New perspectives in the echocardiographic hemodynamics multiparametric assessment of patients with heart failure.

International Guidelines consider left ventricular ejection fraction (LVEF) as an important parameter to categorize patients with heart failure (HF) and to define recommended treatments in clinical practice. However, LVEF has some technical and clinical limitations, being derived from geometric assumptions and is unable to evaluate intrinsic myocardial function and LV filling pressure (LVFP). Moreover, it has been shown to fail to predict clinical outcome in patients with end-stage HF. The analysis of LV antegrade flow derived from pulsed-wave Doppler (stroke volume index, stroke distance, cardiac output, and cardiac index) and non-invasive evaluation of LVFP have demonstrated some advantages and prognostic implications in HF patients. Speckle tracking echocardiography (STE) is able to unmask intrinsic myocardial systolic dysfunction in HF patients, particularly in those with LV preserved EF, hence allowing analysis of LV, right ventricular and left atrial (LA) intrinsic myocardial function (global peak atrial LS, (PALS)). Global PALS has been proven a reliable index of LVFP which could fill the gaps "gray zone" in the previous Guidelines algorithm for the assessment of LV diastolic dysfunction and LVFP, being added to the latest European Association of Cardiovascular Imaging Consensus document for the use of multimodality imaging in evaluating HFpEF. The aim of this review is to highlight the importance of the hemodynamics multiparametric approach of assessing myocardial function (from LVFP to stroke volume) in patients with HF, thus overcoming the limitations of LVEF.

Stress echocardiography in heart failure patients: additive value and caveats.

Heart failure (HF) is a clinical syndrome characterized by well-defined signs and symptoms due to structural and/or myocardial functional impairment, resulting in raised intracardiac pressures and/or inadequate cardiac stroke volume at rest or during exercise. This could derive from direct ischemic myocardial injury or other chronic pathological conditions, including valvular heart disease (VHD) and primary myocardial disease. Early identification of HF etiology is essential for accurate diagnosis and initiation of early and appropriate treatment. Thus, the presence of accurate means for early diagnosis of HF symptoms or subclinical phases is fundamental, among which echocardiography being the first line diagnostic investigation. Echocardiography could be performed at rest, to identify overt structural and functional abnormalities or during physical or pharmacological stress, in order to elicit subclinical myocardial function impairment e.g. wall motion abnormalities and raised ventricular filling pressures. Beyond diagnosis of ischemic heart disease, stress echocardiography (SE) has recently shown its unique value for the evaluation of diastolic heart failure, VHD, non-ischemic cardiomyopathies and pulmonary hypertension, with recommendations from international societies in several clinical settings. All these features make SE an important additional tool, not only for diagnostic assessment, but also for prognostic stratification and therapeutic management of patients with HF. In this review, the unique value of SE in the evaluation of HF patients will be described, with the objective to provide an overview of the validated methods for each setting, particularly for HF management.

Detection of myocardial fibrosis by speckle-tracking echocardiography: from prediction to clinical applications.

Myocardial fibrosis (MF) represents the underlying pathologic condition of many cardiac disease, leading to cardiac dysfunction and heart failure (HF). Biopsy studies have shown the presence of MF in patients with decompensating HF despite apparently normal cardiac function. In fact, basic indices of left ventricular (LV) function, such as LV ejection fraction (EF), fail to recognize subtle LV dysfunction caused by MF. Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) is currently recognized as the gold standard imaging investigation for the detection of focal and diffuse cardiac chambers MF; however, its use is limited by its availability and the use of contrast agents, while echocardiography remains the first level cardiac imaging technique due to its low cost, portability and high accessibility. Advanced echocardiographic techniques, above all speckle-tracking echocardiography (STE), have demonstrated reliability for early detection of structural myocardial abnormalities and for the prediction of prognosis in acute and chronic HF. Myocardial strain of both ventricles and also left atrium has been shown to correlate with the degree of MF, providing useful prognostic information in several diseases, such as HF, cardiomyopathies and valvular heart disease. This paper aims to provide an overview of the pathophysiology of MF and the clinical application of STE for the prediction of left and right heart chambers MF in HF patients.

Efficacy and safety of colchicine in patients with coronary artery disease: A systematic review and meta-analysis of randomized controlled trials.

AIMS: Inflammation plays a central role in the pathogenesis and clinical manifestations of atherosclerosis. Randomized controlled trials have investigated the potential benefit of colchicine in reducing cardiovascular (CV) events in patients with coronary artery disease (CAD) but produced conflicting results. The aim of this meta-analysis was to evaluate the efficacy and safety of colchicine in patients with CAD. METHODS: We systematically searched selected electronic databases from inception until 10 December 2020. Primary clinical endpoints were: major adverse cardiac events; all-cause mortality; CV mortality; recurrent myocardial infarction; stroke; hospitalization; and adverse medication effects. Secondary endpoints were short-term effect of colchicine on inflammatory markers. RESULTS: Twelve randomized controlled trials with a total of 13 073 patients with CAD (colchicine n = 6351 and placebo n = 6722) were included in the meta-analysis. At mean follow-up of 22.5 months, the colchicine group had lower risk of major adverse cardiac events (6.20 vs. 8.87%; P < .001), recurrent myocardial infarction (3.41 vs. 4.41%; P = .005), stroke (0.40 vs. 0.90%; P = .002) and hospitalization due to CV events (0.90 vs. 2.87%; P = .02) compared to the control group. The 2 patient groups had similar risk for all-cause mortality (2.08 vs. 1.88%; P = .82) and CV mortality (0.71 vs. 1.01%; P = .38). Colchicine significantly reduced high-sensitivity C-reactive protein (-4.25, P = .001) compared to controls but did not significantly affect interleukin (IL)-ß1 and IL-18 levels. CONCLUSION: Colchicine reduced CV events and inflammatory markers, high-sensitivity C-reactive protein and IL-6, in patients with coronary disease compared to controls. Its impact on cardiovascular and all-cause mortality requires further investigation.

Carotid Atherosclerosis in Predicting Coronary Artery Disease: A Systematic Review and Meta-Analysis.

[Figure: see text].

Left atrial myocardial intrinsic function remodeling response to repair of primary mitral regurgitation.

Severe mitral regurgitation (MR) is a common valve disease which is associated with high mortality, if only managed medically. MR produces chronic and progressive volume overload with left atrial (LA) and left ventricular (LV) dilatation and dysfunction, atrial fibrillation (AF) and eventually myocardial fibrosis, irrespective of ejection fraction (EF). Surgical correction (mitral valve repair) of MR removes the volume overload, hence unmasks pre-operative LV structure and function disturbances, including reduced EF and global longitudinal and circumferential strain, as well as LA volume and strain. This review aims at describing LA remodeling before and after surgical repair.

The Role of Inflammation in Cardiovascular Disease.

Atherosclerosis is a chronic inflammatory disease, in which the immune system has a prominent role in its development and progression. Inflammation-induced endothelial dysfunction results in an increased permeability to lipoproteins and their subendothelial accumulation, leukocyte recruitment, and platelets activation. Recruited monocytes differentiate into macrophages which develop pro- or anti-inflammatory properties according to their microenvironment. Atheroma progression or healing is determined by the balance between these functional phenotypes. Macrophages and smooth muscle cells secrete inflammatory cytokines including interleukins IL-1ß, IL-12, and IL-6. Within the arterial wall, low-density lipoprotein cholesterol undergoes an oxidation. Additionally, triglyceride-rich lipoproteins and remnant lipoproteins exert pro-inflammatory effects. Macrophages catabolize the oxidized lipoproteins and coalesce into a lipid-rich necrotic core, encapsulated by a collagen fibrous cap, leading to the formation of fibro-atheroma. In the conditions of chronic inflammation, macrophages exert a catabolic effect on the fibrous cap, resulting in a thin-cap fibro-atheroma which makes the plaque vulnerable. However, their morphology may change over time, shifting from high-risk lesions to more stable calcified plaques. In addition to conventional cardiovascular risk factors, an exposure to acute and chronic psychological stress may increase the risk of cardiovascular disease through inflammation mediated by an increased sympathetic output which results in the release of inflammatory cytokines. Inflammation is also the link between ageing and cardiovascular disease through increased clones of leukocytes in peripheral blood. Anti-inflammatory interventions specifically blocking the cytokine pathways reduce the risk of myocardial infarction and stroke, although they increase the risk of infections.

Coronary Artery Ectasia: Review of the Non-Atherosclerotic Molecular and Pathophysiologic Concepts.

Coronary artery ectasia (CAE) is frequently encountered in clinical practice, conjointly with atherosclerotic CAD (CAD). Given the overlapping cardiovascular risk factors for patients with concomitant CAE and atherosclerotic CAD, a common underlying pathophysiology is often postulated. However, coronary artery ectasia may arise independently, as isolated (pure) CAE, thereby raising suspicions of an alternative mechanism. Herein, we review the existing evidence for the pathophysiology of CAE in order to help direct management strategies towards enhanced detection and treatment.

Safe performance of echocardiography during the COVID-19 pandemic: a practical guide.

Coronavirus disease-2019 (COVID-19) outbreak has become a worldwide healthcare emergency, with continuously growing number of infected subjects. Considering the easy virus spread through respiratory droplets produced with cough, sneezes or spit or through close contact with infected people or surfaces, healthcare workers are further exposed to COVID-19. Particularly, echocardiography remains an essential diagnostic service which, due to the close contact with patients during the exam, provides echocardiographers high-risk of contagion. Therefore, the common modalities of performing echocardiography should be improved in this scenario, avoiding performing unnecessary exams, using the appropriate personal protective equipment depending on patients' status and location, optimizing time-effectiveness of the echocardiographic study and accurately sanitizing the environment and devices after each exam. This paper aims to provide a simple guide for the clinicians to balance between providing the best care to each patient and protecting themselves and other patients from the spread of the virus. It also proposes the use of the mnemonic PREVENT to resume the crucial indications to be followed for the execution of appropriate echocardiographic examination during the COVID-19 pandemic.

Diastolic function assessment by echocardiography: A practical manual for clinical use and future applications.

Diastole is an important component of the cardiac cycle, during which time optimum filling of the ventricle determines physiological stroke volume ejected in the succeeding systole. Many factors contribute to optimum ventricular filling including venous return, left atrial filling from the pulmonary circulation, and emptying into the left ventricle. Left ventricular filling is also impacted by the cavity emptying function and also its synchronous function which may suppress early diastolic filling in severe cases of dyssynchrony. Sub-optimum LA emptying increases cavity pressure, causes enlarged left atrium, unstable myocardial function, and hence atrial arrhythmia, even atrial fibrillation. Patients with clear signs of raised left atrial pressure are usually symptomatic with exertional breathlessness. Doppler echocardiography is an ideal noninvasive investigation for diagnosing raised left atrial pressure as well as following treatment for heart failure. Spectral Doppler based increased E/A, shortened E-wave deceleration time, increased E/e', and prolonged atrial flow reversal in the pulmonary veins are all signs of raised left atrial pressure. Left atrial reduced myocardial strain is another correlate of raised cavity pressure (>15 mm Hg). In patients with inconclusive signs of raised left atrial pressure at rest, exercise/stress echocardiography or simply passive leg lifting should identify those with stiff left ventricular which suffers raised filling pressures with increased venous return.

Left ventricular pseudoaneurysm complicating a ruptured isolated congenital diverticulum.

We report a case of 41-year-old woman who presented with chest tightness and shortness of breath. Transthoracic echocardiogram (TTE) showed left ventricular (LV) pseudoaneurysm of the inferior wall with preserved LV systolic function. Coronary angiogram was normal. Surgical repair of the pseudoaneurysm with a pericardial patch was performed, and pathological results confirmed rupture of an isolated congenital LV diverticulum, as the most likely etiology.

Left Ventricular Diastolic and Systolic Functions in Patients with Hypothyroidism.

Background and objectives: Long standing hypothyroidism may impair myocardial relaxation, but its effect on systolic myocardial function is still controversial. The aim of this study was to investigate left ventricular (LV) systolic and diastolic function in patients with hypothyroidism. Materials and Methods: This study included 81 (age 42 ± 13 years, 92% female) patients with hypothyroidism, and 22 age and gender matched controls. All subjects underwent a detailed clinical examination followed by a complete biochemical blood analysis including thyroid function assessment and anthropometric parameters measurements. LV function was assessed by 2-dimensional, M-mode and Tissue-Doppler Doppler echocardiographic examination performed in the same day. Results: Patients had lower waist/hip ratio (p< 0.001), higher urea level (p = 0.002), and lower white blood cells (p = 0.011), compared with controls. All other clinical, biochemical, and anthropometric data did not differ between the two groups. Patients had impaired LV diastolic function (lower E wave [p< 0.001], higher A wave [p = 0.028], lower E/A ratio [p< 0.001], longer E wave deceleration time [p = 0.01], and higher E/e' ratio [p< 0.001]), compared with controls. Although LV global systolic function did not differ between groups, LV longitudinal systolic function was compromised in patients (lateral mitral annular plane systolic excursion-MAPSE [p = 0.005], as were lateral and septal s' [p< 0.001 for both]). Conclusions: In patients with hypothyroidism, in addition to compromised LV diastolic function, LV longitudinal systolic function is also impaired compared to healthy subjects of the same age and gender. These findings suggest significant subendocardial function impairment, reflecting potentially micro-circulation disease that requires optimum management.

The left atrium and the right ventricle: two supporting chambers to the failing left ventricle.

Heart failure (HF) is mainly caused by left ventricular (LV) impairment of function, hence detailed assessment of its structure and function is a clinical priority. The frequent involvement of the left atrium (LA) and the right ventricle (RV) in the overall cardiac performance has recently gained significant interest with specific markers predicting exercise intolerance and prognosis being proposed. The LA and RV are not anatomically separated from the LV, while the LA controls the inlet the RV shares the interventricular septum with the LV. Likewise, the function of the two chambers is not entirely independent from that of the LV, with the LA enlarging to accommodate any rise in filling pressures, which could get transferred to the RV via the pulmonary circulation. In the absence of pulmonary disease, LA and RV function may become impaired in patients with moderate-severe LV disease and raised filling pressures. These changes can often occur irrespective of the severity of systolic dysfunction, thus highlighting the important need for critical assessment of the function of the two chambers. This review evaluates the pivotal role of the left atrium and right ventricle in the management of HF patients based on the available evidence.

Double-chambered left ventricle diagnosis by 2D and 3D echocardiography: From fetus to birth.

Double-chambered left ventricle (DCLV) is a rare cardiac anomaly and is characterized by the division of the left ventricle by abnormal muscle and/or fiber bundles into two chambers. We hereby report a fetus which was diagnosed with DCLV in utero by 2D and 3D Fetal echocardiography and the findings were confirmed after birth.

Left atrial compliance index predicts exercise capacity in patients with heart failure and preserved ejection fraction irrespective of right ventricular dysfunction.

BACKGROUND AND AIM: Predictors of exercise capacity in heart failure (HF) with preserved ejection fraction (HFpEF) remain of difficult determination. The aim of this study was to identify predictors of exercise capacity in a group of patients with HFpEF and right ventricle (RV) dysfunction METHODS: In 143 consecutive patients with HFpEF (age 62 ± 9 years, LV EF ≥45) and 41 controls, a complete echocardiographic study was performed. In addition to conventional measurements, LA compliance was calculated using the formula: [LAV max - LAV min/LAV min × 100]. Exercise capacity was assessed using the six-minute walking test (6-MWT). Tricuspid annular plane systolic excursion (TAPSE) < 1.7 cm was utilized to categorize patients with RV dysfunction (n = 40) from those with maintained RV function (n = 103). RESULTS: Patients with RV dysfunction were older (P = 0.002), had higher NYHA class (P = 0.001), higher LV mass index (P = 0.01), reduced septal and lateral MAPSE (all P < 0.001), enlarged LA (P = 0.001) impaired LA compliance index (P < 0.001) and exhibited a more compromised 6-MWT (P = 0.001). LA compliance index correlated more closely with 6-MWT (r = 0.51, P < 0.001) compared with the other LA indices (AP diameter, transverse diameter and volume indexed; r = -0.30, r = -0.35 and r = -0.38, respectively). In multivariate analysis, LA compliance index <60% was 88% sensitive and 61% specific (AUC 0.80, CI = 0.67-0.92 P = 0.001) in predicting exercise capacity. CONCLUSION: An impairment in LA compliance was profound in patients with HFpEF and RV dysfunction and seems to be most powerful independent predictor of limited exercise capacity.

Carotid arterial stiffness and intima-media thickness: A little impact of uric acid.

Accurate assessment of cardiovascular (CV) risk is essential for clinical decision making. Serum uric acid  has been proposed as a novel additional CV risk.

Carotid IM-GSM is better than IMT for identifying patients with multiple arterial disease.

OBJECTIVE: Atherosclerosis is a systemic inflammatory disease that can affect more than one arterial bed simultaneously. The aim of this study was to determine the relationship between ultrasound markers of atherosclerosis and multiple arterial disease. DESIGN: We have included 87 currently asymptomatic carotid disease patients (mean age 69 ± 6 year, 34% females) in this study. Intima media thickness (IMT) and intima media-grey scale median (IM-GSM) were measured in the common carotid artery (CCA), and correlated with previous and/or current atherosclerotic vascular disease in the coronary, carotid and lower extremities. Patients were divided into three groups: (1) asymptomatic, (2) previous symptoms in one arterial territory and (3) previous symptoms in multiple arterial territories. RESULTS: Patients with previous disease in the coronary arteries had higher IMT (p = .034) and lower IM-GSM (p < .001), and those with prior stroke had lower IM-GSM (p = .007). Neither IMT nor IM-GSM was different between patients with and without previous lower extremity vascular disease. IM-GSM was significantly different between groups, it decreased significantly with increasing number of arterial territories affected (37.7 ± 15.4 vs. 29.3 ± 16.4 vs. 20.7 ± 12.9) p < .001, for asymptomatic, symptoms in one and in multiple arterial systems, respectively. Conventional IMT was not significantly different between groups p = .49. CONCLUSION: Carotid IMT was higher and IM-GSM lower in patients with symptomatic nearby arterial territories but not in those with peripheral disease. In contrast to conventional IMT, IM-GSM can differentiate between numbers of arterial territories affected by atherosclerosis, suggesting that it is a better surrogate for monitoring multiple arterial territory disease.

The impact of age on cardiac electromechanical function in asymptomatic individuals.

BACKGROUND AND AIM: Whether aging affects left ventricular (LV) filling and ejection and the LV electric function is not well established. We investigated the effect of normal aging on echocardiographic measurements of LV morphology and function, LV electric function and the relationship between LV electric and mechanical function in asymptomatic individuals. METHODS: As part of a cross-sectional survey for the prevalence of coronary risk factors in the general population in Caltanissetta, Italy, individuals without signs or symptoms of coronary artery disease or heart failure were randomly selected and underwent electrocardiographic and echocardiographic examination. QRS duration and amplitude, PR, QT and QTc intervals, were automatically measured. Echocardiographic examination included the measurement of LV systolic and diastolic dimensions, volumes and ejection fraction (EF). From the spectral Doppler flow LV early diastolic (E wave) and atrial systolic (A wave) velocities, isovolumic relaxation time (IVRT) and isovolumic contraction time (IVCT) were measured. Global LV dyssynchrony was assessed using the total isovolumic time (T-IVT) and the Tei index. RESULTS: Aging reduced LV long-axis function, LV filling time and E wave velocity and prolonged T-IVT, IVRT and Tei index. It did not affect LV dimensions, ejection fraction, IVCT or QRS amplitude and duration. QRS duration correlated with LV dimensions, wall thickness and left atrial area. QRS amplitude and QTc interval correlated with the markers of LV dyssynchrony T-IVT and Tei index. CONCLUSIONS: Overall, systolic and electric LV function are not affected by age, whereas subendocardial function, diastolic and synchronous function are significantly influenced.

Relationship between QRS measurements and left ventricular morphology and function in asymptomatic individuals.

BACKGROUND AND AIM: QRS amplitude and duration are associated with increased left ventricular (LV) volume, mass and dysfunction. However, the diagnostic concordance between QRS measurements and LV morphology and function, as shown by Doppler echocardiography, is not well established. We investigated the relationships of QRS duration and amplitude with echocardiographic measurements of LV morphology and systolic and diastolic function in normal individuals. METHODS: Individuals without signs or symptoms of coronary artery disease or heart failure, who underwent clinical examination as a part of a cross-sectional survey for the prevalence of coronary risk factors, randomly selected from the population list in Caltanissetta, Italy, were included in the study. QRS duration and amplitude were automatically measured using inbuilt software. LV ejection and filling patterns were studied using Doppler echocardiography. RESULTS: We studied 184 individuals (96 men and 88 women), mean age 55.9 (11.3). QRS duration increased by 5.4 ms for every 100 g increase in LV mass, and by 4.6 ms for each 10 mm increase in LV end-diastolic diameter. The amplitude increased by 0.8 mm for every 100 g increase in LV mass. There was no relationship with LV dimensions. A nonlinear correlation was found between QRS amplitude and indexes of global dyssynchrony. The time-voltage QRS area correlated with LV mass, dimensions and indexes of dyssynchrony. There was no relationship between QRS measurements and ejection fraction. CONCLUSIONS: QRS prolongation and increase in amplitude are strongly influenced by LV increased mass and volume, as well as by dyssynchrony, independently of ejection fraction.

Abnormal ventricular repolarization in long QT syndrome carriers is related to short left ventricular filling time and attenuated stroke volume response during exercise.

BACKGROUND: Long QT syndrome (LQTS) carriers are characterized by abnormal ventricular repolarization, prolonged systole, and mechanical dispersion. Prolonged left ventricular (LV) systole has been shown to result in disproportionate shortening of LV filling in other conditions. The aim of this study was to assess LV filling, diastolic function, and stroke volume (SV) response to dynamic exercise, in a group of LQTS carriers. METHODS: Forty-seven LQTS carriers (45 ± 15 years, 20 symptomatic) and 35 healthy individuals underwent bicycle stress echocardiogram. Electrocardiographic and echocardiographic measurements were obtained at rest, peak exercise, and 4 minutes into recovery. RESULTS: Long QT syndrome carriers and controls did not differ in age, gender, heart rate, QRS duration, or LV ejection fraction. At rest, LQTS carriers had longer QTc and shorter filling time (FT). At peak exercise, QTc increased and remained longer than controls at recovery. A negative correlation was found between QTc and FT (r = -.398, P = .001) with greater fall in FT in LQTS carriers than in controls at peak exercise (-23% ± 10 vs +2% ± 3, P < .0001). FT correlated with SV (r = +.27, P = .001), which increased more in controls than in LQTS carriers (+32% ± 4 vs +2% ± 1, P < .05). These differences were more pronounced in symptomatic LQTS carriers who had shorter FT and smaller SV at peak exercise and during recovery compared to asymptomatics (P < .05). CONCLUSIONS: Long QT syndrome carriers have longer QTc, but also shorter FT. These disturbances worsen at peak exercise (particularly in symptomatics) compromising LV filling and SV, hence a potential pathomechanism for adverse events.