Oxygen Pulse and Its Curve Patterns in Male Patients With Heart Failure and Chronic Obstructive Pulmonary Disease With and in Healthy Men

The Differences in Oxygen Pulse Pattern During Maximum Incremental Exercise Test Between Norms and Patients With Chronic Obstructive Pulmonary Disease and With Chronic Heart Failure - the Possible Mechanisms

Background: In non-invasive cardiopulmonary exercise testing (CPET), oxygen pulse (O2P) is defined as oxygen uptake divided by heart rate and is equal to the product of stroke volume and oxygen extraction by cells. As per, the O2P indicates the capability of oxygen consumption of whole body tissues and cells per heart beat. During exercise, the O2P changes can be deemed as the stroke volume changes as the oxygen extraction by muscle cells are normal. Hence, CPET-O2P can be non-invasively and continuously used to monitor the stroke volume changes during exercise. O2P value (i.e., % of predicted) is related to the severity and prognosis of heart failure and to the severity of constraint of the heart caused by exercise-induced hyperinflation or air trapping in patients with chronic obstructive pulmonary disease (COPD). However, O2P plateau pattern is not uncommonly encountered in the daily practice.

Hypothesis and aims: O2P patterns during incremental exercise are seldom investigated although they have been hypothesized that the plateau or decreasing patterns are related to myocardial failure or ischemia. In this proposal, the O2P patterns are to be thoroughly investigated: (1) the patterns in norms, patients with heart failure and COPD, (2) the relationship between the O2P pattern and cardiac function and/or myocardial ischemia in patients with heart failure and COPD. As yet there are no relative reports on the O2P pattern and its possible mechanisms in the literature, the results of the proposal might tremendously impact the interpretation strategy of CPET reports.

Methods: Multidisciplinary, prospective, comparative cross-sectional study is designed. Subjects aged from 40-85 years with the BMI of 18-28kg/m2 are to be enrolled: sample sizes of the norms, heart failure and COPD groups are 10, 20, and 20, respectively, equally distributed in two years. The definitions of COPD and heart failure with NYHA class I-III are according to the GOLD and ESC guidelines, respectively。All the three groups undergo CPET-NIRS, echocardiography, and the first pass and myocardial perfusion studies using Tc-99. The primary measurements are the O2P patterns and the cardiac function measured with echocardiography, the first pass and myocardial perfusion studies and air trapping in the lungs.。 Statistical analysis: For normal continuous data, t-test or ANOVA is used. For non-normal data, the Mann-Whitney test is used. The chi-square test or Fisher's exact test is used to compare the proportion of categorical variables between the two groups. A p value of less than .05 is considered to be statistically significant. Statistical procedures are performed using the SAS software package version 9.3.

Study Overview

• Status: Completed
• Conditions: Outcome, Fatal
• Intervention / Treatment: Diagnostic test: first pass study; Diagnostic test: cardiopulmonary exercise testing

• Study Type: Observational
• Enrollment (Actual): 90

Contacts and Locations

Study Locations

• Taiwan
  • Taichung, Taiwan
    • Chung Shan Medical University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

COPD. Participants with COPD were referred by pulmonologists, and they all had respiratory symptoms, risk factors and a post-bronchodilator forced expired volume in one second (FEV1)/forced vital capacity (FVC) of <0.7 in accordance with the Global Initiative for Chronic Lung Disease criteria.[23] Participants with a significant post-bronchodilator effect (increase in FEV1 >12% and 200 mL from baseline) were excluded.

HFrEF/HFmrEF. Participants with HFrEF/HFmrEF who had reduced and mildly reduced EFs were referred by cardiologists, and they were enrolled if they had New York Heart Association functional class (NYHA) I-III, and risk factors. A left ventricular EF using two-dimensional echocardiography (2DLVEF) <45-50% was obtained within 2 months before or after commencing the study.[24] Normal controls. Healthy subjects were recruited among the hospital staff and the local community through personal contacts. They were free of known significant diseases.

Description

Inclusion Criteria:

• Subjects aged from 40-85 years with the BMI of 18-28kg/m2 are to be enrolled: sample sizes of the norms, heart failure and COPD groups are 10, 20, and 20, respectively, equally distributed in two years. All of the participants had been in a stable clinical condition for at least 1 month before participating in the study. None of the participants had contraindications for cardiopulmonary exercise tests (CPETs).

Exclusion Criteria:

• Participants with diabetes mellitus, uncontrolled hypertension, arrhythmia, cancer, liver, renal or autoimmune diseases, or anemia were excluded. However, participants with well controlled diabetes mellitus were included in the HFrEF/HFmrEF group as these conditions often co-exist. Physical activity was not encouraged or limited during the study period.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CHF; CHF for chronic heart failure	Diagnostic test: first pass study; Radionuclide assessment of ventricular performance was performed (Symbia T2, Germany); Diagnostic test: cardiopulmonary exercise testing; to measured (mL/min, STPD), CO2 output ( ) (mL/min), and minute ventilation ( ) (L/min, BTPS) breath by-breath (MasterScreen CPX™, Germany)
COPD; COPD for chronic obstructive pulmonary disease	Diagnostic test: first pass study; Radionuclide assessment of ventricular performance was performed (Symbia T2, Germany); Diagnostic test: cardiopulmonary exercise testing; to measured (mL/min, STPD), CO2 output ( ) (mL/min), and minute ventilation ( ) (L/min, BTPS) breath by-breath (MasterScreen CPX™, Germany)
control; control for normal controls	Diagnostic test: first pass study; Radionuclide assessment of ventricular performance was performed (Symbia T2, Germany); Diagnostic test: cardiopulmonary exercise testing; to measured (mL/min, STPD), CO2 output ( ) (mL/min), and minute ventilation ( ) (L/min, BTPS) breath by-breath (MasterScreen CPX™, Germany)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
O2P and its patterns	O2P value and its pattern were measured by exercise gas exchange.	one hour

Collaborators and Investigators

• Sponsor: Chung Shan Medical University
• Investigators: Principal Investigator: Ming-Lung Chuang, M.D., Chung Shan Medical University

Publications and helpful links

General Publications

• Chuang ML, Tsai CF, Ueng KC, Weng JH, Tsai MF, Lo CH, Chen GB, Sia SK, Chuang YT, Wu TC, Kao PF, Hsieh MJ. The Impact of Oxygen Pulse and Its Curve Patterns on Male Patients with Heart Failure, Chronic Obstructive Pulmonary Disease, and Healthy Controls-Ejection Fractions, Related Factors and Outcomes. J Pers Med. 2022 Apr 28;12(5):703. doi: 10.3390/jpm12050703.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): May 27, 2021

Study Registration Dates

• First Submitted: December 28, 2021
• First Submitted That Met QC Criteria: December 28, 2021
• First Posted (Actual): January 12, 2022

Study Record Updates

• Last Update Posted (Actual): January 12, 2022
• Last Update Submitted That Met QC Criteria: December 28, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: exercise testing, oxygen pulse, chronic obstructive pulmonary disease, congestive heart failure, first pass study
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Heart Failure; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: CSH-2019-C-030

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No