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Atrial fibrillation (AF) is common in chronic heart failure (HF) patients and influences the choice and effects of drug and device therapy. In this large real-world HF registry, we studied whether the presence of AF affects the prescription of guideline-recommended HF therapy. We analyzed 8253 patients with chronic HF with reduced ejection fraction (HFrEF) from 34 Dutch outpatient clinics included in the period between 2013 and 2016 treated according to the 2012 ESC guidelines. 2109 (25.6%) of these patients were in AF (mean age 76.8 ± 9.2 years, 65.0% were men) and 6.144 (74.4%) had no AF (mean age 70.7 ± 12.2 years, 63.6% were men). Patients with AF more often received beta-blockers (81.7% vs. 79.7%, p = 0.04), MRAs (57.1% vs. 51.7%, p < 0.01), diuretics (89.7% vs. 80.6%, p < 0.01) and digoxin (40.1% vs. 9.3%, p < 0.01) compared to patients without AF, whereas they less often receive renin-angiotensin-system (RAS)-inhibitors (76.1% vs. 83.1%, p < 0.01). The number of patients who received beta-blockers, RAS-inhibitor and MRA at ≥50% of the recommended target dose was comparable between those with and without AF (16.6% vs. 15.2%, p = 0.07). In this large cohort of chronic HFrEF patients, the prevalence of AF was high and we observed significant differences in prescription of both guideline-recommended HF between patients with and without AF. • HFrEF patients with AF received more often beta-blockers, MRA, diuretics and digoxin. • HFrEF patients with AF received less often RAS-inhibitors. • More insight in the efficacy and adherence of HF therapy in AF patients is needed. [ABSTRACT FROM AUTHOR]

Abstract Background Whether the clinical presentation and in particular prevalence of symptoms and signs of heart failure (HF) is different in elderly versus younger patients and in those with reduced (HFrEF) versus preserved (HFpEF) left ventricular ejection fraction (LVEF) is a matter of ongoing debate. Aims To compare detailed clinical characteristics of these important subgroups and to develop a prediction rule for the differentiation of HFpEF and HFrEF based on clinical parameters. Methods The analysis was based on the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF) comprising 622 patients ≥60 years with HF including the whole LVEF spectrum. Results In the groups ≥75 years and with HFpEF typical symptoms and clinical signs of HF were more prevalent as compared to those <75 years or with HFrEF, respectively. The burden of comorbidities was higher in the older age group. HFrEF could not be differentiated from HFpEF by symptom history and clinical examination alone. However, a combination of age, presence of pulmonary rales, systolic blood pressure, cause of heart failure, osteoporosis, current smoking, NT-proBNP, haemoglobin, QRS width and heart rhythm allowed to identify HFrEF versus HFpEF with a sensitivity of 81% and specificity of 90% (c-statistics 0.91). Conclusions More symptoms and signs of HF were present both in the older age group and in patients with HFpEF. HFpEF versus HFrEF could be differentiated by a set of simple clinical, laboratory and ECG parameters but not by symptom history and physical examination alone. Highlights • Clinical presentation of heart failure was different in patients 60–74 vs ≥75 years. • Clinical presentation of heart failure was different in HFrEF vs HFpEF. • Symptoms and signs of HF were more prevalent in particular in the older age group. • HFrEF vs HFpEF could not be identified by symptom history and physical examination. • HFrEF vs HFrEF might be differentiated by clinical, laboratory and ECG parameters. [ABSTRACT FROM AUTHOR]

Abstract: Heart failure (HF) occurs when the adaptation mechanisms of the heart fail to compensate for stress factors, such as pressure overload, myocardial infarction, inflammation, diabetes, and cardiotoxic drugs, with subsequent ventricular hypertrophy, fibrosis, myocardial dysfunction, and chamber dilatation. Oxidative stress, defined as an imbalance between reactive oxygen species (ROS) generation and the capacity of antioxidant defense systems, has been authenticated as a pivotal player in the cardiopathogenesis of the various HF subtypes. The family of NADPH oxidases has been investigated as a key enzymatic source of ROS in the pathogenesis of HF. In this review, we discuss the importance of NADPH oxidase-dependent ROS generation in the various subtypes of HF and its implications. A better understanding of the pathogenic roles of NADPH oxidases in the failing heart is likely to provide novel therapeutic strategies for the prevention and treatment of HF. [Copyright &y& Elsevier]

Background: Drug-eluting stents (DESs) are associated with late stent thromboses, but the exact mechanism of action is unknown. Objective: The goal of this article was to assess the clinical interaction of glycoprotein IIb/IIIa inhibitors (GPIs) with different stent and vessel types in unselected patients undergoing percutaneous coronary intervention (PCI). Methods: This was a predefined retrospective analysis of the randomized controlled Basel Stent Kosten Effektivitats Trial (BASKET), which compared DES with bare-metal stents (BMSs) in patients undergoing PCI. Patients were compared for major adverse clinical events in relation to GPI use (abciximab and tirofiban) after 18 months. In a subgroup analysis prespecified in the study protocol, specific regard was given to angiographic groups at different risk levels for late events (high-risk vessels [ie, small vessels with a diameter <3.0 mm and saphenous vein grafts], and low-risk vessels [ie, large native vessels ≥3.0 mm]). Baseline differences between patients with or without GPI use were identified and incorporated into a multivariable Cox proportional hazards regression analysis if different at a <0.05 level. Results: A total of 826 patients (650 males, 176 females) were enrolled in BASKET; 301 (36%) received GPI therapy. Of these 301 patients, 255 (85%) received abciximab and 46 (15%) received tirofiban. After 18 months, the rate of cardiac death and nonfatal myocardial infarction was higher in patients with GPI use than in those without GPI use (35/301 [12%] vs 32/525 [6%]; P = 0.005). In patients undergoing PCI in anatomically low-risk vessels and receiving GPI therapy, there was a higher rate of cardiac death and nonfatal myocardial infarction at 18 months with a DES versus a BMS (22/151 [15%] vs 3/66 [5%]; P = 0.033). In patients undergoing PCI in anatomically low-risk vessels and without GPI therapy, there was no significant difference for cardiac death and nonfatal myocardial infarction (DES vs BMS, 11/207 [5%] vs 6/134 [4%]). In the multivariable analysis, GPI use (hazard ratio = 2.93; 95% CI, 1.53-5.63; P = 0.001) and age (hazard ratio = 1.034 per year increase; 95% CI, 1.008-1.062; P = 0.012) remained the only significant independent predictors of outcome. Interaction of stent type and GPI use was significant (P = 0.006). Conclusions: This retrospective analysis of the BASKET data found that GPIs and DESs used in patients with large native vessels may have an adverse interaction in terms of late stent thromboses. However, large prospective studies are needed to confirm these findings. [Copyright &y& Elsevier]

Objectives: We sought to define the incidence of late clinical events and late stent thrombosis in patients treated with drug-eluting (DES) versus bare-metal stents (BMS) after the discontinuation of clopidogrel as well as their timing and outcome. Background: There is growing concern that delayed endothelialization after DES implantation may lead to late stent thrombosis and related myocardial infarction (MI) or death. However, event rates and outcomes after clopidogrel discontinuation versus BMS are unknown. Methods: A consecutive series of 746 nonselected patients with 1,133 stented lesions surviving 6 months without major events were followed for 1 year after the discontinuation of clopidogrel. Patients were assigned randomly 2:1 to DES versus BMS in BASKET (Basel Stent Kosten Effektivitäts Trial). The primary focus of this observation was cardiac death/MI. Results: Rates of 18-month cardiac death/MI were not different between DES and BMS patients. However, after the discontinuation of clopidogrel (between months 7 and 18), these events occurred in 4.9% after DES versus 1.3% after BMS implantation. Target vessel revascularization remained lower after DES, resulting in similar rates of all clinical events for this time period (DES 9.3%, BMS 7.9%). Documented late stent thrombosis and related death/target vessel MI were twice as frequent after DES versus BMS (2.6% vs. 1.3%). Thrombosis-related events occurred between 15 and 362 days after the discontinuation of clopidogrel, presenting as MI or death in 88%. Conclusions: After the discontinuation of clopidogrel, the benefit of DES in reducing target vessel revascularization is maintained but has to be balanced against an increase in late cardiac death or nonfatal MI, possibly related to late stent thrombosis. [Copyright &y& Elsevier]

Orthostatic hypotension (OH) is associated with an increased risk of dementia, potentially attributable to cerebral hypoperfusion. We investigated which patterns and characteristics of OH are related to cognition or to potentially underlying structural brain injury in hemodynamically impaired patients and healthy reference participants. Participants with carotid occlusive disease or heart failure, and reference participants from the Heart-Brain Connection Study underwent OH measurements, neuropsychological assessment and brain MRI. We analyzed the association between OH, global cognitive functioning, white matter hyperintensity (WMH) volume and brain parenchymal fraction with linear regression. We stratified by participant group, severity and duration of OH, chronotropic incompetence and presence of orthostatic symptoms. Of 337 participants (mean age 67.3 ± 8.8 years, 118 (35.0%) women), 113 (33.5%) had OH. Overall, presence of OH was not associated with cognitive functioning (β: −0.12 [−0.24–0.00]), but we did observe worse cognitive functioning in those with severe OH (≥ 30/15 mmHg; β: −0.18 [−0.34 to −0.02]) and clinically manifest OH (β: −0.30 [−0.52 to −0.08]). These associations did not differ significantly by OH duration or chronotropic incompetence, and were similar between patient groups and reference participants. Similarly, both severe OH and clinically manifest OH were associated with a lower brain parenchymal fraction, and severe OH also with a somewhat higher WMH volume. Severe OH and clinically manifest OH are associated with worse cognitive functioning. This supports the notion that specific patterns and characteristics of OH determine its impact on brain health. • Effects of OH on brain health may differ by OH characteristics. • OH characteristics are severity, duration, chronotropic incompetence and symptoms. • Severe OH and clinically manifest OH are related to poorer cognitive functioning. • This coincided with a significantly lower brain parenchymal fraction. • Individuals with severe OH also tended to have larger WMH volumes. [ABSTRACT FROM AUTHOR]

Abstract: Background: Duty-cycled (DC) radiofrequency ablation (RFA) for atrial fibrillation (AF) has been introduced, however, data on large patient series and comparison to conventional RFA are scarce. Methods: Between 2006 and 2008DC RFA was performed in 209 consecutive patients (143 (68%) paroxysmal and 66 (32%) persistent AF). As controls served 211 patients, 155 (73%) with paroxysmal and 56 (27%) with persistent AF (p =0.3). In DC RFA, the pulmonary veins (PV) were isolated followed by ablation at the septum and left atrium, if AF persisted. Conventional PV isolation was followed by anatomical lines at the roof and mitral isthmus. Results: Freedom of paroxysmal AF was demonstrated after 1.08DC RFA procedures per patient in 82% and after 1.19 conventional procedures in 87% after 8.5±6.5months (ns). In persistent AF, success rates were 79% after 1.35DC RFA procedures and 80% after 1.34 conventional procedures after 11.5±8.5months (ns). The subgroup analysis of 119 patients with follow-up ≥12months (17.5 [14.1–23.6] months) showed similar results. Left atrial flutter occurred in 3% and 8% after paroxysmal AF ablation (p <0.05) and in 12% and 23% after persistent AF ablation (p =0.1). Multivariate predictors for success in both groups were age, left atrial size, presence of persistent vs. paroxysmal AF and previous pacemaker implantation, but not the ablation technique used. Non-fatal complications were seen in 2.8% with no differences between the groups. Conclusion: Outcome in DC RFA is similar to conventional RFA with a final success rate exceeding 80% in both paroxysmal and persistent AF in the absence of fatal complications. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to invasively investigate the hemodynamic response to exercise in patients with heart failure with normal ejection fraction (HFNEF) and to evaluate the ability of the peak early diastolic transmitral velocity to peak early diastolic annular velocity ratio (E/e′) to reflect exercise hemodynamics. Background: There is little information regarding the hemodynamic response to exercise in HFNEF. Methods: Patients with HFNEF (n = 14) and asymptomatic controls (n = 8) underwent right-side heart catheterization at rest and during supine cycle ergometer exercise and echocardiography with measurement of resting and peak exercise E/e′. Results: Resting pulmonary capillary wedge pressure (PCWP) (10 ± 4 mm Hg vs. 10 ± 4 mm Hg; p = 0.94) was similar in HFNEF patients and controls, but stroke volume index (SVI) (p = 0.02) was lower, and systemic vascular resistance index (SVRI) (p = 0.01) was higher in patients. Patients stopped exercise at lower work rate (0.63 ± 0.29 W/kg vs. 1.13 ± 0.49 W/kg; p = 0.006). Although peak exercise PCWP was similar in both groups (23 ± 6 mm Hg vs. 20 ± 7 mm Hg; p = 0.31), the peak PCWP/work rate ratio was higher in patients compared with controls (46 ± 31 mm Hg/W/kg vs. 20 ± 9 mm Hg/W/kg; p = 0.03). Peak exercise SVI (p = 0.001) was lower and SVRI was higher (p = 0.01) in patients. Resting E/e′ was modestly elevated in patients (13.2 ± 4.1 vs. 9.5 ± 3.4; p = 0.04). Peak exercise E/e′ did not differ between the groups (11.1 ± 3.4 vs. 9.4 ± 3.4; p = 0.28). Conclusions: The HFNEF patients achieved a similar peak exercise PCWP to that of asymptomatic controls, at a much lower workload. This occurs at a lower SVI and in the setting of higher SVRI. The E/e′ does not reflect the hemodynamic changes during exercise in HFNEF patients. [Copyright &y& Elsevier]

Patients with heart failure (HF) are at risk for vascular brain injury. Cerebral cortical microinfarcts (CMIs) are a novel MRI marker of vascular brain injury. This study aims to determine the occurrence of CMIs in patient with HF and their clinical correlates, including haemodynamic status. From the Heart-Brain Study, a multicenter prospective cohort study, 154 patients with clinically stable HF without concurrent atrial fibrillation (mean age 69.5 ± 10.1, 32% female) and 124 reference participants without HF (mean age 65.6 ± 7.4, 47% females) were evaluated for CMIs on 3 T MRI. CMI presence in HF was tested for associations with vascular risk profile, cardiac function and history, MRI markers of vascular brain injury and cognitive profile. CMI occurrence was higher in patient with HF (17%) than reference participants (7%); after correction for age and sex OR 2.5 [95% CI 1.1–6.0] p =.032; after additional correction for vascular risk factors OR 2.7 [1.0–7.1] p =.052. In patients with HF, CMI presence was associated with office hypertension (OR 2.7 [1.2–6.5] p =.021) and a lower cardiac index (B = -0.29 [−0.55−−0.04] p =.023 independent of vascular risk factors), but not with cause or duration of HF. Presence of CMIs was not associated with cognitive performance in patients with HF. CMIs are a common occurrence in patients with HF and related to an adverse vascular risk factor profile and severity of cardiac dysfunction. CMIs thus represent a novel marker of vascular brain injury in these patients. • Heart failure is associated with an increased risk for vascular brain injury and cognitive impairment. • Cerebral cortical microinfarcts (CMIs) are a novel MRI-marker of vascular brain injury that is associated with reduced cerebral blood flow and predicts cognitive decline. • In this cohort study we demonstrate that CMIs are very common in patients with heart failure and related to severity of cardiac pump-dysfunction. • Future research must indicate whether CMIs predict cognitive decline over time in patients with heart failure. [ABSTRACT FROM AUTHOR]

Background: Patients with non-ST-segment elevation myocardial infarction and elevated high-sensitivity cardiac troponin levels often routinely undergo invasive coronary angiography (ICA), but many do not have obstructive coronary artery disease.Objectives: This study investigated whether cardiovascular magnetic resonance imaging (CMR) or computed tomographic angiography (CTA) may serve as a safe gatekeeper for ICA.Methods: This randomized controlled trial (NCT01559467) in 207 patients (age 64 years; 62% male patients) with acute chest pain, elevated high-sensitivity cardiac troponin T levels (>14 ng/l), and inconclusive electrocardiogram compared a CMR- or CTA-first strategy with a control strategy of routine clinical care. Follow-up ICA was recommended when initial CMR or CTA suggested myocardial ischemia, infarction, or obstructive coronary artery disease (≥70% stenosis). Primary efficacy and secondary safety endpoints were referral to ICA during hospitalization and 1-year outcomes (major adverse cardiac events and complications), respectively.Results: The CMR- and CTA-first strategies reduced ICA compared with routine clinical care (87% [p = 0.001], 66% [p < 0.001], and 100%, respectively), with similar outcome (hazard ratio: CMR vs. routine, 0.78 [95% confidence interval: 0.37 to 1.61]; CTA vs. routine, 0.66 [95% confidence interval: 0.31 to 1.42]; and CMR vs. CTA, 1.19 [95% confidence interval: 0.53 to 2.66]). Obstructive coronary artery disease after ICA was found in 61% of patients in the routine clinical care arm, in 69% in the CMR-first arm (p = 0.308 vs. routine), and in 85% in the CTA-first arm (p = 0.006 vs. routine). In the non-CMR and non-CTA arms, follow-up CMR and CTA were performed in 67% and 13% of patients and led to a new diagnosis in 33% and 3%, respectively (p < 0.001).Conclusions: A novel strategy of implementing CMR or CTA first in the diagnostic process in non-ST-segment elevation myocardial infarction is a safe gatekeeper for ICA. [ABSTRACT FROM AUTHOR]

Background: Soluble suppression of tumorigenesis-2 (sST2) is a biomarker related to inflammation and fibrosis.Objectives: This study assessed the independent prognostic value of sST2 in chronic heart failure (HF).Methods: Individual patient data from studies that assessed sST2 for risk prediction in chronic HF, together with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT), were retrieved.Results: A total of 4,268 patients were evaluated (median age 68 years, 75% males, 65% with ischemic HF, 87% with left ventricular ejection fraction [LVEF] <40%). NT-proBNP, hs-TnT, and sST2 were 1,360 ng/l (interquartile interval: 513 to 3,222 ng/l), 18 ng/l (interquartile interval: 9 to 33 ng/l), and 27 ng/l (interquartile interval: 20 to 39 ng/l), respectively. During a 2.4-year median follow-up, 1,319 patients (31%) experienced all-cause death (n = 932 [22%] for cardiovascular causes). Among the 4,118 patients (96%) with available data, 1,029 (24%) were hospitalized at least once for worsening HF over 2.2 years. The best sST2 cutoff for the prediction of all-cause and cardiovascular death and HF hospitalization was 28 ng/ml, with good performance at Kaplan-Meier analysis (log-rank: 117.6, 61.0, and 88.6, respectively; all p < 0.001). In a model that included age, sex, body mass index, ischemic etiology, LVEF, New York Heart Association functional class, glomerular filtration rate, HF medical therapy, NT-proBNP, and hs-TnT, the risk of all-cause death, cardiovascular death, and HF hospitalization increased by 26%, 25%, and 30%, respectively, per each doubling of sST2. sST2 retained its independent prognostic value across most population subgroups.Conclusions: sST2 yielded strong, independent predictive value for all-cause and cardiovascular mortality, and HF hospitalization in chronic HF, and deserves consideration to be part of a multimarker panel together with NT-proBNP and hs-TnT. [ABSTRACT FROM AUTHOR]

Background In-depth analyses of the measurement properties of the 6-minute walk test (6MWT) in patients with chronic heart failure (CHF) are lacking. We investigated the reliability, construct validity, and determinants of the distance covered in the 6MWT (6MWD) in CHF patients. Methods 337 patients were studied (median age 65 years, 70% male, ejection fraction 35%). Participants performed two 6MWTs on subsequent days. Demographics, anthropometrics, clinical data, ejection fraction, maximal exercise capacity, body composition, lung function, and symptoms of anxiety and depression were also assessed. Construct validity was assessed in terms of convergent, discriminant and known-groups validity. Stepwise linear regression was used. Results 6MWT was reliable (ICC = 0.90, P < 0.0001). The learning effect was 31 m (95%CI 27, 35 m). Older age (≥ 65 years), lower lung diffusing capacity (< 80% predicted) and higher NYHA class (NYHA III) were associated with a lower likelihood of a meaningful increase in the second test (OR 0.45–0.56, P < 0.05 for all). The best 6MWD had moderate-to-good correlations with peak exercise capacity ( r s = 0.54–0.69) and no-to-fair correlations with body composition, lung function, ejection fraction, and symptoms of anxiety and depression ( r s = 0.04–0.49). Patients with higher NYHA classes had lower 6MWD. 6MWD was independently associated with maximal power output during maximal exercise, estimated glomerular filtration rate and age (51.7% of the variability). Conclusion 6MWT was found to be reliable and valid in patients with mild-to-moderate CHF. Maximal exercise capacity, renal function and age were significant determinants of the best 6MWD. These findings strengthen the clinical utility of the 6MWT in CHF. [ABSTRACT FROM AUTHOR]

This study examined associations of neighbourhood walkability with cognitive functioning (i.e., global cognition, memory, language, attention-psychomotor speed, and executive functioning) in participants without or with either heart failure, carotid occlusive disease, or vascular cognitive impairment. Neighbourhood walkability at baseline was positively associated with global cognition and attention-psychomotor speed. These associations were stronger in patients with vascular cognitive impairment. Individuals who live in residential areas with higher walkability levels were less likely to have impairments in language and executive functioning at two-year follow-up. These findings highlight the importance of the built environment for cognitive functioning in healthy and vulnerable groups. • We assessed associations of neighbourhood walkability with cognitive functioning. • We did this in reference participants and various heart-brain axis patient groups. • Walkability was positively cross-sectionally associated with global cognition. • Higher walkability lowered the odds of impaired executive functioning at follow-up. • Some associations were stronger in patients with vascular cognitive impairment. [ABSTRACT FROM AUTHOR]

Background Prediction of events in chronic heart failure (CHF) patients is still difficult and available scores are often complex to calculate. Therefore, we developed and validated a simple-to-use, multidimensional prognostic index for such patients. Methods A theoretical model was developed based on known prognostic factors of CHF that are easily obtainable: Body mass index (B), Age (A), Resting systolic blood pressure (R), Dyspnea (D), N-termInal pro brain natriuretic peptide (NT-proBNP) (I), Cockroft-Gault equation to estimate glomerular filtration rate (C), resting Heart rate (H), and Exercise performance using the 6-min walk test (E) (the BARDICHE-index). Scores were given for all components and added, the sum ranging from 1 (lowest value) to 25 points (maximal value), with estimated risk being highest in patients with highest scores. Scores were categorized into three groups: a low (≤ 8 points); medium (9–16 points), or high (> 16 points) BARDICHE-score. The model was validated in a data set of 1811 patients from two prospective CHF-cohorts (median follow-up 887 days). The primary outcome was 5-year all-cause survival. Secondary outcomes were 5-year survival without all-cause hospitalization and 5-year survival without CHF-related hospitalization. Results There were significant differences between BARDICHE-risk groups for mortality (hazard ratio = 3.63 per BARDICHE-group, 95%-CI 3.10–4.25), mortality or all-cause hospitalization (HR = 2.00 per BARDICHE-group, 95%-CI 1.83–2.19), and mortality or CHF-related hospitalization (HR = 3.43 per BARDICHE-group, 95%-CI 3.01–3.92; all P < 10–50). Outcome was predicted independently of left ventricular ejection fraction (LVEF) and gender. Conclusions The BARDICHE-index is a simple multidimensional prognostic tool for patients with CHF, independently of LVEF. [ABSTRACT FROM AUTHOR]

Background Cardiac remodeling and its reversibility are key in HF outcomes. The ST2-R2 score was recently developed to predict relevant left ventricular (LV) reverse remodeling (R2) in patients with heart failure (HF). In the present study we sought to validate the ST2-R2 score for grading improvement in LV ejection fraction (EF) and LV size at one year, and to evaluate its prognostic implication up to 4 years. Methods A total of 569 patients with baseline LVEF < 40% from three international cohorts (Barcelona, TIME-CHF, and PROTECT) were included in the study. Patients were classified into four strata based on their ST2-R2 score, which took into account concentrations of the biomarker ST2, non-ischemic etiology, absence of left bundle branch block, HF duration, baseline LVEF, and β-blocker treatment. Results A significant relationship was observed between ST2-R2 scores and changes in LVEF and indexed LV sizes. LVEF recovery (from + 5.6% to + 17.3%; p < 0.001), percentage reduction in LV end-systolic volume index (from − 6.1% to − 32.1%; p < 0.001) and in LV end-systolic diameter index (from − 1.1% to − 18.6%; p < 0.001) increased over the ST2-R2 strata. A similar trend was observed with diastolic parameters. Improvement in LV function and size was inversely predictive of mortality. Hazard ratios for risk of death, using the lower ST2-R2 score strata (< 9) as a reference, were 0.49 (p < 0.001; score 9–11), 0.27 (p < 0.001; score 12–14), and 0.17 (p < 0.001; score 15–17). Conclusions The ST2-R2 score predicts reverse LV remodeling in HF patients and is useful for predicting mortality up to 4 years. [ABSTRACT FROM AUTHOR]

Objective Cardiac troponins T (cTnT) and I (cTnI) are the preferred biomarkers to detect myocardial damage. The present study explores the value of measuring cardiac troponins (cTn) in nursing home residents, by investigating its relation to heart failure and 1-year mortality using 1 cTnT and 2 cTnI assays that are widely used in clinical practice. Design All participants underwent extensive clinical examinations and echocardiographic assessment for the diagnosis of heart failure. cTn was measured using high-sensitive (hs)- cTnT (Roche), hs-cTnI (Abbott), and sensitive cTnI (Beckman) assays. The glomerular filtration rate was estimated (eGFR) using serum creatinine and cystatin C concentrations. Data on all-cause mortality were collected at 1-year follow-up. Participants and Setting Participants were 495 long-term nursing home residents, older than 65 years, of 5 Dutch nursing home organizations. Results Median (IQR) concentrations were 20.6 (17.8–30.6), 6.8 (4.1–12.5), and 4.0 (2.0–8.0) ng/L for hs-cTnT, hs-cTnI, and cTnI, respectively. In total, 79% had elevated hs-cTnT concentrations, whereas only 9% and 5% of hs-cTnI and cTnI concentrations were elevated. Most important and independent determinants for higher hs-cTnT and hs-cTnI concentrations were heart failure and renal dysfunction. Whereas both heart failure (odds ratio [OR] 3.4) and eGFR lower than 60 mL/min/1.73 m 2 (OR 3.6) were equal contributors to higher hs-cTnT concentrations (all P < .001), hs-cTnI and cTnI were less associated with renal dysfunction (OR of, respectively, 1.9 and 2.1; P < .01) in comparison with heart failure (OR 4.3 and 4.7, respectively, P < .001). Furthermore, residents with higher hs-cTnT or hs-cTnI concentrations (fourth quartile) had respectively 4 versus 2 times more risk of 1-year mortality compared with lower concentrations. Conclusion Regardless of their cardiac health, hs-cTnT but not hs-cTnI concentrations were elevated in almost all aged nursing home residents, questioning the use of the current diagnostic cutoff in elderly with high comorbidity. Nonetheless, measuring cardiac troponins, especially hs-cTnT, had a promising role in assessing future risk of mortality. [ABSTRACT FROM AUTHOR]

Background: The multifactorial pathogenesis leading to dilated cardiomyopathy (DCM) makes stratification difficult. The recent MOGE(S) (morphofunctional, organ involvement, genetic or familial, etiology, stage) classification addresses this issue.Objectives: The purpose of this study was to investigate the applicability and prognostic relevance of the MOGE(S) classification in patients with DCM.Methods: This study used patients from the Maastricht Cardiomyopathy Registry in the Netherlands and excluded patients with ischemic, valvular, hypertensive, and congenital heart disease. All other patients underwent a complete diagnostic work-up, including genetic evaluation and endomyocardial biopsy.Results: A total of 213 consecutive patients with DCM were included: organ involvement was demonstrated in 35 (16%) and genetic or familial DCM in 70 (33%) patients, including 16 (8%) patients with a pathogenic mutation. At least 1 cause was found in 155 (73%) patients, of whom 48 (23%) had more than 1 possible cause. Left ventricular reverse remodeling was more common in patients with nongenetic or nonfamilial DCM than in patients with genetic or familial DCM (40% vs. 25%; p = 0.04). After a median follow-up of 47 months, organ involvement and higher New York Heart Association functional class were associated with adverse outcome (p < 0.001 and p = 0.02, respectively). Genetic or familial DCM per se was of no prognostic significance, but when it was accompanied by additional etiologic-environmental factors such as significant viral load, immune-mediated factors, rhythm disturbances, or toxic triggers, a worse outcome was revealed (p = 0.03). A higher presence of MOGE(S) attributes (≥2 vs. ≤1 attributes) showed an adverse outcome (p = 0.007).Conclusions: The MOGE(S) classification in DCM is applicable, and each attribute or the gene-environment interaction is associated with outcome. Importantly, the presence of multiple attributes was a strong predictor of adverse outcome. Finally, adaptation of the MOGE(S) involving multiple possible etiologies is recommended. [ABSTRACT FROM AUTHOR]

Objectives: The study aim was to determine the prognostic value of a multimarker strategy for risk-assessment in patients presenting to the emergency department (ED) with dyspnea. Background: Combining biomarkers with different pathophysiological backgrounds may improve risk stratification in dyspneic patients in the ED. Methods: The study prospectively investigated the prognostic value of the biomarkers N-terminal pro–B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), Cystatin-C (Cys-C), high-sensitivity C-reactive protein (hs-CRP), and Galectin-3 (Gal-3) for 90-day mortality in 603 patients presenting to the ED with dyspnea as primary complaint. Results: hs-CRP, hs-cTnT, Cyst-C, and NT-proBNP were independent predictors of 90-day mortality. The number of elevated biomarkers was highly associated with outcome (odds ratio: 2.94 per biomarker, 95% confidence interval [CI]: 2.29 to 3.78, p < 0.001). A multimarker approach had incremental value beyond a single-marker approach. Our multimarker emergency dyspnea-risk score (MARKED-risk score) incorporating age ≥75 years, systolic blood pressure <110 mm Hg, history of heart failure, dyspnea New York Heart Association functional class IV, hs-cTnT ≥0.04 μg/l, hs-CRP ≥25 mg/l, and Cys-C ≥1.125 mg/l had excellent prognostic performance (area under the curve: 0.85, 95% CI: 0.81 to 0.89), was robust in internal validation analyses and could identify patients with very low (<3 points), intermediate (≥3, <5 points), and high risk (≥5 points) of 90-day mortality (2%, 14%, and 44% respectively; p < 0.001). Conclusions: A multimarker strategy provided superior risk stratification beyond any single-marker approach. The MARKED-risk score that incorporates hs-cTnT, hs-CRP, and Cys-C along with clinical risk factors accurately identifies patients with very low, intermediate, and high risk. [ABSTRACT FROM AUTHOR]

Hyperkalemia is a concern in heart failure (HF), especially in older patients with co-morbidities. Previous studies addressing this issue have focused mainly on younger patients. This study was aimed at determining the frequency and predictors of hyperkalemia in older patients with HF undergoing intense medical therapy. Frequency and predictors of hyperkalemia were defined in patients (n = 566) participating in the Trial of Intensified versus Standard Medical Therapy in Elderly Patients with Congestive Heart Failure, in which patients ≥60 years of age were randomized to a standard versus an intensified N-terminal brain natriuretic peptide-guided HF therapy. During an 18-month follow-up 76 patients (13.4%) had hyperkalemia (≥5.5 mmol/L) and 28 (4.9%) had severe hyperkalemia (≥6.0 mmol/L). Higher baseline serum potassium (odds ratio [OR] 2.92 per mmol/L), baseline creatinine (OR 1.11 per 10 μmol/L), gout (OR 2.56), New York Heart Association (NYHA) class (compared to NYHA class II, IV OR 3.08), higher dosage of spironolactone at baseline (OR 1.20 per 12.5 mg/day), and higher dose changes of spironolactone (compared to no dose change: 12.5 mg, OR 1.45; 25 mg, OR 2.52; >25 mg, OR 3.24) were independent predictors for development of hyperkalemia (p <0.05 for all comparisons). In conclusion, hyperkalemia is common in patients ≥60 years of age with HF undergoing intense medical therapy. Risk is increased in patients treated with spironolactone, in addition to patient-specific risk factors such as chronic kidney disease, higher serum potassium, advanced NYHA class, and gout. Careful surveillance of serum potassium and cautious use of spironolactone in patients at risk may help to decrease the incidence of potentially hazardous complications caused by hyperkalemia. [Copyright &y& Elsevier]

Objectives: This study sought to define the importance of 5-year coronary artery disease (CAD) progression after successful stenting. Background: Safety concerns regarding first-generation drug-eluting stents mandate 5-year follow-up studies. However, only limited data exist on the long-term importance of CAD progression relative to late stent–related problems. Methods: This study followed for 5 years, 428 consecutive patients randomized to drug-eluting versus bare-metal stents with successful stenting documented by freedom from symptoms/events and no ischemic perfusion defects (PDs) after 6 months. Rest/stress scintigraphic scans were repeated after 60 months. Late events and new PDs in areas remote from stented vessels indicated CAD progression. Results: During follow-up, 110 of 428 (25.7%) patients had 150 clinical events: 43 patients (10%) died, 36 (8.4%) suffered a myocardial infarction, and 71 (16.6%) needed repeat revascularization. Event rates were lower in remote versus target-vessel areas (9.8% vs. 14.3%, p = 0.019). Remote myocardial infarction and repeat revascularization accounted for 46 of 124 (37.1%) nonfatal events and were similar for both stent types. Five-year scintigraphic studies in patients without follow-up events showed 23.3% new PDs, 71% of which were asymptomatic. Remote defects accounted for 37.5% PDs and were similar for both stent types. Conclusions: Even 5 years after stenting, target-vessel events and/or new PDs remained more frequent than CAD progression assessed by remote events and/or new PDs. Still, remote events accounted for almost 40% of all events with a similar rate of additional new PDs, often silent, and independent of stent type. This documents the importance of CAD progression and stresses the need to differentiate remote from target-vessel events/PDs in long-term stent safety studies. (Basel Stent Kosten-Effektivitäts Trial [BASKET]; ISRCTN75663024) [Copyright &y& Elsevier]

Objectives: We aimed to compare the hemodynamic effects of right-atrial-paced (DDD) and right-atrial-sensed (VDD) biventricular paced rhythm on cardiac resynchronization therapy (CRT). Background: Cardiac resynchronization therapy improves hemodynamics in patients with severe heart failure and left ventricular (LV) dyssynchrony. However, the impact of active right atrial pacing on resynchronization therapy is unknown. Methods: Seventeen CRT patients were studied 10 months (range: 1 to 46 months) after implantation. At baseline, the programmed atrioventricular delay was optimized by timing LV contraction properly at the end of atrial contraction. In both modes the acute hemodynamic effects were assessed by multiple Doppler echocardiographic parameters. Results: Compared to DDD pacing, VDD pacing resulted in much better improvement of intraventricular dyssynchrony assessed by the septal-to-posterior wall motion delay (VDD 106 ± 83 ms vs. DDD 145 ± 95 ms; p = 0.001), whereas the interventricular mechanical delay (difference between onset of pulmonary and aortic outflow) did not differ (VDD 20 ± 21 ms vs. DDD 18 ± 17 ms; p = NS). Furthermore, VDD pacing significantly prolonged the rate-corrected LV filling period (VDD 458 ± 123 ms vs. DDD 371 ± 94 ms; p = 0.0001) and improved the myocardial performance index (VDD 0.60 ± 0.18 vs. DDD 0.71 ± 0.23; p &#60; 0.01). Conclusions: Our findings suggest that avoidance of right atrial pacing results in a higher degree of LV resynchronization, in a substantial prolongation of the LV filling period, and in an improved myocardial performance. Thus, the VDD mode seems to be superior to the DDD mode in CRT patients. [Copyright &y& Elsevier]

Objectives: This study investigated the combination of maximal and low-intensity exercise testing in predicting prognosis in chronic heart failure (CHF), using one single exercise test (two-step protocol).Background: Risk assessment based on any single factor has limited accuracy and reproducibility.Methods: Treadmill exercise testing was performed in 202 consecutive CHF patients (174 male; mean age 52 +/- 11 years) using "breath-by-breath" gas exchange monitoring. Oxygen uptake (VO(2)) kinetics were defined as oxygen deficit (DeltaVO(2) x time [rest to steady state] - Sigma VO(2) [rest to steady state]) and mean response time (MRT = oxygen-deficit/DeltaVO(2)). Peak VO(2) (VO(2)max) was defined as the highest VO(2). Mean follow-up was 873 +/- 628 days. The primary end point was cardiac mortality and the need for urgent heart transplantation.Results: Forty-four patients (22%) died and 15 (7%) were urgently transplanted. In both univariate and multivariate analyses, MRT >50 s was the most powerful predictor of the primary end point (hazard ratio [HR] 4.44), followed by predicted VO(2)max <50% (HR 3.50) and resting systolic blood pressure <105 mm Hg (HR 2.49, all p < 0.001). A majority (n = 130 [64%]) had one or none of these risk factors, with a one-year event rate of only 3%. Patients with two risk factors (n = 45 [22%]) were at medium risk (one-year event rate of 33%). Twenty-seven patients (13%) had all three risk factors, with a one-year event rate of 59%. The area under the curve, using the number of risk factors, was 0.86 +/- 0.04 for the primary end point at one year. These results were independent of medication, in particular, beta-blockade.Conclusions: A combination of low-intensity and maximal exercise test results improves assessment of prognosis in patients with CHF. [ABSTRACT FROM AUTHOR]

: ObjectivesThis study investigated the combination of maximal and low-intensity exercise testing in predicting prognosis in chronic heart failure (CHF), using one single exercise test (two-step protocol).: BackgroundRisk assessment based on any single factor has limited accuracy and reproducibility.: MethodsTreadmill exercise testing was performed in 202 consecutive CHF patients (174 male; mean age 52 ± 11 years) using “breath-by-breath” gas exchange monitoring. Oxygen uptake (Vo2) kinetics were defined as oxygen deficit (ΔVo2 × time [rest to steady state] − Σ Vo2 [rest to steady state]) and mean response time (MRT = oxygen-deficit/ΔVo2). Peak Vo2 (Vo2max) was defined as the highest Vo2. Mean follow-up was 873 ± 628 days. The primary end point was cardiac mortality and the need for urgent heart transplantation.: ResultsForty-four patients (22%) died and 15 (7%) were urgently transplanted. In both univariate and multivariate analyses, MRT >50 s was the most powerful predictor of the primary end point (hazard ratio [HR] 4.44), followed by predicted Vo2max <50% (HR 3.50) and resting systolic blood pressure <105 mm Hg (HR 2.49, all p < 0.001). A majority (n = 130 [64%]) had one or none of these risk factors, with a one-year event rate of only 3%. Patients with two risk factors (n = 45 [22%]) were at medium risk (one-year event rate of 33%). Twenty-seven patients (13%) had all three risk factors, with a one-year event rate of 59%. The area under the curve, using the number of risk factors, was 0.86 ± 0.04 for the primary end point at one year. These results were independent of medication, in particular, beta-blockade.: ConclusionsA combination of low-intensity and maximal exercise test results improves assessment of prognosis in patients with CHF. [Copyright &y& Elsevier]