SBIR-STTR Award

Pulmonary hypertension (PH) is a devastating disease characterized by progressive dyspnea/exercise intolerance, right-heart failure, and carries a high risk of morbidity and early mortality. PH disease progression can be rapid, and any delay in the diagnosis and treatment of PH likely reduces survival. Given its clinical and prognostic significance, early and accurate diagnosis of PH to allow prompt and optimal establishment of clinical care is of critical importance. While traditional maximal/comprehensive cardiopulmonary exercise testing (CPET) has been validated in PH, it has limitations that have hindered its applicability to routine clinical assessment and monitoring. Our preliminary data suggest that the signature ventilatory and pulmonary gas exchange derangements of PH become apparent during even submaximal exercise. Our comprehensive proof-of-concept study (133 patients) supports our hypothesis that the addition of pulmonary gas exchange responses to a standardized 3-minute submaximal exercise test (Shape iCPET) to standard echocardiographic evidence of PH (i.e. RVSP >50 mmHg, suspicion of RV dysfunction) improves the sensitivity for PH detection by almost 40%. The Shape iCPET system is compact and utilizes pattern-recognition software that automates interpretation, making the system ideally suitable for widespread adoption. The overarching objective of this SBIR proposal is to categorically establish the Shape iCPET as a tool that: 1) improves early detection of PH; and 2) provides an objective evidence-based measure of PH therapy efficacy that can be easily used in academic and community practices. We have established a 10-center consortium of academic and community PH centers for this SBIR proposal. Specific Aim 1 will assess the clinical utility of submaximal cardiopulmonary exercise testing as a complementary tool for the identification of pulmonary hypertension. Specific Aim 2 will assess whether pharmacotherapy-induced improvements in pulmonary hypertension severity and disease status are reflected in the physiological responses to a standardized submaximal cardiopulmonary exercise test. We hypothesize that the Shape iCPET will prove to be an efficacious adjunct to traditional clinical metrics to track changes in pulmonary vascular function over time and responses to therapy aimed at alleviating PAH.

Public Health Relevance Statement:
Narrative Pulmonary hypertension (PH) is associated with worsening breathlessness and exercise capacity, right-heart failure, and adverse outcomes including increased mortality. Moreover, PH disease progression can be rapid; pharmaceutical intervention in early-stage PH can improve symptoms and functional capacity, and delayed diagnosis and treatment of PH likely reduces survival.

Project Terms:
Lung; Lung Respiratory System; pulmonary; Morbidity - disease rate; Morbidity; mortality; Patients; Pulmonary Gas Exchange; Research; Rest; Sensitivity and Specificity; Software; Computer software; Standardization; Testing; Time; Measures; Walking; Outcome Measure; improved; Clinical; Physiological; Physiologic; Disease Progression; Right heart dysfunction; Right ventricle dysfunction; Right-sided heart dysfunction; Right Ventricular Dysfunction; Shapes; tool; Severities; System; disease severity; Severity of illness; Cardiopulmonary; early detection; Early Diagnosis; Accuracy of Diagnosis; diagnostic accuracy; Categories; gatekeeper; Gatekeeping; response; Intervention Strategies; interventional strategy; Intervention; Pharmaceutical Agent; Pharmaceuticals; Pharmacological Substance; Pharmacologic Substance; Symptoms; Data; Detection; Diagnostic Specificity; Reproducibility; Community Practice; Newly Diagnosed; Pattern Recognition; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Monitor; Characteristics; Ventricular; pulmonary arterial hypertension; pulmonary artery hypertension; cost; Clinical assessments; Treatment Efficacy; intervention efficacy; therapeutic efficacy; therapy efficacy; clinically significant; clinical significance; high risk; clinical care; evidence base; standard measure; standard of care; symptomatic improvement; improve symptom; symptom improvement; treatment response; response to therapy; response to treatment; therapeutic response; therapy response; adverse outcome; adverse consequence; screening; accurate diagnosis; exercise intolerance; exercise capacity; prognostic significance; patient response; patient specific response; responsive patient; Exercise Test; disease prognosis; disease prognostication; pulmonary arterial pressure; lung artery blood pressure; pressure in pulmonary arteries; pulmonary arterial blood pressure; pulmonary artery pressure; pulmonary artery systolic pressure; right ventricular failure; right heart failure; right sided heart failure; right ventricle failure; right ventricular heart failure; Activities of Daily Living; Activities of everyday life; daily living functionality; functional ability; functional capacity; Adoption; Adult; 21+ years old; Adult Human; adulthood; Blood Vessels; vascular; Communities; Diagnosis; Disease; Disorder; Pharmacotherapy; Drug Therapy; drug treatment; Dyspnea; Breathlessness; Echocardiography; Echocardiogram; Transthoracic Echocardiography; heart sonography; Exercise; Exhibits; Gases; Goals; Cardiac Catheterization Procedures; Cardiac Catheterization; Heart Catheterization; Heart Catheterization Procedure; Insertion of catheter into heart chamber; hemodynamics; Pulmonary Hypertension

Pulmonary hypertension (PH) is a devastating disease characterized by progressive dyspnea/exercise intolerance, right-heart failure, and carries a high risk of morbidity and early mortality. PH disease progression can be rapid, and any delay in the diagnosis and treatment of PH likely reduces survival. Given its clinical and prognostic significance, early and accurate diagnosis of PH to allow prompt and optimal establishment of clinical care is of critical importance. While traditional maximal/comprehensive cardiopulmonary exercise testing (CPET) has been validated in PH, it has limitations that have hindered its applicability to routine clinical assessment and monitoring. Our preliminary data suggest that the signature ventilatory and pulmonary gas exchange derangements of PH become apparent during even submaximal exercise. Our comprehensive proof-of-concept study (133 patients) supports our hypothesis that the addition of pulmonary gas exchange responses to a standardized 3-minute submaximal exercise test (Shape iCPET) to standard echocardiographic evidence of PH (i.e. RVSP >50 mmHg, suspicion of RV dysfunction) improves the sensitivity for PH detection by almost 40%. The Shape iCPET system is compact and utilizes pattern-recognition software that automates interpretation, making the system ideally suitable for widespread adoption. The overarching objective of this SBIR proposal is to categorically establish the Shape iCPET as a tool that: 1) improves early detection of PH; and 2) provides an objective evidence-based measure of PH therapy efficacy that can be easily used in academic and community practices. We have established a 10-center consortium of academic and community PH centers for this SBIR proposal. Specific Aim 1 will assess the clinical utility of submaximal cardiopulmonary exercise testing as a complementary tool for the identification of pulmonary hypertension. Specific Aim 2 will assess whether pharmacotherapy-induced improvements in pulmonary hypertension severity and disease status are reflected in the physiological responses to a standardized submaximal cardiopulmonary exercise test. We hypothesize that the Shape iCPET will prove to be an efficacious adjunct to traditional clinical metrics to track changes in pulmonary vascular function over time and responses to therapy aimed at alleviating PAH.

Public Health Relevance Statement:
Narrative Pulmonary hypertension (PH) is associated with worsening breathlessness and exercise capacity, right-heart failure, and adverse outcomes including increased mortality. Moreover, PH disease progression can be rapid; pharmaceutical intervention in early-stage PH can improve symptoms and functional capacity, and delayed diagnosis and treatment of PH likely reduces survival.

Project Terms:
Activities of everyday life; daily living function; daily living functionality; functional ability; functional capacity; Activities of Daily Living; Adoption; 21+ years old; Adult Human; adulthood; Adult; Blood Vessels; vascular; Communities; Diagnosis; Disease; Disorder; Pharmacotherapy; Drug Therapy; drug treatment; Dyspnea; Breathlessness; Echocardiography; Echocardiogram; Transthoracic Echocardiography; heart sonography; Exercise; Exhibits; Gases; Goals; Cardiac Catheterization Procedures; Cardiac Catheterization; Heart Catheterization; Heart Catheterization Procedure; Insertion of catheter into heart chamber; hemodynamics; Pulmonary Hypertension; Lung; Lung Respiratory System; pulmonary; Morbidity - disease rate; Morbidity; mortality; Patients; Pulmonary Gas Exchange; Research; Rest; Sensitivity and Specificity; Computer software; Software; Standardization; Testing; Time; Measures; Walking; measurable outcome; outcome measurement; Outcome Measure; improved; Clinical; Physiologic; Physiological; Disease Progression; Right heart dysfunction; Right ventricle dysfunction; Right-sided heart dysfunction; Right Ventricular Dysfunction; Shapes; tool; Severities; System; Severity of illness; disease severity; Cardiopulmonary; Early Diagnosis; early detection; diagnostic accuracy; Accuracy of Diagnosis; Gatekeeping; gatekeeper; response; Intervention; Intervention Strategies; interventional strategy; Pharmaceutical Agent; Pharmaceuticals; Pharmacological Substance; pharmaceutical; Pharmacologic Substance; Symptoms; Data; Detection; Diagnostic Sensitivity; Diagnostic Specificity; Reproducibility; Community Practice; Newly Diagnosed; Pattern Recognition; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Monitor; Characteristics; Ventricular; pulmonary arterial hypertension; pulmonary artery hypertension; cost; Clinical assessments; intervention efficacy; therapeutic efficacy; therapy efficacy; Treatment Efficacy; clinical significance; clinically significant; high risk; clinical care; evidence base; standard measure; standard of care; improve symptom; symptom improvement; symptomatic improvement; response to therapy; response to treatment; therapeutic response; therapy response; treatment response; adverse consequence; adverse outcome; screenings; screening; accurate diagnosis; exercise intolerance; exercise capacity; prognostic significance; patient specific response; responsive patient; patient response; Exercise Test; detection sensitivity; disease prognosis; disease prognostication; pulmonary arterial pressure; lung artery blood pressure; pressure in pulmonary arteries; pulmonary arterial blood pressure; pulmonary artery pressure; pulmonary artery systolic pressure; right ventricular failure; right heart failure; right sided heart failure; right ventricle failure; right ventricular heart failure