Publications
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Al-Shammari H, Latif N, Sarathchandra P, et al., 2020, Expression and function of mechanosensitive ion channels in human valve interstitial cells., PLoS One, Vol: 15, Pages: e0240532-e0240532, ISSN: 1932-6203
BACKGROUND: The ability of heart valve cells to respond to their mechanical environment represents a key mechanism by which the integrity and function of valve cusps is maintained. A number of different mechanotransduction pathways have been implicated in the response of valve cells to mechanical stimulation. In this study, we explore the expression pattern of several mechanosensitive ion channels (MSC) and their potential to mediate mechanosensitive responses of human valve interstitial cells (VIC). METHODS: MSC presence and function were probed using the patch clamp technique. Protein abundance of key MSC was evaluated by Western blotting in isolated fibroblastic VIC (VICFB) and in VIC differentiated towards myofibroblastic (VICMB) or osteoblastic (VICOB) phenotypes. Expression was compared in non-calcified and calcified human aortic valves. MSC contributions to stretch-induced collagen gene expression and to VIC migration were assessed by pharmacological inhibition of specific channels. RESULTS: Two MSC types were recorded in VICFB: potassium selective and cation non-selective channels. In keeping with functional data, the presence of both TREK-1 and Kir6.1 (potassium selective), as well as TRPM4, TRPV4 and TRPC6 (cationic non-selective) channels was confirmed in VIC at the protein level. Differentiation of VICFB into VICMB or VICOB phenotypes was associated with a lower expression of TREK-1 and Kir6.1, and a higher expression of TRPV4 and TRPC6. Differences in MSC expression were also seen in non-calcified vs calcified aortic valves where TREK-1, TRPM4 and TRPV4 expression were higher in calcified compared to control tissues. Cyclic stretch-induced expression of COL I mRNA in cultured VICFB was blocked by RN-9893, a selective inhibitor of TRPV4 channels while having no effect on the stretch-induced expression of COL III. VICFB migration was blocked with the non-specific MSC blocker streptomycin and by GSK417651A an inhibitor of TRPC6/3. CONCLUSION: Aortic VIC ex
Sliwa K, Yacoub M, 2020, Catalysing the response to NCDI Poverty at a time of COVID-19., Lancet, Vol: 396, Pages: 941-943
Badran HM, Faheem N, Zidan A, et al., 2020, Effect of Short-Term L-Thyroxine Therapy on Left Ventricular Mechanics in Idiopathic Dilated Cardiomyopathy, JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY, Vol: 33, Pages: 1234-1244, ISSN: 0894-7317
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- Citations: 7
Ibrahim AM, Roshdy M, Elshorbagy S, et al., 2020, An Investigation of Fibulin-2 in Hypertrophic Cardiomyopathy, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol: 21
Al Kindi HN, Shehata M, Ibrahim AM, et al., 2020, Cor Triatriatum Sinister (Divided Left Atrium): Histopathologic Features and Clinical Management, ANNALS OF THORACIC SURGERY, Vol: 110, Pages: 1380-1386, ISSN: 0003-4975
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- Citations: 6
Samaan AA, Said K, El Aroussy W, et al., 2020, Impact of balloon mitral valvuloplasty on left ventricular rotational deformation: Magnetic Resonance Imaging follow up study., Int J Cardiovasc Imaging, Vol: 36, Pages: 1543-1550
In patients with rheumatic mitral stenosis (MS), some previous studies have investigated the influence of balloon mitral valvuloplasty (BMV) on left ventricular (LV) systolic function. However, the impact of BMV on LV twisting motion in this clinical setting has not been studied before yet. To describe changes in LV torsion in patients with rheumatic MS following BMV. Thirty patients (median age 33 years, 22 women) with isolated severe MS were studied. CMR myocardial tissue tagging was used for assessment of LV rotational deformation. LV torsion was calculated as the twist value (the net difference between apical counterclockwise and basal clockwise rotation) normalized to the length of the ventricle and multiplied by the mean radius at the base and apex. All patients had CMR studies before, 6 months and 1 year after successful BMV. At baseline, patients had a mitral valve area of 0.9 (0.6-1.3) cm2, mean pressure gradient of 12.5 (8-24) mmHg across the valve as measured by transthoracic echocardiography. Median LV ejection fraction (LVEF) estimated by CMR was 57 (range: 45-69) %. A significant improvement in LV base-apex torsion was shown at 6 months (3.3° vs. 2.5°, p < 0.001) with a further improvement at 1 year (4.1° vs. 3.3°, p = 0.05). Similar pattern of change was seen in LV base-mid torsion with a significant increase at 6 months (3.6° vs. 2.3°, p < 0.001) and a further increase at 1 year (4.7° vs. 3.6°, p = 0.007). These changes were associated with a significant increase in LVEF (62% vs. 57%, p < 0.001) at 1 year following BMV. Successful BMV is associated with a significant improvement in LV torsion that is accompanied by a significant improvement in LVEF.
Yacoub MH, Tsang V, Sarathchandra P, et al., 2020, Long-term adaptive versus maladaptive remodelling of the pulmonary autograft after the Ross operation, European Journal of Cardio-Thoracic Surgery, Vol: 57, Pages: 977-985, ISSN: 1010-7940
OBJECTIVESFollowing the Ross operation, the pulmonary autograft undergoes structural changes (remodelling). We sought to determine the extent, nature and possible determinants of long-term remodelling in the different components of the pulmonary autograft.METHODSTen pulmonary autografts and 12 normal control valves (6 pulmonary and 6 aortic) were examined by conventional histology, immunocytochemistry and electron microscopy. The structural changes were quantified by morphometry.RESULTSThe leaflets from free-standing root replacement valves demonstrated thickening to levels comparable to the normal aortic leaflets, largely due to the addition of a thin layer of ‘neointima’ formed of radial elastic fibres, collagen bundles and glycoaminoglycans, on the ventricular aspect of the leaflets. The leaflets of valves from sub-coronary implantation demonstrated a significantly thicker fibroelastic layer on the ventricularis and calcium deposition in the fibrosa. The media of the explanted valves showed increased number of lamellar units to levels comparable to normal aortic roots. Electron microscopy of valves inserted as free-standing roots showed increased organization into continuous layers. However, intralamellar components showed varying degrees of ‘disorganization’ in comparison to those in the normal aortic media. In addition, there was a marked increase in the number of vasa vasorum with thickened arteriolar wall in the outer media and adventitia.CONCLUSIONSFollowing the Ross operation, in the very long term, all components of the autograft showed varying degrees of remodelling, which was judged to be largely adaptive. Defining the type, determinants and possible functional effects of remodelling could help in understanding and optimizing the results of the Ross operation.
Durko AP, Yacoub MH, Kluin J, 2020, Tissue Engineered Materials in Cardiovascular Surgery: The Surgeon's Perspective, FRONTIERS IN CARDIOVASCULAR MEDICINE, Vol: 7, ISSN: 2297-055X
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- Citations: 12
Pelliccia F, Alfieri O, Calabro P, et al., 2020, Multidisciplinary evaluation and management of obstructive hypertrophic cardiomyopathy in 2020: Towards the HCM Heart Team, INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 304, Pages: 86-92, ISSN: 0167-5273
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- Citations: 27
Allouba M, Aguib Y, Walsh R, et al., 2020, Analysis of HCM in an understudied population reveals a new mechanism of pathogenicity, Publisher: Cold Spring Harbor Laboratory
Hypertrophic Cardiomyopathy (HCM) is an inherited disease characterized by genetic and phenotypic heterogeneity. MYH7 represents one of the main sarcomere-encoding genes associated with HCM. Missense variants in this gene cause HCM through gain-of-function actions, whereby variants produce an abnormal activated protein which incorporates into the sarcomere as a "poison peptide". Here we report a frameshift variant in MYH7, c.5769delG, that is associated with HCM in an Egyptian cohort (3.3%) compared with ethnically-matched controls. This variant is absent from previously published large-scale Caucasian HCM cohorts. We further demonstrate strong evidence of co-segregation of c.5769delG with HCM in a large family (LOD score: 3.01). The predicted sequence of the variant MYH7 transcript shows that the frameshift results in a premature termination codon (PTC) downstream of the last exon-exon junction of the gene that is expected to escape nonsense-mediated decay (NMD). RNA sequencing of myocardial tissue obtained from a patient with the variant during surgical myectomy confirmed the expression of the variant MYH7 transcript. Our analysis reveals a new mechanism of pathogenicity in the understudied Egyptian population whereby distal PTC in MYH7 may lead to the expression of an abnormal protein.
Kutryb-Zajac B, Jablonska P, Serocki M, et al., 2020, Nucleotide ecto-enzyme metabolic pattern and spatial distribution in calcific aortic valve disease; its relation to pathological changes and clinical presentation, CLINICAL RESEARCH IN CARDIOLOGY, Vol: 109, Pages: 137-160, ISSN: 1861-0684
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- Citations: 14
Mazzarotto F, Hawley M, Beltrami M, et al., 2020, The genetic architecture of left ventricular non-compaction reveals both substantial overlap with other cardiomyopathies and a distinct aetiology in a subset of cases, Publisher: bioRxiv
Rationale: Left ventricular non-compaction (LVNC) is a condition characterised by trabeculations in the myocardial wall and is the subject of considerable conjecture as to whether it represents a distinct pathology or a secondary phenotype associated with other cardiac diseases, particularly cardiomyopathies. Objective: To investigate the genetic architecture of LVNC by identifying genes and variant classes robustly associated with disease and comparing these to other genetically characterised cardiomyopathies. Methods and Results: We performed rare variant association analysis using six different LVNC cohorts comprising 840 cases together with 125,748 gnomAD population controls and compared results to similar analyses with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) cases. We observed substantial overlap in genes and variant classes enriched in LVNC and DCM/HCM, indicating that in many cases LVNC belongs to a spectrum of more established cardiomyopathies, with non-compaction representing a phenotypic variation in patients with DCM- or HCM-causing variants. In contrast, five variant classes were uniquely enriched in LVNC cases, of which truncating variants in MYH7, ACTN2 and PRDM16 may represent a distinct LVNC aetiology. MYH7 truncating variants are generally considered as non-pathogenic but were detected in 2% of LVNC cases compared to 0.1% of controls, including a cluster of variants around a single splice region. Additionally, structural variants (exon deletions) in RYR2 and missense variants in the transmembrane region of HCN4 were enriched in LVNC cases, confirming prior reports regarding the association of these variant classes with combined LVNC and arrhythmia phenotypes. Conclusions: We demonstrated that genetic association analysis can clarify the relationship between LVNC and established cardiomyopathies, highlighted substantial overlap with DCM/HCM but also identified variant classes associated with distinct LVNC and with joint LVN
Gerges M, Yacoub M, 2020, Chronic thromboembolic pulmonary hypertension - Still evolving, Global Cardiology Science and Practice, Vol: 2020
Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the leading causes of severe pulmonary hypertension (PH). The disease is still underdiagnosed, and the true prevalence is unknown. CTEPH is characterized by intraluminal non-resolving thrombus organization and fibrous stenosis, or complete obliteration of pulmonary arteries, promoted by progressive remodeling of the pulmonary vasculature. One consequence of this is an increase in pulmonary vascular resistance and pressure, resulting in PH and progressive right heart failure, leading to death if left untreated. Endovascular disobliteration by pulmonary endarterectomy (PEA) is the preferred treatment for CTEPH patients. PEA surgery is the only technique that can potentially cure CTEPH disease, especially in patients with fresh or organized thrombi of the proximal branches of pulmonary arteries. However, not all patients are eligible for PEA surgery. Recent research has provided evidence suggesting balloon pulmonary angioplasty (BPA) and targeted medical therapy as additional promising available treatments options for inoperable CTEPH and recurrent/persistent PH after PEA surgery. Studies on BPA have shown it to improve pulmonary hemodynamics, symptoms, exercise capacity and RV function in inoperable CTEPH. Subsequently, BPA has developed into an essential component of the modern era of CTEPH treatment. Large randomized controlled trials have demonstrated varying significant improvements with targeted medical therapy in technically inoperable CTEPH patients. Thus, treatment of CTEPH requires a comprehensive multidisciplinary assessment, including an experienced PEA surgeon, PH specialist, BPA interventionist and CTEPH-trained radiologist at expert centers. In this comprehensive review, we address the latest developments in the fast-evolving field of CTEPH. These include advancements in imaging modalities and developments in operative and interventional techniques, which have widened the range of patients w
Idrees M, Butrous G, Mocumbi A, et al., 2020, Pulmonary hypertension in the developing world: Local registries, challenges, and ways to move forward, Global Cardiology Science and Practice, Vol: 2020
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- Citations: 9
Elmogy AA, Gergis M, Hassan A, et al., 2020, Thromboendarterectomy in a patient with systemic lupus and antiphospholipid syndrome: Lessons learned from a complex disease interaction, Global Cardiology Science and Practice, Vol: 2020
Systemic lupus erythematosus (SLE) is the prototypic multisystem autoimmune disorder with a broad spectrum of clinical presentations encompassing almost all organs and tissues1. Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the occurrence of venous and/or arterial thrombosis and pregnancy morbidity in the presence of pathogenic autoantibodies known as antiphospholipid antibodies (aPL)2. Chronic thromboembolism is one of the well-known established pathogenesis of pulmonary hypertension, known as chronic thromboembolic pulmonary hypertension (CTEPH)3. APS may be also associated with other diseases, mainly systemic lupus erythematosus (SLE). The presence of secondary APS in SLE patients further aggravate the condition due to recurrent venous thromboembolic showers to the pulmonary vasculature. Pulmonary endarterectomy (PEA) is the treatment of choice for CTEPH with lifelong anticoagulation4. We herein report a rare cause of CTEPH in a 42-year-old Egyptian man who presented with dyspnea WHO-FC III. The patient was diagnosed as a case of CTEPH due to secondary APS. He underwent PEA and was discharged on lifelong anticoagulation. Clinical follow-ups thereafter showed improvement of functional capacity and pulmonary artery pressures. In conclusion, management of such cases was combination of standard treatment of CTEPH, in addition to specific management of secondary APS to avoid recurrence of the disease.
Mahgoub A, Kotit S, Bakry K, et al., 2020, Thrombosis of mechanical mitral valve prosthesis during pregnancy: An ongoing ‘‘saga’’ in need of comprehensive solutions, Global Cardiology Science and Practice, Vol: 2020
Emergency treatment for thrombosed mechanical valve prothesis during pregnancy is not uncommon in low- and middle-income countries. The presence of a mechanical valve continues to be an important cause of maternal morbidity and mortality. There is a pressing need for increasing awareness and feasible solutions for this huge problem. We here describe four patients who needed emergency treatment for thrombosis of mechanical valve prothesis during pregnancy and review the evolving comprehensive strategies for dealing with this issue.
Hosny H, Said F, Afifi A, et al., 2020, Pulmonary artery banding in a modified mustard operation improves biventricular geometry and function, Global Cardiology Science and Practice, Vol: 2020
Patients with transposition of great arteries, with intact interventricular septum (TGA-IVS) and deconditioned left ventricle, represent a considerable challenge in developing countries. The modified Mustard operation was shown to provide a significant improvement for these patients, particularly by enhancing atrial functions and left ventricular filling. Yet, the problems of the systemic right ventricular dysfunction and the resulting secondary tricuspid regurgitation (TR) remain to be of major concern. In addition, the deviation of the interventricular septum towards the left side markedly impairs ventriculo-ventricular interaction and predisposes to dynamic left ventricular outflow tract obstruction (LVOTO). We report that adding a moderately loose pulmonary artery banding to the modified Mustard operation in a case of TGA-IVS results in improvement of biventricular geometry and function, tricuspid and mitral valve functions and disappearance of dynamic LVOTO.
Butrous G, Maron B, Yacoub M, 2020, The lamp of medicine of ancient Egypt is still burning, Global Cardiology Science and Practice, Vol: 2020
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- Citations: 1
Hosny H, Sedky Y, Romeih S, et al., 2020, Revival and modification of the Mustard operation., J Thorac Cardiovasc Surg, Vol: 159, Pages: 241-249
OBJECTIVE: The neonatal arterial switch operation is currently the procedure of choice for patients with transposition of the great arteries. However, a large number of patients present too late for the arterial switch operation and are best managed with the atrial switch operation. METHODS: We have used the Mustard operation in its original form or following a new modification designed to enhance the atrial functions and filling of the left ventricle in an attempt to improve long-term results. RESULTS: Between July 2013 and November 2018, a total of 101 patients underwent the Mustard operation, 86 with the new modification. The median age at operation was 16 months (6 months to 27 years). A total of 75 patients (74.3%) were male. Median preoperative oxygen saturation was 71%. There were no early deaths and there were 3 late deaths during a median follow-up period of 24.2 months (all in patients with large ventricular septal defect and established pulmonary vascular disease). At the latest follow-up, all patients were in stable sinus rhythm. There were no baffle leaks. Seven patients had asymptomatic narrowing of the superior baffle, and 1 patient required balloon dilatation. Follow-up is 100% complete and includes computed tomography and magnetic resonance imaging at regular intervals (75 patients to date). Computerized analysis of representative subsets showed enhanced rate and pattern of filling of the left ventricle in the modified operation compared with the classic operation. CONCLUSIONS: The use of the Mustard operation, particularly the modified technique should play an important role in treating late-presenting patients with transposition of the great arteries. Improving the pattern of filling of the left ventricle could enhance the long-term results of the Mustard operation.
Badran HM, Soltan G, Almeleigi R, et al., 2019, Prognostic significance of left ventricular end diastolic pressure using E/E' in patients with hypertrophic cardiomyopathy, ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES, Vol: 36, Pages: 2167-2175, ISSN: 0742-2822
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- Citations: 4
Mocumbi AO, Stothard JR, Correia-de-Sá P, et al., 2019, Endomyocardial Fibrosis: an Update After 70 Years., Curr Cardiol Rep, Vol: 21
PURPOSE OF REVIEW: This review aims at highlighting the need to better understand the pathogenesis and natural history of endomyocardial fibrosis when set against its changing endemicity and disease burden, improvements in diagnosis, and new options for clinical management. RECENT FINDINGS: Progress in imaging diagnostic techniques and availability of new targets for drug and surgical treatment of heart failure are contributing to earlier diagnosis and may lead to improvement in patient survival. Endomyocardial fibrosis was first described in Uganda by Davies more than 70 years ago (1948). Despite its poor prognosis, the etiology of this neglected tropical restrictive cardiomyopathy still remains enigmatic nowadays. Our review reflects on the journey of scientific discovery and construction of the current guiding concepts on this mysterious and fascinating condition, bringing to light the contemporary knowledge acquired over these years. Here we describe novel tools for diagnosis, give an overview of the improvement in clinical management, and finally, suggest research themes that can help improve patient outcomes focusing (whenever possible) on novel players coming into action.
Stewart S, Al-Delaimy W, Sliwa K, et al., 2019, Clinical algorithm to screen for cardiopulmonary disease in low-income settings., Nat Rev Cardiol, Vol: 16, Pages: 639-641
El-Menyar A, Sulaiman K, Almahmeed W, et al., 2019, Shock Index in Patients Presenting With Acute Heart Failure: A Multicenter Multinational Observational Study, ANGIOLOGY, Vol: 70, Pages: 938-946, ISSN: 0003-3197
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- Citations: 7
Kalman JM, Lavandero S, Mahfoud F, et al., 2019, Looking back and thinking forwards-15 years of cardiology and cardiovascular research, NATURE REVIEWS CARDIOLOGY, Vol: 16, Pages: 651-660, ISSN: 1759-5002
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- Citations: 10
Ali AM, Dena ASA, Yacoub MH, et al., 2019, Exploring the influence of particle shape and air velocity on the flowability in the respiratory tract: a computational fluid dynamics approach, DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, Vol: 45, Pages: 1149-1156, ISSN: 0363-9045
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- Citations: 2
Al Kindi HN, Yacoub MH, 2019, Transection and Relocation of Anomalous Left Coronary Artery After Aborted Sudden Cardiac Death, ANNALS OF THORACIC SURGERY, Vol: 108, Pages: E25-E28, ISSN: 0003-4975
Afifi A, Hosny H, Yacoub M, 2019, Rheumatic aortic valve disease-when and who to repair?, Annals of Cardiothoracic Surgery, Vol: 8, Pages: 383-389, ISSN: 2225-319X
Rheumatic valve disease is an endemic problem that is responsible for substantial morbidity and mortality in many countries. Unlike the rheumatic mitral valve, aortic repair continues to be challenging. A thorough understanding of the underlying mechanisms; structural and functional, is essential for repair. We here describe various methods of repair and outline our favoured techniques.
Yacoub M, Aguib H, Afifi A, 2019, The yacoub operation, Surgical Management of Aortic Pathology: Current Fundamentals for the Clinical Management of Aortic Disease, Pages: 749-756, ISBN: 9783709148723
This year marks the 35th anniversary of the introduction of the Yacoub operation and the concept of valve-preserving restorative operations for aneurysms of the ascending aorta and root, in 1982. This has aroused a fair amount of debate and controversy coupled with refinements and experience. We here summarise some of these issues.
Luis M, Doss R, Zayed B, et al., 2019, Effect of live oud music on physiological and psychological parameters in patients undergoing cardiac surgery, Global Cardiology Science and Practice, Vol: 2019
Background. Music therapy has emerged as a promising evidence-based adjuvant method of intervention. This study aims to assess the effect of live oud music on physiological and psychological parameters in patients undergoing cardiac surgery, pre- and post-operatively. Methods. Twelve patients undergoing cardiac operations were randomly allocated into either intervention group or control group, six patients in each group. Patients in the intervention group listened to 20 minutes of improvised and personally customized live oud music before and after surgery while patients in the control group heard the normal hospital sounds. While anxiety scores were assessed preoperatively, vital signs and pain scores were assessed postoperatively together with serum levels of cortisol, which was used as a surrogate marker of the stress response. Results. In the intervention group, pain scores and respiratory rates showed statistically significant reduction after listening to music (P values of 0.043 and 0.034 respectively). Additionally, heart rates, anxiety scores and serum cortisol levels showed borderline significant reduction in patients who listened to music with P values, 0.063, 0.066 and 0.068 respectively. These changes were not found in the control group. Conclusions. This preliminary study suggests a role of live oud music therapy in decreasing stress response of the patients undergoing cardiac surgery, in addition to its positive effects on pain perception and anxiety scores.
Badran HM, Faheem N, Soliman M, et al., 2019, Comparison of vector velocity imaging and three-dimensional speckle tracking echocardiography for assessment of left ventricular longitudinal strain in hypertrophic cardiomyopathy, Global Cardiology Science and Practice, Vol: 2019
Background: Vector velocity imaging (VVI) is a two-dimensional wall motion tracking method that can measure cardiac mechanics in hypertrophic cardiomyopathy (HCM). 3D-speckle tracking echocardiography (3D-STE) has been proven to be superior to conventional measures in assessment of LV function. The aim of this study was to compare the two technologies in the assessment of LV longitudinal strain (LS) in HCM patients. Methods: A total of 50 patients with HCM were investigated using VVI and 3D-STE in same setting. 3D-STE allows obtaining longitudinal, circumferential, radial and area strains (AS). Values of longitudinal strain (LS) and AS by 3D-STE were compared to VVI- derived analyses. Thereafter, VVI-LS values were correlated with LV phenotype. Last, the variability of VVI versus 3DE strain measurements as well as recorded time of analysis was assessed. Results: The absolute value of 3D-STE LS and AS is significantly higher than VVI-LS (P < 0.0001). VVI provided complete longitudinal LV strain information, similar to 3D-STE. There is excellent agreement between the two technologies-derived values, however, a greater number of segments could be analyzed using VVI (94.7%), compared with 3DE (62.1%). Despite VVI being more time consuming, VVI-LS is more correlated to LV mass index, mitral regurgitation severity and functional class when compared with 3D-STE LS and AS. Conclusions: VVI is a feasible modality for assessing LV longitudinal strain. Although VVI agreed well with 3D-STE for most of regional and global LS, a better correlation was found between VVI-LS and HCM phenotype. It is hypothesized that this discrepancy originates from the inferior imaging quality using 3D tracking algorithms.
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