Aortic valve disease : novel imaging insights from diagnosis to therapy

The general introduction of this thesis outlines the epidemiology and the impact of aortic valve disease in the western world. The thesis further discusses the current and future role of advanced cardiac imaging modalities, using 3D echocardiography and speckle tracking echocardiography strain imaging in the diagnostic and clinical management of patients with aortic regurgitation. In addition, the clinical applications of multimodality cardiac imaging in (transcatheter aortic valve implantation (TAVI) for the treatment of severe aortic stenosis will be discussed: from pre-procedural patient evaluation, to the understanding of complications post-TAVI such as paravalvular regurgitation, and the assessment and monitoring of patients after TAVI.Ministry of Health Training Scholarship, SingaporeUBL - phd migration 201

Sex-Related Differences in Medically Treated Moderate Aortic Stenosis

BackgroundRecent data showed poor long-term survival in patients with moderate AS. Although sex differences in left ventricular (LV) remodeling and outcome are well described in severe AS, it has not been evaluated in moderate AS.MethodsIn this retrospective, multicenter study, patients with a first diagnosis of moderate AS diagnosed between 2001 and 2019 were identified. Clinical and echocardiographic parameters were recorded at baseline and compared between men and women. Patients were followed up for the primary endpoint of all-cause mortality with censoring at the time of aortic valve replacement.ResultsA total of 1895 patients with moderate AS (age 73 ± 10 years, 52% male) were included. Women showed more concentric hypertrophy and had more pronounced LV diastolic dysfunction than men. During a median follow-up of 34 (13-60) months, 682 (36%) deaths occurred. Men showed significantly higher mortality rates at 3- and 5-year follow-up (30% and 48%, respectively) than women (26% and 39%, respectively) (p = 0.011). On multivariable analysis, male sex remained independently associated with mortality (hazard ratio 1.209; 95% CI: 1.024-1.428; p = 0.025). LV remodeling (according to LV mass index) was associated with worse outcomes (hazard ratio 1.003; CI: 1.001-1.005; p = 0.006), but no association was observed between the interaction of LV mass index and sex with outcomes.ConclusionsLV remodeling patterns are different between men and women having moderate AS. Male sex is associated with worse outcomes in patients with medically treated moderate AS. Further studies investigating the management of moderate AS in a sex-specific manner are needed.</p

Myocardial Structural Alteration and Systolic Dysfunction in Preclinical Hypertrophic Cardiomyopathy Mutation Carriers

BACKGROUND: To evaluate the presence of myocardial structural alterations and subtle myocardial dysfunction during familial screening in asymptomatic mutation carriers without hypertrophic cardiomyopathy (HCM) phenotype. METHODS AND FINDINGS: Sixteen HCM families with pathogenic mutation were studied and 46 patients with phenotype expression (Mut+/Phen+) and 47 patients without phenotype expression (Mut+/Phen-) were observed. Twenty-five control subjects, matched with the Mut+/Phen- group, were recruited for comparison. Echocardiography was performed to evaluate conventional parameters, myocardial structural alteration by calibrated integrated backscatter (cIBS) and global and segmental longitudinal strain by speckle tracking analysis. All 3 groups had similar left ventricular dimensions and ejection fraction. Basal anteroseptal cIBS was the highest in Mut+/Phen+ patients (-14.0+/-4.6 dB, p-19.0 dB basal anteroseptal cIBS or >-18.0% basal anteroseptal longitudinal strain had a sensitivity of 98% and a specificity of 72% in differentiating Mut+/Phen- group from controls. CONCLUSION: The use of cIBS and segmental longitudinal strain can differentiate HCM Mut+/Phen- patients from controls with important clinical implications for the family screening and follow-up of these patients.published_or_final_versio

Role of computed tomography imaging for transcatheter valvular repair/insertion

During the last decade, the development of transcatheter based therapies has provided feasible therapeutic options for patients with symptomatic severe valvular heart disease who are deemed inoperable. The promising results of many nonrandomized series and recent landmark trials have increased the number of percutaneous transcatheter valve procedures in high operative risk patients. Pre-procedural imaging of the anatomy of the aortic or mitral valve and their spatial relationships is crucial to select the most appropriate device or prosthesis and to plan the percutaneous procedure. Multidetector row computed tomography provides 3-dimensional volumetric data sets allowing unlimited plane reconstructions and plays an important role in pre-procedural screening and procedural planning. This review will describe the evolving role of multidetector row computed tomography in patient selection and strategy planning of transcatheter aortic and mitral valve procedures

Asian Pacific Society of Cardiology Consensus Recommendations on the Use of MitraClip for Mitral Regurgitation

Transcatheter mitral valve repair with the MitraClip, a catheter-based percutaneous edge-to-edge repair technique to correct mitral regurgitation (MR), has been demonstrated in Western studies to be an effective and safe MR treatment strategy. However, randomised clinical trial data on its use in Asian-Pacific patients is limited. Hence, the Asian Pacific Society of Cardiology convened an expert panel to review the available literature on MitraClip and to develop consensus recommendations to guide clinicians in the region. The panel developed statements on the use of MitraClip for the management of degenerative MR, functional MR, and other less common indications, such as acute MR, dynamic MR, hypertrophic obstructive cardiomyopathy, and MR after failed surgical repair. Each statement was voted on by each panel member and consensus was reached when 80% of experts voted ‘agree’ or ‘neutral’. This consensus-building process resulted in 10 consensus recommendations to guide general cardiologists in the evaluation and management of patients in whom MitraClip treatment is being contemplated

An updated meta-analysis on the clinical outcomes of percutaneous left atrial appendage closure versus direct oral anticoagulation in patients with atrial fibrillation

The availability of direct oral anticoagulants (DOACs) with known lower bleeding risk compared with warfarin have raised questions about the role of left atrial appendage closure (LAAC). We aimed to perform a meta-analysis to compare the clinical outcomes for LAAC versus DOACs. All studies directly comparing LAAC with DOACs up to January 2023 were included. The outcomes studied included the combined major adverse cardiovascular (CV) events outcomes, ischemic stroke and thromboembolic events, major bleeding, CV mortality, and all-cause mortality. Hazard ratios (HRs) and their 95% confidence interval were extracted or estimated from the data and pooled together with a random-effects model. A total of 7 studies (1 randomized controlled trial, 6 propensity-matched observational studies) were finally included, with a pooled population of 4,383 patients who underwent LAAC and 4,554 patients on DOACs. There were no significant differences between patients who underwent LAAC and patients on DOACs in terms of baseline age (75.0 vs 74.7, p = 0.27), CHA2DS2-VASc score (5.1 vs 5.1, p = 0.33), or HAS-BLED score (3.3 vs 3.3, p = 0.36). After a mean weighted follow-up of 22.0 months, LAAC was associated with significantly lower rates of combined major adverse CV event outcomes (HR 0.73 [0.56 to 0.95], p = 0.02), all-cause mortality (HR 0.68 [0.54 to 0.86], p = 0.02), and CV mortality (HR 0.55 [0.41 to 0.72], p<0.01). There were no significant differences in the rates of ischemic stroke or systemic embolism (HR 1.12 [0.92 to 1.35], p = 0.25), major bleeding (HR 0.94 [0.67 to 1.32], p = 0.71), or hemorrhagic stroke (HR 1.07 [0.74 to 1.54], p = 0.74) between LAAC and DOAC. In conclusion, percutaneous LAAC was found to be as efficacious as DOACs for stroke prevention, with lower all-cause and CV mortality. The rates of major bleeding and hemorrhagic stroke were similar. LAAC has a potential role to play in stroke prevention in patients with atrial fibrillation in the era of DOACs, but further randomized data are needed

Longitudinal analysis of thoracic aortic expansion in non-syndromic real-world patients

Remodeling of the thoracic aorta is commonly seen and viewed as a precursor to an aortic aneurysm. However, while aneurysms have been shown to expand at a rate of approximately 1 mm annually, the expansion of the pre-aneurysmal aorta is poorly characterized, especially in relation to age, gender, and aortic size per se. We identified patients that had undergone echocardiography at least twice at a large university medical center. Diagnosis codes, medications, and blood test results were obtained from hospital records. Syndromic patients were excluded (e.g., Marfan's syndrome, bicuspid aortic valve). Final population comprised n = 24,928 patients (median age 61.2 years (inter-quartile range (IQR): 50.6–71.5); 55.8% males) that had undergone a median of 3 echocardiograms (2–4; range 2–27) during a median of 4.0 years (IQR: 2.3–6.2). Hypertension was present in 39.6% of patients and diabetes in 20.7%, median LV ejection fraction was 56.0% (IQR: 41.0–62.0). Aortic size measurements were analyzed in mixed models while clustering on individual patients. Mean expansion was determined for sinus of Valsalva as 1.93 (95% confidence interval; CI95: 1.87–1.99) mm per decade, and for ascending aorta as 1.76 (CI95: 1.70–1.82) mm per decade. Faster expansion was found in males, with larger aortic size, and younger age (p for interaction <0.05 for all). In conclusion, expansion of the thoracic aorta, in real world, non-syndromic patients, is slow and averages <2 mm per decade. This will help to inform management of this large patient group