The effect of food-restriction-induced weight loss on in vivo cardiac contractility before and during beta-adrenergic stimulation was assessed using left ventricular pressure–volume analysis in a mouse model featuring obesity and Type II diabetes (ob/ob), obesity, Type II diabetes, atherogenic dyslipidaemia, and hypertension (LDLR–/–;ob/ob), or wild-type. In addition, sarcoendoplasmic reticulum (SR) Ca²⁺ reuptake, interstitial collagen accumulation, and aortic atherosclerosis were measured. Food-restriction resulted in a 54% lower weight. Weight loss largely normalized pre- and afterload in both ob/ob and LDLR–/–;ob/ob mice. Contractility and relaxation improved after weight loss, partly explained by improved SR Ca²⁺ reuptake. Ventricular–vascular stiffening, interstitial collagen accumulation, and aortic atherosclerosis were less in food-restricted than in free-fed LDLR–/–;ob/ob mice. In contrast, cardiac reserve was similarly impaired in free-fed and food-restricted ob/ob and LDLR–/–;ob/ob mice.

Food-restriction in obese diabetic mice leads to improved cardiac performance by diminishing cardiac load and by ameliorating the intrinsic contractile properties of the cardiac muscle. However, cardiac reserve under dobutamine stimulation did not increase.

To test the hypothesis that there is a graded relation between SBP and HF risk among subjects with normal SBP, we used data on 18 876 participants who were healthy and were free of HF at baseline. Incident HF cases were ascertained by annual follow-up questionnaires and validated through a review of medical records. Cox proportional hazard model was used to compute multivariable-adjusted hazard ratios with corresponding 95% confidence intervals. Between 1982 and 2008, 1098 cases of HF occurred. There was a 35% increased risk of HF among subjects with SBP 130–139 mmHg compared with people with optimal SBP (<120 mmHg). In addition, there was a linear trend in HF risk across the normal range of SBP.

Our findings suggest a linear relationship between normotensive SBP and HF risk. Strategies to prevent HF, such as lifestyle modification, should be emphasized across all blood pressure ranges.

Gulf RACE is a prospective, multi-national study of all patients hospitalized with ACS in 65 centres in six Arab countries. Data were analysed based on HF on presentation (Killip class II/III) or during hospital stay. The study endpoint was all-cause in-hospital mortality. Of 8000 patients with ACS, 2009 (25%) had HF on presentation or during the hospital stay. Patients with HF were older, more often with co-morbid conditions, and less often treated with evidence-based therapies. Heart failure was associated with higher in-hospital mortality (7.9 vs. 0.9%, P < 0.001), which persisted after adjusting for age, gender, and presentation and treatment characteristics [adjusted odds ratio 4.1 (1.8–9.4)]. There was a significant interaction between age and the prognostic effect of HF on in-hospitality mortality, such that younger patients had a significantly higher increase in mortality related to HF (P for interaction = 0.002).

Heart failure complicates a substantial proportion of ACS admissions in the Arab Middle East and is associated with higher in-hospital death. Younger patients with ACS have a higher relative increase in mortality related to HF.

Data on implantation rates for conventional pacemakers, ICD, CRT, and CRT-D in 15 Western European countries were obtained from the Eucomed Registry for the 5-year period 2004–2008. Implantation of conventional pacemakers increased by 9% in Europe over the 5 years (reaching 907/million in 2008) and there were significant differences between countries. Implantable cardioverter defibrillator implantations increased by 75% from 80/million in 2004 to 140/million in 2008, and differences between countries were larger than those for conventional pacemakers. Implantation rates for CRT-P alone increased slightly from 2004 to 2006, but remained at 25/million thereafter in Europe overall. The total number of CRT implants (CRT-P and -D) markedly increased from 46/million in 2004 to 99/million in 2008 (115%), but this was mainly due to more CRT-D implants, i.e. an increase in the proportion of CRT-D (from 55% in 2004 to 75% in 2008). Implantation rates for ICD, CRT, and CRT-D remained markedly different throughout the study period between countries.

Implantation rates of devices for HF, in particular ICD and CRT-D, have increased significantly between 2004 and 2008 in Europe, but there remain major differences between countries.

Patients referred to a specialist HF clinic between 2001 and 2008 were assessed comprehensively including medical history, echocardiogram, and blood tests. Cox-regression was used to assess the multivariable relationship between RDW, NT-proBNP, and all-cause mortality. A total of 1087 patients were recruited; median (IQR) follow-up was 52 months (29–66); age 72 years (64–78); 74% male; 70% ischaemic heart disease; 20% diabetic; 85% NYHA ≥ 2, and 63% with at least moderate LV impairment (EF < 35% equivalent). In a multivariable model, both RDW and NT-proBNP were independently prognostic (RDW: ² = 21.8 vs. 49.1 both P < 0.001). In a model using quartiles of each variable, the relative risk for each was similar for the second and third quartiles compared with the first. A larger increase in risk for NT-proBNP is seen in the fourth quartile.

Red cell distribution width is a readily available test in the HF-population with similar independent prognostic power to NT-proBNP across the first to third quartiles. Prognostic models in HF should include RDW and further investigation is necessary to determine the pathological mechanism of the relationship.

Plasma levels of RBP 4, insulin, and interleukins (IL) 2, 8, and 10, were assessed in patients with dilated cardiomyopathy (DCM, n = 53), dilated inflammatory cardiomyopathy (DCMi, n = 54), and controls (n = 20). In addition, a possible mechanism of RBP 4 regulation was examined in adipocytes in vitro. Plasma levels of RBP 4 and insulin were measured by a specific ELISA. Interleukin concentrations were obtained by multiplex ELISA. Cell culture with 3T3-L1 adipocytes was performed to measure RBP 4 mRNA expression after stimulation with IL-8. RBP 4 levels were significantly increased in patients with DCMi (52.95 ± 20.42 µg/mL) compared with DCM (35.54 ± 23.08 µg/mL) and the control group (27.3 ± 18.51 µg/mL). RBP 4 was positively correlated with IL-8 (r=0.416, P < 0.05) in human plasma in patients with DCMi. Moreover, increased insulin resistance was observed in patients with DCMi compared with the control and DCM groups. In vitro, IL-8 induced a significant upregulation of RBP 4 mRNA expression in adipocytes.

Elevated RBP 4 plasma concentrations, induced by IL-8, might be one mechanism leading to a higher incidence of diabetes in patients with DCMi.

A total of 130 patients with either idiopathic (n = 70) or ischaemic (n = 60) DCM, and 60 controls underwent clinical examination, standard echocardiography, and RA two-dimensional strain echocardiography (2DSE). Six months after implantation of a cardiac resynchronization therapy (CRT) device, the DCM patients were re-evaluated, if their left ventricular (LV) end-systolic volume had decreased by at least 15% they were defined as echocardiographic responders. All DCM patients were in NYHA class III before CRT, with a mean LV ejection fraction of 29.2 ± 5.5%. After CRT, 94 patients were in NYHA functional class I–II. The patients were subdivided into echocardiographic responders (n = 85) and non-responders (n = 45). Both RA area index (19.7 ± 5.5 cm²/m in non-responders vs. 13.2 ± 4.4 cm²/m in responders; P < 0.001) and RA strain of lateral wall (24.3 ± 10.2% in non-responders vs. 40.2 ± 8.9% in responders; P < 0.001) were significantly different between the two groups. A RA area index ≥16 cm²/m showed a sensitivity and specificity of 87.1 and 95.4%, respectively (P < 0.0001) to predict a negative response to CRT. By multivariable analysis, increased RA area index (P < 0.001), ischaemic aetiology of DCM (P < 0.01), and less severe radial intraventricular dyssynchrony were independent determinants of an unfavourable response to CRT.

Right atrial area index was increased and RA myocardial deformation was impaired in patients with DCM who were non-responders to CRT.

Patients aged 65 years or over with a general practitioner (GP)'s diagnosis of COPD but without a prior diagnosis of heart failure underwent an extensive diagnostic work-up including echocardiography and pulmonary function tests in the period 2001–03. An expert panel then confirmed the presence or absence of COPD according to the GOLD criteria and (previously undiagnosed) heart failure according to the criteria of the ESC heart failure guidelines. This cohort of 405 patients was followed up for a mean duration of 4.2 (SD 1.4) years. The GP's electronic medical files relating to the participants, including any specialist letters, were scrutinized until April 2007 for information about drug use, exacerbations of COPD, pneumonia, hospitalizations, death, and cause of death. The mean age of patients at the start of the study was 73.0 (SD 5.3) years, and 54% were male. The presence of newly detected heart failure significantly increased all-cause mortality independent of gender, age, history of ischaemic heart disease, hypertension, diabetes mellitus, atrial fibrillation, smoking, and cardiovascular drug use at baseline (adjusted hazard ratio, 2.1; 95% confidence interval, 1.2–3.6; P = 0.01).

Heart failure is a strong independent predictor of all-cause mortality in patients with a diagnosis of COPD.

From a cohort of 1790 patients, we formed 230 nested matched triplets by individually matching patients with body mass index (BMI) > 30 kg/m² (Group 3), BMI 20–24.9 k/m² (Group 1) and BMI 25–29.9 kg/m² (Group 2), according to NT-proBNP, age, sex, and NYHA class (triplet = one matched patient from each group). Although in the pre-matching cohort, BMI group was a significant univariable prognostic indicator, it did not retain significance [heart rate (HR): 0.91, 95% CI: 0.78–1.05, ²: 1.67] when controlled for group propensities as covariates. Furthermore, in the matched cohort, 1-year mortality and 3-year mortality did not differ significantly. Here, BMI again failed to reach statistical significance for prognosis, either as a continuous or categorical variable, whether crude or adjusted. This result was confirmed in the patients not selected for matching. NT-proBNP, however, remained statistically significant (log(NT-proBNP): HR: 1.49, 95% CI: 1.13–1.97, ²: 7.82) after multivariable adjustment.

The obesity paradox does not appear to persist in a matched setting with respect to indicators of disease severity and other confounders. NT-proBNP remains an independent prognostic indicator of adverse outcome irrespective of obesity status.

Seventy-one stable outpatients with NICHF, who were already receiving standard therapy for CHF, were randomized to simvastatin (n = 35) or rosuvastatin (n = 36). Plasma levels of brain natriuretic peptide (BNP), total adiponectin, high-sensitive C-reactive protein, HbA1c, and oxidized low-density lipoprotein (oxLDL), a marker of oxidative stress, were measured before and 4 months after treatment with simvastatin or rosuvastatin. There was no difference in the baseline characteristics including left ventricular ejection fraction (LVEF) and biochemical parameters between the two groups. In both groups, plasma BNP levels and LVEF did not change after 4 months. Plasma levels of adiponectin and oxLDL did not change and HbA1c level was slightly increased (6.0 ± 0.9 vs. 6.1 ± 0.9%, P = 0.053) in the simvastatin group. In contrast, plasma adiponectin level was significantly increased (12.3 ± 7.3 vs. 14.0 ± 8.2 µg/mL, P = 0.012) concomitant with a significant reduction in oxLDL and HbA1c (oxLDL: 8.8 ± 4.7 vs. 7.6 ± 4.7 U/mL, P = 0.0059; HbA1c: 6.0 ± 0.7 vs. 5.9 ± 0.7%, P = 0.002) in the rosuvastatin group.

These findings suggest that hydrophilic rosuvastatin but not lipophilic simvastatin increases adiponectin and decreases HbA1c levels in patients with NICHF.

We studied 958 patients enrolled after hospitalization for HF; 37% female; mean age 71 ± 11 years; New York Heart Association class II (51%) or III/IV (49%). Left ventricular ejection fraction: 33% ± 14%, and median BNP level: 454 pg/mL (75% CI, 195–876 pg/mL). In total, 377 patients (39%) had depressive symptoms [Centre for Epidemiological Studies Depression Scale (CES-D) score ≥16] and 200 (21%) had severe depressive symptoms (score ≥24). During 18 months of follow-up, 386 (40%) patients reached the primary endpoint of death or readmission for HF. In multivariate analyses, CES-D was significantly associated with the primary endpoint [hazard ratio (HR) 1.13, P = 0.02], and also with both individual components of the primary endpoint [HF readmission (HR 1.165, P = 0.02) and mortality (HR 1.169, P = 0.02)]. Patients with severe depressive symptoms had a >40% higher risk for HF readmission or death.

In patients with HF, depression is independently associated with poor outcomes. These findings highlight the need for continued exploration of whether improvements in depression lead to better cardiovascular outcomes.

The study was registered at clinical trial (www.trialregister.nl): NCT 98675639.

Eighty patients aged over 65 years who presented at the emergency department with decompensated HF were randomly assigned to IHC or HaH. All patients were studied for 1 year. Seventy-one patients completed the study, of these 34 were admitted to cardiology and 37 received HaH care. No significant differences were found in baseline characteristics, including comorbidity, functional status, and health-related quality of life. Clinical outcomes were similar after initial admission and also after the 12 months of follow-up. Death or re-admission due to HF or another cardiovascular event occurred in 19 patients in IHC and 20 in HaH (P = 0.88). Changes in functional status and health-related quality of life over the follow-up period were not significantly different. The average cost of the initial admission was 4502 ± 2153 in IHC and 2541 ± 1334 in HaH (P < 0.001). During 12 months of follow-up, the average expenditure was 4619 ± 7679 and 3425 ± 4948 (P = 0.83) respectively.

Hospital at home care allows an important reduction in the costs during the index episode compared with hospital care, whilst maintaining similar outcomes with respect to cardiovascular mortality and morbidity and quality of life at 1 year follow-up.

Mesenchymal stem cells from male Sprague–Dawley rat bone marrow were infected with the self-inactive lentiviral vector GFP-wre-CMV/LTR and Flap-Ubiqutin promoter (GCFU) carrying green fluorescent protein (GFP) gene and SVV recombinant vector (GCFU-SVV). In vitro, modification with SVV increased the secretion of vascular endothelial growth factor (VEGF) by 1.28-fold under hypoxic conditions. In vivo, after permanent left anterior descending artery occlusion, rats were randomized (n = 18 per group) to receive intra-myocardial injections of 100 µL of phosphate-buffered saline without cells (group vehicle) or containing 2 million MSC_GFP (group MSC_GFP) or MSC_SVV (group MSC_SVV) cells. Cellular survival assessed by reverse transcriptase–polymerase chain reaction for GFP in the MSC_SVV group was 2.5-fold higher at 7 days and 4.3-fold higher at 28 days after transplantation than in the MSC_GFP group. When compared with transplantation with MSC_GFP, transplantation with MSC_SVV further upregulated VEGF expression at 7 and 28 days after myocardial infarction (MI), increased capillary density by 38%, reduced the infarct size by 12.7%, significantly inhibited collagen deposition, and further improved cardiac function at 28 days after MI.

Transplantation with SVV-engineered MSCs by lentiviral vector leads to better prognosis for MI by enhancing cellular survival.

This was a prospective study of HF conducted over 11.8 years through links with the Swedish hospital discharge and mortality registers. Lipoprotein components and other risk factors were measured in 84 740 men and women during health check-ups. All LC were strongly associated with HF per gender adjusted for risk factors. Relationships were stronger for men than for women. Among LC the apoB/apoA-1 ratio was the strongest risk factor for HF in men and triglycerides (TG) in women, but differences in strength were not large. The Hp and UA added predictive information to that of the apoB/apoA-1 ratio, but glucose did not. There was no detectable interaction (synergistic effects) on relative risk between apoB/apoA-1 and these three additional factors.

Over and above adjustment factors, the apoB/apoA-1 ratio and TG were the most predictive of the LC, but all LC were highly significantly related to the development of HF.

HEARD-IT was a multicentre, prospective study of the diagnostic utility of acoustic cardiography in the emergency department. Dyspnoeic patients more than 40 years were eligible. Two cardiologists independently adjudicated the HF outcome. Using logistic regression, a model adjusting BNP for pertinent covariates was developed (n = 740). The mean age was 66 ± 13 years. Age, gender, ethnicity, body mass index, blood urea nitrogen, and creatinine affected BNP levels independently of HF. The model adjusting BNP for these covariates improved the area under receiver operator characteristic curve for HF compared with BNP alone (0.948, 95% CI 0.934–0.963 vs. 0.937, 95% CI 0.920–0.954; P = 0.004). Net reclassification improvement, a novel metric of model performance, was 3.5% for those without HF (P = 0.05) compared with conventional, unadjusted BNP cut-offs. Thirteen of 116 (11%) patients without HF, but with unadjusted BNP values ≥100 pg/mL, were correctly reclassified as not having HF with the adjusted BNP model.

Adjusting BNP for important covariates may improve its ability to distinguish cardiac from non-cardiac dyspnoea.

sTWEAK levels in plasma samples from 364 patients with systolic heart failure were compared with 36 control patients. The median levels of sTWEAK in heart failure patients were significantly lower than those of the control group (217 pg/mL, interquartile range 136–311 vs. 325 pg/mL, interquartile range 250–394 pg/mL). Moreover, sTWEAK levels were lower in patients with ischaemic cardiomyopathy vs. dilated cardiomyopathy and correlated significantly with functional NYHA class. Patients with plasma levels below a ROC-derived cut-off value of 227 pg/mL had a significantly higher mortality rate after 4 years. Upon univariate and multivariate analyses, sTWEAK levels below 227 pg/mL emerged as an independent predictor of subsequent death.

In contrast to other cytokines shown to be increased in heart failure patients, plasma levels of sTWEAK are significantly reduced in chronic stable heart failure. In addition, lower plasma levels of sTWEAK predict an adverse prognosis independent of established risk markers such as NT-proBNP.

Serum levels of B or C domain containing Tn-C, MMP-9, TIMP-1, -2, and -4 were determined in concentric (left ventricular posterior wall thickness >13 mm and intraventricular septum >13 mm, n = 61) and eccentric (end-diastolic left ventricular diameter >55 mm or end-systolic left ventricular diameter >40 mm, n = 34) LVH by enzyme-linked immunoassays. Levels of B domain containing Tn-C were higher in patients with LVH than in normal volunteers (P = 0.020) and higher in eccentric LVH (EH) compared with concentric LVH (CH) (P = 0.003). A cut-off value of 900 ng/mL might discriminate between these different forms of LVH. Matrix metalloproteinase-9 was higher in patients with LVH than in normal volunteers (P = 0.042), and levels were decreased in EH compared with CH (P = 0.028). Patients with LVH had higher levels of TIMP-1 (P = 0.059), TIMP-2 (P = 0.043), and TIMP-4 (P = 0.163) than normal volunteers, but there were no differences between the LVH groups.

Our data suggest that myocardial remodelling in LVH is associated with changes in serum levels of MMP-9, TIMP-1, -2, -4, and Tn-C splice variants. In addition, B domain containing Tn-C discriminated EH from CH and might be suggested as a potential diagnostic marker.

A total of 40 CHF patients simultaneously underwent overnight simplified respiratory polygraphy and 24 h continuous electrocardiography. Peak TWA during both daytime and nighttime were calculated by the modified moving average method. The patients were divided into two groups; 30 patients with daytime predominant TWA (whose peak TWA was higher during daytime than during nighttime) and 10 with nighttime predominant. Apnoea–hypopnoea index (AHI) was significantly higher in patients with nighttime predominant TWA than in those with daytime predominant (35.9 ± 8.1 vs. 23.9 ± 14.4 events/h, P = 0.02), and was an independent predictor of nighttime predominant TWA (odds ratio, 1.08; 95% confidence interval, 1.01–1.16; P = 0.03). Moreover, peak TWA during the night was correlated positively with AHI (P < 0.001), and AHI was an independent determinant of nocturnal TWA value (r² = 0.27, P = 0.009).

In CHF patients, sleep apnoea induces cardiac electrical instability manifested as TWA, reflecting increased risk of nocturnal SCD. Moreover, some CHF patients with sleep apnoea exhibit nighttime predominant TWA. Therefore, TWA should also be evaluated during the night.

In this pooled analysis of three randomized, double-blind, placebo-controlled studies of anaemic [haemoglobin (Hb) ≤12.0 g/dL or ≤12.5 g/dL] symptomatic HF subjects, DA was administered subcutaneously once every 2 weeks and titrated to achieve and maintain a target Hb of 14.0 ± 1.0 g/dL. In total, 516 subjects were randomized; 231 (44.8%) to placebo, 285 (55.2%) to DA. Darbepoetin alfa was well tolerated, with an adverse event (AE) profile similar to placebo. Most subjects (placebo, 85%; DA, 87%) experienced at least one AE. There was a lower incidence of serious AEs in the DA group (placebo, 43%; DA, 37%) with the most frequent being worsening HF (placebo, 19%; DA, 11%). Treatment-related AEs were reported for 9% and 12% in placebo and DA subjects, respectively. Fewer deaths were reported in DA group (6%) vs. placebo (8%).

Darbepoetin alfa was well tolerated with an AE profile similar to placebo in HF subjects treated to a target Hb of 14.0 ± 1.0 g/dL. Contrary to recent data in other patient populations, there was no evidence of increased risk of mortality or cardiovascular events.

A total of 2332 consecutive patients (average ± SD age 70.1 ± 10.8; 26% female) who presented to a community heart failure clinic were diagnosed as having heart failure due to left ventricular systolic dysfunction. All patients were asked whether they would be prepared to take part in clinical research projects at their initial visit. During a median follow-up in survivors of 55.7 months (interquartile range 30.4–74.3), 792 (34%) patients died. Agreeing to take part in clinical trials strongly predicted a good outcome (approximately halving the risk of death). In multivariate modelling, willingness to take part [hazard ratio (95% confidence intervals) 0.33 (0.26–0.40)] was a predictor of good outcome independent of age, severity of left ventricular dysfunction, renal function, sodium levels, drug use, and comorbidities. In a subset in whom N-terminal pro-B type natriuretic peptide (NT-proBNP) was available (n = 1256), agreeing to take part in trials remained an independent predictor of survival with log [NT-proBNP].

Those patients with chronic heart failure who express a willingness to take part in a clinical trial, appear to have a better prognosis than those who do not.

This is a multi-centre, randomized, double-blind, placebo-controlled study recruiting ambulatory patients with symptomatic CHF with LVEF ≤ 40% (NYHA II) or ≤45% (NYHA III), ID [ferritin <100 ng/mL or ferritin 100–300 ng/mL when transferrin saturation (TSAT) < 20%], and haemoglobin 9.5–13.5 g/dL. Patients were randomized in a 2:1 ratio to receive ferric carboxymaltose (Ferinject^®) 200 mg iron i.v. or saline i.v. weekly until iron repletion (correction phase), then monthly until Week 24 (maintenance phase). Primary endpoints are (i) self-reported PGA at Week 24 and (ii) NYHA class at Week 24, adjusted for baseline NYHA class.

This study will provide evidence on the efficacy and safety of iron repletion with ferric carboxymaltose in CHF patients with ID with and without anaemia.

A multivariable regression analysis of 7599 heart failure patients from the CHARM trial was done to evaluate factors associated with adherence. Adherence was measured as the proportion of time patients took more than 80% of study medication. The mean age was 66 years (SD 11) and 31.5% (n = 2400) were women. Women were slightly less adherent than men (87.3 vs. 89.8%, P = 0.002), even in adjusted, multivariable models (treatment, P = 0.006; placebo P = 0.004; and overall P < 0.001). However, all-cause mortality was lower in women (21.5%) than in men (25.3%) (adjusted hazard ratio, 0.77; 95% CI, 0.69–0.86; P < 0.001), but patients with a low adherence regardless of sex had a higher mortality. Age, severity of heart failure, number of medications, and smoking status were not associated with adherence.

Women, particularly those <75 years of age, were less likely to be adherent in this large sample of patients with symptomatic heart failure. Understanding factors associated with adherence may provide opportunities for intervention.

The 6632 patients of the EPHESUS study were randomized from day 3 to 14 after the index AMI (median = 7 days), of these 3319 were assigned to eplerenone. We analysed the differential effects of time-to-eplerenone initiation vs. placebo, based on the median time to initiation of treatment (<7 days—‘earlier’, ≥7days—‘later’). Effects on outcomes were evaluated over a mean 16-month follow-up, using Cox proportional hazards regression analysis. The earlier eplerenone initiation (<7 days) reduced the risk of all-cause mortality by 31% (P = 0.001) when compared with the ‘earlier’ placebo’ and also reduced the risks of cardiovascular (CV) hospitalization/CV mortality by 24% (P < 0.0001) and sudden cardiac death (SCD) by 34% (P < 0.0001). In contrast, later eplerenone initiation (≥7 days) had no significant effect on outcomes. Interactions between time-to-randomization and treatment were significant. These associations remained substantially unchanged after risk adjustment in multivariable models.

An earlier eplerenone administration (3–7days) post-AMI improved outcomes in patients with LVSD and HF. This benefit was not observed when eplerenone was initiated later (≥7days).

The diabetic model was produced by injection of streptozotocin in Sprague-Dawley rats. Ten weeks after induction of diabetes, AMI was induced by ligation of the left anterior descending coronary artery. Cardiac function and left ventricular (LV) dimensions were evaluated using two-dimensional echocardiography. Structural changes were assessed by histological examination. Gene expression profile was documented by using affymetrix genechip U230 2.0 array and real time-PCR. During 56 days post-AMI, lower survival rates, worse LV function, more severe fibrosis, and larger LV diameters were identified in diabetic rats compared with non-diabetic rats. A total 1221 genes involved in processes, such as glucose metabolism, fatty acid metabolism, extracellular matrix, and apoptosis, were found to be differentially expressed between diabetic and non-diabetic rats, of these 770 were up-regulated and 451 down-regulated. Up-regulation of the genes was found 1–2 weeks earlier in diabetic rats than in non-diabetic rats.

The present data suggest that hyperglycaemia up-regulates remodelling-related genes, which may be responsible for the worse outcomes in diabetics than in non-diabetics after AMI.

The analysis comprised 5299 subjects (41% men, age ~68 years) free from heart failure for whom dietary data were available. During 11.4 years of follow-up, 669 subjects developed heart failure. The relative risk (RR) of heart failure in the top vs. bottom quintile of EPA plus DHA intake was 0.89 (95% CI 0.69–1.14), after adjustment for lifestyle and dietary factors. For fish intakes ≥20 g/day, the RR was 0.96 (0.78–1.18) compared with no fish intake. In sex-specific analysis, a high EPA plus DHA intake tended to be protective in women (RR = 0.75, 0.54–1.04) but not in men (RR = 1.00, 0.73–1.36). An inverse association for EPA plus DHA was also observed in diabetics (RR = 0.58, 0.32–1.06), which was borderline statistically significant.

Our findings do not support a major role for fish intake in the prevention of heart failure. The potentially protective effect of EPA plus DHA in diabetic patients, however, warrants further investigation.

The MeRGE collaboration combines prospective data from 18 studies in HF patients. In this analysis of data from 1157 patients, the primary endpoint was death or hospitalization for worsening HF. In multivariate analysis (Cox proportion hazard model), LA area was associated with prognosis (HR 1.03 per cm², 95% CI 1.02, 1.05; P < 0.0001) independently of age, NYHA class, LV ejection fraction, and restrictive filling pattern (RFP). When LA area was used as a categorical variable, the HR associated with larger LA area (above median) was 1.4 (95% CI 1.13, 1.74) and when LA area index was used, the HR was 2.36 (95% CI 1.80, 3.08). When the patients with and without RFP were divided on the basis of either LA area or LA area index, significantly higher event rates were observed in those with larger LA area.

Left atrial area is a powerful predictor of outcome among HF patients with predominantly impaired systolic function, and is independent of, and provides additional prognostic information beyond LV systolic and diastolic function.

We studied 339 patients (24% women, mean age 65 ± 11 years) referred for assessment of myocardial viability by DHE-CMR. Scar was defined as myocardium with an intensity >2 SD above viable myocardium. Left ventricular scar (defined as a percentage of total LV myocardium), LV volumes, risk factors, cardiac transplantation (CTx), and all-cause mortality were recorded. There were 84 deaths and five CTx over 3.7 ± 1.6 years (median 4 years, interquartile range 2.6–4.9 years). Left ventricular ejection fraction (LVEF) in men was only slightly different from women (23% ± 9 vs. 25% ± 10, P = 0.05), whereas mean scar % was similar in both groups (32 ± 21 vs. 29 ± 20, P = 0.3). On univariable survival analysis, age [hazard ratio, HR, 1.03 (1.01–1.05), P = 0.002], female gender [HR 2.02 (1.31–3.12), P = 0.001], and scar % [HR 1.01 (1.003–1.02), P = 0.009] predicted outcomes; and also on multivariable analysis (² 32, P < 0.0001). Women with scar % greater than the median had more events, compared with men with or without a high scar burden (log-rank P < 0.001).

In patients with CAD and severely reduced LVEF, women have worse outcomes than men, irrespective of myocardial scar burden.

Fifty consecutive patients with DCM (aged 49 ± 13 years) were enrolled prospectively. Forty-seven healthy volunteers served as controls. All subjects underwent clinical examination, 12-lead electrocardiography, and a comprehensive echocardiogram. Basal and apical LV rotation and LV torsion were quantified by speckle tracking echocardiography. Left ventricular systolic rotation and torsion were reduced in patients, compared with controls (P < 0.001). Normally directed (counterclockwise) apical rotation was found in 24 patients (group 1), whereas 26 had reversed (clockwise) apical rotation (group 2). Patients in group 2 had larger LV volume, increased LV sphericity (P ≤ 0.02), more severe systolic dysfunction (ejection fraction 26 ± 7 vs. 33 ± 12%), and higher filling pressures (E/E' ratio 19 ± 10 vs. 14 ± 6; P < 0.05). The main correlates of LV apical rotation were LV volume, sphericity index, and QRS duration.

Reversed apical rotation and loss of LV torsion in patients with DCM is associated with significant LV remodelling, increased electrical dyssynchrony, reduced systolic function, and increased filling pressures, indicating a more advanced disease stage.

We studied 58 HCM patients (mean age 41 years, 37 male). The control population comprised 15 normal subjects. Colour tissue-Doppler imaging was acquired in two-dimensional mode from apical four-chamber and two-chamber views; off-line analysis was performed in four basal and four middle left ventricular segments. Gadolinium-enhanced CMR was performed in 36 HCM patients. In HCM patients, peak systolic strain was not uniform across left ventricular segments; differences were not related to site or thickness of the segment analysed. Paradoxically, positive systolic strain values were measured in six middle segments. Delayed CMR enhancement was associated with lower peak systolic strain (P = 0.007). Regional non-uniformities in peak systolic strain were not observed in normal subjects.

Areas of reduced left ventricular contractility in deformation analysis are associated with delayed CMR enhancement in patients with HCM.

Electronic databases and published bibliographies were systematically searched (1984–2008). We found 14 studies that met our inclusion criteria. Six studies (3543 patients) evaluated BNP to predict SCD in patients without implantable cardioverter defibrillators (ICDs) across a wide range of populations. A raised BNP predicted SCD with a relative risk of 3.68 [95% confidence interval (CI) 1.90, 7.14]. Eight studies (1047 patients) evaluated BNP to predict the occurrence of VA in patients with ICDs. A raised BNP predicted the occurrence of VA with a relative risk of 2.54 (95% CI 1.87, 3.44).

The measurement of BNP has significant value in predicting SCD and VA. However, the benefit of BNP testing in addition to other risk stratification tests is unclear and BNP needs to be evaluated prospectively in combination with other complementary risk stratification tools.

A total of 300 consecutive hospitalized CHF patients were screened for depressive symptomatology using the Zung self-rated depression scale (SDS). Patients with depressive symptoms (Zung SDS ≥40) underwent a 6 min walking test, and evaluation of left ventricular ejection fraction, B-type natriuretic peptide (BNP), and plasma inflammatory/anti-inflammatory factors [interleukin (IL)-6, IL-10, tumour necrosis factor-, soluble intercellular adhesion molecule-1, and vascular cell adhesion molecule-1]. Patients were subsequently followed for up to 1 year for major adverse cardiovascular events (MACE, death or hospitalization due to cardiovascular causes). One hundred and fourteen patients (38%) had a Zung SDS ≥40. One-year event-free survival of these patients was 19% (mean ± SE, 150 ± 12 days). In multivariate analysis, only BNP (HR = 1.001, P = 0.002) and IL-10 (HR = 0.864, P = 0.049) were independent predictors of MACE. Using receiver operator characteristics analysis-derived cut-offs, a BNP value of 290 pg/mL predicted MACE with 86% sensitivity and 69% specificity, whereas an IL-10 value of 5 pg/mL predicted MACE with 61% sensitivity and 78% specificity. Event-free survival differed significantly between patients with BNP < 290 pg/mL and IL-10 > 5 pg/mL (261 ± 44 days) and those with BNP > 290 pg/mL and IL-10 < 5 pg/mL (79 ± 11 days, P = 0.0001).

Neurohormonal activation and defective anti-inflammatory properties are independent predictors of long-term outcome in hospitalized CHF patients with depressive symptoms.

We investigated the effect of intracoronary administration of bone marrow-derived mononuclear cells (BMC) within 7 days after successful reperfusion therapy for AMI, on early (within 4 months) LV remodelling processes assessed by quantitative LV angiography. Overall, 95 patients received BMC and 92 patients received placebo. Remodelling was assessed as the changes in either LVEF and end-systolic volume (ESV) or stroke volume and end-diastolic volume (EDV) at 4 months, respectively. Baseline LVEF was inversely correlated with ESV expansion at 4 months in the placebo group, but not in the BMC group. Likewise, EDV expansion was significantly correlated with baseline LVEF in the placebo (r = –0.36, P < 0.001), but not in the BMC group (r = –0.17, P = 1.0). Analysing the interaction between convalescent LV contractile function and LV volumes revealed that the increase in LVEF or stroke volume did not occur at the expense of increases in ESV or EDV, respectively, in the BMC group.

Intracoronary administration of BMC eliminates the correlation between depressed LVEF after reperfusion therapy and LV expansion during follow-up and, thereby, abrogates early LV remodelling after AMI.

In this multicentred, double-blind, 14-week study, patients were randomized to receive valsartan (V) 80 mg or placebo (P) once daily on top of background medications. The dose of valsartan was force-titrated up to 320 mg. A total of 152 patients were randomized (V = 70, P = 82). Most patients had well-controlled hypertension (V = 91.2%, P = 89.0%) (mean baseline systolic BP ~130 mmHg) and >50% were receiving an angiotensin-converting enzyme inhibitor and/or beta-blocker (V = 57.4%, P = 54.9%). The mean ejection fraction at baseline was 70.48% in the placebo group (n = 64) and 71.52% in the valsartan group (n = 79). Valsartan had no significant effect on exercise time (primary variable), gas exchange variables, 6 min walk test distance, exertion-related symptoms, brain natriuretic peptide levels, echocardiographic parameters, or quality-of-life scores. Valsartan significantly lowered peak exercise systolic BP (–13.1 mmHg vs. placebo; P < 0.001) and improved ratings of perceived exertion (Borg score) (–0.69 vs. placebo; P = 0.008).

In this population, which predominantly included patients with well-controlled hypertension and symptomatic HFPEF, addition of valsartan did not increase exercise time within 14 weeks. However, valsartan 320 mg reduced blood pressure and improved symptoms of perceived exertion (Borg score) during exercise and was generally well-tolerated.

We performed a randomized, double-blind, placebo-controlled trial in 120 ambulatory patients aged ≥18 years with New York Heart Association (NYHA) class II-III chronic heart failure. All patients received conventional medical therapy, as tolerated, and were randomized to either hawthorn 450 mg twice daily or placebo for 6 months. The primary outcome was change in 6 min walk distance at 6 months. Secondary outcomes included quality of life (QOL) measures, peak oxygen consumption, and anaerobic threshold during maximal treadmill exercise testing, NYHA classification, left ventricular ejection fraction (LVEF), neurohormones, and measures of oxidative stress and inflammation. There were no significant differences between groups in the change in 6 min walk distance (P = 0.61), or on measures of QOL, functional capacity, neurohormones, oxidative stress, or inflammation. A modest difference in LVEF favoured hawthorn (P = 0.04). There were significantly more adverse events reported in the hawthorn group (P = 0.02), although most were non-cardiac.

Hawthorn provides no symptomatic or functional benefit when given with standard medical therapy to patients with heart failure.

This trial is registered in ClinicalTrials.gov ID: NCT00343902.

We reviewed the data of 65 consecutive patients who underwent LVAD support for at least 6 months. Anaemia was defined as haemoglobin levels <12.0 g/dL. Follow-up was performed 15 months after implantation. Anaemia was present in 30/65 patients (46%) after 6 months of LVAD support. Anaemic patients had higher levels of pre-implant creatinine (1.8 ± 0.8 vs. 1.4 ± 0.5 mg/dL; P = 0.04). The presence of anaemia after 6 months correlated with higher levels of creatinine and blood urea nitrogen and lower levels of albumin. Multivariate Cox proportional hazards regression analysis revealed that levels of haemoglobin <12 g/dL [risk ratio (RR), 8.94; 95% confidence interval (CI), 1.09–73.01; P = 0.04], creatinine >1.4 mg/dL (RR, 5.39; 95% CI, 1.78–16.30; P = 0.003), and albumin <1.5 g/L (RR, 3.23; 95% CI, 1.10–9.51; P = 0.03) were associated with all-cause mortality at 15 months. Long-term survival evaluated by Kaplan–Meier analysis was two times higher in non-anaemic patients after 6 months of LVAD support than in anaemic patients (P = 0.01).

Anaemia is related to adverse outcomes in patients receiving prolonged LVAD support.

There were 28 (15%) deaths, patients with SUA ≥502 µmol/L (upper quartile) at 1 year post-HTx had an increased risk of total mortality (adjusted HR 2.21, P = 0.03) and cardiac mortality (adjusted HR 4.38, P = 0.03). Elevated SUA was a significant risk factor for development of moderate/severe angiographic CAV (adjusted HR 4.79, P = 0.01). A smaller decline in SUA (<97 µmol/L) during the first year post-HTx was also associated with an increased risk of mortality (P = 0.02). Patients with elevated SUA had significantly higher levels of high-sensitivity C-reactive protein (P = 0.008) and N-terminal probrain natriuretic peptide (P = 0.022), but there was no significant difference in oxidative stress parameters.

Elevated SUA at 1 year post-HTx, or a modest rather than a marked decline in SUA levels during the first year post-HTx, is associated with an increased risk of mortality. Although the pathophysiological mechanism is unclear, our data indicate a potential relationship between SUA and inflammation which should be explored further.

Nineteen patients with cardiac amyloidosis but no obvious involvement of other organs were scheduled for heart transplantation. Four to 6 months later, high-dose melphalan chemotherapy and autologous stem cell transplantation (HDM–ASCT) was planned in patients not in complete remission. Seven of nineteen patients died while waiting for heart transplantation. The remaining 12 patients (complete remission, n = 4) underwent surgery. Chemotherapy in patients not in complete remission consisted of HDM–ASCT (n = 5/12; subsequent complete remission, n = 2; partial remission, n = 3) or melphalan–prednisolone (partial remission, n = 1). Two of twelve patients were ineligible for any chemotherapy. Three of twelve patients died [423.5 (105–2131) days] from progressive disease, relapse, or sepsis. The 1- and 3-year survival rates were 83 and 83%, respectively, similar to those of patients undergoing heart transplantation for standard indications. Corresponding survival rates stratified by haematological response were 100 and 100% for complete remission (partial remission, 100 and 100%; progressive disease, 0 and 0%).

Heart transplantation in advanced cardiac amyloidosis is a promising approach to interrupting the vicious circle of ineligibility for potential curative chemotherapeutic treatment and extremely poor prognosis of cardiac amyloidosis without chemotherapy. Highly urgent heart transplantation combined with subsequent HDM–ASCT appears to offer a successful treatment option to improve the poor outcome of cardiac amyloidosis. However, it should be restricted to highly selected patients in specialized centres.