyond normal dietary intake.