Atrial dysfunction has been widely considered a marker or consequence of other cardiac conditions rather than the cause itself. Here, we propose the term atrial failure as a clinically relevant ...entity, defined as any atrial dysfunction causing impaired heart performance, symptoms, and worsening quality of life or life expectancy. Aspects of the etiology, mechanisms, and consequences of atrial failure are discussed. Recent advances in cardiac electrophysiology and imaging have improved our understanding of the highly complex atrial anatomy and function, underlying the paramount importance of the atria in optimal heart performance. It is time to reappraise the concept of the failing atrium as a primary cause or aggravating factor of the symptoms in many of our patients. The concept of atrial failure may foster basic and translational research to gain a better understanding of how to identify and manage atrial dysfunction.
Background Although frailty has been associated with increased risks for hospitalization and mortality in chronic heart failure, the precise average effect remains uncertain. We performed a ...systematic review and meta-analysis to summarize the hazards for mortality and incident hospitalization in patients with heart failure and frailty compared with those without frailty and explored the heterogeneity underlying the effect size estimates. Methods and Results MEDLINE , EMBASE, and Cochrane databases were queried for articles published between January 1966 and March 2018. Predefined selection criteria were used. Hazard ratios ( HRs ) were pooled for meta-analyses, and where odds ratios were used previously, original data were recalculated for HR . Overlapping data were consolidated, and only unique data points were used. Study quality and bias were assessed. Eight studies were included for mortality (2645 patients), and 6 studies were included for incident hospitalization (2541 patients) during a median follow-up of 1.82 and 1.12 years, respectively. Frailty was significantly associated with an increased hazard for mortality ( HR , 1.54; 95% confidence interval, 1.34-1.75; P<0.001) and incident hospitalization ( HR , 1.56; 95% confidence interval, 1.36-1.78; P<0.001) in chronic heart failure. The Fried phenotype estimated a 16.9% larger effect size than the combined Fried/non-Fried frailty assessment for the end point of mortality ( HR , 1.80; 95% confidence interval, 1.41-2.28; P<0.001), but not for hospitalization ( HR , 1.57; 95% confidence interval, 1.30-1.89; P<0.001). Study heterogeneity was found to be low (I
=0%), and high quality of studies was verified by the Newcastle-Ottawa scale. Conclusions Overall, the presence of frailty in chronic heart failure is associated with an increased hazard for death and hospitalization by ≈1.5-fold.
Inappropriate sinus tachycardia (IST) is a common observation in patients with post-COVID-19 syndrome (PCS) but has not yet been fully described to date. To investigate the prevalence and the ...mechanisms underlying IST in a prospective population of PCS patients. Consecutive patients admitted to the PCS Unit between June and December 2020 with a resting sinus rhythm rate ≥ 100 bpm were prospectively enrolled in this study and further examined by an orthostatic test, 2D echocardiography, 24-h ECG monitoring (heart rate variability was a surrogate for cardiac autonomic activity), quality-of-life and exercise capacity testing, and blood sampling. To assess cardiac autonomic function, a 2:1:1 comparative sub-analysis was conducted against both fully recovered patients with previous SARS-CoV-2 infection and individuals without prior SARS-CoV-2 infection. Among 200 PCS patients, 40 (20%) fulfilled the diagnostic criteria for IST (average age of 40.1 ± 10 years, 85% women, 83% mild COVID-19). No underlying structural heart disease, pro-inflammatory state, myocyte injury, or hypoxia were identified. IST was accompanied by a decrease in most heart rate variability parameters, especially those related to cardiovagal tone: pNN50 (cases 3.2 ± 3 vs. recovered 10.5 ± 8 vs. non-infected 17.3 ± 10; p < 0.001) and HF band (246 ± 179 vs. 463 ± 295 vs. 1048 ± 570, respectively; p < 0.001). IST is prevalent condition among PCS patients. Cardiac autonomic nervous system imbalance with decreased parasympathetic activity may explain this phenomenon.
Abstract Background Neprilysin is a membrane-bound enzyme that breaks down natriuretic peptides. The PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and ...Morbidity in Heart Failure) trial showed that patients with heart failure (HF) treated with an angiotensin receptor neprilysin inhibitor lived longer without being hospitalized for HF than those receiving standard care with enalapril. Objectives This study sought to assess the presence of circulating soluble neprilysin in a real-life cohort of HF patients and correlate neprilysin levels with outcomes. Methods Circulating soluble neprilysin was measured with a modified sandwich immunoassay in consecutive ambulatory patients with HF who were followed up for 4.1 years. Associations between neprilysin level and a composite endpoint that included cardiovascular death or HF hospitalization were explored. Results Median neprilysin concentration in 1,069 patients was 0.642 ng/ml (median quartile 1 to 3: 0.385 to 1.219). Neprilysin weakly but significantly correlated with age (rho = 0.16; p < 0.001). In age-adjusted Cox regression analyses, neprilysin concentrations were significantly associated with the composite endpoint (hazard ratio HR: 1.17; 95% confidence interval CI: 1.06 to 1.29; p = 0.001) and cardiovascular death (HR: 1.19; 95% CI: 1.06 to 1.32; p = 0.002). In comprehensive multivariable analyses, soluble neprilysin remained significantly associated with both the composite endpoint (HR: 1.18; 95% CI: 1.07 to 1.31; p = 0.001) and cardiovascular death (HR: 1.18; 95% CI: 1.05 to 1.32; p = 0.006). Conclusions Identification of circulating neprilysin in HF patients and the positive association of neprilysin with cardiovascular mortality and morbidity further support the importance of NEP inhibition for augmenting natriuretic peptides as a therapeutic target.
Recommendations represent the core messages of guidelines, and are particularly important when the body of scientific evidence is rapidly growing, as in the case of heart failure (HF). The main ...messages from two latest major HF guidelines, endorsed by the European Society of Cardiology (ESC) and the American College of Cardiology/American Heart Association/Heart Failure Society of America (ACC/AHA/HFSA), are partially overlapping, starting from the four pillars of treatment for HF with reduced ejection fraction. Some notable differences exist, in part related to the timing of recent publications (most notably, the Universal Definition of HF paper and the EMPEROR‐Preserved trial), and in part reflecting differing views of the natural history of HF (with a clear differentiation between stages A and B HF in the ACC/AHA/HFSA guidelines). Different approaches are proposed to specific issues such as risk stratification and implantable cardioverter defibrillator use for primary prevention in HFrEF patients with non‐ischaemic aetiology. The ACC/AHA/HFSA guidelines put a greater emphasis on some issues that are particularly relevant to the US setting, such as the cost‐effectiveness of therapies and the impact of health disparities on HF care. A comparison between guideline recommendations may give readers a deeper understanding of the ESC and ACC/AHA/HFSA guidelines, and help them apply sensible approaches to their own practice, wherever that may be in the world. A comparison may possibly also help further harmonization of recommendations between future guidelines, by identifying why some areas have led to conflicting recommendation, even when ostensibly reviewing the same published evidence.
Main similarities and differences between the European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association/Heart Failure Society of America (ACC/AHA/HFSA) heart failure (HF) guidelines. See text for details. ARNI, angiotensin receptor–neprilysin inhibitor; BNP, B‐type natriuretic peptide; CRT, cardiac resynchronization therapy; GL, guidelines; HFmrEF, heart failure with mildly reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; ICD, implantable cardioverter defibrillator; LOE, level of evidence; MCS, mechanical circulatory support; MRA, mineralocorticoid receptor antagonist; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide; RAASi, renin–angiotensin–aldosterone system inhibitor; SGLT2i, sodium–glucose co‐transporter 2 inhibitor.
Congestion explains many of the signs and symptoms of acute heart failure (AHF) and disease progression. However, accurate quantification of congestion is challenging in daily practice. Antigen ...carbohydrate 125 (CA125) or mucin 16 (MUC16), a large glycoprotein synthesized by mesothelial cells, has emerged as a reliable proxy of congestion and inflammation in patients with heart failure (HF). In AHF syndromes, CA125 is strongly associated with right‐sided HF parameters and a higher risk of adverse clinical events beyond standard prognostic factors, including natriuretic peptides. Furthermore, CA125 has the potential for both monitoring and guide HF treatment following a decompensated HF event. The wide availability of CA125 in most clinical laboratories, together with its standardized measurement and reduced cost, makes this marker attractive for routine use in decompensated HF. Further research is required to understand better its biological role and its promising utility as a tool to guide decongestive therapy in HF.
Scheme of the pathophysiology, clinical utility, and logistic advantages of antigen carbohydrate 125 (CA125) in heart failure (HF). In acute HF syndromes, plasma CA125: (i) is associated with proxies of clinical congestion, right‐sided HF, and inflammation; (ii) is positively associated with a higher risk of death and HF readmission; (iii) has emerged as a valuable tool for tailoring diuretic therapy; and (iv) is cheap, and widely available.
Aims
Significant recovery of left ventricular ejection fraction (LVEF) occurs in a proportion of patients with heart failure (HF) and reduced ejection fraction (HFrEF). We analysed outcomes, ...including mortality all‐cause, cardiovascular (CV), HF‐related, and sudden death, and HF‐related hospitalizations in this HF‐recovered group. The primary endpoint was a composite of CV death or HF hospitalization.
Methods and results
LVEF was assessed at baseline and at 1 year in 1057 consecutive HF patients. Patients were classified into three groups: (i) HF‐recovered: LVEF <45% at baseline and ≥45% at 1 year (n = 233); (ii) HF with preserved EF (HFpEF): LVEF ≥45% throughout follow‐up (n = 117); and (iii) HFrEF: LVEF <45% throughout follow‐up (n = 707). Mean follow‐up was 5.6 ± 3.1 years. HF‐recovered patients differed from HFrEF and HFpEF groups in demographic and clinical characteristics. The mean LVEF increase was 21.1 ± 10 points in HF‐recovered patients. Using the HF‐recovered group as a reference, the risks for the primary composite endpoint (n = 376), with non‐CV death as competing risk, for HFpEF and HFrEF groups were: hazard ratio (HR) 2.33 95% confidence interval (CI) 1.60–3.39, P < 0.001 and HR 1.99 (95% CI 1.50–2.65), P < 0.001, respectively. All‐cause (n = 429), CV (n = 245), HF‐related (n = 127), and sudden death (n = 60) were significantly lower in HF‐recovered subjects relative to HFrEF (all P < 0.01). HF‐recovered patients also experienced less recurrent HF hospitalizations (P < 0.001).
Conclusion
One in four treated patients with HFrEF showed recovery of systolic function. HF‐recovered patients had significantly improved mortality and morbidity relative to HFpEF and HFrEF subjects. Further research is needed to identify optimal medications and device indications for HF‐recovered patients.
Cardiovascular diseases are the number one cause of death worldwide and greatly impact quality of life and medical costs. Enormous effort has been made in research to obtain new tools for efficient ...and quick diagnosis and predicting the prognosis of these diseases. Discoveries of epigenetic mechanisms have related several pathologies, including cardiovascular diseases, to epigenetic dysregulation. This has implications on disease progression and is the basis for new preventive strategies. Advances in methodology and big data analysis have identified novel mechanisms and targets involved in numerous diseases, allowing more individualized epigenetic maps for personalized diagnosis and treatment. This paves the way for what is called pharmacoepigenetics, which predicts the drug response and develops a tailored therapy based on differences in the epigenetic basis of each patient. Similarly, epigenetic biomarkers have emerged as a promising instrument for the consistent diagnosis and prognosis of cardiovascular diseases. Their good accessibility and feasible methods of detection make them suitable for use in clinical practice. However, multicenter studies with a large sample population are required to determine with certainty which epigenetic biomarkers are reliable for clinical routine. Therefore, this review focuses on current discoveries regarding epigenetic biomarkers and its controversy aiming to improve the diagnosis, prognosis, and therapy in cardiovascular patients.
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