Expression of epicardial adipose tissue thermogenic genes in patients with reduced and preserved ejection fraction heart failure.

Epicardial adipose tissue has been proposed to participate in the pathogenesis of heart failure. The aim of our study was to assess the expression of thermogenic genes (Uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), and PR-domain-missing 16 (PRDM16) in epicardial adipose tissue in patients with heart failure, stablishing the difference according to left ventricular ejection fraction (reduced or preserved). Among the 75 patients in our study, 42.7% (n=32) had reduced left ventricular ejection fraction. UCP1, PGC1α and PRDM16 mRNA in EAT were significantly lower in patients with reduced left ventricular ejection fraction. Multiple regression analysis showed that age, male gender, body max index, presence of obesity, type-2-diabetes mellitus, hypertension and coronary artery disease and left ventricular ejection fraction were associated with the expression levels of UCP1, PGC1α and PRDM16 mRNA. Thermogenic genes expressions in epicardial adipose tissue (UCP1: OR 0.617, 95%CI 0.103-0.989, p=0.042; PGC1α: OR 0.416, 95%CI 0.171-0.912, p=0.031; PRDM16: OR 0.643, 95%CI 0.116-0.997, p=0.044) were showed as protective factors against the presence of heart failure with reduced left ventricular ejection fraction, and age (OR 1.643, 95%CI 1.001-3.143, p=0.026), presence of coronary artery disease (OR 6.743, 95%CI 1.932-15.301, p<0.001) and type-2-diabetes mellitus (OR 4.031, 95%CI 1.099-7.231, p<0.001) were associated as risk factors. The adequate expression of thermogenic genes has been shown as possible protective factors against heart failure with reduced ejection fraction, suggesting that a loss of functional epicardial adipose tissue brown-like features would participate in a deleterious manner on heart metabolism. Thermogenic genes could represent a future novel therapeutic target in heart failure.

Expression of Sterol Regulatory Element-Binding Proteins in epicardial adipose tissue in patients with coronary artery disease and diabetes mellitus: preliminary study.

Objectives: Sterol regulatory element-binding proteins (SREBP) genes are crucial in lipid biosynthesis and cardiovascular homeostasis. Their expression in epicardial adipose tissue (EAT) and their influence in the development of coronary artery disease (CAD) and type-2 diabetes mellitus remain to be determined. The aim of our study was to evaluate the expression of SREBP genes in EAT in patients with CAD according to diabetes status and its association with clinical and biochemical data. Methods: SREBP-1 and SREBP-2 mRNA expression levels were measured in EAT from 49 patients with CAD (26 with diabetes) and 23 controls without CAD or diabetes. Results: Both SREBPs mRNA expression were significantly higher in patients with CAD and diabetes (p<0.001) and were identified as independent cardiovascular risk factor for coronary artery disease in patients with type-2 diabetes (SREBP-1: OR 1.7, 95%CI 1.1-2.5, p=0.02; SREBP-2: OR 1.6, 95%CI 1.2-3, p=0.02) and were independently associated with the presence of multivessel CAD, left main and anterior descending artery stenosis, and higher total and LDL cholesterol levels, and lower HDL cholesterol levels, in patients with CAD and diabetes. Conclusions: SREBP genes are expressed in EAT and were higher in CAD patients with diabetes than those patients without CAD or diabetes. SREBP expression was associated as cardiovascular risk factor for the severity of CAD and the poor lipid control. In this preliminary study we suggest the importance of EAT in the lipid metabolism and cardiovascular homeostasis for coronary atherosclerosis of patients with diabetes and highlight a future novel therapeutic target.

Infective endocarditis after transcatheter aortic valve implantation: results from a large multicenter registry.

BACKGROUND: We aimed to determine the incidence, predictors, clinical characteristics, management, and outcomes of infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: This multicenter registry included 53 patients (mean age, 79±8 years; men, 57%) who suffered IE after TAVI of 7944 patients after a mean follow-up of 1.1±1.2 years (incidence, 0.67%, 0.50% within the first year after TAVI). Mean time from TAVI was 6 months (interquartile range, 1-14 months). Orotracheal intubation (hazard ratio, 3.87; 95% confidence interval, 1.55-9.64; P=0.004) and the self-expandable CoreValve system (hazard ratio, 3.12; 95% confidence interval, 1.37-7.14; P=0.007) were associated with IE (multivariate analysis including 3067 patients with individual data). The most frequent causal microorganisms were coagulase-negative staphylococci (24%), followed by Staphylococcus aureus (21%) and enterococci (21%). Vegetations were present in 77% of patients (transcatheter valve leaflets, 39%; stent frame, 17%; mitral valve, 21%). At least 1 complication of IE occurred in 87% of patients (heart failure in 68%). However, only 11% of patients underwent valve intervention (valve explantation and valve-in-valve procedure in 4 and 2 patients, respectively). The mortality rate in hospital was 47.2% and increased to 66% at the 1-year follow-up. IE complications such as heart failure (P=0.037) and septic shock (P=0.002) were associated with increased in-hospital mortality. CONCLUSIONS: The incidence of IE at 1 year after TAVI was 0.50%, and the risk increased with the use of orotracheal intubation and a self-expandable valve system. Staphylococci and enterococci were the most common agents. Although most patients presented at least 1 complication of IE, valve intervention was performed in a minority of patients, and nearly half of the patients died during the hospitalization period.

Efficacy and Safety of Empagliflozin Continuation in Patients with Type 2 Diabetes Hospitalised for Acute Decompensated Heart Failure.

There is little evidence on the use of sodium-glucose cotransporter 2 inhibitors in hospitalised patients. This work aims to analyse the glycaemic and clinical efficacy and safety of empagliflozin continuation in patients with type 2 diabetes hospitalised for acute decompensated heart failure. This real-world observational study includes patients treated using our in-hospital antihyperglycaemic regimens (basal-bolus insulin vs. empagliflozin-basal insulin) between 2017 and 2020. A propensity matching analysis was used to match a patient on one regimen with a patient on the other regimen. Our primary endpoints were the differences in glycaemic control, as measured via mean daily blood glucose levels, and differences in the visual analogue scale dyspnoea score, NT-proBNP levels, diuretic response, and cumulative urine output. Safety endpoints were also analysed. After a propensity matching analysis, 91 patients were included in each group. There were no differences in mean blood glucose levels (152.1 ± 17.8 vs. 155.2 ± 19.7 mg/dL, p = 0.289). At discharge, NT-proBNP levels were lower and cumulative urine output greater in the empagliflozin group versus the basal-bolus insulin group (1652 ± 501 vs. 2101 ± 522 pg/mL, p = 0.032 and 16,100 ± 1510 vs. 13,900 ± 1220 mL, p = 0.037, respectively). Patients who continued empagliflozin had a lower total number of hypoglycaemic episodes (36 vs. 64, p < 0.001). No differences were observed in adverse events, length of hospital stay, or in-hospital deaths. For patients with acute heart failure, an in-hospital antihyperglycaemic regimen that includes continuation of empagliflozin achieved effective glycaemic control, lower NT-proBNP, and greater urine output. It was also safer, as it reduced hypoglycaemic episodes without increasing other safety endpoints.

Mortality risk assessment in Spain and Italy, insights of the HOPE COVID-19 registry.

Recently the coronavirus disease (COVID-19) outbreak has been declared a pandemic. Despite its aggressive extension and significant morbidity and mortality, risk factors are poorly characterized outside China. We designed a registry, HOPE COVID-19 (NCT04334291), assessing data of 1021 patients discharged (dead or alive) after COVID-19, from 23 hospitals in 4 countries, between 8 February and 1 April. The primary end-point was all-cause mortality aiming to produce a mortality risk score calculator. The median age was 68 years (IQR 52-79), and 59.5% were male. Most frequent comorbidities were hypertension (46.8%) and dyslipidemia (35.8%). A relevant heart or lung disease were depicted in 20%. And renal, neurological, or oncological disease, respectively, were detected in nearly 10%. Most common symptoms were fever, cough, and dyspnea at admission. 311 patients died and 710 were discharged alive. In the death-multivariate analysis, raised as most relevant: age, hypertension, obesity, renal insufficiency, any immunosuppressive disease, 02 saturation < 92% and an elevated C reactive protein (AUC = 0.87; Hosmer-Lemeshow test, p > 0.999; bootstrap-optimist: 0.0018). We provide a simple clinical score to estimate probability of death, dividing patients in four grades (I-IV) of increasing probability. Hydroxychloroquine (79.2%) and antivirals (67.6%) were the specific drugs most commonly used. After a propensity score adjustment, the results suggested a slight improvement in mortality rates (adjusted-ORhydroxychloroquine 0.88; 95% CI 0.81-0.91, p = 0.005; adjusted-ORantiviral 0.94; 95% CI 0.87-1.01; p = 0.115). COVID-19 produces important mortality, mostly in patients with comorbidities with respiratory symptoms. Hydroxychloroquine could be associated with survival benefit, but this data need to be confirmed with further trials. Trial Registration: NCT04334291/EUPAS34399.

The effect of post-discharge educational intervention on patients in achieving objectives in modifiable risk factors six months after discharge following an episode of acute coronary syndrome, (CAM-2 Project): a randomized controlled trial.

OBJECTIVES: We investigated whether an intervention mainly consisting of a signed agreement between patient and physician on the objectives to be reached, improves reaching these secondary prevention objectives in modifiable cardiovascular risk factors six-months after discharge following an acute coronary syndrome. BACKGROUND: There is room to improve mid-term adherence to clinical guidelines' recommendations in coronary heart disease secondary prevention, specially non-pharmacological ones, often neglected. METHODS: In CAM-2, patients discharged after an acute coronary syndrome were randomly assigned to the intervention or the usual care group. The primary outcome was reaching therapeutic objectives in various secondary prevention variables: smoking, obesity, blood lipids, blood pressure control, exercise and taking of medication. RESULTS: 1757 patients were recruited in 64 hospitals and 1510 (762 in the intervention and 748 in the control group) attended the six-months follow-up visit. After adjustment for potentially important variables, there were, between the intervention and control group, differences in the mean reduction of body mass index (0.5 vs. 0.2; p < 0.001) and waist circumference (1.6 cm vs. 0.6 cm; p = 0.05), proportion of patients who exercise regularly and those with total cholesterol below 175 mg/dl (64.7% vs. 56.5%; p = 0.001). The reported intake of medications was high in both groups for all the drugs considered with no differences except for statins (98.1% vs. 95.9%; p = 0.029). CONCLUSIONS: At least in the short term, lifestyle changes among coronary heart disease patients are achievable by intensifying the responsibility of the patient himself by means of a simple and feasible intervention.

Dobutamine stress echocardiography identifies patients with angina and dynamic left ventricular outflow obstruction in physiological exercise.

BACKGROUND AND METHODS: To determine whether patients with no heart disease who develop dynamic left ventricular outflow obstruction (DLVOTO) during dobutamine echocardiography (DE) reproduce the phenomenon during exercise echocardiography (EE), DE and EE were performed in 78 patients (59 +/- 9 years) with effort angina and no alterations in SPECT. Thirty-eight (48.7%) patients had DLVOTO during DE and 15 (19.2%) during EE. This phenomenon during EE was reproducible in 39.4% of the patients with DLVOTO on DE, and 100% of the patients with DLVOTO during EE had it during DE. Independent factors predicting DLVOTO during EE were the LVOT diameter (OR 0.33 (0.14-0.74)) and the left ventricular (LV) mass index (OR 1.05 (1.01-1.08)). No cardiovascular events were noted after 26+/-3 months. The reproducibility of DLVOTO during EE in patients with unexplained angina and with DLVOTO on DE is associated with the size of the LVOT and the LV mass index. The long-term prognosis is excellent.

Glycaemic efficacy and safety of linagliptin for the management of non-cardiac surgery patients with type 2 diabetes in a real-world setting: Lina-Surg study.

Introduction: The use of dipeptidyl peptidase-4 inhibitors in hospitalized patients is an area of active research. We aimed to compare the efficacy and the safety of the basal-bolus insulin regimen versus linagliptin-basal insulin in non-critically ill non-cardiac surgery patients in a real-world setting. Methods: We enrolled patients with type 2 diabetes hospitalized in non-cardiac surgery departments with admission glycated haemoglobin level < 8%, admission blood glucose concentration < 240 mg/dL, and no at-home injectable treatments who were treated with basal-bolus (n = 347) or linagliptin-basal (n = 190) regimens between January 2016 and December 2017. To match patients on the two regimens, a propensity matching analysis was performed. Results: After matching, 120 patients were included in each group. No differences were noted in mean blood glucose concentration after admission (p = .162), number of patients with a mean blood glucose 100-140 mg/dL (p = .163) and > 200 mg/dL (p = .199), and treatment failures (p = .395). Total daily insulin and number of daily insulin injections were lower in the linagliptin-basal group (both p < .001). Patients on linagliptin-basal insulin had fewer hypoglycaemic events (blood glucose < 70 mg/dL) (p < .001). Conclusion: For type 2 diabetes surgery patients with mild to moderate hyperglycaemia without pre-hospitalization injectable therapies, linagliptin-basal insulin was an effective, safe alternative with fewer hypoglycaemic events in real-world practice. Key messages Treatment with basal-bolus insulin regimens is the standard of care for non-critically ill hospitalized patients with type 2 diabetes. A differentiated treatment protocol that takes into account glycaemic control and clinical factors should be implemented in the hospital setting. Linagliptin-basal insulin is an effective, safe alternative with fewer hypoglycaemic events during the hospitalization of non-critically ill non-cardiac surgery patients with T2D in real-world practice.

Use of Linagliptin for the Management of Medicine Department Inpatients with Type 2 Diabetes in Real-World Clinical Practice (Lina-Real-World Study).

The use of noninsulin antihyperglycaemic drugs in the hospital setting has not yet been fully described. This observational study compared the efficacy and safety of the standard basal-bolus insulin regimen versus a dipeptidyl peptidase-4 inhibitor (linagliptin) plus basal insulin in medicine department inpatients in real-world clinical practice. We retrospectively enrolled non-critically ill patients with type 2 diabetes with mild to moderate hyperglycaemia and no injectable treatments at home who were treated with a hospital antihyperglycaemic regimen (basal-bolus insulin, or linagliptin-basal insulin) between January 2016 and December 2017. Propensity score was used to match patients in both treatment groups and a comparative analysis was conducted to test the significance of differences between groups. After matched-pair analysis, 227 patients were included per group. No differences were shown between basal-bolus versus linagliptin-basal regimens for the mean daily blood glucose concentration after admission (standardized difference = 0.011), number of blood glucose readings between 100⁻140 mg/dL (standardized difference = 0.017) and >200 mg/dL (standardized difference = 0.021), or treatment failures (standardized difference = 0.011). Patients on basal-bolus insulin received higher total insulin doses and a higher daily number of injections (standardized differences = 0.298 and 0.301, respectively). Basal and supplemental rapid-acting insulin doses were similar (standardized differences = 0.003 and 0.012, respectively). There were no differences in hospital stay length (standardized difference = 0.003), hypoglycaemic events (standardized difference = 0.018), or hospital complications (standardized difference = 0.010) between groups. This study shows that in real-world clinical practice, the linagliptin-basal insulin regimen was as effective and safe as the standard basal-bolus regimen in non-critical patients with type 2 diabetes with mild to moderate hyperglycaemia treated at home without injectable therapies.

Influence of 677 C-->T polymorphism of methylenetetrahydrofolate reductase on medium-term prognosis after acute coronary syndromes.

Various common genotypes of the polymorphism 677 C-->T of the methylenetetrahydrofolate reductase enzyme result in lower activity of the enzyme and in a subsequent increase in homocysteine levels. Many studies have analyzed the connection between this polymorphism and the beginning of coronary artery disease. However, conclusions have been controversial, and evidence of a connection between this polymorphism and the prognosis of coronary artery disease has been poorly evaluated. This prospective study evaluated the prognostic relevance of genotype TT in a cohort of 155 patients admitted to our hospital for treatment of an acute coronary syndrome accompanied by evidence of coronary atherosclerosis on coronary angiography. We found that patients with the genotype TT had higher homocysteine levels than did patients with the CT and CC genotypes (15.72 +/- 6.92 micromol/L vs 12.11 +/- 5.40 micromol/L and 12.01 +/- 4.25 micromol/L, P=0.01). After a mean follow-up of 13.4 +/- 7.4 months, we observed similar rates of major adverse cardiovascular events (CC, 29%; CT, 22%; and TT, 25%) and cardiovascular death (CC, 11%; CT, 7%; and TT, 8%). No difference in cardiovascular-death-free survival (log-rank analysis, 0.81; P=0.66) or event-free survival (log-rank analysis, 0.76; P=0.68) was found. The presence of genotype TT was not an independent predictor of prognosis after multivariate analysis by means of the Cox regression survival model. In conclusion, the presence of the TT genotype of the 677 C-->T polymorphism of the methylenetetrahydrofolate reductase enzyme was not related to prognosis in patients admitted to the hospital after an acute coronary syndrome.

[Mild hyperhomocysteinemia, low folate levels and prognosis of acute coronary syndrome without ST elevation]. / Hiperhomocisteinemia moderada, déficit basal de folatos y pronóstico del síndrome coronario agudo sin elevación del segmento ST.

BACKGROUND AND OBJECTIVE: The influence of homocysteine metabolism on the prognosis of acute coronary syndrome without ST elevation is controversial. PATIENTS AND METHOD: Prospective study of 109 patients admitted because of acute coronary syndrome without ST elevation. Basal plasmatic levels of homocysteine and folates were obtained. Clinical features and survival data on follow-up were registered. RESULTS: Both two years-free-of-events and total survival were lower in patients with low folate levels (36.5% vs 72.5%, p = 0.02; 48% vs 94%, p < .001). Patients with high homocysteine levels had lower two years-free-of-events survival (57.4% vs 89.1%, p < .01); but no difference in the total survival was observed (86.3% vs 97.3%, p = 0.11). The multivariate analysis showed that low folate levels was an independent predictor of mortality (odds ratio [OR] = 8.33; 95% confidence interval [CI], 1.88-33.33; p < 0.01), and moderate high homocysteine was an independent predictor of events on follow-up (OR = 4.34; 95% CI, 1.47-12.50; p < 0.01). CONCLUSIONS: Patients with high homocysteine or low folate levels have a poor prognosis compared with those with normal levels. On the other hand, low folate levels and moderate hyiperhomocysteinemia are independent predictors of bad prognosis in the follow-up.

[Effect of exercise on systolic left ventricular outflow velocity in healthy adults]. / Efecto del ejercicio sobre las velocidades de flujo sistólico ventricular izquierdo en adultos sanos.

The occurrence of exercise-induced dynamic obstruction of the left ventricular outflow tract in patients without cardiomyopathy has recently been reported. However, it is not known if this phenomenon is a normal response to exercise in healthy adults. We studied 23 healthy adults using exercise Doppler echocardiography. We measured the left ventricular outflow velocity at rest and after maximum tolerated exercise. After a mean exercise duration of 12 min 45 s (2 min 32 s), the heart rate was 97.61 (6.71)% of the theoretical maximum. Left ventricular outflow velocity increased from 1.07 (0.18) m/s (range: 0.77-1.44 m/s) to 1.58 (0.35) m/s (range: 1.09-2.4 m/s). In healthy adults, exercise increased the left ventricular outflow velocity by 50%, though in no subject was it greater than 2.5 m/s. This observation appears to rule out the possibility that a high intraventricular pressure gradient is a normal response to exercise in healthy adults.

[Stability of NT-ProBNP in patients with systolic heart failure]. / Estabilidad de NT-proBNP en pacientes con insuficiencia cardiaca sistólica.

Natriuretic peptides are extremely useful in the diagnosis and prognosis of patients with heart failure. However, it is not clear whether their values are stable. We carried out a prospective study of 30 consecutive ambulatory patients (mean age, 62.6 [12.2] years) with stable systolic heart failure, as determined by the 6-minute walk test, who were in New York Heart Association class II or III and who had a left ventricular ejection fraction <30% (mean ejection fraction, 24.2% [6.68%]). At baseline, the mean N-terminal pro-brain natriuretic peptide (NT-proBNP) level and the mean distance walked in 6 minutes were 2237.3 pg/mL and 348.26 m, respectively. At 3-month follow-up, the corresponding values were 2096.2 pg/mL and 372.05 m, respectively. No significant difference was observed in NT-proBNP level or in distance walked in 6 minutes between baseline and 3 months (P=.8). Overall, there was a good correlation (r=0.94; P< .001) between the plasma NT-proBNP level at baseline and at 3 months in patients with stable chronic heart failure due to systolic dysfunction in New York Heart Association class II or III.

[Effect of statin treatment begun early after acute myocardial infarction on endothelial function in patients with normal levels of cholesterol. VAATOPE Study (VAlue of ATOrvastatin in Postinfarction Endothelium)]. / Influencia del tratamiento temprano con estatinas en la función endotelial tras el infarto de miocardio en pacientes con valores normales de colesterol. Estudio VAATOPE (VAlue of ATOrvastatin in Postinfarction Endothelium).

BACKGROUND AND OBJECTIVE: Recent studies have suggested that statins reduce the rate of subsequent coronary events when these drugs are indicated early alter an acute coronary event. One potential mechanism by which these drugs might reduce the likelihood of such events is by enhancing endothelial function. The aim of this study was to determine whether early cholesterol reduction with atorvastatin improved endothelial function after acute myocardial infarction in patients with normal cholesterol levels. PATIENTS AND METHOD: Patients with a first acute myocardial infarction and normal levels of cholesterol were assigned to treatment with 10 mg atorvastatin (n = 15) or placebo (n = 15) for 8 weeks. Patients who had previously received treatment with statins were excluded. Brachial ultrasound was used to measure endothelium-dependent flow-mediated dilation and response to endothelium-independent nitroglycerin. Total and LDL cholesterol levels and the distribution of risk factors were similar on admission and before randomization in both groups. All patients were assessed between 5 and 7 days postinfarction and after 8 weeks. RESULTS: Total and LDL cholesterol levels were significantly decreased after atorvastatin treatment. Total cholesterol decreased by 11% (p < 0.01) and LDL cholesterol by 18% (p < 0.01). Without atorvastatin flow-mediated dilation was unchanged (mean [SEM] 9.3 [1.7%] to 10.6 [1.7%]) but it increased with atorvastatin (8.9 [1.4%] to 16.5 [1.7%], p < 0.05). The response to nitroglycerin was similar in both groups during the period of study. CONCLUSIONS: The early administration of atorvastatin appears to enhance endothelial function in patients with acute myocardial infarction and normal levels of cholesterol.

[Role of serum leptin in the severity of coronary artery disease in patients with stable angina]. / Papel de la leptina sérica en la gravedad de la enfermedad coronaria en pacientes con angina estable.

BACKGROUND AND OBJECTIVES: Leptin is a plasmatic peptide hormone that has been related to cardiovascular homeostasis and atherosclerosis but much is still unknown about its relationship with coronary artery disease. The aim of this study was to evaluate the value of serum leptin in patients with stable angina and its relationship with the severity of coronary disease. PATIENTS AND METHODS: 204 patients, 152 with stable angina (coronary artery disease group) and 52 without coronary disease excluded by cardiac computerized tomography (control group) were included. The coronary artery disease group was divided into 2 subgroups according to severity of coronary disease (single or multivessel disease, 46 and 106 patients, respectively). Serum leptin levels were determined by Enzyme-Linked InmunoSorbent Assay. RESULTS: Leptin levels were significantly higher in patients with multivessel disease and were independently associated with a greater severity of coronary artery disease when compared with controls (OR 1.14; 95%CI: 1.03-1.27; p=0.014) and with patients with single vessel disease (OR 1.12; 95%CI: 1.01-1.25; p=0.036). Serum leptin was tested as a diagnostic marker of multivessel disease with an area under the curve obtained from Receiver Operating Characteristics of 0.6764 (95%CI 0.5765-0.7657). CONCLUSIONS: Serum leptin levels were associated in patients with stable angina with the severity of coronary artery disease, suggesting its value in the development of coronary disease and as a future therapeutic target.

[Collagen synthesis and heart failure]. / Síntesis de colágeno e insuficiencia cardíaca.

Little is known about collagen metabolism in heart failure, with or without left ventricular systolic dysfunction. We studied serum concentrations of the carboxy-terminal propeptide of procollagen type I (PIP), a marker of collagen type-I synthesis, and of the carboxy-terminal telopeptide of collagen type I (ICTP), a marker of collagen type-I degradation, in 70 patients admitted for heart failure (35 with depressed left ventricular systolic function and 35 with preserved left ventricular systolic function) and in 30 control subjects. Patients with kidney failure, liver disease, metabolic bone disease, rheumatic disease, recent (within 3 months) major trauma or surgery, or serious wounds were excluded. The concentration of the collagen synthesis marker, PIP, was higher in heart failure patients than control subjects, at 140+/-56.38 mg/L vs 113.66+/-36.6 microg/L, respectively (P=.01). However, there was no difference in the concentration of the collagen degradation marker, ICTP, between heart failure patients and control subjects, at 2.89+/-2.37 mg/L vs 2.26+/-1.7 microg/l, respectively. In heart failure patients, left ventricular systolic function had nonsignificant effect on the PIP or ICTP concentration.