The management of atrial fibrillation in heart failure: an expert panel consensus.

Heart failure (HF) and atrial fibrillation (AF) often coexist, being closely interrelated as the one increases the prevalence and incidence and worsens the prognosis of the other. Their frequent coexistence raises several challenges, including under-diagnosis of HF with preserved ejection fraction in AF and of AF in HF, characterization and diagnosis of atrial cardiomyopathy, target and impact of rate control therapy on outcomes, optimal rhythm control strategy in the era of catheter ablation, HF-related thromboembolic risk and management of anticoagulation in patients with comorbidities, such as chronic kidney disease or transient renal function worsening, coronary artery disease or acute coronary syndromes, valvular or structural heart disease interventions and cancer. In the present document, derived by an expert panel meeting, we sought to focus on the above challenging issues, outlining the existing evidence and identifying gaps in knowledge that need to be addressed.

Practical Recommendations for the Diagnosis and Medical Management of Stable Angina: An Expert Panel Consensus.

Stable angina affects a significant number of coronary artery disease patients, impairing their quality of life and worsening their prognosis. It manifests even despite a history of revascularization and is often poorly controlled with drug therapy. Comorbid conditions are frequently encountered in coronary artery disease patients, affecting their prognosis and rendering the diagnosis and management of angina more challenging. In this article, derived by an expert panel meeting, we attempt a practical approach to stable angina, focusing on symptomatic patients subjected to previous coronary revascularization or not suitable for revascularization and providing handy diagnostic and therapeutic algorithms and comorbidity-adjusted therapeutic approaches in accordance with existing evidence, current recommendations, and locally available therapeutic options.

Impact of renin-angiotensin-aldosterone system polymorphisms on myocardial perfusion: Correlations with myocardial single photon emission computed tomography-derived parameters.

BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) has an important role in atherosclerosis. We investigated the effects of six RAAS gene polymorphisms on myocardial perfusion. METHODS AND RESULTS: We examined 810 patients with known or suspected coronary artery disease (CAD) using stress-rest myocardial single-photon emission computed tomography. Summed stress score (SSS), summed rest score (SRS), summed difference score (SDS), transient ischemic dilation (TID), and lung/heart ratio (LHR) were recorded. The following gene polymorphisms were investigated: angiotensin-converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen (AGT) M235T and T174M, angiotensin II type 1 receptor (AT1R) A1166C, renin (REN) C5312T, and angiotensin II type 2 receptor (AT2R) C3123A. The heterozygotes or homozygotes on ACE D allele were 7.54 times more likely to have abnormal SSS, while the AGT (T174M) heterozygotes were 5.19 times more likely to have abnormal SSS. The homozygotes of ACE D had significantly higher values on TID and LHR, while the AGT (T174M) heterozygotes had higher values on TID. The AT1R heterozygotes had greater odds for having SSS ≥ 3. The patients carried AT1R homozygosity of C allele had significantly higher values on TID, while heterozygotes of AT1R had significantly higher values on LHR. CONCLUSIONS: Among the polymorphisms investigated, ACE D allele had the strongest association with abnormal myocardial perfusion.

Hospitalization affects the anticoagulation patterns of patients with atrial fibrillation.

Scarce data are available on the effects of hospitalization on oral anticoagulation (OAC) patterns in patients with atrial fibrillation (AF). This study aimed to capture the evolving OAC patterns of patients with known non-valvular AF at high risk for stroke (CHA2DS2-Vasc score ≥ 2 for males and ≥ 3 for females) during hospitalization. A total of 561 eligible patients who were admitted to the cardiology ward of a tertiary hospital were studied. Pre- and post-hospitalization OAC patterns [vitamin-K antagonist (VKA), non-vitamin K oral anticoagulants (NOAC), no OAC], changes between these patterns (initiation, switch, discontinuation, no change) and the respective patient profiles and discharge diagnoses were assessed. During hospitalization, OAC administration increased from 73.1 to 86.6% of patients (p for trend < 0.001). NOAC use increased significantly (42.2-56.1%, p for trend < 0.001), whereas VKA use remained stable (30.8-30.5%). Of patients, 17.3% initiated OAC, 7.1% switched between OACs, 3.7% discontinued OAC treatment, while the rest underwent no change in anticoagulation status. Bleeding risk, use of concomitant antiplatelet therapy and incidence of primary discharge diagnosis of AF or ST-elevation myocardial infarction differed significantly between groups of initiation, switch, discontinuation and no change in OAC therapy. In conclusion, in patients with known AF at high risk for stroke, hospitalization was associated with an increase in OAC uptake, driven mainly by NOAC initiation. Three out of 10 patients initiated, switched or discontinued OAC treatment during hospitalization and this was associated with discrete epidemiologic parameters.

Direct Oral Anticoagulants in Nonvalvular Atrial Fibrillation: Practical Considerations on the Choice of Agent and Dosing.

Direct or new oral anticoagulants (NOACs), including the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, have recently revolutionized the field of antithrombotic therapy for stroke and systemic embolism prevention in nonvalvular atrial fibrillation (NVAF). Randomized controlled trials have shown that these agents have at least comparable efficacy with vitamin K antagonists along with superior safety, at least in what concerns intracranial hemorrhage. As a result, NOACs are indicated as first-line anticoagulation therapy for NVAF patients with at least one risk factor for stroke or systemic embolism. The rapid introduction, however, of NOACs in a field dominated for decades by vitamin antagonists and the variety of agents and dosing schemes may create difficulties in decision making. In the present article, we attempt to determine a practical approach to the choice of agent and dose in different clinical scenarios by considering not only the results of seminal randomized trials and post hoc analyses but also data from real-world patient populations as well as the recently available possibility of rapid NOAC reversal.

SPECT and PET in ischemic heart failure.

Heart failure is a common clinical syndrome associated with significant morbidity and mortality worldwide. Ischemic heart disease is the leading cause of heart failure, at least in the industrialized countries. Proper diagnosis of the syndrome and management of patients with heart failure require anatomical and functional information obtained through various imaging modalities. Nuclear cardiology techniques play a main role in the evaluation of heart failure. Myocardial single photon emission computed tomography (SPECT) with thallium-201 or technetium-99 m labelled tracers offer valuable data regarding ventricular function, myocardial perfusion, viability, and intraventricular synchronism. Moreover, positron emission tomography (PET) permits accurate evaluation of myocardial perfusion, metabolism, and viability, providing high-quality images and the ability of quantitative analysis. As these imaging techniques assess different parameters of cardiac structure and function, variations of sensitivity and specificity have been reported among them. In addition, the role of SPECT and PET guided therapy remains controversial. In this comprehensive review, we address these controversies and report the advances in patient's investigation with SPECT and PET in ischemic heart failure. Furthermore, we present the innovations in technology that are expected to strengthen the role of nuclear cardiology modalities in the investigation of heart failure.

Red blood cell distribution width as a prognostic marker in patients with heart failure and diabetes mellitus.

BACKGROUND: Red blood cell distribution width (RDW) is an established prognostic marker in acute and chronic heart failure (HF). Recent studies have pointed out a link among RDW, diabetes mellitus (DM) and inflammation. We sought to investigate the prognostic value and longitudinal pattern of RDW in patients with concomitant HF and DM, which remains unknown. METHODS: A total of 218 patients (71 diabetics) who presented with acute HF had RDW measured at admission, discharge and 4, 8 and 12 months post-discharge. The study endpoint was all-cause mortality or rehospitalization for HF during 1-year follow-up. RESULTS: The study endpoint was met in 33 patients (46.5%) with DM and in 54 patients (36.7%) without DM. RDW at admission was associated with higher event rate both in HF patients with and without DM (adjusted HR: 1.349, p = 0.002, 95% CI 1.120-1.624 and adjusted HR: 1.142, p = 0.033, 95% CI 1.011-1.291 respectively). In addition, a significant interaction was found between diabetes and RDW longitudinal changes (ßinteraction = -0.002; SE = 0.001; p = 0.042). CONCLUSIONS: Despite the similar prognostic significance of RDW in diabetic and non-diabetic HF patients regarding the study endpoint, longitudinal changes were found to be significantly different between these two groups of HF patients. This might be due to the higher inflammatory burden that diabetic HF patients carry and may provide new insights to the pathophysiological mechanism of RDW increase in HF, which remains unknown.

NGAL and ST2 levels in ambulatory patients with chronic heart failure. Clinical and echocardiographic correlates.

AIM: Neutrophil gelatinase-associated lipocalin (NGAL) and ST2 receptor, a member of the interleukin-1 receptor family, are novel biomarkers with a potential role in the diagnosis and risk stratification of patients with chronic heart failure (CHF). There is however scarce data on their relation with clinical characteristics and cardiac function in patients with CHF. METHODS: Consecutive ambulatory patients with CHF were studied. All patients underwent clinical and echocardiographic assessment, and blood samples were collected for the estimation of ST2 and NGAL serum levels during the same assessment. RESULTS: A total of 76 patients (79% male, mean age: 63 ± 14 years), with CHF and left ventricular ejection fraction of 28 ± 7% were included. Median NGAL was 0.16 (0.09-0.275) mg/L and median ST2 was 0.0125 (0.0071-0.0176) mg/L. No association between NGAL and ST2 was observed. Multivariate analysis revealed tissue Doppler-derived right ventricular systolic velocity as an independent predictor of ST2, and the duration of HF and serum creatinine levels as independent predictors of NGAL. CONCLUSIONS: NGAL levels depend on the renal function and the duration of HF, while ST2 levels are affected by the right but not the left ventricular function and show no association with clinical indices of HF.

The emerging role of Galectin-3 and ST2 in heart failure: practical considerations and pitfalls using novel biomarkers.

Heart failure (HF) is a leading cause of morbidity and mortality worldwide and, despite recent advances in therapy HF hospitalization rates remains unacceptably high. Prompt identification and optimal management of HF can affect long-term outcome. A valuable tool with diagnostic, prognostic, and treatment-guiding properties in this respect will be very useful, as exemplified by natriuretic peptides. However, natriuretic peptide levels show biological variation and are dependent on age, renal function, and body mass index. Recent advances in the field of molecular biology and HF pathophysiology have led to the discovery of other novel biomarkers that may have advantages. Among others, Galectin-3 (GAL3) and sST2 are 2 promising biomarkers that have been recently developed and can be used alone or in combination with natriuretic peptides in clinical practice. In the current paper, we review the existing data regarding GAL3 and sST2 in HF.

Epidemiology and importance of renal dysfunction in heart failure patients.

Renal dysfunction (RD) is a frequent comorbid condition and a major determinant of outcomes in patients with heart failure (HF). It is likely that the etiology of RD in patients with HF is much more complex than we first thought and represents a matrix of independent, albeit interacting, pathophysiological pathways with effects on both the kidney and the heart that share a common denominator: aging and inflammation. Renal dysfunction in HF has been attributed, among others, to biochemical, hormonal, and hemodynamic factors, coupled with pharmacological interventions. Regardless of the cause, the development of RD or worsening renal function is common in patients with HF, and is associated with increased morbidity and mortality. There is increasing evidence, however, that transient increases in creatinine in the setting of acute HF are not prognostically important, whereas persistent deterioration does portend a higher mortality in this patient population. In addition, congestion seems to play an important role in the course of renal deterioration, and the combination of congestion and worsening renal function is the most significant clinical prognosticator in HF patients. This review aims to provide an update on the epidemiology and prognostic significance of RD in HF patients, in both the acute and the chronic setting.

The cardiorenal syndrome in heart failure: cardiac? renal? syndrome?

There has been increasing interest on the so-called cardiorenal syndrome (CRS), defined as a complex pathophysiological disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other. In this review, we contend that there is lack of evidence warranting the adoption of a specific clinical construct such as the CRS within the heart failure (HF) syndrome by demonstrating that: (a) the approaches and tools regarding the definition of kidney involvement in HF are suboptimal; (b) development of renal failure in HF is often confounded by age, hypertension, and diabetes; (c) worsening of renal function (WRF) in HF may be largely independent of alterations in cardiac function; (d) the bidirectional association between HF and renal failure is not unique and represents one of the several such associations encountered in HF; and (e) inflammation is a common denominator for HF and associated noncardiac morbidities. Based on these arguments, we believe that dissecting one of the multiple bidirectional associations in HF and constructing the so-called cardiorenal syndrome is not justified pathophysiologically. Fully understanding of all morbid associations and not only the cardiorenal is of great significance for the clinician who is caring for the patient with HF.

Efficacy, efficiency and safety of a cardiac telerehabilitation programme using wearable sensors in patients with coronary heart disease: the TELEWEAR-CR study protocol.

INTRODUCTION: Exercise-based cardiac rehabilitation (CR) is a beneficial tool for the secondary prevention of cardiovascular diseases with, however, low participation rates. Telerehabilitation, intergrading mobile technologies and wireless sensors may advance the cardiac patients' adherence. This study will investigate the efficacy, efficiency, safety and cost-effectiveness of a telerehabilitation programme based on objective exercise telemonitoring and evaluation of cardiorespiratory fitness. METHODS AND ANALYSIS: A supervised, parallel-group, single-blind randomised controlled trial will be conducted. A total of 124 patients with coronary disease will be randomised in a 1:1 ratio into two groups: intervention telerehabilitation group (TELE-CR) (n=62) and control centre-based cardiac rehabilitation group (CB-CR) (n=62). Participants will receive a 12-week exercise-based rehabilitation programme, remotely monitored for the TELE-CR group and standard supervised for the CB-CR group. All participants will perform aerobic training at 70% of their maximal heart rate, as obtained from cardiopulmonary exercise testing (CPET) for 20 min plus 20 min for strengthening and balance training, three times per week. The primary outcomes will be the assessment of cardiorespiratory fitness, expressed as peak oxygen uptake assessed by the CPET test and the 6 min walk test. Secondary outcomes will be the physical activity, the safety of the exercise intervention (number of adverse events that may occur during the exercise), the quality of life, the training adherence, the anxiety and depression levels, the nicotine dependence and cost-effectiveness. Assessments will be held at baseline, end of intervention (12 weeks) and follow-up (36 weeks). ETHICS AND DISSEMINATION: The study protocol has been reviewed and approved by the Ethics Committee of the University of Thessaly (1108/1-12-2021) and by the Ethics Committee of the General University Hospital of Larissa (3780/31-01-2022). The results of this study will be disseminated through manuscript publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT05019157.

Hospitalization epidemic in patients with heart failure: risk factors, risk prediction, knowledge gaps, and future directions.

Patients with heart failure (HF) are hospitalized over a million times annually in the United States. Hospitalization marks a fundamental change in the natural history of HF, leading to frequent subsequent rehospitalizations and a significantly higher mortality compared with nonhospitalized patients. Three-fourths of all HF hospitalizations are due to exacerbation of symptoms in patients with known HF. One-half of hospitalized HF patients experience readmission within 6 months. Preventing HF hospitalization and rehospitalization is important to improve patient outcomes and curb health care costs. To implement cost-effective strategies to contain the HF hospitalization epidemic, optimal schemes to identify high-risk individuals are needed. In this review, we describe the risk factors that have been associated with hospitalization risk in HF and the various multimarker risk prediction schemes developed to predict HF rehospitalization. We comment on areas that represent gaps in our knowledge or difficulties in interpretation of the current literature, representing opportunities for future research. We also discuss issues with using HF readmission rate as a quality indicator.

Prevalence of impaired coronary flow reserve and its association with left ventricular diastolic function in asymptomatic individuals with major cardiovascular risk factors.

AIM: The aims of this study were to evaluate: i) the prevalence of impaired coronary flow reserve (CFR), ii) the association of impaired CFR with indices of left ventricular function, and iii) the independent predictors of impaired CFR in a cohort of high-risk asymptomatic individuals. METHODS: Ninety-nine consecutive individuals (age, 52.5 ± 13.2 years; 68% male; left ventricular ejection fraction, 62 ± 6%) with at least one major cardiovascular risk factor (49% hypertension, 23% diabetes mellitus, 42% hypercholesterolemia, 32% smoking) were evaluated. Based on CFR values, patients were divided into normal (CFR ≥2.5), borderline (2.5>CFR ≥2.0), and abnormal (CFR < 2.0). Left ventricular function was assessed with comprehensive transthoracic echocardiography. RESULTS: Impaired CFR was identified in 39 individuals (borderline, n = 25; abnormal, n = 14). Isovolumic relaxation time was significantly increased for abnormal compared with normal CFR (94 ± 12 vs. 85 ± 11 msec, p < 0.05), as was the left atrial volume index (LAVI) (24 ± 7 cm(3)/m(2) vs. 19.1 ± 5.2, p < 0.01). A stepwise linear regression analysis identified the LAVI and the deceleration time of E wave of transmitral flow as the only independent predictors of CFR value. An ordinal regression analysis model revealed two predictors of CFR categorization: diabetes mellitus (proportional odds ratio (POR) for CFR group deterioration, 4.55; 95% confidence interval (CI), 1.13-18.28; p = 0.033) and LAVI (POR, 1.11 per 1 cm(3)/m(2) increment; 95% CI, 1.01-1.23; p = 0.034). CONCLUSIONS: CFR is often impaired among asymptomatic individuals with major cardiovascular risk factors and is associated with changes in left ventricular diastolic function and left atrial size. The prognostic importance of these early derangements should be assessed in prospective studies.

Impact of dopamine infusion on renal function in hospitalized heart failure patients: results of the Dopamine in Acute Decompensated Heart Failure (DAD-HF) Trial.

BACKGROUND: Worsening renal function (WRF) and hypokalemia related to diuretic use for acute decompensated heart failure (ADHF) are common and associated with poor prognosis. Low-dose dopamine infusion improves renal perfusion; its effect on diuresis or renal function specifically in ADHF is not known. METHODS AND RESULTS: Sixty consecutive ADHF patients (age 75.7 ± 11.2 years; 51.7% female; left ventricular ejection fraction 35.3 ± 12.1%) were randomized, after receiving a 40 mg intravenous furosemide bolus, to either high-dose furosemide (HDF, 20 mg/h continuous infusion for 8 hours) or low-dose furosemide combined with low-dose dopamine (LDFD, furosemide 5 mg/h plus dopamine 5 µg kg(-1) min(-1) continuous infusion for 8 hours). Both strategies were compared for total diuresis, WRF (defined as a rise in serum creatinine of >0.3 mg/dL from baseline to 24 hours), electrolyte balance, and 60-day postdischarge outcomes. Mean hourly excreted urine volume (272 ± 149 mL in HDF vs 278 ± 186 mL in LDFD group; P = .965) and changes in dyspnea score (Borg index: -4.4 ± 2.1 in HDF group vs -4.7 ± 2.0 in LDFD group; P = .575) during the 8 hours of protocol treatment were similar in the two groups. WRF was more frequent in the HDF (n = 9; 30%) than in the LDFD group (n = 2; 6.7%; P = .042). Serum potassium changed from 4.3 ± 0.5 to 3.9 ± 0.4 mEq/L at 24 hours (P = .003) in the HDF group and from 4.4 ± 0.5 to 4.2 ± 0.5 mEq/L at 24 hours (P = .07) in the LDFD group. Length of stay and 60-day mortality or rehospitalization rates (all-cause, cardiovascular, and worsening HF) were similar in the two groups. CONCLUSIONS: In ADHF patients, the combination of low-dose furosemide and low-dose dopamine is equally effective as high-dose furosemide but associated with improved renal function profile and potassium homeostasis.

Management of iron deficiency in chronic heart failure: Practical considerations for clinical use and future directions.

Heart Failure (HF) is a global pandemic with rapidly increasing prevalence. In an attempt to maintain patients well being, the therapeutic interest has expanded to the vicious cycles that confer to HF mortality and morbidity and a number of comorbidities have been targeted. Iron deficiency represents a common comorbid condition that affects outcomes in HF. The treatment of iron deficiency is strongly supported by the cardiologic societies all over the world. Intravenous iron, primarily ferric carboxymaltose, has shown clinical benefit in this setting, irrespective of the anemia status. Practical recommendations though are lacking. In this document, we have tried to cover the practical gap and provide useful details for intravenous iron use.

Left ventricular geometry as a major determinant of left ventricular ejection fraction: physiological considerations and clinical implications.

The limited myocardial fibre thickening and shortening alone cannot explain the marked left ventricular (LV) volume reduction during LV ejection. This can only be achieved with LV helical (spiral) orientation of myocardial fibres, which is determined by the non-contractile LV myocardial components (intrasarcomeric and extrasarcomeric cytoskeleton, extracellular matrix). Preservation of LV ejection fraction (LVEF) in heart failure (HF) is due to the presence of normal ellipsoid LV configuration and spiral myocardial fibre orientation. Conversely, reduction of LVEF in HF results from spherical LV configuration associated with impaired myocardial fibre orientation. These mechanisms are supported by the fact that biomarkers of inflammation and fibrosis are strong predictors of LV reverse remodelling in HF with reduced LVEF (HFrEF) and therapeutic interventions in HFrEF that retard or inhibit extracellular matrix remodelling are effective, whereas those that increase myocardial contractility are ineffective. Thus, current classification of HF, based on LVEF, should be revised, and future therapy in HF should focus on interventions affecting the non-contractile LV myocardial components rather than on LV myocardial contractility.

A 6-month follow-up of intermittent levosimendan administration effect on systolic function, specific activity questionnaire, and arrhythmia in advanced heart failure.

BACKGROUND: Levosimendan (LS) improves cardiac contractility without increasing myocardial oxygen demand. We administrated LS on a monthly intermittent 24-hour protocol and evaluated the clinical effect after 6 months in a randomized, open, prospective study. METHODS AND RESULTS: Fifty patients (age 45-65 years) with LV systolic dysfunction and New York Heart Association (NYHA) III or IV were randomized in 2 groups. LS group (n = 25) was compared with a control group (n = 25) matched for sex, age, and NYHA class. LS was given monthly on a 24-hour intravenous protocol for 6 months. Patients were evaluated by specific activity questionnaire (SAQ) and echocardiography (ECHO) before and 3 to 5 days after last drug administration, whereas 24-hour Holter recording was performed before and during last drug administration. Patients in LS and control group had same baseline SAQ, ECHO, and Holter parameters. At the end of the study, a larger proportion of patients in the levosimendan group reported improvement in symptoms (dyspnea and fatigue) (65% versus 20% in controls, P < .01). After 6 months, the LS group had a significant increase in LV ejection fraction versus controls (28 +/- 7 versus 21 +/- 4 %, P = .003), LV shortening fraction (15 +/- 3 versus 11 +/- 3 %, P = .006) and a decrease in mitral regurgitation (1.5 +/- 0.8 versus 2.7 +/- 0.6, P = .0001). There was no increase in supraventricular or ventricular beats or supraventricular tachycardia and VT episodes in LS group, compared with controls. Two patients from the LS group died in the 6-month follow-up period, compared with 8 patients in the control group (8% versus 32%, P < .05). CONCLUSIONS: A 6-month intermittent LS treatment in patients with decompensated advanced heart failure improved symptoms and LV systolic function.

Association between copayment, medication adherence and outcomes in the management of patients with diabetes and heart failure.

OBJECTIVE: To determine the association between copayment, medication adherence and outcomes in patients with Heart failure (HF) and Diabetes Mellitus (DM). METHODS: PubMed, Scopus and Cochrane databases were searched using combinations of four sets of key words for: drug cost sharing; resource use, health and economic outcomes; medication adherence; and chronic disease. RESULTS: Thirty eight studies were included in the review. Concerning the direct effect of copayment changes on outcomes, the scarcity and diversity of data, does not allow us to reach a clear conclusion, although there is some evidence indicating that higher copayments may result in poorer health and economic outcomes. Seven and one studies evaluating the relationship between copayment and medication adherence in DM and HF population, respectively, demonstrated an inverse statistically significant association. All studies (29) examining the relationship between medication adherence and outcomes, revealed that increased adherence is associated with health benefits in both DM and HF patients. Finally, the majority of studies in both populations, showed that medication adherence was related to lower resource utilization which in turn may lead to lower total healthcare cost. CONCLUSION: The results of our systematic review imply that lower copayments may result in higher medication adherence, which in turn may lead to better health outcomes and lower total healthcare expenses. Future studies are recommended to reinforce these findings.

Left atrial volume index in patients with heart failure and severely impaired left ventricular systolic function: the role of established echocardiographic parameters, circulating cystatin C and galectin-3.

Backround: Left atrial (LA) enlargement plays an important role in the development of heart failure (HF) and is a robust prognostic factor. Fibrotic processes have also been advocated to evoke HF through finite signalling proteins. METHODS: We examined the association of two such proteins, cystatin C (CysC) and galectin-3 (Gal-3), and other clinical, echocardiographic and biochemical parameters with LA volume index (LAVi) in patients with HF with severely impaired left ventricular ejection fraction (LVEF). Severe renal, liver, autoimmune disease and cancer were exclusion criteria. RESULTS: A total of 40 patients with HF (31 men, age 66.6 ± 1.7) with LVEF = 25.4 ± 0.9% were divided into two groups according to the mean LAVi (51.03 ± 2.9 ml/m2) calculated by two-dimensional transthoracic echocardiography. Greater LAVi was positively associated with LV end-diastolic volume ( p = 0.017), LV end-systolic volume ( p = 0.025), mitral regurgitant volume (MRV) ( p = 0.001), right ventricular systolic pressure (RVSP) ( p < 0.001), restrictive diastolic filling pattern ( p = 0.003) and atrial fibrillation ( p = 0.005). Plasma CysC was positively correlated with LAVi ( R2 = 0.135, p = 0.019) and log-transformed plasma Gal-3 ( R2 = 0.109, p = 0.042) by simple linear regression analysis. Stepwise multiple linear regression analysis showed that only MRV ( t = 2.236, p = 0.032), CysC ( t = 2.467, p = 0.019) and RVSP ( t = 2.155, p = 0.038) were significant predictors of LAVi. CONCLUSIONS: Apart from known determinants of LAVi, circulating CysC and Gal-3 were associated with greater LA dilatation in patients with HF with reduced LVEF. Interestingly, the correlation between these two fibrotic proteins was positive.