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Implanted Hemodynamic Monitoring: Realized & Potential Applications Robert C. Bourge, MD Professor of Medicine, Radiology and Surgery M. G. Waters Chair of Cardiovascular Medicine Director, Division of Cardiovascular Disease The University of Alabama at Birmingham <[email protected]> I will discuss off label use and/or investigational use of the following drugs/devices in my presentation: Chronicle® Implanted Hemodynamic Monitor I have the following relationships to disclose: Medtronic, Cardiomems, Remon Techonologies: (Grant Support, Advisory Board, Consultant, Honoraria) Congestive Heart Failure: Definition “Heart failure occurs when an abnormality of cardiac function causes the heart to fail to pump blood at a rate required by the metabolizing tissues or when the heart can do so only with an elevated filling pressure.” Report of the Task Force on Research in Heart Failure. National Heart, Lung and Blood Institute, 1994. U.S. Population > 65 Years 100 75.6 80 60 40 20 0 16.6 9.2 60 34.9 31. 25.6 1 11.3 12.5 12.7 53.6 Millions 16.6 20.7 % of total 70 80 90 00 10 20 30 40 Year Courtesy of R. Rodeheffer, Mayo Congestive Heart Failure Heart Failure Signs and Symptoms are Insensitive and Non-specific Symptoms Include: Dyspnea Fatigue Peripheral Edema Orthopnea Weight gain Rales Shortness of breath Feeling of tiredness Swelling of legs and ankles Pulmonary congestion Due to fluid retention Abnormal lung sounds Diagnosis and Evaluation of of CHF: Clinical Challenge The symptoms and signs of heart failure like shortness of breath and edema have a broad differential diagnosis The physical exam is neither sensitive nor specific for volume overload and, even in good hands, there are often errors. Chest X-Ray findings have limited accuracy for CHF One-third to one-half of patients with CHF have normal systolic function The needed routine estimate of left sided filling pressures in the medical management of heart failure is difficult and fraught with error. Even with frequent clinic visits, the average patient with CHF is usually seen less than once a month. Adapted and Expanded from Maisel A. et al. J Am Coll Cardiol 2001;37(2):379-85 Weight and Edema are Unreliable over Time Weight may stay stable when fluid increases, if appetite decreases. Weight may increase despite stable fluid status over longer period when patients eat better Edema usually indicates > 2 L of fluid retention Many patients never get edema despite severe volume overload Edema and Weight are Unreliable Indices of Congestion; Especially At Home (Remotely) Edema usually indicates >2 L of fluid retention Many patients never exhibit edema despite severe volume overload Edema in older populations is more sensitive, less specific Weight may stay stable when fluid increases, if appetite falls Weight may increase over time when patients eat better With chronic heart failure, significant increases in pressure may occur with little symptoms, especially at rest. Acute Exacerbations Contribute to the Progression of the Disease Clinical Status With each event, hemodynamic alterations/myocardial injury contribute to progressive ventricular dysfunction Acute event Heart failure progression may be accelerated by the aggressive therapies initiated during hospitalization Time Jain P et al. Am Heart J. 2003;145:S3-S17. Congestive Heart Failure Congestion (as measured by increased intracardiac end diastolic pressures) Symptoms and Survival Physiological Premise of IHM Guided Care (1) Heart Failure Event Symptoms Pressure Changes -21 -14 -7 Proactive 0 Days Reactive Physiological Premise of IHM Guided Care (2) Medical Intervention Averted Heart Failure Event Pressure Changes -21 -14 Proactive -7 0 Days Changes in BNP Levels and Pulmonary Wedge Pressure During 24 Hours of Treatment 1300 33 PAW BNP 29 1200 1100 27 25 1000 23 900 21 800 19 700 17 600 15 baseline 4 8 12 16 Hours 15 Heart failure patients responding to vasodilators and diuretics 20 24 BNP (pg/ml) PAW (mm Hg) 31 Clinical Utility of Serum BNP Levels Serum BNP < 100 pg/ml Normal or well compensated heart failure Serum BNP = 100-200 pg/ml Well compensated heart failure Normal (elderly, female, BB use) Cor pulmonale (right heart failure), Hypertension, Diastolic Dysfunction Ischemic Heart Disease,normal resting LVEDP Serum BNP = 200 – 400 pg/ml Mild - Moderate Decompensated Acute Heart Failure; moderate to severe HF in obese patient Compensated Chronic Heart Failure Serum BNP > 400 pg/ml Severe Congestive Heart Failure (hypervolemia) Adapted & expanded from W. Miller, MD, Mayo Clinic and A. Maisel, UCSD. Chronicle® Implantable Hemodynamic Monitor (Medtronic, Inc.) Implantable Hemodynamic Monitor (IHM), RV lead 4+ year battery life (SVO-Lithium) Internal memory 512k RAM, 96k ROM Programable “resolution” from 2 sec - 52 min (mean, range) and trend data storage from 3.5 hr – 3 months Parameters Measured/Calculated/Stored Include: PA systolic (RV systolic) pressure PA diastolic (ePAD from RV pressure at +dP/dtmax) RV diastolic pressure (RA) Maximum positive and negative RV dP/dt (calculated) Heart Rate, Temperature, Patient Activity Pressure and Electrogram Waveforms Programmable and Patient Initiated Trigger for high-res. data store Additional System Components: External Pressure Reference (EPR) – size of “pager” Telemetry data download-upload (office/phone) Chronicle web site data review via internet browser Chronicle® Implantable Hemodynamic Monitor (Medtronic, Inc.) 25g, 14cc Chronicle IHM - Lead Positioning Pressure Sensor Capsule Chronicle Pressure Measurements EGM 1 = RVDP at QRS detection 2 2 = RVSP at peak of waveform 3 3 = ePAD at maximal dP/dt 1 RVP dP/dt Chronicle Data ECG Variables collection RVSP RV Diastolic Pressure (RVDP) ePAD (PAD=RVP) PA press RV Systolic Pressure (RVSP) Estimated Pulmonary Artery Diastolic Pressure (ePAD) RV press RVDP RV dP/dt 1. Ohlsson A et al.J Cardiac Failure 1995; 1:161-168 2. Chuang PP et al., Journal of Cardiac Failure Vol. 2 No.1 1996:41-46 3. Reynolds DW et al., J Am Coll Cardiol 1995;25:1176-1182. Accuracy of Intracardiac Pressure Monitoring 20 40 60 80 100 120 Swan-Ganz RV Systolic Pressure (mmHg) 80 40 60 r = 0.84 0 20 40 60 Chronicle PAD Pressure (mmHg) r = 0.87 20 60 40 20 0 ePAD 0 Chronicle RV Diastolic Pressure (mmHg) r = 0.95 80 100 120 Diastolic 0 Chronicle RV Systolic Pressure (mmHg) Systolic 0 20 40 60 Swan-Ganz RV Diastolic Pressure (mmHg) 0 20 40 60 80 Swan-Ganz PAD Pressure (mmHg) N = 32 patients, 217 measurements at rest (supine, siting), Valsalva, exercise) Magalski, A, et al. Continuous Ambulatory Right Heart Pressure Measurements with an Implantable Hemodynamic Monitor: a Multi-center, 12 Month Follow-up Study of Patients with Chronic Heart Failure, J Card Failure. 2002;8(2):63-70. 120 r = 0.94 20 40 60 80 100 120 6 Months 0 20 40 60 80 100 120 Swan-Ganz RV Systolic Pressure (mmHg) 100 120 80 60 40 20 0 20 40 60 80 100 120 Swan-Ganz RV Systolic Pressure (mmHg) Chronicle RV Systolic Pressure (mmHg) Swan-Ganz RV Systolic Pressure (mmHg) 0 Chronicle RV Systolic Pressure (mmHg) 100 12 Months 100 120 80 r = 0.94 80 60 60 40 40 20 r = 0.95 20 60 40 20 0 0 3 Months 0 r = 0.96 80 100 120 Implant 0 Chronicle RV Systolic Pressure (mmHg) Chronicle RV Systolic Pressure (mmHg) Chronicle Phase I Validation 0 20 40 60 80 100 120 Swan-Ganz RV Systolic Pressure (mmHg) Magalsky A. et al., J Card Failure 2002;vol.8 n.2:63-70 Chronicle System & Information Flow Chronicle IHM Remote Monitor Secure Network Clinician Access Chronicle IHM System Web Site 94th percentile Median 6th percentile Bourge, RC et al. J Am Coll Cardiol 2008;51:1073-9 The Implantable Hemodynamic Monitor: Potential Clinical Applications Improve our understanding of the hemodynamic alterations that occur with heart failure and the hemodynamic response to therapy Allow more precise titration and tailoring of heart failure and pulmonary vascular disease (PH) therapy Provide “early warning” of hemodynamic deterioration Aid in the diagnosis of symptomatic events in the outpatient setting (home or clinic) Provide method by which to develop, refine, and optimize the use of chronic hemodynamic data for longterm patient management Possibly affect the intermediate and long term morbidity and mortality in patients with heart failure Daily e-PAD Mean and Variability in pts with or without events Daily Mean Daily Variability mmHg mmHg 35 6 With events 30.5+6.6 No events With events 4.2+3.1 30.1+8.2 30 No events 4.0+2.2 4 3.2+2.1 2.7+1.7 25.3+6.1 25.4+5.9 25 2 P<0.001 P<0.001 20 P=0.031 P<0.001 Chronicle Control 0 Chronicle Control The Implantable Hemodynamic Monitor: Potential Clinical Applications Improve our understanding of the hemodynamic alterations that occur with heart failure and the hemodynamic response to therapy Allow more precise titration and tailoring of heart failure and pulmonary vascular disease (PH) therapy Provide “early warning” of hemodynamic deterioration Aid in the diagnosis of symptomatic events in the outpatient setting (home or clinic) Provide method by which to develop, refine, and optimize the use of chronic hemodynamic data for longterm patient management Possibly affect the intermediate and long term morbidity and mortality in patients with heart failure Sys / Dia RVP (mmHg) Chronicle Patient E4 100 90 80 70 60 50 40 30 20 10 0 -10 -20 0 18-Nov-99 7 14 Time (days) 6-Dec-99 See speaker notes. Median No activity 08-Dec 07-Dec 06-Dec 05-Dec 04-Dec 03-Dec 02-Dec 01-Dec 30-Nov 29-Nov 28-Nov 27-Nov 26-Nov 25-Nov 24-Nov 23-Nov 22-Nov 21-Nov 20-Nov 19-Nov Data points: 18-Nov 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0.0 -10.0 17-Nov mmHg UAB E4: Systolic / Diastolic, Days 0-18; Lo days See speaker notes. Median No days 20-Jun 19-Jun 18-Jun 17-Jun 16-Jun 15-Jun 14-Jun Data points: 13-Jun 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0.0 -10.0 12-Jun mmHg E4: Systolic / Diastolic, 6/13-6/19 The Implantable Hemodynamic Monitor: Potential Clinical Applications Improve our understanding of the hemodynamic alterations that occur with heart failure and the hemodynamic response to therapy Allow more precise titration and tailoring of heart failure and pulmonary vascular disease (PH) therapy Provide “early warning” of hemodynamic deterioration Aid in the diagnosis of symptomatic events in the outpatient setting (home or clinic) Provide method by which to develop, refine, and optimize the use of chronic hemodynamic data for longterm patient management Possibly affect the intermediate and long term morbidity and mortality in patients with heart failure Heart Rate UAB E11 Chronically Implanted Hemodynamic Monitor 68y/o male DM, IHD, EF 45%, severe diastolic dysfunction, renal insufficiency, morbidly obese; intermittently noncompliant with salt and fluid restriction. Rx: torsemide 150 bid metolazone spironolactone 50 bid atenolol 25 qDay RV Systolic Pressure (mmHg) 40 RV Diastolic Pressure (mmHg) 20 ePAD (estimated PA diastolic) Pressure (mmHg) Nesiritide + IV diuretics Heart Rate UAB E11 68y/o male DM, IHD, EF 45%, severe diastolic dysfunction, renal insufficiency, morbidly obese; intermittently noncompliant with salt and fluid restriction. Rx: torsemide 150 bid metolazone spironolactone 50 bid atenolol 25 qDay After episode of nausea and diarrhea, consumed beef and chicken bouillon (high in salt). Admitted with hyperkalemia (7.7mm/l) and class IV CHF, 3 lb weight gain. RV Systolic Pressure (mmHg) 40 RV Diastolic Pressure (mmHg) 20 ePAD (estimated PA diastolic) Pressure (mmHg) Nesiritide + IV diuretics Heart Rate UAB E19 RV systolic RV diastolic RV pulse pressure The Implantable Hemodynamic Monitor: Potential Clinical Applications Improve our understanding of the hemodynamic alterations that occur with heart failure and the hemodynamic response to therapy Allow more precise titration and tailoring of heart failure and pulmonary vascular disease (PH) therapy Provide “early warning” of hemodynamic deterioration Aid in the diagnosis of symptomatic events in the outpatient setting (home or clinic) Provide method by which to develop, refine, and optimize the use of chronic hemodynamic data for longterm patient management Possibly affect the intermediate and long term morbidity and mortality in patients with heart failure Chronicle™ Implantable Hemodynamic Monitor: Patient Example UAB Pt E1: Heart Rate and Activity 120 10.0 Implant 9.0 8.0 100 7.0 90 6.0 5.0 80 4.0 70 3.0 2.0 60 activity counts (blue) bpm 110 1.0 50 0.0 13-Oct 14-Oct 15-Oct 16-Oct 17-Oct 18-Oct 19-Oct 20-Oct 21-Oct 22-Oct days All data, mean of 2 min resolution Clinic Visit See speaker notes. Chronicle™ Implantable Hemodynamic Monitor: Patient Example UAB Pt E1: Systolic and Diastolic 80 70 Implant 60 RVsys mmHg 50 40 30 20 RVdiast 10 0 -10 13-Oct 14-Oct 15-Oct 16-Oct 17-Oct 18-Oct days 19-Oct 20-Oct Clinic Visit 21-Oct 22-Oct Chronicle™ Implantable Hemodynamic Monitor: Patient Example UAB Pt E1: ePAD 45 Implant 40 mmHg 35 30 25 20 15 10 13-Oct 14-Oct 15-Oct 16-Oct 17-Oct 18-Oct 19-Oct 20-Oct days Clinic Visit 21-Oct 22-Oct Chronicle™ Implantable Hemodynamic Monitor: Patient Example UAB Pt E1: Temperature 40.0 39.5 39.0 degrees C Implant 38.5 38.0 37.5 37.0 36.5 36.0 13-Oct 14-Oct 15-Oct 16-Oct 17-Oct 18-Oct 19-Oct 20-Oct days Clinic Visit 21-Oct 22-Oct The Implantable Hemodynamic Monitor: Potential Clinical Applications Improve our understanding of the hemodynamic alterations that occur with heart failure and the hemodynamic response to therapy Allow more precise titration and tailoring of heart failure and pulmonary vascular disease (PH) therapy Provide “early warning” of hemodynamic deterioration Aid in the diagnosis of symptomatic events in the outpatient setting (home or clinic) Provide method by which to develop, refine, and optimize the use of chronic hemodynamic data for longterm patient management Possibly affect the intermediate and long term morbidity and mortality in patients with heart failure Things are not always as they seem! Chronicle® Offers Management to Patients with Advanced Signs & Symptoms of Heart Failure (COMPASS-HF): Ambulatory Hemodynamic Guided Management of Heart Failure Robert C. Bourge, MD Mark F. Aaron , MD Anthony Magalski , MD Lynne W. Stevenson , MD Andrew L. Smith , MD Mark A. O'Shaughnessy , MD William T. Abraham, MD Juan M. Aranda, Jr., MD Philip B. Adamson , MD Michael R. Zile , MD Frank W. Smart , MD Mariell L. Jessup , MD For the COMPASS-HF Investigators and Coordinators Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9 COMPASS-HF Study Hypothesis A management strategy based on continuously monitored intra-cardiac pressures in patients with heart failure already on optimal medical care improves patient morbidity Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9 COMPASS-HF Primary Study Endpoints Primary Efficacy Endpoint HF-related hospitalizations HF-related Emergency Department visits requiring IV therapy HF-related urgent clinic visits requiring IV therapy Safety Endpoints Freedom from system-related complications at 6 months is 80% Freedom from pressure sensor lead failure at 6 months is 90% Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9 Patient Selection Diagnosed with chronic NYHA class III-IV heart failure and on standard medical therapy for at least 3 months At least one prior heart failure related hospitalization or a heart failure related Emergency Department visit necessitating intravenous treatment within 6 months prior to baseline evaluation Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9 Methodology Subjects were blinded to their randomization assignment through their 6 month follow-up visit a randomized single-blind study All patients transmitted data at least once weekly via a home-based remote monitor Standardized communication scripts were used to maintain subject blind Scheduled surveillance calls were made to the Control (blocked clinician access) group to minimize bias All major events: primarily hospitalizations, emergency department and urgent clinic visits were adjudicated by an Independent Physician Review Committee blinded to randomization assignment Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9 Statistical Methodology Hypothesized heart failure event rate was 1.2 for 6 months resulting in a minimum sample size of 274 patients and cumulative, randomized follow-up of 1354 patient months Analyzed dataset reports results through June 3, 2005, which was when all patients completed randomized follow-up (total of 1,620 patient months) Normalized HF-related event rates were analyzed using both Poisson and negative binomial regression model An intention to treat principle was used for all study endpoints Pre-specified sub-groups were evaluated for interaction with outcome and for treatment effect within those prespecified sub-groups Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9 COMPASS-HF Study Design / Enrollment Baseline Evaluation Withdrew prior to implant = 24 n = 301 Implant Attempted Unsuccessful implant = 3 n = 277 Total Clinician Access Group = 134 CHRONICLE Randomization - 274 (stratified by LVEF or 50%) Blocked Clinician Access Group =140 CONTROL 1 Month Follow-up 1 Month Follow-up 3 Month Follow-up 3 Month Follow-up 6 Month Follow-up 6 Month Follow-up At 6 months Chronicle guided care enabled in all patients Study timeline: First implant March 18, 2003; Database closed June 3, 2005 Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9 Study Clinical Care Guidelines Pressure State • • (RV systolic, RV diastolic, Estimated PAD) Treatment strategy Hypervolemic • Medication titration • Modify dietary restrictions • ? Hospitalize, ? IV therapy Optivolemic • Ongoing management & assessment Hypovolemic • Medication titration • Modify dietary restrictions • ? hospitalize, ? fluid administration Ranges were determined for each patient at baseline and assessed over time Guidelines were followed in 96% of patient state assessments COMPASS Patient Baseline Characteristics Chronicle n=134 Control n=140 p-value 58 14 58 13 0.75 Gender (% female) 34 36 0.80 Ethnicity (% Caucasian) 47 53 0.71 Etiology (% Ischemic) 47 44 0.72 NYHA (% Class III) 84 87 0.49 2.2 1.9 2.4 1.7 0.29 Concomitant Devices (%) 43 37 0.39 Diuretic Use (%) 93 99 0.02 ACE-I or ARB Use (%) 83 80 0.64 Beta Blockade Use (%) 81 79 0.88 Age, years (mean ± sd) Prior HF Events (mean ± sd)* *Six months prior to implantation RESULTS: All Safety Objectives Exceeded Number of patients at risk Number of complications (patients) Complication-free survival at 6 months (95% CI) System 277* 24 (23) 91.5% (88.7%-94.3%) Sensor 274 0 (0) 100% (98.9%-100%) * 3 patients had unsuccessful implant Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9 Comparison of Observed Call Rates During Randomized Period Call Type Group Mean Call Rate (Calls/Patient) CHRONICLE 20.7 Clinician-Initiated 0.88 CONTROL 21.2 CHRONICLE 3.0 Patient-Initiated 0.51 CONTROL 2.8 CHRONICLE 23.7 Overall Call Rate 0.94 CONTROL CHRONICLE (n=134) CONTROL (n=140) p-value 24.0 Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9 Efficacy Objective Control (n = 140) # of Pts with Events 44 60 Total HF Related Events 84 113 Hospitalizations 72 99 Emergency Department Visits 10 11 2 3 0. 67 0.85 Urgent Clinic Visits Event Rate / 6months* % Reduction in Event Rate 1. 2. Cumulative Events 120 Chronicle Control 100 Events Chronicle (n =134) (p=0.091; 21% p=0.332) 80 60 40 20 0 1 2 4 Months Poisson model - Scaled Deviance = 1.8 Negative Binomial model - Scaled Deviance = 0.8 Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9 6 Major Component of Primary Endpoint: HF-related Hospitalization Time to Event Analysis Freedom from HF-related hospitalization 100% 80% Chronicle Control 60% 40% RR = 0.64 (95%CI = 0.42 - 0.96) p=0.03 20% 0% 0 50 100 150 200 Days Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9 Pre-specified Sub-group Analysis: Interaction with Primary Endpoint Sub-group (patients%) Systolic HF (74%) Chronicle Control Events Events 65 88 Diastolic HF (26%) 19 25 Ischemic (46%) 46 60 Non-Ischemic (54%) 38 53 NYHA Class III (85%) 58 99 NYHA Class IV (15%) 26 14 No Device Rx (60%) 37 64 Device Rx (40%) 47 49 Interaction p-value Poisson Negative Binomial 0.95 0.95 0.95 0.86 0.01 0.08 0.15 0.31 Efficacy in NYHA Class III Patients Control (n = 122) # of Pts with Events 35 51 Total HF Related Events 58 99 50 86 Emergency Department Visits 6 11 Urgent Clinic Visits 2 3 0. 54 0.85 Hospitalizations Event Rate / 6months 1 % Reduction in Event Rate 1. 2. Cumulative Events 120 100 Events Chronicle (n =112) Chronicle Control 80 60 40 20 0 2 (p=0.0061; 36% p=0.0582) 4 6 Months Poisson model - Scaled Deviance = 1.7 Negative Binomial model - Scaled Deviance = 0.8 Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9 Heart Failure Hospitalizations through 12 Months Follow-up (All Patients) Randomized Follow-up Period (Implant to 6 months) Post Randomized Follow-up Period (6 to 12 months) Number of Events Rate / 6 months Number of Events Rate / 6 months CHRONICLE (n=102) 57 0.56 48 0.54 CONTROL (n=105) 95 0.90 48 0.53 INVESTIGATOR ADJUDICATED HEART FAILURE HOSPITALIZATIONS 207 patients completing 12 month follow-up visit, or died or withdrew between 6-12 months Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9 Pressure Changes Associated with Volume Overload Events (Daily e-PAD) Chronicle Group 45 ** Daily ePAD (mmHg) Daily ePAD (mmHg) 45 Control Group 40 35 30 * 40 ** 35 30 25 25 20 20 -49 -28 -14 -1 Days from hospitalization 5 -49 -28 -14 -1 Days from hospitalization * = p<0.05 vs pressure at 5 days after hospitalization ** =p<0.005 vs pressure at 5 days after hospitalization 5 Body Weight and RV Diastolic Pressure Before Hospitalization Body Weight Lbs RV Diastolic Pressure mmHg 300 25 250 20 200 * * Chronicle Control 150 15 * * 100 7 weeks 4 weeks 2 weeks 1 day prior 5 days post 10 7 weeks 4 weeks * = p<0.05 vs 1 day prior hospitalization 2 weeks 1 day prior 5 days post Decreased Heart Failure Hospitalizations Associated With Use of Chronicle Information (NYHA Class III) Randomized Follow-up Period (Implant to 6 mos) Post Randomized Follow-up Period (6 to 12 mos) Number of Events Rate / 6 months Number of Events Rate / 6 months CHRONICLE (n=97) 49 0.51 38 0.45 CONTROL (n=108) 87 0.80 48 0.51 Investigator adjudicated heart failure hospitalizations 205 patients with paired data after 6 months randomized period Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9 Mean Changes in Pressures from Baseline to 12 Months (RVSP) CHRONICLE CONTROL 1st 6 months CONTROL to IHM 2nd 6 months Change from Baseline (mm Hg) 5 4 3 2 1 2 4 6 8 10 12 0 -1 -2 p=0.21 vs baseline -3 -4 p=0.0012 vs baseline -5 Months COMPASS-HF Summary Chronicle IHM system is safe and reliable A 21% reduction in rate of heart failure events, beyond currently available HF therapies (p=0.33) Nearly three times as many adjustments of medications were made in CHRONICLE group, with no evidence of over-diuresis A 36% reduction in relative risk of a HF-related hospitalization (post-hoc, p=0.03) Additional trials are necessary to establish the clinical benefit of IHM guided care Bourge, RC J Am Coll Cardiol 2008;51:1073-9 Implanted Monitor Derived Hemodynamics in Pulmonary Arterial Hypertension N=8, a sub-study of a pilot implanted hemodynamic monitor (Chronicle® Device) study in PAH RV pressure waveforms recorded utilizing the implantable monitor and SG catheter Breath-by-breath cardiac output was recorded during acute IV epoprostenol infusion at 3, 6 and 9 ng/kg/min. Late systolic pressure augmentation and the cardiac output were estimated using the right ventricular pressure waveforms and correlated with direct measurement of cardiac output (Fick) Karamanoglu, M, et al. Manuscript Submitted CO= 30 x(P1st-PES)x(STI-PEI)/RR AP=PSYS-P1st Implanted Monitor Derived Hemodynamics in PAH Psys P1st 40 Qmax ePAD mmHg The basic features of the RV pressure waveform and the identification of these feature points using the first derivative of the RV pressure waveform. Three of these points identify the turning points of the PA flow waveform (in mmHg), PEI, T1st and STI, where PEI = time of dP/dtmax, T1st = time of the early shoulder of the RV pressure waveform, and STI = time of dP/dtmin. The area of the triangle (shaded area) = (P1st-Pes)x ED/2 corresponds to estimated stroke volume (SV). RR = R-R interval PES SV SV ED T1st 0 PEI STI RR dP/dtmax 0 mmHg/s The augmented pressure (AP) caused by the presence of wave reflection is the difference between the late systolic pressure (Psys) and the early systolic shoulder (P1st). dP/dtmin Fig 1, Karamanoglu, M, et al. Manuscript Submitted -1000 500 ms 6 500 4 300 200 2 mmHg L/min/m2 400 100 0 0 Measured (L/min/m2) Implanted Monitor Derived Hemodynamics in Pulmonary Arterial Hypertension Cardiac Index 6 5 4 Y=X, r2=0.95 3 2 1 0 0 1 2 3 4 5 6 Estimated Measured Dose L/min/m2 6 4 2 0 01 03 05 06 07 09 31 34 Difference (L/min/m2) Estimated (L/min/m2) 1.0 +95% CI=0.37 L/min/m2 0.5 Mean=0.0 L/min/m2 0.0 -95% CI=0.37 L/min/m2 -0.5 Bland - Altman Plot -1.0 0 1 2 3 4 5 2 Average (L/min/m ) Fig 6 & 7, Karamanoglu, M, et al. Manuscript Submitted 6 ™ ® Savacor HeartPOD Heart Failure Therapy System Senses: Left Atrial Pressure Temperature IEGM ‘Chip’ in tip RF power / telemetry Personalized-realtime: LASIX® (Furosemide) 40 mg 1 white tablet Drug management CRM programming RA LA LASIX® 40 Recheck in 12h CardioMEMS Wireless Heart Failure Sensor HF Sensor technology based on clinically proved commercially available system for abdominal aneurysms repair monitoring AAA Sensor HF Sensor Externally powered – no battery CardioMEMS Wireless Heart Failure Sensor • Miniaturized, wireless sensor implanted in the pulmonary artery using a simple catheter-based technique • Clinical evaluation has demonstrated safety, stability and excellent correlation to swan-ganz catheter Regression Plot of Sensor vs. SG Mean Pressure Measurements for All Patients Sensor reading (mm Hg) 70 60 R2 = 0.9788 50 40 30 20 10 0 0 20 40 SG reading (mm Hg) 60 80 HF Sensor CardioMEMS Wireless Heart Failure Sensor Remon Tech (Boston Scientific): Acoustic-Non Data Recording Miniature pressure transducer, attached to self expanding anchor device, inserted into pulmonary artery via percutaneous venous approach Implant activated, measurements taken, data transmitted via ultrasound External unit operated by patient, displays Anchoring device and records data Implant may communicate with other implanted devices using acoustic telemetry Micro battery, life > 5 years; may be recharged using acoustic energy Remon (Boston Scientific): Acoustic-Non Data Recording The Implantable Hemodynamic Monitor: Potential Clinical Applications Improve our understanding of the hemodynamic alterations that occur with heart failure and the hemodynamic response to therapy Allow more precise titration and tailoring of heart failure and pulmonary vascular disease (PH) therapy Provide “early warning” of hemodynamic deterioration Aid in the diagnosis of symptomatic events in the outpatient setting (home or clinic) Provide method by which to develop, refine, and optimize the use of chronic hemodynamic data for longterm patient management Possibly affect the intermediate and long term morbidity and mortality in patients with heart failure Historical Therapy of Heart Failure: Bloodletting "The importance of blood-letting , as a medicinal agent, in comparison with other means of cure, is shown in various respects...it is the least equivocal of remedies: its good effects, when properly administered, are, in most cases, so immediate and striking as not to be mistaken...In short, blood-letting is a remedy which, when judiciously employed, it is hardly possible to estimate too highly." On the Proper Administration of Blood-Letting, for the Prevention and Cure of Disease, (London, 1840) by Henry Clutterbuck, M.D., Member of the Royal College of Physicians.* Anatomical points for Bloodletting: Castellani, Giovani Marie (1585-1655). Filactirion della flebotomia et arteriotomia... (Viterbo, 1619).* Instruments used in Blood Letting; Scultetus, Johannes (1595-1645). Armamentarium hirurgicum...(Lugdunum Batavorum, 1693).).* Leach Bowl: Bossche, Willem van den. Historia Medica (Bruxellae,1639). (Image from: Lyons & Petrucelli. Medicine, an illustrated history. (New York, 1978).* * From the UCLA Biomedical Library: www.library.ucla.edu/libraries/biomed END Robert C Bourge MD The University of Alabama at Birmingham < [email protected] >