A. Sinhal

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.

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. # Novelty and Significance {#article-title-41}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.

Initial experience with the balloon expandable Edwards-SAPIEN Transcatheter Heart Valve in Australia and New Zealand: The SOURCE ANZ registry: Outcomes at 30 days and one year

BACKGROUND We report the findings of the SOURCE-ANZ registry of the clinical outcomes of the Edwards SAPIEN™ Transcatheter Heart Valve (THV) in the Australian and New Zealand (ANZ) clinical environment. METHODS This single arm registry of select patients treated in eight centres, represent the initial experience within ANZ with the balloon expandable Edwards SAPIEN THV delivered by transfemoral (TF) and transapical (TA) access. RESULTS The total enrolment for the study was 132 patients, 63 patients treated by TF, 56 by TA, and 2 patients were withdrawn from the study. The mean ages: 83.7 (TF) and 81.7 (TA), female: 34.3% (TF) and 61.3% (TA), logistic EuroSCORE: 26.8% (TF) and 28.8% (TA), and with procedural success (successful implant without conversion to surgery or death): 92.4% (TF) and 87.1% (TA) (p=0.32). Outcomes were not significantly different between TF and TA implants. These included one year mortality of 13.6% (TF) and 21.7% (TA) (p=0.24), MACCE: 16.7% (TF) and 28.3% (TA) (p=0.12), pacemaker: 4.6% (TF) and 8.3% (TA) (p=0.39), and VARC major vascular complication of 4.6% (TF) and 5.0% (TA) (p=0.91). CONCLUSION TAVI in the ANZ clinical environment has demonstrated excellent outcomes for both the TA and TF approaches in highly selected patients. These results are consistent with those demonstrated in European, Canadian registries and the pivotal US clinical trials. ACTRN12611001026910.

Balloon aortic valvuloplasty to bridge and triage patients in the era of trans-catheter aortic valve implantation

To describe the use of balloon aortic valvuloplasty (BAV) as a method of selecting patients for definitive aortic valve therapy.

Catheter-based renal denervation for resistant hypertension: Twenty-four month results of the EnligHTN I first-in-human study using a multi-electrode ablation system.

BACKGROUND Long term safety and efficacy data of multi-electrode ablation system for renal denervation (RDN) in patients with drug resistant hypertension (dRHT) are limited. METHODS AND RESULTS We studied 46 patients (age: 60 ± 10 years, 4.7 ± 1.0 antihypertensive drugs) with drug resistant hypertension (dRHT). Reduction in office BP at 24 months from baseline was -29/-13 mmHg, while the reduction in 24-hour ambulatory BP and in home BP at 24 months were -13/-7 mmHg and -11/-6 mmHg respectively (p<0.05 for all). A correlation analysis revealed that baseline office and ambulatory BP were related to the extent of office and ambulatory BP drop. Apart from higher body mass index (33.3 ± 4.7 vs 29.5 ± 6.2 kg/m(2), p<0.05), there were no differences in patients that were RDN responders defined as ≥10 mmHg decrease (74%, n=34) compared to non-responders. Stepwise logistic regression analysis revealed no prognosticators of RDN response (p=NS for all). At 24 months there were no new serious device or procedure related adverse events. CONCLUSIONS The EnligHTN I study shows that the multi-electrode ablation system provides a safe method of RDN in dRHT accompanied by a clinically relevant and sustained BP reduction.

Early effects of transcatheter aortic valve implantation and aortic valve replacement on myocardial function and aortic valve hemodynamics: Insights from cardiovascular magnetic resonance imaging

OBJECTIVES There remains a paucity of mechanistic data on the effect of transcatheter aortic valve implantation (TAVI) on early left and right ventricular function and quantitative aortic valve regurgitation. We sought to assess and compare the early effects on myocardial function and aortic valve hemodynamics of TAVI and aortic valve replacement (AVR) using serial cardiovascular magnetic resonance (CMR) imaging and echocardiography. METHODS A prospective comparison study of 47 patients with severe aortic stenosis undergoing either TAVI (n = 26) or high-risk AVR (n = 21). CMR (for left ventricle/right ventricle function, left ventricular mass, left atrial volume, and aortic regurgitation) was carried out before the procedure and early postprocedure (<14 days). RESULTS Groups were similar with respect to Society of Thoracic Surgeons score (TAVI, 7.7 vs AVR, 5.9; P = .11). Preoperative left ventricular (TAVI, 69% ± 13% vs AVR, 73% ± 10%; P = .10) and right ventricular (TAVI, 61% ± 11% vs AVR, 59% ± 8%; P = .5) ejection fractions were similar. Postoperative left ventricular ejection fraction was preserved in both groups. In contrast, decline in right ventricular ejection fraction was more significant in the TAVI group (61%-54% vs 59%-58%; P = .01). Postprocedure aortic regurgitant fraction was significantly greater in the TAVI group (16% vs 4%; P = .001), as was left atrial size (110 vs 84 mL; P = .02). Further analysis revealed a significant relationship between the increased aortic regurgitant fraction and greater left atrial size (P = .006), and a trend toward association between the decline in right ventricle dysfunction and increased postprocedure aortic regurgitation (P = .08). CONCLUSIONS There was no significant difference in early left ventricular systolic function between techniques. Whereas right ventricle systolic function was preserved in the AVR group, it was significantly impaired early after TAVI, possibly reflecting a clinically important pathophysiologic consequence of paravalvular aortic regurgitation.

New Antiplatelet Agents and the Role of Platelet Function Testing in Acute Coronary Syndromes

BACKGROUND Dual antiplatelet therapy is a guideline mandated for patients with acute coronary syndromes (ACS). Despite its use, thrombotic events continue to occur both early and late. Platelet function testing has been used to define the in vitro effects of new antiplatelet agents, and it has been suggested that it be used to choose therapy. The role of platelet function testing, particularly with newer antiplatelet agents, remains unclear. OBJECTIVE We review the rationale for platelet function testing and its application in monitoring patients on antiplatelet therapy. We also review recent clinical trials of newer antiplatelet agents. On the basis of this review, we reach conclusions on the current role of antiplatelet function testing in monitoring modern antiplatelet therapy and the role of the new antiplatelet agents in the treatment of ACS. METHODS We reviewed recent publications on platelet function testing and clinical trials of newer antiplatelet therapies compared with clopidogrel. RESULTS Platelet function testing is complex, but there is now a bedside test, VerifyNow. High platelet reactivity has been associated with worse cardiovascular outcomes in patients undergoing percutaneous coronary intervention. Recent clinical trials have not found any advantage in outcomes in patients who have their therapy adjusted by monitoring their platelet function. Newer agents, prasugrel, ticagrelor, and cangrelor, produce more rapid, complete, less variable effects on platelet function than clopidogrel. Prasugrel was found to improve outcomes compared with clopidogrel in patients with ACS undergoing percutaneous intervention. Ticagrelor is beneficial in all patients with ACS and reduces cardiovascular mortality compared with clopidogrel. Cangrelor improves outcomes in patients undergoing stenting. Recent studies to assess the role of platelet function monitoring of the effects of clopidogrel and modifying treatments have not been successful. CONCLUSION Recent clinical trials have indicated that newer antiplatelet agents have advantages over clopidogrel in the treatment of ACS. Platelet function testing gives us a guide to the timing, efficacy, and variability of therapy and can correlate with poor patient outcomes; however, the use of antiplatelet function testing to tailor therapy does not seem appropriate.

Changes of left ventricular mechanics after trans-catheter aortic valve implantation and surgical aortic valve replacement for severe aortic stenosis: A tissue-tracking cardiac magnetic resonance study

BACKGROUND Left ventricular (LV) mechanics are impaired in patients with severe aortic stenosis (AS). The aim of the present study was to assess their changes early and late after trans-catheter aortic valve implantation (TAVI) and surgical aortic valve replacement (AVR) using cardiac magnetic resonance (CMR) tissue-tracking imaging. METHODS In 59 patients with severe AS undergoing either TAVI (n=35) or surgical AVR (n=24), CMR with late gadolinium enhancement (LGE) imaging was performed before and early post-procedure to evaluate LV function and mass, and presence/extent of LGE. A third CMR scan was performed in 29 patients after a mean follow-up of 15±4months. Tissue-tracking analysis was applied to cine CMR images, to assess LV global longitudinal (GLS), circumferential (GCS) and radial (GRS) strains. RESULTS The TAVI and surgical AVR groups were similar with respect to baseline (p=0.14) and early post-procedure (p=0.16) LV ejection fraction. However, baseline LV GLS was significantly impaired in TAVI patients compared to surgical AVR patients (p=0.025). Early post-procedure, TAVI resulted in a significant improvement of LV GLS (p=0.003), while a significant worsening of LV GLS was observed early after surgical AVR (p=0.012). At longer term follow-up, both TAVI and surgical AVR groups experienced a significant reduction of LV mass and a significant improvement of LV myocardial mechanics in all the three directions. CONCLUSIONS Treatment-specific differences in the changes of LV myocardial mechanics early after afterload release by TAVI and surgical AVR are present. Later, both interventions are associated with an improvement of LV myocardial deformation, alongside a regression of LV hypertrophy.

Transcatheter aortic valve implantation: current trends and future directions

Transcatheter aortic valve implantation (TAVI) has been increasingly utilized for the treatment of severe symptomatic aortic stenosis in inoperable and high surgical risk patients. Recent advances in valve technology include repositionable scaffolds and smaller delivery systems, as well as improvement in periprocedural imaging. These advances have resulted in reduction of vascular complications, rates of paravalvular aortic regurgitation and periprocedural stroke and improved overall outcomes. Increasingly, TAVI is the preferred treatment for high-risk surgical patients with severe aortic stenosis. Consequently, there is growing interest for the use of TAVI in lower surgical risk patients. Furthermore, the role of TAVI has expanded to include valve-in-valve procedures for the treatment of degenerative bioprosthetic valves and bicuspid aortic valves. Questions remain in regard to the optimal management of concurrent coronary artery disease, strategies to minimize valve leaflet restriction and treatment of conduction abnormalities as well as identifying newer indications for its use.

Prognostic impact of moderate or severe mitral regurgitation (MR) irrespective of concomitant comorbidities: a retrospective matched cohort study

Objective We sought to objectively quantify the independent impact of significant mitral regurgitation (MR) on prognosis in patients with multiple comorbidities and ascertain the extent to which median survival is affected by increasing comorbidities. Methods This was a retrospective matched cohort study using a clinical-echocardiography reporting database linked to a clinical and administrative database in an Australian tertiary hospital. We identified our study cohort (patients with significant MR) and control cohort (without MR) on transthoracic echocardiographies performed between 2005 and 2010. The main outcome measures were mortality and heart failure rehospitalisation. A Cox proportional hazards model was used to adjust for clinical covariates and the ‘win ratio’ methodology was utilised to estimate the impact of MR on main outcomes. Results A total of 218 matched patients with and without significant MR were followed-up for 1 year. Significant MR was associated with an adjusted HR for mortality of 1.83 (95% CI 1.28 to 2.62, p<0.001). The win ratio for death and death or heart failure readmission was 0.57 (95% CI 0.40 to 0.78, p=0.0002) and 0.53 (95% CI 0.39 to 0.71, p<0.0001), respectively. Significant MR with left ventricular (LV) systolic dysfunction and age between 75 and 85 years were associated with a substantial reduction in median survival by 2.3 years. Significant MR with LV systolic dysfunction, age beyond 85 and advance comorbidities were associated with a lesser reduction in median survival by 0.2 years. Conclusions Significant MR in patients with multiple comorbidities leads to increase in death and heart failure rehospitalisation with reduced estimated median survival. However, its impact diminishes with increasing comorbidities.