Mitral annular plane systolic excursion (MAPSE) in shock: a valuable echocardiographic parameter in intensive care patients.

BACKGROUND: Assessing left ventricular (LV) dysfunction by echocardiography in ICU patients is common. The aim of this study was to investigate mitral annular plane systolic excursion (MAPSE) in critically ill patients with shock and its relation to LV systolic and diastolic function, myocardial injury and to outcome. METHODS: In a prospective, observational, cohort study we enrolled 50 patients with SIRS and shock despite fluid resuscitation. Transthoracic echocardiography (TTE) measuring LV function was performed within 12 hours after admission and daily for a 7-day observation period. TTE and laboratory measurements were related to 28-day mortality. RESULTS: MAPSE on day 1 correlated significantly with LV ejection fraction (LVEF), tissue Doppler indices of LV diastolic function (é, E/é) and high-sensitive troponin T (hsTNT) (p< 0.001, p= 0.039, p= 0.009, p= 0.003 respectively) whereas LVEF did not correlate significantly with any marker of LV diastolic function or myocardial injury. Compared to survivors, non-survivors had a significantly lower MAPSE (8 [IQR 7.5-11] versus 11 [IQR 8.9-13] mm; p= 0.028). Other univariate predictors were age (p=0.033), hsTNT (p=0.014) and Sequential Organ Failure Assessment (SOFA) scores (p=0.007). By multivariate analysis MAPSE (OR 0.6 (95% CI 0.5- 0.9), p= 0.015) and SOFA score (OR 1.6 (95% CI 1.1- 2.3), p= 0.018) were identified as independent predictors of mortality. Daily measurements showed that MAPSE, as sole echocardiographic marker, was significantly lower in most days in non-survivors (p<0.05 at day 1-2, 4-6). CONCLUSIONS: MAPSE seemed to reflect LV systolic and diastolic function as well as myocardial injury in critically ill patients with shock. The combination of MAPSE and SOFA added to the predictive value for 28-day mortality.

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.

High-sensitive cardiac Troponin T is superior to echocardiography in predicting 1-year mortality in patients with SIRS and shock in intensive care.

BACKGROUND: Left ventricular (LV) dysfunction is well documented in the critically ill. We assessed 1-year mortality in relation to cardiac biomarkers and LV function parameters by echocardiography in patients with shock. METHODS: A prospective, observational, cohort study of 49 patients. B-natriuretic peptide (BNP), high-sensitive troponin T (hsTNT) and transthoracic echocardiography (TTE) were assessed within 12 h of study inclusion. LV systolic function was measured by ejection fraction (LVEF), mean atrioventricular plane displacement (AVPDm), peak systolic tissue Doppler velocity imaging (TDIs) and velocity time integral in the LV outflow tract (LVOT VTI). LV diastolic function was evaluated by transmitral pulsed Doppler (E, A, E/A, E-deceleration time), tissue Doppler indices (é, á, E/é) and left atrial volume (La volume). APACHE II (Acute Physiology and Chronic Health Evaluation) and SOFA (Sequential Organ Failure Assessment) scores were calculated. RESULTS: hsTNT was significantly higher in non-survivors than in survivors (60 [17.0-99.5] vs 168 [89.8-358] ng/l, p = 0.003). Other univariate predictors of mortality were APACHE II (p = 0.009), E/é (p = 0.023), SOFA (p = 0.024) and age (p = 0.031). Survivors and non-survivors did not differ regarding BNP (p = 0.26) or any LV systolic function parameter (LVEF p = 0.87, AVPDm p = 0.087, TDIs p = 0.93, LVOT VTI p = 0.18). Multivariable logistic regression analysis identified hsTNT (p = 0.010) as the only independent predictor of 1-year mortality; adjusted odds ratio 2.0 (95% CI 1.2- 3.5). CONCLUSIONS: hsTNT was the only independent predictor of 1-year mortality in patients with shock. Neither BNP nor echocardiographic parameters had an independent prognostic value. Further studies are needed to establish the clinical significance of elevated hsTNT in patients in shock.

Impact of hypoxia, simulated ischemia and reperfusion in HL-1 cells on the expression of FKBP12/FKBP12.6 and intracellular calcium dynamics.

AIMS: To establish a cardiac cell culture model for simulated ischemia and reperfusion and in this model investigate the impact of simulated ischemia and reperfusion on expression of the calcium handling proteins FKBP12 and FKBP12.6, and intracellular calcium dynamics. METHODS: HL-1 cell cultures were exposed to normoxia (as control), hypoxia, simulated ischemia (HEDA) or HEDA+reactive oxygen species (ROS) for up to 24 h and after HEDA, with or without ROS, followed or not by simulated reperfusion (REPH) for 6 h. Viability was analyzed with a trypan blue exclusion method. Cell lysates were analyzed with real-time PCR and Western blot (WB) for FKBP12 and FKBP12.6. Intracellular Ca(2+)measurements were performed using dual-wavelength ratio imaging in fura-2 loaded cells. RESULTS: A time-dependent drop in viability was shown after HEDA (P<0.001). Viability was not further influenced by addition of ROS or REPH. The general patterns of FKBP12 and FKBP12.6 mRNA expression showed upregulation after hypoxia, downregulation after ischemia and normalization after reperfusion, which was partially attenuated if ROS was added during HEDA. The protein contents were unaffected after hypoxia, tended to increase after ischemia and, for FKBP12.6, a further increase after reperfusion was shown. Hypoxia or HEDA, with or without REPH, resulted in a decreased amplitude of the Ca(2+) peak in response to caffeine. In addition, cells subjected to HEDA for 3 h or HEDA for 3 h followed by 6 h of REPH displayed irregular Ca(2+) oscillations with a decreased frequency. CONCLUSION: A threshold for cell survival with respect to duration of ischemia was established in our cell line model. Furthermore, we could demonstrate disturbances of calcium handling in the sarcoplasmic reticulum as well as alterations in the expressions of the calcium handling proteins FKBP12 and FKBP12.6, why this model may be suitable for further studies on ischemia and reperfusion with respect to calcium handling of the sarcoplasmic reticulum.

Initial results of inflammatory response, matrix remodeling, and reactive oxygen species following PCI in acute ischemic myocardial injury in man.

BACKGROUND: Neutrophils and reactive oxygen species (ROS) are suggested to be involved in irreversible myocardial reperfusion injury and stunning. We investigated the relations between circulating biochemical markers and myocardium at risk (MaR), myocardial infarct (MI) size, salvage, and recovery of function in man. METHODS AND RESULTS: In patients undergoing PCI serial blood samples were acquired for markers of inflammatory response (myeloperoxidase [MPO], neutrophil-gelatinase-associated lipocalin [NGAL], interleukins 6 and 8 [IL-6/8], tumor necrosis factor-a [TNF-a], high-sensitive C-reactive protein [hsCRP]), matrix remodeling (matrixmetalloproteinase-9 [MMP-9]) and ROS (malondialdehyde [MDA], isoprostane [IsoP]). Samples were obtained before PCI and 1.5, 3, and 24 hours after reperfusion. Myocardial perfusion SPECT (MPS) was used to assess MaR. Late gadolinum-enhanced cardiac magnetic resonance imaging was performed for regional function in the acute setting, at 1 week and 6 months, and at 1 week also for MI size. Sixteen patients (15 men; 42-78 years) were enrolled, 12 of whom underwent MPS. Peak and cumulative NGAL and cumulative MMP-9 showed inverse correlations to MaR. No correlation was found for MI size. Peak MPO correlated inversely to salvage and to recovery of regional function in the infarcted segments at 1 week and 6 months. CONCLUSIONS: This is the first study in man to show inverse relations between circulating NGAL and MMP-9 and MaR. The current results do not support that ROS has a role in stunning in man. MI size showed no significant correlation to any parameter, challenging inflammatory treatment in reperfusion.

Assessing left ventricular systolic function in shock: evaluation of echocardiographic parameters in intensive care.

INTRODUCTION: Assessing left ventricular (LV) systolic function in a rapid and reliable way can be challenging in the critically ill patient. The purpose of this study was to evaluate the feasibility and reliability of, as well as the association between, commonly used LV systolic parameters, by using serial transthoracic echocardiography (TTE). METHODS: Fifty patients with shock and mechanical ventilation were included. TTE examinations were performed daily for a total of 7 days. Methods used to assess LV systolic function were visually estimated, "eyeball" ejection fraction (EBEF), the Simpson single-plane method, mean atrioventricular plane displacement (AVPDm), septal tissue velocity imaging (TDIs), and velocity time integral in the left ventricular outflow tract (VTI). RESULTS: EBEF, AVPDm, TDIs, VTI, and the Simpson were obtained in 100%, 100%, 99%, 95% and 93%, respectively, of all possible examinations. The correlations between the Simpson and EBEF showed r values for all 7 days ranging from 0.79 to 0.95 (P < 0.01). the Simpson correlations with the other LV parameters showed substantial variation over time, with the poorest results seen for TDIs and AVPDm. The repeatability was best for VTI (interobserver coefficient of variation (CV) 4.8%, and intraobserver CV, 3.1%), and AVPDm (5.3% and 4.4%, respectively), and worst for the Simpson method (8.2% and 10.6%, respectively). CONCLUSIONS: EBEF and AVPDm provided the best, and Simpson, the worst feasibility when assessing LV systolic function in a population of mechanically ventilated, hemodynamically unstable patients. Additionally, the Simpson showed the poorest repeatability. We suggest that EBEF can be used instead of single-plane Simpson when assessing LV ejection fraction in this category of patients. TDIs and AVPDm, as markers of longitudinal function of the LV, are not interchangeable with LV ejection fraction.

High-frequency electrocardiogram as a supplement to standard 12-lead ischemia monitoring during reperfusion therapy of acute inferior myocardial infarction.

BACKGROUND: Resolution of ST-segment elevation in the electrocardiogram (ECG) is used as a reperfusion sign during thrombolytic therapy in acute myocardial infarction. Analysis of high-frequency QRS components (HF-QRS) might provide additional information. The study compares changes in HF-QRS (150-250 Hz) to ST-segment changes in the standard ECG during thrombolytic therapy. METHODS: Twelve patients receiving intravenous thrombolytic therapy were included. A continuous 12-lead ECG recording was acquired for 4 hours. RESULTS: After 1 hour of therapy, 3 patients showed ST-elevation resolution as well as an increase in HF-QRS. These changes in ST and HF-QRS occurred simultaneously. No other patient showed significant changes in ST or HF-QRS after 1 hour. After 2 and 4 hours, there was less concordance between the standard and high-frequency ECGs. CONCLUSIONS: In patients with early ST-elevation resolution, the standard and high-frequency ECGs show similar results. Later changes are more disparate and may provide different clinical information.

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.

Infarct evolution in man studied in patients with first-time coronary occlusion in comparison to different species - implications for assessment of myocardial salvage.

BACKGROUND: The time course of infarct evolution, i.e. how fast myocardial infarction (MI) develops during coronary artery occlusion, is well known for several species, whereas no direct evidence exists on the evolution of MI size normalized to myocardium at risk (MaR) in man. Despite the lack of direct evidence, current literature often refers to the "golden hour" as the time during which myocardial salvage can be accomplished by reperfusion therapy. Therefore, the aim of the present study was to investigate how duration of myocardial ischemia affects infarct evolution in man in relation to previous animal data. Consecutive patients with clinical signs of acute myocardial ischemia were screened and considered for enrollment. Particular care was taken to assure uniformity of the patients enrolled with regard to old MI, success of revascularization, collateral flow, release of biochemical markers prior to intervention etc. Sixteen patients were ultimately included in the study. Myocardium at risk was assessed acutely by acute myocardial perfusion single photon emission computed tomography (MPS) and by T2 imaging (T2-STIR) cardiovascular magnetic resonance (CMR) after one week in 10 of the 16 patients. Infarct size was measured by late gadolinium enhancement (LGE) at one week. RESULTS: The time to reach 50% MI of the MaR (T50) was significantly shorter in pigs (37 min), rats (41 min) and dogs (181 min) compared to humans (288 min). There was no significant difference in T50 when using MPS compared to T2-STIR (p = 0.53) for assessment of MaR (288 +/- 23 min vs 310 +/- 22 min, T50 +/- standard error). The transmural extent of MI increased progressively as the duration of ischemia increased (R2 = 0.56, p < 0.001). CONCLUSION: This is the first study to provide direct evidence of the time course of acute myocardial infarct evolution in relation to MaR in man with first-time MI. Infarct evolution in man is significantly slower than in pigs, rats and dogs. Furthermore, infarct evolution assessments in man are similar when using MPS acutely and T2-STIR one week later for determination of MaR, which significantly facilitates future clinical trials of cardioprotective therapies in acute coronary syndrome by the use of CMR.

Mannose-binding lectin as a risk factor for acute coronary syndromes.

BACKGROUND: Mannose-binding lectin (MBL) is a multifunctional protein involved in innate immunity. We tested whether MBL and elevated viral and bacterial antibodies were risk factors for acute coronary events. DESIGN: Controlled cohort study. METHODS: A total of 354 patients with unstable angina pectoris (UA) or acute myocardial infarction (AMI) were compared with 334 paired controls. RESULTS: Enterovirus titres were associated with increased risk of UA (odds ratio 10.04, P<0.001) and AMI (odds ratio 3.18, P=0.003), but titres did not correlate with either MBL concentration or genotype. Chlamydia pneumoniae heat shock protein 60 IgG concentrations were also associated with increased risk of UA (odds ratio 1.63, P=0.049). Compared to asymptomatic controls, patients had lower complement C3 serum concentrations (P<0.001), higher MBL serum concentration, and more frequently had MBL genotypes that determined high MBL levels (P<0.001). High MBL genotypes had odds ratios of 1.16 (P=0.010) for UA and 1.12 (P=0.007) for AMI. The elevation of MBL concentrations in the acute phase correlated with MBL concentrations after recovery (r=0.85, P<0.001). CONCLUSIONS: Elevated microbial titres, indicating an on-going inflammation, were associated with cardiovascular events. MBL might have a dual role both decreasing susceptibility to infections and increasing the risk of acute coronary syndromes.

Serum chlamydial lipopolysaccharide as a prognostic factor for a new cardiovascular event.

BACKGROUND: Infections caused by Chlamydia pneumoniae are considered to participate in inflammatory processes leading to coronary artery disease. After a primary infection, the bacteria remain dormant intracellularly causing a chronic inflammatory stimulus. MATERIALS AND METHODS: Blood samples were obtained from 235 patients with acute myocardial infarction (AMI) and 108 patients with unstable angina pectoris (UA). We evaluated the prognostic significance of bacterial and viral antibody titers, serum troponin T, C-reactive protein, and chlamydial lipopolysaccharide (cLPS) concentrations during acute coronary syndrome of patients with AMI and UA for cardiovascular death and new UA and AMI that required hospital care during a 6-year follow-up. RESULTS: Serum cLPS levels correlated with C-reactive protein and serum troponin T concentrations during acute coronary events. Patients with AMI had significantly higher serum concentration of cLPS compared with patients with UA. Enterovirus antibody titers and cholesterol-lowering therapy at admission of the index event were negatively correlated with cLPS concentration (r = -.198, P = .0003 and r = -.26, P = .019, respectively). The presence of circulating cLPS was associated with a hazard ratio of 2.04 for a new cardiovascular event during the follow-up period (P = .006). The area under the curve in the receiver operating graph was .572. CONCLUSION: cLPS is evidently liberated from the infected atherosclerotic tissue during an acute coronary event. Our study supports the view that inflammation caused by C. pneumoniae infection is an important but as yet poorly understood factor in the development of atherosclerosis and may play a role in acute vascular events.

In search of the best method to predict acute coronary syndrome using only the electrocardiogram from the emergency department.

INTRODUCTION: The aim of this study was to compare different methods to predict acute coronary syndrome (ACS) using only data from a single electrocardiogram (ECG) in the emergency department (ED). METHOD: We compared the ACS prediction abilities of classical ECG criteria, human expert ECG interpretation, a logistic regression model and an artificial neural network ensemble (ANN). The ED ECG and discharge diagnoses were retrieved for 861 patient visits to the ED for chest pain. Cross-validation was used to estimate the generalization performance of the logistic regression and the ANN model. RESULTS: The logistic regression model had the overall best performance in predicting ACS with an area under the receiver operating characteristic curve of 0.88. The sensitivities of logistic regression, ANN, expert physicians, and classical ECG criteria were 95%, 95%, 82%, and 75%, respectively, and the specificities were 54%, 44%, 63%, and 69%. CONCLUSION: Our logistic regression model was the best overall method to predict ACS, followed by our ANN. Decision support models have the potential to improve even experienced ECG readers' ability to predict ACS in the ED.

A randomised trial of a pre-synaptic stimulator of DA2-dopaminergic and alpha2-adrenergic receptors on morbidity and mortality in patients with heart failure.

BACKGROUND: By pre-synaptic stimulation of DA(2)-dopaminergic and alpha(2)-adrenergic receptors, nolomirole inhibits norepinephrine secretion from sympathetic nerve endings. We performed a clinical study with nolomirole in patients with heart failure (HF). METHODS: The study was designed as a multicentre, double blind, parallel group trial of 5 mg b.i.d. of nolomirole (n=501) versus placebo (n=499) in patients with severe left ventricular systolic dysfunction, recently in New York Heart Association (NYHA) class III/IV. The primary endpoint was time to all cause death or hospitalisation for HF, whichever came first. The study was event driven and required 420 primary events. The study was completed as scheduled. RESULTS: Mean age of patients was 70 years, and 73% were male. Heart rate and blood pressure were not different in the two treatment groups. There were no changes in blood pressure. There were 233 primary events in the nolomirole group versus 208 in the placebo group (p=0.1). There were 142/145 deaths and 369/374 all cause hospitalisations in the nolomirole/placebo groups. There were no differences in walking distance, quality of life or NYHA class. CONCLUSION: A dose of 5 mg b.i.d. of nolomirole was not beneficial (or harmful) in patients with heart failure.

Elevated infection parameters and infection symptoms predict an acute coronary event.

BACKGROUND: The etiology and significance of flu-like symptoms often appearing before myocardial infarction should be clarified. METHODS: In a case-control study of 323 matched controls and a random sample of 110 out of 351 cases the presence of infection symptoms during the preceding four weeks before admission were asked and blood samples taken. RESULTS: Enterovirus (EV), herpes simplex virus (HSV), and Chlamydia pneumoniae IgA titers were significantly higher in cases than in controls (p<0.001, 0.008 and 0.046, respectively). Flu-like symptoms appeared significantly more often in patients than in controls the most common one being fatigue (p<0.001). In controls with fatigue, EV and HSV titers showed a trend to be higher (1.50 vs 1.45 and 4.29 vs 3.73) than in controls without fatigue but only HSV titers were statistically significantly higher (3.47 vs 3.96, p = 0.02). Even CRP and amyloid A concentrations (3.49 vs 2.08, p<0.0001 and 5.70 vs 3.77 mg/l, p = 0.003, respectively) as well as C4 (0.40 vs 0.44, p = 0.02) were higher in controls with fatigue. CONCLUSIONS: Odds ratios for a coronary event in a logistic regression model were 4.79 for fatigue and 2.72 for EV antibody levels in their fourth quartile. A linear-by-linear association test showed increasing number of single symptoms with higher EV titer quartiles (p = 0.004).

Dissociation of the Inflammatory Reaction following PCI for Acute Myocardial Infarction.

OBJECTIVES: Neutrophils are activated and infiltrate the myocardium after ischemia and reperfusion. The involvement of neutrophils in irreversible reperfusion injury is suggested by numerous experimental studies. The aim of this study was to investigate markers of neutrophil activation following reperfusion of acute myocardial infarction (AMI) accomplished with percutaneous coronary intervention (PCI) and their relationship to markers of lipid peroxidation, cytokines and highly-sensitive C-reactive protein (hsCRP). DESIGN: Non-consecutive patients with their first myocardial infarction were evaluated. Setting. University hospital as primary referral center, single center. PATIENTS AND METHODS: Forty-nine patients with AMI were evaluated. All were treated with primary PCI and infusion of abciximab. Reperfusion was verified by angiography. Blood samples for analyses of myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9), malondialdehyde (MDA), 8-isoprostane-prostaglandin F2alpha (Iso-P), interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factoralpha (TNFalpha), hsCRP, creatine kinase-monobasic fraction (CK-MB) and troponin-T (TnT) were obtained at baseline with the occluded coronary vessel, and subsequently after verified reperfusion at 1.5, 3 and 24 hours. RESULTS: Significant increases in MMP-9, IL-6, IL-8, TNFalpha and hsCRP were observed, and a significant decrease in MPO and MDA was also observed over the same period. No significant changes in Iso-P and NGAL were found. CONCLUSION: We found a dissociation of the inflammatory reaction after PCI for AMI: a decrease of markers of neutrophil activation and MDA, but an increase in cytokines and hsCRP. An antineutrophil effect of the PCI procedure including treatment with abciximab, an antiplatelet drug and a modulator of inflammation, is conceivable.

Perspectives that lay persons with and without health problems show toward coronary heart disease: An integrated biopsychosocial approach.

OBJECTIVE: We studied what patients with acute coronary heart disease (CHD) considered the three most stressful factors experienced during the month before testing and what they attributed their heart disease to. METHODS: We studied the occurrence and severity of physiologic, psychologic, and psychosocial stressors in 117 patients with acute CHD and 117 referents, not diagnosed with CHD, matched by age, sex, and municipality. The subjects were first to select the factors they considered stressful from a list of potentially stressful factors. They were then to select the three they regarded as most stressful and to provide situational accounts of these. RESULTS: The patients with CHD were found to less frequently live with a partner, to more frequently have a body mass index higher than 30.0, and to report a greater number of stressors. The stressors best differentiating them from the referents were fatigue, shortness of breath, pain, and high blood pressure. The causal factors they most frequently named were heart problems, smoking, heredity, high workload, and poor eating habits. CONCLUSIONS: The situational accounts the patients provided illustrate the biopsychosocial complexities involved in the various categories of stressful factors.

Peak CKMB and cTnT accurately estimates myocardial infarct size after reperfusion.

OBJECTIVES: To find the time-to-peak for creatine kinase MB(mass) (CKMB) and cardiac troponin T (cTnT) after acute reperfusion, to compare peak and cumulative values to estimate infarct size (IS), and to evaluate clinical routine sampling for assessment of IS. DESIGN: Acute primary percutaneous coronary intervention (PCI) was performed in 38 patients with first-time myocardial infarction. In 21 patients, CKMB and cTnT were acquired before PCI and at 1.5, 3, 6, 12, 18, 24, and 48 hours thereafter. In 17 patients, clinical routine samples were acquired at arrival, and at 10 and 20 h. IS was assessed by delayed contrast-enhanced MRI (DE-MRI). RESULTS: Time-to-peak was 7.6+/-3.6 h for CKMB and 8.1+/-3.4 h for cTnT. Peak values correlated strongly to cumulative values (r(s)=0.97-0.98) as well as to DE-MRI (r(s)=0.8-0.82). Clinical routine sampling showed lower rs values (0.47-0.60). CONCLUSIONS: Peak values are likely captured if CKMB and cTnT are acquired at 3, 6, and 12 h after acute PCI. These peak values can be used to estimate myocardial infarct size after acute PCI.

Dual role of infections as risk factors for coronary heart disease.

AIMS: The aim of the study was to explore whether exposure to microbial agents determines the prevalence of acute coronary events. METHODS AND RESULTS: Patients with unstable angina pectoris and myocardial infarction (N=335) and their paired controls were investigated. The subjects answered a questionnaire about their childhood contagious diseases: varicella, scarlet fever, measles, rubella, mononucleosis and mumps. Blood samples were taken for bacterial and viral serology. The odds ratio for CHD was highest in the upper quartile of the enterovirus (EV), herpes simplex virus (HSV) and Chlamydia pneumoniae HSP60 IgG antibody titers (1.86, p=0.001, 1.57, p<0.048 and 1.70, p=0.016, respectively). The antibody titers increased cumulatively the risk for CHD (odds ratios 1.89, 2.24, 3.92 and p-values <0.001, 0.001 and 0.047). Childhood contagious diseases (n=6) had a protecting effect against CHD (odds ratio 0.86, p=0.013). The risk for acute coronary events decreased significantly with increasing number of childhood contagious diseases (p=0.007). CONCLUSIONS: Infections have a dual role in the genesis of CHD. EV, HSV and C. pneumoniae heat shock protein 60 IgG antibodies are associated with increased risk for CHD. Protection from infections usually suffered during the childhood before the era of MMR vaccination may predispose the individual to CHD.

Neurohumoral changes in patients with left ventricular dysfunction following acute myocardial infarction and the effect of nitrate therapy: a randomized, double-blind, placebo-controlled long-term study.

BACKGROUND: Several neurohumoral mechanisms involved in cardiovascular regulation are activated in the failing heart, but only limited information is available regarding the influence of long-term nitrate therapy. MATERIALS AND METHODS: This was a double-blind, randomized comparison of isosorbide-5-mononitrate (IS-5-MN), 60 mg given orally, once daily for 11 months to patients (n = 47) with left ventricular (LV) dysfunction following acute myocardial infarction (AMI). Forty-five patients received placebo. All patients received ramipril.Plasma natriuretic peptides (atrial [ANP] and brain [BNP] natriuretic peptide), epinephrine, norepinephrine (NEPI), antidiuretic hormone, aldosterone (Aldo), renin activity (PRA), substance P, neuropeptide Y-like immunoreactivity, calcitonin gene-related peptide, and vasoactive intestinal peptide were measured at baseline and at the end of the treatment period. Clinical, echocardiographic, and hemodynamic data were also obtained. RESULTS AND CONCLUSIONS: Chronic nitrate therapy does not significantly affect the neurohumoral status in patients with LV dysfunction after AMI, apart from a decrease in ANP. Some hormones are more closely associated with diastolic dysfunction/increased volume load (ANP and BNP) and others are more closely associated with systolic dysfunction (PRA, NEPI, Aldo). There is a temporal dissociation of these 2 groups of hormones 1 year post infarction: ANP and BNP decrease, whereas NEPI and Aldo show a slight increase. BNP levels do not reflect all important pathophysiologic mechanisms in heart failure. Consequently, the use of other neurohormonal factors than BNP for monitoring of heart failure therapy should be explored.