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Background: In coronary artery disease (CAD), circulating angiogenic factors have been seen to increase, possibly as a response to ischaemia. Regular physical activity (PA) is recommended for prevention and treatment of CAD, but more research is needed to optimise PA regimes. We investigated the effect of home-based high frequency exercise (HFE) on angiogenic cytokines and cardiac markers in patients with stable CAD., Design: This was a randomised case-control study, Methods: Sixty-two patients, with stable CAD, were randomised to HFE (n = 33), (aerobic exercise 70% of max, 30 min, five times/week and resistance exercise three times/week), performed at home, or usual lifestyle (control, n = 29). After eight weeks, percutaneous coronary intervention (PCI) was performed in both groups, and the HFE group continued another six months of exercise. Serum vascular endothelial growth factor (VEGF) and stromal derived factor-1 (SDF-1), plasma N-terminal-brain natriuretic peptide (NT-proBNP), high-sensitive troponin T (TnT) and copeptin were analysed., Results: Data are presented as median (25(th), 75(th) percentile) of relative changes (%) from baseline. Values of p are given for the difference between the HFE and controls. HFE decreased circulating VEGF levels, before PCI (-5% (-15%, -2%)), while VEGF levels increased in the control group (5% (-3%, 20%) p = 0.004). A significant difference in VEGF remained at three months post-PCI (HFE (-1%(-12%, 5%), control (7% (0%, 14%), p = 0.04), but not at six months after PCI. SDF-1, NT-proBNP, TnT and copeptin levels did not differ significantly. In addition, VEGF levels were positively correlated to NT pro-BNP., Conclusions: Home-based HFE decreased circulating VEGF in patients with stable CAD, suggesting a reduced ischaemic burden. HFE does not increase markers of cardiac dysfunction, suggesting that it is a safe therapeutic intervention in these patients., (© The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Objectives: The aim of this study was to report the frequency, patient and lesion-related characteristics, and outcomes of subclinical, nonculprit plaque ruptures in the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study., Background: Plaque rupture and subsequent thrombosis is the most common cause of acute coronary syndrome (ACS). Secondary, subclinical, nonculprit plaque ruptures have been seen in both stable patients and patients with ACS; however, reports of the natural history of these secondary plaque ruptures are limited., Methods: After successful stenting in 697 patients with ACS, 3-vessel grayscale and intravascular ultrasound virtual histology (IVUS-VH) was performed in the proximal-mid segments of all 3 coronary arteries as part of a prospective multicenter study., Results: Among 660 patients with complete IVUS data, 128 plaque ruptures were identified in 105 nonculprit lesions in 100 arteries from 93 patients (14.1%). Although the minimum lumen area (MLA) was similar, the plaque burden was significantly greater in nonculprit lesions with a plaque rupture compared with nonculprit lesions without a plaque rupture (66.0% [95% confidence interval: 64.5% to 67.4%] vs. 56.0% [95% confidence interval: 55.6% to 56.4%]; p < 0.0001). IVUS-VH analysis revealed that a nonculprit lesion with a plaque rupture was more often classified as a fibroatheroma than a nonculprit lesion without a plaque rupture (77.1% vs. 51.4%; p < 0.0001). Independent predictors of a plaque rupture were lesion length (per 10 mm; odds ratio: 1.30; p < 0.0001), plaque burden at the MLA site (per 10%; odds ratio: 2.56; p < 0.0001), vessel area at the MLA site (per 1 mm(2); odds ratio: 1.13; p < 0.0001), and VH-thin-cap fibroatheroma (odds ratio: 1.80; p = 0.016). During 3 years of follow-up, the incidence of overall major adverse cardiac events did not differ significantly between the patients with and patients without subclinical, nonculprit plaque ruptures., Conclusions: Secondary, nonculprit plaque ruptures were seen in 14% of patients with ACS and were associated with a fibroatheroma phenotype with a residual necrotic core but not with adverse outcomes if patients were treated with optimal medical therapy as part of a multicenter study. (Providing Regional Observations to Study Predictors of Events in the Coronary Tree [PROSPECT]; NCT00180466)., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to use angiography and grayscale and intravascular ultrasound-virtual histology to assess coronary lesions that caused events during a median follow-up period of 3.4 years., Background: Vulnerable plaque-related events are assumed to be the result of substantial progression of insignificant lesions., Methods: In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, 697 patients with acute coronary syndromes underwent treatment of all culprit lesions followed by 3-vessel imaging to assess the natural history of culprit and untreated nonculprit (NC) lesions. Future adverse cardiovascular events adjudicated to NC lesions were divided into those with versus without substantial lesion progression (SLP) (≥ 20% angiographic diameter stenosis increase)., Results: NC lesion events occurred in 72 patients, 44 (61%) with and 28 (39%) without SLP. Myocardial infarctions (n = 6) occurred only in patients with SLP. Conversely, patients without SLP presented only with unstable or increasing angina requiring rehospitalization. Lesions with versus without SLP occurred later (median time to event 401 vs. 223 days, p = 0.07); were less severe at baseline (median diameter stenosis 26.4% vs. 53.8%, p < 0.0001) but more severe at the time of the event (mean diameter stenosis 73.8% vs. 56%, p < 0.0001); and had comparable baseline median plaque burden (68.7% vs. 70.1%, p = 0.17), minimum luminal area (3.7 vs. 4.0 mm(2), p = 0.60), and intravascular ultrasound-virtual histology phenotype (83.3% vs. 90.9%, p = 0.68; classified as fibroatheromas at baseline)., Conclusions: NC lesions responsible for future cardiovascular events showed angiographic increase during 3.4 years of follow-up, whereas SLP underlay many but not all of them. NC events due to lesions with SLP were angiographically less severe and presented with a delayed time course but were otherwise indistinguishable from NC events that were not associated with SLP., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to evaluate the impact of chronic kidney disease (CKD) on coronary atherosclerotic plaque composition, morphology, and outcomes in patients with acute coronary syndromes (ACS)., Background: CKD patients presenting with ACS are at increased risk for adverse events. Whether or not this increased risk reflects differences in coronary plaque composition remains unknown., Methods: In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, patients presenting with ACS in whom percutaneous coronary intervention was successful underwent 3-vessel grayscale and radiofrequency intravascular ultrasound imaging. Lesions were prospectively characterized, and patients were followed for a median of 3.4 years. We conducted a patient-level and lesion-level analysis of study participants by comparing intravascular ultrasound parameters of untreated nonculprit lesions in patients with and without CKD., Results: Patients with CKD (n = 73, 11.3%) were older, more often female and diabetic compared to those without CKD (n = 573). Nonculprit lesions in patients with (n = 280) versus without (n = 2,390) CKD were more likely to have plaque burden ≥ 70% (11.8% vs. 8.5%, p = 0.05) and minimal luminal area ≤ 4.0 mm(2) (25.9% vs. 19.2%, p = 0.005). The percentage of plaque comprised of necrotic core (15.0% vs. 13.0%, p = 0.0001) and dense calcium (8.2% vs. 6.4%, p < 0.0001) was higher while fibrous tissue (57.7% vs. 59.8%, p < 0.0001) was lower in CKD versus non-CKD lesions. The 3-year composite rate of cardiac death, cardiac arrest, or myocardial infarction (15.1% vs. 3.3%, p < 0.0001) was significantly higher in patients with than in those without CKD, although there were no differences in the rates of events adjudicated to nonculprit lesions., Conclusions: Following percutaneous coronary intervention of all culprit lesions in ACS, patients with versus without CKD have more extensive and severe atherosclerosis remaining in their coronary tree with plaque composed of greater necrotic core and less fibrous tissue. These influences resulted in nonsignificantly different rates of non-culprit lesion-related adverse events, although cardiac death, arrest, or myocardial infarction were more common in patients with CKD., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to correlate adverse events at long-term follow-up in patients after an acute coronary syndrome with coronary plaque characteristics derived from simultaneous evaluation of their mechanical and compositional properties using virtual histology (intravascular ultrasound virtual histology) and palpography., Background: Fibroatheroma is the plaque morphology with the highest risk of causing adverse cardiac events. Palpography can potentially assess the local mechanical plaque properties with the possibility of identifying fibroatheroma with the highest risk of rupture., Methods: A total of 114 patients with acute coronary syndrome from the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) trial underwent a single ultrasound imaging investigation of their 3 coronary vessels with the co-registration of intravascular ultrasound virtual histology and palpography. Major adverse cardiac events (MACE) (cardiac death, cardiac arrest, myocardial infarction, or unstable or progressive angina) were collected up to a median follow-up of 3.4 years and adjudicated to originally treated culprit versus untreated nonculprit lesions., Results: In total, 488 necrotic core-rich plaques were identified and subclassified as thin-cap fibroatheroma (n = 111), calcified thick-cap fibroatheroma (n = 213), and noncalcified thick-cap fibroatheroma (n = 164) and matched to their co-registered palpography data. A total of 16 MACE, adjudicated to untreated nonculprit lesions, were recorded at follow-up. In patients in whom MACE developed, fibroatheroma were larger (plaque area 10.0 mm(2) [range: 8.4 to 11.6 mm(2)] vs. 8.2 mm(2) [range: 7.7 to 8.8 mm(2)] (p = 0.03) compared with patients who were MACE free. By palpography, the maximum and the density strain values did not differ between the varying subtypes of fibroatheroma of patients with or without MACE during follow-up., Conclusions: In acute coronary syndromes, patients treated with stents and contemporary pharmacotherapy, palpography did not provide additional diagnostic information for the identification of fibroatheroma with a high risk of rupture and MACE during long-term follow-up. (Providing Regional Observations to Study Predictors of Events in the Coronary Tree [PROSPECT]: An Imaging Study in Patients With Unstable Atherosclerotic Lesions; NCT00180466)., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Everolimus reduces the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant (HTx) recipients, but the influence on established CAV is unknown., Methods: In this Nordic Certican Trial in Heart and lung Transplantation substudy, 111 maintenance HTx recipients (time post-HTx 5.8 ± 4.3 years) randomized to everolimus+reduced calcineurin inhibitor (CNI) or standard CNI had matching (intravascular ultrasound) examinations at baseline and 12 months allowing accurate assessment of CAV progression., Results: No significant difference in CAV progression was evident between the treatment groups (P = 0.30). When considering patients receiving concomitant azathioprine (AZA) therapy (n = 39), CAV progression was attenuated with everolimus versus standard CNI (Δmaximal intimal thickness 0.00 ± 0.04 and 0.04 ± 0.04 mm, Δpercent atheroma volume 0.2% ± 3.0% and 2.6% ± 2.5%, and Δtotal atheroma volume 0.25 ± 14.1 and 19.8 ± 20.4 mm(3), respectively [P < 0.05]). When considering patients receiving mycophenolate mofetil (MMF), accelerated CAV progression occurred with everolimus versus standard CNI (Δmaximal intimal thickness 0.06 ± 0.12 vs. 0.02 ± 0.06 mm and Δpercent atheroma volume 4.0% ± 6.3% vs. 1.4% ± 3.1%, respectively; P < 0.05). The levels of C-reactive protein and vascular cell adhesion molecule-1 declined significantly with AZA+everolimus, whereas MMF+everolimus patients demonstrated a significant increase in levels of C-reactive protein, vascular cell adhesion molecule-1, and von Willebrand factor., Conclusions: Conversion to everolimus and reduced CNI does not influence CAV progression among maintenance HTx recipients. However, background immunosuppressive therapy is important as AZA+everolimus patients demonstrated attenuated CAV progression and a decline in inflammatory markers, whereas the opposite pattern was seen with everolimus+MMF. The different effect of everolimus when combined with AZA versus MMF could potentially reflect hitherto unknown interactions.

We evaluated an extensive profile of clinical variables and immune markers to assess the inflammatory milieu associated with cardiac allograft vasculopathy (CAV) assessed by intravascular ultrasound (IVUS) and virtual histology (VH). In total, 101 heart transplant (HTx) recipients were included and underwent IVUS/VH examination and measurement of plasma C-reactive protein (CRP), soluble tumor necrosis factor receptor-1, interleukin-6, osteoprotegerin, soluble gp130, von Willebrand factor, vascular cell adhesion molecule-1 (VCAM-1) and neopterin. Mean Maximal Intimal Thickness (MIT) was 0.61 +/- 0.19 mm and mean fibrotic, fibrofatty, dense calcified and necrotic core components were 55 +/- 15, 14 +/- 10, 15 +/- 13 and 17 +/- 9%, respectively. In multivariate analysis, CRP > 1.5 mg/L (OR 4.6, p < 0.01), VCAM-1 > 391 ng/mL (adjusted OR 3.2, p = 0.04) and neopterin > 7.7 nmol/L (OR 3.8, p = 0.02) were independently associated with MIT > 0.5 mm. Similarly, CRP > 1.5 mg/L (OR 3.7, p < 0.01) and VCAM-1 > 391 (OR 2.7, p = 0.04) were independently associated with an increased intimal inflammatory component (dense calcified/necrotic core component > 30%). Advanced CAV is associated with elevated CRP, VCAM-1 and neopterin and the two former biomarkers are also associated with an increased intimal inflammatory component. Forthcoming studies should clarify if routine measurements of these markers can accurately identify HTx recipients at risk of developing advanced CAV and vulnerable lesions.

Objective: Physical activity is effective in primary and secondary prevention of cardiovascular disease. In this study, we tested the hypothesis that exercise training improves glucose and lipid metabolism, the inflammatory/anti-inflammatory balance, and the outcome of elective percutaneous coronary intervention (PCI) in patients with stable coronary disease., Methods: Sixty-two patients scheduled to undergo PCI for stable angina were randomized to intensive physical activity (n=33) consisting of home-based exercise on a bicycle ergometer or maintain their usual sedentary life (n=29). The training program started 2 months before PCI and terminated 6 months afterwards. Clinical examination, blood sampling (fasting glucose, glycated hemoglobin, lipid profile, apolipoprotein B, apolipoprotein A1, C-reactive protein, serum amyloid A, interleukin-6, interleukin-8, and interleukin-10), and maximal exercise tests were performed at inclusion, 1 week before PCI, and 3 and 6 months afterwards., Results: Fifty-six patients [28 per group, 45 men, mean age 63 (SD 7.8) years] completed the follow-up. According to self-reports, patients in the training group exercised more often and longer [4.9 (SD 1.1) vs. 0.6 (SD 1.3) days/week, 36 (SD 12) vs. 15 (SD 31) min/session, P<0.0001]. Improvement in maximal exercise capacity was significantly better in the training group [27 (SD 27) vs. 9 (SD 27) W, P=0.02]. Exercise had no significant effects on glucose and lipid metabolism, plasma cytokines, or acute-phase reactants., Conclusion: A home-based training program significantly improved maximal exercise capacity but did not affect glucose or lipid metabolism or markers of inflammation.

Background: The aim of this study was to evaluate the effects of high frequency exercise for patients before and after an elective percutaneous coronary intervention (PCI), with special reference to maximal aerobic capacity, muscle function, health related quality of life (HRQoL), waist-hip ratio (WHR) and restenosis., Methods: A randomised, controlled study was performed in Sweden between 2004 and 2006 in thirty-seven patients (five women) with stable coronary artery disease (CAD), age 63.6+/-6.9 years, randomised to either high frequency exercise or control group. The patients in the training group performed three endurance resistance exercises and trained on a cycle ergometer 30 min, 5 times a week for 8 months at 70% of VO(2max)., Results: Patients in the training group significantly improved their maximal aerobic capacity (15 (9-46) vs. 8 (0-18)% p

Measuring heart rate variability (HRV) is a way to assess the autonomic regulation of the heart. Decreased HRV, indicating reduced parasympathetic tone, has previously been found in depression and anxiety disorders. The objective of this study was to assess HRV in women with premenstrual dysphoric disorder (PMDD). To this end, time domain variables and frequency domain variables were assessed in 28 women with PMDD and in 11 symptom-free controls during both the symptomatic luteal phase and the non-symptomatic follicular phase of the menstrual cycle. Two variables reflecting vagal activity in the time domain, the root mean square of differences of successive normal RR intervals (rMSSD) and standard deviation of normal RR intervals (SDNN) were lower in PMDD patients, but this difference was statistically significant in the follicular phase only. The most important vagal measure in the frequency domain, supine high frequency (HF), also appeared lower in PMDD subjects during the follicular phase. It is suggested that PMDD may be associated with reduced vagal tone compared to controls and that this difference is most apparent in the non-symptomatic follicular phase of the menstrual cycle.

Background: Routine angio-guided stent deployment results in a relatively high restenosis rate, which is mostly due to stent sub-expansion. Several different intravascular ultrasound (IVUS) criteria for optimal stent deployment have been proposed. A minimal in-stent restenosis and a minimal in-stent lumen area of > or = 9 mm2 have been associated with low rates of restenosis and target lesion revascularization (TLR) at 6 months. The role of high-pressure stent deployment and/or upsizing the post-dilatation balloon has not yet been clarified. The aim of this study was to evaluate the possibility of achieving accepted IVUS criteria safely without IVUS guidance with the combination of high-pressure deployment and post-dilatation with a 0.25 mm oversized balloon., Methods: Thirty-four stents (26 NIR, 3 AVE GFX, 3 ACS GFX, 1 Bard, 1 Jostent) were implanted in 30 patients until optimal angiographical results were obtained (< 10% residual stenosis visually). Forty percent of the patients had unstable angina pectoris, forty-four percent had complex lesions (B2 and C) and 29% were occlusions. Mean inflation pressure was 12.6 +/- 1.6 atm, mean stent diameter was 3.2+/- 0.4 mm and mean stent length was 15.1+/- 5.4 mm. Post-dilatation was performed with the same stent using a short (compared to the angiographic reference segment), 0.25 mm oversized Scimed Maxxum Energy 3.5 +/- 0.4 mm balloon using high pressure (16.1 +/- 1.7 atm) followed by an off-line IVUS examination of the stents. There was clinical follow-up for 1 year. Results in patients with single-vessel disease were compared with those of non-randomized controls, who were stented with high pressure but without over-dilatation., Results: No stent achieved the nominal diameter, in spite of over-dilatation. Mean minimal stent diameter (MLD) according to IVUS was 2.9 +/- 0.4 mm (92% of the angiographic reference diameter). Mean minimal lumen area (MLA) was 7.7 +/- 2.2 mm2. An in-stent MLA > or = 90% of the distal reference segment (AVID criteria) and an MLA > or = 100% or > or = 90% of the smallest/average reference segment (MUSIC criteria) was found in 67% and 57%, respectively. MLA > or = 9 mm2 was achieved in 38%. All stents had good apposition and obtained a symmetry index > or = 0.7 mm. No acute perforations, dissections or other serious complications occurred during the over-dilatation. At 1 year, five patients had re-angina leading to a new coronary angiography; only 1 patient had a significant in-stent restenosis requiring re-PTCA. Compared to non-overdilated historical controls, the standardized over-dilatation seemed to give a larger MLD (3.0 +/- 0.4 mm vs. 2.7 +/- 0.4 mm; p = 0.03), more patients who fulfilled AVID criteria (70% vs. 32%; p = 0.048) and more stents with MLA > or = 9 mm2 (46% vs. 11%; p = 0.02)., Conclusion: A standardized 0.25 mm over-dilatation of stents never achieved nominal stent size, but did improve lumen gain and was associated with low target vessel revascularization without adding complications to the routine stenting procedure.

The resistance of the atherosclerotic lesion counteracts the expansion of the stent, resulting in suboptimal stent expansion. Intravascular ultrasound provides more precise information on stent expansion than coronary angiography but adds cost and time to the percutaneous transluminal coronary angiography procedure. The aim of this study was to evaluate the need for intravascular ultrasound at routine angiography-guided high pressure stent implantation by comparing stent expansion with predefined intracoronary ultrasound criteria for optimal stent implantation. In 32 patients, 48 stents (35 NIR, 12 AVE, and 1 Cordis) were implanted in A, B, and C stenoses using a high-pressure inflation technique until an optimal result was achieved according to angiography. Stent expansion was then evaluated by intravascular ultrasound as minimal lumen diameter, minimal lumen area, proximal and distal stent area, and a minimal lumen area symmetry index. These variables were then compared with the nominal stent size in vitro. Finally the stents were also evaluated with respect to the MUSIC criteria, ie, strict criteria regarding symmetry, apposition, and vessel geometry according to intravascular ultrasound after stent expansion. Forty-five stents could be completely analyzed. The mean balloon inflation pressure was 12.8 (range, 10-17) atm. The nominal stent size was not achieved in any patient. Minimal lumen diameter attained 77% and minimal lumen area 78% of expected nominal values (p<0.0001), distal stent area 88% (p < 0.001), and proximal stent area 92% (ns). Application of the MUSIC criteria showed that almost all stents (96%) had good stent apposition and symmetry index. Optimal proximal stent entrance was found in 70%. Optimal minimal lumen area in comparison to the reference areas was present in 41%. This lead to fulfilling of all MUSIC criteria in 47% of the stents. If nominal stent size had been achieved, symmetry index and apposition would have been fulfilled in all cases and optimal minimal lumen area increased to 75%. Acceptable proximal entrance however would have decreased to 55% and the fulfillment of all MUSIC criteria would increase only to 52%. In routine angiography-guided stent implantation in stenoses with a wide range of severities using modern stents and high pressure inflation technique to reach a visually optimal result, the nominal stent size was never achieved mainly due to residual intrastent stenosis. If nominal stent size had been achieved, the results would have improved only marginally and would still be suboptimal in almost half of the stents. These results highlight the shortcoming of angiography and the need for intravascular ultrasound in choosing correct stent size.

Background: Observational studies in selected patients have shown remarkably low restenosis rates after ultrasound-guided stent implantation. However, it is unknown whether this implantation strategy improves long-term angiographic and clinical outcome in routine clinical practice. Methods and Results-- A total of 550 patients with a symptomatic coronary lesion or silent ischemia were randomly assigned to either ultrasound-guided or angiography-guided implantation of

Background: Reduced heart rate variability (HRV) is a risk factor for cardiac death. Animal studies have shown increased HRV and reduced mortality after physical training. We evaluated the change in exercise capacity and HRV in cardiac rehabilitation patients, randomised to routine or home-based intensive training. The design was prospective, stratified randomisation with pre-specified subgroup analysis., Methods: Maximal bicycle exercise test and 24-h Holter were performed 1 (baseline), 4 and 12 months after myocardial infarction (MI) or coronary artery by-pass surgery (CABG). Patients were randomised to physical training either two (N) or six (I) times per week for 3 months Sixty-two patients (43 MI and 19 CABG patients) were evaluated., Results: Exercise capacity increased significantly more after 3 months of training in group I (mean (S.E.)); 29.0 (3.4) vs. 7.2 (2.6) watts, P<0.001). One year later the difference in exercise capacity remained (26.5 (3.3) vs. 11.8 (3.8) watts, P<0.001). Global HRV measurements SDNN and SDANN increased significantly more in group I after training (17.1 (5.6) vs. 1.7 (3.7) and 16.2 (4.9) vs. 2.8 (3.1) ms, P<0.05) and 1 year later the differences were still significant. Subgroup analysis showed more pronounced HRV response in CABG than MI patients., Conclusion: Intensive exercise training in cardiac rehabilitation increases exercise capacity and global HRV, which could be of prognostic significance.

Background: Incidence of sudden cardiac death peaks during the early morning hours when there is a rapid withdrawal of vagal and an increase of sympathetic tone. The rate of autonomic change could be of prognostic importance., Patients and Methods: A total of 65 patients with angina pectoris, free from other diseases and drug free, were Holter monitored for 24 h. A total of 30 patients were also monitored on isosorbide-5-mononitrate (IS-5-MN) and on metoprolol respectively. A total of 33 age-matched healthy subjects served as controls. Spectral components of heart rate variability (HRV) were analysed hourly, with special reference to the rapid changes of autonomic tone during the night and early morning hours. Circadian variation was assessed in two ways: (1) Mean HRV day (8 a.m.-8 p.m.) and night (0-5 a.m.) were compared. (2) For the morning/night hours (0-10 a.m.), individual hourly values for max. and min. HRV, the difference max.-min. (gradient), the rate of change per hour between max. and min. (velocity) and the largest difference between two consecutive hours (max. velocity) were recorded and the mean value for the group calculated., Results: During the night/morning hours, healthy controls demonstrated faster HF max. velocity (P=0.002) and higher HF gradient (P=0.011) than angina patients. Metoprolol and IS-5-MN increased the HF gradient (P=0.008 and P=0.003, respectively), and metoprolol tended to increase the max. velocity (P=0.02). Metoprolol substantially decreased the LF/HF gradient (P=0.001), velocity (P=0.008) and max. velocity (P=0.0001)., Conclusion: Rapid vagal withdrawal seemed to be a sign of a healthy autonomic nervous system in the control group but was significantly slower in angina patients. IS-5-MN and metoprolol tended to normalise vagal withdrawal and metoprolol slowed down the rapid increase in sympathetic predominance in the morning in patients.

Background: Compared to coronary angiography, intravascular ultrasound (IVUS) gives additional information important for the percutaneous transluminal coronary angioplasty (PTCA) procedure, but is time-consuming and may cause complications., Aim: To evaluate, during a period of intensive use of IVUS, the impact of IVUS on the final decision on balloon/stent diameter, consumption of devices, time-consumption and IVUS-related complications., Method: During a 6-month period, IVUS was contemplated in all PTCA procedures and the reason for not using IVUS was specified. We used CVIS during the first, and Endosonics during the last 3 months, and both periods started with 1 week of hands-on practice. All procedures were to be planned according to an initial quantitative coronary angiography (QCA), and the finally achieved result, material used and complications were registered., Results: The proportion of IVUS/PTCA was 37% during, 8% 6 months before and 12% 6 months after the study period. Three hundred and twenty-three patients were included in the study (57% of all patients), 199 of them were subjected to IVUS. The indications for PTCA during the study period were stable angina (58%), unstable angina (32%) and acute myocardial infarction (10%). The main reasons for not doing IVUS were use of 6F guiding catheter (13%), urgent procedure (12%) and occluded vessel (11%). Initial QCA detected 253 stenoses in 199 patients and 64 additional stenoses were treated, most of them probably detected by IVUS. QCA systematically underestimated vessel size, particularly in small vessels. There was a non-significant trend to more accurate estimations towards the end of the study in small vessels. Dissection, probably due to IVUS, occurred in two cases (1%). There were no significant differences in the number of devices used in IVUS compared to non-IVUS patients. The procedural time was 24 min longer in IVUS than in non-IVUS cases and more stenoses were treated per procedure in the IVUS group., Conclusion: Coronary angiography often underestimated balloon/stent size but in an unpredictable way, with a substantial proportion of significant stenoses being undetected. IVUS had few serious complications, did not increase device consumption but prolonged procedural time.

Aim: To investigate whether uncomplicated chronic coronary artery disease causes changes in heart rate variability and if so, whether the heart rate variability pattern is different from that described in patients with acute myocardial infarction., Methods: Heart rate variability was studied in 65 patients with angina who had no previous myocardial infarcts, no other diseases, and were on no drug that could influence the sinus node. Results were compared with 33 age matched healthy subjects. The diagnosis of coronary artery disease in angina patients was established by coronary angiography in 58, by thallium scintigraphy in six, and by exercise test only in one. Patients and controls were Holter monitored 24 hours outside hospital, and heart rate variability was calculated in the frequency domain as global power (GP: 0.01-1.00 Hz), low frequency peak (LF: 0. 04-0.15 Hz), high frequency peak (HF: 0.15-0.40 Hz), LF/HF in ms(2), and in the time domain as SDNN (SD of normal RR intervals), SDANN (SD of all five minute mean normal RR intervals), SD (mean of all five minute SDs of mean RR intervals), rMSSD (root mean square of differences of successive normal RR intervals) (all in ms), and pNN50 (proportion of adjacent normal RR intervals differing more than 50 ms from the preceding RR interval) as per cent., Results: The mean age in patients and controls was 60.4 (range 32-81) and 59.1 (32-77) years, respectively (NS), the male/female ratio, 57/65 and 24/33 (NS), and the mean time of Holter monitoring, 23.0 (18-24) and 22.8 (18-24) hours (NS). Mortality in angina patients was 0% (0/65) at one year, 0% (0/56) at two years, and 3% (1/33) at three years. Compared with healthy subjects angina patients showed a reduction in GP (p = 0.007), HF (p = 0.02), LF (p = 0.02), SD (p = 0.02), rMSSD (p = 0.01), and pNN50 (p = 0.01). No significant difference was found in RR, LF/HF, SDNN, or SDANN., Conclusions: Uncomplicated coronary artery disease without previous acute myocardial infarction was associated with reduced high and low frequency heart rate variability, including vagal tone. SDANN and SDNN, expressing ultra low and very low frequencies which are known to reflect prognosis after acute myocardial infarction, were less affected. This is in agreement with the good prognosis in uncomplicated angina in this study.

Background: Reduced heart rate variability (HRV) after acute myocardial infarction (AMI) indicates poor prognosis. HRV in patients with uncomplicated coronary artery disease is reduced, and an association with poor prognosis has been suggested. The mechanism of the HRV reduction is not known, but ischemia is a possibility., Aim: To evaluate, in angina patients with no prior AMI, no other disease and drug-free, if complete revascularization and thus important reduction of ischemia by means of PTCA influences HRV., Patients and Methods: Twenty-four-hour Holter recordings were performed at baseline prior to PTCA in 48 patients with angina and in 41 age-matched healthy control subjects. The recording was repeated 1 and 6 months after complete revascularization. In addition, HRV was registered during controlled respiration in the supine and standing positions and during cold pressure test at baseline in all angina patients and controls and in 17 consecutive angina patients 6 months after PTCA., Results: Compared to controls, angina patients had a significantly reduced mean RR interval (p = 0.02), SD (p = 0.003), rMSSD (p = 0.03), pNN50 (p = 0.03), total power (p = 0.003), low- (p = 0.004) and high-frequency peak (p = 0.04), but normal SDNN, SDANN and LF/HF. One and 6 months after PTCA, 42/46 and 32/40 follow-up patients, respectively, were free of angina. Six months after PTCA, there was a significant recovery of vagal modulation seen in the frequency domain during controlled respiration, but only nonsignificant trends in HRV parameters analyzed over 24 h., Conclusion: Patients with uncomplicated angina had reduced HRV, mainly affecting vagal activity, but normal low frequency variability associated with mortality. Complete revascularization caused a partial normalization of vagal modulation indicating that ischemia may be one of but not the only mechanism of the HRV reduction in uncomplicated chronic coronary artery disease.

Unlabelled: We evaluated short and long-term effects on QT dispersion and autonomic balance after endoscopic transthoracic sympathicotomy (ETS). Heart rate variability (HRV) reflects autonomic balance of the heart. QT dispersion is a marker of cardiac electrical instability in patients with ischemic heart disease. Holter recordings for 24 h and a twelve-lead ECG were made prior to, 1 month, 1 year and 2 years after ETS. HRV was analysed in time domain and spectral analysis was performed during controlled respiration in supine position and during head up tilt. Dispersion of QT time and QTc were calculated. Of 88 patients, 62 (60) were eligible for HRV (QT-dispersion) analysis after 1 month, 39 (38) patients after 1 year and 23 (24) patients after 2 years. The HRV analysis showed a significant change of indices reflecting sympatho-vagal balance indicating significantly reduced sympathetic (LF) and increased vagal (HF, rMSSD) tone. These changes still persisted after 2 years. Global HRV increased over time with significant elevation of SDANN after 2 years. QT dispersion was significantly reduced 1 month after surgery and the dispersion was further diminished 2 years later., Conclusion: ETS changed HRV and QT dispersion which could imply reduced risk for malignant arrhythmias and death after ETS.

Beta-Blockers reduce mortality in patients with congestive heart failure and a proposed mechanism has been changes of autonomic tone. Heart rate variability is a non-invasive tool to estimate cardiac autonomic tone. The aim was to study changes of heart rate variability in patients with congestive heart failure on placebo, on the beta1-selective antagonist metoprolol or 24 h after metoprolol withdrawal. Forty-five patients with congestive heart failure were studied with Holter recordings. Heart rate variability measurements were performed before, after 6-12 months of treatment with 150 mg metoprolol/placebo, or 24 h after discontinued metoprolol. After treatment, patients on beta-blockade had a significantly longer mean RR interval and changes of heart rate variability, suggesting elevated vagal tone. Patients monitored in the rebound phase of beta-blocker withdrawal had a significant vagal reduction to the level of the placebo group. There was also a nonsignificant trend towards increased sympathetic tone (LF/HF over 24 h), compared with the beta-blockade group. Heart rate variability indicates an elevated vagal tone during treatment with metoprolol but beta-blockade withdrawal shifts the autonomic balance towards lower vagal and higher sympathetic tone within 24 h. These results could imply a potential risk when abruptly discontinuing beta-blockade medication in these patients.

Background: Beta-blockers reduce sympathetic tone, increase vagal tone and improve prognosis in ischaemic heart disease. Nitroglycerin, being a vasodilator, may theoretically have an opposite effect and worsen the prognosis. The purpose of the present study was to analyse heart rate variability (HRV), which reflects autonomic tone, in angina patients on isosorbide-5-mononitrate (IS-5-MN) and/or metoprolol., Methods and Results: Thirty-two patients (32-81 years old), with recently developed angina (median duration: 3 months), showing no other disease and on no drugs, were Holter-monitored 24-48 h at baseline and after 4-5 days on IS-5-MN (mean daily dose: 33 mg), on metoprolol (mean daily dose: 184 mg) and on the combined treatment. Recordings were analysed on the Marquette Series 8000 Holter scanner. Both IS-5-MN and metoprolol significantly reduced myocardial ischaemia (ST integral) and ventricular tachycardias. Metoprolol induced significant changes in the following parameters (baseline versus metoprolol): high-frequency peak 9 +/- 4 versus 11 +/- 4 ms (p < 0.001), low-to-high frequency ratio 2.5 +/- 0.6 versus 1.9 +/- 0.6 (p < 0.0001), root mean square of RR interval difference 23 +/- 7 versus 31 +/- 9 ms (p < 0.0001), RR intervals differing more than 50 ms from the preceding one 4.8 +/- 3.9 versus 10.0 +/- 7.0% (p < 0.0001), mean of all 5-min standard deviations 50 +/- 12 versus 56 +/- 11 ms (p < 0.001) and mean RR interval 819 +/- 90 versus 1,019 +/- 120 ms (p < 0.00001). The combined treatment caused approximately the same HRV changes as metoprolol alone. IS-5-MN had no significant effect on any HRV parameter, neither alone nor in combination with metoprolol., Conclusion: A clinically effective dose of metoprolol had potentially positive effects on HRV with increase in vagal and decrease in sympathetic tone while IS-5-MN had no effect on HRV, neither positive nor negative, neither alone nor in combination with metoprolol.

In order to reduce mortality and the need for hospital care for patients suffering from acute asthma, an emergency programme was set up. An ambulance crew, trained in coronary-pulmonary resuscitation was instructed in dealing with acute asthma and delegated to give 24 h treatment with bronchodilators (inhaled salbutamol and ipratropium bromide). If there was no, or only slight, improvement with this therapy, nurses (daytime) were delegated to give injections with corticosteroids (terbutaline and theophylline). Over a period of 2 years, 240 patients, 115 women and 125 men, were treated on 367 occasions. In 127 patients (53%), two or more treatments were given. The number of times treatment was given, as well as the proportion of females to males, increased the younger the patients were. Out of all the cases, more than 70% improved after treatment. On arrival, 21 patients (6%) were unconscious. After therapy, 15/21 patients (71%) survived. This may correspond to a similar reduction in mortality (population about 350,000 inhabitants), as it is unlikely that unconscious patients can survive without intensive care.

Background: Cardiac sympathetic blockade by thoracic epidural anesthesia (TEA) dilates stenotic coronary arteries and has been used to control pain in patients with unstable angina. The aim of the present study was to evaluate the potential anti-ischemic effects of cardiac sympathetic blockade by TEA in severe, refractory, unstable angina., Methods and Results: Forty patients with unstable angina refractory to standard anti-anginal therapy were randomized to receive either continuous epidural infusion of bupivacaine (TEA, Th1 to Th5) or to standard anti-anginal therapy including beta-blockers, calcium antagonists, aspirin, heparin, and nitroglycerin infusion (control group). The primary end points were number of anginal attacks and severity of myocardial ischemia assessed by 48-hour ambulatory Holter monitoring. The incidence of myocardial ischemia was lower in the TEA group (22% versus 61%; P<.05). The number of ischemic episodes per patient was 1.0+/-0.6 in the TEA group and 3.6+/-0.9 in the control group (P<.05). The episode duration per patient was 4.1+/-2.5 minutes and 19.7+/-6.2 minutes in the TEA and the control groups, respectively (P<.05). The mean area-under-the-ST-time-curve was 6.8+/-4.3 and 32.2+/-14.3 (mm-min) in the TEA and the control groups, respectively (P<.05). Fifteen anginal attacks were recorded in the control group and one attack in the TEA group (0.83+/-0.21 versus 0.06+/-0.06/patient, respectively, P<.01)., Conclusions: The anti-ischemic and anti-anginal effects of continuous TEA are superior to those of conventional therapy in the treatment of refractory unstable angina.

Unlabelled: Heart rate variability (HRV) reflects autonomous activity that influences the heart. It has been shown that HRV is depressed during acute myocardial infarction (AMI) and that it recovers with time. Beta-blockers reduce mortality after AMI and changes in sympathico-vagal activity have been suggested to be of importance. Under certain animal experimental conditions, metoprolol has been reported to increase vagal tone more than atenolol, which could have clinical implications. The purpose of the present study was to compare the effects of atenolol and metoprolol treatments on HRV during 6 weeks after AMI and to follow the post MI changes in HRV in patients on betablockers., Methods: In an open, randomised cross-over study, 28 patients were randomised to 3+3 weeks' treatment with atenolol or metoprolol starting 2-5 days after AMI. Twenty-four hour Holter recordings were made before randomisation and after 3 and 6 weeks. HRV was analysed as HR, SDRR, SDANN, SD, rMSSD and pNN50 in the time domain and as coefficient of component variance (CCV) of HF and LF, and as LF/HF ratio in the frequency domain., Results: The average daily dose in our study population was 106 mg of metoprolol and 54 mg of atenolol. There were trends toward lower heart rates daytime, lower LF/HF ratio daytime and higher rMSSD on atenolol compared to metoprolol. In the total group of 28 patients we found during the first 3 weeks, a significant increase of SDNN, SDANN (p<0.0001) and LF/HF ratio daytime and CCV-HF night-time (p<0.01). All differences and trends were unchanged between 3 and 6 weeks., Conclusions: There was no evidence of more increased vagal tone with metoprolol compared to atenolol as has been suggested from animal models. In patients also on chronic treatment with beta blockers, an increase of HRV was seen during the first weeks post MI.

The aim of the study was to evaluate, in a controlled setting, the effects of a 5-month dynamic peripheral training programme in patients with clinical signs of congestive heart failure with special reference to their anaerobic threshold, muscle function, heart rate variability and quality of life. Twenty-four randomized patients with clinical signs of heart failure in NYHA II-III entered the study. Training resulted in a significant (p = 0.01) change in the anaerobic threshold, the patients' ability to lift weights (p = 0.01) and performance of heel-lift (p = 0.01). The heart rate recorded during the training exercises decreased significantly (p = 0.04). There were no significant differences in peak oxygen uptake, isokinetic and isometric strength, HRV and quality of life except for three items in the control group. The results of this study indicate that peripheral training is beneficial for patients with clinical signs of congestive heart failure.

Endoscopic transthoracic sympathicotomy (ETS) is a recently developed technique to divide sympathetic nerves. ETS has been shown to improve symptoms and reduce ischemia in patients with severe angina pectoris. Low heart rate variability (HRV) in patients with ischemic heart disease carries an adverse prognosis. HRV reflects autonomic response of the heart and a shift in the sympathovagal balance towards parasympathetic dominance could be a marker of improved prognosis. HRV might also be used as an indicator of surgical success in sympathetic heart denervation. Heart rate was recorded in 57 patients before and after ETS. Registration was recorded during controlled respiration in the supine position and at tilt test over 10 minutes and spectral analysis was performed. Twenty-four hour Holter recordings were analyzed in the time domain. During the controlled setting, the high-frequency (HF) component (0.15 to 0.40 Hz) increased significantly whereas the low-frequency (LF) component (0.04 to 0.15 Hz) did not change significantly. The LF/HF ratio at tilt test was reduced from 1.3 to 0.8 (p <0.01). The time-domain analysis showed a significant increase of the mean RR interval (923 to 1,006 ms, p <0.001) and indexes reflecting parasympathetic tone also increased significantly (the root-mean square of difference measured from 24.3 to 29.5 ms, p <0.001 and the proportion of adjacent RR intervals >50% measured from 5.5% to 8.2%, p <0.01), whereas measurements reflecting global HRV did not change. In addition to relief of symptoms and reduced ischemia in severe angina pectoris, ETS caused a shift of sympathovagal balance toward parasympathetic tone. This might explain the anti-ischemic effect and have prognostic implications.

Aim: To describe the occurrence, characteristics and outcome among patients with out-of-hospital cardiac arrest who required continuation of cardiopulmonary resuscitation (CPR) on admission to the emergency department., Patients: all patients in the municipality of Göteborg who suffered out-of-hospital cardiac arrest, were reached by the emergency medical service (EMS) system and in whom CPR was initiated. Period for inclusion in study: 1 Oct. 1980-31 Dec. 1992., Results: of 334 out-of-hospital cardiac arrests, 2,319 (68%) were receiving on-going CPR at the time of admission to hospital. Of these, 137 patients (6%) were hospitalized alive and 28 (1.2%) could be discharged from hospital. Of these patients, 39% had a cerebral performance categories (CPC) score of 1 (no cerebral deficiency), 18% had a CPC score of 2 (moderate cerebral deficiency), 36% had a CPC score of 3 (severe cerebral deficiency) and 7% had a CPC score of 4 (coma) at discharge. Among patients discharged. 76% were alive after 1 year., Conclusion: among consecutive patients with out-of-hospital cardiac arrest, CPR was ongoing in 68% of them on admission to hospital. Among these patients, 6% were hospitalized alive and 1.2% were discharged from hospital. Thus, among patients with ongoing CPR on admission to hospital, survivors can be found but they are few in numbers and extensive cerebral damage is frequently present.

Background: A large proportion of cardiac arrests outside hospital are caused by ventricular fibrillation. Although it is frequently used, the exact role for treatment with lidocaine in these patients remains to be determined., Aim: To describe the proportion of patients with witnessed out-of-hospital cardiac arrest found in ventricular fibrillation who survived and were discharged from hospital in relation to whether they were treated with lidocaine prior to hospital admission., Patients and Treatment: All the patients with out-of-hospital cardiac arrest found in ventricular fibrillation in Göteborg between 1980 and 1992 in whom cardiopulmonary resuscitation (CPR) was initiated by our emergency medical service (EMS). During the observation period, some of the EMS staff were authorized to give medication and some were not., Results: In all, 1,360 patients were found in ventricular fibrillation, with detailed information being available in 1,212 cases (89%). Lidocaine was given in 405 of these cases (33%). Among patients with sustained ventricular fibrillation, those who received lidocaine had a return of spontaneous circulation (ROSC) more frequently (P < 0.001) and were hospitalized alive more frequently (38% vs. 18%, P < 0.01). However, the rate of discharge from hospital did not significantly differ between the two groups. Among patients who were converted to a pulse-generating rhythm, those who received lidocaine on that indication were more frequently alive than those who did not receive such treatment (94% vs. 84%; P < 0.05). However, the rate of discharge did not significantly differ between the two groups., Conclusion: In a retrospective analysis comparing patients who received lidocaine with those who did not in sustained ventricular fibrillation and after conversion to a pulse-generating rhythm, such treatment was associated with a higher rate at ROSC and hospitalization but was not associated with an increased rate of discharge from hospital.

Aim: To describe the prognosis of patients with out-of-hospital cardiac arrest judged to be caused by the deterioration of obstructive pulmonary disease., Patients: All patients in the community of Göteborg Sweden who suffered out-of-hospital cardiac arrest between 1980 and 1992 attended by our emergency medical service and in whom cardiopulmonary resuscitation was initiated., Methods: The etiology of cardiac arrest was determined according to clinical history, observations at resuscitation and findings at autopsy., Results: There were 3434 cardiac arrests of which 130 (4%) were judged to have been caused by deterioration of obstructive pulmonary disease. Of these patients 50% were found in asystole, 40% in pulseless electrical activity, and only 7% in ventricular fibrillation. Among patients with cardiac arrest caused by obstructive pulmonary disease 21 (16%) were hospitalized alive and six (5%) were discharged from hospital. Among patients who developed cardiac arrest after arrival of the ambulance, 16% were discharged from hospital versus 0% among patients who had arrest prior to arrival of the ambulance., Conclusion: Among patients with out-of-hospital cardiac arrest caused by deterioration of obstructive pulmonary disease, half were found in asystole. Overall, the survival rate was low. This highlights the importance of effective treatment early in the course of deterioration of obstructive pulmonary disease in order to avoid cardiac arrest.

Outcome after cardiac arrest is strongly related to whether the patient has ventricular fibrillation at the time the emergency medical service (EMS) arrives on the scene. The occurrence of various arrhythmias at the time of EMS arrival among patients with out-of-hospital cardiac arrest was studied in relation to the interval from collapse and whether cardiopulmonary resuscitation (CPR) was initiated by a bystander. The patients studied were all those with out-of-hospital cardiac arrest in Goteborg, Sweden, between 1980 and 1992 in whom CPR was attempted by the arriving EMS and for whom the interval between collapse and the arrival of EMS was known. In all, information on the time of collapse and the arrival of EMS was available for 1,737 patients. Among patients for whom EMS arrived within 4 minutes of collapse, 53% were found in ventricular fibrillation/tachycardia. There was a successive decline in occurrence of such arrhythmias with time. However, when the interval exceeded 20 minutes, ventricular fibrillation/tachycardia was still observed in 27% of cases. Bystander CPR increased the occurrence of such arrhythmias regardless of the interval between collapse and EMS arrival.

Background: A large proportion of cardiac arrests outside hospital are caused by ventricular fibrillation. Although it is frequently used, the exact role of treatment with adrenaline in these patients remains to be determined., Aim: To describe the proportion of patients with witnessed out-of-hospital cardiac arrest found in ventricular fibrillation who survived and were discharged from hospital in relation to whether they were treated with adrenaline prior to hospital admission., Patients and Treatment: All the patients with out-of-hospital cardiac arrest found in ventricular fibrillation in Göteborg between 1981 and 1992 in whom cardiopulmonary resuscitation (CPR) was initiated by our emergency medical service (EMS). During the observation period, some of the EMS staff were authorized to give medication and some were not., Results: In all, 1360 patients were found in ventricular fibrillation and detailed information was available in 1203 cases (88%). Adrenaline was given in 417 cases (35%). Among patients with sustained ventricular fibrillation, those who received adrenaline experienced the return of spontaneous circulation more frequently (P < 0.001) and were hospitalized alive more frequently (P < 0.01). However, the rate of discharge from hospital did not differ significantly between the 2 groups. Among patients who converted to asystole or electromechanical dissociation, those who received adrenaline experienced the return of spontaneous circulation more frequently (P < 0.001) and were hospitalised alive more frequently (P < 0.001). However, the rate of discharge from hospital did not differ significantly between the 2 groups., Conclusions: On the basis of 2 treatment regimens during a 12-year survey, we explored the usefulness of adrenaline in out-of-hospital ventricular fibrillation. Both patients with sustained ventricular fibrillation and those who converted to asystole or electromechanical dissociation had an initially more favourable outcome if treated with adrenaline. However, the final outcome was not significantly affected. This study does not confirm the hypothesis that adrenaline increases survival among patients with out-of-hospital cardiac arrest who are found in ventricular fibrillation.