Anemia and Management of Heart Failure Patients.

Anemia is common in heart failure with preserved and reduced ejection fraction. It is independently associated with poor functional status, hospitalization, and reduced survival. Its etiology is complex and multifactorial. Hemodynamic and nonhemodynamic compensatory mechanisms have been discussed as a response to chronic anemia. Whether anemia is a risk marker of advanced disease or a risk factor for progressive heart failure is debated. Current guidelines recommend a diagnostic workup as a part of standard management. Studies investigating intravenous iron administration reported beneficial effects on clinical outcomes. This article reviews current information on anemia.

Reversible left ventricular diastolic dysfunction-Overview and clinical implications.

Strong evidence supports a pathophysiological link between left ventricular diastolic dysfunction (LVDD) and symptoms in many patients with heart failure, including those with normal LV ejection fraction. Thus, echocardiographic assessment of LV diastolic function is currently recommended when evaluating patients with dyspnea of suspected or known cardiac origin. Beyond the well-established role in the diagnostic algorithm of heart failure, LVDD is an independent predictor of cardiovascular events in various patient cohorts and in the general population. Moreover, several studies suggested a dynamic link between ventricular relaxation, filling dynamics, and prognosis. Thus, worsening of LVDD emerged as a marker of worse prognosis, whereas its improvement is associated with better outcomes. From this perspective, it is important for clinicians to recognize the potentially reversible causes of LVDD that can be identified and treated with symptomatic and/or prognostic benefits. The purpose of this review is to discuss several clinical conditions associated with reversible LVDD, from possible mechanisms to potential clinical implications.

Correlation between global longitudinal strain and QRS voltage on electrocardiogram in patients with left ventricular hypertrophy.

PURPOSE: Left ventricular hypertrophy (LVH) is as an independent risk factor. Discrepancies were reported between LV mass (LVM) estimated by echocardiography and electrocardiography (ECG) findings. We hypothesized that QRS voltage criteria may reflect not only anatomical changes (LVM) but also changes in LV function and we tested the relationship between QRS voltage and echocardiographic parameters of LV function in patients (pts) with different types of LVH. METHODS: We prospectively enrolled pts with LVH and preserved ejection fraction (LVEF >50%): 20 pts with isolated arterial hypertension, HTN, 20 pts with severe aortic stenosis, AS (indexed aortic valve area <0.6 cm(2)/m(2)), and 20 pts with symmetric hypertrophic cardiomyopathy, HCM. Standard 12-lead ECG (including Sokolow and Cornell voltage indices) and a comprehensive two-dimensional (2D) echocardiography were performed in all. Left ventricular mass was calculated according to Devereux formula. Global longitudinal strain (GLS) was assessed by speckle tracking echocardiography. RESULTS: A significant correlation was found between both ECG indices and LVM assessed by echocardiography. Moreover, significant correlations were found between Sokolow-Lyon voltage and LVEF (r = 0.26; P = 0.03), GLS (r = 0.59; P < 0.001) and E/e' average (r = 0.43; P < 0.001). Cornell voltage index correlated significantly only with GLS. In multivariable analysis GLS emerged as the only independent correlate of both Sokolow-Lyon (ß = 0.6, P < 0.001) and Cornell voltage indices (ß = 0.45, P < 0.001). CONCLUSION: These findings suggest that in pts with LVH, ECG should no longer be used only as a surrogate method for LVM estimation (structural changes only), but rather as an investigation complementary to imaging, incorporating information on overall LV remodeling (changes in structure and function).

Diagnosing diastolic dysfunction and heart failure with preserved ejection fraction in patients with atrial fibrillation: a clinical challenge.

Left ventricular (LV) diastolic dysfunction, atrial fibrillation (AF), and heart failure with preserved ejection fraction (HFpEF) share common risk factors and are closely related to one another and to adverse cardiovascular events. Exertional dyspnoea in patients with AF should trigger a comprehensive LV diastolic function evaluation since AF frequently precedes incident HFpEF. An echocardiographic assessment of LV diastolic function in patients with AF is challenging, mainly because of variability in cycle length, the absence of atrial contraction, and the frequent occurrence of left atrial enlargement regardless of LV filling pressures (LVFPs). The algorithm of the 2016 recommendations for the evaluation of LV diastolic function cannot be directly applied in this setting. This review discusses the modalities available for diastolic function assessment and HFpEF diagnosis in patients with AF. Based on currently available data, a reasonable clinical target of diastolic function evaluation in AF would be to reach a binary conclusion: LVFP elevated or not. Recently, a two-step algorithm that combined several echocardiographic parameters plus the inclusion of body mass index has been proposed to differentiate normal from elevated LVFP in patients with AF. The echocardiographic evaluation must be complemented by a thorough clinical evaluation along with natriuretic peptides and cardiac catheterization in selected cases. If a diagnosis of HFpEF cannot be ascertained, a close follow-up for timely identification of diastolic dysfunction markers, along with monitoring and correction of modifiable risk factors, is recommended.

Evaluation of left ventricular filling pressure by echocardiography in patients with atrial fibrillation.

BACKGROUND: Echocardiography is widely used to evaluate left ventricular (LV) diastolic function in patients suspected of heart failure. For patients in sinus rhythm, a combination of several echocardiographic parameters can differentiate between normal and elevated LV filling pressure with good accuracy. However, there is no established echocardiographic approach for the evaluation of LV filling pressure in patients with atrial fibrillation. The objective of the present study was to determine if a combination of several echocardiographic and clinical parameters may be used to evaluate LV filling pressure in patients with atrial fibrillation. RESULTS: In a multicentre study of 148 atrial fibrillation patients, several echocardiographic parameters were tested against invasively measured LV filling pressure as the reference method. No single parameter had sufficiently strong association with LV filling pressure to be recommended for clinical use. Based on univariate regression analysis in the present study, and evidence from existing literature, we developed a two-step algorithm for differentiation between normal and elevated LV filling pressure, defining values ≥ 15 mmHg as elevated. The parameters in the first step included the ratio between mitral early flow velocity and septal mitral annular velocity (septal E/e'), mitral E velocity, deceleration time of E, and peak tricuspid regurgitation velocity. Patients who could not be classified in the first step were tested in a second step by applying supplementary parameters, which included left atrial reservoir strain, pulmonary venous systolic/diastolic velocity ratio, and body mass index. This two-step algorithm classified patients as having either normal or elevated LV filling pressure with 75% accuracy and with 85% feasibility. Accuracy in EF ≥ 50% and EF < 50% was similar (75% and 76%). CONCLUSIONS: In patients with atrial fibrillation, no single echocardiographic parameter was sufficiently reliable to be used clinically to identify elevated LV filling pressure. An algorithm that combined several echocardiographic parameters and body mass index, however, was able to classify patients as having normal or elevated LV filling pressure with moderate accuracy and high feasibility.

Electrocardiographic and Echocardiographic Predictors of Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy.

Background: Patients with hypertrophic cardiomyopathy (HCM) have an increased prevalence of atrial fibrillation (AF) compared to the general population, and left atrium (LA) remodeling is strongly correlated with the risk of AF. This prospective, monocentric study aimed to assess the role of LA electrocardiographic and echocardiographic (structural and functional) parameters in predicting the risk for incident AF in patients with HCM. Methods and Results: The study population consisted of 126 HCM patients in sinus rhythm (52.6 ± 16.2 years, 54 men), 118 of them without documented AF. During a median follow-up of 56 (7-124) months, 39 (30.9%) developed a new episode of AF. Multivariable analysis showed that LA booster pump function (assessed by ASr, HR = 4.24, CI = 1.84-9.75, and p = 0.038) and electrical dispersion (assessed by P wave dispersion - Pd, HR = 1.044, CI = 1.029-1.058, and p = 0.001), and not structural parameters (LA diameter, LA volume) were independent predictors of incident AF. Seventy-two patients had a LA diameter < 45 mm, and 16 of them (22.2%) had an AF episode during follow-up. In this subgroup, only Pd emerged as an independent predictor for incident AF (HR = 1.105, CI = 1.059-1.154, and p = 0.002), with good accuracy (AUC = 0.89). Conclusion: Left atrium booster pump function (ASr) and electrical dispersion (Pd) are related to the risk of incident AF in HCM patients. These parameters can provide further stratification of the risk for AF in this setting, including in patients considered at lower risk for AF based on the conventional assessment of LA size.

Left ventricular torsional dynamics in aortic stenosis: relationship between left ventricular untwisting and filling pressures. A two-dimensional speckle tracking study.

AIMS: The contribution of left ventricular (LV) untwisting to LV suction and early-diastolic filling was previously demonstrated, but this was not yet tested in patients with aortic stenosis (AS). We sought to assess the relationship between LV untwisting and LV filling pressures in patients with severe AS and normal left ventricular ejection fraction (LVEF) using speckle tracking echocardiography. METHODS AND RESULTS: Sixty-one consecutive patients (66 +/- 9 years) with severe AS, preserved LVEF (63 +/- 6%), and 40 normal subjects (47 +/- 12 years) were prospectively enrolled. A comprehensive echocardiographic examination was performed in all. LV rotation and twisting were assessed using speckle tracking echocardiography. Peak apical back rotation rate, peak LV untwisting rate, and time intervals from QRS onset (ECG) to each of them were measured. Brain natriuretic peptide (BNP) levels were determined in 30 patients. Patients with AS were older than normal subjects (P < 0.001). LV mass, LA volume, LV filling pressures as well as peak apical back rotation rate and time to peak apical back rotation rate were increased in patients (P < 0.05 for all). In patients with AS, both time to peak LV untwisting rate and time to peak apical back rotation rate were significantly related to E/E' ratio and to BNP levels (P < 0.04 for all). CONCLUSION: In patients with severe AS and preserved LVEF, there is a significant relationship between LV untwisting and LV filling pressures, suggesting a role for impaired LV untwisting in the pathophysiology of diastolic dysfunction in this setting.

Carotid arterial stiffness is increased and related to left ventricular function in patients with hypertrophic cardiomyopathy.

AIMS: To assess the carotid mechanical properties in patients with hypertrophic cardiomyopathy and the relation between arterial stiffness and left ventricular function in this setting. METHODS AND RESULTS: We have prospectively enrolled 71 patients (52 ± 16 years, 34 men) with hypertrophic cardiomyopathy, divided into two groups depending on the presence (46 patients) or absence (25 patients) of cardiovascular risk factors associated with increased arterial stiffness. Twenty-five normal subjects similar by age and gender with hypertrophic cardiomyopathy patients without risk factors formed the control group. A comprehensive echocardiography was performed in all subjects. Carotid arterial stiffness index (ß index), pressure-strain elastic modulus, arterial compliance, and pulse wave velocity were also obtained using an echo-tracking system. ß index, pulse wave velocity, and pressure-strain elastic modulus were significantly higher in hypertrophic cardiomyopathy patients without risk factors compared to controls. After linear regression analysis, the increase in carotid ß index was independently correlated with the presence of hypertrophic cardiomyopathy [beta = 0.49, 95% confidence interval (CI) = 1.04-3.02; P < 0.001]. In the entire hypertrophic cardiomyopathy population arterial stiffness parameters correlated with age, gender, hypertension degree, presence of hypercholesterolaemia, and the E/e' ratio. In multivariable analysis, ß index (beta = 0.36, 95% CI = 0.32-1.25; P = 0.001), global left ventricular longitudinal strain, and the presence of left ventricular outflow tract obstruction were independently correlated with the E/e' ratio. CONCLUSION: In patients with hypertrophic cardiomyopathy arterial stiffness is increased independently of age or presence of cardiovascular risk factors. Carotid artery stiffness is independently related to left ventricular filling pressure, increased arterial stiffness representing a possible marker of a more severe phenotype.

Respiratory maneuvers in echocardiography: a review of clinical applications.

During echocardiographic examination, respiration induces cyclic physiological changes of intracardiac haemodynamics, causing normal variations of the right and left ventricle Doppler inflows and outflows and physiological variation of extracardiac flows. The respiration related hemodynamic variation in intra and extracardiac flows may be utilized in the echocardiography laboratory to aid diagnosis in different pathological states. Nevertheless, physiologic respiratory phases can cause excessive translational motion of cardiac structures, lowering 2D image quality and interfering with optimal Doppler interrogation of flows or tissue motion.This review focuses on the impact of normal respiratory cycle and provocative respiratory maneuvers in echocardiographic examination, both in physiological and pathological states, emphasizing their applications in specific clinical situations.

Echo-tracking assessment of carotid artery stiffness in patients with aortic valve stenosis.

BACKGROUND: There is little information about mechanical properties of large arteries in patients (pts) with aortic stenosis (AS). METHODS: Nineteen patients with AS (aortic valve area: 0.88 +/- 0.29 cm(2)) and 24 control subjects without AS but with a similar distribution of risk factors were recruited. beta index, pressure-strain elastic modulus (Ep), arterial compliance (AC), augmentation index (AIx), and local pulse-wave velocity (PWV) were obtained at the level of right common carotid artery (CCA) by a real time echo-tracking system. Time to dominant peak of carotid diameter change waveform, corrected for heart rate (tDPc), and maximum rate of rise of carotid diameter (dD/dt) were measured. Systemic arterial compliance (SAC) was also calculated. Parameters of AS severity (mean gradient, valve area, stroke work loss [SWL]) were determined. RESULTS: tDPc was higher in patients with AS than in controls (7.9 +/- 0.6 vs. 6.6 +/- 0.7, P < 0.0001) while dD/dt was lower (5.3 +/- 3.6 mm/s vs. 7.8 +/- 2.8 mm/s, P = 0.01). AIx was significantly higher in AS group (32.5 +/- 13.6% vs. 20.6 +/- 12.2%, P = 0.005) and had a linear correlation both with tDPc (r = 0.63, P < 0.0001) and with dD/dt (r =-0.38, P = 0.01). There was a significant correlation between carotid AC and SAC (r = 0.49, P = 0.03), but only carotid AC was related to SWL (r = 0.51, P = 0.02), while SAC was not (P = 0.26). CONCLUSIONS: AIx was the only parameter of arterial rigidity found to be higher in patients with AS than in controls. Carotid AC showed a significant correlation with SAC and it seemed to be more closely related to AS severity than to SAC.

Left Atrial Dysfunction as an Independent Correlate of Heart Failure Symptoms in Patients With Severe Aortic Stenosis and Preserved Left Ventricular Ejection Fraction.

BACKGROUND: Data regarding the contribution of left atrial (LA) dysfunction to the occurrence of heart failure in patients with severe aortic stenosis (AS) are scarce. The aim of this study was to assess the relationship between LA deformation and symptomatic status in this clinical setting. METHODS: A total of 361 consecutive patients with severe AS (aortic valve area [AVA] index ≤ 0.6 cm2/m2) referred to the echocardiography laboratory were prospectively screened. Two hundred forty-eight patients with preserved left ventricular (LV) ejection fraction (≥50%), in sinus rhythm, and with no more than mild aortic or mitral regurgitation (202 symptomatic and 46 asymptomatic) were enrolled. Asymptomatic status was confirmed by exercise echocardiography or electrocardiography, as clinically indicated. All patients underwent comprehensive echocardiography, including speckle-tracking analysis of LV and LA deformation. RESULTS: No significant differences were found between the two groups regarding age and cardiovascular risk factors. LV ejection fraction and geometric parameters were similar between groups despite higher indexed AVA in asymptomatic patients. In symptomatic patients, brain natriuretic peptide values, average E/e' ratio, and LA size were higher, whereas LV global longitudinal strain and peak LA longitudinal strain and strain rate parameters were lower compared with asymptomatic patients. AVA and peak systolic LA longitudinal strain rate were the only independent correlates of heart failure symptoms (P = .04 and P = .01, respectively). CONCLUSIONS: LA systolic strain rate, in addition to AVA, emerged as an independent correlate of the presence of heart failure in patients with severe AS and preserved LV ejection fraction. The echocardiographic evaluation of LA function by speckle-tracking may become useful for risk stratification in patients with asymptomatic AS, but larger prospective studies are needed.

Revascularization in a 17-Year-Old Girl with Neurofibromatosis and Severe Hypertension Caused by Renal Artery Stenosis.

Renal artery stenosis caused by neurofibromatosis is a rare cause of renovascular hypertension. This hypertension can develop during childhood and is one of the leading causes of poor outcome. We report the case of a 17-year-old girl who was incidentally diagnosed with severe hypertension. During her examination for secondary hypertension, we reached a diagnosis of neurofibromatosis type 1 on the basis of a cluster of typical findings: optic nerve glioma, café au lait spots, nodular neurofibromas, and axillary freckling. Renal angiograms revealed a hemodynamically significant left renal artery stenosis (70%). Renal angioplasty with a self-expanding stent was performed one month later for rapidly progressive renal artery stenosis (90%) and uncontrolled blood pressure. Excellent blood pressure control resulted immediately and was maintained as of the 2-year follow-up evaluation. We think that percutaneous transluminal renal angioplasty can be effective in select patients who have neurofibromatosis type 1 and refractory hypertension caused by renal artery stenosis.

Left atrial dysfunction as a determinant of pulmonary hypertension in patients with severe aortic stenosis and preserved left ventricular ejection fraction.

In patients with severe aortic stenosis (AS), the presence of pulmonary hypertension (PH) has been linked to a poor prognosis. We aimed to assess the main determinants of PH in patients with severe AS and preserved left ventricular ejection fraction (LVEF). We prospectively enrolled 108 consecutive patients with isolated severe AS (indexed aortic valve area <0.6 cm2/m2) and LVEF >50%, in sinus rhythm. Left atrial (LA) function was assessed using longitudinal deformation parameters (by speckle tracking echocardiography). PH (defined as systolic pulmonary artery pressure >40 mmHg) was present in 20 patients. Patients with severe AS and PH were older (p = 0.05), had higher BNP values (p = 0.05) and a greater degree of LV diastolic dysfunction: higher E/e' and E/A ratios and lower EDT values (p < 0.03 for all) compared to patients without PH. There were no differences between groups regarding AS severity and LV systolic function parameters. Patients with PH had a more impaired LA function: lower septal and lateral late diastolic peak velocity a' (p < 0.001 and p = 0.04 respectively) and lower LA peak longitudinal strain and strain rate parameters (p ≤ 0.005 for all). In multivariable analysis, LA late diastolic longitudinal strain rate was the only independent correlate of PH in our patients (p = 0.04). Patients with isolated severe AS, preserved LVEF and PH had larger LA volumes, a more impaired LA function, and higher LV filling pressures compared to those without PH. LA booster pump function, reflected by late diastolic longitudinal strain rate, emerged as an independent correlate of PH in these patients.

Echo-Doppler estimation of left ventricular filling pressure: results of the multicentre EACVI Euro-Filling study.

AIMS: The present Euro-Filling report aimed at comparing the diagnostic accuracy of the 2009 and 2016 echocardiographic grading algorithms for predicting invasively measured left ventricular filling pressure (LVFP). METHOD AND RESULTS: A total of 159 patients who underwent simultaneous evaluation of echo estimates of LVFP and invasive measurements of LV end-diastolic pressure (LVEDP) were enrolled at nine EACVI centres. Thirty-nine (25%) patients had a reduced LV ejection fraction (<50%), 77 (64%) were in NYHA ≥ II, and 85 (53%) had coronary artery disease. Sixty-four (40%) patients had elevated LVEDP (≥15 mmHg). Taken individually, all echocardiographic Doppler estimates of LVFP (E/A, E/e', left atrial volume, tricuspid regurgitation jet velocity) were marginally correlated with LVEDP. By using the 2016 recommendations, 65% of patients with normal non-invasive estimate of LVFP had normal LVEDP, while 79% of those with elevated non-invasive LVFP had elevated invasive LVEDP. By using 2009 recommendations, 68% of the patients with normal non-invasive LVFP had normal LVEDP, while 55% of those with elevated non-invasive LVFP had elevated LVEDP. The 2016 recommendations (sensitivity 75%, specificity 74%, positive predictive value 39%, negative predictive value 93%, AUC 0.78) identified slightly better patients with elevated invasive LVEDP (≥ 15 mmHg) as compared with the 2009 recommendations (sensitivity 43%, specificity 75%, positive predictive value 49%, negative predictive value 71%, AUC 0.68). CONCLUSION: The present Euro-Filling study demonstrates that the new 2016 recommendations for assessing LVFP non-invasively are fairly reliable and clinically useful, as well as superior to the 2009 recommendations in estimating invasive LVEDP.

A Congenital Gerbode Defect associated with a Rare Structural Abnormality of the Mitral Valve Diagnosed in an Adult Patient.

We report the case of a rare association of a congenital Gerbode defect with severe mitral regurgitation due to abnormal linear structure of mitral valve, diagnosed in an adult patient. The case highlights the importance of a thorough examination interpreting the echocardiographic findings on a pathophysiological basis. It also underlines the complementary role of different imaging techniques with transesophageal echocardiography, allowing the precise assessment of both structural and functional abnormalities in such a complex case. The patient underwent mitral valve replacement with a bileaflet mechanical prosthesis and repair of the Gerbode defect. The imaging findings were confirmed during the surgical procedure, leading to a good outcome.

Left ventricular shape and mass impact torsional dynamics in asymptomatic patients with chronic aortic regurgitation and normal left ventricular ejection fraction.

Chronic aortic regurgitation (AR) is associated with a unique pattern of left ventricular (LV) volume and pressure overload, leading to LV remodelling. LV torsional motion, a key component of LV performance, can be altered in this setting. We aimed to assess the impact of LV remodelling on LV torsional dynamics parameters using speckle-tracking echocardiography (STE) in asymptomatic AR patients. We prospectively enrolled 60 patients with chronic AR and LVEF > 50% and 55 healthy controls. LV rotation, twisting and untwisting were assessed using STE. Patients with AR had higher LV diameters, volumes and mass, a more spherical LV shape than controls, but similar LVEF. In AR patients we found reduced peak LV apical rotation and decreased (2.1 ± 0.8 vs 2.9 ± 0.9°/cm, p < 0.001) and delayed (time to peak LV twist: 0.94 ± 0.12 vs 0.99 ± 0.09, p = 0.004) peak LV torsion. Also, peak LV untwisting velocity was decreased (-123.5 ± 41.5 vs -152.3 ± 55.0°/s, p = 0.002) due to lower peak LV apical diastolic rotation rate. LV shape influenced LV torsional dynamics, a more spherical LV displaying reduced peak LV apical rotation and diastolic rotation rate and decreased LV twist. A more hypertrophied LV had a lower peak LV torsion, peak LV apical diastolic rotation rate and peak LV untwisting velocity. LV apical rotation and torsion are decreased and LV twist is delayed in patients with chronic AR and normal LVEF, detecting early subclinical LV dysfunction before LVEF declines. Also, LV untwisting is reduced in these patients. LV remodelling impairs LV torsional dynamics parameters in this setting.

Right ventricular remodeling, its correlates, and its clinical impact in hypertrophic cardiomyopathy.

BACKGROUND: Structural right ventricular (RV) abnormalities are present in a substantial proportion of patients with hypertrophic cardiomyopathy (HCM), but the trigger for RV hypertrophy remains unclear. The aim of this study was to assess the relationship between RV and left ventricular (LV) remodeling and the impact of biventricular involvement on clinical status in this setting. METHODS: Ninety-nine patients with HCM and 30 normal subjects with a similar age and gender distribution were prospectively enrolled. Comprehensive echocardiography was performed in all, including the assessment of LV and RV function by tissue Doppler and speckle-tracking echocardiography. Measurement of RV free wall thickness (RVWT) was performed at end-diastole, in a zoomed subcostal view, focusing on the RV midwall. RESULTS: Patients with HCM had increased RVWT (6.4 ± 1.9 vs 3.6 ± 0.8 mm, P < .001) and lower values of RV global longitudinal strain (-19.4 ± 4.4% vs -23.8 ± 2.7%, P < .001) compared with control subjects. RVWT was independently related to LV mass and LV global longitudinal strain. Increased RVWT was correlated with New York Heart Association class (r = 0.20, P = .04) and calculated sudden cardiac death risk score (r = 0.52, P < .001) and was independently related to the presence of ventricular arrhythmias (odds ratio, 2.02; 95% CI, 1.28-3.19; P = .002). CONCLUSIONS: In patients with HCM, the presence of RV hypertrophy was associated with increased LV mass and reduced LV longitudinal strain, correlated with increased calculated sudden cardiac death risk score, and independently related to the presence of ventricular arrhythmias. These data suggest more severe disease in patients with biventricular HCM.