Cvrx, Inc. · NASDAQ:CVRX
Cvrx — Technical Presentation (August 2012)
19 slides from Cvrx's technical presentation, Aug 30, 2012
Slide 1: Carotid Baroreflex Physiology and Baroreflex Activation Therapy Mechanism of Action
Carotid Baroreflex Physiology and Baroreflex Activation Therapy Mechanism of Action Paris - ESC 30 August 2012 Alberto Alberto Zanchetti Zanchetti Centro Centro di di Fisiologia Fisiologia Clinica Clinica ee Ipertensione Ipertensione Università di Milano, Istituto Auxologico Università Auxologico It
Slide 2: Afferents CNS Efferents
Afferents CNS Efferents HEART RATE Arterial ACh Baroreceptors + Parasympathetic NTS Efferents NE Cardiac Receptors Mechanosensitive VASCULAR RESISTANCE Lung, GI NE Receptors - Sympathetic Efferents 1760 Z
Slide 3: 5 sec
150 mmHg 100 5 sec 1761 Z
Slide 4: Electrical Stimulation of Carotid Sinus Nerves in the Sixties
Electrical Stimulation of Carotid Sinus Nerves in the Sixties Severe hypertension (vascular resistance ) Refractory angina pectoris - Bradycardia - Preload (venodilatation) - Afterload (arteriodilatation) - Myocardial contractility - Cardiac O2 consumption - Coronary blood flow? Effects v
Slide 5: Reasons for Failure of Early Use of Carotid Baroreceptor Stimulation in Hypertension
Reasons for Failure of Early Use of Carotid Baroreceptor Stimulation in Hypertension Effects typically short-lasting Opposition of aortic / cardiac mechano (baro) receptors Opposition by simultaneous carotid chemoreceptor stimulation Failure to increase stimulation parameters because of side effects
Slide 6: Slope of Linear Regression between Systolic Pressure induced by Angiotensin and Lengthening of R-R Interval
Slope of Linear Regression between Systolic Pressure induced by Angiotensin and Lengthening of R-R Interval Normal Normal subject subject msec Slope = 27.3 1200 1000 Hypertensive Hypertensive subject subject msec 800 750 Slope = 1.6 800 700 100 110 120 160 170 180 190 Systolic pressure Systolic pres
Slide 7: Baroreflex sensitivity (log slope)
Baroreflex sensitivity (log slope) 2 Normotensive Normotensive rr == 0.739, 0.739, pp << 0.001 0.001 Hypertensive Hypertensive rr == 0.621, 0.621, pp << 0.001 0.001 1 0 10 20 30 40 50 60 70 Age (y) 1765 Z Gribbin R. et al., Circ Res 1971
Slide 8: Ludbrook, Mancia, Ferrari and Zanchetti, Clin Sci Mol Biol 1977
1766 Z Ludbrook, Mancia, Ferrari and Zanchetti, Clin Sci Mol Biol 1977; 53: 165-171
Slide 9: Hemodynamic Responses to Activation of the Carotid Baroreceptors
Hemodynamic Responses to Activation of the Carotid Baroreceptors by Application of Negative (-35 ± 1 mmHg) or Positive (+33 ± 1 mmHg) Pressures within a neck Chamber in 27 Subjects MAP MAP CO CO TPR TPR HR HR SV SV mmHg l/min units b/min ml 160 7 29 90 90 150 27 * 80 80 140 * 6 25 130 23 70 70 1
Slide 10: Responses to Carotid Baroreceptor Deactivation and Stimulation in Normotension and Hypertension
MAP (i.a. measurements) Responses to Carotid Baroreceptor Deactivation and Stimulation in Normotension and Hypertension Early Early Steady -State Steady-State 0.8 0.8 Regression coeff. for increased NTP 0.6 0.6 Reduced 0.4 0.4 Baroreceptor Activity 0.2 0.2 Normotensive Normotensive 0 0 (n=11) (n=11)
Slide 11: Increases in P-P Interval induced by Distending the Carotid Sinuses
Increases in P-P Interval induced by Distending the Carotid Sinuses through Application of 0.6-S Negative Pressures within a Neck Chamber Normotensive Normotensive 0.4 Mild Mildborderline borderline More Moresevere severeborderline borderline ∆ P-P interval (mmHg) 0.3 NS P < 0.001 0.2 0.1 0.0 100 12
Slide 12: Schematic Drawing of the Stimulus-response Curves Relating Arterial BP and Carotid Baroreceptor Firing
Schematic Drawing of the Stimulus-response Curves Relating Arterial BP and Carotid Baroreceptor Firing at Different BPs and the Concomitant Migration of the Reflex Set-point mmHg 180 % Baroreceptor discharge 160 100 MBP response 140 SH 80 120 MH 60 N MH SH 100 40 N 80 20 60 60 60 80 100 120 140 160
Slide 13: Differential Baroreflex Control of Cardiovascular Targets
Differential Baroreflex Control of Cardiovascular Targets Arterial baroreflex control of BP and HR in Hypertension Impaired baroreflex control of HR Preserved (with resetting) baroreflex control of BP and MSNA 1771 Z
Slide 14: Sympathetic and Baroreflex Cardiovascular Control in Hypertension-related Left Ventricular Dysfunction
Sympathetic and Baroreflex Cardiovascular Control in Hypertension-related Left Ventricular Dysfunction MSNA MSNA bs/min bs/100 hb ** 70 85 ** * * ** 55 70 ** 40 55 25 40 10 25 NT HT HTD NT HT HTD (n = 20) (n = 20) (n = 17) (n = 20) (n = 20) (n = 17) 1772 Z Grassi G et al., Hypertension 2009; 53: 205
Slide 15: Sympathetic Activity (Peroneal Nerve) in Different Clinical Conditions
Sympathetic Activity (Peroneal Nerve) in Different Clinical Conditions ** 80 ** 80 * * * bs/100 hb bs/100 hb 60 60 40 40 20 20 N MH SH C SDH ISH ** 80 80 ** ** ** * ** * ** bs/100 hb bs/100 hb 60 ** 60 ** 40 40 20 20 C O H O+H L L O O No OSA OSA No OSA OSA 1773 Z Grassi et al Hypertens.1998; J Hyper
Slide 16: Afferents CNS Efferents
Afferents CNS Efferents HEART RATE Arterial ACh Baroreceptors Chemoreceptors Parasympathetic NTS Efferents NE Cardiac Receptors Mechanosensitive Chemosensitive VASCULAR RESISTANCE Lung, GI NE Receptors Sympathetic Efferents 1774 Z
Slide 17: Difficulties in Antagonizing Sympathetic Hyperactivity with Drugs
Difficulties in Antagonizing Sympathetic Hyperactivity with Drugs Peripheral Blockade Ganglion blockers: indiscriminate blockade of sympathetic and parasympathetic activity ; ileus, impotence, orthostatic hypotension Blockers of post-ganglionic neuron endings: failure to ejaculate, orthostatic hypot
Slide 18: Afferents CNS Efferents
Afferents CNS Efferents HEART RATE Arterial ACh Baroreceptors Chemoreceptors Parasympathetic NTS Efferents NE Cardiac Receptors Mechanosensitive Chemosensitive VASCULAR RESISTANCE Lung, GI NE Receptors Sympathetic Efferents 1774 Z
Slide 19: The First Generation CVRx Rheos System
The First Generation CVRx Rheos® System Programming System Baroreflex Activation Leads Baroreflex Activation Therapy Implantable Pulse Generator • Established Mechanism of Action • Targeted and specific Worldwide Experience: • Personalized and programmable 400+ patients, >5 yrs • Guarantees complian