Myocardial perfusion in cardiac amyloidosis.

AIMS: Cardiac involvement is the main driver of clinical outcomes in systemic amyloidosis and preliminary studies support the hypothesis that myocardial ischaemia contributes to cellular damage. The aims of this study were to assess the presence and mechanisms of myocardial ischaemia using cardiovascular magnetic resonance (CMR) with multiparametric mapping and histopathological assessment. METHODS AND RESULTS: Ninety-three patients with cardiac amyloidosis (CA) (light-chain amyloidosis n = 42, transthyretin amyloidosis n = 51) and 97 without CA (three-vessel coronary disease [3VD] n = 47, unobstructed coronary arteries n = 26, healthy volunteers [HV] n = 24) underwent quantitative stress perfusion CMR with myocardial blood flow (MBF) mapping. Twenty-four myocardial biopsies and three explanted hearts with CA were analysed histopathologically. Stress MBF was severely reduced in patients with CA with lower values than patients with 3VD, unobstructed coronary arteries and HV (CA: 1.04 ± 0.51 ml/min/g, 3VD: 1.35 ± 0.50 ml/min/g, unobstructed coronary arteries: 2.92 ± 0.52 ml/min/g, HV: 2.91 ± 0.73 ml/min/g; CA vs. 3VD p = 0.011, CA vs. unobstructed coronary arteries p < 0.001, CA vs. HV p < 0.001). Myocardial perfusion abnormalities correlated with amyloid burden, systolic and diastolic function, structural parameters and blood biomarkers (p < 0.05). Biopsies demonstrated abnormal vascular endothelial growth factor staining in cardiomyocytes and endothelial cells, which may be related to hypoxia conditions. Amyloid infiltration in intramural arteries was associated with severe lumen reduction and severe reduction in capillary density. CONCLUSION: Cardiac amyloidosis is associated with severe inducible myocardial ischaemia demonstrable by histology and CMR stress perfusion mapping. Histological evaluation indicates a complex pathophysiology, where in addition to systolic and diastolic dysfunction, amyloid infiltration of the epicardial arteries and disruption and rarefaction of the capillaries play a role in contributing to myocardial ischaemia.

A patient-specific multi-modality abdominal aortic aneurysm imaging phantom.

PURPOSE: Multimodality imaging of the vascular system is a rapidly growing area of innovation and research, which is increasing with awareness of the dangers of ionizing radiation. Phantom models that are applicable across multiple imaging modalities facilitate testing and comparisons in pre-clinical studies of new devices. Additionally, phantom models are of benefit to surgical trainees for gaining experience with new techniques. We propose a temperature-stable, high-fidelity method for creating complex abdominal aortic aneurysm phantoms that are compatible with both radiation-based, and ultrasound-based imaging modalities, using low cost materials. METHODS: Volumetric CT data of an abdominal aortic aneurysm were acquired. Regions of interest were segmented to form a model compatible with 3D printing. The novel phantom fabrication method comprised a hybrid approach of using 3D printing of water-soluble materials to create wall-less, patient-derived vascular structures embedded within tailored tissue-mimicking materials to create realistic surrounding tissues. A non-soluble 3-D printed spine was included to provide a radiological landmark. RESULTS: The phantom was found to provide realistic appearances with intravascular ultrasound, computed tomography and transcutaneous ultrasound. Furthermore, the utility of this phantom as a training model was demonstrated during a simulated endovascular aneurysm repair procedure with image fusion. CONCLUSION: With the hybrid fabrication method demonstrated here, complex multimodality imaging patient-derived vascular phantoms can be successfully fabricated. These have potential roles in the benchtop development of emerging imaging technologies, refinement of novel minimally invasive surgical techniques and as clinical training tools.

Five-year follow-up of intracoronary autologous cell therapy in acute myocardial infarction: the REGENERATE-AMI trial.

AIMS: The long-term outcomes of the intracoronary delivery of autologous bone marrow-derived cells (BMCs) after acute myocardial infarction are not well established. Following the promising 1 year results of the REGENERATE-AMI trial (despite it not achieving its primary endpoint), this paper presents the analysis of the 5 year clinical outcomes of these acute myocardial infarction patients who were treated with an early intracoronary autologous BMC infusion or placebo. METHODS AND RESULTS: A 5 year follow-up of major adverse cardiac events (defined as the composite of all-cause death, recurrent myocardial infarction, and all coronary revascularization) and of rehospitalization for heart failure was completed in 85 patients (BMC n = 46 and placebo n = 39). The incidence of major adverse cardiac events was similar between the BMC-treated patients and the placebo group (26.1% vs. 18.0%, P = 0.41). There were no cases of cardiac death in either group, but an increase in non-cardiac death was seen in the BMC group (6.5% vs. 0%, P = 0.11). The rates of recurrent myocardial infarction and repeat revascularization were similar between the two groups. There were no cases of rehospitalization for heart failure in either group. CONCLUSION: This 5 year follow-up analysis of the REGENERATE-AMI trial did not show an improvement in clinical outcomes for patients treated with cell therapy. This contrasts with the 1 year results which showed improvements in the surrogate outcome measures of ejection fraction and myocardial salvage index.

Quantitative cardiovascular magnetic resonance myocardial perfusion mapping to assess hyperaemic response to adenosine stress.

AIMS: Assessment of hyperaemia during adenosine stress cardiovascular magnetic resonance (CMR) remains a clinical challenge with lack of a gold-standard non-invasive clinical marker to confirm hyperaemic response. This study aimed to validate maximum stress myocardial blood flow (SMBF) measured using quantitative perfusion mapping for assessment of hyperaemic response and compare this to current clinical markers of adenosine stress. METHODS AND RESULTS: Two hundred and eighteen subjects underwent adenosine stress CMR. A derivation cohort (22 volunteers) was used to identify a SMBF threshold value for hyperaemia. This was tested in a validation cohort (37 patients with suspected coronary artery disease) who underwent invasive coronary physiology assessment on the same day as CMR. A clinical cohort (159 patients) was used to compare SMBF to other physiological markers of hyperaemia [splenic switch-off (SSO), heart rate response (HRR), and blood pressure (BP) fall]. A minimum SMBF threshold of 1.43 mL/g/min was derived from volunteer scans. All patients in the coronary physiology cohort demonstrated regional maximum SMBF (SMBFmax) >1.43 mL/g/min and invasive evidence of hyperaemia. Of the clinical cohort, 93% had hyperaemia defined by perfusion mapping compared to 71% using SSO and 81% using HRR. There was no difference in SMBFmax in those with or without SSO (2.58 ± 0.89 vs. 2.54 ± 1.04 mL/g/min, P = 0.84) but those with HRR had significantly higher SMBFmax (2.66 1.86 mL/g/min, P < 0.001). HRR >15 bpm was superior to SSO in predicting adequate increase in SMBF (AUC 0.87 vs. 0.62, P < 0.001). CONCLUSION: Adenosine-induced increase in myocardial blood flow is accurate for confirmation of hyperaemia during stress CMR studies and is superior to traditional, clinically used markers of adequate stress such as SSO and BP response.

Assessment of Multivessel Coronary Artery Disease Using Cardiovascular Magnetic Resonance Pixelwise Quantitative Perfusion Mapping.

OBJECTIVES: The authors sought to compare the diagnostic accuracy of quantitative perfusion maps to visual assessment (VA) of first-pass perfusion images for the detection of multivessel coronary artery disease (MVCAD). BACKGROUND: VA of first-pass stress perfusion cardiac magnetic resonance (CMR) may underestimate ischemia in MVCAD. Pixelwise perfusion mapping allows quantitative measurement of regional myocardial blood flow, which may improve ischemia detection in MVCAD. METHODS: One hundred fifty-one subjects recruited at 2 centers underwent stress perfusion CMR with myocardial perfusion mapping, and invasive coronary angiography with coronary physiology assessment. Ischemic burden was assessed by VA of first-pass images and by quantitative measurement of stress myocardial blood flow using perfusion maps. RESULTS: In patients with MVCAD (2-vessel [2VD] or 3-vessel disease [3VD]; n = 95), perfusion mapping identified significantly more segments with perfusion defects (median segments per patient 12 [interquartile range (IQR): 9 to 16] by mapping vs. 8 [IQR: 5 to 9.5] by VA; p < 0.001). Ischemic burden (IB) measured using mapping was higher in MVCAD compared with IB measured using VA (3VD mapping 100 % (75% to 100%) vs. first-pass 56% (38% to 81%) ; 2VD mapping 63% (50% to 75%) vs. first-pass 41% (31% to 50%); both p < 0.001), but there was no difference in single-vessel disease (mapping 25% (13% to 44%) vs. 25% (13% to 31%). Perfusion mapping was superior to VA for the correct identification of extent of coronary disease (78% vs. 58%; p < 0.001) due to better identification of 3VD (87% vs. 40%) and 2VD (71% vs. 48%). CONCLUSIONS: VA of first-pass stress perfusion underestimates ischemic burden in MVCAD. Pixelwise quantitative perfusion mapping increases the accuracy of CMR in correctly identifying extent of coronary disease. This has important implications for assessment of ischemia and therapeutic decision-making.

Duration of type 2 diabetes mellitus and systolic blood pressure as determinants of severity of coronary stenosis and adverse events in an asymptomatic diabetic population: PROCEED study.

BACKGROUND: Evidence from imaging studies suggests a high prevalence of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). However, there are no criteria for initiating screening for CAD in this population. The current study investigated whether clinical and demographic characteristics can be used to predict significant CAD in patients with T2DM. METHODS: Computed tomography coronary angiography (CTCA) and laboratory assessments were performed in 259 patients diagnosed with T2DM attending clinics in Northwest London, UK. Coronary artery calcium (CAC) was calculated during CTCA. Significant plaque was defined as one causing more than 50% luminal stenosis. Associations between groups and variables were evaluated using Student's t test, Chi-square tests and univariate and multivariate regression analysis. P < 0.05 was considered statistically significant. RESULTS: Among patients with a median duration of T2DM of 13 years and a mean age of 62.0 years, median CAC score was 105.91 Agatston Units. In a multivariate analyses, duration of diabetes, CAC score and the presence and number of coronary artery plaques and presence of significant plaque were significant predictors of cardiovascular adverse events. Systolic blood pressure (SBP) had borderline significance as a predictor of cardiovascular events (p = 0.05). In a receiver operating characteristic curve (ROC) analysis, duration of diabetes of > 10.5 years predicted significant CAD (sensitivity, 75.3%; specificity 48.2%). Area under the ROC curve was 0.67 when combining duration of T2DM > 10.5 years and SBP of > 139 mm Hg. Adverse cardiovascular events after a median follow-up of 22.8 months were also significantly higher in those with duration of T2DM > 10.5 years and SBP > 140 mm Hg (log rank p = 0.02 and 0.009, respectively). CONCLUSIONS: Routine screening for CAD using CTCA should be considered for patients with a diagnosis of T2DM for > 10.5 years and SBP > 140 mm Hg. Trial registration Clinicaltrials.gov identifier: NCT02109835, 10 April 2014 (retrospectively registered).

Automated Pixel-Wise Quantitative Myocardial Perfusion Mapping by CMR to Detect Obstructive Coronary Artery Disease and Coronary Microvascular Dysfunction: Validation Against Invasive Coronary Physiology.

OBJECTIVES: This study sought to assess the performance of cardiovascular magnetic resonance (CMR) myocardial perfusion mapping against invasive coronary physiology reference standards for detecting coronary artery disease (CAD, defined by fractional flow reserve [FFR] ≤0.80), microvascular dysfunction (MVD) (defined by index of microcirculatory resistance [IMR] ≥25) and the ability to differentiate between the two. BACKGROUND: Differentiation of epicardial (CAD) and MVD in patients with stable angina remains challenging. Automated in-line CMR perfusion mapping enables quantification of myocardial blood flow (MBF) to be performed rapidly within a clinical workflow. METHODS: Fifty patients with stable angina and 15 healthy volunteers underwent adenosine stress CMR at 1.5T with quantification of MBF and myocardial perfusion reserve (MPR). FFR and IMR were measured in 101 coronary arteries during subsequent angiography. RESULTS: Twenty-seven patients had obstructive CAD and 23 had nonobstructed arteries (7 normal IMR, 16 abnormal IMR). FFR positive (epicardial stenosis) areas had significantly lower stress MBF (1.47 ± 0.48 ml/g/min) and MPR (1.75 ± 0.60) than FFR-negative IMR-positive (MVD) areas (stress MBF: 2.10 ± 0.35 ml/g/min; MPR: 2.41 ± 0.79) and normal areas (stress MBF: 2.47 ± 0.50 ml/g/min; MPR: 2.94 ± 0.81). Stress MBF ≤1.94 ml/g/min accurately detected obstructive CAD on a regional basis (area under the curve: 0.90; p < 0.001). In patients without regional perfusion defects, global stress MBF <1.82 ml/g/min accurately discriminated between obstructive 3-vessel disease and MVD (area under the curve: 0.94; p < 0.001). CONCLUSIONS: This novel automated pixel-wise perfusion mapping technique can be used to detect physiologically significant CAD defined by FFR, MVD defined by IMR, and to differentiate MVD from multivessel coronary disease. A CMR-based diagnostic algorithm using perfusion mapping for detection of epicardial disease and MVD warrants further clinical validation.

Myocardial Edema and Prognosis in Amyloidosis.

BACKGROUND: Prognosis in light-chain (AL) and transthyretin (ATTR) amyloidosis is influenced by cardiac involvement. ATTR amyloidosis has better prognosis than AL amyloidosis despite more amyloid infiltration, suggesting additional mechanisms of damage in AL amyloidosis. OBJECTIVES: The aim of the study was to assess the presence and prognostic significance of myocardial edema in patients with amyloidosis. METHODS: The study recruited 286 patients: 100 with systemic AL amyloidosis, 163 with cardiac ATTR amyloidosis, 12 with suspected cardiac ATTR amyloidosis (grade 1 on 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid), 11 asymptomatic individuals with amyloidogenic TTR gene mutations, and 30 healthy volunteers. All subjects underwent cardiovascular magnetic resonance with T1 and T2 mapping and 16 underwent endomyocardial biopsy. RESULTS: Myocardial T2 was increased in amyloidosis with the degree of elevation being highest in untreated AL patients (untreated AL amyloidosis 56.6 ± 5.1 ms; treated AL amyloidosis 53.6 ± 3.9 ms; ATTR amyloidosis 54.2 ± 4.1 ms; each p < 0.01 compared with control subjects: 48.9 ± 2.0 ms). Left ventricular (LV) mass and extracellular volume fraction were higher in ATTR amyloidosis compared with AL amyloidosis while LV ejection fraction was lower (p < 0.001). Histological evidence of edema was present in 87.5% of biopsy samples ranging from 5% to 40% myocardial involvement. Using Cox regression models, myocardial T2 predicted death in AL amyloidosis (hazard ratio: 1.48; 95% confidence interval: 1.20 to 1.82) and remained significant after adjusting for extracellular volume fraction and N-terminal pro-B-type natriuretic peptide (hazard ratio: 1.32; 95% confidence interval: 1.05 to 1.67). CONCLUSIONS: Myocardial edema is present in cardiac amyloidosis by histology and cardiovascular magnetic resonance T2 mapping. T2 is higher in untreated AL amyloidosis compared with treated AL and ATTR amyloidosis, and is a predictor of prognosis in AL amyloidosis. This suggests mechanisms additional to amyloid infiltration contributing to mortality in amyloidosis.

Microparticles in acute coronary syndrome.

BACKGROUND: Emerging evidence supports the role of cell-derived microparticles (MPs) in the pathophysiology of acute coronary syndrome (ACS). OBJECTIVES: To explore the relationship between coronary and systemic MP levels, investigate the correlation between MPs, inflammatory markers and Troponin T in patients with ACS. METHODS: Thirty seven patients with ACS scheduled for percutaneous coronary interventions (PCI) were studied. Eleven patients with stable angina (SA) were included as a control group. AnnexinV+MPs (AnV+MPs) and activated platelet-monocyte aggregates (PMA) from right atrium (RA) and culprit coronary artery (CO) distal to culprit lesion were measured using flow cytometry. High sensitivity C-reactive protein (CRP), Interleukin - 6 (IL-6), tumour necrosis factor - α (TNF-α), serum amyloid A (SAA) and Troponin T were assayed. RESULTS: Total and cell specific AnV+MP expression were higher in the ACS group in both the CO and RA, with greater levels detected in the CO. Platelet activation showed positive correlation with Troponin-T and platelet MP in both CO and RA of the ACS group (r=0.4 for both; p=0.04 & p=0.03 respectively). Inflammatory markers levels did not differ between the ACS and SA patients. CONCLUSIONS: Elevated coronary and systemic MP levels and positive correlation of platelet activation with Troponin-T and platelet MPs suggest a pathogenic role for MPs in ACS.

Superior long term outcome associated with native vessel versus graft vessel PCI following secondary PCI in patients with prior CABG.

BACKGROUND: Secondary percutaneous coronary intervention (PCI) in patients with prior coronary artery bypass graft surgery is increasingly common. Graft vessel PCI has higher rates of adverse events compared with native coronary vessel PCI. AIM: To investigate the clinical outcomes of patients with prior CABG who underwent secondary PCI of either a graft vessel (GV), a native coronary vessel (NV) or both graft and native (NG) vessels. METHODS: 220 patients (84% male) who underwent PCI in our institution to either GV (n=89), NV (n=103) or both GV and NV (NG group) (n=28) were studied. The study population underwent 378 procedures (GV group; n=126, NV group; n=164 and NG group; n=88). Median follow up was for 36months [range 2-75months]. RESULTS: Target vessel revascularisation (TVR) occurred in 12.5% of the GV group and 3.6% in the NV group [p=0.0004], and was predominantly due to in-stent restenosis. Patients who had PCI due to TVR were more likely to suffer from diabetes and peripheral vascular disease. History of chronic renal failure was associated with higher risk (HR 2.21, p=0.005) whereas preserved left ventricular ejection fraction (LVEF) with lower risk (HR 0.17, p=0.0007) of death. The median survival (interval between CABG and end of follow-up period) was lower in the GV compared with the NV group (315 vs 372months p=0.005). CONCLUSION: This registry demonstrates inferior long term outcome for patients undergoing secondary PCI of GV versus NV. Where possible, a strategy of NV rather than GV target PCI should be considered in patients with prior CABG. CONDENSED ABSTRACT: Secondary PCI in patients with prior CABG surgery is increasingly common. Graft vessel PCI has inferior outcomes with high rates of restenosis and occlusion compared with native coronary vessel PCI. We studied the clinical outcomes of 220 patients with prior CABG who underwent secondary PCI to either a graft vessel (GV), a native coronary vessel (NV) or both graft and native (NG) vessels. Target vessel revascularisation was 5 times higher in the GV compared with the NV group. History of CRF and impaired left ventricular function were associated with higher risk of death. We also found that the median survival (interval between CABG and end of follow-up period) was better in the NV group compared with GV group. This registry study demonstrates inferior long term outcome for patients undergoing secondary PCI of GV. A strategy of NV rather than GV target PCI should be considered in patients with prior CABG.

Cardiovascular risk stratification in familial hypercholesterolaemia.

Familial hypercholesterolaemia (FH) is a common autosomal-dominant disorder in most European countries. Patients with FH are characterised by a raised level of low-density lipoprotein cholesterol and a high risk of premature coronary heart disease (CHD). Currently there is no consensus regarding the clinical utility to predict future coronary events or testing for the presence of subclinical atherosclerotic disease in asymptomatic patients with FH. Family screening of patients with FH as recommended by the UK National Institute of Health and Care Excellence guideline would result in finding many young individuals with a diagnosis of FH who are clinically asymptomatic. The traditional CHD risk scores, that is, the Framingham score, are insufficient in risk prediction in this group of young individuals. In addition, a better understanding of the genetic aetiology of the FH phenotype and CHD risk in monogenic FH and polygenic hypercholesterolaemia is needed. Non-invasive imaging methods such as carotid intima-media thickness measurement might produce more reliable information in finding high-risk patients with FH. The potential market authorisation of novel therapeutic agents such as PCSK9 monoclonal inhibitors makes it essential to have a better screening programme to prioritise the candidates for treatment with the most severe form of FH and at higher risk of coronary events. The utility of new imaging techniques and new cardiovascular biomarkers remains to be determined in prospective trials.

A randomized double-blind control study of early intra-coronary autologous bone marrow cell infusion in acute myocardial infarction: the REGENERATE-AMI clinical trial†.

AIMS: Clinical trials suggest that intracoronary delivery of autologous bone marrow-derived cells (BMCs) 1-7 days post-acute myocardial infarction (AMI) may improve left ventricular (LV) function. Earlier time points have not been evaluated. We sought to determine the effect of intracoronary autologous BMC on LV function when delivered within 24 h of successful reperfusion therapy. METHODS AND RESULTS: A multi-centre phase II randomized, double-blind, and placebo-controlled trial. One hundred patients with anterior AMI and significant regional wall motion abnormality were randomized to receive either intracoronary infusion of BMC or placebo (1:1) within 24 h of successful primary percutaneous intervention (PPCI). The primary endpoint was the change in left ventricular ejection fraction (LVEF) between baseline and 1 year as determined by advanced cardiac imaging. At 1 year, although LVEF increased compared with baseline in both groups, the between-group difference favouring BMC was small (2.2%; 95% confidence interval, CI: -0.5 to 5.0; P = 0.10). However, there was a significantly greater myocardial salvage index in the BMC-treated group compared with placebo (0.1%; 95% CI: 0.0-0.20; P = 0.048). Major adverse events were rare in both treatment groups. CONCLUSION: The early infusion of intracoronary BMC following PPCI for patients with AMI and regional wall motion abnormality leads to a small non-significant improvement in LVEF when compared with placebo; however, it may play an important role in infarct remodelling and myocardial salvage.

Diagnostic role of coronary calcium scoring in the rapid access chest pain clinic: prospective evaluation of NICE guidance.

BACKGROUND: Coronary artery calcium (CAC) imaging by unenhanced computed X-ray tomography (CT) is recommended as an initial diagnostic test for patients with stable chest pain symptoms but a low likelihood (10-29%) of underlying obstructive coronary artery disease (CAD) after clinical assessment. The recommendation has not previously been tested prospectively in a rapid access chest pain clinic (RACPC). METHODS: We recruited 300 consecutive patients presenting with stable chest pain to the RACPC of three hospitals. All patients underwent CAC imaging, followed by invasive coronary angiography (ICA) in patients with CAC ≥ 1000 Agatston units (Au) and CT coronary angiography (CTCA) in those with CAC <1000. Patients with 50-70% stenosis on CTCA underwent myocardial perfusion scintigraphy (MPS) while those with ≥ 70% stenosis underwent ICA. Obstructive CAD was defined as ≥ 70% stenosis on ICA or the presence of inducible ischaemia on MPS. Patients were followed up clinically for a mean of 17 (SD 6) months. RESULTS: The mean patient age was 60.6 (SD 9.6) years and 48% were males. Obstructive CAD was found in 56 (19%) patients, of whom 42 (14%) underwent revascularization. CAC was zero in 131 (44%) patients, of whom two (1.5%) had obstructive CAD and one (0.8%) underwent revascularization. The sensitivity, specificity, negative predictive value, and positive predictive value of CAC ≥ 1 for detection of obstructive CAD were 96, 53, 32, and 98%, respectively. None of the 57 patients with low pre-test probability of CAD and zero CAC had obstructive CAD or suffered a cardiovascular event during the follow-up. CONCLUSION: Patients with stable chest pain symptoms but a low likelihood of CAD can safely be diagnosed as not having obstructive CAD in the absence of detectable coronary calcification by unenhanced CT. Patients with CAC >400 Au have a high prevalence of obstructive CAD and further investigation with ICA or functional imaging may be warranted rather than CTCA. These findings support NICE guidance for the investigation of stable chest pain. ClinicalTrials gov identifier: NCT01464203.

Depressed mood, positive affect, and heart rate variability in patients with suspected coronary artery disease.

OBJECTIVE: To test associations between heart rate variability (HRV), depressed mood, and positive affect in patients with suspected coronary artery disease (CAD). Depression is associated with impaired HRV post acute cardiac events, but evidence in patients with stable coronary artery disease (CAD) is inconsistent. METHODS: Seventy-six patients (52 men, 24 women; mean age = 61.1 years) being investigated for suspected CAD on the basis of symptomatology and positive noninvasive tests, completed 24-hour electrocardiograms. The Beck Depression Inventory (BDI) was administered, and positive and depressed affect was measured over the study period with the Day Reconstruction Method (DRM). A total of 46 (60.5%) patients were later found to have definite CAD. HRV was analyzed, using spectral analysis. RESULTS: Typical diurnal profiles of HRV were observed, with greater normalized high frequency (HF) and lower normalized low frequency (LF) power in the night compared with the day. BDI depression scores were not consistently associated with HRV. But positive affect was associated with greater normalized HF power (p = .039) and reduced normalized LF power (p = .007) independently of age, gender, medication with beta blockers, CAD status, body mass index, smoking, and habitual physical activity level. In patients with definite CAD, depressed affect assessed using the DRM was associated with reduced normalized HF power and heightened normalized LF power (p = .007) independently of covariates. CONCLUSIONS: Relationships between depression and HRV in patients with CAD may depend on affective experience over the monitoring period. Enhanced parasympathetic cardiac control may be a process through which positive affect protects against cardiovascular disease.

Tumour necrosis factor-alpha and interleukin-6 release during primary percutaneous coronary intervention for acute myocardial infarction is related to coronary collateral flow.

OBJECTIVES: We tested the hypothesis that there was an association between tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) release and measured coronary collateral flow in patients undergoing primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). BACKGROUND: Tumour necrosis factor-alpha and IL-6 increase during acute myocardial infarction (AMI). However, their relation to coronary collateral flow is unknown. METHODS: Twelve patients with AMI due to complete thrombotic coronary occlusion underwent primary PCI within 12 h of symptom onset. Doppler-derived collateral flow index (CFI) was measured during first balloon inflation. TNF-alpha, IL-6, creatine kinase (CK), CK-MB fraction were measured from venous plasma samples serially for 24 h. Area at risk was determined off-line by coronary arteriography. Ejection fraction (EF) was measured using biplane left ventricular angiography. RESULTS: Maximal CK release varied between 569 and 6276 U/l and area at risk varied between 7 and 47% of myocardium. Tumour necrosis factor-alpha (peak 4.4+/-0.5 pg/ml) and IL-6 (peak 35.5+/-3.0 pg/ml) increased in all patients. Peak TNF-alpha and IL-6 release was independent of CK, CKMB. No minimal threshold of myocardial necrosis for cytokine expression could be detected. Similarly, TNF-alpha and IL-6 release was also independent of time to reperfusion, area at risk or EF. Using univariate regression analysis, peak TNF-alpha inversely correlated with CFI (r = 0.67, P = 0.017) whereas IL-6 positively correlated with CFI (r = 0.76, P = 0.004). CONCLUSIONS: Acute myocardial infarction is associated with a significant rise in TNF-alpha and IL-6 levels independent of infarct size or myonecrosis. Tumour necrosis factor-alpha and IL-6 correlate dichotomously with CFI indicating differing roles in reperfused AMI.

Learning on the Web. Case 2: patent foramen ovale (PFO) and paradoxical embolism.

A 36 year old woman ruptured her right Achilles tendon in a skiing accident. Previous medical history is unremarkable except for a history of migraine for many years. She is married with three children with no history of spontaneous miscarriage. She smokes 15 cigarettes a day and takes the oral contraceptive pill. She is admitted to a local hospital where surgery to repair the Achilles tendon is performed followed by fitting of a plaster cast. Due to pain from the plaster cast she is slow to mobilise. On day 7 postoperatively she develops increasing pain in the right leg. When the plaster is removed the right calf is found to be painful, warm, and swollen. The next day while straining on the toilet she collapsed with left arm weakness. Clinical examination revealed dysarthria with pyramidal weakness of the left arm. The significance of these symptoms, the diagnosis, and the short and long term treatment of these postoperative problems are discussed in an interactive case presentation.