Left main stem stenosis angioplasty with intravascular ultrasound optimisation criteria guidance using a new generation everolimus drug-eluting stent.

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.

Intravascular imaging-guided treatment of severe coronary artery calcification with orbital atherectomy: A prospective single-centre registry.

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.

Manual or auto-mode: Does this affect radiation dose in digital mammography without compromising image quality?

INTRODUCTION: In current practice, auto-filter exposure mode is used for most screening mammography examinations. However, with better understanding of the side effects of radiation, it is important to examine exposure parameters and practises to minimise radiation dose to patients. The purpose of this phantom study is to investigate the impact that different exposure modes (manual, auto-time and auto-filter) have on radiation dose, while maintaining images of diagnostic quality. METHODS: This study was conducted in three stages. In the first stage, 125 images were taken using a Gammex 156 phantom with polymethyl methacrylate blocks to reflect varying thicknesses (4.5, 5.0, 5.5, 6.0 and 6.5 cm). In the second stage, three mammographers independently assessed image quality and assigned scores based on the number of distinct fibers, masses and speck groups visible. Images with acceptable quality were further investigated in the third stage by comparing their average glandular dose (AGD) using the Kruskal-Wallis H test and Dunn's post-hoc pairwise analysis. RESULTS: Significant differences in AGD were shown between the auto-filter mode and manual mode techniques for 6.0 cm, and between auto-time mode and manual mode techniques for 6.5 cm (p < 0.05). CONCLUSION: For 4.5, 5.0 and 5.5 cm phantoms, as AGD was not significantly different among the different modes, the auto-filter may remain the most practical option. However, significant reductions in AGD were obtained for the 6.0 and 6.5 cm phantoms when manual mode techniques were used. IMPLICATIONS FOR PRACTICE: Manual mode techniques can potentially provide dose-saving opportunity in 6.0 and 6.5 cm breast thickness though future work on human breast should be done to confirm this. Results from this study will support future research based on patient data.

Treatment of severe coronary artery calcification with intravascular lithotripsy: Initial experience of a prospective single centre registry.

INTRODUCTION: Coronary artery calcification can lead to suboptimal results when performing coronary angioplasty with conventional techniques. Shockwave intravascular lithotripsy (IVL) has recently been introduced as a new modality to treat heavily calcified coronary arteries. The purpose of this study was to determine the procedural success and safety of IVL in calcified lesions. MATERIALS AND METHODS: This was a prospective single-centre study regarding the utility of IVL in treatment of calcified coronary arteries. Intravascular ultrasound (IVUS) was used in all cases to characterise the lesions pre procedure and to assess procedural success post procedure. The primary end point was procedural success, defined by IVL treatment and successful stent implantation. The secondary end point was in-hospital and 30-day major adverse cardiovascular event (MACE). RESULTS: Five patients with severely calcified lesions were successfully treated with IVL. The primary end point was achieved in all patients. All of the lesions were severely calcified with concentric calcium. Multiple calcium fractures were identified on IVUS after IVL in all cases. None of the patients suffered in-hospital or 30-day MACE. The average diameter stenosis at baseline was 1.8±0.4mm and the post PCI diameter stenosis was 2.9±0.1mm, with significant acute luminal gain of 1.2±0.3mm (p<0.01). There were no complications of coronary dissection, slow or no reflow, stent thrombosis, or vessel perforation. CONCLUSION: Our initial experience demonstrates the feasibility and safety of IVL in the management of calcified coronary stenosis. The shockwave IVL is an effective treatment approach to disrupt coronary calcification, facilitating stent implantation with optimal results. It is a safe procedure with a good success rate and low rate of complications.

Intravascular ultrasound guided treatment of severe coronary artery calcification with Shockwave Intravascular Lithotripsy.

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.

Renal Denervation in the treatment of Resistant Hypertension.

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.

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.

Definite stent thrombosis among Malaysian population: predictors and insights of mechanisms from intracoronary imaging.

INTRODUCTION: Stent thrombosis (ST) is an uncommon, but significant complication following angioplasty. We aimed to examine the predictors, clinical outcomes and mechanism of definite ST cases among patients who underwent percutaneous coronary intervention (PCI). METHODS: This was a retrospective observational registry of 14,935 patients from the year 2011 till 2015. Clinical characteristics, clinical outcome and intracoronary imaging data were recorded in all the patients. The SPSS Statistic version 24 was used for statistical analysis. The Cox regression hazard model was used to report calculate the hazard ratio (HR) with a 95% confidence interval (95%CI). Independent predictors of ST were identified by univariate logistic regression analysis. Variables that showed a statistically significant effect in univariate analyses were entered in a multivariate Cox proportional hazards model. A p-value<0.05 was regarded as significant. RESULTS: The incidence of definite ST was 0.25% (37 out of 14935 patients). 75% of ST group patients presented with ST elevation myocardial infarction (75% vs. 19.8%, p<0.01). There was higher mortality among patients with ST when compared to the group without ST (Hazard Ratio, HR=10.69, 95%CI: 1.13, 100). Two independent predictors of ST were 1) previous history of acute myocardial infarction (HR=2.36, 95%CI: 1.19, 4.70) and 2) PCI in the context of acute coronary syndrome when compared to elective PCI (HR=37, 95%CI: 15.7, 91.5). Examination of 19 ST cases with intracoronary imaging identified nine cases (47%) of underexpanded stents and five cases (26%) of malopposition of stents. CONCLUSIONS: ST is associated with high mortality. PCI in acute coronary syndrome setting and a previous history of acute myocardial infarction were significant predictors for ST. Intracoronary imaging identified stent underexpansion and malopposition as common reasons for ST. In cases where the risk of ST is high, the use of intracoronary imaging guided PCI is recommended.

Evaluation of the predictive performance of bleeding risk scores in patients with non-valvular atrial fibrillation on oral anticoagulants.

WHAT IS KNOWN AND OBJECTIVE: Bleeding risk scores (BRSs) aid in the assessment of oral anticoagulant-related bleeding risk in patients with atrial fibrillation. Ideally, the applicability of a BRS needs to be assessed, prior to its routine use in a population other than the original derivation cohort. Therefore, we evaluated the performance of 6 established BRSs to predict major or clinically relevant bleeding (CRB) events associated with the use of oral anticoagulant (OAC) among Malaysian patients. METHODS: The pharmacy supply database and the medical records of patients with non-valvular atrial fibrillation (NVAF) receiving warfarin, dabigatran or rivaroxaban at two tertiary hospitals were reviewed. Patients who experienced an OAC-associated major or CRB event within 12 months of follow-up, or who have received OAC therapy for at least 1 year, were identified. The BRSs were fitted separately into patient data. The discrimination and the calibration of these BRSs as well as the factors associated with bleeding events were then assessed. RESULTS: A total of 1017 patients with at least 1-year follow-up period, or those who developed a bleeding event within 1 year of OAC use, were recruited. Of which, 23 patients experienced a first major bleeding event, whereas 76 patients, a first CRB event. Multivariate logistic regression results show that age of 75 or older, prior bleeding and male gender are associated with major bleeding events. On the other hand, prior gastrointestinal bleeding, a haematocrit value of less than 30% and renal impairment are independent predictors of CRB events. All the BRSs show a satisfactory calibration for major and CRB events. Among these BRSs, only HEMORR2 HAGES (C-statistic = 0.71, 95% CI 0.60-0.82, P < .001) and ATRIA score (C-statistic = 0.70, 95% CI 0.58-0.82, P < .001) show acceptable discrimination performance for major bleeding events. All the 6 BRSs, however, lack acceptable predictive performance for CRB events. WHAT IS NEW AND CONCLUSION: To the best of our knowledge, this is the first evaluation study of the predictive performance of these 6 BRSs on clinically relevant bleeding events applied to the same cohort consisting of mainly Asian novel oral anticoagulant users. These BRSs show poor to acceptable predictive performance on OAC-induced major or CRB events. An improvement in the existing BRSs for OAC users is warranted.

A comparison of dabigatran and warfarin for stroke prevention in elderly Asian population with nonvalvular atrial fibrillation: An audit of current practice in Malaysia.

INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia with significant morbidity and mortality in relation to thromboembolic stroke. Our study aimed to evaluate the safety and efficacy of dabigatran in stroke prevention in elderly patient with nonvalvular AF with regard to the risk of ischemic stroke and intracranial haemorrhage (ICH) in real-world setting. METHODS: A retrospective cohort study of 200 patients on dabigatran and warfarin from January 2009 till September 2016 was carried out. Data were collected for 100 patients on dabigatran and 100 patients on warfarin. RESULTS: The mean follow-up period was 340.7±322.3 days for dabigatran group and 410.5±321.2 days for warfarin group. The mean time in therapeutic range (TTR) was 52±18.7%. The mean CHA2DS2 -VASc score for dabigatran group was 4.4±1.1 while 5.0±1.5 for warfarin group. None in dabigatran group experienced ischemic stroke compared to one patient in warfarin group (p=0.316). There was one patient in dabigatran group suffered from ICH compared to none in warfarin group (p=0.316). Four patients in warfarin group experienced minor bleeding, while none from dabigatran group (p=0.043). CONCLUSION: Overall bleeding events were significantly lower in dabigatran group compared to warfarin group. In the presence of suboptimal TTR rates and inconveniences with warfarin therapy, non-vitamin-K antagonist oral anticoagulants (NOAC) are the preferred agents for stroke prevention in elderly Asian patients for nonvalvular AF.

The myth of pulmonary Raynaud's phenomenon: the contribution of pulmonary arterial vasospasm in patients with systemic sclerosis related pulmonary arterial hypertension.

OBJECTIVE: To investigate the contribution of cold induced pulmonary vasospasm by peripheral and central cold stimulus in exacerbating pulmonary arterial hypertension (PAH) in patients with systemic sclerosis undergoing cardiac catheterisation. METHODS: In a prospective pilot study, 21 patients with systemic sclerosis and catheter proven PAH had mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac output (CO) measured before and after peripheral (hand immersion into cold water at 10-15 degrees C for two minutes if tolerated) and central (direct cold water at 4 degrees C injected into the right atrium) cold pressor challenge. Markers of endothelial activation, platelet function, and nitric oxide degradation were measured in blood sampled from the pulmonary artery. RESULTS: 19 of the patients (mean (SD) age, 56 (4) years; baseline mPAP, 34 (8) mm Hg; PVR, 420 (87) dyne.s.cm(-5); CO, 6.4 (1.8) l/min) tolerated cold hand immersion for the maximum two minute duration. All 21 tolerated central cold pressor challenge (three to five injections of 10 ml saline boluses at 4 degrees C). There was no significant change in haemodynamics after cold challenge by either route of provocation. Levels of endothelin-1, von Willebrand factor, fibrinogen, and 3-nitrotyrosine were raised compared with control values in patients with systemic sclerosis but without PAH, but did not change significantly after peripheral cold challenge. CONCLUSIONS: Pulmonary vasospasm in response to peripheral and centrally administered cold pressor challenge is unlikely to contribute to persistence of pulmonary arterial hypertension in patients with systemic sclerosis.

Significance of plasma N-terminal pro-brain natriuretic peptide in patients with systemic sclerosis-related pulmonary arterial hypertension.

OBJECTIVES: A single centre pilot study to investigate the role of the plasma N-terminal pro-brain natriuretic peptide (N-T proBNP) assay to risk stratify patients with suspected pulmonary arterial hypertension (PAH) from a background SSc population. METHODS: Out of 49 SSc patients, 23 had and 26 did not have PAH. Right ventricular haemodynamic variables, six-minute walk test and plasma N-T proBNP levels were recorded from patients catheterised for suspected PAH (23 with PAH and 11/26 without PAH). RESULTS: Mean value of N-T proBNP for SSc patients with PAH was 3365 (standard error 1095) pg/ml compared to 347 (174) pg/ml for patients without PAH. There was a statistically significant correlation (P < 0.05) between N-T proBNP values and (i) mean pulmonary artery pressure (r = 0.53), (ii) right ventricular end diastolic pressure (r = 0.59) and (iii) pulmonary vascular resistance (r = 0.49). Receiver operator characteristic curve analysis showed that a cut-off value of 395.34 pg/ml had a sensitivity of 0.69 and specificity of 1.0. CONCLUSIONS: N-T proBNP estimation in systemic sclerosis-related pulmonary hypertension is a potentially useful diagnostic tool with a high specificity and negative predictive value. This test has the potential to have an important role in risk stratification and monitoring of therapy in the future.

Undetectable postoperative cortisol does not always predict long-term remission in Cushing's disease: a single centre audit.

OBJECTIVE: An undetectable postoperative serum cortisol has been regarded as a definition of cure in Cushing's disease. However, we noted disease recurrence amongst patients with Cushing's disease despite undetectable postoperative cortisol levels, and this led us to audit our data. We have also previously assessed surgical outcome for acromegaly and microprolactinoma for a single surgeon. The aims of this study were two-fold: (i) to investigate the treatment and surgical outcome of patients with Cushing's disease. In particular, we wished to compare the data with outcome for other pituitary tumours in our centre; and (ii) to determine whether undetectable cortisol following surgery is predictive of long-term cure for Cushing's disease. PATIENTS AND METHODS: We performed a retrospective audit of 97 patients; mean age 39.1 (range: 14-82) years, 78/97 (80.4%) female, mean follow-up 92 months (range: 6 months to 29 years), with Cushing's disease seen in our unit between 1969 and 1998. We documented diagnostic investigation, immediate surgical outcome and disease recurrence in these patients. RESULTS: All patients had elevated urinary free cortisol (mean 1270.6 nmol/l, range: 327-3245 nmol/l). In total, 95.5% of patients did not suppress with low-dose dexamethasone suppression testing. Hypokalaemia (K < 3.2 mmol/l) was present in 15.6% of patients; 17.5% of patients did not show cortisol suppression with high-dose dexamethasone and 15.8% of patients did not show an ACTH rise of > 50% following corticotrophic releasing hormone (CRH) administration. There was no significant (> 3) gradient in ACTH or cortisol following CRH during inferior petrosal sinus sampling in 27.3% of patients who had the test. A pituitary tumour was demonstrated on imaging in 55.8% of patients; 10.3% were macroadenomas. Mortality rate following trans-sphenoidal surgery was 1%. Following surgery, the immediate postoperative remission rate (undetectable postoperative cortisol) was 68.5%. However, 11.5% of these patients developed disease recurrence during a mean follow-up period of 36.3 months. Considering microadenomas, Cushing's disease patients had an immediate postoperative remission rate of 63.2% which is significantly lower (P < 0.05) compared to a remission rate of 91.1% in acromegaly. Additionally, new postoperative gonadotrophin deficiency (13.9%) and TSH deficiency (25.8%) was higher in patients with Cushing's disease compared to patients with acromegaly or microprolactinoma. Immediate postoperative remission rates improved from 50% in the first decade of a surgeon's career to consistently above 60% in the second and third decades, demonstrating a trend which may be attributed to surgical experience. CONCLUSIONS: (i) Despite strict criteria for immediate postoperative remission and recurrence, undetectable postoperative cortisol is not always predictive of long-term remission. (ii) Despite an aggressive surgical approach, immediate postoperative remission rates for Cushing's disease are lower compared to other microadenomas. The development of new pituitary hormonal deficiency following surgery is also commoner than that seen amongst other microadenomas. These data have important implications for the follow-up of patients with Cushing's disease.