Corrigendum to: A rare cause of culture negative bioprosthetic valve endocarditis: a case report of Aggregatibacter aphrophilus infection.

[This corrects the article DOI: 10.1093/ehjcr/ytab003.].

A rare cause of culture negative bioprosthetic valve endocarditis: a case report of Aggregatibacter aphrophilus infection.

Background: The prevalence of culture negative infective endocarditis (IEC) is reported as 2-7% though this figure may be as high as 70% in developing countries.1 This higher rate will, at least in part, be due to reduced diagnostic facilities though some data suggests higher rates even when appropriate cultures were taken. The frequency is significantly elevated in patients who have already been exposed to antibiotics prior to blood cultures.1 , 2 A rare cause of culture negative IEC is the HACEK group of organisms that are normal habitants of the oropharyngeal flora and account for 1-3% of native valve endocarditis.3 Aggregatibacter aphrophilus (A. aphrophilus) is a member of the HACEK group of organisms. Case summary: A 32-year-old gentleman with a previous bioprosthetic aortic valve presented with a 1-week history of diarrhoea, vomiting, malaise, and weight loss. He was awaiting redo surgery for stenosis of the bioprosthesis, which had been inserted aged 17 for aortic stenosis secondary to a bicuspid valve. The initial blood tests revealed liver and renal impairment with anaemia. A transoesophageal echocardiogram demonstrated a complex cavitating aortic root abscess, complicated by perforation into the right ventricle. He underwent emergency redo surgery requiring debridement of the aortic abscess, insertion of a mechanical aortic prosthesis (St Jude Medical, USA), annular reconstruction and graft replacement of the ascending aorta. Despite antibiotic therapy, he remained septic with negative blood and tissue cultures. Bacterial 16S rRNA gene sequencing confirmed A. aphrophilus infection, for which intravenous ceftriaxone was initiated. This was subsequently changed to ciprofloxacin due to neutropenia. The patient self-discharged from the hospital during the third week of antibiotic therapy. One week later, he was re-admitted with fever, night sweats, and dyspnoea. Transthoracic echocardiogram revealed a large recurrent aortic abscess cavity around the aortic annulus fistulating into the right heart chambers; this was confirmed by a computed tomography scan. There was dehiscence of the patch repair. Emergency redo aortic root replacement (25 mm mechanical valve conduit, ATS Medical, USA) and annular reconstruction was performed with venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. VA-ECMO was weaned after 3 days. The patient completed a full course of intravenous meropenem and ciprofloxacin and made a good recovery. Discussion: IEC with oropharyngeal HACEK organisms is rare and difficult to diagnose, due to negative blood culture results. The broad-range polymerase chain reaction and gene sequencing with comparison to the DNA database is useful in these circumstances. This case demonstrates the importance of the 16S rRNA gene sequencing for HACEK infection diagnosis and appropriate antibiotic treatment.

Patient-specific 3D hemodynamics modelling of left coronary artery under hyperemic conditions.

The purpose of this study is to investigate the effect of various degrees of percentage stenosis on hemodynamic parameters during the hyperemic flow condition. 3D patient-specific coronary artery models were generated based on the CT scan data using MIMICS-18. Numerical simulation was performed for normal and stenosed coronary artery models of 70, 80 and 90% AS (area stenosis). Pressure, velocity, wall shear stress and fractional flow reserve (FFR) were measured and compared with the normal coronary artery model during the cardiac cycle. The results show that, as the percentage AS increase, the pressure drop increases as compared with the normal coronary artery model. Considerable elevation of velocity was observed as the percentage AS increases. The results also demonstrate a recirculation zone immediate after the stenosis which could lead to further progression of stenosis in the flow-disturbed area. Highest wall shear stress was observed for 90% AS as compared to other models that could result in the rupture of coronary artery. The FFR of 90% AS is found to be considerably low.

The influence of artery wall curvature on the anatomical assessment of stenosis severity derived from fractional flow reserve: a computational fluid dynamics study.

This study aims to investigate the influence of artery wall curvature on the anatomical assessment of stenosis severity and to identify a region of misinterpretation in the assessment of per cent area stenosis (AS) for functionally significant stenosis using fractional flow reserve (FFR) as standard. Five artery models of different per cent AS severity (70, 75, 80, 85 and 90%) were considered. For each per cent AS severity, the angle of curvature of the arterial wall varied from straight to an increasingly curved model (0°, 30°, 60°, 90° and 120°). Computational fluid dynamics was performed under transient physiologic hyperemic flow conditions to investigate the influence of artery wall curvature on the pressure drop and the FFR. The findings in this study may be useful in in vitro anatomical assessment of functionally significant stenosis. The FFR decreased with increasing stenosis severity for a given curvature of the artery wall. Moreover, a significant decrease in FFR was found between straight and curved models discussed for a given severity condition. These findings indicate that the curvature effect was included in the FFR assessment in contrast to minimum lumen area (MLA) or per cent AS assessment. The MLA or per cent AS assessment may lead to underestimation of stenosis severity. From this numerical study, an uncertainty region could be evaluated using the clinical FFR cutoff value of 0.8. This value was observed at 81.98 and 79.10% AS for arteries with curvature angles of 0° and 120° respectively. In conclusion, the curvature of the artery should not be neglected in in vitro anatomical assessment.

Feasibility and Efficacy of Herculink Elite ((TM)) Biliary Stent Implantation in Large Coronary Arteries (≥ 5 mm) and Venous Conduits: An Observational Study.

BACKGROUND AND OBJECTIVES: Percutaneous coronary intervention (PCI) in patients with lesions of large calibre coronary arteries (≥ 5 mm) and saphenous venous grafts (≥ 5 mm) can be challenging. There are no separate guidelines available to treat these vessels with PCI. Standard coronary stents of 4 mm diameter are used to treat these lesions conventionally but carry the risk of under deployment, distortion of stent architecture and future stent thrombosis even if they are subsequently expanded beyond 5 mm. METHODS AND RESULTS: Biliary stents (Herculink Elite™) provide a better alternative to standard coronary stents in these patients. These stents are of larger diameter (5-7 mm) and can be safely delivered over a 6 French sheath. In our case series, we demonstrate the use of intravascular ultrasound examination to confirm that biliary stents provide improved stent strut apposition within the coronary artery associated with extremely low repeat revascularisation rates. CONCLUSION: Our paper highlights that PCI of lesions in patients with large calibre coronary arteries can successfully be achieved using biliary stents.

Blood thrombogenicity is independently associated with serum TSH levels in post-non-ST elevation acute coronary syndrome.

CONTEXT: Higher serum TSH levels, both within the reference range and in those with subclinical hypothyroidism (SCH), have been associated with increased risk of atherosclerosis and cardiovascular (CV) events in a number of cross-sectional and longitudinal studies. OBJECTIVE: Our objective was to evaluate blood thrombogenicity in patients post-non-ST elevation acute coronary syndrome (NSTE-ACS) in relation to their thyroid function. DESIGN, PATIENTS, AND OUTCOME MEASURE: At 1 week after troponin-positive NSTE-ACS, 70 patients who had been treated with optimal antiplatelet and secondary prevention therapy were studied. Patients with known thyroid disease or on medications affecting thyroid function were excluded. Blood thrombogenicity was assessed using the ex vivo Badimon perfusion chamber. RESULTS: Serum TSH was associated with higher thrombus burden (ß = .30; P = .01) independent of other well-established CV risk factors. Patients with SCH (n = 12; 17%) had a higher thrombus burden than euthyroid individuals as evidenced by the area of the thrombus: mean (SD) 23 608 (10 498) vs 16 661 (10 902) µm(2)/mm (P = .02). However, this association was not evident when the analysis was limited to patients with serum TSH within the reference range. In addition, neither serum free T4 nor free T3 had any significant association with thrombus area. CONCLUSION: Serum TSH levels, particularly in the SCH range, are associated with higher thrombus burden despite optimal recommended secondary prevention therapy after NSTE-ACS. This may explain the higher CV risk seen in SCH patients. Future trials to assess the effect of individualized antithrombotic as well as thyroid hormone replacement therapy to reduce atherothrombotic risk in this population are needed.

Differences in thrombus structure and kinetics in patients with type 2 diabetes mellitus after non ST elevation acute coronary syndrome.

INTRODUCTION: Despite optimal secondary prevention therapy following non-ST elevation acute coronary syndrome (NSTE-ACS), recurrent thrombotic events are more frequent in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This exploratory study was aimed to evaluate quantitative and qualitative aspects of thrombus. In 28 patients with and without T2DM treated with aspirin and clopidogrel we assessed thrombus quantity using an ex-vivo chamber, platelet reactivity, thrombus ultrastructure and thrombus kinetics one week after NSTE-ACS. RESULTS: T2DM was associated with increased thrombus [14861 (8003 to 30161) vs 8908 (6812 to 11996), µ(2)/mm, median (IQR), p=0.045] and platelet reactivity. In addition, diabetic thrombus showed lower visco-elastic tensile strength [(-0.2(-1.7 to 0.7) vs 1.0(-0.9 to 3.3), p=0.044)] and was more resistant to autolysis [(27.8(11.7 to 70.7) vs 78.8(68.5 to109.6) mm/min, p=0.002)]. On SEM, fibrin fibres in diabetes were thinner, with higher lateral interlinkage and mesh-like organisation. Thrombus quantity correlated inversely with thrombus retraction (r=-0.450 p=0.016) but not with platelet reactivity (r=0.153, p=0.544). CONCLUSIONS: Despite optimal antiplatelet therapy, T2DM patients after NSTE-ACS developed increased thrombus of lower tensile strength and slower retraction. SEM revealed loosely arranged fibrin fibres. Our data showed significant differences in the magnitude as well as structural and mechanistic characteristics of thrombus in patients with T2DM.

Effect of porous media of the stenosed artery wall to the coronary physiological diagnostic parameter: a computational fluid dynamic analysis.

Functional assessment of a coronary artery stenosis severity is generally assessed by fractional flow reserve (FFR), which is calculated from pressure measurements across the stenosis. The purpose of this study is to investigate the effect of porous media of the stenosed arterial wall on this diagnostic parameter. To understand the role of porous media on the diagnostic parameter FFR, a 3D computational simulations of the blood flow in rigid and porous stenotic artery wall models are carried out under steady state and transient conditions for three different percentage area stenoses (AS) corresponding to 70% (moderate), 80% (intermediate), and 90% (severe). Blood was modeled as a non Newtonian fluid. The variations of pressure drop across the stenosis and diagnostic parameter were studied in both models. The FFR decreased in proportion to the increase in the severity of the stenosis. The relationship between the percentage AS and the FFR was non linear and inversely related in both the models. The cut-off value of 0.75 for FFR was observed at 81.89% AS for the rigid artery model whereas 83.61% AS for the porous artery wall model. This study demonstrates that the porous media consideration on the stenotic arterial wall plays a substantial role in defining the cut-off value of FFR. We conclude that the effect of porous media on FFR, could lead to misinterpretation of the functional severity of the stenosis in the region of 81.89 %-83.61% AS.

Evaluation of functional severity of coronary artery disease and fluid dynamics' influence on hemodynamic parameters: A review.

Coronary Artery Disease (CAD) is responsible for most of the deaths in patients with cardiovascular diseases. Diagnostic coronary angiography analysis offers an anatomical knowledge of the severity of the stenosis. The functional or physiological significance is more valuable than the anatomical significance of CAD. Clinicians assess the functional severity of the stenosis by resorting to an invasive measurement of the pressure drop and flow. Hemodynamic parameters, such as pressure wire assessment fractional flow reserve (FFR) or Doppler wire assessment coronary flow reserve (CFR) are well-proven techniques to evaluate the physiological significance of the coronary artery stenosis in the cardiac catheterization laboratory. Between the two techniques mentioned above, the FFR is seen as a very useful index. The presence of guide wire reduces the coronary flow which causes the underestimation of pressure drop across the stenosis which leads to dilemma for the clinicians in the assessment of moderate stenosis. In such condition, the fundamental fluid mechanics is useful in the development of new functional severity parameters such as pressure drop coefficient and lesion flow coefficient. Since the flow takes place in a narrowed artery, the blood behaves as a non-Newtonian fluid. Computational fluid dynamics (CFD) allows a complete coronary flow simulation to study the relationship between the pressure and flow. This paper aims at explaining (i) diagnostic modalities for the evaluation of the CAD and valuable insights regarding FFR in the evaluation of the functional severity of the CAD (ii) the role of fluid dynamics in measuring the severity of CAD.

Thrombus and antiplatelet therapy in type 2 diabetes mellitus. A prospective study after non-ST elevation acute coronary syndrome and a randomised, blinded, placebo-controlled study in stable angina.

Type 2 diabetes mellitus (T2DM) is associated with higher rates of thrombotic complications in patients with coronary artery disease (CAD) despite optimal medical therapy. Thrombus area was measured in T2DM and non-diabetic patients receiving aspirin and clopidogrel 7-10 days after troponin positive Non ST-elevation acute coronary syndrome (NSTE-ACS). Secondly, we assessed response to clopidogrel in naive patients with T2DM and stable CAD in a randomised controlled trial. Thrombus area was measured by Badimon chamber and platelet reactivity by VerifyNow®. In T2DM patients presenting with NSTE-ACS, thrombus area was greater compared to non-diabetic patients (mean ± SD, 20,512 ± 12,567 [n=40] vs. 14,769 ± 8,531 [n=40] µm²/mm, p=0.02) Clopidogrel decreased thrombus area among stable CAD patients with T2DM (mean ± SD, Clopidogrel [n=45]: 13,978 ± 5,502 to 11,192 ± 3,764 µm²/mm vs. placebo [n=45]: 13,959 ± 7,038 to 14,201 ± 6,780 µm²/mm, p<0.001, delta values: clopidogrel vs. placebo, mean ± SD, 2,786 ± 4,561 vs. -249 ± 2,478, p<0.0005). Only 44% of patients with CAD and T2DM responded to clopidogrel as per VerifyNow® (cut-off PRUz value of ≥ 240). Importantly, no correlation was observed between thrombus area and VerifyNow® values (rho 0.08, p=0.49). Thrombus area values were similar among hypo-responders and good responders to clopidogrel (mean thrombus area ± SD: 12,186 ± 4,294 vs. 10,438 ± 3,401; p=0.17). Type 2 diabetes mellitus is associated with an increased blood thrombogenicity among NSTE-ACS patients on currently recommended medical therapy. Thrombus area was significantly reduced in all stable CAD patients independently of their response to clopidogrel therapy.

Increased atherothrombotic burden in patients with diabetes mellitus and acute coronary syndrome: a review of antiplatelet therapy.

Patients with diabetes mellitus presenting with acute coronary syndrome have a higher risk of cardiovascular complications and recurrent ischemic events when compared to nondiabetic counterparts. Different mechanisms including endothelial dysfunction, platelet hyperactivity, and abnormalities in coagulation and fibrinolysis have been implicated for this increased atherothrombotic risk. Platelets play an important role in atherogenesis and its thrombotic complications in diabetic patients with acute coronary syndrome. Hence, potent platelet inhibition is of paramount importance in order to optimise outcomes of diabetic patients with acute coronary syndrome. The aim of this paper is to provide an overview of the increased thrombotic burden in diabetes and acute coronary syndrome, the underlying pathophysiology focussing on endothelial and platelet abnormalities, currently available antiplatelet therapies, their benefits and limitations in diabetic patients, and to describe potential future therapeutic strategies to overcome these limitations.

Glycoprotein IIb/IIIa inhibitor associated severe thrombocytopenia in patients with coronary artery disease: Clinical course and outcomes.

Thrombocytopenia, both at baseline and acquired throughout admission is associated with poor clinical outcomes in patients with coronary artery disease. It is not known whether severe thrombocytopenia in patients receiving glycoprotein IIb/IIIa inhibitors (GPI) carries the same risk as thrombocytopenia from other aetiologies. We identified 50 consecutive patients referred for percutaneous coronary intervention (PCI) who developed severe thrombocytopenia (<50 × 10(9) cells/l) and followed their clinical course to 30 days. Two groups were compared: (1) severe thrombocytopenia following GPI usage and (2) severe thrombocytopenia without exposure to GPI. Baseline platelet counts were higher in GPI group (201 ± 62 vs. 112 ± 83 × 10(9) cells/l, p < 0.05). Patients in GPI group had more profound thrombocytopenia yet quicker recovery of platelet counts. The GPI group received fewer blood product transfusions (red cells: 0.1 ± 0.4 vs. 1.3 ± 2.0, p < 0.05, platelets: 0.22 ± 0.6 vs. 1.1 ± 1.7, p < 0.05) and had lower event rates for the primary end point of 30-day mortality (3.7% vs. 42.1%, p < 0.05), and for major bleeding (0% vs. 15.8%, p < 0.05). In conclusion, GPI associated severe thrombocytopenia follows a distinct clinical course when compared to severe thrombocytopenia due to other aetiologies. Our results suggest that patients who develop severe thrombocytopenia following GPI therapy may be managed conservatively with careful monitoring.

Unfractionated heparin during elective PCI: fixed dose or weight adjusted?

INTRODUCTION: To assess two different dosing strategies of unfractionated heparin (UFH) during elective percutaneous coronary intervention (PCI). AIMS: The optimal dose of heparin during elective PCI in patients with stable angina is unknown. Existing guidelines are based on limited data. We interrogated data from the PCI database. Patients with stable angina undergoing planned transradial PCI for uncomplicated single lesions were included. The main endpoint was troponin I release. We compared a fixed heparin dose (3000 U) UFH to a weight-adjusted dose. RESULTS: Of 698 patients 244 (35.0%) received fixed dose (3000 U) and 454 (65.0%) 70 U/kg weight-adjusted UFH. There was no significant difference in median troponin between the fixed dose and the weight-adjusted groups; 0.17 ng/mL versus 0.14; P= 0.21. The proportion of troponin positive patients was similar in both groups (61.9% in the fixed dose group vs. 58.1%; P= 0.37). There were no deaths or major ischemic events during hospitalization. There was no bleeding requiring transfusion or delaying hospital discharge. CONCLUSION: In conclusion, this retrospective observational study of elective transradial PCI demonstrated that a reduced, fixed dose of periprocedural heparin was associated with similar postprocedural troponin levels when compared to a standard weight-adjusted regime. Our study further questions the optimal dose of heparin required during elective PCI and suggests a need for further trials.

Mitral valve involvement as a predominant feature of cardiac amyloidosis.

Cardiac involvement in systemic amyloidosis carries poor prognosis with a median survival of 5 months.(1) The authors report an unusual presentation of cardiac amyloidosis in the form of predominant mitral regurgitation. The patient responded very well to medical therapy with subsequent improvement of mitral valve dysfunction. The authors would like to highlight this multisystem involvement and the presence of a complex overlap of systemic features.

Transfemoral contralateral technique to retrieve knotted coronary artery catheter using Amplatz Goose Neck snare catheter.

Performing coronary angiography in very older patients can prove a challenge due to vessels calcification and torturousity. Manipulation of coronary catheters to engage the artery ostium may result in over twisting and can result in complications ranging from a minor 'kink' to a complex 'knot'. The authors describe a novel method to retrieve the complex twisted coronary catheter using snare technique, after usual steps to remove the coronary catheter failed.