The AUStralian MEDiterranean Diet Heart Trial (AUSMED Heart Trial): A randomized clinical trial in secondary prevention of coronary heart disease in a multiethnic Australian population: Study protocol.

The Mediterranean diet was first characterized as a heart-protective diet in the 1960s. The significant cardioprotective effects of the Mediterranean diet in comparison to the standard-care low-fat diet have been established in the primary prevention of cardiovascular disease (CVD); however, there is insufficient evidence in secondary prevention research to influence the current standard of care. Opportunity exists to assess the Mediterranean diet as a therapeutic target for secondary CVD prevention within Australia's ethnoculturally diverse communities. The AUSMED Heart Trial is a multisite randomized controlled trial that will evaluate the efficacy of the Mediterranean diet for secondary prevention of CVD in the Australian health care setting. This trial aims to evaluate the effect of a 6-month Mediterranean diet intervention (delivered by dietitians) versus a "standard-care" low-fat diet in reducing the composite incidence of cardiovascular events at 12 months and at trial end in participants with documented evidence of a previous acute myocardial infarction at trial entry. The quality of the diet at baseline and follow-up will be assessed using comprehensive dietary questionnaires and diaries as well as relevant dietary biomarkers (such as urinary polyphenols and erythrocyte fatty acids). Cardiovascular risk markers, including novel measures of immune and inflammatory status, endothelial function, vascular compliance, platelet activity, and body composition, will be collected to explore possible mechanisms for treatment effect. Cost-effectiveness will also be estimated to support policy translation. We plan to recruit 1,032 participants (516 per arm) from cardiology clinics in major Australian hospitals in Melbourne, Adelaide, and Brisbane.

N-terminal pro-B-type Natriuretic Peptides' Prognostic Utility Is Overestimated in Meta-analyses Using Study-specific Optimal Diagnostic Thresholds.

BACKGROUND: N-terminal fragment B-type natriuretic peptide (NT-proBNP) prognostic utility is commonly determined post hoc by identifying a single optimal discrimination threshold tailored to the individual study population. The authors aimed to determine how using these study-specific post hoc thresholds impacts meta-analysis results. METHODS: The authors conducted a systematic review of studies reporting the ability of preoperative NT-proBNP measurements to predict the composite outcome of all-cause mortality and nonfatal myocardial infarction at 30 days after noncardiac surgery. Individual patient-level data NT-proBNP thresholds were determined using two different methodologies. First, a single combined NT-proBNP threshold was determined for the entire cohort of patients, and a meta-analysis conducted using this single threshold. Second, study-specific thresholds were determined for each individual study, with meta-analysis being conducted using these study-specific thresholds. RESULTS: The authors obtained individual patient data from 14 studies (n = 2,196). Using a single NT-proBNP cohort threshold, the odds ratio (OR) associated with an increased NT-proBNP measurement was 3.43 (95% CI, 2.08 to 5.64). Using individual study-specific thresholds, the OR associated with an increased NT-proBNP measurement was 6.45 (95% CI, 3.98 to 10.46). In smaller studies (<100 patients) a single cohort threshold was associated with an OR of 5.4 (95% CI, 2.27 to 12.84) as compared with an OR of 14.38 (95% CI, 6.08 to 34.01) for study-specific thresholds. CONCLUSIONS: Post hoc identification of study-specific prognostic biomarker thresholds artificially maximizes biomarker predictive power, resulting in an amplification or overestimation during meta-analysis of these results. This effect is accentuated in small studies.

Practical experience with ticagrelor: an Australian and New Zealand perspective.

OBJECTIVE: Ticagrelor is recommended in local and international guidelines as first-line therapy in combination with aspirin in patients presenting with acute coronary syndromes (ACS). The purpose of this article is to provide practical guidance regarding the use of ticagrelor in this setting. METHODS AND RESULTS: Ticagrelor, a direct-acting, reversible P2Y12 receptor antagonist, has a faster onset, and a more potent and predictable antiplatelet effect compared with clopidogrel. The authors recommend considering the use of ticagrelor in moderate-to-high risk ACS patients treated with an invasive approach and those managed non-invasively who have elevated troponin levels. Consistent with outcomes observed in the PLATO trial overall, ticagrelor was superior to clopidogrel treatment in patients with chronic kidney disease, a history of stroke or transient ischemic attack, the elderly, and patients requiring surgical revascularization. CONCLUSIONS: When switching from clopidogrel to ticagrelor, patients established on clopidogrel therapy can be switched directly without loading; patients not loaded with clopidogrel and not taking maintenance dose clopidogrel for at least 5 days should first be loaded with ticagrelor. Guidelines recommend discontinuing ticagrelor 5 days before surgery if antiplatelet effects are not desired and recommencing therapy as soon as safe following surgery. Ticagrelor should be avoided in individuals with a history of intracranial hemorrhage, moderate-to-severe hepatic impairment, high bleeding risk, within 24 hours of thrombolytic therapy, and in those treated with oral anticoagulants. Local, real-world experience suggests low bleeding rates with ticagrelor therapy. Dyspnoea is a common symptom in patients with ACS and is also a side-effect of ticagrelor therapy. Discontinuation of ticagrelor due to dyspnoea has been uncommon in clinical trials. However, local registry data suggest higher discontinuation rates (2-9%) related to dyspnoea in the real-world setting, indicating that clinicians may need to consider other potential causes of dyspnoea before discontinuing ticagrelor.

Effects of intravenous caffeine on fractional flow reserve measurements in coronary artery disease.

BACKGROUND: Intravenous adenosine is used to minimise the coronary micro-resistance to achieve maximal hyperaemia along with nitrates for optimal fractional flow reserve (FFR) measurements. We hypothesise that caffeine, being a competitive inhibitor of adenosine, would influence adenosine-mediated FFR readings. METHODS: Consecutive patients undergoing angiogram and FFR measurements were enrolled after abstaining from caffeine for 24 h. Patients with any contraindications to intravenous adenosine or caffeine were excluded. FFR measurements were taken using nitrates and adenosine pre and post 4 mg/kg intravenous caffeine administration and results were compared. RESULTS: 10 patients were analysed (80% men, age 59.9±9.4, weight 87.5±15.6). Baseline caffeine levels were undetectable in all patients and increased significantly postintravenous caffeine administration (16.4±5.5 µg/mL). Baseline preadenosine FFR values were similar before and after caffeine administration (0.91±0.06 vs 0.91±0.07; p=0.41). Postadenosine FFR readings were 0.79±0.07, which increased non-significantly to 0.82±0.11 postcaffeine (p=0.15). Two significant FFR readings (≤0.8) changed to non-significant after caffeine administration (0.77-0.93 and 0.8-0.91). CONCLUSIONS: Caffeine may affect FFR results in some patients. Larger studies are warranted to clarify the extent and magnitude of caffeine/adenosine interaction particularly due to ubiquitous nature of caffeine and increasing importance of FFR in clinical practice.

Predictors and outcomes of early coronary angiography in patients with prior coronary artery bypass surgery presenting with non-ST elevation myocardial infarction.

INTRODUCTION: The best strategy in patients with prior coronary artery bypass graft surgery (CABG) who present with non-ST elevation myocardial infarction (NSTEMI) remains less well defined. We compare the characteristics, therapeutic interventions and outcomes of patients with prior CABG presenting with NSTEMI. METHODS: All patients who presented to our hospital during 2007-2012 with available electronic records were analysed retrospectively. Outcomes were compared between patients who underwent coronary angiography or percutaneous coronary intervention (PCI) versus those who were treated medically. RESULTS: A total of 117 patients were analysed. Of that, 79 patients were managed medically while 38 underwent early angiography, of which only 11 (9.5%) received PCI. Patients treated medically (did not undergo angiography) were older (74±10 vs70±8; p=0.05). ECG changes were the only independent predictor for early angiography (OR 0.4, 95% CI 0.15 to 0.99; p=0.05) while recurrent chest pain (OR 0.2, 95% CI 0.05 to 0.97; p=0.05) predicted PCI on multivariate analysis. The PCI group had higher Global Registry of Acute Cardiac Events (GRACE) score (176±29 vs 150±31; p=0.01). No significant difference was found in readmission rates, morbidity (unstable angina pectoris, NSTEMI, ST elevation myocardial infarction (STEMI), or combination) or mortality at 12 months between the groups who underwent angiography, PCI, or treated medically on univariate and multivariate analysis. CONCLUSIONS: The opportunity to intervene in prior CABG patients presenting with NSTEMI is often low. Initial medical management may be a reasonable option in carefully selected patients particularly in the absence of ongoing symptoms, ECG changes or very high GRACE scores. Further studies are required to evaluate the safety of non-invasive strategies in managing this population.

Use of ivabradine and atorvastatin in emergent orthopedic lower limb surgery and computed tomography coronary plaque imaging and novel biomarkers of cardiovascular stress and lipid metabolism for the study and prevention of perioperative myocardial infarction: study protocol for a randomized controlled trial.

BACKGROUND: The incidence of perioperative myocardial infarction (PMI) globally is known to be around 2 to 3% and can prolong hospitalization, increased morbidity and mortality. Little is known about the pathophysiology and risk factors for PMI. We investigate the presence of elevated novel cardiac markers and preoperative coronary artery plaque through contemporary laboratory techniques to determine the correlation with PMI, as well as studying ivabradine and atorvastatin as protective pharmacotherapies against PMI in the context of orthopedic surgery. METHODS/DESIGN: We aim to enroll 200 patients aged above 60 years who suffer from neck of femur fracture requiring surgery. Patients will be randomized to four arms (no study drugs, atorvastatin only, ivabradine only and ivabradine and atorvastatin). Our primary outcome is incidence of PMI. All patients will receive an electrocardiogram, cardiac echocardiography, measurement of novel cardiac biomarkers and computed tomography (CT) coronary angiography. A telephone interview post discharge will be conducted at 30 days, 60 days and 1 year. DISCUSSION: We postulate that ivabradine and atorvastatin will reduce the rate and magnitude of PMI following surgery by reducing heart rate and attenuating catecholamine-induced tachycardia postoperatively. Secondly, we postulate that postoperative reduction in heart rate and catecholamine-induced tachycardia with ivabradine will correlate with a reduction in cardiovascular novel biomarkers which will reduce atrial stretch and postoperative incidence of arrhythmia. We aim to demonstrate that treatment with ivabradine and atorvastatin will cause a reduction in the incidence and magnitude of PMI, the benefit of which is derived primarily in patients with greater atherosclerotic burden as measured by higher CT coronary calcium scores. TRIAL REGISTRATION: This study protocol has been listed in the Australia New Zealand Clinical Trial Registry (registration number: ACTRN12612000340831) on 23 March 2012.

Platypnoea orthodeoxia after hepatic surgery.

Platypnoea orthodeoxia is a rare clinical syndrome characterised by dyspnoea and deoxygenation exhibited in upright position with improvement in supine posture. Previously described aetiologies include cardiac (pericardial effusion or constrictive pericarditis), pulmonary (pneumonectomy, emphysema or amiodarone toxicity), abdominal (cirrhosis or ileus) or vascular (abdominal aortic aneurysm) causes. We report an unusual case of platypnoea orthodeoxia associated with patent foramen ovale and partial hepatic resection.

Radiation exposure with the radial approach for diagnostic coronary angiography in a centre previously performing purely the femoral approach.

INTRODUCTION: Use of the radial approach for coronary angiography and percutaneous coronary intervention (PCI) is known to improve many patient outcome measures. However, there is some concern that it may be associated with increased patient radiation exposure. This study explores radiation exposure with the radial approach compared with the femoral approach in a centre previously performing purely femoral approach. PATIENTS AND METHODS: Data was collected retrospectively for all patients undergoing diagnostic coronary angiography over a six month period. PCIs and procedures with inherent technical difficulty or use of additional techniques (graft studies, optical coherence tomography, fractional flow reserve) were excluded. Dose area product (DAP) and fluoroscopy time (FT) were analysed for all remaining procedures (n=389), comparing radial (n=109) and femoral (n=280) approaches. RESULTS: The overall mean FT for transradial cases (7.45 mins) was significantly higher than for transfemoral cases (4.59 mins; p<0.001). The overall mean DAP for transradial cases (95.64 G Gycm(2)) was significantly higher than for transfemoral cases (70.25 Gycm(2), p<0.05)). Neither the FT nor the DAP decreased over the six month period. CONCLUSION: The radial approach was associated with significantly higher DAP and FT compared to the femoral approach during an initial introductory phase which was likely insufficient to develop radial proficiency. The results of this study are consistent with previous studies and may influence choice of access for non-emergent diagnostic coronary angiography before radial proficiency has been established, particularly for patients more susceptible to radiation risks.

The prognostic value of pre-operative and post-operative B-type natriuretic peptides in patients undergoing noncardiac surgery: B-type natriuretic peptide and N-terminal fragment of pro-B-type natriuretic peptide: a systematic review and individual patient data meta-analysis.

OBJECTIVES: The objective of this study was to determine whether measuring post-operative B-type natriuretic peptides (NPs) (i.e., B-type natriuretic peptide [BNP] and N-terminal fragment of proBNP [NT-proBNP]) enhances risk stratification in adult patients undergoing noncardiac surgery, in whom a pre-operative NP has been measured. BACKGROUND: Pre-operative NP concentrations are powerful independent predictors of perioperative cardiovascular complications, but recent studies have reported that elevated post-operative NP concentrations are independently associated with these complications. It is not clear whether there is value in measuring post-operative NP when a pre-operative measurement has been done. METHODS: We conducted a systematic review and individual patient data meta-analysis to determine whether the addition of post-operative NP levels enhanced the prediction of the composite of death and nonfatal myocardial infarction at 30 and ≥180 days after surgery. RESULTS: Eighteen eligible studies provided individual patient data (n = 2,179). Adding post-operative NP to a risk prediction model containing pre-operative NP improved model fit and risk classification at both 30 days (corrected quasi-likelihood under the independence model criterion: 1,280 to 1,204; net reclassification index: 20%; p < 0.001) and ≥180 days (corrected quasi-likelihood under the independence model criterion: 1,320 to 1,300; net reclassification index: 11%; p = 0.003). Elevated post-operative NP was the strongest independent predictor of the primary outcome at 30 days (odds ratio: 3.7; 95% confidence interval: 2.2 to 6.2; p < 0.001) and ≥180 days (odds ratio: 2.2; 95% confidence interval: 1.9 to 2.7; p < 0.001) after surgery. CONCLUSIONS: Additional post-operative NP measurement enhanced risk stratification for the composite outcomes of death or nonfatal myocardial infarction at 30 days and ≥180 days after noncardiac surgery compared with a pre-operative NP measurement alone.

Residual ischemia after revascularization in multivessel coronary artery disease: insights from measurement of absolute myocardial blood flow using magnetic resonance imaging compared with angiographic assessment.

BACKGROUND: Revascularization strategies for multivessel coronary artery disease include percutaneous coronary intervention and coronary artery bypass grafting. In this study, we compared the completeness of revascularization as assessed by coronary angiography and by quantitative serial perfusion imaging using cardiovascular magnetic resonance. METHODS AND RESULTS: Patients with multivessel coronary disease were recruited into a randomized trial of treatment with either coronary artery bypass grafting or percutaneous coronary intervention. Angiographic disease burden was determined by the Bypass Angioplasty Revascularization Investigation (BARI) myocardial jeopardy index. Cardiovascular magnetic resonance first-pass perfusion imaging was performed before and 5 to 6 months after revascularization. Using model-independent deconvolution, hyperemic myocardial blood flow was evaluated, and ischemic burden was quantified. Sixty-seven patients completed follow-up (33 coronary artery bypass grafting and 34 percutaneous coronary intervention). The myocardial jeopardy index was 80.7±15.2% at baseline and 6.9±11.3% after revascularization (P<0.0001), with revascularization deemed complete in 62.7% of patients. Relative to cardiovascular magnetic resonance, angiographic assessment overestimated disease burden at baseline (80.7±15.2% versus 49.9±29.2% [P<0.0001]), but underestimated it postprocedure (6.9±11.3% versus 28.1±33.4% [P<0.0001]). Fewer patients achieved complete revascularization based on functional criteria than on angiographic assessment (38.8% versus 62.7%; P=0.015). After revascularization, hyperemic myocardial blood flow was significantly higher in segments supplied by arterial bypass grafts than those supplied by venous grafts (2.04±0.82 mL/min per gram versus 1.89±0.81 mL/min per gram, respectively; P=0.04). CONCLUSIONS: Angiographic assessment may overestimate disease burden before revascularization, and underestimate residual ischemia after revascularization. Functional data demonstrate that a significant burden of ischemia remains even after angiographically defined successful revascularization.

Electrocardiograph changes, troponin levels and cardiac complications after orthopaedic surgery.

INTRODUCTION: The relationship between electrocardiograph (ECG) changes and troponin levels after the emergency orthopaedic surgery are not well characterised. The aim of this study was to determine the correlation between ECG changes (ischaemia or arrhythmia), troponin elevations perioperatively and cardiac complications. MATERIALS AND METHODS: One hundred and eighty-seven orthopaedic patients over 60 years of age were prospectively tested for troponin I and ECGs were performed on the fi rst 3 postoperative mornings or until discharge. RESULTS: The incidences of pre- and postoperative troponin elevation were 15.5% and 37.4% respectively, the majority were asymptomatically detected. Most of the patients who sustained a troponin rise did not have any concomitant ECG changes (51/70 or 72.9%). Postoperative ECG changes were noted in 18.4% (34/185) and of those with ECG changes, slightly more than half (55.9%) had a troponin elevation. Most ECG changes occurred on postoperative day 1 and were non-ST elevation in type. ECG changes occurred more frequently with higher troponin levels. Postoperative troponin elevation (P = 0.018) and not preoperative troponin level (P = 0.060) was associated with ECG changes on univariate analysis. Two premorbid factors were predictors of postoperative ECG changes using multivariate logistical regression; age [odds ratio (OR), 1.05; 95% CI, 1.005 to 1.100, P = 0.029) and sex OR, 2.4; 95% CI, 1.069 to 5.446, P = 0.034). Twenty patients sustained postoperative cardiac complications; 9 (45%) were associated with ECG changes and 16 (80%) with postoperative troponin elevation. Pre- or postoperative troponin elevation better predicted cardiac complications compared with preoperative ECG changes. CONCLUSION: Electrocardiograph changes do not necessarily accompany troponin elevations after the emergency orthopaedic surgery but are more likely to have higher troponin levels. The best predictor of postoperative cardiac complications is troponin elevation.

Does cardiology intervention improve mortality for post-operative troponin elevations after emergency orthopaedic-geriatric surgery? A randomised controlled study.

OBJECTIVES: Troponin elevations are common after emergency orthopaedic surgery and confer a higher mortality at one year. The objective was to determine if comprehensive cardiology care after emergency orthopaedic surgery reduces mortality at one year in patients who sustain a post-operative troponin elevation versus standard care. METHODS: A randomised controlled trial was conducted at a metropolitan teaching hospital in Melbourne, Australia. 187 consecutive patients were eligible with 70 patients randomised. Troponin I was tested peri-operatively and patients with a troponin elevation were randomised to cardiology care versus standard ward management. The main outcome measure was one year mortality. RESULTS: The incidence of a post-operative troponin elevation was 37.4% (70/187) and these 70 patients were randomised. In-hospital cardiac complications were similar between the randomised groups: standard care (7/35 or 20.0%) versus cardiology care (8/35 or 22.9%). There was no difference in 1 year mortality between the randomised groups (6/35 or 17.1% in each group). Multivariate predictors of 1 year mortality were post-operative troponin elevation OR 4.3 (95% CI, 1.1-16.4, p=0.035), age OR 1.1 (95% CI, 1.02-1.2, p=0.016) and number of comorbidities OR 2.1 (95% CI, 1.3-3.5, p=0.004). At 1 year 35/187 (18.7%) sustained a cardiac complication and 23/35 (65.7%) had a troponin elevation. CONCLUSIONS: There was no difference in mortality between patients with a post-operative troponin elevation randomised to cardiology care compared with standard care. Troponin elevation predicted one year mortality. Further research is needed to find an effective intervention to reduce mortality.

N-terminal pro-brain natriuretic peptide and angiotensin-converting enzyme-2 levels and their association with postoperative cardiac complications after emergency orthopedic surgery.

The prognostic usefulness of the cardiac biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP) and angiotensin-converting enzyme 2 (ACE-2), in predicting adverse cardiac outcomes after orthopedic surgery is not well studied. The aim of our study was to determine the usefulness of perioperative NT-proBNP and ACE-2 for predicting cardiac events after emergency orthopedic surgery. The perioperative NT-proBNP and ACE-2 levels were determined in 187 consecutive patients aged >60 years who underwent orthopedic surgery with 1 year of follow-up for any cardiac complications (defined as acute myocardial infarction, congestive cardiac failure, atrial fibrillation, or major arrhythmia) and death. Of the 187 patients, 20 (10.7%) sustained an in-hospital postoperative cardiac complication. The total all-cause in-hospital and 1-year mortality rate was 1.6% (3 of 187) and 8.6% (16 of 187), respectively. The median preoperative and postoperative NT-proBNP level was greater in patients who sustained an in-hospital cardiac event than in those who had not (386 vs 2,273 pg/ml, p <0.001, and 605 vs 4,316 pg/ml, p <0.001, respectively). Similarly, the postoperative median ACE-2 levels were significantly greater in the patients with an in-hospital cardiac event than in those without (25.3 vs 39.5 pmol/ml/min, p = 0.012). A preoperative NT-proBNP level of ≥741 pg/ml (odds ratio 4.5, 95% confidence interval 1.3 to 15.2, p = 0.017), postoperative troponin elevation (odds ratio 4.9, 95% confidence interval 1.3 to 18.9, p = 0.022), and number of co-morbidities (odds ratio 1.8, 95% confidence interval 1.2 to 2.8, p = 0.009) independently predicted in-hospital cardiac complications on multivariate analysis. The pre- and postoperative NT-proBNP level independently predicted 1-year cardiovascular complications but not the ACE-2 levels. In conclusion, elevated perioperative NT-proBNP predicted in-hospital and 1-year cardiac events in an emergency orthopedic population but the ACE-2 levels did not, which requires additional study for validation.

A case of acute stent thrombosis during treatment with the thrombopoietin receptor agonist peptide--romiplostim.

Romiplostim is a thrombopoietin receptor agonist that increases platelet counts and restores platelet function in patients with chronic immune thrombocytopenia (ITP). Increase in platelet count and platelet activation has been associated with increased thromboembolic risk. The present case report describes an interesting case of acute stent thrombosis in a patient with chronic immune thrombocytopenic purpura (ITP) being treated with romiplostim.

Cardiac injury and troponin testing after orthopaedic surgery.

BACKGROUND: Cardiac injury after orthopaedic surgery is an increasing problem particularly in an ageing population. The detection of cardiac injury has been aided by the use of cardiac troponins which has also raised questions about the utility of this enzyme in the post-operative setting. OBJECTIVE: This review evaluates the diagnosis and pathophysiology of myocardial infarction after orthopaedic surgery and examines how myocardial injury is detected, with particular emphasis on the role of troponin testing. SUBJECTS: Eight recent orthopaedic trials evaluating the use of troponin were identified in the literature and included in this review. RESULTS: This review found that the diagnosis of myocardial infarction ismore difficult after surgery since classic symptoms may be atypical or absent. Therefore, there ismore reliance on the typical rise and fall in troponin to diagnose cardiac injury especially because electrocardiograph changes may be hard to detect. The pathophysiology of ischaemia after orthopaedic surgery may be different to ischaemia in the non-surgical setting. The incidence of troponin elevation is between 22 and 52.9% after emergency orthopaedic operations. Of note, patients sustaining a troponin elevation are often asymptomatic. Small studies have found troponin to be a prognostic marker of in-hospital cardiac complications, increased length of stay, increased likelihood of discharge to residential care and death at 1 year. No interventional studies have been published to date. CONCLUSION: Cardiac injury is an important complication after orthopaedic surgery. Studies have found that troponin testing can detect asymptomatic cardiac injury. These patients are at risk of poorer outcomes and future research should be directed towards treatment of these patients.

Early diagnosis of perioperative myocardial infarction after coronary bypass grafting: a study using biomarkers and cardiac magnetic resonance imaging.

BACKGROUND: Myocardial injury related to coronary artery bypass grafting (CABG) is poorly characterized, and understanding the characteristic release of biomarkers associated with revascularization injury might provide novel therapeutic opportunities. This study characterized early changes in biomarkers after revascularization injury during on-pump CABG. METHODS: This prospective study comprised 28 patients undergoing on-pump CABG and late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (CMRI) who underwent measurements of cardiac troponin I (cTnI), creatine kinase-MB, and inflammatory markers (C-reactive protein, serum amyloid A, myeloperoxidase, interleukin 6, tumor necrosis factor-α, matrix metalloproteinase 9a, monocyte chemotactic protein-1, plasminogen activator inhibitor-1a) at baseline, at 1, 6, 12, and 24 hours, and at 1 week (inflammatory markers only) post-CABG. Biomarker results at 1 hour were studied for a relationship to new myocardial infarction as defined by CMRI-LGE, and the diagnostic utility of combining positive biomarkers was assessed. RESULTS: All patients had an uneventful recovery, but 9 showed a new myocardial infarction demonstrated by new areas of hyperenhancement on CMR. Peak cTnI at 24 hours (ρ = 0.66, p < 0.001) and CK-MB (ρ = 0.66, p < 0.001) correlated with the amount of new LGE. At 1 hour, 3 biomarkers--cTnI, interleukin 6, and tumor necrosis factor-α--were significantly elevated in patients with vs those without new LGE. Receiver operating curve analysis showed cTnI was the most accurate at detecting new LGE at 1 hour: a cutoff of cTnI exceeding 5 µg/L at 1 hour had 67% sensitivity and 79% specificity for detecting new LGE. CONCLUSIONS: Unexpected CABG-related myocardial injury occurs in a significant proportion of patients. A cTnI test at 1 hour after CABG could potentially differentiate patients with significant revascularization injury.

Myocardial perfusion imaging after coronary artery bypass surgery using cardiovascular magnetic resonance: a validation study.

BACKGROUND: Absolute quantification of perfusion with cardiovascular magnetic resonance has not previously been applied in patients with coronary artery bypass grafting (CABG). Owing to increased contrast bolus dispersion due to the greater distance of travel through a bypass graft, this approach may result in systematic underestimation of myocardial blood flow (MBF). As resting MBF remains normal in segments supplied by noncritical coronary stenosis (<85%), measurement of perfusion in such territories may be utilized to reveal systematic error in the quantification of MBF. The objective of this study was to test whether absolute quantification of perfusion with cardiovascular magnetic resonance systematically underestimates MBF in segments subtended by bypass grafts. METHODS AND RESULTS: The study population comprised 28 patients undergoing elective CABG for treatment of multivessel coronary artery disease. Eligible patients had angiographic evidence of at least 1 myocardial segment subtended by a noncritically stenosed coronary artery (<85%). Subjects were studied at 1.5 T, with evaluation of resting MBF using model-independent deconvolution. Analyses were confined to myocardial segments subtended by native coronary arteries with <85% stenosis at baseline, and MBF was compared in grafted and ungrafted segments before and after revascularization. A total of 249 segments were subtended by coronary arteries with <85% stenosis at baseline. After revascularization, there was no significant difference in MBF in ungrafted (0.82±0.19 mL/min/g) versus grafted segments (0.82±0.15 mL/min/g, P=0.57). In the latter, MBF after revascularization did not change significantly from baseline (0.86±0.20 mL/min/g, P=0.82). CONCLUSIONS: Model-independent deconvolution analysis does not systematically underestimate blood flow in graft-subtended territories, justifying the use of this methodology to evaluate myocardial perfusion in patients with CABG.

With the "universal definition," measurement of creatine kinase-myocardial band rather than troponin allows more accurate diagnosis of periprocedural necrosis and infarction after coronary intervention.

OBJECTIVES: We aimed to assess the differential implications of creatine kinase-myocardial band (CK-MB) and troponin measurement with the universal definition of periprocedural injury after percutaneous coronary intervention. BACKGROUND: Differentiation between definitions of periprocedural necrosis and periprocedural infarction has practical, sociological, and research implications. Troponin is the recommended biomarker, but there has been debate about the recommended diagnostic thresholds. METHODS: Thirty-two patients undergoing multivessel percutaneous coronary intervention and late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging in a prospective study had cardiac troponin I, CK-MB, and inflammatory markers (C-reactive protein, serum amyloid A, myeloperoxidase, tumor necrosis factor alpha) measured at baseline, 1 h, 6 h, 12 h, and 24 h after the procedure. Three "periprocedural injury" groups were defined with the universal definition: G1: no injury (biomarker <99th percentile); G2: periprocedural necrosis (1 to 3 × 99th percentile); G3: myocardial infarction (MI) type 4a (>3 × 99th percentile). Differences in inflammatory profiles were analyzed. RESULTS: With CK-MB there were 17, 10, and 5 patients in groups 1, 2, and 3, respectively. Patients with CK-MB-defined MI type 4a closely approximated patients with new CMR-LGE injury. Groups defined with CK-MB showed progressively increasing percentage change in C-reactive protein and serum amyloid A, reflecting increasing inflammatory response (p < 0.05). Using cardiac troponin I resulted in 26 patients defined as MI type 4a, but only a small minority had evidence of abnormality on CMR-LGE, and only 3 patients were defined as necrosis. No differences in inflammatory response were evident when groups were defined with troponin. CONCLUSIONS: Measuring CK-MB is more clinically relevant for diagnosing MI type 4a, when applying the universal definition. Current troponin thresholds are oversensitive with the arbitrary limit of 3 × 99th percentile failing to discriminate between periprocedural necrosis and MI type 4a. (Myocardial Injury following Coronary Artery bypass Surgery versus Angioplasty: a randomised controlled trial using biochemical markers and cardiovascular magnetic resonance imaging; ISRCTN25699844).

Myocardial injury following coronary artery surgery versus angioplasty (MICASA): a randomised trial using biochemical markers and cardiac magnetic resonance imaging.

AIMS: To compare the frequency and extent of Troponin I and late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) defined injury following PCI compared with CABG in patients with multivessel and/or left main coronary artery disease (CAD), and interpret these finding in light of the new ESC/ACCF/AHA/WHF Task Force definitions for necrosis and infarction. METHODS AND RESULTS: Prospective, registered, single centre randomised controlled trial. Eighty patients with 3 vessel CAD (≥ 50% stenoses), or 2 vessel CAD including a type C lesion in the LAD, and/or left main disease were enrolled. Mean SYNTAX and EuroSCOREs were similar for both groups. Forty patients underwent PCI with drug eluting stents and 39 underwent CABG (one died prior to CABG). In the PCI group 6/38 (15.8%) patients had LGE, compared with 9/32 (28.1%) CABG patients (p = 0.25). Using the new Task Force definitions, necrosis occurred in 30/40 (75%) PCI patients and 35/35 (100%) CABG patients (p = 0.001), whilst infarction occurred in 30/40 (75%) PCI patients and 9/32 (28.1%) CABG patients (p = 0.0001). CONCLUSIONS: Periprocedural necrosis according to the Task Force definition was significantly lower in the PCI group, and universal in the CABG group. The incidence and extent of CMR defined infarction following PCI did not differ compared with CABG. This demonstrates that PCI can achieve revascularisation in complex patients without increased procedural myocardial damage.