SlideShare a Scribd company logo
The Case for Systematic Risk
Assessment in PAH
H. James Ford MD
Associate Professor of Medicine
Director, Pulmonary Hypertension Program
University of North Carolina at Chapel Hill
Disclosures
• Consulting—United Therapeutics, Altavant, Acceleron/Merck,
Polarean
Validated Risk Assessment Tools in Medicine
• CHA₂DS₂-VASc Score for Atrial Fibrillation Stroke Risk
• Wells’ Score for DVT/PE risk
• Maddrey’s Discriminant Function for Alcoholic Hepatitis Prognosis
• Many more……
• Ideal tools:
• Utilize as few input variables as possible
• Utilize noninvasive metrics
• Can easily be used by non-experts
• Have a strong concordance in predicting the outcome of interest
(morbidity/mortality)
Why Use Systematic Risk Calculators?
• They are an important tool in the toolbox, a crucial piece of the puzzle
• They impart objectivity into the patient assessment
• They are ever-evolving to improve, and as such they are a work in progress
• They compel us to improve our prognosticating ability
• Current PAH guidelines recommend regular interval multi-parametric risk
assessment, with goal of achieving low risk status.
• Disclaimers
• There are shortcomings/opportunities for improvement
• There are discrepancies
Historical Perspective
REVEAL 1.0
2010
REVEAL 2.0
2019
REVEAL Lite 2
2021
European 3-
strata
2015
Enhanced 3-
strata
European 4-
strata
2022
Later validated in:
• Swedish registry (n = 530)
• Comparative, Prospective Registry of Newly Initiated Therapies for
Pulmonary Hypertension (COMPERA;multinational, n = 1,588)
• French registry (FPHR; n = 1,017)
Initially developed from expert opinion
REVEAL registry, US-based (2,555 prevalent, 960 incident), 2006-2009
Emergence of Therapies vs Risk Assessment Tools
Case Study
• 42 y/o female with SSc-PAH
• Diagnostic RHC: mPAP 46, RA 12, CI
2.2, PVR 10.6 WU, SVO2 59%
• 6 MWT 385 meters
• Functional Class 2
• Pro BNP 1375
• Creatinine 0.7
• BP 105/65
• HR 100
• No syncope, no pericardial effusion on
echo.
• RA mildly dilated on echo
• Risk assessment of this patient?
• A) Low
• B) Intermediate
• C) High
• D) need more information
Why Use Risk Assessment Tools?
• Anchor treatment and treatment escalation decisions to real world
outcomes data
• Gestalt is imperfect
• Ability to detect more subtle trends towards clinical worsening
Clinician Gestalt vs Model-Derived Risk
Simons JE. Adv Ther. 2019; 36
• 90 physicians
• 623 patients
• Mean age 56.4 yrs
• Abbreviated
ERS/ESC:
• FC, 6mWD, BNP, RAP,
CI, SvO2
• Scored 1 - 3
Clinician Gestalt vs Model-Derived Risk
• Retrospective chart review
• COMPERA, noninvasive French and
REVEAL 2.0
• Telephone interview with providers
• US based
• 153 patient charts, 38 physicians
• Factors associated with
incongruency:
• Less frequent echo
• Higher patient physical activity
• Systemic hypertension
• Autoimmune disease
REVEAL
Includes non-modifiable variables
Only modifiable variables
Inclusion of renal function
REVEAL Risk Tools
REVEAL 1.0 REVEAL 2.0 REVEAL Lite 2
Group 1 subgroup CTD/POPH/HPAH CTD/POPH/HPAH -------------
Demographics Male > 60 Male > 60 -------------
Comorbidities Renal insufficiency eGFR < 60 eGFR < 60
Functional class 1 vs 3 vs 4 1 vs 3 vs 4 1 vs 3 vs 4
Vital signs SBP<110, HR >92 SBP <110, HR >96 SBP <110, HR >96
6 MWD >440 m, < 165 m >440, 320-440, <165 m >440, 320-440, <165 m
All cause hospitalization in
last 6 months
-------- +1 -------------
Natriuretic peptides BNP < 50, > 180 BNP or NT pro BNP, 3
strata
BNP or NT pro BNP, 3
strata
Echocardiogram Pericardial effusion Pericardial effusion -------------
PFT DLCO >80% pred, < 32%
pred
DLCO < 50% predicted -------------
RHC/hemodynamics RAP > 20, PVR >32 WU RAP >20, PVR <5 -------------
C = 0.76
C = 0.74 C = 0.73
European 3 Strata Models
C = 0.64
Nonmodifiable factors not included
European 4-Strata (COMPERA 2.0)
C = 0.70
European 4-Strata (COMPERA 2.0)
Hoeper MM. Eur Respir J. 2022; 60(1)
Baseline First follow-up
6th WSPH vs ERS/ESC 2022 Treatment
Algorithm
Humbert M. Eur Respir J. 2022
Case Study Revisited
• 42 y/o female with SSc-PAH
• Diagnostic RHC: mPAP 46, RA 12, CI 2.2, PVR
10.6 WU, SVO2 59%
• 6 MWT 385 meters
• Functional Class 2
• Pro BNP 1375
• Creatinine 0.7
• BP 105/65
• HR 100
• No syncope, no pericardial effusion on echo.
• RA mildly dilated on echo
• REVEAL 2.0 Risk
• High risk
• REVEAL Lite 2
• High risk
• ESC/ERS 3 strata table
• Intermediate Risk
• European 4 strata
• Intermediate-low risk
?
Role for Risk Assessment in Clinical Trials
(FREEDOM EV)
• FREEDOM-EV--placebo-controlled, event-driven study, randomized
690 PAH participants 1:1 to oral treprostinil (TRE) or placebo.
• Potential role for ensuring placebo and active treatment arms are
truly comparable
• In Freedom EV study, contemporary risk scores were therapy
responsive and early improvements predicted subsequent outcomes
(? Surrogate for clinical worsening)
• At baseline, treatment and placebo groups were imbalanced with
respect to systematic risk assessment (treatment arm was higher risk
status overall). White et al. Am J Respir Crit Care Med. 2020; 201: 707-717
Benza et al, JHLT, VOLUME 41, ISSUE 11, P1572-1580,
REVEAL 1.0, 2.0 and REVEAL Lite 2 in PATENT
1/2
• PATENT and extension trial:
riociguat vs placebo for PAH
• REVEAL Lite 2 and original RRS
scores at baseline and Week
12 were significantly
associated with survival and
CWFS in patients with PAH
receiving riociguat.
• Significantly increased
proportion of patients with
REVEAL Lite 2 Low risk status
at PATENT 1 and 2 week 12 (tx
group) and PATENT 2 week 12
(pbo group).
Benza et al. J Heart Lung Transplant. 2022 Mar;41(3):411-420.
What Needs to Improve?
• Inclusion of more nuanced phenotypes (including within the “IPAH”
tent)
• Age adjusted impacts on mortality
• Comorbidities
• Additional RV imaging parameters (TAPSE, CMRI)
• Racial/ethnic differences
• Genetics
• Inclusion of patient reported outcomes
Summary
• Risk assessment tools continue to evolve, with ever-improving discriminatory power and
risk group stratification
• Gestalt alone remains unreliable
• Opportunities to better balance clinical trial treatment and placebo arms, as well as use
risk calculators in serial reassessment as surrogates of clinical worsening/CWFS.
• Simpler tools make risk assessment easy and accessible in clinical practice
• Complex calculators should remain an important tool. Don’t just rely on simpler tools.
• An increasingly complex array of PAH therapy options likely in the future—tools needed
to aid clinicians in treatment choices (how many, which, when?)
• WE SHOULD NOT ABANDON THESE TOOLS, RATHER WORK TO CONTINUE TO IMPROVE
THEM

More Related Content

Similar to The Case for Systematic Risk Assessment in PAH.pptx

Strong HF trial ppt.pptx
Strong HF trial ppt.pptxStrong HF trial ppt.pptx
Strong HF trial ppt.pptx
ssuser2b7a9d
 
Evidence Based Approach to Pulmonary Thromboembolism
Evidence Based Approach to Pulmonary ThromboembolismEvidence Based Approach to Pulmonary Thromboembolism
Evidence Based Approach to Pulmonary Thromboembolism
Kristopher Maday
 
ASCO 2015 Lymphoma update
ASCO 2015 Lymphoma updateASCO 2015 Lymphoma update
ASCO 2015 Lymphoma update
Chandan K Das
 
Hbp Stategy Hypertension Management Initiative Feb07
Hbp Stategy Hypertension Management Initiative Feb07Hbp Stategy Hypertension Management Initiative Feb07
Hbp Stategy Hypertension Management Initiative Feb07
primary
 
Acute Heart Failure: Current Standards and Evolution of Care.2015
Acute Heart Failure: Current Standards and Evolution of Care.2015Acute Heart Failure: Current Standards and Evolution of Care.2015
Acute Heart Failure: Current Standards and Evolution of Care.2015
hivlifeinfo
 
Hodgkin Lymphoma: Latest Concepts
Hodgkin Lymphoma: Latest ConceptsHodgkin Lymphoma: Latest Concepts
Hodgkin Lymphoma: Latest Concepts
spa718
 
Back to the Bedside: Internal Medicine Bedside Ultrasound Program
Back to the Bedside: Internal Medicine Bedside Ultrasound ProgramBack to the Bedside: Internal Medicine Bedside Ultrasound Program
Back to the Bedside: Internal Medicine Bedside Ultrasound Program
Allina Health
 
Health economic modelling in the diagnostics development process
Health economic modelling in the diagnostics development processHealth economic modelling in the diagnostics development process
Health economic modelling in the diagnostics development process
cheweb1
 
Actigraphy as a Metric in PAH Research and Clinical Care
Actigraphy as a Metric in PAH Research and Clinical CareActigraphy as a Metric in PAH Research and Clinical Care
Actigraphy as a Metric in PAH Research and Clinical Care
Duke Heart
 
Limited stage DLBCL role of radiotherapy
Limited stage DLBCL role of radiotherapyLimited stage DLBCL role of radiotherapy
Limited stage DLBCL role of radiotherapy
Narayan Adhikari
 
Cardiovascular Biomarkers Lecture
Cardiovascular Biomarkers LectureCardiovascular Biomarkers Lecture
Cardiovascular Biomarkers Lecture
Dr Felipe Templo Jr
 
James Januzzi, Assessment of Heart Failure: Early Identification and Across t...
James Januzzi, Assessment of Heart Failure: Early Identification and Across t...James Januzzi, Assessment of Heart Failure: Early Identification and Across t...
James Januzzi, Assessment of Heart Failure: Early Identification and Across t...
Cleveland HeartLab, Inc.
 
ESOT 2015 Report of Survey for Consensus on Thoracic Donors
ESOT 2015 Report of Survey for Consensus on Thoracic DonorsESOT 2015 Report of Survey for Consensus on Thoracic Donors
ESOT 2015 Report of Survey for Consensus on Thoracic Donors
Cristiano Amarelli
 
Doctor James Doran
Doctor James DoranDoctor James Doran
Doctor James Doran
NACCHOpresentations
 
Prostate cancer Risk stratification and choice of initial treatment final.pptx
Prostate cancer Risk stratification and choice of initial treatment final.pptxProstate cancer Risk stratification and choice of initial treatment final.pptx
Prostate cancer Risk stratification and choice of initial treatment final.pptx
Ahmed Eliwa
 
Hospital Medicine Update, VA ACP Meeting 2015
Hospital Medicine Update, VA ACP Meeting 2015Hospital Medicine Update, VA ACP Meeting 2015
Hospital Medicine Update, VA ACP Meeting 2015
Jon Sweet
 
Validation of a 46 gene expression signature in early-stage non-small-cell lu...
Validation of a 46 gene expression signature in early-stage non-small-cell lu...Validation of a 46 gene expression signature in early-stage non-small-cell lu...
Validation of a 46 gene expression signature in early-stage non-small-cell lu...
MyriadGenetics
 
PD Technique Failure.pptx
PD Technique Failure.pptxPD Technique Failure.pptx
PD Technique Failure.pptx
NayyarSaleem2
 
Acute Decompensated Heart Failure : What is New ?
Acute Decompensated Heart Failure : What is New ?Acute Decompensated Heart Failure : What is New ?
Acute Decompensated Heart Failure : What is New ?
drucsamal
 
JCP/?PRESENTATION IN A JOURNAL CLUB.....
JCP/?PRESENTATION IN A JOURNAL CLUB.....JCP/?PRESENTATION IN A JOURNAL CLUB.....
JCP/?PRESENTATION IN A JOURNAL CLUB.....
Dr. Ajit Surya Singh
 

Similar to The Case for Systematic Risk Assessment in PAH.pptx (20)

Strong HF trial ppt.pptx
Strong HF trial ppt.pptxStrong HF trial ppt.pptx
Strong HF trial ppt.pptx
 
Evidence Based Approach to Pulmonary Thromboembolism
Evidence Based Approach to Pulmonary ThromboembolismEvidence Based Approach to Pulmonary Thromboembolism
Evidence Based Approach to Pulmonary Thromboembolism
 
ASCO 2015 Lymphoma update
ASCO 2015 Lymphoma updateASCO 2015 Lymphoma update
ASCO 2015 Lymphoma update
 
Hbp Stategy Hypertension Management Initiative Feb07
Hbp Stategy Hypertension Management Initiative Feb07Hbp Stategy Hypertension Management Initiative Feb07
Hbp Stategy Hypertension Management Initiative Feb07
 
Acute Heart Failure: Current Standards and Evolution of Care.2015
Acute Heart Failure: Current Standards and Evolution of Care.2015Acute Heart Failure: Current Standards and Evolution of Care.2015
Acute Heart Failure: Current Standards and Evolution of Care.2015
 
Hodgkin Lymphoma: Latest Concepts
Hodgkin Lymphoma: Latest ConceptsHodgkin Lymphoma: Latest Concepts
Hodgkin Lymphoma: Latest Concepts
 
Back to the Bedside: Internal Medicine Bedside Ultrasound Program
Back to the Bedside: Internal Medicine Bedside Ultrasound ProgramBack to the Bedside: Internal Medicine Bedside Ultrasound Program
Back to the Bedside: Internal Medicine Bedside Ultrasound Program
 
Health economic modelling in the diagnostics development process
Health economic modelling in the diagnostics development processHealth economic modelling in the diagnostics development process
Health economic modelling in the diagnostics development process
 
Actigraphy as a Metric in PAH Research and Clinical Care
Actigraphy as a Metric in PAH Research and Clinical CareActigraphy as a Metric in PAH Research and Clinical Care
Actigraphy as a Metric in PAH Research and Clinical Care
 
Limited stage DLBCL role of radiotherapy
Limited stage DLBCL role of radiotherapyLimited stage DLBCL role of radiotherapy
Limited stage DLBCL role of radiotherapy
 
Cardiovascular Biomarkers Lecture
Cardiovascular Biomarkers LectureCardiovascular Biomarkers Lecture
Cardiovascular Biomarkers Lecture
 
James Januzzi, Assessment of Heart Failure: Early Identification and Across t...
James Januzzi, Assessment of Heart Failure: Early Identification and Across t...James Januzzi, Assessment of Heart Failure: Early Identification and Across t...
James Januzzi, Assessment of Heart Failure: Early Identification and Across t...
 
ESOT 2015 Report of Survey for Consensus on Thoracic Donors
ESOT 2015 Report of Survey for Consensus on Thoracic DonorsESOT 2015 Report of Survey for Consensus on Thoracic Donors
ESOT 2015 Report of Survey for Consensus on Thoracic Donors
 
Doctor James Doran
Doctor James DoranDoctor James Doran
Doctor James Doran
 
Prostate cancer Risk stratification and choice of initial treatment final.pptx
Prostate cancer Risk stratification and choice of initial treatment final.pptxProstate cancer Risk stratification and choice of initial treatment final.pptx
Prostate cancer Risk stratification and choice of initial treatment final.pptx
 
Hospital Medicine Update, VA ACP Meeting 2015
Hospital Medicine Update, VA ACP Meeting 2015Hospital Medicine Update, VA ACP Meeting 2015
Hospital Medicine Update, VA ACP Meeting 2015
 
Validation of a 46 gene expression signature in early-stage non-small-cell lu...
Validation of a 46 gene expression signature in early-stage non-small-cell lu...Validation of a 46 gene expression signature in early-stage non-small-cell lu...
Validation of a 46 gene expression signature in early-stage non-small-cell lu...
 
PD Technique Failure.pptx
PD Technique Failure.pptxPD Technique Failure.pptx
PD Technique Failure.pptx
 
Acute Decompensated Heart Failure : What is New ?
Acute Decompensated Heart Failure : What is New ?Acute Decompensated Heart Failure : What is New ?
Acute Decompensated Heart Failure : What is New ?
 
JCP/?PRESENTATION IN A JOURNAL CLUB.....
JCP/?PRESENTATION IN A JOURNAL CLUB.....JCP/?PRESENTATION IN A JOURNAL CLUB.....
JCP/?PRESENTATION IN A JOURNAL CLUB.....
 

More from Duke Heart

From LVAD to Transplant: State of the Art of Advanced Heart Failure Management
From LVAD to Transplant: State of the Art of Advanced Heart Failure ManagementFrom LVAD to Transplant: State of the Art of Advanced Heart Failure Management
From LVAD to Transplant: State of the Art of Advanced Heart Failure Management
Duke Heart
 
When Everything Fails - Advanced Heart Failure: When to Refer?
When Everything Fails - Advanced Heart Failure: When to Refer?When Everything Fails - Advanced Heart Failure: When to Refer?
When Everything Fails - Advanced Heart Failure: When to Refer?
Duke Heart
 
Navigating Worsening HF Events: What is Worsening HF and How to Recognize It?
Navigating Worsening HF Events: What is Worsening HF and How to Recognize It?Navigating Worsening HF Events: What is Worsening HF and How to Recognize It?
Navigating Worsening HF Events: What is Worsening HF and How to Recognize It?
Duke Heart
 
Obesity Management in Heart Failure: Best Practices to Date
Obesity Management in Heart Failure: Best Practices to DateObesity Management in Heart Failure: Best Practices to Date
Obesity Management in Heart Failure: Best Practices to Date
Duke Heart
 
Cardiometabolic Revolution: Comprehensive Metabolic Care in Heart Failure
Cardiometabolic Revolution: Comprehensive Metabolic Care in Heart FailureCardiometabolic Revolution: Comprehensive Metabolic Care in Heart Failure
Cardiometabolic Revolution: Comprehensive Metabolic Care in Heart Failure
Duke Heart
 
Remote Monitoring: Tracking Congestion & Beyond
Remote Monitoring: Tracking Congestion & BeyondRemote Monitoring: Tracking Congestion & Beyond
Remote Monitoring: Tracking Congestion & Beyond
Duke Heart
 
Congestion Matters! How to Assess It: Old and New Methods
Congestion Matters! How to Assess It: Old and New MethodsCongestion Matters! How to Assess It: Old and New Methods
Congestion Matters! How to Assess It: Old and New Methods
Duke Heart
 
Percutaneous Valve Therapies in Heart Failure
Percutaneous Valve Therapies in Heart FailurePercutaneous Valve Therapies in Heart Failure
Percutaneous Valve Therapies in Heart Failure
Duke Heart
 
Devices in the Management of Chronic Heart Failure
Devices in the Management of Chronic Heart FailureDevices in the Management of Chronic Heart Failure
Devices in the Management of Chronic Heart Failure
Duke Heart
 
Mechanical Circulatory Support Devices in the Management of Cardiogenic Shock
Mechanical Circulatory Support Devices in the Management of Cardiogenic ShockMechanical Circulatory Support Devices in the Management of Cardiogenic Shock
Mechanical Circulatory Support Devices in the Management of Cardiogenic Shock
Duke Heart
 
Opening Doors to Better Care: Initiating and Sustaining Open Access & Medicat...
Opening Doors to Better Care: Initiating and Sustaining Open Access & Medicat...Opening Doors to Better Care: Initiating and Sustaining Open Access & Medicat...
Opening Doors to Better Care: Initiating and Sustaining Open Access & Medicat...
Duke Heart
 
Multidisciplinary Strategies for Improved Care Coordination in Heart Failure
Multidisciplinary Strategies for Improved Care Coordination in Heart FailureMultidisciplinary Strategies for Improved Care Coordination in Heart Failure
Multidisciplinary Strategies for Improved Care Coordination in Heart Failure
Duke Heart
 
Duke HF - Heart Failure Transitional Care
Duke HF - Heart Failure Transitional CareDuke HF - Heart Failure Transitional Care
Duke HF - Heart Failure Transitional Care
Duke Heart
 
Genetic Cardiomyopathy & Sarcoidosis Clinic: Is There Room to Subspecialize?
Genetic Cardiomyopathy & Sarcoidosis Clinic: Is There Room to Subspecialize?Genetic Cardiomyopathy & Sarcoidosis Clinic: Is There Room to Subspecialize?
Genetic Cardiomyopathy & Sarcoidosis Clinic: Is There Room to Subspecialize?
Duke Heart
 
Cardiac Amyloidosis: Diagnostic & Therapeutic Approaches
Cardiac Amyloidosis: Diagnostic & Therapeutic ApproachesCardiac Amyloidosis: Diagnostic & Therapeutic Approaches
Cardiac Amyloidosis: Diagnostic & Therapeutic Approaches
Duke Heart
 
Functional testing in ambulatory heart failure: What to test and how often?
Functional testing in ambulatory heart failure: What to test and how often?Functional testing in ambulatory heart failure: What to test and how often?
Functional testing in ambulatory heart failure: What to test and how often?
Duke Heart
 
Treatment for HFpEF-Current State of the Art and Ongoing Trials
Treatment for HFpEF-Current State of the Art and Ongoing TrialsTreatment for HFpEF-Current State of the Art and Ongoing Trials
Treatment for HFpEF-Current State of the Art and Ongoing Trials
Duke Heart
 
Heart Failure with Preserved Ejection Fraction: Diagnostic Updates
Heart Failure with Preserved Ejection Fraction: Diagnostic UpdatesHeart Failure with Preserved Ejection Fraction: Diagnostic Updates
Heart Failure with Preserved Ejection Fraction: Diagnostic Updates
Duke Heart
 
Contemporary Principles for the Management of Heart Failure
Contemporary Principles for the Management of Heart FailureContemporary Principles for the Management of Heart Failure
Contemporary Principles for the Management of Heart Failure
Duke Heart
 
Evolving Pharmacological Treatment Strategies for HFrEF
Evolving Pharmacological Treatment Strategies for HFrEFEvolving Pharmacological Treatment Strategies for HFrEF
Evolving Pharmacological Treatment Strategies for HFrEF
Duke Heart
 

More from Duke Heart (20)

From LVAD to Transplant: State of the Art of Advanced Heart Failure Management
From LVAD to Transplant: State of the Art of Advanced Heart Failure ManagementFrom LVAD to Transplant: State of the Art of Advanced Heart Failure Management
From LVAD to Transplant: State of the Art of Advanced Heart Failure Management
 
When Everything Fails - Advanced Heart Failure: When to Refer?
When Everything Fails - Advanced Heart Failure: When to Refer?When Everything Fails - Advanced Heart Failure: When to Refer?
When Everything Fails - Advanced Heart Failure: When to Refer?
 
Navigating Worsening HF Events: What is Worsening HF and How to Recognize It?
Navigating Worsening HF Events: What is Worsening HF and How to Recognize It?Navigating Worsening HF Events: What is Worsening HF and How to Recognize It?
Navigating Worsening HF Events: What is Worsening HF and How to Recognize It?
 
Obesity Management in Heart Failure: Best Practices to Date
Obesity Management in Heart Failure: Best Practices to DateObesity Management in Heart Failure: Best Practices to Date
Obesity Management in Heart Failure: Best Practices to Date
 
Cardiometabolic Revolution: Comprehensive Metabolic Care in Heart Failure
Cardiometabolic Revolution: Comprehensive Metabolic Care in Heart FailureCardiometabolic Revolution: Comprehensive Metabolic Care in Heart Failure
Cardiometabolic Revolution: Comprehensive Metabolic Care in Heart Failure
 
Remote Monitoring: Tracking Congestion & Beyond
Remote Monitoring: Tracking Congestion & BeyondRemote Monitoring: Tracking Congestion & Beyond
Remote Monitoring: Tracking Congestion & Beyond
 
Congestion Matters! How to Assess It: Old and New Methods
Congestion Matters! How to Assess It: Old and New MethodsCongestion Matters! How to Assess It: Old and New Methods
Congestion Matters! How to Assess It: Old and New Methods
 
Percutaneous Valve Therapies in Heart Failure
Percutaneous Valve Therapies in Heart FailurePercutaneous Valve Therapies in Heart Failure
Percutaneous Valve Therapies in Heart Failure
 
Devices in the Management of Chronic Heart Failure
Devices in the Management of Chronic Heart FailureDevices in the Management of Chronic Heart Failure
Devices in the Management of Chronic Heart Failure
 
Mechanical Circulatory Support Devices in the Management of Cardiogenic Shock
Mechanical Circulatory Support Devices in the Management of Cardiogenic ShockMechanical Circulatory Support Devices in the Management of Cardiogenic Shock
Mechanical Circulatory Support Devices in the Management of Cardiogenic Shock
 
Opening Doors to Better Care: Initiating and Sustaining Open Access & Medicat...
Opening Doors to Better Care: Initiating and Sustaining Open Access & Medicat...Opening Doors to Better Care: Initiating and Sustaining Open Access & Medicat...
Opening Doors to Better Care: Initiating and Sustaining Open Access & Medicat...
 
Multidisciplinary Strategies for Improved Care Coordination in Heart Failure
Multidisciplinary Strategies for Improved Care Coordination in Heart FailureMultidisciplinary Strategies for Improved Care Coordination in Heart Failure
Multidisciplinary Strategies for Improved Care Coordination in Heart Failure
 
Duke HF - Heart Failure Transitional Care
Duke HF - Heart Failure Transitional CareDuke HF - Heart Failure Transitional Care
Duke HF - Heart Failure Transitional Care
 
Genetic Cardiomyopathy & Sarcoidosis Clinic: Is There Room to Subspecialize?
Genetic Cardiomyopathy & Sarcoidosis Clinic: Is There Room to Subspecialize?Genetic Cardiomyopathy & Sarcoidosis Clinic: Is There Room to Subspecialize?
Genetic Cardiomyopathy & Sarcoidosis Clinic: Is There Room to Subspecialize?
 
Cardiac Amyloidosis: Diagnostic & Therapeutic Approaches
Cardiac Amyloidosis: Diagnostic & Therapeutic ApproachesCardiac Amyloidosis: Diagnostic & Therapeutic Approaches
Cardiac Amyloidosis: Diagnostic & Therapeutic Approaches
 
Functional testing in ambulatory heart failure: What to test and how often?
Functional testing in ambulatory heart failure: What to test and how often?Functional testing in ambulatory heart failure: What to test and how often?
Functional testing in ambulatory heart failure: What to test and how often?
 
Treatment for HFpEF-Current State of the Art and Ongoing Trials
Treatment for HFpEF-Current State of the Art and Ongoing TrialsTreatment for HFpEF-Current State of the Art and Ongoing Trials
Treatment for HFpEF-Current State of the Art and Ongoing Trials
 
Heart Failure with Preserved Ejection Fraction: Diagnostic Updates
Heart Failure with Preserved Ejection Fraction: Diagnostic UpdatesHeart Failure with Preserved Ejection Fraction: Diagnostic Updates
Heart Failure with Preserved Ejection Fraction: Diagnostic Updates
 
Contemporary Principles for the Management of Heart Failure
Contemporary Principles for the Management of Heart FailureContemporary Principles for the Management of Heart Failure
Contemporary Principles for the Management of Heart Failure
 
Evolving Pharmacological Treatment Strategies for HFrEF
Evolving Pharmacological Treatment Strategies for HFrEFEvolving Pharmacological Treatment Strategies for HFrEF
Evolving Pharmacological Treatment Strategies for HFrEF
 

Recently uploaded

Part II - Body Grief: Losing parts of ourselves and our identity before, duri...
Part II - Body Grief: Losing parts of ourselves and our identity before, duri...Part II - Body Grief: Losing parts of ourselves and our identity before, duri...
Part II - Body Grief: Losing parts of ourselves and our identity before, duri...
bkling
 
Vestibulocochlear Nerve by Dr. Rabia Inam Gandapore.pptx
Vestibulocochlear Nerve by Dr. Rabia Inam Gandapore.pptxVestibulocochlear Nerve by Dr. Rabia Inam Gandapore.pptx
Vestibulocochlear Nerve by Dr. Rabia Inam Gandapore.pptx
Dr. Rabia Inam Gandapore
 
Ketone bodies and metabolism-biochemistry
Ketone bodies and metabolism-biochemistryKetone bodies and metabolism-biochemistry
Ketone bodies and metabolism-biochemistry
Dhayanithi C
 
vonoprazan A novel drug for GERD presentation
vonoprazan A novel drug for GERD presentationvonoprazan A novel drug for GERD presentation
vonoprazan A novel drug for GERD presentation
Dr.pavithra Anandan
 
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptx
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptx8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptx
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptx
Holistified Wellness
 
Cell Therapy Expansion and Challenges in Autoimmune Disease
Cell Therapy Expansion and Challenges in Autoimmune DiseaseCell Therapy Expansion and Challenges in Autoimmune Disease
Cell Therapy Expansion and Challenges in Autoimmune Disease
Health Advances
 
Journal Article Review on Rasamanikya
Journal Article Review on RasamanikyaJournal Article Review on Rasamanikya
Journal Article Review on Rasamanikya
Dr. Jyothirmai Paindla
 
Artificial Intelligence Symposium (THAIS)
Artificial Intelligence Symposium (THAIS)Artificial Intelligence Symposium (THAIS)
Artificial Intelligence Symposium (THAIS)
Josep Vidal-Alaball
 
Efficacy of Avartana Sneha in Ayurveda
Efficacy of Avartana Sneha in AyurvedaEfficacy of Avartana Sneha in Ayurveda
Efficacy of Avartana Sneha in Ayurveda
Dr. Jyothirmai Paindla
 
Integrating Ayurveda into Parkinson’s Management: A Holistic Approach
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachIntegrating Ayurveda into Parkinson’s Management: A Holistic Approach
Integrating Ayurveda into Parkinson’s Management: A Holistic Approach
Ayurveda ForAll
 
Osteoporosis - Definition , Evaluation and Management .pdf
Osteoporosis - Definition , Evaluation and Management .pdfOsteoporosis - Definition , Evaluation and Management .pdf
Osteoporosis - Definition , Evaluation and Management .pdf
Jim Jacob Roy
 
Hemodialysis: Chapter 4, Dialysate Circuit - Dr.Gawad
Hemodialysis: Chapter 4, Dialysate Circuit - Dr.GawadHemodialysis: Chapter 4, Dialysate Circuit - Dr.Gawad
Hemodialysis: Chapter 4, Dialysate Circuit - Dr.Gawad
NephroTube - Dr.Gawad
 
The Electrocardiogram - Physiologic Principles
The Electrocardiogram - Physiologic PrinciplesThe Electrocardiogram - Physiologic Principles
The Electrocardiogram - Physiologic Principles
MedicoseAcademics
 
The Nervous and Chemical Regulation of Respiration
The Nervous and Chemical Regulation of RespirationThe Nervous and Chemical Regulation of Respiration
The Nervous and Chemical Regulation of Respiration
MedicoseAcademics
 
TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by...
TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by...TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by...
TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by...
Donc Test
 
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotes
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPromoting Wellbeing - Applied Social Psychology - Psychology SuperNotes
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotes
PsychoTech Services
 
Does Over-Masturbation Contribute to Chronic Prostatitis.pptx
Does Over-Masturbation Contribute to Chronic Prostatitis.pptxDoes Over-Masturbation Contribute to Chronic Prostatitis.pptx
Does Over-Masturbation Contribute to Chronic Prostatitis.pptx
walterHu5
 
TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd...
TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd...TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd...
TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd...
Donc Test
 
Diabetic nephropathy diagnosis treatment
Diabetic nephropathy diagnosis treatmentDiabetic nephropathy diagnosis treatment
Diabetic nephropathy diagnosis treatment
arahmanzai5
 
Histopathology of Rheumatoid Arthritis: Visual treat
Histopathology of Rheumatoid Arthritis: Visual treatHistopathology of Rheumatoid Arthritis: Visual treat
Histopathology of Rheumatoid Arthritis: Visual treat
DIVYANSHU740006
 

Recently uploaded (20)

Part II - Body Grief: Losing parts of ourselves and our identity before, duri...
Part II - Body Grief: Losing parts of ourselves and our identity before, duri...Part II - Body Grief: Losing parts of ourselves and our identity before, duri...
Part II - Body Grief: Losing parts of ourselves and our identity before, duri...
 
Vestibulocochlear Nerve by Dr. Rabia Inam Gandapore.pptx
Vestibulocochlear Nerve by Dr. Rabia Inam Gandapore.pptxVestibulocochlear Nerve by Dr. Rabia Inam Gandapore.pptx
Vestibulocochlear Nerve by Dr. Rabia Inam Gandapore.pptx
 
Ketone bodies and metabolism-biochemistry
Ketone bodies and metabolism-biochemistryKetone bodies and metabolism-biochemistry
Ketone bodies and metabolism-biochemistry
 
vonoprazan A novel drug for GERD presentation
vonoprazan A novel drug for GERD presentationvonoprazan A novel drug for GERD presentation
vonoprazan A novel drug for GERD presentation
 
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptx
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptx8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptx
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptx
 
Cell Therapy Expansion and Challenges in Autoimmune Disease
Cell Therapy Expansion and Challenges in Autoimmune DiseaseCell Therapy Expansion and Challenges in Autoimmune Disease
Cell Therapy Expansion and Challenges in Autoimmune Disease
 
Journal Article Review on Rasamanikya
Journal Article Review on RasamanikyaJournal Article Review on Rasamanikya
Journal Article Review on Rasamanikya
 
Artificial Intelligence Symposium (THAIS)
Artificial Intelligence Symposium (THAIS)Artificial Intelligence Symposium (THAIS)
Artificial Intelligence Symposium (THAIS)
 
Efficacy of Avartana Sneha in Ayurveda
Efficacy of Avartana Sneha in AyurvedaEfficacy of Avartana Sneha in Ayurveda
Efficacy of Avartana Sneha in Ayurveda
 
Integrating Ayurveda into Parkinson’s Management: A Holistic Approach
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachIntegrating Ayurveda into Parkinson’s Management: A Holistic Approach
Integrating Ayurveda into Parkinson’s Management: A Holistic Approach
 
Osteoporosis - Definition , Evaluation and Management .pdf
Osteoporosis - Definition , Evaluation and Management .pdfOsteoporosis - Definition , Evaluation and Management .pdf
Osteoporosis - Definition , Evaluation and Management .pdf
 
Hemodialysis: Chapter 4, Dialysate Circuit - Dr.Gawad
Hemodialysis: Chapter 4, Dialysate Circuit - Dr.GawadHemodialysis: Chapter 4, Dialysate Circuit - Dr.Gawad
Hemodialysis: Chapter 4, Dialysate Circuit - Dr.Gawad
 
The Electrocardiogram - Physiologic Principles
The Electrocardiogram - Physiologic PrinciplesThe Electrocardiogram - Physiologic Principles
The Electrocardiogram - Physiologic Principles
 
The Nervous and Chemical Regulation of Respiration
The Nervous and Chemical Regulation of RespirationThe Nervous and Chemical Regulation of Respiration
The Nervous and Chemical Regulation of Respiration
 
TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by...
TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by...TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by...
TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by...
 
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotes
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPromoting Wellbeing - Applied Social Psychology - Psychology SuperNotes
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotes
 
Does Over-Masturbation Contribute to Chronic Prostatitis.pptx
Does Over-Masturbation Contribute to Chronic Prostatitis.pptxDoes Over-Masturbation Contribute to Chronic Prostatitis.pptx
Does Over-Masturbation Contribute to Chronic Prostatitis.pptx
 
TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd...
TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd...TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd...
TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd...
 
Diabetic nephropathy diagnosis treatment
Diabetic nephropathy diagnosis treatmentDiabetic nephropathy diagnosis treatment
Diabetic nephropathy diagnosis treatment
 
Histopathology of Rheumatoid Arthritis: Visual treat
Histopathology of Rheumatoid Arthritis: Visual treatHistopathology of Rheumatoid Arthritis: Visual treat
Histopathology of Rheumatoid Arthritis: Visual treat
 

The Case for Systematic Risk Assessment in PAH.pptx

  • 1. The Case for Systematic Risk Assessment in PAH H. James Ford MD Associate Professor of Medicine Director, Pulmonary Hypertension Program University of North Carolina at Chapel Hill
  • 2. Disclosures • Consulting—United Therapeutics, Altavant, Acceleron/Merck, Polarean
  • 3. Validated Risk Assessment Tools in Medicine • CHA₂DS₂-VASc Score for Atrial Fibrillation Stroke Risk • Wells’ Score for DVT/PE risk • Maddrey’s Discriminant Function for Alcoholic Hepatitis Prognosis • Many more…… • Ideal tools: • Utilize as few input variables as possible • Utilize noninvasive metrics • Can easily be used by non-experts • Have a strong concordance in predicting the outcome of interest (morbidity/mortality)
  • 4. Why Use Systematic Risk Calculators? • They are an important tool in the toolbox, a crucial piece of the puzzle • They impart objectivity into the patient assessment • They are ever-evolving to improve, and as such they are a work in progress • They compel us to improve our prognosticating ability • Current PAH guidelines recommend regular interval multi-parametric risk assessment, with goal of achieving low risk status. • Disclaimers • There are shortcomings/opportunities for improvement • There are discrepancies
  • 5. Historical Perspective REVEAL 1.0 2010 REVEAL 2.0 2019 REVEAL Lite 2 2021 European 3- strata 2015 Enhanced 3- strata European 4- strata 2022 Later validated in: • Swedish registry (n = 530) • Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA;multinational, n = 1,588) • French registry (FPHR; n = 1,017) Initially developed from expert opinion REVEAL registry, US-based (2,555 prevalent, 960 incident), 2006-2009
  • 6. Emergence of Therapies vs Risk Assessment Tools
  • 7. Case Study • 42 y/o female with SSc-PAH • Diagnostic RHC: mPAP 46, RA 12, CI 2.2, PVR 10.6 WU, SVO2 59% • 6 MWT 385 meters • Functional Class 2 • Pro BNP 1375 • Creatinine 0.7 • BP 105/65 • HR 100 • No syncope, no pericardial effusion on echo. • RA mildly dilated on echo • Risk assessment of this patient? • A) Low • B) Intermediate • C) High • D) need more information
  • 8. Why Use Risk Assessment Tools? • Anchor treatment and treatment escalation decisions to real world outcomes data • Gestalt is imperfect • Ability to detect more subtle trends towards clinical worsening
  • 9. Clinician Gestalt vs Model-Derived Risk Simons JE. Adv Ther. 2019; 36 • 90 physicians • 623 patients • Mean age 56.4 yrs • Abbreviated ERS/ESC: • FC, 6mWD, BNP, RAP, CI, SvO2 • Scored 1 - 3
  • 10. Clinician Gestalt vs Model-Derived Risk • Retrospective chart review • COMPERA, noninvasive French and REVEAL 2.0 • Telephone interview with providers • US based • 153 patient charts, 38 physicians • Factors associated with incongruency: • Less frequent echo • Higher patient physical activity • Systemic hypertension • Autoimmune disease
  • 11. REVEAL Includes non-modifiable variables Only modifiable variables Inclusion of renal function
  • 12. REVEAL Risk Tools REVEAL 1.0 REVEAL 2.0 REVEAL Lite 2 Group 1 subgroup CTD/POPH/HPAH CTD/POPH/HPAH ------------- Demographics Male > 60 Male > 60 ------------- Comorbidities Renal insufficiency eGFR < 60 eGFR < 60 Functional class 1 vs 3 vs 4 1 vs 3 vs 4 1 vs 3 vs 4 Vital signs SBP<110, HR >92 SBP <110, HR >96 SBP <110, HR >96 6 MWD >440 m, < 165 m >440, 320-440, <165 m >440, 320-440, <165 m All cause hospitalization in last 6 months -------- +1 ------------- Natriuretic peptides BNP < 50, > 180 BNP or NT pro BNP, 3 strata BNP or NT pro BNP, 3 strata Echocardiogram Pericardial effusion Pericardial effusion ------------- PFT DLCO >80% pred, < 32% pred DLCO < 50% predicted ------------- RHC/hemodynamics RAP > 20, PVR >32 WU RAP >20, PVR <5 ------------- C = 0.76 C = 0.74 C = 0.73
  • 13. European 3 Strata Models C = 0.64 Nonmodifiable factors not included
  • 14. European 4-Strata (COMPERA 2.0) C = 0.70
  • 15. European 4-Strata (COMPERA 2.0) Hoeper MM. Eur Respir J. 2022; 60(1) Baseline First follow-up
  • 16. 6th WSPH vs ERS/ESC 2022 Treatment Algorithm Humbert M. Eur Respir J. 2022
  • 17. Case Study Revisited • 42 y/o female with SSc-PAH • Diagnostic RHC: mPAP 46, RA 12, CI 2.2, PVR 10.6 WU, SVO2 59% • 6 MWT 385 meters • Functional Class 2 • Pro BNP 1375 • Creatinine 0.7 • BP 105/65 • HR 100 • No syncope, no pericardial effusion on echo. • RA mildly dilated on echo • REVEAL 2.0 Risk • High risk • REVEAL Lite 2 • High risk • ESC/ERS 3 strata table • Intermediate Risk • European 4 strata • Intermediate-low risk ?
  • 18. Role for Risk Assessment in Clinical Trials (FREEDOM EV) • FREEDOM-EV--placebo-controlled, event-driven study, randomized 690 PAH participants 1:1 to oral treprostinil (TRE) or placebo. • Potential role for ensuring placebo and active treatment arms are truly comparable • In Freedom EV study, contemporary risk scores were therapy responsive and early improvements predicted subsequent outcomes (? Surrogate for clinical worsening) • At baseline, treatment and placebo groups were imbalanced with respect to systematic risk assessment (treatment arm was higher risk status overall). White et al. Am J Respir Crit Care Med. 2020; 201: 707-717 Benza et al, JHLT, VOLUME 41, ISSUE 11, P1572-1580,
  • 19. REVEAL 1.0, 2.0 and REVEAL Lite 2 in PATENT 1/2 • PATENT and extension trial: riociguat vs placebo for PAH • REVEAL Lite 2 and original RRS scores at baseline and Week 12 were significantly associated with survival and CWFS in patients with PAH receiving riociguat. • Significantly increased proportion of patients with REVEAL Lite 2 Low risk status at PATENT 1 and 2 week 12 (tx group) and PATENT 2 week 12 (pbo group). Benza et al. J Heart Lung Transplant. 2022 Mar;41(3):411-420.
  • 20. What Needs to Improve? • Inclusion of more nuanced phenotypes (including within the “IPAH” tent) • Age adjusted impacts on mortality • Comorbidities • Additional RV imaging parameters (TAPSE, CMRI) • Racial/ethnic differences • Genetics • Inclusion of patient reported outcomes
  • 21. Summary • Risk assessment tools continue to evolve, with ever-improving discriminatory power and risk group stratification • Gestalt alone remains unreliable • Opportunities to better balance clinical trial treatment and placebo arms, as well as use risk calculators in serial reassessment as surrogates of clinical worsening/CWFS. • Simpler tools make risk assessment easy and accessible in clinical practice • Complex calculators should remain an important tool. Don’t just rely on simpler tools. • An increasingly complex array of PAH therapy options likely in the future—tools needed to aid clinicians in treatment choices (how many, which, when?) • WE SHOULD NOT ABANDON THESE TOOLS, RATHER WORK TO CONTINUE TO IMPROVE THEM

Editor's Notes

  1. A number of PAH therapeutics were approved prior to the first risk assessment models coming into practice.
  2. Noninvaseive FPHR showed the same findings
  3. C 0.5 random concordance, 1.0 perfect concordance. 0.7 or higher is considered significant
  4. Development of 4 strata COMPERA 2.0 has lead to more nuanced treatment algorithm, particularly at the follow up, evolving from a dichotomous pathway to a more complex potential path of tx approaches based on additional risk strata.
  5. This speaks to the challenges of which Risk assessment tool to use when there are discrepancies, and what direction to go when higher risk in one vs the other.