Beyond standard echocardiography: Strain imaging as the AI-powered key to comprehensive cardiac function evaluation.

Application of left ventricular and left atrial strain to distinguish cardiac from non-cardiac dyspnea.

Irbesartan in Marfan syndrome (AIMS): a double-blind, placebo-controlled randomised trial.

BACKGROUND: Irbesartan, a long acting selective angiotensin-1 receptor inhibitor, in Marfan syndrome might reduce aortic dilatation, which is associated with dissection and rupture. We aimed to determine the effects of irbesartan on the rate of aortic dilatation in children and adults with Marfan syndrome. METHODS: We did a placebo-controlled, double-blind randomised trial at 22 centres in the UK. Individuals aged 6-40 years with clinically confirmed Marfan syndrome were eligible for inclusion. Study participants were all given 75 mg open label irbesartan once daily, then randomly assigned to 150 mg of irbesartan (increased to 300 mg as tolerated) or matching placebo. Aortic diameter was measured by echocardiography at baseline and then annually. All images were analysed by a core laboratory blinded to treatment allocation. The primary endpoint was the rate of aortic root dilatation. This trial is registered with ISRCTN, number ISRCTN90011794. FINDINGS: Between March 14, 2012, and May 1, 2015, 192 participants were recruited and randomly assigned to irbesartan (n=104) or placebo (n=88), and all were followed for up to 5 years. Median age at recruitment was 18 years (IQR 12-28), 99 (52%) were female, mean blood pressure was 110/65 mm Hg (SDs 16 and 12), and 108 (56%) were taking ß blockers. Mean baseline aortic root diameter was 34·4 mm in the irbesartan group (SD 5·8) and placebo group (5·5). The mean rate of aortic root dilatation was 0·53 mm per year (95% CI 0·39 to 0·67) in the irbesartan group compared with 0·74 mm per year (0·60 to 0·89) in the placebo group, with a difference in means of -0·22 mm per year (-0·41 to -0·02, p=0·030). The rate of change in aortic Z score was also reduced by irbesartan (difference in means -0·10 per year, 95% CI -0·19 to -0·01, p=0·035). Irbesartan was well tolerated with no observed differences in rates of serious adverse events. INTERPRETATION: Irbesartan is associated with a reduction in the rate of aortic dilatation in children and young adults with Marfan syndrome and could reduce the incidence of aortic complications. FUNDING: British Heart Foundation, the UK Marfan Trust, the UK Marfan Association.

Echocardiography 2020: Toward deciphering the "Rosetta stone" of left ventricular diastolic function.

In the year 1997, nearly a quarter-century ago, Nishimura and Tajik (J Am Coll Cardiol. 1997;30:8) suggested that Doppler echocardiography was the "Rosetta stone" (a metaphor for decrypting secrets of diastole) of left ventricular diastole, based solely on transmitral E/A ratio and its progression from grade I through IV, supported by cardiac catheterization, as the filling pressure started to increase to over 15 mm Hg. Ten years later, in 2007, the same Mayo group (Nagueh et al, J Am Coll Cardiology. 2008;51:679) was searching to decipher the secrets of diastole using multiple measures such as left atrial (LA) volume, E/E' ratio, pulmonary venous flow, and mitral inflow propagation velocity. This substantial leap from E/A ratio led to the more formal recommendation proposed by the American Society of Echocardiography in 2009 (Nagueh et al, J Am Soc Echocardiogr. 2009;22:107) and, as an update, in the year 2016 (Nagueh et al, J Am Soc Echocardiogr. 2016;29:277): the later version gained popularity for the simplified approach to identify diastolic dysfunction in healthy subjects as well as in those with poorly contracting left ventricle. Despite 30 years of continuous search, we are not sure if we have been able to decipher the hidden secrets of diastolic function. With this background, the Echocardiography Journal under the leadership of Dr Navin Nanda as the Editor-in-Chief has taken this initiative to publish a theme issue on left ventricular diastolic function and when this becomes dysfunctional to diminish life.

Biatrial and right ventricular deformation imaging: Implications of the recent EACVI consensus document in the clinics and beyond.

In this review, right ventricular (RV), right atrial (RA), and left atrial (LA) strain in some selected clinical situations has been discussed in light of the current literature. To exemplify the significance of the use of multichamber strain, we have provided some illustrations of common cardiac problems. The recently published European Association of Cardiovascular Imaging (EACVI) consensus document for standardization of RV, RA, and LA strain, using the currently available software, has fulfilled the aspirations of investigators world over who have been studying atrial strain using a bailed-out algorithm designed principally to quantify left ventricular deformation. The purpose of this review was to reiterate the value of the application of RV and biatrial strain imaging in research and day-to-day clinical practice, using the 2-dimensional speckle tracking echocardiography (2D-STE). Also, we present a short report on how RA strain may remain coupled to pulmonary hemodynamics. Besides, we have highlighted the technical challenges of atrial strain quantification. We have not used the nomenclature of chamber deformation proposed by the EACVI document as the publications cited in this review have used different sets of nomenclature.

Deformation imaging of the atria using 2D strain: A noninvasive modality to characterize operating compliance?

This viewpoint with two illustrated case summaries of biventricular and biatrial mechanical function/dysfunction emphasizes the importance of continued research in deformation imaging beyond the left ventricle, as there are no Cinderellas in the heart and we just cannot afford to be nonchalant toward the atria, particularly the right atrium.

Incremental prognostic value of multichamber deformation imaging and renal function status to predict adverse outcome in heart failure with reduced ejection fraction.

AIMS: Deformation imaging, particularly of left-sided heart, is fast becoming an essential tool in clinical cardiology. However, data are scant regarding the value of biventricular and bi-atrial deformation in association with comorbidities in heart failure with reduced left ventricular ejection fraction (HFREF). METHODS AND RESULTS: Forty-nine subjects (72 ± 13 years; 28 male) with HFREF and 14 age-matched controls underwent deformation imaging including LV global longitudinal strain (LVGLS%), right ventricular strain (RVS%), and left atrial reservoir strain (LARS%). Standard echo parameters included LVEF%, E/E' ratio, and pulmonary artery systolic pressure (PASP). Mean ± SD of LVEF, LVGLS%, and RVS% were 31% ± 8%, 7% ± 3%, and 17% ± 7%, respectively, and were significantly lower compared with controls (all P < .0001). Over a follow-up period of 4.2 years, 24% of patients died and 48% had a composite outcome of death and heart failure hospitalization. In the logistic regression model, taking the composite of death and heart failure hospitalization as a dichotomous variable, RVS%, E/E' ratio, and PASP were the only significant univariate predictors of adverse outcome (R2  = .68, all P < .05). In the multivariate model, however, only PASP predicted adverse outcome. PASP also had the largest AUC (0.8) in the ROC analysis. A creatinine level of >88 µmol/L (SCREAT) and a cutoff value of LA reservoir strain (LARS %) at <16.7% provided the best sensitivity (86%) and specificity (40%) with an odds ratio of 3.8. In the Kaplan-Meier survival estimate, LARS%-SCREAT predicted all-cause mortality and HF hospitalization. CONCLUSION: Multichamber deformation imaging along with renal function and PASP could best predict adverse outcome in HFREF.

The role of advanced echocardiography and cardiovascular magnetic resonance in the assessment of myocardial function in Marfan syndrome-An update.

Cardiovascular assessment of patients with Marfan syndrome has normally focused on the aortic root and vascular manifestations of the disease due to the high risk of aortic dissection. Although primary myocardial impairment has long been suspected in these patients, the evidence has been controversial. Advanced echocardiography and cardiovascular magnetic resonance imaging have proven to be effective, accurate, and more sensitive in the detection of subtle cardiac dysfunction. The application of these techniques to Marfan syndrome over the last 10 years has made significant progress in demonstrating the presence of primary myocardial impairment in these patients, but further work is still required to obtain confirmatory molecular, pathophysiological, and prognostic clinical data. Phenotypic expression of the disease has prognostic value, also suggesting potential effective medical therapy.

Prognostic value of left atrial expansion index and exercise-induced change in atrial natriuretic peptide as long-term predictors of atrial fibrillation recurrence.

AIMS: We propose to assess the value of exercise-induced change in N-terminal-pro atrial natriuretic peptide (NT-proANP) and left atrial expansion index (LAEI) in predicting AFR after cardioversion and their effect on AF-free survival. METHODS AND RESULTS: Fifty-five patients with persistent AF of <18 months duration needing cardioversion were recruited for the study. Fifty-four patients were successfully cardioverted. At 3 months 28/54 (51%) were in SR and at 12 months 21/53 (39%). On multivariate analysis, only exercise-induced change in NT-proANP and LAEI were found to be predictive of AFR up to 12 months post-cardioversion and had an effect on AF-free survival. N-terminal-pro brain natriuretic peptide was elevated in all persistent AF patients but did not predict recurrent AF. CONCLUSIONS: Left atrial expansion index and exercise-induced atrial natriuretic peptide change show promise as predictors of AFR after cardioversion. These predictors may identify patients at an early stage in their disease with intact neurohumoral feedback systems and less advanced atrial remodelling. Further studies are required to confirm these findings.

Value of two-dimensional speckle tracking and real time three-dimensional echocardiography for the identification of subclinical left ventricular dysfunction in patients referred for routine echocardiography.

BACKGROUND: While speckle tracking echocardiography (2DSTE) can be used to study longitudinal, circumferential, and radial function, real time 3D echocardiography (3DE) generates dynamic time-volume curves, offering a wide array of new parameters for characterizing mechanical and volumetric properties of the left ventricle (LV). Our aim was to investigate the merit of these new techniques to separate normal from abnormal echocardiograms as well as to identify subclinical disease in reportedly normal subjects. METHODS: Eighty-one patients (mean age 61 ± 16 years) underwent standard 2D echocardiography (2DE) enhanced by 2DSTE and 3DE. The data included LV volumes and ejection fraction (EF), velocities, strain/strain rate, and peak ejection/filling rates. The patients were divided into Group 1: normal (n = 42) and Group 2: abnormal (n = 39) on the basis of an expert interpretation of the resting 2DE. RESULTS: Global longitudinal strain (%) was 17 ± 4 in Group1 and 14 ± 4 in Group2 (P < 0.002). Strain rates (SR, 1/sec) at peak systole (1.1 ± 0.2 vs 0.9 ± 0.3, P < 0.001) and early diastole (1.3 ± 0.3 vs 0.9 ± 0.3, P < 0.001) were also higher in Group1. Three-dimensional peak ejection and filling rates (EDV/sec) were significantly higher in Group1 (-2.5 ± 0.4 vs -2.1 ± 0.7, and 1.8 ± 0.2 vs 1.5 ± 0.5, P < 0.002, P < 0.001, respectively). The best discriminatory power for predicting a normal 2DE was systolic SR with a sensitivity of 82% and a specificity of 54% using a cutoff value of 1.09. Interestingly, 19/41 (46%) of Group1 patients had systolic SR < 1.09, suggesting subclinical disease. CONCLUSIONS: 2DSTE and 3DE can discriminate between normal and abnormal echocardiograms and have the potential to detect subclinical LV dysfunction.

Assessment of aortic stiffness in marfan syndrome using two-dimensional and Doppler echocardiography.

BACKGROUND: Extracellular matrix remodeling in the aortic wall results in increased aortic stiffness (AoS) in Marfan syndrome (MFS). Pulsed-wave velocity (PWV) constitutes the best indirect AoS measurement. We aimed to assess PWV in MFS patients using two-dimensional (2D) and Doppler echocardiography. METHODS: Thirty-one MFS patients, (mean age 31 ± 14 years, 16 men) and 31 controls were examined. Blood flow was recorded in the aorta near the aortic valve and immediately after in the descending aorta with simultaneous electrocardiography. PWV was calculated by dividing the distance between the two sample volume positions (D) by the time difference (TD) between the intervals from the QRS start to the ascending and descending aortic flow onsets. B-stiffness was also measured. RESULTS: TD (described in "Methods" section) and, aortic arch length were significantly increased in MFS patients, P < 0.001. Thus, PWV values were significantly higher in patients when compared with controls, 7.20 m/s (5.12, 9.43) versus 4.64 m/s (3.37, 6.24), P < 0.001. B-stiffness was also significantly increased in MFS patients; 5.15 (3.69, 7.65) versus 2.44 (1.82, 3.66), P < 0.001. Multiple regression analysis showed a positive association with MFS diagnosis and age, (P = 0.002 and 0.009, respectively). Reproducibility of PWV measurements was <5%. CONCLUSIONS: AoS was significantly higher in MFS patients as expected. Our data demonstrated that PWV measurements can be performed, in the absence of serious musculoskeletal abnormalities in MFS adults, as part of a cardiac ultrasound scan. This technique can be helpful in diagnosis and management in MFS.

Impaired biventricular deformation in Marfan syndrome: a strain and strain rate study in adult unoperated patients.

OBJECTIVE: To investigate the presence of any regional myocardial deformation abnormalities in Marfan syndrome (MFS) and determine the benefits of using advanced echocardiography compared to conventional techniques. BACKGROUND: Myocardial dysfunction in MFS may be caused by extracellular matrix remodeling thus, resulting in uniform reduced functionality. However, increased aortic stiffness may cause segmental ventricular abnormalities. Strain rate imaging (SRI) constitutes a validated technique to assess regional deformation in various clinical conditions. With this in mind, we aimed to investigate biventricular function in MFS using SRI. METHODS: Forty-four MFS patients (mean age 30 ± 12 years, 26 men) and 49 controls without valvular disease were examined using SRI. Ejection fraction (EF) was calculated by the Simpson's biplane method. Biventricular deformation was assessed by measuring strain/strain rate. Strain values were divided by left ventricular (LV) end-diastolic volume to adjust LV deformation for geometry changes providing a strain index (SI). Aortic stiffness was evaluated using the ß-stiffness index. RESULTS: EF (%) was reduced in MFS patients (59 ± 5 vs 72 ± 4, P < 0.001), whereas ß-stiffness was increased (P < 0.001). LV radial and LV and right ventricular (RV) long-axis strain values (%) were reduced in the patient group (70 ± 17 vs 93 ± 10; 19 ± 2 vs 25 ± 2; 30 ± 9 vs 36 ± 8, respectively, P < 0.001). Strain rate measurements were also reduced (P < 0.001). In a multiple regression analysis, MFS diagnosis was negatively associated with LV SI (-0.262 [-0.306, -0.219], P < 0.001). ß-Stiffness was negatively associated with SI obtained from the septum, inferior and anterior walls. ROC analyses demonstrated that SRI, when compared with conventional echocardiography, had higher sensitivity and specificity in predicting biventricular dysfunction in MFS. CONCLUSIONS: Our study showed a uniform reduction in biventricular deformation in MFS. These findings suggest that assessment of myocardial function using advanced echocardiographic techniques could be more accurate in MFS patient evaluation than conventional echocardiography alone.

Cardiovascular manifestations in men and women carrying a FBN1 mutation.

AIMS: In patients with Marfan syndrome and other type-1 fibrillinopathies, genetic testing is becoming more easily available, leading to the identification of mutations early in the course of the disease. This study evaluates the cardiovascular (CV) risk associated with the discovery of a fibrillin-1 (FBN1) mutation. METHODS AND RESULTS: A total of 1,013 probands with pathogenic FBN1 mutations were included, among whom 965 patients [median age: 22 years (11-34), male gender 53%] had data suitable for analysis. The percentage of patients with an ascending aortic (AA) dilatation increased steadily with increasing age and reached 96% (95% CI: 94-97%) by 60 years. The presence of aortic events (dissection or prophylactic surgery) was rare before 20 years and then increased progressively, reaching 74% (95% CI: 67-81%) by 60 years. Compared with women, men were at higher risk for AA dilatation [≤ 30 years: 57% (95% CI: 52-63) vs. 50% (95% CI: 45-55), P = 0.0076] and aortic events [≤ 30 years: 21% (95% CI: 17-26) vs. 11% (95% CI: 8-16), P < 0.0001; adjusted HR: 1.4 (1.1-1.8), P = 0.005]. The prevalence of mitral valve (MV) prolapse [≤ 60 years: 77% (95% CI: 72-82)] and MV regurgitation [≤ 60 years: 61% (95% CI: 53-69)] also increased steadily with age, but surgery limited to the MV remained rare [≤ 60 years: 13% (95% CI: 8-21)]. No difference between genders was observed (for all P> 0.20). From 1985 to 2005 the prevalence of AA dilatation remained stable (P for trend = 0.88), whereas the percentage of patients with AA dissection significantly decreased (P for trend = 0.01). CONCLUSION: The CV risk remains important in patients with an FBN1 gene mutation and is present throughout life, justifying regular aortic monitoring. Aortic dilatation or dissection should always trigger suspicion of a genetic background leading to thorough examination for extra-aortic features and comprehensive pedigree investigation.

Principles and clinical applications of strain imaging.

M-Mode echocardiography, 2-D grey scale imaging and standard Doppler that constitute conventional echocardiography has been used for over many decades now. Although these modalities form the backbone in routine clinical echocardiography, its inability to objectively quantify left ventricular function at regional and global levels as well as its loading and heart rate dependency make conventional echocardiography an incomplete tool in clinical situations. Tissue Doppler imaging (which includes myocardial velocity, displacement and strain) has been successfully used in a variety of clinical situations, from investigations of diastolic function to implantation of bi-ventricular pacing for cardiac resynchronization therapy and even in preclinical diagnosis of genetic diseases such as hypertrophic cardiomyopathy. Strain imaging has been found to be superior to velocity in a variety of clinical conditions and enables us to quantify deformation as a measurable number in terms of regional myocardial deformation. Strain and strain rate have to be assessed together since they provide complementary information somewhat analogous to ejection fraction and contraction. This article has tried to simplify its principles, understand its limitations and know its utility to ensure having a better knowledge of this promising tool before one starts to actively use it. In this review, focus has been made on the physical, technical and also clinical aspects of strain imaging. In the new world of multi-modality imaging, cardiac magnetic resonance imaging (CMR) and nuclear perfusion scintigraphy (NPS) are the competitors of echocardiography, but it would be of interest to note that even these modalities are also adapting concepts of strain imaging (in CMR) and left ventricular synchronicity (in NPS). This only emphasizes the role of advanced echocardiography as a more economical and stand-alone modality visa vis the other two related technologies. The sooner we adapt to these advanced applications, stronger would be the ground to resolve technical and clinical issues. Strain imaging in its present form cannot win the game alone in this era of multi-modality imaging, but it is almost certain that with continued advancement, tissue Doppler and speckle tracking echocardiography based strain could play a pivotal role in a variety of clinical situations providing much needed incremental information.

Current concepts in the pathogenesis of atrial fibrillation.

Current evidence suggests that the pathogenesis of atrial fibrillation (AF) is multifactorial. The observation that AF, once present, alters the electrophysiologic properties of the atrial myocardium causing self-perpetuation of the arrhythmia raised the importance of electrical remodeling in its pathogenesis. Although these changes are potentially reversible, maintenance of AF continues even after electrical remodeling has occurred. Clinical and experimental studies have highlighted the role of a susceptible atrial anatomical substrate with features of myocyte degeneration and interstitial fibrosis in the initiation and maintenance of AF. Finally, the association of increased inflammatory burden with the presence and future development of AF has implicated inflammation in the pathogenesis of the arrhythmia. The purpose of this review is to provide current evidence on the dominant theories on AF pathogenesis, namely, electrical remodeling, structural remodeling, and inflammation; describe the various experimental models and methods used; and identify a cause-effect association, when present. In addition, the interrelation between different mechanisms responsible for AF will be demonstrated, providing further insight into the complex pathophysiology.

Impaired right ventricular systolic function demonstrated by reduced atrioventricular plane displacement in adults with Marfan syndrome.

AIMS: The right ventricle (RV) ejects the same volume of blood at the same rate as the left ventricle (LV). Mild LV dysfunction has been demonstrated in Marfan syndrome (MFS). However, little attention has been paid to the functioning of the RV. The aim of this study was to assess RV function in unoperated adult MFS patients. METHODS AND RESULTS: In 66 unoperated (15-58 years) MFS patients and 61 controls, rate of pressure rise (dp/dt) in RV, and tricuspid annular motion (TAM) were studied using conventional echocardiography and tissue Doppler imaging (TDI). When compared with controls, MFS patients showed impaired RV systolic function as expressed by a reduced dp/dt, TAM obtained by M-mode echocardiography, and peak TDI systolic velocities at the basal lateral wall (745.36+/-37.85 vs. 1103.30+/-27.30 mmHg, P<0.001; 2.2+/-0.05 vs. 2.5+/-0.05 cm, P<0.001; and 0.13+/-0.002 vs. 0.16+/-0.002 m/s, P<0.001, respectively). CONCLUSION: This study demonstrated a primary impairment of RV systolic function in MFS. This is the first study to report RV dysfunction in MFS. Such data could prove valuable during the peri-operative and long-term medical management of MFS patients.

Biventricular and atrial diastolic function assessment using conventional echocardiography and tissue-Doppler imaging in adults with Marfan syndrome.

AIMS: Previous studies provided evidence about left ventricular systolic and diastolic dysfunction in adults with Marfan syndrome (MFS). However, in the literature, data on right ventricular and bi-atrial diastolic function are limited. We aimed to investigate whether, in the absence of significant valvular disease, diastolic dysfunction is present not only in both ventricles but also in the atrial cavities. METHODS AND RESULTS: Seventy-two adult unoperated MFS patients and 73 controls without significant differences in age, sex, and body surface area from the patient group were studied using two-dimensional, pulsed, and colour-Doppler and tissue-Doppler imaging (TDI). Biventricular early filling measurements were significantly decreased in MFS patients when compared with controls (P < 0.001). Pulsed TDI early filling measurements obtained from five mitral annular regions and over the lateral tricuspid valve corner were significantly reduced in the patient group (P < 0.001). Indices reflecting atrial function at the reservoir, conduit and contractile phases were also significantly decreased in MFS patients (P < 0.001). CONCLUSION: This study demonstrated significant biventricular diastolic and biatrial systolic and diastolic dysfunction in MFS patients. Our findings suggest that MFS affects diastolic function independently. Diastolic abnormalities could be attributed to fibrillin-1 deficiency and dysregulation of transforming growth factor-beta activity in the cardiac extracellular matrix.