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Renal Denervation in the treatment of Resistant Hypertension

Yap LB, Balachandran K

Med J Malaysia, 2021 Nov;76(6):893-897.
PMID: 34806679

Hypertension is a risk factor for coronary artery disease and stroke. Only about half of the patients with hypertension are adequately controlled on medical therapy, and about a quarter may develop severe or resistant hypertension. Resistant hypertension is defined as failure to achieve target blood pressure of <140/90mmHg while on full doses of an appropriate three-drug regimen that includes a diuretic. Increasingly more attention has been paid to the potential of renal denervation (RDN) as treatment for resistant hypertension, guided by a better understanding of renal nerve anatomy. RDN is undergoing transformation as a technology for the treatment of resistant hypertension. Early studies demonstrated efficacy in treating resistant hypertension patients with significant reduction in office blood pressure (BP). However, the randomised sham-controlled trial, Symplicity HTN-3, did not demonstrate any significant difference in BP reduction between the RDN and the sham control arm. Since then, further improvements have been made in developing second generation systems. Subsequent studies showed the importance of more distal and branch renal artery ablation, and multielectrode systems have been utilised. Two randomised shamcontrolled trials, the SPYRAL HTN-OFF MED and SPYRAL HTN-ON MED studies showed the effectiveness of RDN with the second-generation radiofrequency ablation system. These studies showed that RDN significantly reduced office and 24-hour ambulatory BP when compared with sham control treatment. The RADIANCE-HTN SOLO trial also demonstrated efficacy using an ultrasound-based catheter system for RDN treatment of resistant hypertension. These trials have reinvigorated current clinical interest in RDN as treatment for resistant hypertension. There is increasing evidence for RDN as an effective treatment for uncontrolled or resistant hypertension. The RDN procedure has also evolved with time, with an improved practice of delivering a larger number of ablations to distal vessels in addition to main renal arteries. The RDN procedure has a low complication rate and may provide an approach that could potentially reduce the morbidity and mortality risks associated with resistant hypertension in Malaysia.
Renal sympathetic denervation in the treatment of resistant hypertension

Yap LB, Choy CN, Balachandran K

Med J Malaysia, 2021 Sep;76(5):777-780.
PMID: 34508396

Hypertension is a significant cardiovascular risk factor. Although the mainstay of treatment remains medication, there are a number of patients with resistant hypertension who have elevated blood pressure despite multiple medications. Failure to achieve adequately controlled blood pressures despite medications put these patients at risk of target organ damage and significant morbidity from hypertension. The renal denervation procedure involves the application of radiofrequency energy or ultrasound at the renal arteries to modulate afferent and efferent sympathetic renal activity. This treatment potentially can improve blood pressure control in patients who have resistant hypertension despite medication. This article presents two case reports of successful treatment of resistant hypertension using radiofrequency renal sympathetic denervation (RDN) at a private medical centre using the latest Spyral catheter. We also reviewed the latest RDN trials to give some insights into this procedure.
Intravascular ultrasound guided treatment of severe coronary artery calcification with Shockwave Intravascular Lithotripsy

Yap LB, Choy CN, Balachandran K

Med J Malaysia, 2022 Jan;77(1):116-118.
PMID: 35087010

Coronary artery calcification is a pathological deposition of calcium in the intimal and medial layer of the arterial wall. Shockwave intravascular lithotripsy (IVL) has evolved as a new modality to treat heavily calcified coronary arteries. IVL involves using a percutaneous device to produce acoustic pressure waves resulting in the delivery of sufficient energy to break up superficial and deep calcium deposits. We present a case where highly dense coronary calcium was successfully treated with intravascular ultrasound (IVUS) guided coronary angioplasty and IVL treatment. IVUS demonstrated heavy calcification at the proximal LAD with a 360° calcium arc. Post procedure, IVUS demonstrated multiple fractures of coronary calcium. Stent deployment was done successfully with good stent strut apposition. There was no procedure related complication. The case demonstrates an example where IVL is an important adjunctive tool in the cardiac catheterization laboratory for lesion preparation and optimal percutaneous coronary intervention.
Complete resolution of constrictive pericarditis after coronary bypass surgery

Paneer SKM, Christina SR, Adli Azam MR, Balachandran K, Deventhiran P

Med J Malaysia, 2021 Sep;76(5):747-749.
PMID: 34508388

Classical constrictive pericarditis (CP) is an unusual and rare complication after coronary artery bypass grafting. It can be transient, progressive or fixed form of cardiac constriction. However recently recognized transient variant of constrictive pericarditis can be managed with medical therapy, though other progressive and irreversible forms may require pericardiectomy. We describe a 65-year-old male patient who developed a classical but a very early transient CP, just within two weeks as a result of post cardiac injury syndrome after coronary bypass surgery. The patient had a complete recovery following medical treatment.
Intravascular imaging-guided treatment of severe coronary artery calcification with orbital atherectomy: A prospective single-centre registry

Yap LB, Choy CN, Navin S, Koh KW, Jeyamalar R, Balachandran K

Med J Malaysia, 2023 Jan;78(1):7-13.
PMID: 36715184

INTRODUCTION: Coronary artery calcification can lead to suboptimal results when performing coronary angioplasty with conventional techniques. The presence of severe coronary artery calcium increases the complications of percutaneous coronary intervention as it may impede stent delivery and optimal stent expansion. The purpose of this study was to determine the procedural success and safety of orbital atherectomy (OA) in calcified lesions.
MATERIALS AND METHODS: This was a prospective single-centre study regarding the utility of OA in the treatment of calcified coronaries. Intravascular ultrasound (IVUS) or optical coherence tomography (OCT) was used in all cases to characterise the severity of calcium pre-procedure, guide vessel sizing and assess procedural success. The primary endpoint was procedural success, defined by successful stent implantation following OA treatment. The secondary endpoint was in-hospital and 30-day major adverse cardiovascular event (MACE).
RESULTS: Ten patients with severely calcified lesions were successfully treated with OA. The primary endpoint was achieved in all patients. All of the lesions were severely calcified with concentric calcium. None of the patients suffered in-hospital or 30-day MACE. The average minimal luminal diameter at baseline was 1.7 ± 0.3 mm and the post- PCI luminal diameter was 3.0 ± 0.3 mm, with a significant luminal gain of 1.3 ± 0.3 mm (p < 0.01). Slow flow during procedure occurred in 2 (20%) cases and dissection occurred in 1 (10%) case during procedure. These were successfully treated with stent delivery to achieve TIMI III flow. There were no cases of stent thrombosis or vessel perforation.
CONCLUSION: Our experience demonstrates the feasibility and safety of OA in the management of calcified coronary stenosis. Intravascular imaging is an important adjunct to the use of OA to assess the severity of calcified coronary lesions, success of OA treatment and to aid sizing of the vessel for stent implantation. OA is an effective treatment approach to disrupt coronary calcification, facilitating stent implantation with optimal results. It is a safe procedure with good success rate and low rate of complications.
Fulltext Identification of Potential Biomarkers and Small Molecule Drugs for Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ): An Integrated Bioinformatics Study Using Big Data

Balachandran K, Ramli R, Karsani SA, Abdul Rahman M

Int J Mol Sci, 2023 May 11;24(10).
PMID: 37239981 DOI: 10.3390/ijms24108635

This study aimed to identify potential molecular mechanisms and therapeutic targets for bisphosphonate-related osteonecrosis of the jaw (BRONJ), a rare but serious side effect of bisphosphonate therapy. This study analyzed a microarray dataset (GSE7116) of multiple myeloma patients with BRONJ (n = 11) and controls (n = 10), and performed gene ontology, a pathway enrichment analysis, and a protein-protein interaction network analysis. A total of 1481 differentially expressed genes were identified, including 381 upregulated and 1100 downregulated genes, with enriched functions and pathways related to apoptosis, RNA splicing, signaling pathways, and lipid metabolism. Seven hub genes (FN1, TNF, JUN, STAT3, ACTB, GAPDH, and PTPRC) were also identified using the cytoHubba plugin in Cytoscape. This study further screened small-molecule drugs using CMap and verified the results using molecular docking methods. This study identified 3-(5-(4-(Cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-hydroxybenzo[d]isoxazol-6-yl) methoxy) phenyl) propanoic acid as a potential drug treatment and prognostic marker for BRONJ. The findings of this study provide reliable molecular insight for biomarker validation and potential drug development for the screening, diagnosis, and treatment of BRONJ. Further research is needed to validate these findings and develop an effective biomarker for BRONJ.
Invasive Fungal Laryngotracheitis Causing Laryngotracheal Separation

Baharudin N, Palanisamy V, Azman M, Balachandran K, Arif F

Cureus, 2024 Oct;16(10):e71558.
PMID: 39553147 DOI: 10.7759/cureus.71558

Fungal laryngotracheitis (FLT) is rare, and the diagnosis can be challenging, as its presentation lacks specificity and may resemble other conditions such as granulomatous disease, gastroesophageal reflux, or malignancy. FLT can be very invasive, causing complete laryngotracheal separation, leading to a non-functioning larynx. We report a 39-year-old Indian woman with diabetes who presented to the emergency department with a sore throat, hoarseness, dysphagia, and stridor for two days. Initially treated for diabetic ketoacidosis due to acute tonsillopharyngitis, she required intubation for airway obstruction and severe metabolic acidosis. Fourteen days post-intubation, an airway assessment revealed bilateral vocal fold edema and pus in the subglottic and cervical trachea. CT imaging showed circumferential fluid around the trachea and a distorted larynx. Examination under anesthesia and neck exploration revealed pus around the thyroid gland and trachea, leading to a tracheostomy and sample collection. Histopathology indicated a fungal infection, confirmed as Candida guillermondii with Escherichia coli. The patient was treated with oral fluconazole and intravenous cefuroxime for four weeks. Despite treatment, a repeat CT indicated a non-functioning larynx, prompting a proposal for a total laryngectomy. After a multidisciplinary discussion, it was decided to continue antifungal therapy due to the patient's clinical improvement. At follow-up a month later, she was stable, tolerating oral intake with a double-lumen tracheostomy tube. This case underscores the importance of a high index of suspicion for FLT and the need for patient-specific decisions regarding total laryngectomy in a non-functioning larynx.
Left main stem stenosis angioplasty with intravascular ultrasound optimisation criteria guidance using a new generation everolimus drug-eluting stent

Yap LB, Choy CN, Koh KW, Kannan P, Jeyamalar R, Navin S, et al.

Med J Malaysia, 2023 Mar;78(2):139-144.
PMID: 36988521

INTRODUCTION: Intravascular ultrasound (IVUS) is recommended in the use of left main stem (LMS) percutaneous coronary intervention (PCI). Since the LMS diameter is usually larger than other coronary arteries, a new generation everolimus drug-eluting stent (DES), Synergy Megatron DES (Boston Scientific) has better axial and radial strength allowing more post implant overexpansion and consequently better suited for LMS lesions. We performed a study to evaluate the clinical outcomes of PCI using 1) an improved IVUS protocol with optimisation targets and 2) the use of Megatron stents.
MATERIALS AND METHODS: This was a study involving LMS PCI coronary lesions using the Synergy Megatron DES. An IVUS protocol using predefined optimisation targets to evaluate for stent malapposition, longitudinal stent deformation, optimal stent expansion >90% of reference lumen and appropriate distal landing zone was used in all cases. The primary end-point was procedural success, defined by successful stent implantation with <30% residual stenosis. The secondary end-point was in-hospital and 30-day major adverse cardiovascular event (MACE).
RESULTS: Eight patients with significant LMS stenosis were successfully treated with the Megatron stent. The primary end-point was achieved in all patients. There were no cases of stent malapposition or longitudinal stent deformation, one case did not have optimal LMS stent expansion and one case did not have an appropriate distal landing zone. IVUS optimisation criteria were met in 6 (75%) cases. There were no complications of coronary dissection, slow or no reflow, stent thrombosis or vessel perforation. None of the patients suffered in-hospital or 30-day MACE. The average LMS MLD at baseline was 2.1 ± 0.1mm and the post-PCI LMS MLD was 4.0 ± 0.5mm, with a significant acute luminal gain of 1.9 ± 0.7mm (p<0.01). A post-PCI MSA of 17 ± 3.9 mm2 was numerically superior compared to those documented in other LMS PCI trials.
CONCLUSION: This study demonstrates low rates of shortterm major adverse cardiovascular events among patients with LMS PCI using the Megatron stents. It highlights the usefulness of IVUS-guided optimisation in LMS PCI. With the use of intravascular imaging, the new generation stent technology can improve the treatment of large proximal vessels and PCI of LMS lesions.
Fulltext Role of microbial electrosynthesis system in CO2 capture and conversion: a recent advancement toward cathode development

Ibrahim I, Salehmin MNI, Balachandran K, Hil Me MF, Loh KS, Abu Bakar MH, et al.

Front Microbiol, 2023;14:1192187.
PMID: 37520357 DOI: 10.3389/fmicb.2023.1192187

Microbial electrosynthesis (MES) is an emerging electrochemical technology currently being researched as a CO2 sequestration method to address climate change. MES can convert CO2 from pollution or waste materials into various carbon compounds with low energy requirements using electrogenic microbes as biocatalysts. However, the critical component in this technology, the cathode, still needs to perform more effectively than other conventional CO2 reduction methods because of poor selectivity, complex metabolism pathways of microbes, and high material cost. These characteristics lead to the weak interactions of microbes and cathode electrocatalytic activities. These approaches range from cathode modification using conventional engineering approaches to new fabrication methods. Aside from cathode development, the operating procedure also plays a critical function and strategy to optimize electrosynthesis production in reducing operating costs, such as hybridization and integration of MES. If this technology could be realized, it would offer a new way to utilize excess CO2 from industries and generate profitable commodities in the future to replace fossil fuel-derived products. In recent years, several potential approaches have been tested and studied to boost the capabilities of CO2-reducing bio-cathodes regarding surface morphology, current density, and biocompatibility, which would be further elaborated. This compilation aims to showcase that the achievements of MES have significantly improved and the future direction this is going with some recommendations. Highlights - MES approach in carbon sequestration using the biotic component.- The role of microbes as biocatalysts in MES and their metabolic pathways are discussed.- Methods and materials used to modify biocathode for enhancing CO2 reduction are presented.