Background: Coronary computed tomography angiography (CCTA) can identify high-risk coronary plaque types. However, the inter-observer variability for high-risk plaque features, including low attenuation plaque (LAP), positive remodelling (PR), and the Napkin-Ring sign (NRS), may reduce their utility, especially amongst less experienced readers.Methodology: In a prospective study, we compared the prevalence, location and inter-observer variability of both conventional CT-defined high-risk plaques with a novel index based on quantifying the ratio of necrotic core to fibrous plaque using individualised X-ray attenuation cut-offs (the CT-defined thin-cap fibroatheroma -CT-TCFA) in 100 patients followed-up for 7 years.Results: In total, 346 plaques were identified in all patients. Seventy-two (21%) of all plaques were classified by conventional CT parameters as high-risk (either NRS or PR and LAP combined), and 43 (12%) of plaques were considered high-risk using the novel CT-TCFA definition of (Necrotic Core/fibrous plaque ratio of >0.9). The majority (80%) of the high-risk plaques (LAP & PR, NRS and CT-TCFA) were located in the proximal and mid-LAD and RCA. The kappa co-efficient of inter-observer variability (k) for NRS was 0.4 and for PR and LAP combined 0.4. While the kappa co-efficient of inter-observer variability (k) for the new CT-TCFA definition was 0.7. During follow-up, patients with either conventional high-risk plaques or CT-TCFAs were significantly more likely to have MACE (Major adverse cardiovascular events) compared to patients without coronary plaques (p value 0.03 & 0.03, respectively).Conclusion: The novel CT-TCFA is associated with MACE and has improved inter-observer variability compared with current CT-defined high-risk plaques.

Objective The primary objective was to investigate the long-term survival of patients who underwent single-vessel coronary revascularization with minimally invasive direct coronary artery bypass surgery with or without hybrid revascularization. The secondary outcome measures were repeat revascularization either by coronary artery bypass grafting or by percutaneous coronary intervention and the incidence of myocardial infarction or recurrent angina. Methods This is a retrospective study of prospectively collected data of patients who underwent minimally invasive direct coronary artery bypass procedure in our center between January 2001 and December 2015. Procedures were performed either through small left anterolateral thoracotomy or lower midline sternotomy. Results A total of 182 patients were identified: 100 underwent minimally invasive direct coronary artery bypass to the left anterior descending artery and 82 underwent hybrid revascularization (percutaneous coronary intervention to coronary arteries other than the left anterior descending artery along with minimally invasive direct coronary artery bypass to the left anterior descending artery). The mean ± SD age was 62 ± 10.1 years. Preoperatively 82% were male, and 72.5% patients had good left ventricular function. The median follow-up period was 10.9 years. There was no inhospital or 30-day mortality. The 10-year actuarial survival was 84.8%. Freedom from repeat revascularization was 98.9% at 1 year and 89.9% at 10 years. At follow-up, freedom from myocardial infarction was 96.7% whereas freedom from angina was 92.9%. Conclusions Within the limitations imposed by retrospective analyses, our study demonstrates excellent long-term outcome in patients undergoing minimally invasive direct coronary artery bypass with or without hybrid revascularization. For isolated left anterior descending artery disease minimally invasive direct coronary artery bypass should be considered, whereas hybrid revascularization (percutaneous coronary intervention and minimally invasive direct coronary artery bypass) should be considered for multivessel disease.

SUMMARY Twentyninepatients whohad hadrefractory supraventricular tachycardia were studied 4-36(mean16)monthsafter transvenousfulguration oftheatrioventricular junction. Twentytwohadcomplete atrioventricular block, five partial atrioventricular block, andtwohad atrioventricular conduction via an accessoryatrioventricular pathway. Thoughallpatients were freeofpalpitation after theprocedure, exertional dyspnoea haddeveloped in13andintwo patients pre-existing dyspnoea hadworsened. Duringventricular demandpacing, exercise time was reduced to43O% ofthepredicted value fortheir age andsex.The16patients withrate responsive pacemakers demonstrated a significantly better butstill impaired exercise capacity during physiological pacing ascompared withtheir performance during constantratepacing. Inpatients withcomplete atrioventricular block there was an increase inspontaneousventricular rateduring exercise insevenpatients andinresponsetotheValsalva manoeuvre ineight patients. Thissuggeststhat theintrinsic ventricular pacemaker isinfluenced byautonomic nervous system activity insome patients. Itisconcluded thatthough transvenousfulguration issuccessful incontrolling tachycardia it may reduce exercise capacity. Mostpatients remain incomplete atrioventricular block after the procedure and,incontrast withthepractice asdescribed inearly reports, wouldbenefit from physiological pacing-though even withthis modeexercise capacity islikely tobeabnormal. Transvenous fulguration ofatrioventricular conduction isanewtechnique usedtotreat recurrent supraventricular tachycardia inpatients whodo not respond adequately to,orwhocannot tolerate, drug treatment andinwhom antitachycardia pacing, whereapplicable, hasproved ineffective.' l Little is knownaboutitslongtermsequelae, though earlier reports havedocumented therhythms produced.4 Thisstudywasprompted bythefrequent complaints ofbreathlessness andreduced exercise tolerancefrompatients after transvenous fulguration of atrioventricular conduction. Theaimsweretoassess exercise capacity andspontaneous heartrhythm, including response toexercise andtheValsalva manoeuvre, after atrioventricular fulguration.

Objective To assess the utility of left bundle branch block (LBBB) as an activation criterion for primary percutaneous coronary intervention (PPCI).Design Retrospective observational cohort study.Setting Single UK heart attack centre.Patients Consecutive patients referred for PPCI September 2008-December 2011 (n=2192).Interventions Demographic and outcome data were obtained by review of case notes, angiograms and interrogation of local/national databases.Main outcome measures Angiographic culprit lesion assessment defined appropriate and inappropriate activations. Patients outcomes were assessed by Major adverse cardiac events (MACE), defined as a composite of mortality and unplanned revascularisation at 1-year.Results LBBB-activation occurred in 120 patients (5.5%), of whom 21 (17.5%) had acute coronary occlusion angiographically, and were adjudicated appropriately. Compared with appropriate activations for ST segment elevation, appropriate LBBB-activations were older (71.0 +/- 9.6 vs 64.2 +/- 12.4 years, p=0.01) and more likely to be in cardiogenic shock (19.0% vs 4.3%, p<0.01). Extent of disease quantified by the SYNTAX score did not differ (median 21.5, IQR 11.0-27.0 vs 19, 11.0-25.5, p=0.66), but amount of myocardium at-risk was higher in appropriate LBBB-activations (culprit jeopardy score median 4, IQR 2-6 vs 2, 2-4, p=0.02). Final diagnoses for LBBB- activations were acute coronary syndrome (39.2%), non-acute coronary syndrome cardiac chest pain (33.3%) and non-cardiac chest pain (27.5%). In appropriate LBBB-activations 1-year mortality and MACE were higher (23.8% vs 6.6%, p=0.002 and 28.6% vs 10.5%, p=0.007, respectively).Conclusions Our data suggests that despite its poor specificity for identifying acute coronary occlusion, LBBB should at the present time remain an activation criterion for PPCI and such patients should continue to be transferred to heart attack centres for assessment and treatment.

Objective— Leukocyte telomere length (LTL), a marker of cellular senescence, is inversely associated with cardiovascular events. However, whether LTL reflects plaque extent or unstable plaques, and the mechanisms underlying any association are unknown. Methods and Results— One hundred seventy patients with stable angina or acute coronary syndrome referred for percutaneous coronary intervention underwent 3-vessel virtual histology intravascular ultrasound; 30 372 mm of intravascular ultrasound pullback and 1096 plaques were analyzed. LTL was not associated with plaque volume but was associated with calcified thin-capped fibroatheroma (OR, 1.24; CI, 1.01–1.53; P =0.039) and total fibroatheroma numbers (OR, 1.19; CI, 1.02–1.39; P =0.027). Monocytes from coronary artery disease patients showed increased secretion of proinflammatory cytokines. To mimic leukocyte senescence, we disrupted telomeres and binding and expression of the telomeric protein protection of telomeres protein-1, inducing DNA damage. Telomere disruption increased monocyte secretion of monocyte chemoattractant protein-1, IL-6, and IL-1β and oxidative burst, similar to that seen in coronary artery disease patients, and lymphocyte secretion of IL-2 and reduced lymphocyte IL-10. Conclusion— Shorter LTL is associated with high-risk plaque morphology on virtual histology intravascular ultrasound but not total 3-vessel plaque burden. Monocytes with disrupted telomeres show increased proinflammatory activity, which is also seen in coronary artery disease patients, suggesting that telomere shortening promotes high-risk plaque subtypes by increasing proinflammatory activity.

Papworth Hospital NHS Foundation Trust, Papworth Everard, Cambridge, UK Received 5 December, 2009 Revised 1 February, 2010 Accepted 5 February, 2010 Correspondence to Peter M. Schofield, Papworth Hospital NHS Foundation Trust, Papworth Everard, Papworth, Cambridge CB23 3RE, UK E-mail: [email protected]

OBJECTIVES The purpose of this study was to determine whether thin-capped fibroatheromata (TCFA) identified by virtual histology intravascular ultrasound (VH-IVUS) are associated with major adverse cardiac events (MACE) on individual plaque or whole patient analysis.BACKGROUND Post-mortem studies have identified TCFA as the substrate for most myocardial infarctions. However, little is known about the natural history of individual TCFA and their link with MACE. VH-IVUS provides a method of identifying plaques in vivo that are similar (although not identical) to histologically defined TCFA, and has been validated in human atherectomy and post-mortem studies.METHODS One hundred seventy patients with stable angina or troponin-positive acute coronary syndrome referred for percutaneous coronary intervention (PCI) were prospectively enrolled and underwent 3-vessel VH-IVUS pre-PCI and also post-PCI in the culprit vessel. MACE consisted of death, myocardial infarction, or unplanned revascularization.RESULTS In all, 30,372 mm of VH-IVUS were analyzed. Eighteen MACE occurred in 16 patients over a median follow-up of 625 days (interquartile range: 463 to 990 days); 1,096 plaques were classified, and 19 lesions resulted in MACE (13 nonculprit lesions and 6 culprit lesions). Nonculprit lesion factors associated with nonrestenotic MACE included VHTCFA (hazard ratio [HR]: 7.53, p = 0.038) and plaque burden >70% (HR: 8.13, p = 0.011). VHTCFA (HR: 8.16, p = 0.007), plaque burden >70% (HR: 7.48, p < 0.001), and minimum luminal area <4 mm(2) (HR: 2.91, p = 0.036) were associated with total MACE. On patient-based analysis, the only factor associated with nonrestenotic MACE was 3-vessel noncalcified VHTCFA (HR: 1.79, p = 0.004).CONCLUSIONS VH-IVUS TCFA was associated with nonrestenotic and total MACE on individual plaque analysis, and noncalcified VHTCFA was associated with nonrestenotic and total MACE on whole-patient analysis, demonstrating that VH-IVUS can identify plaques at increased risk of subsequent events. The preservation of the association between VHTCFA and MACE despite various analyses emphasizes its biological importance. (J Am Coll Cardiol Img 2011;4:894-901) (C) 2011 by the American College of Cardiology Foundation

Background— Myocyte necrosis as a result of elective percutaneous coronary intervention (PCI) occurs in approximately one third of cases and is associated with subsequent cardiovascular events. This study assessed the ability of remote ischemic preconditioning (IPC) to attenuate cardiac troponin I (cTnI) release after elective PCI. Methods and Results— Two hundred forty-two consecutive patients undergoing elective PCI with undetectable preprocedural cTnI were recruited. Subjects were randomized to receive remote IPC (induced by three 5-minute inflations of a blood pressure cuff to 200 mm Hg around the upper arm, followed by 5-minute intervals of reperfusion) or control (an uninflated cuff around the arm) before arrival in the catheter laboratory. The primary outcome was cTnI at 24 hours after PCI. Secondary outcomes included renal dysfunction and major adverse cardiac and cerebral event rate at 6 months. The median cTnI at 24 hours after PCI was lower in the remote IPC compared with the control group (0.06 versus 0.16 ng/mL; P =0.040). After remote IPC, cTnI was <0.04 ng/mL in 44 patients (42%) compared with 24 in the control group (24%; P =0.01). Subjects who received remote IPC experienced less chest discomfort ( P =0.0006) and ECG ST-segment deviation ( P =0.005) than control subjects. At 6 months, the major adverse cardiac and cerebral event rate was lower in the remote IPC group (4 versus 13 events; P =0.018). Conclusion— Remote IPC reduces ischemic chest discomfort during PCI, attenuates procedure-related cTnI release, and appears to reduce subsequent cardiovascular events.

Remote ischaemic pre-conditioning (RIPC) reduces distant tissue ischaemia reperfusion injury. We tested the hypothesis that RIPC would protect the left ventricle (LV) from ischaemic dysfunction and stunning.Forty-two patients with single vessel coronary disease and normal LV function were prospectively recruited. Twenty patients had repeated conductance catheter assessment of LV function during serial coronary occlusions with/without RIPC and a further 22 patients underwent serial dobutamine stress echocardiography and tissue Doppler analysis with/without RIPC. Remote ischaemic pre-conditioning was induced by three 5 min inflations of a blood pressure cuff around the upper arm. RIPC did not diminish the degree of ischaemic LV dysfunction during coronary balloon occlusion (Tau, ms: 59.2 (2.8) vs. 62.8 (2.8), P = 0.15) and there was evidence of cumulative LV dysfunction despite RIPC [ejection fraction (EF), %: 54.3 (5.8) vs. 44.9 (3.7), P = 0.03]. Remote ischaemic pre-conditioning did not improve contractile recovery during reperfusion (EF, %: 51.7 (3.6) vs. 51.5 (5.7), P = 0.88 and Tau, ms: 55.6 (2.8) vs. 56.0 (2.0), P = 0.85). A neutral effect of RIPC on LV function was confirmed by tissue Doppler analysis of ischaemic segments at peak dobutamine (V(s), cm s(-1) control: 8.2 (0.4) vs. RIPC 8.1 (0.4), P = 0.43) and in recovery.RIPC does not attenuate ischaemic LV dysfunction in humans.

Background An elevation in cardiac troponin-I (cTnI) after elective percutaneous coronary intervention (PCI) is because of cardiac necrosis and has prognostic implications. Primary microvascular dysfunction, evident before PCI, and paucity of coronary collaterals at baseline may influence cTnI.Methods We selected 22 patients awaiting elective PCI for a single-vessel, type-A coronary stenosis, with normal left ventricular function and a normal preprocedure cTnI. Intracoronary pressure and Doppler flow were measured during coronary balloon occlusion to derive microvascular resistance: R-p=[P-d(occl)-P-v]/APV(occl), and collateral resistance: R-coll=[P-a-P-d(occl)]/APV(occl), at each stage of PCI, where P-a is mean aortic pressure, P-v is central venous pressure, P-d(occl) is mean distal pressure, R-p is coronary microvascular resistance, R-coll is coronary collateral resistance, and APVoccl is average peak velocity during coronary balloon occlusion. The resistance indices were compared with postprocedural cTnI levels measured at 24h.Results There was a relationship between baseline R-p before PCI and elevated plasma cTnI levels at 24 h. Mean (SEM) R-p (mmHg/cm/s) increased for each cTnI tertile: T1 (mean cTnI 0.04 ng/ml): 1.3 (0.3), T2 (mean cTnI 0.13 ng/ml): 3.1 (0.4), and T3 (mean cTnI 2.5 ng/ml): 4.6 (0.7) (P=0.002). Baseline R-coll (mmHg/cm/s) was similarly related to cTnI result and mean values showed an increasing trend: T1: 11.1 (1.9), T2: 14.5 (2.3), and T3: 19.5 (3.4) (P=0.12). Serial coronary balloon occlusions did not significantly alter R-p (P=0.82) or recruit coronary collaterals (P=0.69).Conclusion Primary coronary microvascular dysfunction and poor collaterals at baseline are associated with post-PCI necrosis. Coron Artery Dis 20:253-259 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.

BACKGROUND:The EuroQoL 5D (EQ-5D) has been widely used in studies of cardiac disease, but its measurement properties in this group are not well established. The study aimed to quantify the relationship between measures commonly used in studies of cardiac disease and the EQ-5D index across different levels of disease severity. METHODS:Patient-level data from 7 studies of cardiac interventions were used, which included randomised trials and observational studies. Relationships between the EQ-5D index and commonly used cardiac measures, Canadian Cardiovascular Society (CCS) angina severity class, treadmill exercise time (ETT) and scales of the Seattle Angina Questionnaire (SAQ) were examined. Mixed effects linear regression was used to assess these relationships, with the EQ-5D index as the response. RESULTS:Study sample sizes ranged from 68 to 2419. Mean baseline EQ-5D index ranged from 0.77 in patients at diagnosis (95% CI 0.75, 0.78) to 0.43 in patients with advanced disease (95% CI 0.39, 0.48) and differed significantly across studies (p < 0.001). There was evidence of a ceiling effect in patients at diagnosis. The minimum clinically important difference of a one minute increase in ETT was associated with a 0.019 (95% CI 0.014, 0.025) increase in EQ-5D index. One class increase in CCS was associated with a 0.11 (95% CI 0.09, 0.13) decrease in EQ-5D index. A 10 unit increase in SAQ scales was associated with increases between 0.04 and 0.07 in EQ-5D index (95% CIs 0.03, 0.05 and 0.05, 0.08). Tests of heterogeneity indicated the EQ-5D-covariate relationships were consistent across levels of disease severity for ETT and the treatment satisfaction scale of the SAQ, but heterogeneous for age, gender, CCS angina class and other scales of the SAQ. CONCLUSION:The EQ-5D index varies with coronary disease severity. The relationship between the EQ-5D index and an outcome measure used in cardiac intervention studies, ETT, was consistent across disease severity levels, but the relationship between demographic variables, CCS angina class and most of the SAQ scales and the EQ-5D index was heterogeneous for patients with different levels of coronary disease. Differences in the EQ-5D index associated with clinically important differences in cardiac measures can be quantified and vary between three important examples - angina class, ETT and SAQ.

The response to sleep-disordered breathing (SDB)-directed therapy was evaluated using the Clear Path home-based monitoring system. There were 26 patients with heart failure enrolled in the Sleep Events, Arrhythmias, and Respiratory Analysis in Chronic Heart Failure (SEARCH) study with SDB requiring treatment (apnea-hypopnea index [AHI] >or=15 events/h). Patients were monitored using both standard polysomnography and the Clear Path system to determine the change in SDB parameters before and after initiation of therapy. Accuracy of the Clear Path system compared with polysomnography was >or=87% to detect SDB events. A marked reduction in the mean number of sleep time respiratory disturbances was observed by both techniques after the initiation of SDB-directed therapy, and 21 patients (87.5%) experienced a 16.7-events/h mean reduction in AHI. Thus, the Clear Path system appears to be a useful device to monitor response to SDB-directed treatment for apnea in patients with heart failure.