Left bundle branch pacing and cardiac remodeling in HF patients with type 2 diabetes mellitus: epigenetic pathways and clinical outcomes.

Background: Left bundle branch (LBB) pacing could achieve cardiac resynchronization therapy (CRT) in patients who cannot be resynchronized via the placement of the left ventricle (LV) lead into the coronary sinus. LBB pacing could improve cardiovascular outcomes in heart failure (HF) patients with LBB block who are affected by type 2 diabetes mellitus (T2DM). Study hypothesis: LBB pacing could increase the number of CRT responders and lead to the best clinical outcomes in HF patients with T2DM, inducing cardiac remodeling and improving left ventricle ejection fraction (LVEF) via microRNA (miR) modulation. Methods: In a multicenter observational study, we enrolled 334 HF patients with LBB block and an indication to receive LBB pacing for CRT. In these patients, we evaluated the CRT responder rate, clinical outcomes, and miR expression at 1 year of follow-up. Results: At 1 year of follow-up, we had 223 responders (66.8%), 132 hospitalizations for HF (39.5%), 24 cardiac deaths (7.2%), and 37 all-cause deaths (11.1%), with a higher rate of HF hospitalizations (77 (69.4%) vs 55 (24.7%), p < 0.05), and cardiac deaths (13 (11.7% vs 11 (4.9%), p < 0.05) in non-responders vs responders. At the end of follow-up, we found the lowest expression of miR-26, miR-29, miR-30, miR-92, and miR-145 in LBB-pacing non-responders vs responders (p < 0.05), and a direct correlation between miR-30 (0.340, [0.833-1.915]; p 0.001), the 6-minute-walking test (6MWT; 0.168, [0.008-0.060]; p 0.011), angiotensin-receptor-neprilysin inhibitors (ARNI; 0.157, [0.183-4.877]; p 0.035), sodium-glucose-transporter-2 inhibitors (0.245, [2.242-7.283]; p 0.001), and LVEF improvements. C reactive protein (CRP) inversely correlated with LVEF improvement (-0.220, [-(0.066-0.263)]; p 0.001). ARNI (1.373, CI 95% [1.007-1.872], p 0.045), miR-30 (2.713, CI 95% [1.543-4.769], p 0.001), and 6MWT (1.288, CI 95% [1.084-1.998], p 0.001) were predictors of LBB pacing responders at 1 year of follow-up. Conclusion: LBB-pacing responders evidenced miR modulation, which was linked to significant improvement of the cardiac pump. Specifically, miR-30 was linked to cardiac pump improvement and predicted responders at 1 year of follow-up in patients with T2DM.

Multimodality Cardiovascular Imaging of Cardiotoxicity Due to Cancer Therapy.

Cancer therapies have revolutionized patient survival rates, yet they come with the risk of cardiotoxicity, necessitating effective monitoring and management. The existing guidelines offer a limited empirical basis for practical approaches in various clinical scenarios. This article explores the intricate relationship between cancer therapy and the cardiovascular system, highlighting the role of advanced multimodality imaging in monitoring patients before, during, and after cancer treatment. This review outlines the cardiovascular effects of different cancer therapy classes, offering a comprehensive understanding of their dose- and time-dependent impacts. This paper delves into diverse imaging modalities such as echocardiography, cardiac magnetic resonance imaging, cardiac computed tomography, and nuclear imaging, detailing their strengths and limitations in various conditions due to cancer treatment, such as cardiac dysfunction, myocarditis, coronary artery disease, Takotsubo cardiomyopathy, pulmonary hypertension, arterial hypertension, valvular heart diseases, and heart failure with preserved ejection fraction. Moreover, it underscores the significance of long-term follow-up for cancer survivors and discusses future directions.

Vericiguat: The Fifth Harmony of Heart Failure with Reduced Ejection Fraction.

Heart failure with reduced ejection fraction is a chronic and progressive syndrome that continues to be a substantial financial burden for health systems in Western countries. Despite remarkable advances in pharmacologic and device-based therapy over the last few years, patients with heart failure with reduced ejection fraction have a high residual risk of adverse outcomes, even when treated with optimal guideline-directed medical therapy and in a clinically stable state. Worsening heart failure episodes represent a critical event in the heart failure trajectory, carrying high residual risk at discharge and dismal short- or long-term prognosis. Recently, vericiguat, a soluble guanylate cyclase stimulator, has been proposed as a novel drug whose use is already associated with a reduction in heart failure-related hospitalizations in patients in guideline-directed medical therapy. In this review, we summarized the pathophysiology of the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate cascade in patients with heart failure with reduced ejection fraction, the pharmacology of vericiguat as well as the evidence regarding their use in patients with HFrEF. Finally, tips and tricks for its use in standard clinical practice are provided.

How to Select Patients for Left Ventricular Assist Devices? A Guide for Clinical Practice.

In recent years, a significant improvement in left ventricular assist device (LVAD) technology has occurred, and the continuous-flow devices currently used can last more than 10 years in a patient. Current studies report that the 5-year survival rate after LVAD implantation approaches that after a heart transplant. However, the outcome is influenced by the correct selection of the patients, as well as the choice of the optimal time for implantation. This review summarizes the indications, the red flags for prompt initiation of LVAD evaluation, and the principles for appropriate patient screening.

The Effects of Device-Based Cardiac Contractility Modulation Therapy on Left Ventricle Global Longitudinal Strain and Myocardial Mechano-Energetic Efficiency in Patients with Heart Failure with Reduced Ejection Fraction.

BACKGROUND: Virtually all patients with heart failure with reduced ejection fraction have a reduction of myocardial mechano-energetic efficiency (MEE). Cardiac contractility modulation (CCM) is a novel therapy for the treatment of patients with HFrEF, in whom it improves the quality of life and functional capacity, reduces hospitalizations, and induces biventricular reverse remodeling. However, the effects of CCM on MEE and global longitudinal strain (GLS) are still unknown; therefore, this study aims to evaluate whether CCM therapy can improve the MEE of patients with HFrEF. METHODS: We enrolled 25 patients with HFrEF who received an Optimizer Smart implant (the device that develops CCM therapy) between January 2018 and January 2021. Clinical and echocardiographic evaluations were performed in all patients 24 h before and six months after CCM therapy. RESULTS: At six months, follow-up patients who underwent CCM therapy showed an increase of left ventricular ejection fraction (30.8 ± 7.1 vs. 36.1 ± 6.9%; p = 0.032) as well a rise of GLS 10.3 ± 2.7 vs. -12.9 ± 4.2; p = 0.018), of MEE (32.2 ± 10.1 vs. 38.6 ± 7.6 mL/s; p = 0.013) and of MEE index (18.4 ± 6.3 vs. 24.3 ± 6.7 mL/s/g; p = 0.022). CONCLUSIONS: CCM therapy increased left ventricular performance, improving left ventricular ejection fraction, GLS, as well as MEE and MEEi.

Levosimendan as a "Bridge to Optimization" in Patients with Advanced Heart Failure with Reduced Ejection-A Single-Center Study.

Background: Patients with advanced heart failure with reduced ejection fraction often cannot tolerate target doses of guideline-directed medical therapy due to symptomatic hypotension, renal dysfunction, and associated electrolyte abnormalities. While levosimendan can facilitate the titration of ß-blockers in patients with advanced HFrEF, it is unclear whether ambulatory levosimendan infusions would offer the same benefit. In this prospective study, we investigate the effects of intermittent ambulatory levosimendan infusions on the uptitration of disease-modifying drugs. Methods: We enrolled 37 patients with advanced HFrEF who received repeated ambulatory infusions of levosimendan between January 2018 and January 2021. The demographic, clinical, and laboratory data were acquired 24 h before the first and the last ambulatory levosimendan infusion. Results: At the 1 year follow-up, the enrolled patients were on significantly higher doses of guideline-directed medical therapy, including bisoprolol (3.2 ± 2.8 mg vs. 5.9 ± 4.1 mg; p = 0.02), sacubitril/valsartan (41.67 ± 32.48 mg vs. 68.5 ± 35.72 mg; p = 0.01), and eplerenone (12.7 ± 8.5 mg vs. 22.8 ± 13.6 mg; p = 0.03). Furthermore, a substantial decrease in the furosemide dose was observed (123.2 ± 32.48 mg vs. 81.6 ± 19.47 mg; p < 0.0001). Conclusions: Levosimendan facilitates the optimization of disease-modifying heart failure medications in previously intolerant advanced HFrEF patients.

Reference Ranges of Left Ventricular Hemodynamic Forces in Healthy Adults: A Speckle-Tracking Echocardiographic Study.

BACKGROUND: The normal limits of left ventricular (LV) hemodynamic forces (HDFs) are not exactly known. The aim of this study was to explore the full spectrum of HDF parameters in healthy subjects and determine their physiologic correlates. METHODS: 269 healthy subjects were enrolled (mean age: 43 ± 14 years; 123 (45.7%) men). All participants underwent an echo-Doppler examination. Tri-plane tissue tracking from apical views was used to measure 2D global endocardial longitudinal strain (GLS), circumferential strain (GCS), and LV HDFs. HDFs were normalized with LV volume and divided by specific weight. RESULTS: LV systolic longitudinal HDFs (%) were higher in men (20.8 ± 6.5 vs. 18.9 ± 5.6, p = 0.009; 22.0 ± 6.7 vs. 19.8 ± 5.6, p = 0.004, respectively). There was a significant correlation between GCS (increased) (r = -0.240, p < 0.001) and LV longitudinal HDFs (reduced) (r = -0.155, p = 0.01) with age. In a multivariable analysis age, BSA, pulse pressure, heart rate and GCS were the only independent variables associated with LV HDFs (ß coefficient = -0.232, p < 0.001; 0.149, p = 0.003; 0.186, p < 0.001; 0.396, p < 0.001; -0.328, p < 0.001; respectively). CONCLUSION: We report on the physiologic range of LV HDFs. Knowledge of reference values of HDFs may prompt their implementation into clinical routine and allow a more comprehensive assessment of the LV function.

Feasibility of semi-recumbent bicycle exercise Doppler echocardiography for the evaluation of the right heart and pulmonary circulation unit in different clinical conditions: the RIGHT heart international NETwork (RIGHT-NET).

Exercise Doppler echocardiography (EDE) is a well-validated tool in ischemic and valvular heart diseases. However, its use in the assessment of the right heart and pulmonary circulation unit (RH-PCU) is limited. The aim of this study is to assess the semi-recumbent bicycle EDE feasibility for the evaluation of RH-PCU in a large multi-center population, from healthy individuals and elite athletes to patients with overt or at risk of developing pulmonary hypertension (PH). From January 2019 to July 2019, 954 subjects [mean age 54.2 ± 16.4 years, range 16-96, 430 women] underwent standardized semi-recumbent bicycle EDE with an incremental workload of 25 watts every 2 min, were prospectively enrolled among 7 centers participating to the RIGHT Heart International NETwork (RIGHT-NET). EDE parameters of right heart structure, function and pressures were obtained according to current recommendations. Right ventricular (RV) function at peak exercise was feasible in 903/940 (96%) by tricuspid annular plane systolic excursion (TAPSE), 667/751 (89%) by tissue Doppler-derived tricuspid lateral annular systolic velocity (S') and 445/672 (66.2%) by right ventricular fractional area change (RVFAC). RV-right atrial pressure gradient [RV-RA gradient = 4 × tricuspid regurgitation velocity2 (TRV)] was feasible in 894/954 patients (93.7%) at rest and in 816/954 (85.5%) at peak exercise. The feasibility rate in estimating pulmonary artery pressure improved to more than 95%, if both TRV and/or right ventricular outflow tract acceleration time (RVOT AcT) were considered. In high specialized echocardiography laboratories semi-recumbent bicycle EDE is a feasible tool for the assessment of the RH-PCU pressure and function.

Role of Cardiac Magnetic Resonance Imaging in Heart Failure.

This review describes the current role and potential future applications of cardiac magnetic resonance (CMR) for the management of heart failure (HF). CMR allows noninvasive morphologic and functional assessment, tissue characterization, blood flow, and perfusion evaluation. CMR overcomes echocardiography limitations (geometric assumptions, interobserver variability and poor acoustic window) and provides incremental information in relation to cause, prognosis, and treatment monitoring of patients with HF.

A multicentric quality-control study of exercise Doppler echocardiography of the right heart and the pulmonary circulation. The RIGHT Heart International NETwork (RIGHT-NET).

PURPOSE: This study was a quality-control study of resting and exercise Doppler echocardiography (EDE) variables measured by 19 echocardiography laboratories with proven experience participating in the RIGHT Heart International NETwork. METHODS: All participating investigators reported the requested variables from ten randomly selected exercise stress tests. Intraclass correlation coefficients (ICC) were calculated to evaluate the inter-observer agreement with the core laboratory. Inter-observer variability of resting and peak exercise tricuspid regurgitation velocity (TRV), right ventricular outflow tract acceleration time (RVOT Act), tricuspid annular plane systolic excursion (TAPSE), tissue Doppler tricuspid lateral annular systolic velocity (S'), right ventricular fractional area change (RV FAC), left ventricular outflow tract velocity time integral (LVOT VTI), mitral inflow pulsed wave Doppler velocity (E), diastolic mitral annular velocity by TDI (e') and left ventricular ejection fraction (LVEF) were measured. RESULTS: The accuracy of 19 investigators for all variables ranged from 99.7 to 100%. ICC was > 0.90 for all observers. Inter-observer variability for resting and exercise variables was for TRV = 3.8 to 2.4%, E = 5.7 to 8.3%, e' = 6 to 6.5%, RVOT Act = 9.7 to 12, LVOT VTI = 7.4 to 9.6%, S' = 2.9 to 2.9% and TAPSE = 5.3 to 8%. Moderate inter-observer variability was found for resting and peak exercise RV FAC (15 to 16%). LVEF revealed lower resting and peak exercise variability of 7.6 and 9%. CONCLUSIONS: When performed in expert centers EDE is a reproducible tool for the assessment of the right heart and the pulmonary circulation.

Cardiovascular Magnetic Resonance in Right Heart and Pulmonary Circulation Disorders.

Right heart and pulmonary circulation disorders are generally caused by right ventricle (RV) pressure overload, volume overload, and cardiomyopathy, and they are associated with distinct clinical courses and therapeutic approaches, although they often may coexist. Cardiac magnetic resonance (CMR) provides a noninvasive accurate and reproducible multiplanar anatomic and functional assessment, tissue characterization, and blood flow evaluation of the right heart and pulmonary circulation. This article reviews the current status of the CMR, the most recent techniques, the new parameters and their clinical utility in diagnosis, prognosis, and therapeutic management in the right heart and pulmonary circulation disorders.

Right Ventricular Size and Function in Chronic Heart Failure: Not to Be Forgotten.

A comprehensive multi-imaging evaluation of the right heart structure, function, and pressures represents an essential step in the diagnostic and prognostic algorithm of patients with heart failure. Furthermore, it provides important information for detecting early signs of right ventricular unfavorable remodeling, and consequently, guiding appropriate therapeutic interventions.

Echocardiographic assessment of left ventricular systolic function: from ejection fraction to torsion.

Assessment of left ventricular (LV) systolic function is the cornerstone of the echocardiographic examination. There are many echocardiographic parameters that can be used for clinical and research purposes, each one with its pros and cons. The LV ejection fraction is the most used one due to its feasibility and predictability, but it also has many limits, related to both the imaging technique used for calculation and to the definition itself. LV longitudinal function is expression of subendocardial fibers contraction. Because the subendocardium is often involved early in many pathological processes, its analysis has been a fertile field for the development of sensitive parameters. Longitudinal function can be evaluated in many ways, such as M-mode echocardiography, tissue Doppler imaging, and speckle tracking echocardiography. This latter is a relatively new tool to assess LV function through measurement of myocardial strain, with a high temporal and spatial resolution and a better inter- and intra-observer reproducibility compared to Doppler strain. It is angle independent, not affected by translation cardiac movements, and can assess simultaneously the entire myocardium along all the three-dimensional geometrical (longitudinal, circumferential, and radial) axes. Speckle tracking echocardiography also allows the analysis of LV torsion. The aim of this paper was to review the main echocardiographic parameters of LV systolic function and to describe its pros and cons.

4D flow MRI and T1 -Mapping: Assessment of altered cardiac hemodynamics and extracellular volume fraction in hypertrophic cardiomyopathy.

PURPOSE: Hypertrophic cardiomyopathy (HCM) is associated with altered hemodynamics in the left ventricular outflow tract (LVOT) and myocardial tissue abnormalities such as fibrosis. The aim of this study was to quantify changes in LVOT 3D hemodynamics and myocardial extracellular volume fraction (ECV, measure of fibrosis) and to investigate relationships between elevated flow metrics and left ventricular (LV) tissue abnormalities. MATERIALS AND METHODS: Cardiac magnetic resonance imaging (MRI) including 4D flow (field strength = 1.5T, resolution = 2.1-4.0 × 2.1-4.0 × 2.5-3.2 mm(3) ; venc = 150-250 cm/s; TE/TR/FA = 2.2-2.5msec/4.6-4.9msec/15°) for the in vivo assessment of 3D blood flow velocities with full coverage of the LVOT was applied in 35 patients with HCM (54 ± 15 years) and 10 age-matched healthy controls (45 ± 14 years). In addition, pre- and postcontrast myocardial T1 -mapping (resolution = 2.3 × 1.8 mm, slice thickness = 8 mm, TE/TR-FA = 1.0-1.1msec/2.0-2.2msec/35°) of the LV (basal, mid-ventricular, apical short axis) was performed in a subgroup of 23 HCM patients. Analysis included the segmentation of the LVOT and quantification of peak systolic LVOT pressure gradients and rate of viscous energy loss EL ' as well as left ventricular ECV. RESULTS: HCM patients demonstrated significantly elevated peak systolic LVOT pressure gradients (21 ± 16 mmHg vs. 9 ± 2 mmHg) and energy loss EL ' (3.8 ± 2.5 mW vs. 1.5 ± 0.7 mW, P < 0.005) compared to controls. There was a significant relationship between increased LV fibrosis (ECV) with both elevated pressure gradients (R(2) = 0.44, P < 0.001) and energy loss EL ' (R(2) = 0.46, P < 0.001). CONCLUSIONS: The integration of 4D-flow and T1 -mapping-MRI allowed for the evaluation of tissue and flow abnormalities in HCM patients. Our findings suggest a mechanistic link between abnormal LVOT flow, increased LV loading, and adverse myocardial remodeling in HCM.

Circulating miR-29a, among other up-regulated microRNAs, is the only biomarker for both hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy.

OBJECTIVES: The purpose of this paper was to determine whether microRNAs (miRNAs) involved in myocardial remodeling were differentially expressed in the blood of hypertrophic cardiomyopathy (HCM) patients, and whether circulating miRNAs correlated with the degree of left ventricular hypertrophy and fibrosis. BACKGROUND: miRNAs-small, noncoding ribonucleic acids (RNAs) that regulate gene expression by inhibiting RNA translation-modulate cellular function. Myocardial miRNAs modulate processes such as cardiomyocyte (CM) hypertrophy, excitation-contraction coupling, and apoptosis; non-CM-specific miRNAs regulate myocardial vascularization and fibrosis. Recently, the possibility that circulating miRNAs may be biomarkers of cardiovascular disease has been raised. METHODS: Forty-one HCM patients were characterized with conventional transthoracic echocardiography and cardiac magnetic resonance. Peripheral plasma levels of 21 miRNAs were assessed by quantitative real-time polymerase chain reaction and were compared with levels in a control group of 41 age- and sex-matched blood donors. RESULTS: Twelve miRNAs (miR-27a, -199a-5p, -26a, -145, -133a, -143, -199a-3p, -126-3p, -29a, -155, -30a, and -21) were significantly increased in HCM plasma. However, only 3 miRNAs (miR-199a-5p, -27a, and -29a) correlated with hypertrophy; more importantly, only miR-29a correlated also with fibrosis. CONCLUSIONS: Our data suggest that cardiac remodeling associated with HCM determines a significant release of miRNAs into the bloodstream: the circulating levels of both cardiac- and non-cardiac-specific miRNAs are significantly increased in the plasma of HCM patients. However, correlation with left ventricular hypertrophy parameters holds true for only a few miRNAs (i.e., miR-199a-5p, -27a, and -29a), whereas only miR-29a is significantly associated with both hypertrophy and fibrosis, identifying it as a potential biomarker for myocardial remodeling assessment in HCM.

Speckle-tracking analysis based on 2D echocardiography does not reliably measure left ventricular torsion.

PURPOSE: Worldwide left ventricular (LV) twist is measured by 2D speckle tracking acquiring apical short axis at a LV level where papillary muscles are no longer visible; however, we hypothesized that this methodological recommendation is not enough accurate to obtain a reliable measurement of apical rotation. METHODS: We measured twist and untwist rate in 30 healthy subjects by following the earlier method. By 3D echocardiography, we identified two LV apex levels: (i) 3D Apex, defined as the last apical slice at which LV cavity was visible; (ii) 2D Apex, defined as the level where diameters are equal to those of apical LV short axis used for twist analysis in the same subject. The ratio between the distance of 2D Apex and 3D Apex from LV base was calculated and expressed as percentage (2D Apex/3D Apex). RESULTS: 2D Apex/3D Apex was strongly related to the magnitude of twist and untwisting rate (r = 0·82, P<0·001; r = -0·46, P = 0·015, respectively). The only determinant of twist was 2D Apex/3D Apex (r(2)  = 0·68; r = 0·82; F ratio: 52·6, P<0·001); whereas untwisting rate was influenced by 2D Apex/3D Apex and age (r(2)  = 0·42; r = 0·65; F ratio: 7·7; P = 0·003 for 2D Apex/3D Apex; and P = 0·011 for age). CONCLUSIONS: Left ventricular apical level acquisition, even when recorded in a standard manner, determines variability of twist mechanics measurements. Thus, current anatomical markers used to identify LV apex for twist analysis are not reliable and need different standardization. 3D echocardiography may help in such standardization.

Percutaneous treatment of patients with heart diseases: selection, guidance and follow-up. A review.

Aortic stenosis and mitral regurgitation, patent foramen ovale, interatrial septal defect, atrial fibrillation and perivalvular leak, are now amenable to percutaneous treatment. These percutaneous procedures require the use of Transthoracic (TTE), Transesophageal (TEE) and/or Intracardiac echocardiography (ICE). This paper provides an overview of the different percutaneous interventions, trying to provide a systematic and comprehensive approach for selection, guidance and follow-up of patients undergoing these procedures, illustrating the key role of 2D echocardiography.

Aortic valve sclerosis in patients with peripheral and/or coronary arterial disease.

BACKGROUND: Aortic valve sclerosis (AVS) is a marker of cardiovascular risk; its prevalence increases in elderly and in patients with hypertension and/or coronary arterial disease (CAD). There are no data available in patients with peripheral arterial disease (PAD) and with both CAD and PAD. METHODS: To investigate the presence of AVS, 57 patients with stable CAD, 38 with PAD, and 62 with CAD + PAD where studied by echocardiography. RESULTS: The prevalence of AVS progressively increased within groups (P = 0.005). The prevalence of AVS in PAD doubled that in CAD group (42.1% vs. 22.8%, P < 0.05). PAD patients had a 4.634 (95% CI: 1.02-17.88; P = 0.026) fold increased risk of AVS compared to CAD. Also CAD + PAD group had a higher prevalence of aortic sclerosis when compared to CAD group (50.8% vs. 22.8%, P = 0.001). CAD + PAD showed a 3.799 (95% CI: 1.26-11.45; P < 0 .01) fold greater risk of aortic sclerosis than CAD group. There were no differences in AVS prevalence between CAD + PAD and PAD group (50.8% vs. 42.1%; P = 0.36). Age was related to AVS in both analysis (PAD vs. CAD and CAD + PAD vs. CAD: OR = 1.09, 95% CI: 1.02-1.16, P = 0.011 and OR = 1.13, 95% CI: 1.07-1.21; P < 0.001) but no classical cardiovascular risk factors. CONCLUSIONS: PAD patients have an elevated prevalence of AVS greater than CAD patients. In patients with both disease, the prevalence of AVS is similar to that of patients with PAD alone.

Myocardial fibrosis and diastolic dysfunction in patients on chronic haemodialysis.

BACKGROUND: Left ventricular (LV) diastolic dysfunction is linked to myocardial collagen content in many cardiac diseases. There are no data regarding such relationship in patients with end-stage renal disease (ESRD) undergoing haemodialysis. METHODS: Twenty-five patients with ESRD undergoing haemodialysis were studied by echocardiography. LV diastolic function was investigated by Doppler echocardiography, by analysing LV filling velocities at rest and during loading manoeuvres, which represent an estimate of LV filling pressure. According to the Doppler pattern, LV filling pressure in a given patient was judged to be normal or slightly increased or to be moderately or severely increased. The presence of myocardial fibrosis was estimated by ultrasound tissue characterization with integrated backscatter, which in diastole correlates with the collagen content of the myocardium. RESULTS: Integrated backscatter was higher in patients with moderate or severely increased than in patients with normal or slightly increased LV filling pressure (integrated backscatter: 51.0 +/- 9.8 vs 41.6 +/- 5.6%; P = 0.008). Integrated backscatter was a strong and independent determinant of diastolic dysfunction (odds ratio = 1.212; P = 0.040). CONCLUSION: Our data support the hypothesis that, in a selected population of patients with ESRD undergoing haemodialysis, myocardial fibrosis is associated with LV diastolic myocardial properties.