Coronary Artery Lesion Lipid Content and Plaque Burden in Diabetic and Nondiabetic Patients: PROSPECT II.

BACKGROUND: Patients with diabetes have increased rates of major adverse cardiac events (MACEs). We hypothesized that this is explained by diabetes-associated differences in coronary plaque morphology and lipid content. METHODS: In PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree), 898 patients with acute myocardial infarction with or without ST-segment elevation underwent 3-vessel quantitative coronary angiography and coregistered near-infrared spectroscopy and intravascular ultrasound imaging after successful percutaneous coronary intervention. Subsequent MACEs were adjudicated to either treated culprit lesions or untreated nonculprit lesions. This substudy stratified patients by diabetes status and assessed baseline culprit and nonculprit prevalence of high-risk plaque characteristics defined as maximum plaque burden ≥70% and maximum lipid core burden index ≥324.7. Separate covariate-adjusted multivariable models were performed to identify whether diabetes was associated with nonculprit lesion-related MACEs and high-risk plaque characteristics. RESULTS: Diabetes was present in 109 of 898 patients (12.1%). During a median 3.7-year follow-up, MACEs occurred more frequently in patients with versus without diabetes (20.1% versus 13.5% [odds ratio (OR), 1.94 (95% CI, 1.14-3.30)]), primarily attributable to increased risk of myocardial infarction related to culprit lesion restenosis (4.3% versus 1.1% [OR, 3.78 (95% CI, 1.12-12.77)]) and nonculprit lesion-related spontaneous myocardial infarction (9.3% versus 3.8% [OR, 2.74 (95% CI, 1.25-6.04)]). However, baseline prevalence of high-risk plaque characteristics was similar for patients with versus without diabetes concerning culprit (maximum plaque burden ≥70%: 90% versus 93%, P=0.34; maximum lipid core burden index ≥324.7: 66% versus 70%, P=0.49) and nonculprit lesions (maximum plaque burden ≥70%: 23% versus 22%, P=0.37; maximum lipid core burden index ≥324.7: 26% versus 24%, P=0.47). In multivariable models, diabetes was associated with MACEs in nonculprit lesions (adjusted OR, 2.47 [95% CI, 1.21-5.04]) but not with prevalence of high-risk plaque characteristics (adjusted OR, 1.21 [95% CI, 0.86-1.69]). CONCLUSIONS: Among patients with recent myocardial infarction, both treated and untreated lesions contributed to the diabetes-associated ≈2-fold increased MACE rate during the 3.7-year follow-up. Diabetes-related plaque characteristics that might underlie this increased risk were not identified by multimodality imaging. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02171065.

Automatic Estimation of Coronary Blood Flow Velocity Step 1 for Developing a Tool to Diagnose Patients With Micro-Vascular Angina Pectoris.

Aim: Our aim was to automatically estimate the blood velocity in coronary arteries using cine X-ray angiographic sequence. Estimating the coronary blood velocity is a key approach in investigating patients with angina pectoris and no significant coronary artery disease. Blood velocity estimation is central in assessing coronary flow reserve. Methods and Results: A multi-step automatic method for blood flow velocity estimation based on the information extracted solely from the cine X-ray coronary angiography sequence obtained by invasive selective coronary catheterization was developed. The method includes (1) an iterative process of segmenting coronary arteries modeling and removing the heart motion using a non-rigid registration, (2) measuring the area of the segmented arteries in each frame, (3) fitting the measured sequence of areas with a 7° polynomial to find start and stop time of dye propagation, and (4) estimating the blood flow velocity based on the time of the dye propagation and the length of the artery-tree. To evaluate the method, coronary angiography recordings from 21 patients with no obstructive coronary artery disease were used. In addition, coronary flow velocity was measured in the same patients using a modified transthoracic Doppler assessment of the left anterior descending artery. We found a moderate but statistically significant correlation between flow velocity assessed by trans thoracic Doppler and the proposed method applying both Spearman and Pearson tests. Conclusion: Measures of coronary flow velocity using a novel fully automatic method that utilizes the information from the X-ray coronary angiographic sequence were statistically significantly correlated to measurements obtained with transthoracic Doppler recordings.

Aerobic interval training in patients with heart failure and an implantable cardioverter defibrillator: a controlled study evaluating feasibility and effect.

BACKGROUND: Aerobic interval training (AIT) has been shown to be superior to moderate continuous exercise training in improving exercise capacity and endothelial function in patients with both coronary artery disease and heart failure (HF). The objective of this study was to evaluate this training modality in patients with HF and an implantable cardioverter defibrillator (ICD) with regard to feasibility, safety, and effect. METHODS: We prospectively included 38 patients with an ICD: 26 patients participated in an AIT programme for 3 months, while 12 patients served as controls. At baseline and 12-week follow up, patients were assessed with a maximal ergospirometry stress test, echocardiography, endothelial function testing, and ICD interrogation. RESULTS: No exercise-related adverse events occurred during or soon after the training sessions. ICD interrogation revealed no sustained arrhythmias, antitachycardia pacing, or ICD discharge related to exercise sessions. The AIT programme led to a significant increase in peak oxygen uptake, cycle ergometer workload, and endothelial function compared to the control group. The training programme was safe and not associated with any adverse events or ICD-related complications. CONCLUSIONS: An AIT programme is feasible and seems safe in a well-treated, stable ICD population. Further, AIT for 3 months results in significantly increased aerobic capacity and endothelial function in this population.

Comparison of outcomes in patients with ST-segment elevation myocardial infarction discharged on versus not on statin therapy (from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction Trial).

Statin therapy is indicated after ST-segment elevation myocardial infarction (STEMI) to reduce recurrent ischemic events, but approximately 6% of patients with STEMI do not receive a statin prescription at discharge. This substudy aimed to define the clinical outcomes and patient characteristics associated with statin nonprescription after STEMI. We compared clinical, angiographic, and procedural characteristics and in-hospital, 30-day, 1-year, 2-year, and 3-year outcomes in 3,512 patients discharged after STEMI with and without (6%) statin prescriptions in the harmonizing outcomes with revascularization and stents in acute myocardial infarction trial (www.clinicaltrials.gov, NCT00433966). Statin nonprescription was associated with female sex, nonwhite race, previous bypass surgery, heart failure, renal impairment, anemia, thrombocytopenia, care in the United States, lower prescription rates of antiplatelets and neurohormonal antagonists, less percutaneous coronary intervention and stents, and, in 26% of cases, angiographically normal or nonobstructed coronary arteries. At every time point of follow-up after discharge, patients with no discharge statin prescription had significantly higher rates of net adverse clinical events, major adverse cardiac events, major bleeding unrelated to bypass surgery, and death. After multivariable adjustment, absence of a discharge statin prescription independently predicted 3-year major adverse cardiac event (hazard ratio 1.54, 95% confidence interval 1.15 to 2.07, p=0.0037) and death (hazard ratio 2.30, 95% confidence interval 1.41 to 3.77, p=0.0009). In conclusion, within the framework of this randomized trial of patients presenting with STEMI, approximately 6% of patients were discharged without statin therapy. Absence of a discharge statin prescription after STEMI was an independent predictor of ischemic events including death.

Perceptions of healthcare professionals' support, shock anxiety and device acceptance among implantable cardioverter defibrillator recipients.

AIMS: To investigate the extent to which perceived support from healthcare professionals and shock anxiety is related to device acceptance among implantable cardioverter defibrillator recipients. BACKGROUND: Device acceptance can be influenced by several factors, one of which is shock anxiety associated with poor device acceptance. Reduced shock anxiety, as well as increased device acceptance, has been reported after psycho-educational programmes. As healthcare professionals appear to play a significant role in providing support and education during regular follow-up visits, they may constitute an important social support system that could be another factor influencing device acceptance. However, little is known about the relationship between perceived support from healthcare professionals and device acceptance among recipients. DESIGN: A cross-sectional survey design. METHODS: A sample comprising implantable cardioverter defibrillator recipients completed questionnaires assessing perceived support from healthcare professionals, shock anxiety and device acceptance. Demographic and clinical data were collected by self-report and from medical records in September-October 2010. RESULTS: The descriptive results indicated that approximately 85% of the recipients experienced high device acceptance. Regression analysis demonstrated that constructive support from healthcare professionals was positively associated with device acceptance and moderated the negative relationship between shock anxiety and device acceptance. Non-constructive support and shock anxiety had a negative statistical association with device acceptance. CONCLUSIONS: Healthcare professionals may represent a valuable constructive support system that can enhance device acceptance among implantable cardioverter defibrillator recipients, partly by preventing shock anxiety from leading to poor device acceptance. Non-constructive communication on the part of healthcare professionals could hinder device acceptance.

Perceived support from healthcare professionals, shock anxiety and post-traumatic stress in implantable cardioverter defibrillator recipients.

AIMS AND OBJECTIVES: To investigate (1) the extent to which shock anxiety and perceived support from healthcare professionals are related to post-traumatic stress disease (PTSD) symptoms and (2) the extent to which perceived support from healthcare professionals moderates the relationship between shock anxiety and PTSD symptoms in implantable cardioverter defibrillator recipients. An additional aim was to describe the level of PTSD symptoms and perceptions of support from healthcare professionals. BACKGROUND: Studies examining PTSD symptoms among implantable cardioverter defibrillator recipients are still sparse. In addition, little is known about how perceived support from healthcare professionals is related to PTSD symptoms. DESIGN: Cross-sectional survey design. METHODS: Recipients (n = 167) with implantable cardioverter defibrillator attending an outpatient device clinic completed questionnaires assessing shock anxiety, PTSD symptoms and perceived support from healthcare professionals. RESULTS: The results indicated that between ten and 15% of the recipients experienced moderate to severe symptoms of PTSD. Although a majority perceived constructive support from healthcare professionals, 12% perceived nonconstructive support. Regression analysis demonstrated that shock anxiety and perceived nonconstructive support from healthcare professionals had a statistically significant (p < 0·01) association with PTSD symptoms. Moreover, the results suggest that associations between shock anxiety and PTSD symptoms were significantly (p < 0·01) moderated by perceived nonconstructive support from healthcare professionals. Young age, short time since implantation and secondary prevention indication were also significantly associated with PTSD symptoms. CONCLUSIONS: The results indicate that nonconstructive support from healthcare professionals can increase the tendency to develop PTSD symptoms, particularly in those who experience shock anxiety. RELEVANCE TO CLINICAL PRACTICE: Healthcare professionals should pay more attention to the way in which they communicate information to the recipients during follow-up visits. Clinically based strategies and interventions targeting shock anxiety and PTSD symptoms should be carried out.

Is it safe to use TNF-α blockers for systemic inflammatory disease in patients with heart failure? Importance of dosage and receptor specificity.

Tumor necrosis factor-alpha (TNF-α) blockers are widely used in the treatment of chronic inflammatory diseases, especially chronic arthritis. Current guidelines advise against the use of such agents in patients who have a concomitant heart failure. Consequently, a group of patients with a devastating inflammatory disease cannot benefit from an excellent treatment option. After a critical review of the current literature, we conclude that there is not sufficient evidence to warn against such a regimen if recommended standard doses are used. A negative effect on the heart function seems to occur if unconventional high doses of TNF-α blockers are given. The theoretical background for this is discussed.

Increased confidence to engage in physical exertion: older ICD recipients' experiences of participating in an exercise training programme.

BACKGROUND: Research suggests that exercise training (ET) programmes may improve both physical and psychosocial functioning in implantable cardioverter defibrillator (ICD) recipients. Most of this research has been conducted by means of quantitative methods. However, knowledge of older ICD recipients' experiences of participating in such programmes is sparse. There is thus a need for more detailed qualitative data from the perspective of older patients. AIM: To describe older ICD recipients' experiences of participating in an ET programme. METHODS: A qualitative design with semistructured interviews involving 12 older ICD recipients who had participated in a 3-month ET programme. Mini-disc recordings of the interviews were transcribed verbatim and analysed using content analysis. RESULTS: The analysis revealed two major themes: (1) 'increased confidence to engage in physical exertion'; and (2) 'increased satisfaction with life'. The first theme is illustrated by three subthemes: 'perceived support from physiotherapists', 'perceiving the heart rate monitor as a motivation to exercise', and 'perceiving peers as motivators for enjoyment and making the effort to exercise'. The second theme was illustrated by the following subthemes: 'perceived psychosocial benefits', 'perceived physical benefits', and 'exercise as a new health habit'. CONCLUSION: The findings indicate that exercising in a cardiac rehabilitation centre together with peers and supervised by skilled healthcare professionals may increase motivation to exert oneself, leading to emotional and physical benefits as well as a more social and active lifestyle for older ICD recipients.

Effect of exercise training on interleukin-6, tumour necrosis factor alpha and functional capacity in heart failure.

Background. We pooled data from four studies, to establish whether exercise training programs were able to modulate systemic cytokine levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). A second aim was to establish if differences in ExT regimens are related to degree of change in cytokines and peak VO(2). Methods. Data from four centres relating to training protocol, exercise capacity, and cytokine measures (TNF-alpha and IL-6) were pooled for analysis. Results. Data for 106 CHF patients were collated (98 men, age 62 ± 10 yrs, wt 79 ± 14 Kg). Patients were moderately impaired (peak VO(2) 16.9 ± 4.4 mls/kg/min), with moderate LV systolic dysfunction (EF 30 ± 6.9%), 78% (83) had ischaemic cardiomyopathy. After ExT, peak VO(2) increased 1.4 ± 3.4 ml/kg/min (P < .001), serum TNF-alpha decreased 1.9 ± 8.6 pg/ml (P = .02) and IL-6 was not significantly changed (0.5 ± 5.4 pg/ml, P = .32) for the whole group. Baseline and post-training peak VO(2) changes were not correlated with change in cytokine levels. Conclusions. Exercise training reduces levels TNF-alpha but not IL-6 in CHF. However, across a heterogenic patient group, change in peak VO(2) was not correlated with alterations in cytokine levels. While greater exercise volume (hours) was superior in improving peak VO(2), no particular characteristic of ExT regimes appeared superior in effecting change in serum cytokines.

Inflammatory response to percutaneous coronary intervention in stable coronary artery disease.

Percutaneous coronary intervention (PCI) can be regarded as a model for mechanical induced plaque rupture. The objective of this study was to evaluate the inflammatory response to PCI in stable coronary artery disease (CAD) by analysing plasma levels of a wide range of inflammatory mediators. Consecutively, we included 36 patients with stable angina pectoris after successful revascularization by PCI with implantation of a bare metal stent (BMS) or a drug eluting stent (DES). Patients were followed for 7 days with serial measurements of inflammatory mediators in plasma. C-reactive protein (CRP) and Pentraxin 3 showed a statistical significant early increase after PCI peaking at 3 days and 3 h, respectively. Vascular cell adhesion molecule-1 (VCAM-1) increased significantly with a peak at 3 days, while E-selectin showed a statistical significant gradual decrease. Markers of platelet mediated inflammation showed increasing (CD40 ligand) and decreasing (P-selectin) levels after PCI. While monocyte chemoattractant protein, CCL21 and CXCL16 increased rapidly in response to PCI, Interleukin-8, CCL19 and RANTES decreased. Patients with DES had significantly lower levels of VCAM-1 and RANTES compared to those with BMS. A femoral access site was associated with higher CRP levels than a radial access site. The use of glycoprotein-IIb/IIIa-inhibitors was associated with significantly higher CD40L and RANTES levels. Our findings underscore the complex nature of the inflammatory responses during PCI in stable CAD, and suggest that simultaneous measurements of several markers may be needed to characterize these PCI-related responses. The responses were only in a minor degree influenced by stent type, access site and the use of glycoprotein-IIb/IIIa-inhibitors.

A history of late and very late stent thrombosis is not associated with increased activation of the contact system, a case control study.

BACKGROUND: The pathophysiological pathways resulting in Late Stent Thrombosis (LST) remain uncertain. Findings from animal studies indicate a role of the intrinsic coagulation pathway in arterial thrombus formation, while clinical studies support an association with ischemic cardiovascular disease. It is currently unknown whether differences in the state of the contact system might contribute to the risk of LST or Very Late Stent Thrombosis (VLST). We assessed the relation between levels of several components involved in the contact system and a history of LST and VLST, termed (V)LST in a cohort of 20 patients as compared to a matched control group treated with PCI. METHODS AND RESULTS: Activated factor XII (FXIIa), FXII zymogen (FXII), FXIIa-C1-esterase inhibitor (C1-inhibitor), Kallikrein-C1-inhibitor, FXIa-C1-inhibitor and FXIa-alpha1-antitrypsin (AT-inhibitor) complexes were measured by Enzyme-linked immunosorbent assy (ELISA) methodology.Cases and controls showed similar distributions in sex, age, baseline medications and stent type. Patients with a history of (V)LST had a significantly greater stent burden and a higher number of previous myocardial infarctions than the control patients.There were no significant between-group differences in the plasma levels of the components of the contact system. CONCLUSION: In a cohort of patients with a history of (V)LST, we did not observe differences in the activation state of the intrinsic coagulation system as compared to patients with a history of percutaneous coronary intervention without stent thrombosis.

High-intensity interval exercise training improves heart rate variability in patients following percutaneous coronary intervention for angina pectoris.

BACKGROUND: Low time domain measures of heart rate variability (HRV) have been shown to predict outcome after myocardial infarction (MI). The predictive value of HRV, when measured in patients with coronary artery disease (CAD) without MI is less clear. Further, little is known about the mechanisms of how autonomic imbalance affects outcome. METHODS AND DESIGN: Forty patients following percutaneous coronary intervention (PCI) with stent implantation for angina pectoris were prospectively randomized to a six month supervised high-intensity interval training program (n=20) or to a control group (n=20). All patients underwent a 24-hour Holter monitoring to assess measures of HRV at baseline and at six months. RESULTS: At baseline there were no significant differences between groups. In the training group all time domain indices and the frequency domain indices, total power and ultralow frequency of HRV, increased significantly during the training period. Mean heart rate decreased significantly. In the control group only the root mean square of differences between successive NN intervals (ln RMSSD) increased significantly. Changes in standard deviations of the average NN intervals (SDANN) and ln RMSSD were significantly correlated to changes in peak VO(2) (R=0.47 and 0.39; p<0.01 and p=0.03 respectively). HRV measures were not significantly correlated to endothelial function. CONCLUSIONS: High-intensity exercise training over 6 months significantly improved time and frequency domain measures of HRV in patients following PCI with stent implantation. The effect on HRV was correlated to changes in peak VO(2), but not to changes in endothelial function.

Variations in population-based levels of C-reactive protein, cardiovascular morbidity and all-cause mortality: an analysis of the relationship between C-reactive protein, Troponin-T, cardiovascular morbidity and death rates in an unselected population in Southwest Norway.

BACKGROUND: Large population-based studies link inflammation to the prospective development of cardiovascular events. We investigated the time-dependent associations between variations in infectious disease as reflected by alterations of C-reactive protein (CRP)-levels in the general population and the number of cardiovascular events and death rates. METHODS: Retrospectively, we studied CRP- and Troponin T (TNT) values drawn for any clinical reason, the number of cardiovascular events and the death rates in the population of Southern Rogaland, Norway over a 2 year period. RESULTS: The mean and the sum of CRP values per week were significantly correlated with the number of patients with a TNT> or =0.03 microg/l in the same week (R=0.42, R=0.43, respectively, p<0.001 for both analysis). Further, we found a significant correlation between the mean and the sum of CRP values per week and the number of patients admitted with a cardiovascular event 2 weeks later (R=0.20, R=0.26; p=0.047, p=0.009, respectively). The sum of CRP values per week was significantly correlated to the death rates in the following week (R=0.30, p=0.002). CONCLUSIONS: These findings further support the hypothesis that inflammation assessed by CRP levels is linked to the prospective development of cardiovascular events and all cause mortality.

High-intensity interval training may reduce in-stent restenosis following percutaneous coronary intervention with stent implantation A randomized controlled trial evaluating the relationship to endothelial function and inflammation.

BACKGROUND: High-intensity interval training has been shown to be superior to moderate continuous exercise training in improving exercise capacity and endothelial function in patients with coronary artery disease. The objective of this study was to evaluate this training model on in-stent restenosis following percutaneous coronary intervention for stable or unstable angina. METHODS AND RESULTS: We prospectively randomized 40 patients after percutaneous coronary intervention with implantation of a bare metal stent (n = 30) or drug eluting stent (n = 32) to a 6-month supervised high-intensity interval exercise training program (n = 20) or to a control group (n = 20). At six months, restenosis, measured as in-segment late luminal loss of the stented coronary area, was smaller in the training group 0.10 (0.52) mm compared to the control group 0.39 (0.38) mm (P = .01). Reduction of late luminal loss in the training group was consistent with both stent types. Peak oxygen uptake increased in the training and control group by 16.8% and 7.8%, respectively (P < .01). Flow-mediated dilation improved 5.2% (7.6) in the training group and decreased -0.1% (8.1) in the control group (P = .01). Levels of high-sensitivity C-reactive protein decreased by -0.4 (1.1) mg/L in the training group and increased by 0.1 (1.2) mg/L in the control group (P = .03 for trend). CONCLUSIONS: Regular high-intensity interval exercise training was associated with a significant reduction in late luminal loss in the stented coronary segment. This effect was associated with increased aerobic capacity, improved endothelium function, and attenuated inflammation.