Interpretation of pre-morbid cardiac 3T MRI findings in overweight and hypertensive young adults.

In young adults, overweight and hypertension possibly already trigger cardiac remodeling as seen in mature adults, potentially overlapping non-ischemic cardiomyopathy findings. To this end, in young overweight and hypertensive adults, we aimed to investigate changes in left ventricular mass (LVM) and cardiac volumes, and the impact of different body scales for indexation. We also aimed to explore the presence of myocardial fibrosis, fat and edema, and changes in cellular mass with extracellular volume (ECV), T1 and T2 tissue characteristics. We prospectively recruited 126 asymptomatic subjects (51% male) aged 27-41 years for 3T cardiac magnetic resonance imaging: 40 controls, 40 overweight, 17 hypertensive and 29 hypertensive overweight. Myocyte mass was calculated as (100%-ECV) * height2.7-indexed LVM. Absolute LVM was significantly increased in overweight, hypertensive and hypertensive overweight groups (104 ± 23, 109 ± 27, 112 ± 26 g) versus controls (87 ± 21 g), with similar volumes. Body surface area (BSA) indexation resulted in LVM normalization in overweights (48 ± 8 g/m2) versus controls (47 ± 9 g/m2), but not in hypertensives (55 ± 9 g/m2) and hypertensive overweights (52 ± 9 g/m2). BSA-indexation overly decreased volumes in overweight versus normal-weight (LV end-diastolic volume; 80 ± 14 versus 92 ± 13 ml/m2), where height2.7-indexation did not. All risk groups had lower ECV (23 ± 2%, 23 ± 2%, 23 ± 3%) than controls (25 ± 2%) (P = 0.006, P = 0.113, P = 0.039), indicating increased myocyte mass (16.9 ± 2.7, 16.5 ± 2.3, 18.1 ± 3.5 versus 14.0 ± 2.9 g/m2.7). Native T1 values were similar. Lower T2 values in the hypertensive overweight group related to heart rate. In conclusion, BSA-indexation masks hypertrophy and causes volume overcorrection in overweight subjects compared to controls, height2.7-indexation therefore seems advisable.

DeepStrain Evidence of Asymptomatic Left Ventricular Diastolic and Systolic Dysfunction in Young Adults With Cardiac Risk Factors.

Purpose: To evaluate if a fully-automatic deep learning method for myocardial strain analysis based on magnetic resonance imaging (MRI) cine images can detect asymptomatic dysfunction in young adults with cardiac risk factors. Methods: An automated workflow termed DeepStrain was implemented using two U-Net models for segmentation and motion tracking. DeepStrain was trained and tested using short-axis cine-MRI images from healthy subjects and patients with cardiac disease. Subsequently, subjects aged 18-45 years were prospectively recruited and classified among age- and gender-matched groups: risk factor group (RFG) 1 including overweight without hypertension or type 2 diabetes; RFG2 including hypertension without type 2 diabetes, regardless of overweight; RFG3 including type 2 diabetes, regardless of overweight or hypertension. Subjects underwent cardiac short-axis cine-MRI image acquisition. Differences in DeepStrain-based left ventricular global circumferential and radial strain and strain rate among groups were evaluated. Results: The cohort consisted of 119 participants: 30 controls, 39 in RFG1, 30 in RFG2, and 20 in RFG3. Despite comparable (>0.05) left-ventricular mass, volumes, and ejection fraction, all groups (RFG1, RFG2, RFG3) showed signs of asymptomatic left ventricular diastolic and systolic dysfunction, evidenced by lower circumferential early-diastolic strain rate (<0.05, <0.001, <0.01), and lower septal circumferential end-systolic strain (<0.001, <0.05, <0.001) compared with controls. Multivariate linear regression showed that body surface area correlated negatively with all strain measures (<0.01), and mean arterial pressure correlated negatively with early-diastolic strain rate (<0.01). Conclusion: DeepStrain fully-automatically provided evidence of asymptomatic left ventricular diastolic and systolic dysfunction in asymptomatic young adults with overweight, hypertension, and type 2 diabetes risk factors.

Cardiac Alterations on 3T MRI in Young Adults With Sedentary Lifestyle-Related Risk Factors.

Background: Young adult populations with the sedentary lifestyle-related risk factors overweight, hypertension, and type 2 diabetes (T2D) are growing, and associated cardiac alterations could overlap early findings in non-ischemic cardiomyopathy on cardiovascular MRI. We aimed to investigate cardiac morphology, function, and tissue characteristics for these cardiovascular risk factors. Methods: Non-athletic non-smoking asymptomatic adults aged 18-45 years were prospectively recruited and underwent 3Tesla cardiac MRI. Multivariate linear regression was performed to investigate independent associations of risk factor-related parameters with cardiac MRI values. Results: We included 311 adults (age, 32 ± 7 years; men, 49%). Of them, 220 subjects had one or multiple risk factors, while 91 subjects were free of risk factors. For overweight, increased body mass index (per SD = 5.3 kg/m2) was associated with increased left ventricular (LV) mass (+7.3 g), biventricular higher end-diastolic (LV, +8.6 ml), and stroke volumes (SV; +5.0 ml), higher native T1 (+7.3 ms), and lower extracellular volume (ECV, -0.38%), whereas the higher waist-hip ratio was associated with lower biventricular volumes. Regarding hypertension, increased systolic blood pressure (per SD = 14 mmHg) was associated with increased LV mass (+6.9 g), higher LV ejection fraction (EF; +1.0%), and lower ECV (-0.48%), whereas increased diastolic blood pressure was associated with lower LV EF. In T2D, increased HbA1c (per SD = 9.0 mmol/mol) was associated with increased LV mass (+2.2 g), higher right ventricular end-diastolic volume (+3.2 ml), and higher ECV (+0.27%). Increased heart rate was linked with decreased LV mass, lower biventricular volumes, and lower T2 values. Conclusions: Young asymptomatic adults with overweight, hypertension, and T2D show subclinical alterations in cardiac morphology, function, and tissue characteristics. These alterations should be considered in cardiac MRI-based clinical decision making.

Balancing Speed and Accuracy in Cardiac Magnetic Resonance Function Post-Processing: Comparing 2 Levels of Automation in 3 Vendors to Manual Assessment.

Automating cardiac function assessment on cardiac magnetic resonance short-axis cines is faster and more reproducible than manual contour-tracing; however, accurately tracing basal contours remains challenging. Three automated post-processing software packages (Level 1) were compared to manual assessment. Subsequently, automated basal tracings were manually adjusted using a standardized protocol combined with software package-specific relative-to-manual standard error correction (Level 2). All post-processing was performed in 65 healthy subjects. Manual contour-tracing was performed separately from Level 1 and 2 automated analysis. Automated measurements were considered accurate when the difference was equal or less than the maximum manual inter-observer disagreement percentage. Level 1 (2.1 ± 1.0 min) and Level 2 automated (5.2 ± 1.3 min) were faster and more reproducible than manual (21.1 ± 2.9 min) post-processing, the maximum inter-observer disagreement was 6%. Compared to manual, Level 1 automation had wide limits of agreement. The most reliable software package obtained more accurate measurements in Level 2 compared to Level 1 automation: left ventricular end-diastolic volume, 98% and 53%; ejection fraction, 98% and 60%; mass, 70% and 3%; right ventricular end-diastolic volume, 98% and 28%; ejection fraction, 80% and 40%, respectively. Level 1 automated cardiac function post-processing is fast and highly reproducible with varying accuracy. Level 2 automation balances speed and accuracy.

Clinical importance of urinary sodium excretion in acute heart failure.

AIMS: Urinary sodium assessment has recently been proposed as a target for loop diuretic therapy in acute heart failure (AHF). We aimed to investigate the time course, clinical correlates and prognostic importance of urinary sodium excretion in AHF. METHODS AND RESULTS: In a prospective cohort of 175 consecutive patients with an admission for AHF we evaluated urinary sodium excretion 6 h after initiation of loop diuretic therapy. Clinical outcome was all-cause mortality or heart failure rehospitalization. Mean age was 71 ± 14 years, and 44% were female. Median urinary sodium excretion was 130 (67-229) mmol at 6 h, 347 (211-526) mmol at 24 h, and decreased from day 2 to day 4. Lower urinary sodium excretion was independently associated with male gender, younger age, renal dysfunction and pre-admission loop diuretic use. There was a strong association between urinary sodium excretion at 6 h and 24 h urine volume (beta = 0.702, P < 0.001). Urinary sodium excretion after 6 h was a strong predictor of all-cause mortality after a median follow-up of 257 days (hazard ratio 3.81, 95% confidence interval 1.92-7.57; P < 0.001 for the lowest vs. the highest tertile of urinary sodium excretion) independent of established risk factors and urinary volume. Urinary sodium excretion was not associated with heart failure rehospitalization. CONCLUSION: In a modern, unselected, contemporary AHF population, low urinary sodium excretion during the first 6 h after initiation of loop diuretic therapy is associated with lower urine output in the first day and independently associated with all-cause mortality.

Comorbidities in Heart Failure.

Comorbidities frequently accompany chronic heart failure (HF), contributing to increased morbidity and mortality, and an impaired quality of life. We describe the prevalence of several high-impact comorbidities in chronic HF patients and their impact on morbidity and mortality. Furthermore, we try to explain the underlying pathophysiological processes and the complex interaction between chronic HF and specific comorbidities. Although common risk factors are likely to contribute, it is reasonable to believe that factors associated with HF might cause other comorbidities and vice versa. Potential factors are inflammation, neurohormonal activation, and hemodynamic changes.

Dynamics of cerebral blood flow in patients with mild non-ischaemic heart failure.

AIMS: Heart failure (HF) is associated with tissue hypoperfusion and congestion leading to organ dysfunction. Although cerebral blood flow (CBF) is preserved over a wide range of perfusion pressures in healthy subjects, it is impaired in end-stage HF. We aimed to compare CBF, autoregulation, and cognitive function in patients with mild non-ischaemic HF with healthy controls. METHODS AND RESULTS: Fifteen patients with mild idiopathic dilated cardiomyopathy and 15 matched healthy controls were studied. Co-existing cerebrovascular disease was excluded. All subjects, except five patients with an implantable cardioverter defibrillator, underwent magnetic resonance imaging for measurements of both CBF by arterial spin labelling and quantitative volume flow entering the brain. Cardiocerebral vascular function was assessed with Doppler techniques testing cerebral dynamic autoregulation and vasomotor reactivity. Cognitive analysis was performed by neuropsychological testing. Global and regional CBF did not differ between HF patients (44.3 mL/100 g.min) and controls (42.1 mL/100 g.min). Basilar but not carotid artery inflow was reduced in patients (1.95 mL/s vs. 2.51 mL/s, P = 0.009). Testing autoregulation revealed fewer dampened blood flow fluctuations in HF patients vs. controls (0.96% vs. 0.67%, P < 0.001). Vasomotor reactivity in HF patients showed a reduced CBF velocity (48.4% vs. 61.0%, P = 0.05) and regional cerebral oxygen saturation (18.3% vs. 23.8%, P = 0.02). Cognitive function overall was not affected. CONCLUSION: Although global CBF was unaffected in patients with mild HF, significant changes in basilar inflow volume, cerebral autoregulation and vasomotor reactivity were observed. We describe a model of dynamic cerebral mechanisms required to compensate for the impaired haemodynamics in early-stage HF.

The value of telemonitoring and ICT-guided disease management in heart failure: Results from the IN TOUCH study.

AIM: It is still unclear whether telemonitoring reduces hospitalization and mortality in heart failure (HF) patients and whether adding an Information and Computing Technology-guided-disease-management-system (ICT-guided-DMS) improves clinical and patient reported outcomes or reduces healthcare costs. METHODS: A multicenter randomized controlled trial was performed testing the effects of INnovative ICT-guided-DMS combined with Telemonitoring in OUtpatient clinics for Chronic HF patients (IN TOUCH) with in total 179 patients (mean age 69 years; 72% male; 77% in New York Heart Association Classification (NYHA) III-IV; mean left ventricular ejection fraction was 28%). Patients were randomized to ICT-guided-DMS or to ICT-guided-DMS+telemonitoring with a follow-up of nine months. The composite endpoint included mortality, HF-readmission and change in health-related quality of life (HR-QoL). RESULTS: In total 177 patients were eligible for analyses. The mean score of the primary composite endpoint was -0.63 in ICT-guided-DMS vs. -0.73 in ICT-guided-DMS+telemonitoring (mean difference 0.1, 95% CI: -0.67 +0.82, p=0.39). All-cause mortality in ICT-guided-DMS was 12% versus 15% in ICT-guided-DMS+telemonitoring (p=0.27); HF-readmission 28% vs. 27% p=0.87; all-cause readmission was 49% vs. 51% (p=0.78). HR-QoL improved in most patients and was equal in both groups. Incremental costs were €1360 in favor of ICT-guided-DMS. ICT-guided-DMS+telemonitoring had significantly fewer HF-outpatient-clinic visits (p<0.01). CONCLUSION: ICT-guided-DMS+telemonitoring for the management of HF patients did not affect the primary and secondary endpoints. However, we did find a reduction in visits to the HF-outpatient clinic in this group suggesting that telemonitoring might be safe to use in reorganizing HF-care with relatively low costs.

Validity and Predictive Value of a Portable Two-Channel Sleep-Screening Tool in the Identification of Sleep Apnea in Patients With Heart Failure.

BACKGROUND: Sleep apnea is an important comorbidity in heart failure (HF) and is associated with an adverse outcome. Diagnosing sleep apnea is difficult, and polysomnography, considered to be the criterion standard, is not widely available. We assessed the validity of a portable 2-channel sleep-screening tool for the identification of sleep apnea in patients with HF. METHODS AND RESULTS: One hundred patients with stable HF had simultaneous recordings of home-based polysomnography and the screening tool (Apnealink). To compare the apnea-hypopnea index of the screening tool with polysomnography, intraclass correlation (ICC), sensitivity, and specificity were calculated, and a Bland-Altman plot and receiver operating characteristic (ROC) curves were constructed. Ninety valid measurements with the screening tool were obtained (mean age 65.5 ± 11.0 y, 72% male, mean left ventricular ejection fraction 34.6 ± 11.0%). Agreement between the screening tool and polysomnography was high (ICC 0.85). The optimal cutoff value was apnea-hypopnea index ≥15/h (area under the ROC curve 0.94). Sensitivity and specificity were 92.9% and 91.9%, respectively. CONCLUSIONS: The screening tool is useful in excluding the presence of sleep apnea in HF patients to refer only high-risk patients for more extensive polysomnography. This method may potentially reduce the need for the more expensive polysomnography.

Nesiritide, renal function, and associated outcomes during hospitalization for acute decompensated heart failure: results from the Acute Study of Clinical Effectiveness of Nesiritide and Decompensated Heart Failure (ASCEND-HF).

BACKGROUND: Contradictory results have been reported on the effects of nesiritide on renal function in patients with acute decompensated heart failure. We studied the effects of nesiritide on renal function during hospitalization for acute decompensated heart failure and associated outcomes. METHODS AND RESULTS: A total of 7141 patients were randomized to receive either nesiritide or placebo and creatinine was recorded in 5702 patients at baseline, after infusion, discharge, peak/nadir levels until day 30. Worsening renal function was defined as an increase of serum creatinine >0.3 mg/dL and a change of ≥25%. Median (25(th)-75(th) percentile) baseline creatinine was 1.2 (1.0-1.6) mg/dL and median baseline blood urea nitrogen was 25 (18-39) mmol/L. Changes in both serum creatinine and blood urea nitrogen were similar in nesiritide-treated and placebo-treated patients (P=0.20 and P=0.41) from baseline to discharge. In a multivariable model, independent predictors of change from randomization to hospital discharge in serum creatinine were a lower baseline blood urea nitrogen, higher systolic blood pressure, lower diastolic blood pressure, previous weight gain, and lower baseline potassium (all P<0.0001). The frequency of worsening renal function during hospitalization was similar in the nesiritide and placebo group (14.1% and 12.8%, respectively; odds ratio with nesiritide 1.12; confidence interval, 0.95-1.32; P=0.19) and was not associated with death alone and death or rehospitalization at 30 days. However, baseline, discharge, and change in creatinine were associated with death alone and death or rehospitalization for heart failure (all tests, P<0.0001). CONCLUSIONS: Nesiritide did not affect renal function in patients with acute decompensated heart failure. Baseline, discharge, and change in renal function were associated with 30-day mortality or rehospitalization for heart failure.

Liver function, in-hospital, and post-discharge clinical outcome in patients with acute heart failure-results from the relaxin for the treatment of patients with acute heart failure study.

BACKGROUND: Elevated plasma concentrations of liver function tests are prevalent in patients with chronic heart failure (HF). Little is known about liver function in patients with acute HF. We aimed to assess the prevalence and prognostic value of serial measurements of liver function tests in patients admitted with acute decompensated HF. METHODS: We investigated liver function tests from all 234 patients from the Relaxin for the Treatment of Patients With Acute Heart Failure study at baseline and during hospitalization. The end points were worsening HF through day 5, 60-day mortality or rehospitalization, and 180-day mortality. RESULTS: Mean age was 70 ± 10 years, 56% were male, and most patients were in New York Heart Association functional class III/IV (73%). Abnormal liver function tests were frequently found for alanine transaminase (ALT; 12%), aspartate transaminase (AST; 21%), alkaline phosphatase (12%), and total bilirubin (19%), and serum albumin (25%) and total protein (9%) were decreased. In-hospital changes were very small. On a continuous scale, baseline ALT and AST were associated with 180-day mortality (hazard ratios [HRs; per doubling] 1.52 [P = .030] and 1.97 [P = .013], respectively) and worsening HF through day 5 (HRs [per doubling] 1.72 [P = .005] and 1.95 [P = .008], respectively). Albumin was associated with 180-day mortality (HR 0.86; P = .001) but not with worsening HF (HR 0.95; P = .248). Total protein was associated with only worsening HF (HR 0.91; P = .004). CONCLUSIONS: Abnormal liver function tests are often present in patients with acute HF and are associated with an increased risk for mortality, rehospitalization, and in-hospital worsening HF.

Anemia is associated with an increased central venous pressure and mortality in a broad spectrum of cardiovascular patients.

BACKGROUND: Anemia is frequently observed in patients with cardiovascular disease. Multiple factors have been associated with anemia, but the role of hemodynamics is largely unknown. Therefore, we investigated the association between hemoglobin (Hb) levels, hemodynamics and outcome in a broad spectrum of cardiovascular patients. METHODS AND RESULTS: A total of 2,009 patients who underwent right heart catheterization at the University Medical Center Groningen, the Netherlands, between 1989 and 2006 were identified and data were extracted from electronic databases. Anemia was defined by the WHO criteria (male, hemoglobin <13.0 g/dL; female, hemoglobin <12.0 g/dL). The associations between central venous pressure (CVP), cardiac index (CI), systemic vascular resistance (SVR), hemoglobin (Hb), anemia and all-cause mortality were assessed with linear, logistic and Cox-proportional hazards analysis. The mean age was 57 ± 15 years, 57 % were male, mean Hb was 13.2 ± 0.4 g/dL, and 27.4 % of the patients were anemic. Patients with anemia had higher CVP levels (7.0 ± 5.4 mmHg) compared to non-anemic patients (5.6 ± 4.1 mmHg; p < 0.001). CI was higher in anemic patients; 3.0 ± 2.9 vs. 2.9 ± 0.8 L/min/m(2) (p < 0.001), whereas SVR was lower (1,212 ± 479 vs. 1,356 ± 555 dyn s cm(-5), p < 0.001). CVP and CI were both independent predictors of anemia (OR 1.49; CI 1.24-1.81, p < 0.001 and OR 1.93; CI 1.54-2.42, p < 0.001, respectively). Hemoglobin and CVP were both independent predictors of survival. Independent of CI and renal function, patients with anemia and an elevated CVP had the worst prognosis (HR 2.17; 95 % CI 1.62-2.90; p < 0.001). CONCLUSION: Anemia is common in cardiovascular patients and independently related to an elevated CVP and CI. Patients with anemia and an elevated CVP have the worst prognosis.

Co-morbidities in patients with heart failure: an analysis of the European Heart Failure Pilot Survey.

AIMS: Co-morbidities frequently accompany heart failure (HF), contributing to increased morbidity and mortality, and an impairment of quality of life. We assessed the prevalence, determinants, regional variation, and prognostic implications of co-morbidities in patients with chronic HF in Europe. METHODS AND RESULTS: A total of 3226 European outpatients with chronic HF were included in this analysis of the European Society of Cardiology (ESC) Heart Failure Pilot Survey. The following co-morbidities were considered: diabetes, hyper- and hypothyroidism, stroke, COPD, sleep apnoea, chronic kidney disease (CKD), and anaemia. Prognostic implications of co-morbidities were evaluated using population attributable risks (PARs), and patients were divided into geographic regions. Clinical endpoints were all-cause mortality and HF hospitalization. The majority of patients (74%) had a least one co-morbidity, the most prevalent being CKD (41%), anaemia (29%), and diabetes (29%). Co-morbidities were independently associated with higher age (P < 0.001), higher NYHA functional class (P < 0.001), ischaemic aetiology of HF (P < 0.001), higher heart rate (P = 0.011), history of hypertension (P < 0.001), and AF (P < 0.001). Only diabetes, CKD, and anaemia were independently associated with a higher risk of mortality and/or HF hospitalization. There were marked regional differences in prevalence and prognostic implications of co-morbidities. Prognostic implications of co-morbidities (PARs) were: CKD = 41%, anaemia = 37%, diabetes = 14%, COPD = 10%, and <10% for all other co-morbidities. CONCLUSION: In this pilot survey, co-morbidities are prevalent in patients with chronic HF and are related to the severity of the disease. The presence of diabetes, CKD, and anaemia was independently related to increased mortality and HF hospitalization, with the highest PAR for CKD and anaemia.

Co-morbidities in heart failure.

Heart failure is a clinical syndrome characterized by poor quality of life and high morbidity and mortality. Co-morbidities frequently accompany heart failure and further decrease in both quality of life and clinical outcome. We describe that the prevalence of co-morbidities in patients with heart failure is much higher compared to age-matched controls. We will specifically address the most studied organ-related co-morbidities, that is, renal dysfunction, cerebral dysfunction, anaemia, liver dysfunction, chronic obstructive pulmonary disease, diabetes mellitus and sleep apnoea. The pathophysiologic processes underlying the interaction between heart failure and co-morbid conditions are complex and remain largely unresolved. Although common risk factors are likely to contribute, it is reasonable to believe that factors associated with heart failure might cause other co-morbid conditions. Inflammation, neurohumoral pathway activation and hemodynamic changes are potential factors. We try to provide explanations for the observed association between co-morbidities and heart failure, as well as its impact on survival.

Prognostic value of plasma neutrophil gelatinase-associated lipocalin for mortality in patients with heart failure.

BACKGROUND: In patients with heart failure, renal dysfunction is associated with a poor outcome. We aimed to assess the prognostic value of plasma neutrophil gelatinase-associated lipocalin (NGAL), a novel marker of renal tubular damage, in patients with heart failure with or without renal dysfunction, and compare it with 2 frequently used biomarkers of chronic kidney disease. METHODS AND RESULTS: Plasma NGAL, estimated glomerular filtration rate (eGFR), and cystatin C were assessed in 562 patients with heart failure. Chronic kidney disease was defined as eGFR<60 mL/min per 1.73 m2. Outcome was all-cause mortality at 36 months. Mean age was 71±11 years, 61% were men, and 97% were in New York Heart Association functional class II/III. Mean baseline eGFR was 54±20 mL/min per 1.73 m2, mean cystatin C was 11.2 (7.7-16.2) mg/L, and median plasma NGAL was 85 (60-123) ng/mL. Higher plasma NGAL levels were independently associated with an increased risk of all-cause mortality, in patients with and without chronic kidney disease (hazard ratio [per SD increase in log NGAL]=1.45 [1.22-1.72]; P<0.001 and hazard ratio=1.51 [1.06-2.16]; P=0.023, respectively). Similarly, both in patients with high and low cystatin C (median cut-off), higher plasma NGAL levels were independently associated with an increased risk of all-cause mortality. Moreover, when NGAL was entered in the multivariable risk prediction model, eGFR (P=0.616) and cystatin C (P=0.937) were no longer associated with mortality. CONCLUSIONS: Plasma NGAL predicts mortality in patients with heart failure, both in patients with and without chronic kidney disease and is a stronger predictor for mortality than the established renal function indices eGFR and cystatin C.

Chronic metformin treatment is associated with reduced myocardial infarct size in diabetic patients with ST-segment elevation myocardial infarction.

PURPOSE: Increased myocardial infarct (MI) size is associated with higher risk of developing left ventricular dysfunction, heart failure and mortality. Experimental studies have suggested that metformin treatment reduces MI size after induced ischaemia but human data is lacking. We aimed to investigate the effect of metformin on MI size in patients presenting with an acute MI. METHODS: All consecutive patients (n = 3,288) presenting to our hospital with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI between January 2004 and December 2010 were included in this retrospective analysis. Patients with diabetes were divided according to metformin versus non-metformin based pharmacotherapy. MI size was estimated using peak values of serum creatine kinase (CK), myocardial band of CK (CK-MB), and troponin-T. RESULTS: We identified 677 (20.6 %) patients with diabetes, of whom 189 (27.9 %) were treated with metformin. Chronic metformin treatment was associated with lower peak levels of CK (1,101 vs. 1,422 U/L, P = 0.005), CK-MB (152 vs. 182 U/L, P = 0.018) and troponin-T (2.5 vs. 4.0 ng/L, P = 0.021) compared to non-metformin using diabetics. After adjustment for age, sex, TIMI flow post PCI, and previous MI, the use of metformin treatment remained an independent predictor of smaller MI size. Patient with diabetes treated with metformin had even smaller MI size than patients without diabetes. CONCLUSIONS: Chronic metformin treatment is associated with reduced MI size compared to non-metformin based strategies in diabetic patients presenting with STEMI. Metformin might have additional beneficial effects beyond glucose lowering efficacy.

Neurohormonal and clinical sex differences in heart failure.

AIMS: Despite disparities in pathophysiology and disease manifestation between male and female patients with heart failure, studies focusing on sex differences in biomarkers are scarce. The purpose of this study was to assess sex-specific variation in clinical characteristics and biomarker levels to gain more understanding of the potential pathophysiological mechanisms underlying sex differences in heart failure. METHODS AND RESULTS: Baseline demographic and clinical characteristics, multiple biomarkers, and outcomes were compared between men and women in 567 patients. The mean age of the study group was 71 ± 11 years and 38% were female. Women were older, had a higher body mass index and left ventricular ejection fraction, more hypertension, and received more diuretic and antidepressant therapy, but less ACE-inhibitor therapy compared with men. After 3 years, all-cause mortality was lower in women than men (37.0 vs. 43.9%, multivariable hazard ratio = 0.64; 95% confidence interval 0.45-0.92, P = 0.016). Levels of biomarkers related to inflammation [C-reactive protein, pentraxin 3, growth differentiation factor 15 (GDF-15), and interleukin 6] and extracellular matrix remodelling (syndecan-1 and periostin) were significantly lower in women compared with men. N-terminal pro-brain natriuretic peptide, TNF-αR1a, and GDF-15 showed the strongest interaction between sex and mortality. CONCLUSION: Female heart failure patients have a distinct clinical presentation and better outcomes compared with male patients. The lower mortality was independent of differences in clinical characteristics, but differential sex associations between several biomarkers and mortality might partly explain the survival difference.

Increased central venous pressure is associated with impaired renal function and mortality in a broad spectrum of patients with cardiovascular disease.

OBJECTIVES: We sought to investigate the relationship between increased central venous pressure (CVP), renal function, and mortality in a broad spectrum of cardiovascular patients. BACKGROUND: The pathophysiology of impaired renal function in cardiovascular disease is multifactorial. The relative importance of increased CVP has not been addressed previously. METHODS: A total of 2,557 patients who underwent right heart catheterization in the University Medical Center Groningen, the Netherlands, between January 1, 1989, and December 31, 2006, were identified, and their data were extracted from electronic databases. Estimated glomerular filtration rate (eGFR) was assessed with the simplified modification of diet in renal disease formula. RESULTS: Mean age was 59 +/- 15 years, and 57% were men. Mean eGFR was 65 +/- 24 ml/min/1.73 m(2), with a cardiac index of 2.9 +/- 0.8 l/min/m(2) and CVP of 5.9 +/- 4.3 mm Hg. We found that CVP was associated with cardiac index (r = -0.259, p < 0.0001) and eGFR (r = -0.147, p < 0.0001). Also, cardiac index was associated with eGFR (r = 0.123, p < 0.0001). In multivariate analysis CVP remained associated with eGFR (r = -0.108, p < 0.0001). In a median follow-up time of 10.7 years, 741 (29%) patients died. We found that CVP was an independent predictor of reduced survival (hazard ratio: 1.03 per mm Hg increase, 95% confidence interval: 1.01 to 1.05, p = 0.0032). CONCLUSIONS: Increased CVP is associated with impaired renal function and independently related to all-cause mortality in a broad spectrum of patients with cardiovascular disease.