Cardiology Update 2013 New Anticoagulants Renal Denervation
Wearable Defibrillators Radial access for Coronary Intervention
Mitral Valve Clip Trans Aortic Valve Replacement Slide 2 New
Approaches for Preventing Stroke in Atrial Fibrillation Slide 3
Anticoagulation Agents Stroke Prevention in Atrial Fibrillation
VTEVTE post- orthopedic surgery ACS Warfarin (Coumadin ) Dabigatran
(Pradaxa ) Rivaroxaban (Xarelto ) Apixaban (Eliquis ) Phase III
data published FDA approved indication Slide 4 Anticoagulant
Overview Indirect anticoagulants: UFH, LMWH, fondaparinux, warfarin
Direct anticoagulants: Bivalirudin, argatroban, dabigatran,
rivaroxaban, apixaban Slide 5 New Oral AC Sites of Action From: Eur
Heart J 2011;32:1968-1976 Slide 6 1-800-BAD-DRUG Slide 7 DABIGATRAN
Slide 8 Dabigatran (Pradaxa ) Direct Thrombin Inhibitor FDA
indication: stroke prevention for non- valvular AF Approved doses:
150 mg BID 75 mg BID for CrCl 15-30 mL/min Data: RE-LY (AF) and
RE-COVER (VTE) Slide 9 RE-LY Randomized, open-label,
non-inferiority Dabigatran 110 mg BID vs 150 mg BID vs Warfarin in
patients with non-valvular AFIB N = 18,113 Age ~71 years, 63% male,
32% HF, 20% prior CVA/TIA Mean CHADS 2 2.1 Median follow-up 2.0
years Mean TTR for warfarin = 64% (Rosendaal) Connolly SJ, et al.
NEJM 2009;361:1139-51 Slide 10 RE-LY: Results Connolly SJ, et al.
NEJM 2009;361:1139-51 Primary Outcome (Stroke or systemic
embolism): Warfarin 1.69%/yr D 110 mg* 1.53%/yr D 150 mg*^ 1.11%/yr
*Non-inferior to warfarin, P94"> LifeVest Experience Experience
with over 75,000 patients Average duration of use is 2 1/2 months
Median daily use is 95% Survival After Deployment >94% Slide 46
LifeVest Experience First shock conversion success: 98%. Shocked
event survival (conscious ER arrival or stayed at home): 94%. Most
(77%) treated within 60 seconds (remaining delayed from response
button use or VT programming Slide 47 Survival with AED 4-7% (1)
In-hospital survival 13-17% (2) Casino 74% (3) WCD 92-94% Survival
Statistics (1)Nichol et al. Circ, April 21, 2008. (2)Peberdy, et
al, RESUSCITATION 58 (2003) 297-308 (3)Valenzuela et al., NEJM. Oct
26, 1206-9, 2000. Slide 48 Slide 49 Summary Constant monitoring and
protection of SCD with superb results: 98% first shock conversion
Designed for transitional SCD risk periods (the coverage gaps in
ICD policy) Medicare and numerous insurances, including many
Medicaid programs, cover wearable defibrillator use Allows time to
determine long term course of treatment as well as ensuring patient
returns for follow-up visit Slide 50 Renal Sympathetic Denervation:
Resistant Hypertension and Beyond 50 Slide 51 Introduction HTN is a
major morbid condition and public concern. Approximately 30-40% of
the adult population in the developed world suffer from this
condition. Over 65 million Americans (half of whom are > 60
years old) suffer from HTN. It is the leading cause of mortality
worldwide causing 7.5 million deaths annually. Every 20/10 mmHg
increase in BP is associated with doubling of CV mortality.
Adherence to life-long pharmacological therapy to an asymptomatic
disease is challenging necessitating the development of new
therapies. 51 Slide 52 Introduction - Definition Resistant HTN:
failure to achieve goal BP in patients who are adhering to use of
adequate doses of three antihypertensive agents from different
classes, including a diuretic. 52 T. Rousan OUHSC Slide 53
Introduction Pathophysiology Renal efferent and afferent nerves
play a major role in the initiation and maintenance of essential
hypertension. Efferent sympathetic outflow stimulates renin
release, increases tubular sodium reabsorption, and reduces renal
blood flow. Afferent signals from the kidneys modulate central
sympathetic outflow and thereby directly contribute to neurogenic
HTN. 53 Slide 54 54 Slide 55 Introduction Surgical sympathectomy
was developed in the 1920s for the treatment of severe
hypertension. Thoracolumbar sympathectomy (resection of the
sympathetic ganglia D2-L2 splanchiectomy) was first performed in
1938 for the treatment of severe HTN. 55 Slide 56 Introduction
Surgical Sympathectomy The operation resulted in a decrease in BP
(21 mmHg systolic and 15 mmHg diastolic in the surgical group
compared to an increase by 7 mmHg and zero in the control group).
It resulted in significant improvement in headache and resolution
of papilledema and retinopathy. Orthostatic hypotension was a major
side effect (occurring in all patients post-op and persisting in
20% of the survivors). Mortality rate (by the end of 10 years) was
41% (mean survival 46 months) in the surgical group and 47% (mean
survival 45 months) in the control group. 56 Slide 57 Symplicity
HTN-1 A nonrandomized, open-label, proof-of- concept study.
Enrolled 153 patients at 19 investigational sites in Australia,
Europe, and the United States between 6/2007, and 5/2010 (initial
patient enrollment was 6/2007-11/2008). Primary efficacy end-point:
Change in office BP. 57 Slide 58 Symplicity HTN-1 - Procedure 58
Slide 59 Symplicity HTN-1 Results/Efficacy 59 T. Rousan OUHSC Slide
60 Symplicity HTN-1 - Results/Efficacy 60 T. Rousan OUHSC Slide 61
Symplicity HTN-2 Multicentre, prospective, randomized trial.
Inclusion criteria: 18-85 years old. BP > 160 mmHg (> 150
mmHg in DMII) despite taking 3 antihypertensive drug classes, 1 of
which was a diuretic, at target or maximal tolerated dose.
Exclusion criteria: eGFR< 45 mL/min per 1. 73 m2 Type 1 DM
Contraindications to MRI Substantial stenotic valvular heart
disease Pregnancy or planned pregnancy during the study A history
of MI, unstable angina, or CVA in the previous 6 months. 61 Esler
MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Bohm M. Renal
sympathetic denervation in patients with treatment-resistant
hypertension (The Symplicity HTN-2 Trial): a randomised controlled
trial. Lancet. Dec 4;376(9756):1903-1909. T. Rousan OUHSC Slide 62
Symplicity HTN-2 Results/Efficacy 62 Slide 63 Symplicity HTN-2 -
Results/Efficacy 63 Slide 64 Symplicity HTN-3 The SYMPLICITY HTN-3
Trial is a regulatory study designed as a prospective, randomized,
masked procedure, single-blind trial evaluating the safety and
effectiveness of catheter-based bilateral renal denervation for the
treatment of resistant hypertension. 64 Slide 65 Symplicity HTN-3
Estimated Enrollment: 530 patients (2:1 enrollment). Study Start
Date: 9/2011 Estimated Primary Completion Date: 3/2013 (Final data
collection date for primary outcome measure). Eighty-seven study
locations in the U.S. 65 T. Rousan OUHSC Slide 66 Beyond Resistant
HTN 66 T. Rousan OUHSC Slide 67 Chronic heart failure. HTN and
symptomatic atrial fibrillation. Ventricular arrhythmias. Metabolic
syndrome. Glucose metabolism. Secondary Prevention for Patients
After Percutaneous Coronary Intervention. Polycystic ovary
syndrome. Obstructive sleep apnea. Hypertension (initial therapy).
67 T. Rousan OUHSC Slide 68 Renal Denervation & Heart Failure
68 Slide 69 Renal Denervation & Heart Failure Renal Artery
Denervation in Chronic Heart Failure Study (REACH) Estimated
Primary Completion Date: August 2014 Renal Sympathetic Modification
in Patients With Heart Failure Estimated Study Completion Date:
April 2017 69 Bilateral renal denervation can be conducted safely
in patients with chronic systolic heart failure. Results suggested
improvements in both symptoms and exercise capacity. T. Rousan
OUHSC Slide 70 Renal Denervation & Afib 70 Electrical and
structural remodeling are important synergistic contributors to the
Afib substrate. Studies have indicated that angiotensin II and
aldosterone might be involved in atrial structural and electrical
remodeling in patients with Afib. HTN is associated with LVH, left
atrial enlargement, and slowing of the atrial conduction velocity.
Renal artery denervation was shown to decrease Afib episodes in
animal models. Slide 71 71 Slide 72 Renal Denervation & Afib 72
T. Rousan OUHSC Slide 73 Renal Denervation & Afib Renal artery
denervation reduces systolic and diastolic blood pressure in
patients with drug-resistant hypertension and reduces AF
recurrences when combined with PVI. Adjunctive Renal Sympathetic
Denervation to Modify Hypertension as Upstream Therapy in the
Treatment of Atrial Fibrillation (H-FIB) Estimated Study Completion
Date: July 2017 Renal Sympathetic Denervation in Patients With
Hypertension and Symptomatic Atrial Fibrillation (RSDforAF)
Estimated Study Completion Date: July 2015 73 Is bilateral renal
denervation (as a sole procedure) safe and effective in controlling
afib and reducing recurrence? T. Rousan OUHSC Slide 74 Renal
Denervation & Glucose Metabolism 74 Activation of the
sympathetic nervous system contributes to insulin resistance, the
metabolic syndrome, is associated with central obesity and risk of
developing DM. Inhibition of the sympathetic nervous system by
moxonidine has been shown to improve glucose metabolism. Renal
sympathetic denervation decreases whole body norepinephrine
spillover. It is plausible to speculate that renal sympathetic
denervation may have a substantial effect on glucose metabolism.
Slide 75 Fifty patients with therapy resistant HTN were enrolled
(13 control and 37 therapy [renal denervation] groups). SBP and
DBP, fasting glucose, insulin, C peptide, hemoglobin A1c,
calculated insulin sensitivity, and glucose levels during OGT test
were measured before and 1 and 3 months after treatment. 75 Slide
76 76 T. Rousan OUHSC Slide 77 Renal Denervation & Glucose
Metabolism Denervation of the REnal Artery in Metabolic Syndrome
(DREAMS) Estimated Study Completion Date: May 2014 Renal
Sympathetic Modification in Patients With Metabolic Syndrome
Estimated Study Completion Date: August 2016 77 Renal denervation
improves glucose metabolism and insulin sensitivity. Slide 78 78
Slide 79 Conclusions The mechanisms of hypertension are complex and
mutifactorial. The neuroadrenergic hypothesis has led to the advent
of renal sympathetic denervation as a promising procedure for the
treatment of resistant HTN. This procedure will lead to a paradigm
shift in the management of a variety of diseases. The results of
the current and undergoing trials should be taken with guarded
optimism awaiting long-term efficacy and safety follow-up results.
79 Slide 80 Slide 81 Slide 82 log rank p-value for all four
categories
