Investigating the impact of non-gated thoracic CT prior to CTCA to reduce layered testing.

AIM: To determine the proportion of computed tomography (CT) coronary angiography (CTCA) referrals with coronary artery calcification (CAC) evident on previous non-cardiac CT imaging and how this impacted the diagnostic yield for CTCA, the requirement for additional diagnostic testing, and the associated costs to confirm or refute obstructive coronary artery disease (CAD). MATERIALS AND METHODS: A retrospective review of CTCA examinations was undertaken between 01/05/2018 and 31/05/2020 in which the examinations were cross referenced for previous non-gated thoracic CT at Royal United Hospitals Bath. Major epicardial vessel CAC on baseline CT was re-evaluated by published semi-quantitative methods, giving a per-patient CAC score (mild = 1-3, moderate = 4-6, severe >6). Subsequent incomplete CTCA diagnostic yield, further testing, and cost implications were examined. RESULTS: Of the 2140 CTCA examinations identified, 13% (280/2140) had a preceding non-gated thoracic CT (53% female, age 63 ± 11 years). The incomplete diagnostic rate increased with CAC grade, mild 32%, (RR 12; 95% CI 4-40), moderate 64% (RR 25; 95% CI 8-80), severe 75%, (RR 29; 95% CI 9-94). Additional diagnostic testing occurred in 4% for the mild CAC category, and 14% and 42% for moderate and severe, respectively. When severe CAC was identified on a non-gated thoracic CT a cost saving of £171/patient (dobutamine stress echo [DSE]) and £61/patient (myocardial perfusion scintigraphy [MPS]) was established with a direct to functional testing pathway. CONCLUSIONS: In patients referred for CTCA where severe CAC was identified on a preceding non-gated thoracic CT a direct to functional testing altered management in 42% of cases and was cost-effective.

Coronary artery calcification on routine CT has prognostic and treatment implications for all ages.

AIMS: Guidelines have recommended reporting coronary artery calcification (CAC) if present on chest CT imaging regardless of indication. This study assessed CAC prevalence, prognosis and the potential clinical impact of its reporting. METHODS: We performed a single-centre retrospective analysis (January-December 2015) of 1400 chest CTs (200 consecutive within each age group: <40, 40-49, 50-59, 60-69, 70-79, 80-89, ≥90). CTs were re-reviewed for CAC presence and severity and excluded if prior coronary intervention. Comorbidities, statin prescription and clinical outcomes (myocardial infarction [MI], stroke, all-cause mortality) were recorded. The impact of reporting CAC was assessed against pre-existing statin prescriptions. RESULTS: 1343 patients were included (mean age 63±20 years, 56% female). Inter- and intra-observer variability for CAC presence at re-review was almost perfect (κ 0.89, p < 0.001; κ 0.90, p < 0.001) and for CAC grading was substantial and almost perfect (κ 0.68, p < 0.001; κ 0.91, p < 0.001). CAC was observed in 729/1343 (54%), more frequently in males (p < 0.001) and rising age (p < 0.001). A high proportion of patients with CAC in all age groups had no prior statin prescription (range: 42% [80-89] to 100% [<40]). The 'number needed to report' CAC presence to potentially impact management across all ages was 2. 689 (51%) patients died (median follow-up 74-months). CAC presence was associated with risk of MI, stroke and all-cause mortality (p < 0.001). After adjusting for confounders, severe calcification predicted risk of all-cause mortality (HR 1.8 [1.2-2.5], p = 0.002). CONCLUSION: Grading of CAC was reproducible, and although prevalence rose with age, prognostic and treatment implications were maintained in all ages.

CT coronary angiography-guided cardiovascular risk screening in asymptomatic patients: is it time?

Cardiovascular disease (CVD) is the leading cause of death in the UK, whilst millions live with various forms of the disease. Coronary artery disease constitutes a significant portion of this morbidity and mortality, and is the leading cause of premature death. Increasing focus is thus being placed on the optimisation of CVD prevention, where risk screening plays a key role. Indeed, the decline in age-adjusted cardiovascular mortality achieved up to now has been largely attributed to primary preventative therapies (e.g., statins) introduced earlier in the disease process. National initiatives exist to improve cardiovascular health at a population level, but in its current form, CVD screening at the individual level is predominantly undertaken using multivariate risk scores based on population-based data. These have multiple innate flaws, highlighted in this review. Non-invasive imaging plays a key role in the screening of other disease processes, helping to personalise the screening process. Although the coronary artery calcium score as a screening tool has a role in national and international guidance, whether a shift to screening with computed tomography coronary angiography (CTCA) is now appropriate is open for discussion. Image acquisition techniques continue to improve with reducing radiation exposure and an ever-expanding evidence-base for additional prognostic data offered by CTCA. This enables the potential identification of sub-clinical atherosclerosis, including with novel artificial intelligence techniques. This review aims to report current guidelines regarding cardiac CT imaging in the asymptomatic primary prevention setting, advances in various CT technologies and future opportunities for progress in this field.

Transcatheter and endovascular stent graft management of coarctation-related pseudoaneurysms.

OBJECTIVE: Surgical correction of congenital aortic coarctation can lead to a number of important problems including late pseudoaneurysm formation. Redo surgery has a significant risk. Endovascular stent graft repair is increasingly used but there are limited data regarding this indication. We describe the experience of two UK congenital referral centres. DESIGN: Retrospective analysis of patients treated with endovascular aortic stent grafting for late pseudoaneurysms. SETTING: Two UK congenital heart centres, Bristol Heart Institute and Leeds General Infirmary. PATIENTS: 17 patients were treated 2006-2012. This represents all patients treated with this technique. MAIN OUTCOME MEASURES: Procedural and postprocedure success and complications. RESULTS: The average time from index repair to endovascular repair of pseudoaneurysm was 24.6 years. The majority (70.6%) had patch aortoplasty as the original surgical procedure and 41.2% were not under follow-up or discharged. Stent grafting procedural success rate was 100%. Median hospital stay postprocedure was 3 days. There was no procedural mortality or immediate complication. There were four minor early and three minor late complications. Imaging follow-up was available for an average of 31.6 months (range 6-65 months). All patients have demonstrated positive remodelling of the pseudoaneurysm with no incidence of continued expansion or stent graft failure up to 5 years following implant. CONCLUSIONS: Endovascular stent graft treatment of pseudoaneurysms show promising results in a population who have a high risk of surgical re-intervention. Complication rates appear to be low and recovery is quick. Longer-term data remain essential to scrutinise stent graft performance in this situation.

Permanent pacemaker insertion after CoreValve transcatheter aortic valve implantation: incidence and contributing factors (the UK CoreValve Collaborative).

BACKGROUND: Permanent pacemaker (PPM) requirement is a recognized complication of transcatheter aortic valve implantation. We assessed the UK incidence of permanent pacing within 30 days of CoreValve implantation and formulated an anatomic and electrophysiological model. METHODS AND RESULTS: Data from 270 patients at 10 centers in the United Kingdom were examined. Twenty-five patients (8%) had preexisting PPMs; 2 patients had incomplete data. The remaining 243 were 81.3±6.7 years of age; 50.6% were male. QRS duration increased from 105±23 to 135±29 milliseconds (P<0.01). Left bundle-branch block incidence was 13% at baseline and 61% after the procedure (P<0.001). Eighty-one patients (33.3%) required a PPM within 30 days. Rates of pacing according to preexisting ECG abnormalities were as follows: right bundle-branch block, 65.2%; left bundle-branch block, 43.75%; normal QRS, 27.6%. Among patients who required PPM implantation, the median time to insertion was 4.0 days (interquartile range, 2.0 to 7.75 days). Multivariable analysis revealed that periprocedural atrioventricular block (odds ratio, 6.29; 95% confidence interval, 3.55 to 11.15), balloon predilatation (odds ratio, 2.68; 95% confidence interval, 2.00 to 3.47), use of the larger (29 mm) CoreValve prosthesis (odds ratio, 2.50; 95% confidence interval, 1.22 to 5.11), interventricular septum diameter (odds ratio, 1.18; 95% confidence interval, 1.10 to 3.06), and prolonged QRS duration (odds ratio, 3.45; 95% confidence interval, 1.61 to 7.40) were independently associated with the need for PPM. CONCLUSION: One third of patients undergoing a CoreValve transcatheter aortic valve implantation procedure require a PPM within 30 days. Periprocedural atrioventricular block, balloon predilatation, use of the larger CoreValve prosthesis, increased interventricular septum diameter and prolonged QRS duration were associated with the need for PPM.

Atrial tachycardia with 1:1 atrioventricular conduction precipitated by propafenone.

A 58-year-old man presented to the emergency department with sudden onset rapid palpitations and significant presyncope while walking on the flat. The previous day he had undergone DC cardioversion for atrial fibrillation (AF) which had been initially successful. However, 6 h after cardioversion he was aware of intermittently raised but regular heart rates. On arrival at the emergency department (ED) he was well with no haemodynamic compromise. The ECG showed an atrial tachycardia instead of AF. Medications consisted of propafenone 300 mg twice daily, bisoprolol 5 mg at night and warfarin. Bisoprolol was increased to 5 mg twice daily and he was discharged with a plan for outpatient ablation. He collapsed in the hospital car park with rapid palpitations, chest tightness and vagal symptoms. On return to the ED he was hypotensive with a heart rate of 200 bpm. The ECG showed 1:1 atrioventricular conduction (AV) of the atrial tachycardia which promptly improved after administering intravenous atenolol. Class 1c antiarrhythmic agents such as propafenone can precipitate 1:1 AV conduction of atrial tachycardias resulting in dangerous exacerbations of ventricular rate or even malignant tachyarrhythmias. It is therefore essential that concomitant AV blocking agents are used both prophylactically or acutely in suspected cases.

Myocardial infarction associated with the administration of intravenous ephedrine and metaraminol for spinal-induced hypotension.

A 31-year-old female with no risk factors for cardiac disease suffered a peri-operative myocardial infarction during an elective gynaecological procedure under spinal anaesthesia. The timing and nature of cardiac symptoms suggest that the myocardial infarction was caused by coronary artery vasospasm secondary to ephedrine and/or metaraminol, which were administered to treat spinal-induced hypotension. We review the recent literature and case reports on myocardial infarction attributed to sympathomimetic drugs, and recommend the use of sublingual or intravenous nitrates when signs or symptoms of coronary arterial vasospasm become evident during their use.

In vitro biological evaluation of beta-TCP/HDPE--A novel orthopedic composite: a survey using human osteoblast and fibroblast bone cells.

Beta-tricalcium phosphate reinforced high density polyethylene (beta-TCP/HDPE) was prepared to simulate bone composition and to study its capacity to act as bone tissue. This material was produced by replacing the mineral component and collagen soft tissue of the bone with beta-TCP and HDPE, respectively. The biocompatibility of the composite samples with different volume fractions of TCP (20, 30 and 40 vol %) was examined in vitro using two osteoblast cell lines G-292 and Saos-2, and also a type of fibroblast cell isolated from bone tissue, namely human bone fibroblast (HBF) by proliferation, and cell adhesion assays. Cell-material interaction with the surface of the composite samples was examined by scanning electron microscopy (SEM). The effect of beta-TCP/HDPE on the behavior of osteoblast and fibroblast cells was compared with those of composite and negative control samples; polyethylene (PE) and tissue culture polystyrene (TPS), respectively. In general, the results showed that the composite samples containing beta-TCP as reinforcement supported a higher rate of proliferation by various bone cells after 3, 7, and 14 days of incubation compared to the composite control sample. Furthermore, more osteoblast cells were attached to the surface of the composite samples when compared to the composite control samples after the above incubation periods (p < 0.05), while in the case of HBF an equal or even higher number of cells adhered to PE was observed. The number of adhered osteoblast cells was almost equal and in some days even higher than the number of adhered cells on negative control sample, while in the case of fibroblast this difference was significantly higher than TPS (p < 0.05). Adhered cells presented a normal morphology by SEM and many of the cells were observed to be undergoing cell division. These findings indicate that beta-TCP/HDPE composites are biocompatible, nontoxic, and act to stimulate proliferation and adhesion of the cells, whether osteoblast or fibroblast.

Flecainide cardiotoxicity precipitated by electrolyte imbalance. Caution with thiazide diuretics.

A man presented with recurrent syncope, weakness and fatigue. His ECG showed marked QRS widening and he had gross hyponatraemia and hypokalaemia. His medications included bendroflumethiazide (long term) and flecainide (started 2 months previously). This presentation was consistent with flacainide cardiotoxicity exacerbated by electrolyte disturbance. The syncopal episodes probably represented life-threatening arrhythmias. The ECG and symptoms resolved completely once the electrolytes were corrected. Increased cardiotoxicity with hypokalaemia is documented, but not widely recognised. Hyponatraemia-induced flecainide cardiotoxicity has not been documented. The clinical effects of flecainide are due to use-dependent block of sodium channels. There are reports that support the use of hypertonic sodium salts to reverse flecainide toxicity via antagonism at the receptor. By this rationale, hyponatraemia would lead to Flecainide toxicity. Flecainide has been shown to reduce salt absorption in animal bowel. It is possible that in combination with bendroflumethiazide it acted synergistically to produce profound electrolyte disturbance. Flecainide cardiotoxicity has a significant mortality and can present non-specifically. Thus, early recognition is essential. This case demonstrates the importance of strict electrolyte control in patients who are on flecainide. We would discourage concomitant use of flecainide and bendroflumethiazide.

The effect of partially stabilized zirconia on the biological properties of HA/HDPE composites in vitro.

The effect of partially stabilized zirconia (PSZ) on the biological properties of the hyroxyapatite - high density polyethylene (HA/HDPE) composites was studied by investigating the simultaneous effect of hydroxyapatite and PSZ volume fractions on the in vitro response of human osteoblast cells. The biocompatibility of composite samples with different volume fraction of HA and PSZ powders was assessed by proliferation, alkaline phosphatase (ALP) and cell attachment assays on the osteoblast cell line (G-292) in different time periods. The effect of composites on the behavior of G-292 cells was compared with those of HDPE and TPS (Tissue Culture Poly Styrene as negative control) samples. Results showed a higher proliferation rate of G-292 cells in the presence of composite samples as compared to the HDPE sample after 7 and 14 days of incubation period. ALP production rate in all composite samples was higher than HDPE and TPS samples. The number of adhered cells on the composite samples was higher than the number adhered on the HDPE and TPS samples after the above mentioned incubation periods. These findings indicates that the addition of PSZ does not have any adverse affect on the biocompatibility of HA/HDPE composites. In fact in some experiments PSZ added HA/HDPE composites performed better in proliferation, differentiation and attachment of osteoblastic cells.

Effect of reinforcement particle size on in vitro behavior of beta-tricalcium phosphate-reinforced high-density polyethylene: a novel orthopedic composite.

Beta-tricalcium phosphate-reinforced high-density polyethylene (beta-TCP/HDPE) is a new biomaterial, which was made to simulate bone composition and study its capacity to act like bony tissues. This material was produced by replacing mineral component and collagen soft tissue of bone with beta-TCP and HDPE, respectively. The biocompatibility of composite samples with different volume fractions of TCP (20, 30, and 40 vol %) and two different particle sizes (80-100 and 120-140 mesh size) was examined in vitro using the osteoblast cell line G-292 by proliferation, alkaline phosphatase (ALP) production, and cell adhesion assays. Cell-material interaction on the surface of the composites was observed by scanning electron microscopy (SEM). The effect of beta-TCP particle size on behavior of the osteoblast cell line was compared between two groups of the composite samples containing smaller and larger reinforcement particle sizes as well as with those of a negative control. In general, results showed that the composite samples containing larger particles supported a higher rate of proliferation and ALP production by osteoblast cells after 3, 7, and 14 days of incubation compared to the composite samples with smaller particle size and control. Furthermore, more cells were attached to the surface of composite samples containing larger particle size when compared to the smaller particle size composites (p<0.05). This number was nearly equal with numbers adhered on negative control [tissue culture polystyrene (TPS)] and significantly higher in comparison with composite control [polyethylene (PE)] (p<0.05). Adhered cells presented a normal morphology by SEM and many of the cells were seen to be undergoing cell division. These findings indicate that beta-TCP/HDPE composites are biocompatible, nontoxic, and in some cases, act to stimulate proliferation of the cells, ALP production, and cell adhesion when compared to the control counterparts. Furthermore, beta-TCP/HDPE samples with larger reinforcement particle size were shown to possess better biological properties.

In vitro evaluation of biocompatibility of beta-tricalcium phosphate-reinforced high-density polyethylene; an orthopedic composite.

Beta-tricalcium phosphate-reinforced high-density polyethylene (beta-TCP/HDPE) is a new biomaterial which was made as a copy of bone composition with the aim of replacement of bony tissues. The composite samples were prepared using medical grade TCP powder and granular polyethylene. The raw materials were first compounded and the resulting composite preforms were compression molded into desired shape. The biocompatibility of composite samples with different volume fractions of TCP (20, 30, and 40 vol %) was assessed by proliferation, alkaline phosphatase (ALP), and cell adhesion assays using G-292 osteoblast cells. Cell-material interaction on the surface of the composites was observed by scanning electron microscopy (SEM). The effect of beta-TCP/HDPE on the behavior of G-292 cells was compared with those of a composite and a negative control samples. Results showed the composite samples had a higher proliferation rate of G-292 cells in the presence of composite samples as compared to the composite control sample after 3, 7, and 14 days of incubation period. ALP production after incubation in the presence of composite samples was seen to peak on the day 7. The number of adhered cells on the composite samples was higher than the numbers adhered on composite and negative control samples after the above incubation periods. Morphology investigation of adhered cells by SEM indicated a normal morphology and also many of the cells were in the process of cell division. The above results indicate that beta-TCP/HDPE samples are biocompatible, nontoxic, and in some cases show an increase in the proliferation rate of the cells, ALP production, and cell adhesion as compared to the control counterparts.

The effect of partially stabilized zirconia on the mechanical properties of the hydroxyapatite-polyethylene composites.

The effect of partially stabilized zirconia (PSZ) on the mechanical properties of the hydroxyapatite-high density polyethylene composites was studied by investigating the effect of hydroxyapatite and the simultaneous effect of hydroxyapatite and PSZ volume fractions on fracture strength, modulus of elasticity, and absorbed energy in the composite samples. The results showed a decrease in fracture strength, and absorbed energy with an increase in the volume fraction of hydroxyapatite content in the hydroxyapatite-polyethylene samples. Partial replacement of hydroxyapatite with PSZ particles was beneficial in the improvement of both the fracture strength and failure energy values in the composite samples. A transition from ductile to brittle behavior was observed as the volume fraction of ceramic filler particles increased in the samples.