Heart

Danson, Edward; Byrne, Jonathan; Groves, Chris; Sapontis, James; Dworakowski, Rafal; MacCarthy, Philip; Shah, Ajay; Hill, Jonathan

doi: 10.1136/heartjnl-2014-306118.87pmid: 24922880

Background: There is limited data describing outcomes in patients undergoing percutaneous coronary intervention (PCI) or medical therapy who have been turned down for surgical revascularisation (CABG) on the basis of prohibitive risk. The independent predictors of morbidity and mortality; and role of clinical or anatomical scoring systems in this patient group are incompletely understood. Methods We analysed cardiovascular outcomes (major adverse clinical event rate, MACE: death; myocardial infarction, MI; target vessel revascularisation, TVR; and stroke) in a retrospective cohort of patients turned down for elective CABG who were treated with PCI or medical therapy in a single centre in 2012. Patients were subdivided into SYNTAX tertiles for comparing outcomes. Clinical data were gathered (age, sex, hypertension, smoking, diabetes, hyperlipidaemia, renal dysfunction, LV dysfunction, COPD, stroke, cognitive impairment, reduced mobility, peripheral vascular disease, neoplaisia, 3 vessel disease, left main disease, chronic occlusion, valve disease, sinus rhythm, permenant pacing, Euroscore II and SYNTAX scores) and independent predictors of 1 year and 30 day MACE and mortality were identified using multivariate stepwise logistic regression analysis. Results: There were a total of 77 patients with a mean(±standard error) age of 74 ± 1.2 years. The total 1 year MACE rate was 22 ± 1.9% (14% death, 8% MI, 1% TVR, 0% stroke) and 30 day MACE rate was 6 ± 1.1% (5% death, 1% MI). Within the low SYNTAX tertile (0–22), the MACE rate was significantly higher in the medically treated group (33 ± 2%) compared to the PCI group (6 ± 1%, Relative Risk Reduction 82%; P < 0.05 Chi-squared test). There was no difference between MACE rates in the intermediate (23–33; Medical: 15 ± 3% vs. PCI: 24 ± 4%) or high SYNTAX groups (>33; Medical: 27 ± 4% vs. PCI: 60 ± 12%). Independent predictors of MACE and mortality were SYNTAX score, the presence of 3 vessel coronary disease and reduced left ventricular function. Surprisingly neither Euroscore II (mean 4.89 ± 0.59%) nor the presence of neoplasia were statistically associated with MACE or mortality on either univariate or multivariate analyses. Conclusion This data supports the use of SYNTAX scoring as a predictor of outcome in patients turned down for CABG in a single-centre setting.Within our cohort of surgically turned down patients, those within the low SYNTAX tertile appeared to be the only group that achieve a clear benefit of PCI over medical therapy.

Malik, Nikesh; Banning, Amerjeet; Gershlick, Anthony

doi: 10.1136/heartjnl-2014-306118.69pmid: 24922858

Introduction Coronary stent thrombosis (ST) is a rare but potentially lethal complication of percutaneous coronary intervention (PCI). Previous studies have identified various patient, lesion and procedure-related risk factors, but there are currently no risk scoring tools in clinical use. In this study, we aimed to develop a scoring system to predict the risk of ST at different time points following PCI, to help guide the potency and duration of antiplatelet treatment. Methods Two research methods were used to identify risk factors for acute (within 24 h), early (within 30 days), late (30 days to 1 year) and very late (more than 1 year after PCI) ST and their associated odds ratios (ORs). This included a systematic literature review and meta-analysis of studies that met certain pre-defined criteria, and a modified Delphi RAND panel to gain expert opinion from eight experienced interventional cardiologists (Figure 1). Abstract 69 Figure 1 A Bayesian model was used to combine the results of both methods to produce a list of risk factors for each time point with associated ORs and confidence intervals (CIs) (Figure 2). Abstract 69 Figure 2 The risk scores were validated by applying them to patient level data from the TRITON-TIMI 38 study and the discriminatory power was tested by developing receiver operator characteristic (ROC) curves for each time point. The ability of the risk scores to predict ST was tested using the Hosmer-Lemeshow goodness-of-fit test. Results In total, 20 risk factors (9 patient-, 3 lesion- and 8 PCI procedure-related) were found to significantly influence the risk of developing ST. The combined ORs with CIs for some of the risk factors common to all time points are shown in Table 1 below. Abstract 69 Table 1 Risk factor Acute STOR (95% CI) Early STOR (95% CI) Late STOR (95% CI) VLSTOR (95% CI) Discontinued dual antiplatelet therapy N/A 3.49 (2.17-5.30) 3.44 (2.09-5.36) 1.75 (0.97-2.92) Bifurcation lesion PCI 1.62 (1.17-2.19) 1.66 (1.18-2.26) 1.57 (1.00-2.34) 1.39 (0.92-2.01) Incomplete stent expansion 1.63 (1.08-2.38) 1.73 (1.14-2.55) 1.91 (1.19-2.94) 1.54 (0.98-2.31) Undersized stent relative to vessel 1.95 (1.18-3.03) 2.00 (1.24-3.07) 1.91 (1.17-2.96) N/A Diabetes mellitus 1.62 (1.24-2.07) 1.69 (1.29-2.18) 1.53 (1.08-2.10) 1.61 (1.04-2.36) The final weighted risk scores, divided into patient-, treated lesion- and PCI procedure-related factors ranged from 0 to 22, 0 to 22 and 0 to 20 for acute, early and late ST respectively. When applied to the patient cohort within the TRITON-TIMI 38 study, the related risk of ST was 0–1.53%, 0–3.85% and 0–0.96% for acute, early and late ST respectively. Model discrimination, measured by area under the ROC curve, was 0.60 (95% CI 0.54–0.67, p = 0.0028) for acute ST, 0.67 (0.61–0.73, p < 0.0001) for early ST and 0.66 (0.58–0.73, p < 0.0001) for late ST, indicating good discriminatory power for all 3 risk scores. Conclusions In conclusion, published data were combined with expert opinion to produce a weighted scoring system to predict the risk of acute, early, late and very late ST following PCI. This will be assessed prospectively in clinical practice. Use of such a tool will be invaluable in combination with established bleeding risk scores to tailor the potency and duration of antiplatelet therapy in patients undergoing PCI.

Rajani, Nikil K; Joshi, Francis R; Babar, Judith; Balan, Anu; Gopalan, Deepa; Rudd, James HF

doi: 10.1136/heartjnl-2014-306118.151pmid: 24922950

Introduction Cardiac computed tomography (CT), consisting of coronary artery calcium (CAC) scoring and CT angiography (CTa), is recommended by NICE for the exclusion of coronary artery disease (CAD) in intermediate-risk symptomatic patients. Coronary calcification is pathognomonic of underlying CAD, but a zero CAC score cannot exclude CAD with certainty due to non-calcified coronary plaques. We evaluated the prevalence of CAD and the rate of major adverse cardiac events (MACE) in patients with a zero CAC score in comparison to patients with a non-zero CAC score. Methods From November 2009 to April 2013, 458 patients with chest pain underwent CT to exclude CAD. All subjects had CAC scoring. The majority of studies included contrast-enhanced, 128-slice, dual-source CTa. Scans were dual-reported by a cardiac radiologist and a cardiologist. MACE and all-cause mortality were determined through searches of regional databases. Results 458 symptomatic patients underwent CAC scoring. 247 patients (53.9%) had a CAC score of zero and 211 (46.1%) had non-zero CAC score, with a median score of 74 (interquartile range [IQR]: 13–223). Patients with a zero CAC score were younger (52 vs. 62 years, p < 0.0001) and more likely to be female (59.9 vs. 39.8%, p < 0.0001), but less likely to be hypertensive (26.3% vs. 44.1%, p < 0.0001), diabetic (6.9 vs. 14.7%, p = 0.0065), or have a smoking history (29.6 vs. 40.8%, p = 0.0121). Current smoking status and obesity did not differ between groups. There was a trend towards a family history being more common in those with zero CAC scores (37.2 vs. 29.9%, p = 0.09). 424 studies (92.6%) included CTa. Table 1 illustrates the breakdown of CTa findings according to CAC score. Abstract 151 Table 1 CTa findings divided according to calcium score; obstructive CAD implies stenosis >50% CTa Results CAC = 0 (n = 227) CAC >0 (n = 197) Normal coronaries 92.1% 0.0% Non-obstructive CAD 5.7% 65.0% Obstructive CAD 3.1% 35.0% Over a median follow-up of 536 days (IQR: 316–925), 2 MACE events (0.8%) were recorded in the cohort with zero CAC (n = 247), compared to a MACE rate of 1.9% (4 events) in those with non-zero CAC scores (n = 211). Both MACE events in the zero CAC group (1 acute MI and 1 emergent revascularisation) occurred in patients with CTa results suggesting normal coronaries.A CAC of zero was associated with a 99.2% negative predictive value for MACE over the course of follow-up. When MACE and all-cause mortality were combined, a CAC score of zero was associated with significant protective effect (Hazard Ratio 0.24, 95% CI: 0.07–0.86, p = 0.028, Figure 1). Abstract 151 Figure 1 Event free survival stratified by CAC (MACE and all-cause mortality combined) Conclusion Cardiac CT is an increasingly important tool for risk stratification. Reassuringly, a zero CAC score is associated with low rates of both obstructive CAD and MACE, emphasising its utility as a means to rule out CAD. Despite the presence of non-calcified CAD in some patients with a CAC of zero, these patients had a good prognosis.

Phan, Thanh; Awan, Mohammad; Shome, Joy; James, Simon; Thornley, Andrew; de Belder, Mark; Linker, Nicholas; Muir, Dougie; Turley, Andrew

doi: 10.1136/heartjnl-2014-306118.21pmid: N/A

Introduction In high-risk patients with severe symptomatic aortic stenosis (AS) surgical AVR (sAVR) or Transcatheter Aortic Valve Implanation (TAVI) are established treatment options. Rates of permanent pacemaker (PPM) insertion post TAVI are dependent on valve type and vary from22.5% for Medtronic CoreValve to 5.9% for the Edwards heart valve system. We examined PPM rates in a real world registry of 136 consecutive TAVI patients to explore pre-TAVI and post-TAVI PPM implantation rates. We also used a comparator group of patients who underwent sAVR following heart team evaluation. Method Our unit is a regional referral centre with a catchment population of 1.5 million. Data was collected prospectively on all patients with severe symptomatic AS assessed in our TAVI heart team MDT (between 2009–2012). TAVI indications were either logistic Euroscore >20% or inoperable status as judged by direct surgical review and heart team discussion. PPMs were implanted prior to TAVI if patients had class I or II indications for pacing. The Edwards Sapien or Sapien XT heart-valve system was used in all TAVI procedures. Prospectively collected data included: co-morbidities, logistic Euroscore, and incidence of urgent/emergency PPM implantation post procedure. Results 136 patients underwent TAVI and 59 underwent sAVR following heart team review. TAVI patients were older and higher risk than sAVR patients (mean age 82 ± 7 vs 80yrs; mean log Euroscore 25 ± 13% vs 15 ± 9.7 %). Patients with existing PPM at baseline in the TAVI and sAVR cohort were 6.6% (n = 9) and 3.4% (n = 2), respectively. Six (4.4%) patients had a PPM electively implanted pre TAVI after heart team review. The incidence of PPM insertion following TAVI and sAVR was 3.7% (n = 5) and 5.1% (n = 3), respectively. In the TAVI cohort, three patients had PPM implanted peri-procedure and two were implanted within five days. sAVR patients had their PPM implanted electively at a mean 118 days post procedure. Conclusion/Implications Standard indications for PPM insertion in elderly patients pre-TAVI are common. Our post TAVI pacing rates are low and compare favourably to those seen in tightly controlled clinical trials. Requirement for PPM insertion post TAVI is also similar to sAVR.

Fazlalizadeh, Helen; Pellicori, Pierpaolo; Kazmi, Syed; Zhang, Jufen; Clark, Andrew; Saveliych, Bokyi; Warden, John; Byass, T; Henderson, C; Freeman, R; Cleland, John GF

doi: 10.1136/heartjnl-2014-306118.45

Moore, Andrew Douglas; Hodgkinson, Conrad; Lapenna, Antonio; Zhang, Feng; Witkowska, Kate; Liang Ng, Fu; Headland, Sarah Emily; Reynolds, Louise; Lees, Delphine; Lechertier, Tanguy; Milsom, Alexandra; Hodivala-Dilke, Kairbaan; Ye, Shu

Niespialowska-Steuden, Maria; Okafor, Osita; Collins, Peter; Rosser, Gareth; Srinivasan, Manivannan; Adrienne Gorog, Diana

doi: 10.1136/heartjnl-2014-306118.15pmid: 24922931

Introduction The outcome of a thrombotic trigger, namely whether lasting vessel occlusion occurs or not, is determined the balance between prothrombotic properties of blood and endogenous thrombolysis. Atrial fibrillation (AF) is a major cause of stroke. Patients affected by AF are known to have enhanced thrombotic tendency. In our study we assessed the effect of novel oral anticoagulants (NOAC) and vitamin K antagonists (VKA) on global thrombotic status. Methods Patients with AF were tested to assess global thrombotic status before and during treatment with NOAC (dabigatran n = 12, rivaroxaban n = 9) and VKA (n = 13). Thrombotic status was assessed using the point-of-care Global Thrombosis Test (GTT). This technique utilises non-anticoagulated blood and assesses the time required for thrombus formation, occlusion (OT) and the time required for endogenous thrombolysis to occur, lysis time (LT). Results Compared to baseline, NOAC therapy resulted in a significant prolongation of OT [median 483s (25th–75th %ile: 395–556) vs. 714s (553–842), P < 0.0001] and reduction of LT [1519s (1137–1927) vs. 724s (280–1592), P = 0.032]. Compared to baseline, VKA also prolonged OT [437s (313–550) vs. 639s (575–644), P = 0.007], with no significant effect on LT [1490s (1386–3368) vs. 1778s (1493–2365), P = 0.724]. The average INR was 2.5 ± 0.6 when the second sample was taken. The baseline thrombotic status for the NOAC and VKA group was similar [OT 483s vs. 437s P = 0.386; LT 1519s vs. 1490s, P = 0.326]. The was no significant difference in efficacy in between rivaroxaban and dabigatran and both agents prolonged OT (43 vs. 52%, P = 0.651) and reduced LT (22 vs. 56%, P = 0.917). The CHA2DS2VASC score was similar in the NOAC and VKA groups (2.8 ± 1.6 vs. 3.1 ± 2, P = 0.636). Conclusions The mechanism of action is different for NOAC and VKA. Both of them reduce platelet reactivity, evidenced by the prolongation of OT. NOAC, but not VKA, improve endogenous thrombolysis. This novel mechanism of action of NOAC may underpin the superiority of some NOAC in stroke reduction over VKA, but may also contribute to enhanced bleeding profiles.

Phan, Thanh; Bandali, Alykhan; Adam, Zulfiquar; Awan, Mohammad; James, Simon; Turley, Andrew; Linker, Nicholas; Thambyrajah, Jeet

doi: 10.1136/heartjnl-2014-306118.146pmid: 24922945

Introduction The response to cardiac resynchronisation therapy (CRT) can be heterogeneous. Most studies aim to improve patient selection in order to achieve better outcomes.However, the adjustment of device timing intervals in conjunction with optimisation of medical therapy may maximise the effectiveness of CRT. This approach provides a new paradigm in the management of advance heart failure where not only medical therapies but also CRT timing intervals are tailored to individual needs. We describe our four years experience with CRT optimisation performed in a consultant-run heart failure (HF) clinic. Methods All patients attending the combined CRT optimisation and HF clinic during the period of 2008–2012 had a clinical assessment followed by echocardiography guided optimisation of their device. A-V optimisation was performed using the Iterative method on a pre-set sequence of paced and sensed AV delays. V-V optimisation was based on the maximal left ventricular outflow tract VTI as a surrogate for stoke volume.The following end-points were used: EuroQol (EQ visual analogue score (VAS)) health questionnaire, 6-minute walk test (6MWT), regional wall motion abnormality scoring (RWMA), left ventricular ejection fraction (LVEF), Yu Index (SD of time to peak systole in a 12 segment LV model as a measure of intra-ventricular dyssynchrony) and the difference between aortic and pulmonary ejection times (IVMD) a marker of inter-ventricular dyssynchrony. Patients were re-assessed after 8–12 weeks at which point optimisations of medical therapy were performed. Results 87 patients underwent CRT optimisation (68 (78%) were males). 92% of patients had NYHA Class II or III. CRT optimisation was performed at a mean 36 weeks post implantation and the follow-up visit took place at a mean of 9 weeks later. Post CRT optimisation there were reduction in intra-ventricular dyssynchrony (Yu Index decreased from 36 to 30ms (p = 0.02)) and inter-ventricular dyssynchrony (IVMD from 20 to 12 ms (P < 0.01). There were improvements in LVEF (from 31 to 34% (p = 0.05)) and RWMA (from 2.1 to 1.9 (P < 0.01)). Clinically there were trends toward an increase in 6MWT (from 274 to 311 m (p = 0.10)), improvement in NYHA from class III to II (p = 0.12) and EQ VAS health questionnaire score (from 60 to 66 (p = 0.07)). Conclusions This study suggests echocardiography guided CRT optimisation results in an improvement in measures of dyssynchrony and LV systolic function with a trend towards clinical improvement. This lends support to the individualisation of CRT timing intervals rather than relying on standard box settings as part of a heart failure service.

Patel, Jyoti; McNeill, Eileen; Douglas, Gillian; Hale, Ashley; de Bono, Joseph; Greaves, David; Channon, Keith

doi: 10.1136/heartjnl-2014-306118.228pmid: 24922804

The regulation of macrophage recruitment and retention into the vascular wall is critical in the progression of atherosclerosis and aortic aneurysm formation. This can be mediated by chemokine activation of multiple G-protein coupled receptors. The Regulator of G-Protein Signalling-1 (RGS-1) acts to deactivate the intracellular response to sustained chemokine stimulation. We have found that RGS-1 is up-regulated with atherosclerotic plaque progression and with monocyte-macrophage activation. However little is known about the role of RGS-1 in macrophage function in vivo . Rgs-1 deficient macrophages have significantly enhanced migratory responses to atherogenic chemokines (p < 0.05) and have impaired desensitisation to repeated chemokine re-stimulation (p < 0.001). In vivo , RGS-1 has a role in the accumulation of macrophages in atherosclerotic lesions and during Angiotensin-II aortic aneurysm rupture. In the absence of RGS1, atherosclerosis is attenuated in early lesions in the aortic root and aortas of ApoE-/- mice (p < 0.001) which is accompanied by fewer macrophages in the aortic root. Rgs1-/-ApoE-/- mice are protected from Angiotensin-II induced aneurysm rupture compared to ApoE-/- mice with 94% survival vs. 56% (p = 0.0147). Rgs1-/-ApoE-/- mice have significantly fewer CD11b+ myeloid cells and CD14+ macrophages in aortas than ApoE-/- mice (p < 0.05) after 5 days of Angiotensin-II infusion. Following bone marrow transplantation, recipient mice receiving ApoE-/- bone marrow were more susceptible to aortic aneurysm rupture (p = 0.0124), indicating bone marrow-derived RGS-1 is required for aneurysm rupture. Furthermore, Angiotensin-II treatment increased systolic blood pressure to a greater extent in Rgs1-/-ApoE-/- mice than ApoE-/- mice suggesting aneurysm formation in these mice is independent of Angiotensin-II induced hypertension and this is mediated by vascular-derived RGS-1.To gain insight into the mechanism by which RGS1 regulates trafficking, we selectively labelled inflammatory monocytes in vivo to track their movement into aortas following Angiotensin-II infusion. We found an accumulation of labelled CD45+ cells in the aortas of ApoE-/- mice from day 3 to day 5 but not in Rgs1-/-ApoE-/- mice indicating RGS-1 as a regulator of macrophage retention in aortic aneurysms. These findings identify a novel role for RGS-1 in leukocyte function and vascular inflammation and identifies RGS-1 as a potential target for the treatment of cardiovascular disease.

Pavitt, Chris; Lazoura, Olga; Lindsay, Alistair; Sriharan, Mona; Rubens, Michael; Padley, Simon; Nicol, Ed

doi: 10.1136/heartjnl-2014-306118.148pmid: 24922947

Introduction Data from cardiac CT (CCT) is often fused with eletrophysiological maps to allow precise pulmonary vein isolation and can detect left atrial appendage (LAA) thrombus in patients undergoing radio-frequency AF ablation (RFA). We present a complete audit cycle that reduced the prevalence of pseudo-thrombus (caused by poor initial mixing of contrast) in the LAA on CCT following implementation of a new protocol. Methods A standard of 100% positive and negative predictive value for the detection of LAA thrombus in patients undergoing CT assessment pre AF ablation was set. 225 consecutive patients were included with 7 patients excluded due to congential heart disease or previous cardiac surgery. 90 consecutive scans included in the initial audit. The diagnostic accuracy (sensitivity, specificity, positive (PPV) and negative predictive value (NPV)) for LAA thrombus detection was determined. A new 2-phase acquisition protocol (additional 60 second delayed scan) was introduced and the subsequent 128 consecutive cases were re-audited to determine if the standard had been met and compared to the published range in the literature. All patients underwent a TOE (as part of the standard clinical work-up) as the gold-standard reference. The additional radiation burden following the introduction of the delayed scan was determined. Results A total of 8 true LAA thrombi were detected (5 and 3 using standard acquisition and 2-phase, respectively). The use of the 2-phase acquisition significantly reduced pseudo-thrombus detection (30 vs. 0 cases; p < 0.0001) improving the specificity and PPV (Table 1). The mean additional radiation burden was 0.4 (0.2) mSv. Abstract 148 Table 1 Group Sensitivity/ % Specificity/ % PPV / % NPV/ % StandardAcquisition 100 85.7 21 100 2-Phase Acquisition 100 100 100 100 Published range 100 72.2 - 98 23 – 93 100 Conclusion Implementation of an additional 60 second delayed scan improved the detection of LAA thrombus in patients referred for RFA potentially negating the need for a separate TOE for this purpose. This incurs a minimal additional radiation dose and requires no additional contrast.