Kevin Duarte

Prognostic Value of Estimated Plasma Volume in Heart Failure

OBJECTIVES The purpose of this study was to assess the prognostic value of the estimation of plasma volume or of its variation beyond clinical examination in a post-hoc analysis of EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study). BACKGROUND Assessing congestion after discharge is challenging but of paramount importance to optimize patient management and to prevent hospital readmissions. METHODS The present analysis was performed in a subset of 4,957 patients with available data (within a full dataset of 6,632 patients). The study endpoint was cardiovascular death or hospitalization for heart failure (HF) between months 1 and 3 after post-acute myocardial infarction HF. Estimated plasma volume variation (ΔePVS) between baseline and month 1 was estimated by the Strauss formula, which includes hemoglobin and hematocrit ratios. Other potential predictors, including congestion surrogates, hemodynamic and renal variables, and medical history variables, were tested. An instantaneous estimation of plasma volume at month 1 was defined and also tested. RESULTS Multivariate analysis was performed with stepwise logistic regression. ΔePVS was selected in the model (odds ratio: 1.01; p = 0.004). The corresponding prognostic gain measured by integrated discrimination improvement was significant (7.57%; p = 0.01). Nevertheless, instantaneous estimation of plasma volume at month 1 was found to be a better predictor than ΔePVS. CONCLUSIONS In HF complicating myocardial infarction, congestion as assessed by the Strauss formula and an instantaneous derived measurement of plasma volume provided a predictive value of early cardiovascular events beyond routine clinical assessment. Prospective trials to assess congestion management guided by this simple tool to monitor plasma volume are warranted.

Serum Chloride and Sodium Interplay in Patients With Acute Myocardial Infarction and Heart Failure With Reduced Ejection Fraction: An Analysis From the High-Risk Myocardial Infarction Database Initiative.

Background— Serum chloride levels were recently found to be independently associated with mortality in heart failure (HF). Methods and Results— We investigated the relationship between serum chloride and clinical outcomes in 7195 subjects with acute myocardial infarction complicated by reduced left ventricular function and HF. The studied outcomes were all-cause mortality, cardiovascular mortality, and hospitalization for HF. Both chloride and sodium had a nonlinear association with the studied outcomes (P<0.05 for linearity). Patients in the lowest chloride tertile (chloride ⩽100) were older, had more comorbidities, and had lower sodium levels (P<0.05 for all). Serum chloride showed a significant interaction with sodium with regard to all studied outcomes (P for interaction <0.05 for all). The lowest chloride tertile (⩽100 mmol/L) was associated with increased mortality rates in the context of lower sodium (⩽138 mmol/L; adjusted hazard ratio [95% confidence interval] for all-cause mortality=1.42 (1.14–1.77); P=0.002), whereas in the context of higher sodium levels (>141 mmol/L), the association with mortality was lost. Spline-transformed chloride and its interaction with sodium did not add significant prognostic information on top of other well-established prognostic variables (P>0.05 for all outcomes). Conclusions— In post–myocardial infarction with systolic dysfunction and HF, low serum chloride was associated with mortality (but not hospitalization for HF) in the setting of lower sodium. Overall, chloride and its interaction with sodium did not add clinically relevant prognostic information on top of other well-established prognostic variables. Taken together, these data support an integrated and critical consideration of chloride and sodium interplay.

Association between mean systolic and diastolic blood pressure throughout the follow-up and cardiovascular events in acute myocardial infarction patients with systolic dysfunction and/or heart failure: an analysis from the High-Risk Myocardial Infarction Database Initiative

Observational data have described the association of blood pressure (BP) with mortality as ‘J‐shaped’, meaning that mortality rates increase below a certain BP threshold. We aimed to analyse the associations between BP and prognosis in a population of acute myocardial infarction (MI) patients with heart failure (HF) and/or systolic dysfunction.

Sequential linear regression with online standardized data

The present study addresses the problem of sequential least square multidimensional linear regression, particularly in the case of a data stream, using a stochastic approximation process. To avoid the phenomenon of numerical explosion which can be encountered and to reduce the computing time in order to take into account a maximum of arriving data, we propose using a process with online standardized data instead of raw data and the use of several observations per step or all observations until the current step. Herein, we define and study the almost sure convergence of three processes with online standardized data: a classical process with a variable step-size and use of a varying number of observations per step, an averaged process with a constant step-size and use of a varying number of observations per step, and a process with a variable or constant step-size and use of all observations until the current step. Their convergence is obtained under more general assumptions than classical ones. These processes are compared to classical processes on 11 datasets for a fixed total number of observations used and thereafter for a fixed processing time. Analyses indicate that the third-defined process typically yields the best results.

Individualizing treatment choices in the systolic blood pressure intervention trial.

Background: Any treatment decision should be tailored to the individual patients‘ characteristics. A personalized approach aims to help better selecting the patients who are likely to benefit most from a treatment decision. In the systolic blood pressure intervention trial, intensive treatment reduced the rate of major cardiovascular events, but increased the rate of serious adverse events (SAEs). Objectives: To assess the trade-off between efficacy and safety to simultaneously quantify an individual patients absolute benefit and absolute harm, helping clinicians making better therapeutic choices in daily practice. Methods: Multivariable Poisson regression models were used to identify independent risk factors for: primary composite cardiovascular outcome and major SAEs = safety. Estimates from the models were used to quantify each individual risk. Results: Subclinical cardiovascular disease, number of antihypertensive agents, current smoking, age, urine albumin-to-creatinine ratio, and serum creatinine were associated with increased risk of both primary outcome events and SAEs. Triglycerides were associated with increased primary outcome events only, and chronic kidney disease and female sex with SAEs only. The models were well calibrated and showed good performance (c-index for safety = 0.69 and c-index for efficacy = 0.72). For the primary outcome, there is a steep gradient in risk by fifths of the predicted model and a similar gradient exists for the safety outcome predicted model. Mortality within 1 year of an efficacy outcome (as assessed by the Kaplan–Meier method) was nearly three-fold higher than following a safety outcome (21.9 vs. 7.5%). If one judges the clinical importance of efficacy and safety outcomes based on their 1-year mortality, then there is a net benefit of intensive therapy for almost all patients. Conclusion: Antihypertensive treatment intensification is associated with lower cardiovascular event rates; however, it increases the risk of adverse events. However, having adverse events has less weight when it comes to therapeutic decisions and antihypertensive therapy intensification is beneficial for the great majority of patients included in the systolic blood pressure intervention trial.

Relationship between left ventricular ejection fraction and mortality after myocardial infarction complicated by heart failure or left ventricular dysfunction

BACKGROUND Identifying risk factors for specific modes of death in patients with heart failure (HF) or left ventricular (LV) dysfunction after acute myocardial infarction (MI) may help to avert events. We sought to evaluate LV ejection fraction (LVEF) as a prognosticator of specific death modes. METHODS AND RESULTS In an individual patient data meta-analysis of four merged trials (CAPRICORN, EPHESUS, OPTIMAAL, and VALIANT), Cox modelling was performed to study the association between baseline LVEF from 19,740 patients and types of death during follow-up. Over a median follow-up of 707 days 3419 deaths occurred. The distribution pattern for mode of death was similar across categories (LVEF < 25%, LVEF 25-35%, and LVEF > 35%). In multivariable models, the risk of all types of death increased with decreasing LVEF. If compared to LVEF > 35%, LVEF < 25% was associated with a 113% increased risk of sudden death (hazard ratio (HR) 2.13, 95% confidence interval (CI) 1.53-2.98), a 170% increased risk of HF death (HR 2.70, 95% CI 1.83-3.98), a 66% increased risk of other cardiovascular (CV) death (HR 1.66, 95% CI 1.14-2.42), and a 90% increased risk of non CV death (HR 1.90, 95% CI 1.15-3.14). CONCLUSION In patients with HF or LV dysfunction after acute MI, low LVEF is a ubiquitous risk marker associated with death regardless of type. The different modes of death are fairly equally represented throughout the categories of LVEF and sudden death remains a significant mode of death also in patients with LVEF > 35%.

Hyperkalaemia prevalence, recurrence and management in chronic haemodialysis: a prospective multicentre French regional registry 2-year survey

Background Observational studies have reported increased mortality rates in hyperkalaemic or hypokalaemic chronic haemodialysis patients. This study assessed the prevalence and recurrence of hyperkalaemia (HK) along with the concomitant prescription of low-potassium (K) dialysis baths and of K-binding agents in a registry within a French regional disease management programme. Methods This was a prospective multicentre (14 chronic haemodialysis centres, Lorraine Region) study encompassing 527 chronic haemodialysis patients followed from 2 January 2014 to 31 December 2015. Predialysis serum K (14 734) measurements, dialysis bath K concentrations and concomitant K binder prescriptions were collected with an electronic health record system. Results At baseline, 26.4%, 13.8% and 4.9% of patients were hyperkalaemic (i.e. K >5.1, 5.5 or 6 mmol/L, respectively) and 12.5%, 1.9% and 0.4% were hypokalaemic (i.e. K<4, 3.5 or 3 mmol/L, respectively). A total of 61% of patients were prescribed a K-binding resin [essentially sodium polystyrene sulfonate (SPS)], while 2 mmol/L and 3 mmol/L K concentration baths were used relatively equally. Over time, the proportion of patients being prescribed any K-binding agent increased up to 78%. The percentage of patients experiencing HK at any time was 73.8% (HK >5.1 mmol/L), 57.9% (HK >5.5 mmol/L) and 34.5% (HK >6 mmol/L). Only 6.3% of patients became normokalaemic within 3 months after an HK >5.5 mmol/L despite dynamic management of K baths and K binders (i.e. increased prescription of 2 mmol/L K baths and increased SPS doses). Conclusions HK was found to be highly prevalent and recurrent in this regional registry despite the widespread and dynamic prescription of low-K dialysis baths and K binders. More effective potassium mitigating strategies are eagerly warranted.