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Fulltext Obstruction of mechanical heart valve--diagnosis, surgical treatment and outcome

Pau KK, Yakub A, Sallehuddin A, Awang Y

Med J Malaysia, 2001 Jun;56(2):196-200.
PMID: 11771080

From 1982 till 1999, our department performed a total of 2970 heart valve replacements--92% of which were with mechanical heart valves. During this period, there were 8 patients who came to our department with mechanical heart valve obstruction. All these patients presented with signs of heart failure or compromised haemodynamic. Confirmatory tests included transthoracic or transoesophageal echocardiography and cine fluoroscopy. Seven patients were operated upon urgently. Four of the patients had valve thrombosis. The time interval between the initial implantation and presentation varies from 4 months to 11.3 years. Six of the seven patients who were operated on recovered well from the surgery.
Fulltext Coarctation of aorta repair at the National Heart Institute (1983-1994)

Adeeb SMSJ, Leman H, Sallehuddin A, Yakub A, Awang Y, Alwi M

Med J Malaysia, 2004 Mar;59(1):11-4.
PMID: 15535329

This retrospective study illustrates our approach to this problem over the years, from performing subclavian flap aortoplasty initially to the more accepted procedure now, which is resection and end-to-end anastomosis. Coarctation of aorta in our population is seen in a varying age groups and are also associated with other cardiac anomalies including both acyanotic and cyanotic congenital cardiac defects. Therefore a wide variety of surgical procedures were performed including resection of the coarcted segment and end-to-end anastomosis, subclavian flap aortoplasty, patch aortoplasty and synthetic tube graft interposition. Subclavian flap aortoplasty is not widely practised anymore in favour of resection with end-to-end anastomosis. Fifty four point four percent of patients had isolated coarctation, 10.5% had associated valvular defects, 28.1% had other simple congenital defects and 7.0% had associated complex cyanotic congenital defects. Perioperative mortality was 5.26% and is correlated with the younger age of patients at time of surgery and severity of cardiac failure at time of presentation. We did not see any difference in mortality for patients with complex congenital disease or between the different surgical procedures. However, we did find that in the early period when resection with end-to-end anastomosis was performed, there was a significantly higher incidence of morbidities.
Mediastinal teratoma in a neonate

Thambi Dorai CR, Muthu Alhagi V, Chee Eng N, Ismail Z, Yakub A

Pediatr Surg Int, 1998 Nov;14(1-2):84-5.
PMID: 9880705

A neonate with severe respiratory distress due to a benign mediastinal teratoma (MT) is reported. Despite early and easy surgical excision of the tumor, the child died due to poor cardiac function. Only ten cases of MT in neonates have been reported in the literature so far. While the tumor has been known to interfere with lung development in utero, postnatal myocardial dysfunction due to poor heart development has not been previously documented.
Syndrome of Ventricular Septal Defect and Aortic Regurgitation - A 22-Year Review of its Management

Krishnasamy S, Sivalingam S, Dillon J, Mokhtar RAR, Yakub A, Singh R

Braz J Cardiovasc Surg, 2021 Feb 01.
PMID: 33577258 DOI: 10.21470/1678-9741-2020-0207

INTRODUCTION: The presence of aortic regurgitation (AR) in the setting of ventricular septal defect (VSD) has always been a management challenge.
METHODS: This is a retrospective study looking at patients who underwent VSD closure with or without aortic valve intervention between January 1st, 1992 and December 31st, 2014 at the Institute Jantung Negara. This study looked at all cases of VSD and AR, where AR was classified as mild, moderate, and severe, the intervention done in each of this grade, and the durability of that intervention. The interventions were classified as no intervention (NI), aortic valve repair (AVr), and aortic valve replacement (AVR).
RESULTS: A total of 261 patients were recruited into this study. Based on the various grades of AR, 105 patients had intervention to their aortic valve during VSD closure. The rest 156 had NI. All patients were followed up for a mean time of 13.9±3.5 years. Overall freedom from reoperation at 15 years was 82.6% for AVr. Various factors were investigated to decide on intervening on the aortic valve during VSD closure. Among those that were statistically significant were the grade of AR, size of VSD, age at intervention, and number of cusp prolapse.
CONCLUSION: We can conclude from our study that all moderate and severe AR with small VSD in older patients with more than one cusp prolapse will need intervention to their aortic valve during the closure of VSD.
Generation and characterization of human cardiac resident and non-resident mesenchymal stem cell

Subramani B, Subbannagounder S, Palanivel S, Ramanathanpullai C, Sivalingam S, Yakub A, et al.

Cytotechnology, 2016 Oct;68(5):2061-73.
PMID: 26820972 DOI: 10.1007/s10616-016-9946-5

Despite the surgical and other insertional interventions, the complete recuperation of myocardial disorders is still elusive due to the insufficiency of functioning myocardiocytes. Thus, the use of stem cells to regenerate the affected region of heart becomes a prime important. In line with this human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have gained considerable interest due to their potential use for mesodermal cell based replacement therapy and tissue engineering. Since MSCs are harvested from various organs and anatomical locations of same organism, thus the cardiac regenerative potential of human cardiac-derived MSCs (hC-MSCs) and human umbilical cord Wharton's Jelly derived MSC (hUC-MSCs) were tested concurrently. At in vitro culture, both hUC-MSCs and hC-MSCs assumed spindle shape morphology with expression of typical MSC markers namely CD105, CD73, CD90 and CD44. Although, hUC-MSCs and hC-MSCs are identical in term of morphology and immunophenotype, yet hUC-MSCs harbored a higher cell growth as compared to the hC-MSCs. The inherent cardiac regenerative potential of both cells were further investigated with mRNA expression of ion channels. The RT-PCR results demonstrated that both MSCs were expressing a notable level of delayed rectifier-like K(+) current (I KDR ) ion channel, yet the relative expression level was considerably varied between hUC-MSCs and hC-MSCs that Kv1.1(39 ± 0.6 vs 31 ± 0.8), Kv2.1 (6 ± 0.2 vs 21 ± 0.12), Kv1.5 (7.4 ± 0.1 vs 6.8 ± 0.06) and Kv7.3 (27 ± 0.8 vs 13.8 ± 0.6). Similarly, the Ca2(+)-activated K(+) current (I KCa ) channel encoding gene, transient outward K(+) current (I to ) and TTX-sensitive transient inward sodium current (I Na.TTX ) encoding gene (Kv4.2, Kv4.3 and hNE-Na) expressions were detected in both groups as well. Despite the morphological and phenotypical similarity, the present study also confirms the existence of multiple functional ion channel currents IKDR, IKCa, Ito, and INa.TTX in undifferentiated hUC-MSCs as of hC-MSCs. Thus, the hUC-MSCs can be exploited as a potential candidate for future cardiac regeneration.
Effect of implantation site on outcome of tissue-engineered vascular grafts

Sologashvili T, Saat SA, Tille JC, De Valence S, Mugnai D, Giliberto JP, et al.

Eur J Pharm Biopharm, 2019 Jun;139:272-278.
PMID: 31004790 DOI: 10.1016/j.ejpb.2019.04.012

OBJECTIVE: Vascular prostheses for small caliber bypass grafts in cardiac and vascular diseases or for access surgery are still missing. Poly (Ɛ-caprolactone) (PCL) has been previously investigated by our group and showed good biocompatibility and mechanical properties in vitro and rapid endothelialisation, cellular infiltration and vascularisation in vivo yielding optimal patency in the abdominal aortic position. The aim of the present study is to evaluate our PCL graft in the carotid position and to compare its outcome to the grafts implanted in the abdominal aortic position.
METHODS: PCL grafts (1 mm ID/10 mm long) were implanted into the left common carotid artery in 20 Sprague-Dawley rats and compared to our previously published series of abdominal aortic implants. The animals were followed up to 3, 6, 12 and 24 weeks. At each time point, in vivo compliance, angiography and histological examination with morphology were performed.
RESULTS: PCL grafts showed good mechanical properties and ease of handling. The average graft compliance was 14.5 ± 1.7%/ mmHg compared to 7.8 ± 0.9% for the abdominal position and 45.1 ± 3.2%/ mmHg for the native carotid artery. The overall patency for the carotid position was 65% as compared to 100% in the abdominal position. Complete endothelialisation was achieved at 3 weeks and cell invasion was more rapid than in the aortic position. In contrast, intimal hyperplasia (IH) and vascular density were less pronounced than in the aortic position.
CONCLUSION: Our PCL grafts in the carotid position were well endothelialised with early cellular infiltration, higher compliance, lower IH and calcification compared to the similar grafts implanted in the aortic position. However, there was a higher occlusion rate compared to our abdominal aorta series. Anatomical position, compliance mismatch, flow conditions may answer the difference in patency seen.
Fulltext A common variant near TGFBR3 is associated with primary open angle glaucoma

Li Z, Allingham RR, Nakano M, Jia L, Chen Y, Ikeda Y, et al.

Hum Mol Genet, 2015 Jul 01;24(13):3880-92.
PMID: 25861811 DOI: 10.1093/hmg/ddv128

Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10(-33)), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.