João Pedro Ferreira

Antithrombotic therapy in heart failure patients with and without atrial fibrillation: update and future challenges

Atrial fibrillation (AF) and heart failure (HF) often coexist, and patients with AF and HF have a higher risk of thromboembolic events and overall mortality compared with those with AF without HF. Additionally, the prevalence of AF increases with the severity of HF. The use of vitamin K antagonists is more unstable in patients with concomitant AF and HF, which is an independent risk factor for reduced time under therapeutic range. More recently, non-vitamin K antagonists oral anticoagulants (NOACs) have emerged as therapeutic alternatives for stroke prevention in patients with non-valvular AF, as they have been shown to be at least as efficacious and safe, with less intracranial bleeding events, compared with vitamin K antagonists. The subgroup analyses of the NOAC trials in patients with AF and HF show that the efficacy and safety of these agents are likely to be similar to those observed in patients with AF and no HF. However, many gaps in evidence exist, since HF has not been consistently defined nor used as an endpoint in these trials. In patients with HF and sinus rhythm, the risk of stroke and other thrombotic events is high, and the use of warfarin has not, to date, been shown to confer outcome benefit. The benefit of the NOAC, rivaroxaban, is being investigated in HF without AF in the ongoing COMMANDER-HF trial. This review aims to provide an insightful perspective on the use of antithrombotic treatments in patients with both AF and HF, and in patients with HF and sinus rhythm, with particular attention to the NOACs, and provides background for therapeutic, outcome and trial improvement.

Heart Failure and Atrial Fibrillation: From Basic Science to Clinical Practice

Heart failure (HF) and atrial fibrillation (AF) are two growing epidemics associated with significant morbidity and mortality. They often coexist due to common risk factors and shared pathophysiological mechanisms. Patients presenting with both HF and AF have a worse prognosis and present a particular therapeutic challenge to clinicians. This review aims to appraise the common pathophysiological background, as well as the prognostic and therapeutic implications of coexistent HF and AF.

Mineralocorticoid receptor antagonist pattern of use in heart failure with reduced ejection fraction: findings from BIOSTAT-CHF

Mineralocorticoid receptor antagonists (MRAs) are recommended (unless contraindicated) to all patients with heart failure with reduced ejection fraction (HFrEF). However, MRAs are still largely underused in routine clinical practice. This study aims to describe the determinants and pattern of use of MRAs in HFrEF.

Tailoring mineralocorticoid receptor antagonist therapy in heart failure patients: are we moving towards a personalized approach?

The aim of personalized medicine is to offer a tailored approach to each patient in order to provide the most effective therapy, while reducing risks and side effects. The use of mineralocorticoid receptor antagonists (MRAs) has demonstrated major benefits in heart failure with reduced ejection fraction (HFrEF), results with challenging inconsistencies in heart failure with preserved ejection fraction (HFpEF), and ‘neutral’ preliminary results in acute heart failure. Data derived from landmark trials are generally applied in a ‘one size fits all’ manner and the development and implementation of more personalized MRA management would offer the potential to improve outcomes and reduce side effects. However, the personalization of pharmacotherapy regimens remains poorly defined in the cardiovascular field (in light of current knowledge) and until further trials targeting specific subpopulations have been conducted, MRAs should be provided to the great majority of HFrEF patients in the absence of contraindication. Spironolactone should be considered for symptomatic HFpEF patients with elevated natriuretic peptides. In the near future, trials should target HFrEF patients using exclusion criteria sourced from landmark trials (e.g. severe renal impairment), select more homogeneous HFpEF populations (e.g. with elevated BNP and structural abnormalities on echocardiography), and determine which patients are likely to benefit from MRAs (e.g. according to prespecified biomarkers).

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.

Intima–Media Thickness Is Linearly and Continuously Associated With Systolic Blood Pressure in a Population‐Based Cohort (STANISLAS Cohort Study)

Background Carotid intima–media thickness (cIMT) is a noninvasive marker of cardiovascular risk. The cIMT may be increased in patients with harmonisation, but little is known regarding the functional form of the association between blood pressure (BP) and cIMT in hypertensive and nonhypertensive persons. We aimed to define the shape of the association between BP and cIMT. Methods and Results We studied cIMT and ambulatory BP monitoring data from a single‐center, cross‐sectional, population‐based study involving 696 adult participants from the STANISLAS cohort, a familial longitudinal cohort from the Nancy region of France. Participants with a history of hypertension were more likely to have a cIMT >900 μm and had higher mean cIMT (both P<0.001). The risk of cIMT >900 μm increased linearly with higher 24‐hour and daytime systolic BP in participants both with and without history of hypertension. The relationship between systolic BP and the risk of cIMT >900 μm was not dependent on hypertension status (all P for interaction >0.10). In multivariable analysis adjusted on cardiovascular risk factors, each 5‐mm Hg increase in systolic BP was associated with an 8‐μm increase in cIMT (β=8.249 [95% CI 2.490–14.008], P=0.005). In contrast, the association between diastolic BP and cIMT was weaker and not significant. Conclusions Systolic BP is linearly and continuously associated with higher cIMT in both hypertensive and nonhypertensive persons, suggesting a detrimental effect of BP on the vascular tree prior to overt hypertension. Similarly, it suggests a detrimental effect of BP at the higher end of the normal range in treated hypertensive patients. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01391442.

Mineralocorticoid receptor antagonists in Patients with heart failure: Current Experience and Future Perspectives

The 2016 European Society of Cardiology Heart Failure society as well as the 2016 American Heart Association/American College of Cardiology/Heart Failure Society of America heart failure (HF) guidelines confirm the class I indication for mineralocorticoid receptor antagonists (MRAs) in patients with chronic HF and a reduced left ventricular ejection fraction (HF-REF). MRAs in addition to an angiotensin converting enzyme inhibitor (ACEi), or an angiotensin receptor antagonist if an ACEi is not tolerated, along with a beta receptor antagonist and a diuretic (if required for congestion relief) make up the baseline therapy for all patients with chronic HF-REF. However, despite the finding that MRAs have been shown to reduce mortality as well as total and repeated hospitalizations in all patients with chronic HF-REF, as well as their class I indication in international guidelines, their use in guideline eligible patients remains suboptimal. Although much has been written about the mechanisms and role of MRAs in HF, this article will review the clinical studies and mechanisms thought responsible for their benefits in an attempt to increase their use in guideline eligible patients with HF as well as to provide the basis for understanding potential new opportunities for their use in patients with HF.

A tentative interpretation of the TOPCAT trial based on randomized evidence from the brain natriuretic peptide stratum analysis

Heart failure with preserved ejection fraction (HFpEF) affects a large proportion of patients with the clinical syndrome of heart failure (HF).1–3 These patients share impaired quality of life and poor prognosis with their HF counterparts with reduced ejection fraction (HRrEF).4,5 Despite the burden of this condition, no treatment tested in a clinical outcome trial has convincingly been shown to improve outcomes in HFpEF.6–8

Predictors and prognostic significance of tachycardiomyopathy: insights from a cohort of 1269 patients undergoing atrial flutter ablation

Atrial flutter‐related tachycardiomyopathy (AFL‐TCM) is a rare and treatable cause of heart failure. Little is known about its epidemiology and long‐term prognosis. Our aims are to determine the prevalence, predictors and outcomes of AFL‐TCM.

High-Sensitivity Troponin T: A Biomarker for Diuretic Response in Decompensated Heart Failure Patients

Background. Patients presenting with acutely decompensated heart failure (ADHF) and positive circulating cardiac troponins were found to be a high-risk cohort. The advent of high-sensitive troponins resulted in a detection of positive troponins in a great proportion of heart failure patients. However, the pathophysiological significance of this phenomenon is not completely clear. Objectives. The aim of this study is to determine the early evolution and clinical significance of high-sensitivity troponin T (hsTnT) in ADHF. Methods. Retrospective, secondary analysis of a prospective study including 100 patients with ADHF. Results. Globally, high-sensitivity troponin T decreased from day 1 to day 3 (P = 0,039). However, in the subgroup of patients who remained decompensated no significant differences in hsTnT from day 1 to day 3 were observed (P = 0,955), whereas in successfully compensated patients a significant reduction in hsTnT levels was observed (P = 0,025). High-sensitivity troponin T decrease was correlated with NTproBNP reduction (P = 0,007). Patients with hsTnT increase had longer length of stay (P = 0,033). Conclusions. Episodes of ADHF are associated with transient increases in the blood levels of hsTnT that are reduced with effective acute episode treatment. The decrease in hsTnT can translate less myocardial damage along with favourable ADHF treatment.