European Heart Journal: Acute Cardiovascular Care

To examine the prognostic value of admission (A) and discharge (D) haemoglobin (Hb) and its relationship with N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) in patients hospitalised for acute heart failure (AHF). The outcomes of interests were rehospitalisation or death after one, six or twelve months after discharge.

317 hospitalised AHF patients (74.7±9.4 years) were enrolled in two academic centres in Belgrade and Rome. Laboratory analyses, including NT-proBNP were assessed at admission, and Hb also at discharge. Patients were divided into two groups according to the presence of anaemia. Follow-up contact was made by telephone. Statistical analyses were performed using SPSS software version 21.0.

According to A and DHb levels (<120 g/l for women and <130 g/l for men), anaemia was present in 55% and 62% of patients, respectively (P=0.497). Lower DHb was associated with the rehospitalisation risk after one (OR=0.96, P=0.004), six (OR=0.97, P<0.001) and 12 months (OR=0.97, P<0.001). For every g/l decrease of DHb, the risk of rehospitalisation after one year was increased by 3.3%. In the first six months, DHb contributed to increased risk of death (OR=0.97, P=0.005), but NT-proBNP showed greater power (OR=2.1, P<0.001).

In AHF patients discharge anaemia is a strong predictor for short and long-term rehospitalisation, while NT-proBNP seems to be a better predictor for mortality. Discharge Hb and NT-proBNP should be assessed together in order to detect the patients with higher risk of future death and rehospitalisation.

Baseline values of N-terminal pro B-type natriuretic peptide (NT-proBNP) and carbohydrate antigen 125 (CA125) predict all-cause mortality in acute heart failure (AHF). However, there is limited information about the added prognostic benefit of using longitudinal values, and how this predictive ability is modified when modelling together. The aim of this study was to determine the mutually-adjusted association between the longitudinal trajectories of NT-proBNP and CA125 with all-cause mortality after an episode of AHF.

We included 946 consecutive patients discharged for AHF. NT-proBNP and CA125 were measured at each physician-patient encounter (median (interquartile range (IQR)):3 (2–4)). The effect on mortality (time-dependent modelling) was assessed using joint modelling (JM) and multi-state Markov. The mean age was 71±11 years and 51% exhibited left ventricular systolic dysfunction. At a median follow-up of 2.64 years (IQR=1.20–5.36), 498 patients died (52.6%). The observed trajectories of both biomarkers markedly differed over survival status, with sustained higher values in patients who died. After being adjusted by established risk factors and by each other, the baseline absolute change in CA125 and NT-proBNP were significantly associated to mortality (hazard ratio (HR)=1.05 (1.01–1.09); p=0.011 (area under the curve (AUC)=0.76) and HR=1.04 (1.02–1.06); p<0.001 (AUC=0.75), respectively). After merging the binary version of NT-proBNP (⩾1000 pg/ml) and CA125 (>35 U/ml) into a four-level variable, we found the highest risk when both were elevated, intermediate risk when either one was low, and lowest risk when both were low.

The combination of long-term longitudinal trajectories of CA125 and NT-proBNP improves risk stratification for all-cause mortality after a hospitalization for AHF.

Renal insufficiency is a well-known predictor of adverse events in patients with acute heart failure syndromes (AHFS). However, it remains unclear whether there are subgroups of AHFS patients in whom renal insufficiency is related to a higher risk of adverse events because of the heterogeneity of this patient population. Therefore, we investigated the relationship between renal insufficiency, clinical features or comorbidities, and the risk of adverse events in patients with AHFS.

Of 4842 patients enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, 4628 patients (95.6%) were evaluated in the present study in order to assess the relationship of renal insufficiency and clinical features or comorbidities with all-cause mortality after admission. Renal insufficiency was defined as an estimated creatinine clearance of ⩽40 mL/min (calculated by the Cockcroft–Gault formula) at admission. The median follow-up period after admission was 524 (391–789) days. The all-cause mortality rate after admission was significantly higher in patients with renal insufficiency (36.7%) than in patients without renal insufficiency (14.4%). Stratified analysis was performed in order to explore the heterogeneity of the influence of renal insufficiency on all-cause mortality. This analysis revealed that an ischaemic aetiology and a history of diabetes, atrial fibrillation, serum sodium, and anaemia at admission had significant influences on the relationship between renal insufficiency and all-cause mortality.

The present study demonstrated that the relationship between renal insufficiency and all-cause mortality of AHFS patients varies markedly with clinical features or comorbidities and the mode of presentation due to the heterogeneity of this patient population.

Intra-aortic balloon pumps (IABPs) provide primarily left ventricular support, yet few data detail the efficacy of this temporary mechanical circulatory support device in patients with concomitant right ventricular failure. We compared the efficacy of IABPs in cardiogenic shock patients with isolated left ventricular versus biventricular failure.

IABP-treated cardiogenic shock patients were identified from our center between 2006 and 2012, with patients stratified by either isolated left ventricular failure or biventricular failure. We compared baseline characteristics and 72-hour and 30-day outcomes between groups. Outcomes of interest included escalation of mechanical circulatory support, a clinical definition of IABP failure, and death.

Among 107 patients, 60 patients (56%) had isolated left ventricular failure compared with 47 patients (44%) having biventricular failure. Patients with isolated left ventricular failure were older and more likely to have coronary artery disease (p<0.05, both). Patients with biventricular failure more often required escalation of mechanical circulatory support at both 72 hours (21% vs. 2%, p<0.001) and 30 days (36% vs. 30%). However, there was no significant difference between groups for failure of IABP therapy at 72 hours (p=0.27) or at 30 days (p=0.62) and death at 30 days (p=0.98). In adjusted analysis, there was no significant difference between groups with regard to risk for a clinical definition of IABP failure at 30 days (odds ratio=0.85, 95% confidence interval (0.27, 2.69)).

IABP-treated cardiogenic shock patients with biventricular failure more often required early escalation of mechanical circulatory support. However, there were no significant differences by type of ventricular failure with regard to 30-day outcomes.

Cardiogenic shock due to severe aortic regurgitation in patients with left ventricle assist devices is a life threatening condition. Here, we consider transcatheter aortic valve implantation as a treatment option.

A patient with a left ventricle assist device was presented to us with cardiogenic shock due to severe aortic regurgitation. We successfully implanted a transcatheter aortic valve in emergency setting. The patient recovered and underwent cardiac transplantation three months afterwards. We performed a systematic literature review and identified 10 cases of patients with a left ventricle assist device undergoing transcatheter aortic valve implantation. In these cases, there was no procedural related mortality reported. In four (40%) patients, transcatheter aortic valve implantation resulted in significant paravalvular aortic regurgitation. In two of these cases it was due to migration of the valve towards the left ventricle.

Our case report and review of literature suggests that transcatheter aortic valve implantation is a feasible and lifesaving treatment option for left ventricle assist device patients presenting with severe aortic regurgitation.

Epicardial potentials (EPs) derived from the body surface potential map (BSPM) improve acute myocardial infarction (AMI) diagnosis. In this study, we compared EPs derived from the 80-lead BSPM using a standard thoracic volume conductor model (TVCM) with those derived using a patient-specific torso model (PSTM) based on body mass index (BMI).

Consecutive patients presenting to both the emergency department and pre-hospital coronary care unit between August 2009 and August 2011 with acute ischaemic-type chest pain at rest were enrolled. At first medical contact, 12-lead electrocardiograms and BSPMs were recorded. The BMI for each patient was calculated. Cardiac troponin T (cTnT) was sampled 12 hours after symptom onset. Patients were excluded from analysis if they had any ECG confounders to interpretation of the ST-segment. A cardiologist assessed the 12-lead ECG for ST-segment elevation myocardial infarction by Minnesota criteria and the BSPM. BSPM ST-elevation (STE) was ⩾0.2 mV in anterior, ⩾0.1 mV in lateral, inferior, right ventricular or high right anterior and ⩾0.05 mV in posterior territories. To derive EPs, the BSPM data were interpolated to yield values at 352 nodes of a Dalhousie torso. Using an inverse solution based on the boundary element method, EPs at 98 cardiac nodes positioned within a standard TVCM were derived. The TVCM was then scaled to produce a PSTM using a model developed from computed tomography in 48 patients of varying BMIs, and EPs were recalculated. EPs >0.3 mV defined STE. A cardiologist blinded to both the 12-lead ECG and BSPM interpreted the EP map. AMI was defined as cTnT ⩾0.1 µg/L.

Enrolled were 400 patients (age 62 ± 13 years; 57% male); 80 patients had exclusion criteria. Of the remaining 320 patients, the BMI was an average of 27.8 ± 5.6 kg/m². Of these, 180 (56%) had AMI. Overall, 132 had Minnesota STE on ECG (sensitivity 65%, specificity 89%) and 160 had BSPM STE (sensitivity 81%, specificity 90%). EP STE occurred in 165 patients using TVCM (sensitivity 88%, specificity 95%; p < 0.001) and in 206 patients using PSTM (sensitivity 98%, specificity 79%; p < 0.001). Of those with AMI by cTnT and EPs ⩽0.3 mV using TVCM (n = 22), 18 (82%) patients had EPs >0.3 mV when an individualised PSTM was used.

Among patients presenting with ischaemic-type chest pain at rest, EPs derived from BSPM using a novel PSTM significantly improve sensitivity for AMI diagnosis.

Elevated admission plasma glucose levels >140 mg/dl are associated with adverse clinical outcomes in both diabetic and non-diabetic patients admitted with acute coronary syndrome (ACS). We aimed to evaluate the association between admission plasma glucose levels <140 mg/dl and the outcome of non-diabetic patients admitted with acute coronary syndrome.

The study population consisted of patients with acute coronary syndrome included in the Acute Coronary Syndrome Israeli Survey during 2000–2013. Diabetic patients were excluded. The primary endpoint was all-cause mortality at one year.

The 4520 patients had a mean age of 61.7±13.5 years and were stratified into four quartiles according to admission plasma glucose (60–94, 95–105, 106–119, 120–140 mg/dl). Patients with higher admission plasma glucose were older and included a higher percentage of smokers. In addition, the higher the glucose so also did they have a poorer risk factor profile including a higher body mass index, total and low-density lipoprotein cholesterol and triglyceride levels, and lower high-density lipoprotein cholesterol levels. During the first year 5.2% of patients died. A comparison of one-year mortality according to admission plasma glucose quartiles demonstrated a significant and progressive increase in mortality risk as admission plasma glucose rose (3.5%, 4.1%, 6.1%, 6.4%, respectively, p=0.001). However, this association lost its clinical significance following a multivariate analysis (p=0.08).

High admission plasma glucose levels within the normal to mildly impaired range are associated with increased one-year mortality in non-diabetic acute coronary syndrome patients. However, the higher glucose level is probably not the cause for the adverse outcome but rather a marker for high risk. Our findings support the definition of 140 mg/dl as the cutoff for clinically acceptable admission glucose levels in patients with acute coronary syndrome.

Previously undetected dysglycaemia is common among patients with acute coronary syndromes (ACSs). The aim of this study was to identify the most reliable method of diagnosing type 2 diabetes mellitus (T2DM) and prediabetes in ACS patients.

Patients admitted to the coronary care unit with ACSs and no previous history of T2DM were consecutively included in the study. Glucose metabolism was measured by glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) with a standard oral glucose tolerance test during hospital admission, and this process was repeated 3 months later. In this study, the diagnosis of T2DM required at least two measurements above the diabetes cut-off point according to current American Diabetes Association and World Health Organization criteria.

A total of 250 patients were included in the study. T2DM was diagnosed in 7.2%. The sensitivities for detecting T2DM were 33.3%, 61.1% and 77.8% during admission and 27.8%, 61.1% and 72.2% at follow-up for HbA1c, FPG and 2hPG, respectively. The positive predictive values (PPVs) for diagnosing T2DM were 100%, 91.7% and 51.9% during admission and 71.4%, 91.7% and 65.0% at follow-up for HbA1c, FPG and 2hPG, respectively. The specificities and negative predictive values were high for all methods. By combining all measurements, the sensitivity was 100% and the PPV was 44.2%, while the combination of all HbA1c and FPG measurements provided 88.9% sensitivity and 80.0% PPV.

Diagnosis of T2DM can be reliably carried out by repeated measurements of FPG and HbA1c in ACS patients, with limited added value of an oral glucose tolerance test.

We investigated the association between epicardial adipose tissue (EAT) thickness and cardiovascular outcomes in a cohort of high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Of 1198 patients undergoing percutaneous coronary intervention, transthoracic echocardiography was performed in 438 patients during the index hospitalization. EAT thickness was measured in the parasternal long-axis view perpendicularly on the free wall of the right ventricle at end-systole in three consecutive cardiac cycles and then averaged. As the primary outcome measure, a composite of major adverse cardiovascular events – including cardiovascular death, non-fatal myocardial infarction and non-fatal stroke – was investigated after three years of follow-up.

Patients were included between 2004 and 2012 and 293 (66.9%) were men. The median EAT thickness was 2.65 mm (interquartile range 2.00–3.00). EAT was correlated with body mass index (R=0.404; p<0.001), weight (R=0.314; p<0.001), baseline creatinine (R=0.118; p=0.014) and baseline glucose (R=0.129; p=0.007). After a follow-up period of three years, a major adverse cardiovascular event occurred in 64 patients (14.6%) corresponding to 36 (8.2%) with cardiovascular death, 21 (4.8%) with myocardial infarction and seven (1.6%) with stroke. Regarding the primary endpoint, EAT thickness revealed a significant predictive effect on univariate Cox regression (hazards ratio 1.479, 95% CI 1.192–1.953; p=0.006) and multivariate Cox regression analysis (hazards ratio 1.524, 95% CI 1.011–2.267; p=0.038) after adjusting for established cardiovascular confounders.

In a cohort of high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention, EAT was associated with established markers of cardiovascular death and had a predictive value for the three-year cardiovascular outcome.

To review systematically the evidence and perform a meta-analysis of benefits and risks associated with use of P2Y₁₂ receptor inhibitors in coronary artery bypass graft-, non-cardiac- and device surgery.

We performed a meta-analysis of published studies. Patients with preoperative use of clopidogrel, ticagrelor or prasugrel (late discontinuation: <5 days before surgery or no discontinuation) were compared with patients without preoperative use of the respective drug (early discontinuation: ⩾5 days before surgery or no users of P2Y₁₂ receptor inhibitors). Outcomes evaluated were re-operation for major bleeding, death, myocardial infarction, combined major adverse cardiac events (MACEs) and major haematoma. Using a random effect model, relative risks (RRs) and 95% confidence intervals (CI) were calculated for each outcome.

Fifty-four studies met the selection criteria and included 50,048 patients. Preoperative use of clopidogrel on top of aspirin in patients undergoing coronary artery bypass graft was associated with a 2.5-fold increased risk of re-operation for bleeding (95% CI: 1.92–3.25; p<0.001) and a 1.47-fold increased risk of death (95% CI: 1.25–1.72; p<0.001), but did not diminish the risk for myocardial infarction (RR: 0.96; 95% CI: 0.75–1.25; p=0.18) or MACE (RR: 1.16; 95% CI: 0.90-–1.50; p=0.30). In patients undergoing non-cardiac surgery, preoperative use of clopidogrel increased the RR of re-operation for major bleeding by 2.05-fold (95% CI: 1.13–3.73; p=0.002) but did not reduce the RR for MACE or death. Clopidogrel use during cardiac device implantation raised the RR for procedure-related haematoma by 3.0-fold (95% CI: 1.30-–6.94; p=0.001). Whereas preoperative ticagrelor use did not increase the risk for mortality (RR: 1.03; 95% CI: 0.49–2.14), preoperative prasugrel use tended to increase the risk for death (RR: 5.06; 95% CI: 0.54–47.65).

Preoperative exposure to clopidogrel on top of aspirin did not reduce the risk of MACE but was associated with increased risk of bleeding and mortality.

Although obesity is a risk factor for coronary heart disease (CHD), it might be associated with a favourable prognosis in patients with CHD. The aim of the study was to evaluate this so called ‘obesity paradox’ during a follow-up period of 20 years in patients who had undergone coronary artery bypass grafting (CABG).

The study population consisted of 922 CHD patients who had undergone CABG between 1993 and 1994. Pre and perioperative data was collected from patient records and supplemented with patient questionnaires, telephone contacts and data from national archives. The 10-year postoperative prognosis of normal-weight patients (body mass index (BMI) 18.5–24.9 kg/m²) was inferior to that of overweight (BMI 25.0–29.9 kg/m²) and obese patients (BMI⩾30.0 kg/m²) and to the background population. Beyond 10 years the prognosis of obese patients deteriorated when compared with the overweight group. At the end of the 20-year follow-up, survival of the normal weight group was 0.68 (95% confidence interval (CI), 0.49–0.87; p<0.001), the overweight group 0.82 (95% CI, 0.71–0.92; p<0.001), and the obese group 0.67 (95% CI, 0.49–0.85; p<0.001), when compared with their background populations (=1.00). Obese patients developed diabetes more frequently and died more frequently of cardiovascular disease than patients in the two other study groups during the second postoperative decade (p<0.01).

During long-term follow-up the obesity paradox seems to disappear due to progression of cardiometabolic disease in patients who have undergone CABG.

Rheumatologic disorders are characterised by inflammation and an increased risk of coronary artery disease (CAD). However, the association between rheumatologic disorders and long-term prognosis in CAD patients undergoing percutaneous coronary intervention (PCI) is unknown. Thus, we aimed to examine the association between rheumatologic disorders and long-term prognosis in CAD patients undergoing PCI.

A post-hoc analysis was performed in 4605 patients (age: 63.3 ± 11.0 years; male: 76.6%) with ST-segment elevation myocardial infarction (STEMI; n = 1396), non-STEMI (n = 1541), and stable CAD (n = 1668) from the all-comer stent trials, the BAsel Stent Kosten-Effektivitäts Trial-PROspective Validation Examination (BASKET-PROVE) I and II trials. We evaluated the association between rheumatologic disorders and 2-year major adverse cardiac events (MACEs; cardiac death, nonfatal myocardial infarction (MI), and target vessel revascularisation (TVR)) by Cox regression analysis. Patients with rheumatologic disorders (n = 197) were older, more often female, had a higher prevalence of renal disease, multi-vessel coronary disease, and bifurcation lesions, and had longer total stent lengths. During the 2-year follow-up, the MACE rate was 8.6% in the total cohort. After adjustment for potential confounders, rheumatologic disorders were associated with MACEs in the total cohort (adjusted hazard ratio: 1.55; 95% confidence interval (CI): 1.04–2.31) driven by the STEMI subgroup (adjusted hazard ratio: 2.38; 95% CI: 1.26–4.51). In all patients, rheumatologic disorders were associated with all-cause death (adjusted hazard ratio: 2.05; 95% CI: 1.14–3.70), cardiac death (adjusted hazard ratio: 2.63; 95% CI: 1.27–5.43), and non-fatal MI (adjusted hazard ratio: 2.64; 95% CI: 1.36–5.13), but not with TVR (adjusted hazard ratio: 0.81; 95% CI: 0.41–1.58).

The presence of rheumatologic disorders appears to be independently associated with worse outcome in CAD patients undergoing PCI. This calls for further studies and focus on this high-risk group of patients following PCI.