Safety and efficacy of a multi-electrode renal sympathetic denervation system in resistant hypertension: The EnligHTN I trial

Aims: Catheter-based renal artery sympathetic denervation has emerged as a novel therapy for treatment of patients with drug-resistant hypertension. Initial studies were performed using a single electrode radiofrequency catheter, but recent advances in catheter design have allowed the development of multi-electrode systems that can deliver lesions with a pre-determined pattern. This study was designed to evaluate the safety and efficacy of the EnligHTN™ multi-electrode system. Methods and results: We conducted the first-in-human, prospective, multi-centre, non-randomized study in 46 patients (67% male, mean age 60 years, and mean baseline office blood pressure 176/96 mmHg) with drug-resistant hypertension. The primary efficacy objective was change in office blood pressure from baseline to 6 months. Safety measures included all adverse events with a focus on the renal artery and other vascular complications and changes in renal function. Renal artery denervation, using the EnligHTN™ system significantly reduced the office blood pressure from baseline to 1, 3, and 6 months by −28/10, −27/10 and −26/10 mmHg, respectively (P < 0.0001). No acute renal artery injury or other serious vascular complications occurred. Small, non-clinically relevant, changes in average estimated glomerular filtration rate were reported from baseline (87 ± 19 mL/min/1.73 m2) to 6 months post-procedure (82 ± 20 mL/min/1.73 m2). Conclusion: Renal sympathetic denervation, using the EnligHTN™ multi-electrode catheter results in a rapid and significant office blood pressure reduction that was sustained through 6 months. The EnligHTN™ system delivers a promising therapy for the treatment of drug-resistant hypertension.Stephen G. Worthley, Costas P. Tsioufis, Matthew I. Worthley, Ajay Sinhal, Derek P. Chew, Ian T. Meredith, Yuvi Malaiapan, and Vasilios Papademetrio

An overview of PCI in the very elderly

Cardiovascular disease, and in particular ischemic heart disease (IHD), is a major cause of morbidity and mortality in the very elderly (> 80 years) worldwide. These patients represent a rapidly growing cohort presenting for percutaneous coronary intervention (PCI), now constituting more than one in five patients treated with PCI in real-world practice. Furthermore, they often have greater ischemic burden than their younger counterparts, suggesting that they have greater scope of benefit from coronary revascularization therapy. Despite this, the very elderly are frequently under-represented in clinical revascularization trials and historically there has been a degree of physician reluctance in referring them for PCI procedures, with perceptions of disappointing outcomes, low success and high complication rates. Several issues have contributed to this, including the tendency for older patients with IHD to present late, with atypical symptoms or non-diagnostic ECGs, and reservations regarding their procedural risk-to-benefit ratio, due to shorter life expectancy, presence of comorbidities and increased bleeding risk from antiplatelet and anticoagulation medications. However, advances in PCI technology and techniques over the past decade have led to better outcomes and lower risk of complications and the existing body of evidence now indicates that the very elderly actually derive more relative benefit from PCI than younger populations. Importantly, this applies to all PCI settings: elective, urgent and emergency. This review discusses the role of PCI in the very elderly presenting with chronic stable IHD, non ST-elevation acute coronary syndrome, and ST-elevation myocardial infarction. It also addresses the clinical challenges met when considering PCI in this cohort and the ongoing need for research and development to further improve outcomes in these challenging patients.Vimalraj Bogana Shanmugam, Richard Harper, Ian Meredith, Yuvaraj Malaiapan, Peter J Psalti

Outcomes after primary percutaneous coronary intervention for ST-elevation myocardial infarction caused by ectatic infarct related arteries

Background: There is minimal published data on outcomes of patients presenting with ST elevation myocardial infarction (STEMI) due to an ectatic infarct-related artery (EIRA). The aim of this study was to analyse the clinical characteristics and outcomes of these patients presenting for primary percutaneous coronary intervention (P-PCI) in comparison with non-EIRA. Methods: Of the 1834 patients who presented at our institution for P-PCI between February 2008 and November 2013, 25 (1.4%) were identified as having an EIRA. These patients were compared with those with non-EIRA (80 patients) who were age, gender and lesion matched. Further sub-group analysis on in-hospital and long-term outcomes was done comparing EIRA stented and non-stented patients. Clinical events evaluated include death, recurrent infarction, unstable angina, or target lesion revascularisation (TLR). Results: Baseline characteristics were similar between patients with EIRA and non-EIRA although none of those with EIRA had diabetes mellitus. By comparison to the non-EIRA group, the major procedural differences for patients with EIRA were (1) a greater incidence of large thrombus burden (96.0% vs 22.5%, p = 0.0001), (2) increased usage of peri-procedural glycoprotein IIb/IIIa inhibitors (72.0% vs 37.5%, p = 0.01) and post-procedural anticoagulation (28.0% vs 5.0%, p = 0.004), (3) larger mean stent dimension (3.9 ± 0.8 mm vs 3.4 ± 0.6 mm, p = 0.04) and (4) a higher percentage of P-PCI cases that did not have stent deployment (44.0% vs 7.5%, p = 0.0001). Patients with STEMI from EIRA had similar in-hospital outcomes but a higher long-term incidence of composite cardiovascular events at mean follow-up of 36.6 ± 14.1 months (44.0% vs 16.3% for non-EIRA, p = 0.01). Although patients with EIRA who received stenting had better in-hospital outcomes than the non-stented cohort (composite cardiovascular event rate: 0.0% vs 36.4%, p = 0.03), long-term outcomes were comparable (35.7% vs 54.6%, p = 0.59) due to a relatively high frequency of non-fatal MI and unstable angina in both groups. Conclusion: Patients with STEMI due to EIRA carry worse long-term outcomes than those with non-EIRA. While successful stent deployment in the setting of EIRA improves procedural and inpatient success rates, it does not necessarily convey benefit to long-term event rates due to recurrent acute coronary syndromes.Vimalraj Bogana Shanmugam, Peter J. Psaltis, Dennis T.L. Wong, Ian T. Meredith, Yuvaraj Malaiapan, Wally Ahma

Procedural and clinical outcomes in management of bifurcational lesions in ST elevation myocardial infarction

BACKGROUND:Bifurcation percutaneous coronary intervention (PCI) remains a challenging frontier in interventional cardiology, especially in the setting of ST-elevation myocardial infarction (STEMI). We examined the procedural and clinical outcomes of this patient subset. METHODS:We conducted a retrospective case-control study. Between February 2006 and March 2011, 129 patients with STEMI underwent bifurcation PCI at our institution. One hundred and twenty-nine (129) control STEMI patients with non-bifurcation PCI were selected from the institutional database, matched for age, gender, culprit vessel, and lesion location. Patients with cardiac arrest, cardiogenic shock, or who required mechanical ventilation were excluded. Twelve (12)-month follow-up data were collected by telephone calls and examination of the medical records. RESULTS:The average age of patients presenting with STEMI was 61.6 ± 13.1 in the bifurcation group and 61.5 + 31.1 in the non-bifurcation group. There was no difference in lesion type, use of thrombus aspiration catheters, or glycoprotein inhibitors (GPI) among them. Also, the use of drug eluting stent (DES), total cumulative length of stent used, and diameter of the post-dilation balloon were similar. Final kissing balloon post-dilation was performed in 40.3% of bifurcation PCI cases. The incidence of procedural failure (TIMI 0 flow) was 1.5% vs. 0%; p = 0.478. At 12-months follow-up, the bifurcation PCI group had higher incidence of target lesion revascularisation (TLR) (10.9% vs. 3.9%, p = 0.050), mortality (10.1% vs. 2.3%, p = 0.020), and stent thrombosis (9.3% vs. 1.6%; p = 0.013); comprising one acute, nine subacute, and two late vs. two subacute stent thromboses. CONCLUSIONS:During acute STEMI, bifurcation PCI has excellent acute procedural outcomes, but significantly increased incidence of TLR, stent thrombosis and mortality at 12 months.Vimalraj Bogana Shanmugam, Peter J. Psaltis, Leslie Tay, Yuvaraj Malaiapan, Wally Ahma

Area Of Myocardium At Risk And Lesion Length Are Predictors Of Functionally Significant Coronary Artery Stenoses Assessed By Fractional Flow Reserve

Cardiolog

Safety and efficacy of a multi-electrode renal sympathetic denervation system in resistant hypertension: The EnligHTN I trial

Aims: Catheter-based renal artery sympathetic denervation has emerged as a novel therapy for treatment of patients with drug-resistant hypertension. Initial studies were performed using a single electrode radiofrequency catheter, but recent advances in catheter design have allowed the development of multi-electrode systems that can deliver lesions with a pre-determined pattern. This study was designed to evaluate the safety and efficacy of the EnligHTN ™ multi-electrode system. Methods and results: We conducted the first-in-human, prospective, multi-centre, non-randomized study in 46 patients (67% male, mean age 60 years, and mean baseline office blood pressure 176/96 mmHg) with drug-resistant hypertension. The primary efficacy objective was change in office blood pressure from baseline to 6 months. Safety measures included all adverse events with a focus on the renal artery and other vascular complications and changes in renal function. Renal artery denervation, using the EnligHTN™ system significantly reduced the office blood pressure from baseline to 1, 3, and 6 months by -28/10, -27/10 and -26/10 mmHg, respectively (P &amp;lt; 0.0001). No acute renal artery injury or other serious vascular complications occurred. Small, non-clinically relevant, changes in average estimated glomerular filtration rate were reported from baseline (87 ± 19 mL/min/1.73 m2) to 6 months post-procedure (82 ± 20 mL/min/1.73 m2). Conclusion: Renal sympathetic denervation, using the EnligHTN™ multi-electrode catheter results in a rapid and significant office blood pressure reduction that was sustained through 6 months. The EnligHTN™ system delivers a promising therapy for the treatment of drug-resistant hypertension. © The Author 2013

Catheter-based renal denervation for resistant hypertension: 12-month results of the EnligHTN I first-in-human study using a multielectrode ablation system

Renal denervation has emerged as a novel approach for the treatment of patients with drug-resistant hypertension. To date, only limited data have been published using multielectrode radiofrequency ablation systems. In this article, we present the 12-month data of EnligHTN I, a first-in-human study using a multielectrode ablation catheter. EnligHTN I enrolled 46 patients (average age, 60±10 years; on average 4.7±1.0 medications) with drug-resistant hypertension. Eligible patients were on ≥3 antihypertensive medications and had a systolic blood pressure (BP) ≥160 mm Hg (≥150 mm Hg for diabetics). Bilateral renal artery ablation was performed using a percutaneous femoral approach and standardized techniques. The average baseline office BP was 176/96 mm Hg, average 24-hour ambulatory BP was 150/83 mm Hg, and average home BP was 158/90 mm Hg. The average reductions (mm Hg) at 1, 3, 6, and 12 months were as follows: office: -28/-10, -27/-10, -26/-10, and -27/-11 mm Hg (P<0.001 for all); 24-hour ambulatory: -10/-5, -10/-5, -10/-6 (P<0.001 for all), and -7/-4 for 12 months (P<0.0094). Reductions in home measurements (based on 2-week average) were -9/-4, -8/-5,-10/-7, and -11/-6 mm Hg (P<0.001 at 12 months). At 12 months, there were no signals of worsening renal function and no new serious or life-threatening adverse events. One patient with baseline nonocclusive renal artery stenosis progressed to 75% diameter stenosis, requiring renal artery stenting. The 12-month data continue to demonstrate safety and efficacy of the EnligHTN ablation system in patients with drug-resistant hypertension. Home BP measurements parallel measurements obtained with 24-hour ambulatory monitoring.Vasilios Papademetriou, Costas P. Tsioufis, Ajay Sinhal, Derek P. Chew, Ian T. Meredith, Yuvi Malaiapan, Matthew I. Worthley, Stephen G. Worthle

Area of Myocardium at Risk and Lesion Length are Predictors of Functionally Significant Coronary Artery Stenoses Assessed by Fractional Flow Reserve

Cardiolog

Quantitative and qualitative coronary plaque assessment using computed tomography coronary angiography: a comparison with intravascular ultrasound

BACKGROUND:To compare computed tomography coronary angiography (CTCA) with intravascular ultrasound (IVUS) in quantitative and qualitative plaque assessment. METHODS:Patients who underwent IVUS and CTCA within 3 months for suspected coronary artery disease were retrospectively studied. Plaque volumes on CTCA were quantified manually and with automated-software and were compared to IVUS. High-risk plaque features were compared between CTCA and IVUS. RESULTS:There were 769 slices in 32 vessels (27 patients). Manual plaque quantification on CTCA was comparable to IVUS per slice (mean difference of 0.06±0.07, p=0.44; Bland-Altman 95% limits of agreement -2.19-2.08 mm3, bias of -0.06mm3) and per vessel (3.1mm3 ± -2.85mm3, p=0.92). In contrast, there was significant difference between automated-software and IVUS per slice (2.3±0.09mm3, p<0.001; 95% LoA -6.78 to 2.25mm3, bias of -2.2mm3) and per vessel (33.04±10.3 mm3, p<0.01). The sensitivity, specificity, positive and negative predictive value of CTCA to detect plaques that had features of echo-attenuation on IVUS was 93.3%, 99.6%, 93.3% and 99.6% respectively. The association of ≥2 high-risk plaque features on CTCA with echo attenuation (EA) plaque features on IVUS was excellent (86.7%, 99.6%, 92.9% and 99.2%). In comparison, the association of high-risk plaque features on CTCA and plaques with echo-lucency on IVUS was only modest. CONCLUSION:Plaque volume quantification by manual CTCA method is accurate when compared to IVUS. The presence of at least two high-risk plaque features on CTCA is associated with plaque features of echo attenuation on IVUS.Ravi Kiran Munnur, Jordan Andrews ... Peter Psaltis ... Stephen Nicholls ... Jordan Andrews ... Yu Kataoka ... et al

Stenotic flow reserve derived from quantitative coronary angiography has modest but incremental value in predicting functionally significant coronary stenosis as evaluated by fractional flow reserve

Background: Stenotic flow reserve (SFR) derived from quantitative coronary angiography (QCA) has been correlated with myocardial ischaemia as determined by pharmacological stress echocardiography. However, the diagnostic accuracy of SFR in predicting functionally significant coronary stenosis as assessed by the gold standard, fractional flow reserve (FFR), has not been previously characterised. Methods: Patients who underwent coronary angiography and FFR assessment between January 2010 and February 2012 in a single tertiary centre were retrospectively assessed. QCA parameters such as minimal lumen diameter (MLD), lesion length, diameter stenosis (DS), SFR, turbulent resistance (TR) and Poiseuille resistance (PR) were assessed. Significant FFR was defined as FFR ≤0.8. The diagnostic accuracy of QCA parameters to predict significant FFR was assessed by independent t-test and receiver operator characteristic (ROC) curve. Statistical significance was defined as P value of 50% (AUC =0.64). Using a retrospectively determined optimal cut-off value of 3.51, the sensitivity of stenotic-flow-reserve was modest at 56% with good specificity of 81%. DS >50% had a sensitivity of 47% and specificity of 82% in predicting significant FFR. There was incremental predictive value when SFR was added to DS >50% on integrated discrimination improvement index (IDI =0.103, P50% for predicting significant FFR.Elizabeth L. Potter, Colin Machado, Yuvaraj Malaiapan, Om Narayan, Brian S.H. Ko, Peter J. Psaltis, Kiran Munnur, James D. Cameron, Ian T. Meredith, Dennis Thiam Leong Won