Exercise CMR-Derived Work-Volume Loop in Exercise-Induced HFpEF

Presenting Author(s)

• 

  Fahime Ghanbari, MD

  Fellow
  Harvard medical school, Beth Israel Deaconess Medical Center

Primary Author(s)

• 

  Fahime Ghanbari, MD

  Fellow
  Harvard medical school, Beth Israel Deaconess Medical Center

Co-Author(s)

• JR

  Jennifer Rodriguez

  Clinical Trials Specialist
  Beth Israel Deaconess Medical Center
• AC

  Adele Carty, MSc

  Statistician
  Beth Israel Deaconess Medical Center
• CT

  Connie Tsao, MD, MPH

  Physician
  Beth Israel Deaconess Medical Center
• JR

  Jeremy Robbins, MD

  Assistant Professor
  Beth Israel Deaconess Medical Center
• DG

  Deepa Gopal, MD

  Assistant Professor
  Division of Cardiovascular Medicine, Boston University Chobanian & Avedisian School of Medicine
• DS

  David Systrom, MD

  Assistant Professor
  Division of Pulmonary and Critical Care, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School
• AW

  Aaron Waxman, MD

  Associate professor
  Division of Pulmonary and Critical Care, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School
• WM

  Warren J. Manning, MD

  Section Chief, Non-invasive Cardiac Imaging
  Beth Israel Deaconess Medical Center/Harvard Medical School
  Beth Israel Deaconess
• RN

  Reza Nezafat, PhD

  Professor
  Harvard Medical School

Background: Dyspnea is a hallmark of exercise-induced HFpEF. However, distinguishing it from non-cardiac (NC) dyspnea is challenging and often requires advanced diagnostics such as invasive cardiopulmonary exercise testing (iCPET). Exercise CMR (Ex-CMR) can detect abnormalities in dynamic ventricular volumes that are not present at rest. Furthermore, exercise-intolerance can be assessed by a patient’s exercise workload using physiological stress. We propose a non-invasive work-volume (W-V) loop that integrates volumetric dynamics and workload, and assess its potential in distinguishing Ex-induced HFpEF from NC-dyspnea.

Methods: Ex-CMR was performed using a supine ergometer (Fig. 1A) and a highly accelerated, single-beat cine with AI-based reconstruction (full-heart coverage, 1.9 × 1.9 mm², 37 ms) (Fig. 1B). Subjects were imaged at rest and immediately post exercise. Key parameters—end-systolic (ESV) and end-diastolic volumes (EDV) at rest and post stress, along with maximum workload (W)—were used to form W-V loop (Fig. 2A). ESVs and EDVs were plotted on the X-axis, and W on the Y-axis. Loop characteristics included area and two base angles (𝜃₁, 𝜃₂), representing rest-stress deviations based on slope changes in the W-V loop (Fig. 2A). The enclosed area reflects the mean stroke volumes, multiplied by W. In a prospective multi-center study, we recruited consecutive patients with unexplained dyspnea referred for iCPET and included those consistent with Ex-induced HFpEF or NC-dyspnea. Ex-induced HFpEF was defined by stress PCWP >25 mmHg or ΔPCWP/ΔCO >2. NC-dyspnea patients had normal PCWPs with no clinical evidence of cardiac involvement (Fig. 1C). Resting pulmonary hypertension (PH) was excluded, but Ex-induced HFpEF could present with concomitant Ex-induced PH. A healthy cohort was also recruited. W-V loops were created, and loop angles and areas were compared using one-way ANOVA. Reproducibility was tested in 15 subjects by re-imaging with the same protocol one year later.

Results: Of 74 patients referred to iCPET, 36 (55±12 years, 11 males) met the inclusion criteria (12 Ex-induced HFpEF, 24 NC-dyspnea). The healthy cohort included 40 subjects (45±16 years, 19 males) and was used to create the reference loop (Fig. 2B). There were no differences in loop characteristics between NC-dyspnea and healthy cohorts. NC-dyspnea and Ex-induced HFpEF cohorts reached a similar % of max predicted heart rate at peak exercise (70±12% vs. 71±13%). Distinctive loop patterns and significant differences in W-V loop characteristics between the patient cohorts were observed (Fig. 3A). 𝜃₁ and 𝜃₂ differed significantly (𝜃₁: 105 ± 5° vs. 93 ± 4°, p< 0.01; 𝜃₂: 100 ± 3° vs. 105 ± 4°, p< 0.01). The loop area was significantly smaller in Ex-induced HFpEF (p=0.01). The reproducibility of the loop characteristics between the two visits was good to excellent (Fig. 3B).

Conclusion: The proposed reproducible W-V loop captures the interplay between volumetric dynamics and workload and can potentially improve our ability to phenotype patients with unexplained dyspnea.

Figure 1. A) Exercise protocol. B) Image Examples. C. Cohorts’ criteria. All patients were symptomatic (NYHA II-IV). No patients had pulmonary hypertension at rest. Patients with exercise-induced HFpEF could present concomitant exercise-induced PH. RHC: right heart catheterization; iCPET: invasive cardiopulmonary exercise testing; PCWP: pulmonary capillary wedge pressure; CO: cardiac output; PH: pulmonary hypertension.

Figure 2 A) Work-Volume (W-V) loop construction. (B) The reference loop was derived from the mean Ex-CMR data of 40 healthy adults (45 ± 16 years, 19 males). The solid loop shows the mean W-V loop, with dashed lines representing the 95% confidence intervals (CI).

Figure 3. A) W-V loops derived from mean parameter values for each cohort: healthy (n=40), non-cardiac (NC) dyspnea (n=24), and exercise-induced HFpEF (n=12).The W-V loops reveal distinct patterns between NC-dyspnea and Ex-induced HFpEF, with significant differences in angles and a smaller loop area in Ex-induced HFpEF compared to NC-dyspnea. B) Reproducibility of W-V loops between the two visits one year apart (solid: visit 1; dashed: visit 2), including a breakdown of measurements for loop characteristics and intraclass correlation coefficients (ICCs).