Alison Calver

Does Routine Pressure Wire Assessment Influence Management Strategy at Coronary Angiography for Diagnosis of Chest Pain? The RIPCORD Study

Background—The use of coronary angiography (CA) for diagnosis and management of chest pain (CP) has several flaws. The assessment of coronary artery disease using fractional flow reserve (FFR) is a well-validated technique for describing lesion-level ischemia and improves clinical outcome in the context of percutaneous coronary intervention. The impact of routine FFR at the time of diagnostic CA on patient management has not been determined. Methods and Results—Two hundred patients with stable CP underwent CA for clinical indications. The supervising cardiologist (S.C.) made a management plan based on CA (optimal medical therapy alone, percutaneous coronary intervention, coronary artery bypass grafting, or more information required) and also recorded which stenoses were significant. An interventional cardiologist then measured FFR in all patent coronary arteries of stentable diameter (≥2.25 mm). S.C. was then asked to make a second management plan when FFR results were disclosed. Overall, after disclosure of FFR data, management plan based on CA alone was changed in 26% of patients, and the number and localization of functional stenoses changed in 32%. Specifically, of 72 cases in which optimal medical therapy was recommended after CA, 9 (13%) were actually referred for revascularization with FFR data. By contrast, of 89 cases in whom management plan was optimal medical therapy based on FFR, revascularization would have been recommended in 25 (28%) based on CA. Conclusions—Routine measurement of FFR at CA has important influence both on which coronary arteries have significant stenoses and on patient management. These findings could have important implications for clinical practice. Clinical Trial Registration—URL: http://www.clinicaltrial.gov. Unique identifier: NCT01070771.

Personalised antiplatelet therapy in stent thrombosis: observations from the Clopidogrel Resistance in Stent Thrombosis (CREST) registry

Objective Previous studies have demonstrated significant heterogeneity in responses to antiplatelet therapy (APT), and high residual platelet reactivity is associated with the risk of ischaemic events, including stent thrombosis (ST). The prevalence of APT hyporesponsiveness in a ‘real world’ registry of ST patients and the feasibility of personalising APT are reported. Patients and setting 39 consecutive patients admitted to a single regional cardiothoracic centre with definite ST were prospectively evaluated. Interventions Response to aspirin and clopidogrel was measured following discharge using short thrombelastography (TEG), a rapid, well validated near patient platelet function test. Treatment modification in hyporesponders comprised an increase in aspirin dose and/or changing clopidogrel to prasugrel or ticagrelor. Short TEG was repeated following treatment modification to ensure an adequate response had been achieved. Results 12 (31%) patients had an adequate response to both aspirin and clopidogrel, 16 (41%) were hyporesponsive to clopidogrel alone, one (3%) was hyporesponsive to aspirin alone and 10 (26%) were hyporesponsive to both aspirin and clopidogrel. Following treatment modification, an adequate response to aspirin and P2Y12 agent was achieved in 10 (91%) and 22 (85%) patients, respectively. None has presented with a further ST episode. Conclusions There is a high prevalence of hyporesponsiveness to APT in patients with ST. Improved APT efficacy can be achieved by tailored therapy. Short TEG is a plausible platelet function test that can be used to deliver point of care personalised APT.

Effect of clopidogrel withdrawal on platelet reactivity and vascular inflammatory biomarkers 1 year after drug-eluting stent implantation: results of the prospective, single-centre CESSATION study

Background The optimal duration of clopidogrel treatment, particularly following drug-eluting stent (DES) implantation, remains contentious. Previous studies have observed a clustering of adverse events following clopidogrel cessation 1u2005year after DES, the aetiology of which is poorly understood. Objective To investigate, in the prospective CESSATION study, the effect of clopidogrel withdrawal at 1u2005year after DES implantation on (i) arachidonic acid (AA)- and adenosine diphosphate (ADP)-induced platelet aggregation, and (ii) biomarkers of vascular inflammation, including soluble CD40 ligand (sCD40L), high-sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6). Methods and results The prospective CESSATION study was undertaken in 33 patients receiving aspirin and due to discontinue clopidogrel 1u2005year after DES. Platetet reactivity was measured using short thromboelastography, and compliance with aspirin determined from serum thromboxane B2 (TXB2) levels. Venesection was performed at 4u2005weeks and 24u2005h before, and at 24u2005h, 48u2005h, 1, 2 and 4u2005weeks after, clopidogrel cessation. Following clopidogrel withdrawal, there was (i) a predictable increase in ADP-induced platelet aggregation (ii) an unexpected significant increase in AA-induced platelet aggregation (iii) a decline in IL-6 and hsCRP at 1 week and 4 weeks respectively; and (iv) a non-significant increase in sCD40L at 4 weeks TXB2 levels were consistently suppressed, indicating complete inhibition of cyclo-oxygenase-1 by aspirin. Conclusion An aspirin-independent, time-dependent increase in AA-induced platelet activation following clopidogrel withdrawal in patients with a DES has been described. New insights into a potential mechanism for the observed clustering of adverse events that occur early after clopidogrel cessation have been provided. These findings raise the question as to whether AA-induced clotting is an appropriate test of aspirin sensitivity.

Haemodynamic significance of ostial side branch nipping following percutaneous intervention at bifurcations: a pressure wire pilot study

Stenting of a coronary artery narrowing across a bifurcation with a side branch artery may result in a significant angiographic stenosis (nipping) of the side branch. If this causes symptoms of chest pain or ischaemic ECG changes at the time of the procedure, additional angioplasty (with or without stent insertion) through the stent struts is usually undertaken to improve blood flow into the side branch, but this increases subsequent risks of restenosis and stent thrombosis in the main vessel. In the absence of symptoms or ECG abnormalities, the functional significance of side branch nipping is uncertain and opinion on whether to treat a nipped side branch remains divided.1–4nnThe coronary pressure-derived fractional flow reserve (FFR) is a lesion-specific means of determining the functional significance of coronary artery narrowings, but its value in assessing side branch nipping is not known.nnThis pilot study aimed to assess the correlation between the FFR across nipped side branch arteries that have been crossed by main vessel stents, with the degree of angiographic narrowing at the side branch ostium. The potential role of the coronary pressure wire in guiding treatment of the nipped side branch is considered.nnThis study was registered with Southampton University NHS Trust R&D Department and approved by the local ethics committee. All patients gave written informed consent.nnAll patients were scheduled for elective percutaneous intervention (PCI) for symptoms of chronic stable …

Intracoronary Multi-link stents: experience in 218 patients using aspirin alone

Objectives To assess procedural outcome, complications, and clinical follow up in 218 patients who underwent treatment with 297 Multi-link (Guidant) stents implanted without the use of intravascular ultrasound (IVUS) or quantitative coronary angiography (QCA), and using aspirin alone as antiplatelet therapy. Methods The case records and angiograms were reviewed and the patients were contacted by telephone to determine their symptoms and any adverse events at follow up. Data were analysed using Fisher’s exact test. Results Of the 218 patients included in the study, 45 had multivessel intracoronary intervention, and 55 had unstable angina. The mean (SD) length of hospital stay following the procedure was 2.0 (2.1) days. There were two early deaths at less than 30 days, and two deaths during follow up at more than 100 days. Ten patients suffered complications during the first 30 days: four had subacute stent thrombosis, of whom two died and two were treated successfully with coronary artery bypass grafting; five had a non-Q wave myocardial infarction; and one had a femoral false aneurysm. Patient outcome was analysed according to stent diameter (3.0u2009mm or less, or 3.5u2009mm or more) and by angina status (stable or unstable). In patients in whom at least one stent was 3.0u2009mm diameter, four of 86 patients suffered acute stent occlusion, whereas in the 132 patients in whom all stents were at least 3.5u2009mm diameter there were no cases of stent occlusion (pu2009=u20090.02). In the unstable angina group two of 55 patients suffered acute stent occlusion compared to two of 163 patients in the stable angina group (NS). In patients with unstable angina and at least one stent of 3.0u2009mm diameter, the acute occlusion rate was 7.1% (two of 28 patients). Three of the four patients with stent occlusion had undergone complex procedures. Twenty eight patients were restudied for recurrent symptoms during the follow up period. Of these, eight patients had restenosis within their stent. In seven of these patients the stent size was 3.0u2009mm diameter, and in the remaining patient the stent size was 4.0u2009mm diameter. Three of the 28 patients restudied had developed new disease remote from the stented site, and 17 had patent stents and no significant other coronary lesion. Conclusions This study suggests that coronary intervention using the Multi-link stent is safe and effective using aspirin alone, without IVUS or QCA, when stent diameter is greater than 3.0u2009mm. All cases of stent occlusion in this series occurred in patients in whom at least one stent was 3.0u2009mm diameter, with stent occlusion being higher in patients with unstable angina compared to those with stable angina. Additional antiplatelet therapy may be beneficial in those patients in whom Multi-link stent diameter is less than 3.5u2009mm, particularly in those with unstable angina, but is not necessary for patients receiving Multi-link stents of 3.5u2009mm diameter or greater.

Lesson of the month 1: Beware the atypical presentation: eosinophilic granulomatosis with polyangiitis presenting as acute coronary syndrome

We describe the case of a 45-year-old woman presenting with troponin positive cardiac-sounding chest pain. An initial emergency angiogram demonstrated two vessel coronary disease, including a distal right coronary artery occlusion. No percutaneous coronary intervention was performed and the patient was treated medically. At re-presentation with further pain a few days later, coronary angiography demonstrated no significant coronary lesions. After consideration of other multisystem symptoms and raised eosinophil count, the patient was diagnosed with eosinophilic granulomatosis with polyangiitis (formerly known as Churg-Strauss syndrome) presenting with coronary arteritis. This case should remind physicians to be vigilant and to consider non-atherosclerotic causes of acute coronary syndrome presentation, which should not always result in a stent.

Uterine artery embolisation for massive uterine fibroids in the presence of submassive pulmonary emboli

A 46-year-old woman was admitted to our hospital with acute shortness of breath and pre-syncope. She had known massive uterine fibroids with a history of menorrhagia and dysmenorrhoea, and had been awaiting total abdominal hysterectomy and bilateral salpingo-oophorectomy. She had no past or family history of venous thromboembolism (VTE). She was an ex-smoker with a 16-pack/year smoking history. On examination, she looked unwell, was sweaty and clammy, but apyrexial. Her heart rate was 130 per minute and her blood pressure was 140/95 mmHg. She was tachypnoeic with a respiratory rate of 28 breaths per minute; however, her chest was clear. Abdominal examination revealed an enormous uterus, equivalent to the size of a 30-week pregnancy. There was no clinical evidence of deep vein thrombosis (DVT). She was hypoxic: oxygen saturation on air was 88%; arterial blood gas measurement on 100% oxygen—pH 7.4, PO2 29.0mmHg, PCO2 3.5mmHg, bicarbonate 18.5mmol/L, base excess of 7.5 mol/L. Her full blood count revealed a microcytic anaemia with a mean cellular volume of 67.9 fl (normal: 81–99 fl) and haemoglobin of 9.4 g/dL (normal: 12.0–15.0 g/L). Her D-dimer was significantly elevated at 1.7 Ag/mL (normal: <0.5 Ag/mL). Other blood tests including renal profile, liver function, thyroid function, C-reactive protein and clotting profile were all within normal limits. Her 12 lead electrocardiogram demonstrated sinus rhythm with right bundle branch block and T wave inversion in V1-3 with classic ‘S1QIIITIII’ changes. Her Chest X-ray showed blunting of the basal pulmonary arteries particularly on the right. Transthoracic echocardiography findings were consistent with submassive pulmonary embolism: the left ventricular size and function was normal; the right ventricle was dilated with moderately impaired systolic function; the right atrium was also dilated; the inferior vena cava was distended and failed to collapsewith inspiration; the estimated right ventricular systolic pressure was 50 mmHg. A contrast CT pulmonary angiogram revealed occlusive thrombus in the proximal basal left and mid and basal right pulmonary arteries. She was initially managed with aggressive fluid resuscitation and was commenced on intravenous unfractionated heparin (target APTT ratio of 2.0–3.0). On day 3 she began to heavily menstruate and required a total of nine units of blood over the ensuing 10 days. She was given subcutaneous Zoladex and 30 mg TDS provera to reduce her menstrual blood loss. On day 13 she underwent iliac venography and inferior cavography with insertion of a temporary IVC filter. No free intravascular thrombus was seen in either common iliac vein or within the IVC. There was however significant compression on all three of these veins. Immediately following this, she underwent uterine artery embolisation (UAE). At the time of UAE, her uterus and dominant fibroid measured 3800 and 3220 mL, respectively. Two weeks post-UAE her caval filter was removed, via a jugular route, without complication. A follow up pelvic MRI, one month later, confirmed complete fibroid degeneration with migration of the fibroid into the endometrial cavity (Fig. 1). The uterus measured 2200 mL and the fibroid 1000 mL, correlating with a 42% and 69% respective relative reduction in size. At six weeks she passed a large ‘steak-sized’ degenerate fibroid. At three months pelvic ultrasound showed that the uterus had reduced to 315 mL and the fibroid volume was 1.5 mL. The patient has made a complete recovery and has been given life-long warfarin.

37 Transoesophageal Echocardiography Underestimates Transvalvular Gradients following Trans-Catheter Aortic Valve Implantation (TAVI) – Implications for Clinical Practice

Background Trans-catheter aortic valve implantation (TAVI) is an effective treatment for high risk patients with severe aortic stenosis. As with all prosthetic valves, it is important to document accurate post-procedural gradients for future comparison. This study aimed to determine whether there was a difference between gradients measured immediately post-procedure by trans-oesophageal echocardiography (TOE) compared with the pre-discharge trans-thoracic echocardiogram (TTE). We also compared pre-TAVI gradients obtained by TTE vs. TOE. Methods We used local and national databases to gather demographics on TAVI patients from our centre and to identify peak and mean aortic gradients measured by TTE and TOE prior to TAVI and also immediately following TAVI deployment (TOE) and prior to discharge (TTE). Data were compared using the paired t-test. Results We identified 106 TAVI patients with complete echocardiographic data-sets. The mean age was 81+/-8 yrs and 62(54%) were male. All patients received an Edwards Sapien valve. Pre-TAVI, there were no significant differences between TOE and TTE for both peak (72.2+/-24.8 mmHg vs 71.9+/- 24.0 mmHg, p = 0.83) and mean (41.4+/-15.0 mmHg vs 42.4+/-14.9 mmHg,p = 0.22) gradients. However, following TAVI, the peak trans-valvular gradients by TOE vs. TTE were 12+/-6 mmHg vs 22+/-9 mmHg (p < 0.001) and mean trans-valvular gradients were 6+/-3 mmHg vs 11+/-5 mmHg (p < 0.001). There were 36 patients with LV dysfunction: the results were unchanged after excluding these patients (peak gradient 12+/-6 mmHg vs. 23+/-9 mmHg, p < 0.001). Conclusions Although TTE and TOE perform similarly prior to TAVI, the immediate post-procedural assessment of trans-aortic gradients by TOE leads to significant under-estimation compared to TTE. Intra-procedural TOE should not be used to define baseline peak and mean aortic gradients after TAVI.Abstract 37 Figure 1 Pre-TAVI TTE (A) vs TOE (B) and post-TAVI TOE (C) vs TTE (D)