Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure.

BACKGROUND: Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients. METHODS AND RESULTS: We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensin-converting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74-0.94; P=0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52-0.85; P=0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P<0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction, P=0.005), to receive intravenous positive inotropic agents (31% risk reduction, P<0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction, P=0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro-B-type natriuretic peptide and troponin) versus enalapril. CONCLUSIONS: Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.

Idiopathic dilated cardiomyopathy and chronic atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is common in idiopathic dilated cardiomyopathy (IDC). We explored the clinical characteristics of IDC patients with chronic AF compared with those with sinus rhythm (SR). METHODS: A group of patients with IDC underwent extensive non-invasive and invasive evaluation during a hospitalization period. The patients were further divided into two groups with AF (n = 19) and SR (n = 68). RESULTS: Left atrial diameter was greater (P<0·001), left ventricular end-diastolic diameter smaller (P<0·05), left ventricular end-diastolic and end-systolic volumes smaller (P<0·01 for all), mean pulmonary artery pressure and pulmonary capillary wedge pressure higher (P<0·05 for both), cardiac output and maximal oxygen consumption lower (P<0·01 and P<0·05, respectively), and the levels of N-terminal pro-brain natriuretic peptide and interleukin-6 higher (P<0·05 for both) in AF group compared with SR group. Left ventricular ejection fraction and left ventricular end-diastolic pressure were similar in both groups. CONCLUSIONS: In spite of otherwise more unfavourable prognostic factor profile, left ventricular size was observed to be smaller in chronic AF compared with SR in well-characterized patients with IDC. The confirmation and possible explainers of this paradoxical phenomenon need further studies in larger patient cohorts.

Low-grade inflammation and the phenotypic expression of myocardial fibrosis in hypertrophic cardiomyopathy.

OBJECTIVE: To investigate the role of inflammation in the phenotypic expression of myocardial fibrosis in hypertrophic cardiomyopathy (HCM). DESIGN: Clinical study. SETTING: Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland. SUBJECTS: Twenty-four patients with a single HCM-causing mutation D175N in the α-tropomyosin gene and 17 control subjects. MAIN OUTCOME MEASURES: Endomyocardial biopsy samples taken from the patients with HCM were compared with matched myocardial autopsy specimens. Levels of high-sensitivity C-reactive protein (hsCRP) and proinflammatory cytokines were measured in patients and controls. Myocardial late gadolinium enhancement (LGE) in cardiac MRI (CMRI) was detected. RESULTS: Endomyocardial samples in patients with HCM showed variable myocyte hypertrophy and size heterogeneity, myofibre disarray, fibrosis, inflammatory cell infiltration and nuclear factor kappa B (NF-κB) activation. Levels of hsCRP and interleukins (IL-1ß, IL-1RA, IL-6, IL-10) were significantly higher in patients with HCM than in control subjects. In patients with HCM, there was a significant association between the degree of myocardial inflammatory cell infiltration, fibrosis in histopathological samples and myocardial LGE in CMRI. Levels of hsCRP were significantly associated with histopathological myocardial fibrosis. hsCRP, tumour necrosis factor α and IL-1RA levels had significant correlations with LGE in CMRI. CONCLUSIONS: A variable myocardial and systemic inflammatory response was demonstrated in patients with HCM attributable to an identified sarcometric mutation. Inflammatory response was associated with myocardial fibrosis, suggesting that myocardial fibrosis in HCM is an active process modified by an inflammatory response.

Late gadolinium enhanced cardiovascular magnetic resonance of lamin A/C gene mutation related dilated cardiomyopathy.

BACKGROUND: The purpose of this study was to identify early features of lamin A/C gene mutation related dilated cardiomyopathy (DCM) with cardiovascular magnetic resonance (CMR). We characterise myocardial and functional findings in carriers of lamin A/C mutation to facilitate the recognition of these patients using this method. We also investigated the connection between myocardial fibrosis and conduction abnormalities. METHODS: Seventeen lamin A/C mutation carriers underwent CMR. Late gadolinium enhancement (LGE) and cine images were performed to evaluate myocardial fibrosis, regional wall motion, longitudinal myocardial function, global function and volumetry of both ventricles. The location, pattern and extent of enhancement in the left ventricle (LV) myocardium were visually estimated. RESULTS: Patients had LV myocardial fibrosis in 88% of cases. Segmental wall motion abnormalities correlated strongly with the degree of enhancement. Myocardial enhancement was associated with conduction abnormalities. Sixty-nine percent of our asymptomatic or mildly symptomatic patients showed mild ventricular dilatation, systolic failure or both in global ventricular analysis. Decreased longitudinal systolic LV function was observed in 53% of patients. CONCLUSIONS: Cardiac conduction abnormalities, mildly dilated LV and depressed systolic dysfunction are common in DCM caused by a lamin A/C gene mutation. However, other cardiac diseases may produce similar symptoms. CMR is an accurate tool to determine the typical cardiac involvement in lamin A/C cardiomyopathy and may help to initiate early treatment in this malignant familiar form of DCM.

Natriuretic peptides and collagen biomarkers in patients with medical treatment for hypertension.

OBJECTIVE: The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-BPLA) showed that an amlodipine-based regimen prevented more cardiovascular events than an atenolol-based regimen in patients at high risk of hypertension.The basis of this difference is partly unknown and may be due to their divergent effects on the remodelling process of hypertensive heart disease. METHODS AND RESULTS: We measured plasma levels of aminoterminal propeptide of atrial natriuretic peptide (NT-proANP) and aminoterminal propeptide of B-type natriuretic peptide and serum levels of the aminoterminal propeptide of type I procollagen (PINP), aminoterminal propeptide of type III procollagen and type I collagen telopeptide in 93 patients randomized in the ASCOT study at baseline and after two and four years and compared them with echocardiographic parameters and blood pressure. NT-proANP decreased at two years by 22 (-484 - 153) pmol/l in the amlodipine-based regimen and increased by 109 (-297 - 1545) pmol/l in the atenolol-based regimen (P < 0.001), whereas no significant difference in NT-proBNP between the arms was found. PINP levels increased by 1.8 (-29 -31) microg/l in the amlodipine-based regimen and decreased by 4.7 (-27- 31) microg/I in the atenolol-based regimen, whereas no differences were found in other collagen markers between the arms. Major echocardiographic changes were not found. CONCLUSIONS: Our results show that the two treatment regimens of ASCOT-BPLA had different effects on plasma natriuretic peptides and serological markers of collagen turnover, probably reflecting divergent effects in cardiac remodelling.

Markers of renal function and acute kidney injury in acute heart failure: definitions and impact on outcomes of the cardiorenal syndrome.

AIMS: Acute kidney injury (AKI) in patients hospitalized for acute heart failure (AHF) is part of the cardiorenal syndrome and has been associated with increased morbidity and mortality. However, definitions and prognostic impact of AKI in AHF have been variable. Cystatin C is a prospective new marker of AKI. The objective of this study was to investigate the use of cystatin C as a marker of early AKI in AHF. METHODS AND RESULTS: Patients (n = 292) hospitalized for AHF had measurements of cystatin C on admission and at 48 h. We assessed the incidence of a rise in cystatin C between the two measurements and evaluated the effect of an increase in cystatin C on outcomes up to 12 months. The population was on average 75 years old and 49% were female. On admission, median cystatin C was 1.25 mg/L (interquartile range 0.99-1.61 mg/L). A rise in cystatin C by >0.3 mg/L within 48 h after hospitalization (AKI(cysC)) occurred in 16% of patients and resulted in 3 days (P = 0.01) longer hospital stay and was associated with significantly higher in-hospital mortality, odds ratio 4.0 [95% confidence intervals (CI) 1.3-11.7, P = 0.01]. During follow-up, AKI(cysC) was an independent predictor of 90 days mortality, adjusted odds ratio 2.8 (95% CI 1.2-6.7, P = 0.02). CONCLUSION: Cystatin C appears to be a useful marker of early AKI in patients hospitalized for AHF. A decline in renal function detected by cystatin C during the first 48 h after hospitalization occurs frequently in AHF and has a detrimental impact on prognosis.

The activation of the inflammatory cytokines in overweight patients with mild obstructive sleep apnoea.

It is widely accepted that obstructive sleep apnoea (OSA) is linked with cardiovascular diseases. The relationship is complex and remains still poorly understood. The presence of chronic systemic inflammation has been connected with pathogenesis of both OSA and cardiovascular diseases. While atherogenesis is believed to be a process of many years, little is known about the potential impact of the largest OSA subgroup, mild OSA, on the development of cardiovascular diseases. The aim of the present study was to assess whether untreated mild OSA is associated with an activation of inflammatory cytokine system. The adult study population consisted of two groups: 84 patients with mild OSA [apnoea-hypopnoea index (AHI) 5-15 h(-1)] and 40 controls (AHI <5 h(-1)). Serum concentrations of pro- and anti-inflammatory cytokines were measured before any interventions. After adjustments for age, sex, body mass index, fat percentage, most important cardiometabolic and inflammatory diseases, and non-steroidal anti-inflammatory medication, the mean level of tumour necrosis factor-alpha was significantly elevated (1.54 versus 1.17 pg mL(-1), P = 0.004), whereas the level of interleukin-1 beta (IL-1 beta) was reduced (0.19 versus 0.23 pg mL(-1), P = 0.004) in patients with mild OSA compared with controls. The concentrations of the protective anti-inflammatory cytokines, interleukin-10 (1.28 versus 0.70 pg mL(-1), P < 0.001) and interleukin-1 receptor antagonist (478 versus 330 pg mL(-1), P = 0.003) were elevated in the OSA group. The concentrations of C-reactive protein increased, but IL-1 beta decreased along with the increase of AHI. Mild OSA was found to be associated not only with the activation of the pro-inflammatory, but also with the anti-inflammatory systems.

Cardiac sympathetic activity is associated with inflammation and neurohumoral activation in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Idiopathic dilated cardiomyopathy (IDC) is characterized by sympathetic nervous overactivity, inflammation and neurohumoral activation; however, their interrelationships are poorly understood. METHODS AND RESULTS: We studied 99 patients with IDC (age 54 +/- 1 years, left ventricular ejection fraction (EF) 40 +/- 1%, maximum oxygen uptake (VO(2)max) 20 +/- 1 ml kg(-1) min(-2), mean +/- SEM) by using (123)I-metaiodobenzylguanidine (MIBG) imaging. MIBG washout and MIBG heart/mediastinum (H/M)-ratio at 4 h postinjection were calculated. In addition, the plasma levels of interleukin (IL)-6 and N-terminal B-type natriuretic peptide (NT-proBNP) were measured. MIBG washout and MIBG H/M ratio had a significant correlation with IL-6 (r = 0.42, P<0.001 and r = -0.31, P<0.01) and NT-proBNP (r = 0.48, P<0.001 and r = -0.40, P<0.001). During a median follow-up of 4.1 years, 20 patients (20%) had an adverse cardiac event (death, heart transplantation or application of biventricular pacemaker or implantable cardioverter-defibrillator). In these patients, MIBG washout was higher (53 +/- 4 versus 40 +/- 2%, P = 0.01) and H/M ratio lower (1.38 +/- 0.04 versus 1.51 +/- 0.02, P = 0.01) than in patients without an event. CONCLUSIONS: In dilated cardiomyopathy, myocardial sympathetic innervation and activity are related to inflammation and neurohumoral activation. These relationships are at least partly independent of left ventricular function and exercise capacity.

Clinical significance of cardiac troponins I and T in acute heart failure.

BACKGROUND: Elevated cardiac troponin (cTn) levels are relatively common in acute heart failure (AHF). AIMS: To evaluate the prevalence and prognostic significance of elevated cTnI and cTnT in AHF. METHODS: FINN-AKVA is a prospective, multicenter study in AHF. In this analysis, 364 non-ACS patients with measurements of cTnI and cTnT taken on admission and 48 h thereafter were analyzed. RESULTS: Of the 364 AHF patients, 51.1% had cTnI and 29.7% cTnT levels above the cut-off value. Six-month all-cause mortality was 18.7%. Both cTnI (OR 2.0, 95% CI 1.2-3.5, p=0.01) and cTnT (OR 2.6, 95% CI 1.5-4.4, p=0.0006) were associated with adverse outcome. The mortality risk was proportional to the magnitude of cTn release. On multivariable analysis, Cystatin C (OR 6.3, 95% CI 3.2-13, p<0.0001), logNT-proBNP (OR 1.4, 95% CI 1.0-1.8, p=0.03) and systolic blood pressure on admission (/10 mm Hg increase, OR 0.9, 95% CI 0.8-0.9, p=0.0004) were independent risk markers, whereas the troponins were not significantly associated with increased mortality. CONCLUSIONS: cTn elevations are frequent in AHF patients without ACS. cTnI is more often elevated than cTnT. Both cTnI and cTnT elevations are associated with increased mortality proportional to the degree elevation but they do not act as independent risk markers.

Prognostic role of pro- and anti-inflammatory cytokines and their polymorphisms in acute decompensated heart failure.

BACKGROUND: Cytokines play an important role in chronic heart failure (HF), but little is known about their involvement in acute decompensated heart failure (ADHF). AIM: To evaluate the prognostic role of inflammatory cytokines in patients with ADHF. METHODS: Levels of interleukin (IL)-6, tumour necrosis factor alpha (TNF-alpha), IL-10 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured in 423 patients with ADHF. In addition, appropriate cytokine gene polymorphisms were determined. Survival was followed up to 12 months, and prognostic factors were evaluated. RESULTS: Elevated levels of IL-6 and TNF-alpha were strongly associated with increased 12-month mortality (P<0.001 for both), whereas the level of IL-10 was predictive only of 6-month mortality (P<0.01). In multivariate analysis IL-6, chronic renal insufficiency, NT-proBNP, age/10 years' increase and TNF-alpha were identified as the most powerful predictors of 12-month mortality. Furthermore, high levels of both IL-6 and NT-proBNP were associated with >7-fold mortality. Cytokine gene polymorphisms were not associated with outcome. CONCLUSIONS: Circulating levels of pro-inflammatory cytokines IL-6 and TNF-alpha, and the level of an anti-inflammatory cytokine IL-10, but not their gene polymorphisms, provide novel and important prognostic information in patients with ADHF. Combining measurements of pro-inflammatory cytokines and NT-proBNP seems a promising tool in the prognostic assessment of these patients.

Cytokines, interstitial collagen and ventricular remodelling in dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is associated with myocardial fibrosis, and proinflammatory cytokines may play a role in this. METHODS: N-terminal type I and III procollagen propeptides (PINP, PIIINP) and cross-linked telopeptide of type I collagen (ICTP) were measured from serum samples of 73 patients with DCM and 56 age and sex matched controls. Circulating cytokine levels were determined in DCM patients. RESULTS: Serum levels of PINP and PIIINP were lower in patients than in controls (p<0.05 and p=0.001). In patients with DCM, the levels of PIIINP and ICTP correlated significantly with each other (p<0.01), and the proinflammatory cytokines, tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6), correlated positively with ICTP (p<0.001, p<0.05), PIIINP/PINP ratio (p<0.05, p<0.01) and left atrial size (p<0.01, p<0.05). Presence of atrial fibrillation was associated with lower serum PINP level and higher PIIINP/PINP ratio (p<0.05). CONCLUSIONS: Our results suggest that interstitial myocardial collagen metabolism is altered in DCM patients and regulated by proinflammatory cytokines. These changes in collagen metabolism are associated with presence of atrial fibrillation, but do not reflect left ventricular remodelling. Treatment with beta-blockers and inhibitors of the renin angiotensin aldosterone system seem to effectively inhibit overall type I and III collagen syntheses.

Prognostic value of cystatin C in acute heart failure in relation to other markers of renal function and NT-proBNP.

AIMS: Cystatin C, a novel marker of renal function, has been implicated as a prognostic marker in cardiovascular disease. We investigated the prognostic value of cystatin C in acute heart failure (AHF) in comparison to other markers of renal function and NT-proBNP. METHODS AND RESULTS: Patients with cystatin C measurements (n = 480) from a prospective multicentre study on AHF were included. All-cause mortality at 12 months was 25.4%. Cystatin C, creatinine, age, gender, and systolic blood pressure on admission were identified as independent prognostic risk factors. Cystatin C above median (1.30 mg/L) was associated with the highest adjusted hazard ratio, 3.2 (95% CI 2.0-5.3), P < 0.0001. Mortality increased significantly with each tertile of cystatin C. Combining tertiles of NT-proBNP and cystatin C improved risk stratification further. Moreover, in patients with normal plasma creatinine, elevated cystatin C was associated with significantly higher mortality at 12 months: 40.4% vs. 12.6% in patients with both markers within normal range, P < 0.0001. CONCLUSION: Cystatin C is a strong and independent predictor of outcome at 12 months in AHF. Furthermore, cystatin C identifies patients with poor prognosis despite normal plasma creatinine. Cystatin C seems to be a promising risk marker in patients hospitalized for AHF.

Utility of plasma apelin and other indices of cardiac dysfunction in the clinical assessment of patients with dilated cardiomyopathy.

Apelin is a recently discovered peptide ligand reported to be involved in the regulation of cardiovascular homeostasis. The exact role of apelin in the pathophysiology of congestive heart failure has remained obscure, and the reported circulating levels of apelin in patients with heart failure have been contradictory. To establish the role of apelin in the assessment of cardiac dysfunction we measured plasma apelin levels in 65 patients with congestive heart failure caused by idiopathic dilated cardiomyopathy (IDC) and 14 healthy volunteers by specific radioimmunoassay. IDC patients were carefully examined including echocardiography, both-sided cardiac catheterization and cardiopulmonary exercise test. In addition, plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), N-terminal pro-atrial natriuretic peptide (NT-proANP), interleukin (IL)-6, tumor necrosis factor alpha (TNF-alpha), epinephrine and norepinephrine were determined. Plasma apelin levels were similar in IDC patients (median 26.5 pg/ml, range<3.40-97.6 pg/ml) and in control subjects (median 24.1 pg/ml, range 19.0-28.7 pg/ml; p=NS). Unlike the levels of NT-proBNP, IL-6, TNF-alpha, and norepinephrine, plasma apelin levels did not reflect the severity of heart failure. Our study demonstrates that although disturbed apelin-APJ signalling in heart may play a role in the pathophysiology of heart failure, circulating apelin levels cannot be applied in the clinical assessment of patients with chronic left ventricular dysfunction.

Atrial natriuretic peptide, B-type natriuretic peptide, and serum collagen markers after acute myocardial infarction.

Experimental data suggest that atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) act locally as antifibrotic factors in heart. We investigated the interrelationships of natriuretic peptides and collagen markers in 93 patients receiving thrombolytic treatment for their first acute myocardial infarction (AMI). Collagen formation following AMI, evaluated as serum levels of amino terminal propeptide of type III procollagen, correlated with NH(2)-terminal proANP (r = 0.45, P < 0.001), BNP (r = 0.55, P < 0.001) and NH(2)-terminal proBNP (r = 0.50, P < 0.01) on day 4 after thrombolysis. Levels of intact amino terminal propeptide of type I procollagen decreased by 34% (P < 0.001), and levels of carboxy terminal cross-linked telopeptide of type I collagen (ICTP) increased by 65% (P < 0.001). ICTP levels correlated with NH(2)-terminal proBNP (r = 0.25, P < 0.05) and BNP (r = 0.28, P < 0.05) on day 4. Our results suggest that ANP and BNP may act as regulators of collagen scar formation and left ventricular remodeling after AMI in humans. Furthermore, degradation of type I collagen is increased after AMI and may be regulated by BNP.

Serum myoglobin/carbonic anhydrase III ratio as a marker of reperfusion after myocardial infarction.

BACKGROUND: Coronary patency is important for short- and long-term outcome after myocardial infarction. Serum myoglobin concentration is a sensitive marker of myocardial damage and its specificity can be improved by simultaneous measurement of carbonic anhydrase III, a skeletal muscle marker. In the present study we evaluated the role of myoglobin/carbonic anhydrase III ratio as a non-invasive marker of reperfusion. METHODS: We measured myoglobin, carbonic anhydrase III and creatine kinase MB-fraction release serially in 29 patients with acute myocardial infarction treated with thrombolysis and in 28 patients treated with primary coronary angioplasty. RESULTS: Thrombolytic therapy was followed by a 9.1+/-2.2-fold increase in myoglobin and 10.8+/-3.3-fold increase in creatine kinase MB-fraction during the first hour of treatment, while carbonic anhydrase III remained unchanged. The peak value of myoglobin/carbonic anhydrase III ratio was found at 2 h and that of creatine kinase MB-fraction at 8 h after thrombolysis. Knowledge of the reperfusion time point during primary angioplasty and follow-up of cardiac markers revealed that cut-off points of 3 and 10 h for the peak values of myoglobin/carbonic anhydrase III ratio and creatine kinase MB-fraction can be used as indicators for reperfusion, respectively. Myoglobin/carbonic anhydrase III ratio measured before treatment and at 2 and 4 h after the onset of treatment screened 23 of those 25 patients with probable reperfusion after thrombolysis. CONCLUSIONS: We conclude that measuring myoglobin/carbonic anhydrase III ratio during the first hours after initiation of thrombolysis may be useful in evaluating the success of reperfusion after acute myocardial infarction.

Interleukin-6 and tumor necrosis factor alpha in relation to myocardial infarct size and collagen formation.

BACKGROUND: Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) levels increase after acute myocardial infarction (AMI) in humans. Experimental data suggest that these cytokines regulate the initiation of scar formation after AMI. We investigated the interrelationships of IL-6 and TNF-alpha, tissue injury, infarct size, cardiac function, and collagen formation in humans. METHODS: Serum and plasma samples were taken on 93 patients receiving thrombolytic treatment for their first AMI. Collagen formation was evaluated by measuring concentrations of serum aminoterminal propeptide of type III procollagen (PIIINP). RESULTS: IL-6 levels increased by 44% (P<.001) and peaked at 24 hours. Peak IL-6 levels correlated positively with area under the curve of creatine kinase MB mass (r=.31, P<.01), peak troponin T level (r=.34, P<.005), and PIIINP measured at discharge (r=.46, P<.001). There were no changes in TNF-alpha levels, and patients with left ventricular dysfunction (EF<40%) had similar TNF-alpha levels as those with preserved left ventricular function. CONCLUSIONS: IL-6 may regulate collagen formation and thus remodeling of the left ventricle after AMI. In addition, TNF-alpha measurement is useless in the assessment of infarct size or left ventricular function during the immediate post-infarction period.

Gap between guidelines and management of patients with acute coronary syndrome without persistent ST elevation. Finnish prospective follow-up survey.

OBJECTIVE: To evaluate how new treatment guidelines of acute coronary syndrome (ACS) without ST elevation have been implemented into clinical practice in Finland. DESIGN: A prospective survey on 501 consecutive patients (mean age 68 [range 27-96] years) admitted to nine hospitals in Finland with suspected ACS without persistent ST elevation between January and March 2001. RESULTS: The rate of death was 4.2% in hospital and 9.8% at 6 months. Six-month composite incidence of death, new myocardial infarction, refractory angina or readmission for unstable angina was 25.4%. The majority of patients had beta-blocker and aspirin both in hospital and at 6 months. Low molecular weight heparin was used in 76% of patients. Statins were used in 52% of patients in hospital and in 64% at 6 months. Glycoprotein (GP) IIb/IIIa receptor antagonists were used in 18% of all patients. The overall rate of coronary angiography was 40% in hospital and 54% at 6 months, but there was large interhospital variation. Overall, only 45% of very high-risk patients underwent angiography during initial hospitalization. Very high-risk patients had longer waiting times for angiography than low-risk patients (5.8 vs 4.5 days, p < 0.05). CONCLUSION: Traditional medication with aspirin and beta-blocker is widely used in ACS, whereas statins, GPIIb/IIIa receptor antagonists and invasive therapy are underused. Well-known risk factors were poor predictors of receiving in-hospital angiography. Implementation of new ESC guidelines into clinical practice needs further education and more resources.

Underuse of evidence-based treatment modalities in diabetic patients with non-ST elevation acute coronary syndrome. A prospective nation wide study on acute coronary syndrome (FINACS).

This study was designed to evaluate how new treatment guidelines of acute coronary syndrome (ACS) without ST elevation have been implemented in clinical practice especially in diabetic patients. A prospective follow-up was performed on 501 consecutive patients with suspected ACS without ST elevation admitted to nine hospitals in Finland between 15 January and 11 March 2001. The study group included 143 (29%) diabetic patients. Their risk profile was more severe than in non-diabetic patients; ST-depression on admission electrocardiography 57 versus 38%; P<0.0001, elevated troponin levels 66 versus 56%; P<0.05. Six months composite incidence of death, new myocardial infarction (MI), refractory angina or readmission for unstable angina was 39% in diabetic patients and 20% in non-diabetic patients (P<0.0001). In spite of this more severe risk profile, glycoprotein (GP) IIb/IIIa receptor antagonists and statins were used with similar frequency in non-diabetic and diabetic patients (15 vs. 19 and 48 vs. 54%, respectively; P=NS for both). In diabetic patients mean delay for in hospital coronary angiography was longer (6.4 vs. 4.2 days, P<0.05) and it was performed less often (32 vs. 45% P<0.05). Our results show that diabetic patients with ACS have higher risk profile and worse outcome than non-diabetic patients. Despite their indisputable benefits in diabetic patients, statins, GP IIb/IIIa receptor antagonists and invasive strategy were underused or often neglected. Further education is needed to change attitudes and to better implement new guidelines into clinical practice.

Serum myoglobin/carbonic anhydrase III ratio in the diagnosis of perioperative myocardial infarction during coronary bypass surgery.

OBJECTIVE: The purpose of the present study was to evaluate the usefulness of the myoglobin/carboanhydrase III (Myo/CAIII) ratio in the diagnosis of perioperative myocardial infarction during coronary artery bypass surgery. DESIGN: Thirty patients undergoing elective coronary artery bypass grafting (CABG) were included in the series. The patients were randomized in two groups: one received conventional normothermic retrograde blood cardioplegia, while the other was subjected to a 5-min period of ischemic preconditioning before cardioplegia. Biochemical markers for myocardial and skeletal muscle injury were measured in serial blood samples taken postoperatively from 4 h after aortic declamp. RESULTS: Three patients were diagnosed to have suffered from perioperative myocardial infarction on the basis of significant elevations of troponin T and creatine kinase MB-isoenzyme (CK-MB) concentrations. In these particular patients the Myo/CAIII ratio increased rapidly after aortic declamping. In uncomplicated patients, the median value of the Myo/CAIII ratio remained within normal limits. There was a positive correlation between the net output of lactate during the aortic cross-clamping period and postoperative Myo/CAIII ratio. The Myo/CAIII ratio proved to be a more specific indicator for myocardial damage than myoglobin alone. The Myo/CAIII ratio was higher in the preconditioning group than in the control group. CONCLUSION: Myo/CAIII ratio is a sensitive and specific marker for perioperative myocardial infarction increasing rapidly after aortic declamping. This ratio could also be used when assessing the extent of ischemic myocardial injury and comparing different surgical and cardioprotective techniques.