Effect of PEEP on Cardiac Function

The Effect of Positive End-Expiratory Pressure on Biventricular Mechanics in the Perioperative Setting

The purpose of this single-center, prospective study is to evaluate the physiologic effect of changes in PEEP on biventricular mechanics and RV-pulmonary arterial (RV-PA) coupling in adult patients undergoing cardiac surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiac Surgery Subjects
• Intervention / Treatment: Procedure: EIT Guided PEEP Trial

Detailed Description

Positive end-expiratory pressure (PEEP) is a critical modality of mechanical ventilation but has important and often underappreciated effects on biventricular mechanics. PEEP is frequently selected based primarily on respiratory mechanics and oxygenation targets; however, increasing intrathoracic pressure may reduce RV preload by elevating right atrial pressure, while increasing transpulmonary pressure may increase RV afterload by compressing intra-alveolar pulmonary vessels and redistributing pulmonary blood flow. This is important specifically in the context of cardiac surgery where right ventricular (RV) function plays a critical role in determining postoperative morbidity and mortality. Perioperative RV dysfunction has been consistently associated with adverse outcomes, including prolonged vasopressor and inotrope requirements, difficulty weaning from cardiopulmonary bypass, longer intensive care unit stays, and increased mortality.

Right ventricular-pulmonary arterial (RV-PA) coupling provides a physiologically integrated assessment of RV performance by quantifying the relationship between RV contractility and afterload. Animal studies have shown that incremental PEEP increases can impair biventricular mechanics and precipitate RV-PA uncoupling. However, these physiologic effects have not been systematically characterized in the perioperative setting in the cardiac surgery population. This protocol seeks to address this knowledge gap by systematically evaluating biventricular mechanics and RV-PA coupling across varying PEEP levels in a controlled setting, using tools already employed in routine cardiac surgical care (pulmonary artery catheter and intraoperative TEE).

The overarching goal of this proposal is to define how perioperative positive end-expiratory pressure alters biventricular mechanics and right ventricular-pulmonary arterial coupling, to inform physiologically guided, RV-protective ventilatory strategies during cardiac surgery.

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Arian Karimitar, PhD; Phone Number: 6176328056; Email: akarimit@bidmc.harvard.edu
• Study Contact Backup: Name: Vahid Kiarad, MD, MPH; Email: vkiarad@bidmc.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Beth Israel Deaconess Medical Center
      • Contact: Arian Karimitar, PhD; Phone Number: 6176328056; Email: akarimit@bidmc.harvard.edu
      • Contact: Vahid Kiarad, MD, MPH; Email: vkiarad@bidmc.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Age ≥ 18 years
• 2. Scheduled to undergo cardiac surgery requiring general anesthesia
• 3. Planned use of intraoperative transesophageal echocardiography (TEE) as part of routine clinical care

• 4. Planned placement of a pulmonary artery catheter as part of clinical care (Pulmonary artery catheter placement will be performed solely based on clinical judgment by the treating anesthesia and surgical teams. At our institution, pulmonary artery catheters are routinely placed in cardiac surgery patients with clinical indications including:

  • preoperative pulmonary hypertension (e.g., estimated PCWP >20 mmHg or elevated filling pressures on preoperative echocardiography),
  • right ventricular dysfunction or suspected RV failure (preoperative visual TTE assessment),
  • significant cardiopulmonary comorbidity,
  • or anticipated complex, prolonged, or high-acuity cardiac surgery. The research team will not influence decisions regarding catheter placement. Only patients already scheduled to receive a clinically indicated pulmonary artery catheter will be eligible for enrollment.)
• 5. Able and willing to provide written informed consent prior to surgery

Exclusion Criteria:

• 1. Significant arrhythmia (e.g., atrial fibrillation with uncontrolled ventricular response or other rhythm disturbances) that would interfere with reliable pressure waveform or echocardiographic measurements.
• 2. Severe valvular disease where protocol-related PEEP changes may pose unacceptable hemodynamic risk, as determined by the clinical team.
• 3. Significant chronic lung disease or other pulmonary pathology where PEEP adjustments may be unsafe (e.g., severe COPD with dynamic hyperinflation, bullous lung disease), at the discretion of the anesthesia team.
• 4. Contraindication to changes in PEEP, including inability to tolerate the planned PEEP titration due to hemodynamic instability or clinician concern.
• 5. Any contraindication to TEE (if clinically required TEE is not performed or is contraindicated, the subject will not be eligible)
• 6. Investigator or clinical team discretion (e.g., safety concerns, inability to obtain reliable measurements, or conflict with other perioperative research protocols)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Optimized PEEP Group; These are patients undergoing cardiac surgery who will undergo an incremental/decremental PEEP trial using Electrical Impedance Tomography (EIT).	Procedure: EIT Guided PEEP Trial; Electrical impedance tomography (EIT) will be used to guide identification of "optimal PEEP" based on lung mechanics. After induction of anesthesia and initiation of controlled mechanical ventilation, EIT data will be collected during a brief standardized PEEP titration maneuver to assess lung recruitment and overdistension.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Right ventricle-pulmonary artery coupling (Ees/Ea)	Right ventricle-pulmonary artery (RV-PA) coupling ratio (Ees/Ea) assessed using simultaneous transesophageal echocardiography and hemodynamic monitoring at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]) during a standardized stepwise PEEP titration sequence.	During the standardized PEEP titration sequence after induction of anesthesia and before surgical intervention (approximately 20-25 minutes)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Right ventricular end-diastolic volume at predefined PEEP levels	Three-dimensional right ventricular end-diastolic volume (RVEDV) measured by transesophageal echocardiography at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]).	During PEEP titration sequence (approximately 20-25 minutes after induction of anesthesia and prior to surgical incision)
Right ventricular end-systolic volume at predefined PEEP levels	Three-dimensional right ventricular end-systolic volume (RVESV) assessed by three-dimensional transesophageal echocardiography at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]).	During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes)
Right ventricular stroke volume at predefined PEEP levels	Right ventricular stroke volume derived from three-dimensional transesophageal echocardiography at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]).	During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes)
Right ventricular end-diastolic pressure at predefined PEEP levels	Right ventricular end-diastolic pressure measured via pulmonary artery catheter at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]).	During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes)
Right ventricular end-systolic pressure at predefined PEEP levels	Right ventricular end-systolic pressure estimated using waveform-based calculation methods from pulmonary artery catheter data at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]).	During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes)
Pulmonary artery systolic pressure at predefined PEEP levels	Pulmonary artery systolic pressure measured via pulmonary artery catheter at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]).	During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes)
Mean pulmonary artery pressure at predefined PEEP levels	Mean pulmonary artery pressure measured via pulmonary artery catheter at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]).	During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes)
Right ventricular end-systolic elastance at predefined PEEP levels	Right ventricular end-systolic elastance (Ees) derived using single-beat pressure-volume analysis at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]).	During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes)
Effective arterial elastance at predefined PEEP levels	Effective arterial elastance (Ea) derived from pressure-volume analysis at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]).	During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes)
Three-dimensional right ventricular ejection fraction	Three-dimensional right ventricular ejection fraction (3D RVEF) assessed by transesophageal echocardiography at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]) during a standardized stepwise PEEP titration sequence.	During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes)
Left ventricular ejection fraction at predefined PEEP levels	Three-dimensional left ventricular ejection fraction (LVEF) assessed by transesophageal echocardiography at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]).	During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes)
Left ventricular stroke volume at predefined PEEP levels	Left ventricular stroke volume derived from echocardiographic measurements at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]).	During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxygen saturation at predefined PEEP levels	Peak airway pressure recorded from the ventilator at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]).	During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes)
Plateau pressure at predefined PEEP levels	Plateau airway pressure measured during inspiratory hold maneuvers at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]).	During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes)

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center

Publications and helpful links

General Publications

• Bellofiore A, Vanderpool R, Brewis MJ, Peacock AJ, Chesler NC. A novel single-beat approach to assess right ventricular systolic function. J Appl Physiol (1985). 2018 Feb 1;124(2):283-290. doi: 10.1152/japplphysiol.00258.2017. Epub 2017 Oct 12.
• Araos J, Glocker F, Owyang CG, Teran F, Kim J, Nieman G, Heerdt PM. Biventricular Response to Positive End-expiratory Pressure in Swine: Assessment Based on Beat-to-beat Pressure Waveform Analysis. Anesthesiology. 2025 Apr 1;142(4):767-769. doi: 10.1097/ALN.0000000000005363. Epub 2025 Feb 13. No abstract available.
• Wood G, Madsen TL, Kim WY, Lyhne MD. Increasing Levels of Positive End-expiratory Pressure Cause Stepwise Biventricular Stroke Work Reduction in a Porcine Model. Anesthesiology. 2024 Feb 1;140(2):240-250. doi: 10.1097/ALN.0000000000004821.
• Acosta P, Santisbon E, Varon J. "The use of positive end-expiratory pressure in mechanical ventilation". Crit Care Clin. 2007 Apr;23(2):251-61, x. doi: 10.1016/j.ccc.2006.12.012.
• Ahmed U, Mahmood F, Nicoara A, Kiarad V. Right Ventricular Function and Echocardiographic Pressure-Volume Loops: Overview and Perioperative Clinical Implications. J Cardiothorac Vasc Anesth. 2025 Oct;39(10):2857-2865. doi: 10.1053/j.jvca.2025.05.019. Epub 2025 May 17.
• Kiarad V, Mahmood F, Hedayat M, Yunus R, Nicoara A, Liu D, Chu L, Senthilnathan V, Kai M, Khabbaz K. Intraoperative right ventricular end-systolic pressure-volume loop analysis in patients undergoing cardiac surgery: A proof-of-concept methodology. JTCVS Open. 2024 Sep 26;22:225-234. doi: 10.1016/j.xjon.2024.09.020. eCollection 2024 Dec.

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2026
• Primary Completion (Estimated): July 30, 2028
• Study Completion (Estimated): October 30, 2028

Study Registration Dates

• First Submitted: April 9, 2026
• First Submitted That Met QC Criteria: April 9, 2026
• First Posted (Actual): April 15, 2026

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Coronary Artery Disease; Mechanical Ventilation; PEEP Titration; Right Ventricular Impairment
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Heart Failure; Coronary Artery Disease
• Other Study ID Numbers: 2026P000077

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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