Impact of Genotype-Phenotype Interactions on Cardiovascular Function in Paediatric Loeys-Dietz Syndrome.

Background: The relationship between genotype and phenotypical vascular and cardiac properties in paediatric Loeys-Dietz syndrome (LDS) patients are not well characterized. This study explores the phenotypical differences in aortic properties and cardiac structural and functional parameters between paediatric LDS patients with TGFBR1 and TGFBR2 mutations. Methods: We included 32 LDS patients with either TGFBR1 (n = 17) or TGFBR2 (n = 15) mutations. Echocardiographic data included aortic dimensions, distensibility, strain, and stiffness at the level of the annulus, sinuses of Valsalva, sinotubular junction, ascending aorta, and descending aorta. Parameters for left ventricular size and function were also recorded. Results: Demographics were similar between the groups. Patients with TGFBR2 were more likely to have undergone aortic surgery (47% vs 12%, P = 0.057) and use angiotensin receptor blockers (93% vs 47%, P = 0.015). Aortic z scores were significantly larger in the TGFBR2 group at the level of the aortic valve annulus (P = 0.007), sinuses of Valsalva (P = 0.001), sinotubular junction (P = 0.001), and ascending aorta (P = 0.054). Patients with TGFBR2 also had significantly lower aortic distensibility and strain coupled with higher stiffness index at the level of the annulus, sinotubular junction, and ascending aorta. Parameters for the descending aorta, cardiac morphology, and cardiac function were similar between the groups. Conclusions: Paediatric LDS patients with TGFBR2 present with more severe cardiovascular phenotypes than patients with TGFBR1 with larger aortic dimensions and increased aortic stiffness. Our findings suggest that genotypes should be taken into consideration in the clinical management of paediatric LDS patients.

Contexte: Les liens entre le génotype des enfants atteints du syndrome de Loeys-Dietz (SLD) et les particularités phénotypiques vasculaires et cardiaques n'ont pas encore été bien caractérisés. La présente étude vise à explorer les différences phénotypiques entre les propriétés de l'aorte et les paramètres cardiaques structuraux et fonctionnels des enfants atteints du SLD qui présentent une mutation du gène TGFBR1 et ceux qui présentent une mutation du gène TGFBR2. Méthodologie: Nous avons inclus dans notre analyse 32 patients atteints du SLD présentant une mutation de TGFBR1 (n = 17) ou de TGFBR2 (n = 15). Les données échocardiographiques colligées incluaient les dimensions de l'aorte, sa distensibilité, sa déformation (strain) et sa rigidité au niveau de l'anneau aortique, des sinus de Valsalva, de la jonction sinotubulaire, de l'aorte ascendante et de l'aorte descendante. Les paramètres ayant trait à la taille et à la fonction du ventricule gauche ont également été consignés. Résultats: Les caractéristiques démographiques étaient comparables dans les deux groupes. Les patients présentant une mutation du gène TGFBR2 étaient plus susceptibles d'avoir subi une intervention chirurgicale de l'aorte (47 % vs 12 %, p = 0,057) et de prendre un antagoniste des récepteurs de l'angiotensine (93 % vs 47 %, p = 0,015). Les scores z aortiques étaient significativement plus élevés chez les patients présentant une mutation de TGFBR2 pour les dimensions de l'anneau de la valve aortique (p = 0,007), des sinus of Valsalva (p = 0,001), de la jonction sinotubulaire (p = 0,001) et de l'aorte ascendante (p = 0,054). Les patients avec une mutation de TGFBR2 présentaient aussi une élasticité et une déformation aortiques significativement plus faibles ainsi qu'une rigidité accrue au niveau de l'anneau aortique, de la jonction sinotubulaire et de l'aorte ascendante. Les paramètres de l'aorte descendante, les caractéristiques morphologiques cardiaques et la fonction cardiaque étaient comparables pour les deux groupes. Conclusions: Chez les enfants atteints du SLD, une mutation du gène TGFBR2 se traduisait par des phénotypes plus défavorables que dans le cas d'une mutation du gène TGFBR1 et se caractérisait par des dimensions et une rigidité aortiques accrues. Nos observations indiquent qu'il convient de prendre le génotype des patients en considération lors de la prise en charge clinique des enfants atteints du SLD.

The common pathobiology between coronary artery disease and calcific aortic stenosis: Evidence and clinical implications.

Calcific aortic valve stenosis (CAS), the most prevalent valvular disease worldwide, has been demonstrated to frequently occur in conjunction with coronary artery disease (CAD), the third leading cause of death worldwide. Atherosclerosis has been proven to be the main mechanism involved in CAS and CAD. Evidence also exists that obesity, diabetes, and metabolic syndrome (among others), along with specific genes involved in lipid metabolism, are important risk factors for CAS and CAD, leading to common pathological processes of atherosclerosis in both diseases. Therefore, it has been suggested that CAS could also be used as a marker of CAD. An understanding of the commonalities between the two conditions may improve therapeutic strategies for treating both CAD and CAS. This review explores the common pathogenesis and disparities between CAS and CAD, alongside their etiology. It also discusses clinical implications and provides evidence-based recommendations for the clinical management of both diseases.

Use of Blumensaat's line for assessment of cranial tibial subluxation in dogs with cranial cruciate ligament deficiency.

BACKGROUND: This study aimed to determine whether Blumensaat's line, a consistently present radiographic feature delineating the peak of the femoral intercondylar fossa, could be used to assess for cranial tibial subluxation in canine stifles with cranial cruciate ligament disease. METHODS: Thirty sequential, neutrally positioned, standing-angle stifle radiographs were taken from dogs presenting to a specialist referral centre for treatment of cruciate ligament disease. Thirty similarly positioned radiographs of healthy canine stifles were used as a control group. The radiographs were anonymised and submitted to blinded observers for measurement of the tibial plateau angle, patella tendon angle, Blumensaat's line length and the length of Blumensaat's line cranial to the tibial mechanical axis. RESULTS: Finding that the tibial mechanical axis intersects Blumensaat's line cranial to its midpoint, as a marker of cranial tibial subluxation, had a positive predictive value of 76% for subsequent surgical identification of cruciate ligament disease. CONCLUSIONS: Tibial cranial subluxation is detectable and quantifiable radiographically using the intersection of the tibial mechanical axis and Blumensaat's line. Once quantified, this measurement could be used both as a radiographic marker of cruciate ligament disease and to adjust tibial osteotomy procedures to minimise the risk of under advancement of the tibial tuberosity resulting in a persistently unstable stifle.

Intraoperative and major postoperative complications and survival of dogs undergoing surgical management of epiglottic retroversion: 50 dogs (2003-2017).

OBJECTIVE: To report intraoperative and major postoperative complications in dogs treated surgically for epiglottic retroversion (ER), compare the incidence of major postoperative complications between procedures, and report survival of surgically treated dogs. STUDY DESIGN: Multi-institutional retrospective study. SAMPLE POPULATION: Fifty dogs treated with 78 procedures. METHODS: Medical records of dogs diagnosed and surgically treated for ER from 2003 to 2017 at 11 institutions were reviewed. Complications were divided into intraoperative and major postoperative complications. RESULTS: Intraoperative complications occurred during 2 of 78 (2.6%) procedures. Thirty-six major postoperative complications were documented in 22 dogs after 36 of 74 (48.7%) procedures. Postoperative complications occurred after 7 of 12 (58.3%) nonincisional epiglottopexy, 23 of 43 (53.5%) incisional epiglottopexy, 2 of 4 (50%) partial epiglottectomy, 2 of 12 (16.7%) subtotal epiglottectomy, and 2 of 3 (66.7%) other surgical procedures. Epiglottopexy failure was the most common major postoperative complication. The incidence of major postoperative complications did not differ between procedures (P = .1239), although, when combined, epiglottopexy procedures (30/55) had a higher incidence of complications than epiglottectomy procedures (4/16; P = .048). Thirty (60%) dogs were alive at a median of 928 days (range, 114-2805), 8 (16%) were lost to follow-up after 411 days (range, 43-1158), and 12 (24%) were dead/euthanized after 301.5 days (range, 3-1212). Median survival time was not reached after a median of 716 days. CONCLUSION: Although intraoperative complications were uncommon, major postoperative complications were common, especially after epiglottopexy procedures. CLINICAL SIGNIFICANCE: Although surgical treatment of ER is associated with a high rate of major postoperative complications, especially epiglottopexy procedures, long-term survival can be achieved.