Review findings included diminished coronary flow reserve after surgery in children with congenital heart disease and inflammation.

AIM: The aim of this review was to develop a deeper knowledge of the physiology of coronary blood flow and coronary flow reserve in young patients with congenital heart disease and inflammatory diseases. METHODS: We searched for papers published in English on coronary blood flow and coronary flow reserve using the PubMed and Google search databases. This identified 42 papers extending back to 1976 and a book from 2008 (Davis et al. Microcirculation. Boston, MA: Elsevier, 2008: 161-284). RESULTS: Our review showed that the implications of coronary blood flow and coronary flow reserve in paediatric patients with congenital heart disease and inflammatory diseases are still not fully understood. However, a key finding was that coronary flow reserve was diminished in patients with congenital heart disease and inflammation after surgery, with or without a cardiopulmonary bypass. Other findings discussed by this review relate to volume and pressure overload in acyanotic congenital heart disease, reduced myocardial perfusion and cyanotic congenital heart disease. CONCLUSION: We still have much to discover about paediatric patients with congenital heart disease and inflammatory diseases. Understanding the pathophysiology of coronary blood flow could help the postoperative treatment of such patients.

Serum MMP-9 Diagnostics, Prognostics, and Activation in Acute Coronary Syndrome and Its Recurrence.

Matrix metalloproteinase (MMP)-9 is crucial in atherosclerotic plaque rupture and tissue remodeling after a cardiac event. The balance between MMP-9 and endogenous inhibitor, tissue inhibitors of matrix metalloproteinase 1 (TIMP-1), is important in acute coronary syndrome (ACS). This is an age- and gender-matched case-control study of ACS (N = 669). Patients (45.7%) were resampled after recovery, and all were followed up for 6 years. The molecular forms of MMP-9 were investigated by gelatin zymography. Diagnostically, MMP-9 and the MMP-9/TIMP-1 molar ratio were associated with ACS (OR 5.81, 95% CI 2.65-12.76, and 4.96, 2.37-10.38). The MMP-9 concentrations decreased 49% during recovery (p < 0.001). The largest decrease of these biomarkers between acute and recovery phase (ΔMMP-9) protected the patients from major adverse cardiac events, especially the non-fatal events. The fatal events were associated with in vitro activatable MMP-9 levels (p = 0.028). Serum MMP-9 and the MMP-9/TIMP-1 molar ratio may be valuable in ACS diagnosis and prognosis. High serum MMP-9 activation potential is associated with poor cardiovascular outcome.

HLA, infections and inflammation in early stages of atherosclerosis in children with type 1 diabetes.

AIMS: This prospective study focuses on risk factors for arterial damage in children with type 1 diabetes (T1D). METHODS: Eighty children and adolescents with T1D were investigated twice, approximately 2 years apart, for carotid artery intima-media thickness (cIMT) and compliance (CAC), flow-mediated dilatation (FMD) of the brachial artery, and plasma levels of matrix metalloproteinase (MMP)-8. All subjects were genotyped for HLA. The number of respiratory tract infections (RTI) during the past year was obtained by a questionnaire in 56 patients. RESULTS: cIMT progression, defined as percentage (%) change of cIMT from baseline, correlated inversely with the % changes of both CAC (p = 0.04, r = - 0.3; n = 62) and FMD (p = 0.03, r = - 0.3; n = 47). In multivariate analysis, RTI frequency correlated significantly with cIMT progression irrespective of age, diabetes duration, BMI, and HbA1c (p = 0.03, r = 0.3). When patients were divided in relation to RTI, the association of DQ2/8 with cIMT progression remained significant in patients with over three infections/year (p = 0.04, r = 0.3). During follow-up, the group of DQ2/8 patients with hsCRP > 1 mg/l showed significantly higher levels of plasma MMP-8 than the non-DQ2/8 group. CONCLUSIONS: The diabetes-risk genotype DQ2/8 and systemic inflammation contribute to pro-atherosclerotic vascular changes in children and adolescents with T1D.

Adaptation to acute coronary syndrome-induced stress with lowering of testosterone: a possible survival factor.

OBJECTIVE: The objective of this study was to explore whether circulating testosterone (T) concentration is associated with the occurrence and risk for acute coronary syndromes (ACS). METHOD: This case-control study included male patients with acute myocardial infarction (AMI) (n=174) or unstable angina pectoris (UAP) (n=90) and healthy controls (n=238). Patients gave serum samples during the acute (n=264) and recovery (n=132) phases after a median of 10.5 months after the incident event. Secondary events (ACS or cardiovascular death) were registered during the following 6 years. RESULTS: During the acute phase, AMI and UAP patients had similar significantly reduced concentrations of serum testosterone in comparison to controls. Testosterone associated inversely with weight, the degree of inflammation (i.e. C-reactive protein concentration) and signs of a chronic infection. In a multiadjusted Cox regression, when compared to testosterone concentrations considered high-normal (14.91-34.0  nmol/l), low-normal testosterone (9.26-14.90  nmol/l) in the acute phase predicted better prognosis for cardiovascular death rate with a hazard ratio (HR) of 0.17 (0.04-0.68, P=0.012). The increased testosterone concentrations after the recovery period did not associate with future cardiovascular disease events. CONCLUSION: Low-normal testosterone levels in the acute phase of ACS predicted better survival. The observation may indicate better adaptation to stress in survivors and warrants further study.

Coronary flow dynamics in children after repair of Tetralogy of Fallot.

OBJECTIVES: To assess the possible effect of a stiff right ventricle on the coronary flow (CF) in patients with post-operative Tetralogy of Fallot (TOF). BACKGROUND: Right ventricular restrictive physiology i.e. forward flow during atrial contraction (RVRP), is characteristic to many patients with post-operative TOF. METHODS: A total of 34 patients with TOF anatomically corrected through transatrial repair were included. Coronary flow parameters were registered with transthoracic Doppler echocardiography from posterior descending (PDCA) and left anterior descending (LAD) coronary arteries in the same patient in 24/34 (71%) patients. Twenty age-matched healthy children were used as controls. Cardiac magnetic resonance (CMR) imaging was used to detect myocardial fibrosis, RV volume, and RVRP. RESULTS: The mean age at investigation was 10.2 ± 2.8 years. RV end diastolic and end systolic volumes indexed for BSA were larger in patients with RVRP (p=0.002 and 0.008 respectively). Peak flow velocity in diastole and flow velocity time integral was increased in patients compared to controls. They were increased in the LAD in patients with fibrosis of RV (n=11) compared to patients without fibrosis (n=9) (p=0.01 and 0.047 respectively). LAD coronary flow was especially increased in patients with RVRP (n=9) as compared with those without (n=11), (p=0.006). CONCLUSIONS: Patients at mid-term followup after correction of TOF show increase of coronary flow. This increase is more pronounced in patients with fibrosis and RVRP of the RV.

Early changes in myocardial repolarization and coronary perfusion after cardiopulmonary bypass surgery for ASD repair in children.

BACKGROUND: In adults, impaired myocardial repolarization and increased risk of arrhythmia are known consequences of open heart surgery. Little is known, however, about post-operative consequences of cardiopulmonary bypass surgery in children. The aim of this study was to assess ventricular repolarization and coronary perfusion after bypass surgery for atrial septal defect (ASD) repair in children. METHODS: Twelve patients with ASD were assessed one day before and 5-6 days after ASD repair. Myocardial repolarization (corrected QT interval, QTc, QT dispersion, QTd, and PQ interval) was determined on 12-lead electrocardiograms. Coronary flow in proximal left anterior descending artery (peak flow velocity in diastole, PFVd) was assessed by transthoracic Doppler echocardiography. RESULTS: Ten of the 12 (83%) children had normal myocardial repolarization before and after surgery. After surgery, QTc increased 1-9% in 5 (42%) patients, decreased 2-11% in 5 (42%) patients and did not change in 2 (16%) patients. Post-op QTc positively correlated with bypass time (R=0.686, p=0.014) and changes in PFVd (R=0.741, p=0.006). After surgery, QTd increased 33-67% in 4 (33%) patients, decreased 25-50% in 6 patients (50%) and did not change in 2 (16%) patients. After surgery, PQ interval increased 5-30% in 4 (33%) patients, decreased 4-29% in 6 (50%) patients and did not change in 1 (8%) patient. Post-op PQ positively correlated with bypass time (R=0.636, p=0.027). As previously reported, PFVd significantly increased after surgery (p<0.001). CONCLUSIONS: Changes in QTc, PQ and PFVd are common in young children undergoing surgery for ASD repair. Post-op QTc significantly correlates with bypass time, suggesting prolonged cardiopulmonary bypass may impair ventricular repolarization. Post-op QTc significantly correlates with PFVd changes, suggesting increased coronary flow may also impair ventricular repolarization. The clinical significance and reversibility of these alternations require further investigations.

Coronary flow and reactivity, but not arrhythmia vulnerability, are affected by cardioplegia during cardiopulmonary bypass in piglets.

BACKGROUND: Surgery under cardiopulmonary bypass (CPB) is still associated with significant cardiovascular morbidity in both pediatric and adult patients but the mechanisms are not fully understood. Abnormalities in coronary flow and function have been suggested to play an important role. Prior studies suggest protective effects on coronary and myocardial function by short intravenous (i.v.) infusion of cyclosporine A before CPB. METHODS: Barrier-bred piglets (10-12 kg, n=20) underwent CPB for 45 min, with or without antegrade administration of cardioplegic solution. Prior to CPB, half of the animals in each group received an i.v. infusion of 100 mg/kg cyclosporine A. The left anterior descending coronary flow velocity responses to adenosine, serotonin, and atrial pacing, as well as left ventricular function and postsurgical vulnerability to atrial fibrillation (Afib) were assessed by intracoronary Doppler, epicardial echocardiography, and in vivo electrophysiological study, before and 8 hours after surgery. Plasma C-reactive protein (CRP) and fibrinogen were measured at both time-points. RESULTS: Cyclosporine infusion did not influence any of the studied variables (p>0.4). Coronary peak flow velocity (cPFV) rose significantly after surgery especially in the cardioplegia group (p<0.01 vs. non-cardioplegia group and pre-surgery). cPFV responses to adenosine, but not to serotonin, tended to decrease (p=0.06) after surgery only in cardioplegia group (p=0.06; p=0.8 in non-cardioplegia group vs pre-surgery). Also, cPFV response to atrial pacing was lower in the cardioplegia than in the non-cardioplegia group (p=0.02). Neither vulnerability nor duration of induced Afib after CPB differed between groups (Chi-square p=0.4). Cyclosporine had no significant effect on coronary indexes or arrhythmia vulnerability (p>0.4). There was no difference in systolic myocardial function between groups at any time point. CONCLUSION: In piglets, CPB with cardioplegia was associated with profound abnormalities in coronary vasomotor tone and receptor-related flow regulation, whereas arrhythmia vulnerability appeared to be comparable with that in non-cardioplegia group. In this study, preconditioning with cyclosporine had no detectable protective effect on coronary circulation or arrhythmia vulnerability after CPB.

Endothelial cell death and intimal foam cell accumulation in the coronary artery of infected hypercholesterolemic minipigs.

Apoptosis of endothelial cells (ECs) has been suggested to play a role in atherosclerosis. We studied the synergism of hypercholesterolemia with Chlamydia pneumoniae and influenza virus infections on EC morphology and intimal changes in a minipig model. The coronary artery was excised at euthanasia (19 weeks of age) and serial sections were processed for the detection of EC apoptosis, histology, and transmission electron microscopy (TEM) studies. There was a significantly higher number of TUNEL-positive ECs in infected compared to noninfected groups [0.2942 % (interquartile ranges (IR), 0.2941; n = 26) versus 0 % (IR, 0; n = 12), p < 0.01]. Caspase-3 staining was negative. Cholesterol diet together with infections induced widening of the subendothelial space and appearance of increased numbers of foam cells. TEM revealed degenerative changes in cytoplasmic organelles and signs of EC necrosis. In conclusion, infection leads to an increase in coronary EC death and seems to exacerbate cholesterol-induced intimal thickening and foam cell accumulation.

Restrictive right ventricular physiology after tetralogy of Fallot repair is associated with fibrosis of the right ventricular outflow tract visualized on cardiac magnetic resonance imaging.

AIMS: To determine whether the restrictive physiology seen in Tetralogy of Fallot (TOF) patients can be explained by fibrosis of the right ventricular (RV) outflow tract. The aetiology for restrictive RV physiology after TOF repair is not known. METHODS AND RESULTS: TOF patients (n = 31, 13 girls, 10.2 years ± 2.8) were included 9.2 ± 2.9 years after total correction and examined with cardiac magnetic resonance (CMR) and Doppler echocardiography. Cine, flow, and late gadolinium contrast enhanced (LGE) CMR imaging were performed to quantify RV volumes, pulmonary flow and regurgitation (PR), and fibrosis. Healthy children (n = 12) were investigated with CMR of the pulmonary flow. Forward flow during atrial contraction above mean + 2 SD of healthy subjects was set as a marker of restrictive physiology. Four patients were excluded due to suboptimal LGE-CMR. Fisher's exact test was used to determine the association between restrictive physiology and fibrosis. Sixteen patients showed fibrosis in the right ventricular outflow tract (RVOT) on LGE-CMR and 14 of them showed restrictive physiology on CMR. Of the 11 patients without fibrosis in the RVOT, 1 showed restrictive physiology. The odds ratio for RVOT fibrosis in patients with restrictive RV physiology was 70.0 (CI: 5.6-882.7, P < 0.001). The transannular patch repair did not differ between the groups (P = 0.37). The degree of RVOT fibrosis correlated positively with PR (r(2) = 0.38, P < 0.001) and RV volumes (r(2) = 0.51 for end-diastolic volume and r(2) = 0.47 for end-systolic volume, P < 0.001). CONCLUSION: There is a strong association between the restrictive RV physiology detected on CMR and fibrosis of the RVOT in children after TOF repair.

The balance of serum matrix metalloproteinase-8 and its tissue inhibitor in acute coronary syndrome and its recurrence.

BACKGROUND: Matrix metalloproteinase-8 (MMP-8) is involved in the breakdown of the extracellular matrix increasing the vulnerability of atherosclerotic lesions. We analysed the diagnostic value of serum MMP-8 and tissue inhibitor of metalloproteinase-1 (TIMP-1) concentrations in acute coronary syndrome (ACS) and their prognostic value in ACS recurrence. METHODS: The population comprised 343 patients with ACS [including 108 unstable angina pectoris and 235 acute myocardial infarctions (AMI)] and 326 healthy controls. Additionally, 157 (45.8%) patients were resampled during the recovery. The ACS patients were followed up for 6 years. RESULTS: MMP-8, TIMP-1, and their molar ratio distinguished the cases from the controls; C-statistic of the multivariate model (95% CI, p-value) including the MMP-8/TIMP-1 ratio regarding its discriminating ability for AMI was 0.922 (0.893-0.950, p<0.001). After the acute phase of ACS, median MMP-8 and TIMP-1 concentrations decreased (p<0.001) by 34.5 and 28.7%, respectively, but ended up on a different level than those found in the controls. In the follow-up, acute phase and recovery period TIMP-1 concentrations associated with cardiovascular death with hazard ratios 4.31 (2.00-9.26, p<0.001) and 4.69 (1.10-20.01, p=0.037), respectively. CONCLUSIONS: The increase of serum MMP-8 and TIMP-1 concentrations may reflect plaque instability and tissue damage. TIMP-1 concentrations are associated with poor outcome in patients with ACS. The findings may have practical implications in both diagnostics and therapeutics.

The outcome of patients with right atrial isomerism is poor.

Right-atrial isomerism (RAI) is a heterotaxy syndrome with disturbances of left-right axis development resulting in complex heart malformations and anomalies of the thoracic and abdominal organs. To study the outcome of RAI, all data from patients diagnosed with this syndrome at Helsinki University Hospital between January 1976 and December of 2010 were reviewed. The outcomes were studied for 32 patients (38 % girls). The overall survival was 22 % at a median follow-up time of 13.8 years (range 0.1-33). Extracardiac malformations, mostly asplenic, occurred in 91 % of patients. Cardiac defects included dextrocardia in 44 % and common atrioventricular valve in 100 % of patients. Ventriculoarterial discordance or double-outlet ventricle was seen in 56 and 44 % of patients, respectively. Total anomalous pulmonary venous drainage occurred in 75 % and partially anomalous venous drainage in 13 % of patients. Pulmonary outflow-tract obstruction was identified in 91 % of patients. Cardiac arrhythmias were noted in nine patients (28 %), two of them with atrioventricular block. Cardiovascular surgery was performed in 71 % patients (N = 25), seven patients were inoperable. Biventricular repair was not possible in any of the patients. During long-term follow-up there was no significant difference between the patients with total, normal, or partially anomalous pulmonary venous drainage (P = 0.5). In conclusion, RAI is one of the most severe forms of congenital cardiac diseases. The prognosis remains poor despite modern surgical techniques. When RAI is identified during pregnancy, prenatal counseling, termination, or planning for prompt cardiac treatment after the birth is necessary.

Long-term outcome following catheter valvotomy for pulmonary atresia with intact ventricular septum.

OBJECTIVES: This study investigated the outcome for all patients undergoing catheter valve perforation for pulmonary atresia with intact ventricular septum (PAIVS) 21 years after the first procedure at their center. BACKGROUND: Catheter perforation for PAIVS is now an established procedure. However, the management of the borderline right ventricle (RV) is controversial, and there may be a place for novel techniques such as stenting of the arterial duct. METHODS: There were 37 successful valve perforations (total 39 patients). Median length of follow-up was 9.2 years (range 2.2 to 21.0 years). Seventeen patients had stenting of the arterial duct. The mean (SD) initial z-score for the tricuspid valve was -5.1 (±3.4), and a further 142 sets of measurements were taken to assess the growth of the RV of survivors. RESULTS: There were 8 deaths (21%), and no deaths after the first 35 days. There were no late arrhythmias or ischemic events. Twenty-five patients (83% of survivors) have a biventricular circulation. For patients who had stenting of the arterial duct, significant reductions in early reintervention (0 vs. 7 patients, p = 0.009) and hospital stay (17.4 ± 18.1 days vs. 33.8 ± 28.6 days, p = 0.012) occurred, with no increase in mortality or morbidity. There was no catch-up growth of the RV in patients who had a biventricular outcome (z-score increase +0.08/year, p = 0.26). CONCLUSIONS: Long-term survival is good, and even small RVs may be amenable to this procedure. Multiple interventions may be required to achieve biventricular circulation, but stenting of the arterial duct may reduce hospital stay and repeat procedures.

Coronary flow in neonates with impaired intrauterine growth.

BACKGROUND: Subclinical myocardial injury has been reported in newborns with fetal weights < 2 SDs for gestational age. Intrauterine growth restriction might affect cardiac function and coronary flow (CF). METHODS: Seventeen newborns with intrauterine growth restriction and 15 age-matched healthy controls were enrolled in the study. Blood flow in the umbilical artery and maternal uterine artery was assessed using Doppler velocimetry. Cardiac function and left anterior descending coronary artery CF were measured using transthoracic Doppler echocardiography at 1 week of age. RESULTS: The mean growth deviation of the newborns from normal was -2.5 ± 0.2 SDs. Percentage left ventricular shortening fraction was 39 ± 4.3% in patients and 42 ± 4.1% in controls (P = .40), and the mean left ventricular mass index was 86.6 g/m(2) in patients and 73.7 g/m(2) in controls (P < .01). The mean left anterior descending coronary artery diameter was 0.99 ± 0.1 mm in patients and 0.8 ± 0.1 mm in controls (P = .002). The left anterior descending coronary artery flow velocity-time integral was correlated with left ventricular mass index (r = 0.31, P = .007) and with mitral peak E/A ratio (r = 0.74, P = .01). Intrauterine growth restriction was associated with increased peak flow velocity in diastole (34.5 ± 4 vs 19 ± 6 cm/sec in controls, P = .0001), as well as increased CF (37 ± 7.3 vs 8.2 ± 3.0 mL/min in controls, P = .001). CONCLUSIONS: CF is significantly increased in neonates with impaired intrauterine growth. Left ventricular mass index is increased, but systolic and diastolic function remains normal. The clinical significance of increased CF is unclear, but it might lead to decreased CF reserve.

Quantification of left-to-right shunt through patent ductus arteriosus by colour Doppler in children admitted for a device closure.

PURPOSE: Our animal model suggests that quantification of ductal flow from colour Doppler pixels is possible. We aimed to clarify whether this method can be used to determine a clinically significant ductal shunt in children. METHODS: We retrospectively quantified ductal flow from saved images from 20 children who had been admitted for device occlusion of patent ductus arteriosus. Colour Doppler images over the main stem of the pulmonary artery were obtained in longitudinal cross-sections. The colour pixel percentages during diastole, representing ductal flow, were correlated with the documented shunt, measured invasively according to Fick's principle. RESULTS: The ratio of pulmonary to systemic flow correlated best with the sum of the percentages of green colour pixels (r = 0.73, r2 = 0.54, p < 0.001). When the shunt was 1.5:1 or more, 12 out of 13 infants had 50% or more of the region of interest covered with green pixels--sensitivity 92%, specificity 71%. The correlation between ductal diameter and pulmonary-to-systemic flow ratio was less significant (r = 0.6, r2 = 0.37, p < 0.03). CONCLUSIONS: We conclude that clinically significant shunts with pulmonary-to-systemic flow ratio over 1.5 can be diagnosed with this method where neither the size of the patient nor echocardiographic settings seem to be critical. The method could be used to provide an objective indication for ductal closure, but further prospective studies in children are needed to verify the power of the method.

Infection-induced coronary dysfunction and systemic inflammation in piglets are dampened in hypercholesterolemic milieu.

The synergism of infection with conventional cardiovascular risk factors in atherosclerosis is much debated. We hypothesized that coronary arterial injury correlates with infection recurrence and pathogen burden and is further aggravated by hypercholesterolemia. Forty-two Göttingen minipigs were assigned to repeated intratracheal inoculation of PBS, Chlamydia pneumoniae (Cpn), or both Cpn and influenza virus at 8, 11, and 14 wk of age. Animals were fed either standard or 2% cholesterol diet (chol-diet). At 19 wk of age coronary vasomotor responses to acetylcholine (ACh) and adenosine were assessed in vivo and blood and tissue samples were collected. Nonparametric tests were used to compare the groups. In cholesterol-fed animals, total cholesterol/HDL was significantly increased in infected animals compared with noninfected animals [3.13 (2.17-3.38) vs. 2.03 (1.53-2.41), respectively; P = 0.01]. C-reactive protein (CRP) rose in infected animals [10.60 (4.96-18.00) vs. 2.47 (1.44-3.01) µg/ml in noninfected; P < 0.01] without significant difference between the mono- and coinfected groups. Among coinfected animals, both CRP and haptoglobin were lower in those fed chol-diet than in those fed standard diet (P < 0.05). The vasoconstricting response to ACh was most prominent in coinfected animals {769.3 (594-1,129) cm; P = 0.03 vs. noninfected [342 (309-455) cm] and P = 0.07 vs. monoinfected [415 (252.5-971.8) cm]}. Among monoinfected animals, similar to CRP, a trend for less vasoconstriction was observed in those fed chol-diet (P = 0.08). Coinfection of piglets appears to be associated with more pronounced coronary muscarinic vasomotor dysfunction. In monoinfected animals, use of chol-diet seems to dampen both coronary dysfunction and systemic inflammation induced by infection.

Pathophysiology of coronary blood flow in congenital heart disease.

OBJECTIVES: The aim was to investigate the effects of volume and pressure overload and increased coronary perfusion pressure on coronary flow (CF) in congenital heart disease (CHD) patients. BACKGROUND: The effects of CHD on CF are poorly mapped. METHODS: A total of 65 patients with acyanotic CHD and 49 age-matched healthy controls were examined by transthoracic Doppler echocardiography. Posterior descending artery flow was measured in patients with pulmonary valve stenosis (PS) and atrial septal defects (ASDs) i.e. in lesions with right ventricular pressure or volume overload, and left anterior descending artery flow in patients with coarctation of the aorta (CoA) and ventricular septal defect (VSD), in lesions with left ventricular pressure or volume overload. The CF data in each patient group were expressed as the percent of the median for healthy controls from the same age group. RESULTS: The CF values were in VSD 172%, ASD 185%, PS 233%, and CoA 773% patients. In CoA patients body surface area (r=0.90, p<0.0001), systolic blood pressure (r=0.72, p<0.0001), diastolic blood pressure (r=0.77, p<0.0001), systolic wall tension (r=-0.77, p=0.004), and signs of inflammation (log CRP, r=-0.75, p=0.007) correlated with CF. CONCLUSIONS: The increase in CF and velocity was most significant in patients with CoA. In newborns, increased coronary perfusion pressure seems to be the most important factor for increased CF, even if the pressure is not assumed to cause a significant increase in flow over the auto-regulatory range of 70-130mmHg. We also showed that inflammation decreases CF.

Late coronary complications after arterial switch operation and their treatment.

OBJECTIVES: To report the late coronary complications and their treatment after arterial switch operation (ASO). BACKGROUND: Asymptomatic patients after ASO may have coronary ostial stenosis or obstruction. METHODS: Since 1980, 279 patients were operated with ASO. At the time of preparing this article, selective follow-up coronary angiograms were done on 81 patients. RESULTS: Coronary stenosis was found in six patients. A 6-year-old patient with left coronary artery (LCA) ostial stenosis and a 9-year-old patient with conus branch occlusion had good collaterals without a need for further treatment. One patient with LCA obstruction, myocardial infarction, and left ventricular failure was operated with osteoplasty at age of 16 years. In three essentially asymptomatic patients, stenting of LCA ostium stenosis was done: in two of them with drug-eluting stents at 9 and 10 years of age and in one with bare-metal stent at 18 years of age. One of these patients was earlier treated with balloon dilatation at 5 years of age which caused intimal dissection. CONCLUSIONS: Asymptomatic patients with an uneventful course after ASO may have coronary obstruction. This necessitates follow-up coronary evaluation in all patients. Stenting of the coronary arteries is an option for treatment.

Infections as a stimulus for coronary occlusion, obstruction, or acute coronary syndromes.

BACKGROUND: Atherosclerosis is considered to be an inflammatory disease. Infections are a significant cause of inflammation. Acute infections might precipitate acute coronary syndromes (ACS) whereas chronic infections might be stimuli for the development of atherosclerosis. METHODS: Coronary angiograms were done on 211 of 335 patients with ACS and the percentage of coronary obstruction was determined. Serum antibody levels to Chlamydia pneumoniae, C. pneumoniae heat shock protein 60 (CpnHSP60), human heat shock protein 60 (hHSP60), enterovirus (EV), herpes simplex virus (HSV), cytomegalovirus (CMV), and two major periodontal pathogens, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, were measured in healthy controls (n = 355) and all patients. RESULTS: Serum antibody levels to periodontal pathogens did not correlate with ACS. However, IgA-class antibody levels to Aggregatibacter actinomycetemcomitans (p = 0.021), CpnHSP60 (p = 0.048) an hHSP60 (p = 0.038) were higher in patients with coronary occlusion or obstruction compared to those without any obstruction. Odds ratios for coronary changes in the highest quartile as compared to the lower quartiles were for A. actinomycetemcomitans IgA 7.84 (95% CI 1.02-60.39, p = 0.048), for CpnHSP60 IgA 8.61 (1.12-65.89, p = 0.038), and for human HSP60 IgA 3.51 (0.79-15.69, p = 0.100). CONCLUSIONS: We have previously reported that EV and HSV titres correlated significantly to acute coronary events. They do not correlate to the degree of coronary obstruction as shown here. However, infection by A. actinomycetemcomitans or C. pneumoniae or host response against them associated with coronary obstruction. Clinical coronary events may arise by the effect of acute infections and obstructing lesions by a chronic inflammatory stimulus.