Vena Cava Occlusion Reveals Site-Specific Preload Dynamics: Implications for Volume Management in Heart Failure

Abstract

Heart failure (HF) is marked by impaired ventricular function, neurohormonal activation, and volume overload. While therapies target remodeling and neurohormonal pathways, preload management remains pivotal for symptom relief and preventing decompensation. Pressure-volume (PV) loop analysis enables precise characterization of cardiac performance during acute loading changes. To define the differential hemodynamic impact of transient inferior vena cava occlusion (IVCO) versus superior vena cava occlusion (SVCO) using PV loop analysis in a large-animal model. Controlled IVCO and SVCO were performed in healthy animals to reduce preload. PV-derived indices included stroke volume (SV), cardiac output (CO), end-systolic elastance (Ees), volume-axis intercept (V₀), and preload recruitable stroke work (PRSW). IVCO, removing ~70% of venous return, produced a marked leftward PV loop shift, decreased SV and CO, and a near-zero V₀, consistent with near-complete ventricular unloading. The end-systolic pressure-volume relationship steepened, suggesting an acute compensatory inotropic response, though Ees remained unchanged, indicating preserved intrinsic contractility. In contrast, SVCO (~30% venous return) caused only modest PV loop shifts, with preserved end-diastolic volume and stable or slightly rightward V₀. Across both interventions, preload, not intrinsic contractility, accounted for changes in mechanical work and PRSW. IVCO and SVCO elicit distinct preload-dependent hemodynamic profiles. Interpretation of PV loop-derived metrics must account for dynamic loading conditions. These findings provide mechanistic insight into acute volume regulation and warrant validation in HF-specific models to inform decongestive management strategies.

Keywords

Transient preload reduction / IVC vs. SVC occlusion / HF with preserved ejection fraction (HFpEF)

Statement of the Use of Generative AI and AI-Assisted Technologies in the Writing Process

During the preparation of this manuscript, the authors used Microsoft Copilot to support drafting and editing. All content generated by the tool was reviewed and revised as necessary, and the authors take full responsibility for the final published work.

Ethics Statement

Ethical review and approval were waived due to the analysis of existing data. Study was based on a retrospective record review, examining historical data without active intervention, and use of de-identified datasets and specimens.

Informed Consent Statement

Not Applicable.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Funding

This research received no external funding.

Declaration of Competing Interest

The author declares that he has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References

[1] Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur. Heart J. 2016, 37, 2129-2200. DOI:10.1093/eurheartj/ehw128; in Eur. Heart J. 2018, 39, 860. DOI:10.1093/eurheartj/ehw383

[2] Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2022, 145, e895-e1032. DOI:10.1161/CIR.0000000000001063;ErratuminCirculation2023,147,e674. DOI:10.1161/CIR.0000000000001142

[3] McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur. J. Heart Fail. 2022, 24, 4-131. DOI:10.1002/ejhf.2333

[4] Wattanachayakul P, Kittipibul V, Salah HM, Yaku H, Gustafsson F, Baratto C, et al. Invasive haemodynamic assessment in heart failure with preserved ejection fraction. ESC Heart Fail. 2025, 12, 1558-1570. DOI:10.1002/ehf2.15163

[5] Rosalia L, Ozturk C, Wang SX, Quevedo-Moreno D, Saeed MY, Mauskapf A, et al. Modulating Cardiac Hemodynamics Using Tunable Soft Robotic Sleeves in a Porcine Model of HFpEF Physiology for Device Testing Applications. Adv. Funct. Mater. 2024, 34, 2310085. DOI:10.1002/adfm.202310085

[6] Vyas R, Patel M, Khouri SJ, Moukarbel GV. A profile on the CardioMEMS HF system in the management of patients with early stages of heart failure: An update. Expert Rev. Med. Devices 2023, 20, 621-631. DOI:10.1080/17434440.2023.2228683

[7] Sharifov OF, Gupta H. What Is the Evidence That the Tissue Doppler Index E/e’ Reflects Left Ventricular Filling Pressure Changes After Exercise or Pharmacological Intervention for Evaluating Diastolic Function? A Systematic Review. J. Am. Heart Assoc. 2017, 6, e004766. DOI:10.1161/JAHA.116.004766

[8] Opotowsky AR, Hess E, Maron BA, Brittain EL, Barón AE, Maddox TM, et al. Thermodilution vs Estimated Fick Cardiac Output Measurement in Clinical Practice: An Analysis of Mortality from the Veterans Affairs Clinical Assessment, Reporting, and Tracking (VA CART) Program and Vanderbilt University. JAMA Cardiol. 2017, 2, 1090-1099. DOI:10.1001/jamacardio.2017.2945

[9] Istratoaie S, Frost CL, Donal E. Non-Invasive Hemodynamic Assessment of Heart Failure with Preserved Ejection Fraction. Korean Circ. J. 2025, 55, 165-184. DOI:10.4070/kcj.2024.0370

[10] Jani V, Konecny F, Shelby A, Kulkarni A, Hammel J, Schuster A, et al. Influence of right ventricular pressure and volume overload on right and left ventricular diastolic function. J. Thorac. Cardiovasc. Surg. 2022, 163, e299-e308. DOI:10.1016/j.jtcvs.2021.07.040

[11] Berboth L, Zirngast B, Manninger M, Steendijk P, Tschöpe C, Scherr D, et al. Graded lower body negative pressure induces intraventricular negative pressures and incremental diastolic suction: A pressure-volume study in a porcine model. J. Appl. Physiol. 2022, 133, 20-26. DOI:10.1152/japplphysiol.00110.2022

[12] Habigt MA, Krieger M, Gesenhues J, Ketelhut M, Mechelinck M, Hein M. Non-linearity of end-systolic pressure-volume relation in afterload increases is caused by an overlay of shortening deactivation and the Frank-Starling mechanism. Sci. Rep. 2021, 11, 3353. DOI:10.1038/s41598-021-82791-3

[13] Mohyuddin R, Dietrichs ES, Sundaram P, Kondratiev T, Figenschou MF, Sieck GC, et al. Cardiovascular Effects of Epinephrine During Experimental Hypothermia (32 °C) With Spontaneous Circulation in an Intact Porcine Model. Front. Physiol. 2021, 12, 718667. DOI:10.3389/fphys.2021.718667

[14] McCall FC, Telukuntla KS, Karantalis V, Suncion VY, Heldman AW, Mushtaq M, et al. Myocardial infarction and intramyocardial injection models in swine. Nat. Protoc. 2012, 7, 1479-1496. DOI:10.1038/nprot.2012.075

[15] Monge García MI, Jian Z, Hatib F, Settels JJ, Cecconi M, Pinsky MR. Dynamic Arterial Elastance as a Ventriculo-Arterial Coupling Index: An Experimental Animal Study. Front. Physiol. 2020, 11, 284. DOI:10.3389/fphys.2020.00284

[16] Pinsky MR. Dynamic right and left ventricular interactions in the pig. Exp. Physiol. 2020, 105, 1293-1315. DOI:10.1113/EP088550

[17] Weil BR, Techiryan G, Suzuki G, Konecny F, Canty JM, Jr. Adaptive Reductions in Left Ventricular Diastolic Compliance Protect the Heart From Stretch-Induced Stunning. JACC Basic Transl. Sci. 2019, 4, 527-541. DOI:10.1016/j.jacbts.2019.04.002

[18] Kapur NK, Kiernan MS, Gorgoshvili I, Yousefzai R, Vorovich EE, Tedford RJ, et al. Intermittent Occlusion of the Superior Vena Cava to Improve Hemodynamics in Patients With Acutely Decompensated Heart Failure: The VENUS-HF Early Feasibility Study. Circ. Heart Fail. 2022, 15, e008934. DOI:10.1161/CIRCHEARTFAILURE.121.008934

[19] Ellenbroek GH, van Hout GP, Timmers L, Doevendans PA, Pasterkamp G, Hoefer IE. Primary Outcome Assessment in a Pig Model of Acute Myocardial Infarction. J. Vis. Exp. 2016, 116, 54021. DOI:10.3791/54021

[20] Morimont P, Guiot J, Desaive T, Tchana-Sato V, Janssen N, Cagnina A, et al. Veno-venous extracorporeal CO₂ removal improves pulmonary hemodynamics in a porcine ARDS model. Acta Anaesthesiol. Scand. 2015, 59, 448-456. DOI:10.1111/aas.12497

[21] Kutty S, Kottam AT, Padiyath A, Bidasee KR, Li L, Gao S, et al. Validation of admittance computed left ventricular volumes against real-time three-dimensional echocardiography in the porcine heart. Exp. Physiol. 2013, 98, 1092-1101. DOI:10.1113/expphysiol.2012.070821

[22] Mikhova KM, Don CW, Laflamme M, Kellum JA, Mulligan MS, Verrier ED, et al. Effect of cytokine hemoadsorption on brain death-induced ventricular dysfunction in a porcine model. J. Thorac. Cardiovasc. Surg. 2013, 145, 215-224. DOI:10.1016/j.jtcvs.2012.08.002

[23] Lionetti V, Romano SL, Bianchi G, Bernini F, Dushpanova A, Mascia G, et al. Impact of acute changes of left ventricular contractility on the transvalvular impedance: validation study by pressure-volume loop analysis in healthy pigs. PLoS ONE 2013, 8, e80591. DOI:10.1371/journal.pone.0080591

[24] Marshall KD, Muller BN, Krenz M, Hanft LM, McDonald KS, Dellsperger KC, et al. Heart failure with preserved ejection fraction: chronic low-intensity interval exercise training preserves myocardial O 2 balance and diastolic function. J. Appl. Physiol. 2013, 114, 131-147. DOI:10.1152/japplphysiol.01059.2012

[25] Morimont P, Lambermont B, Desaive T, Janssen N, Chase G, D’Orio V. Arterial dP/dtmax accurately reflects left ventricular contractility during shock when adequate vascular filling is achieved. BMC Cardiovasc. Disord. 2012, 12, 13. DOI:10.1186/1471-2261-12-13

[26] McDonald KS, Hanft LM, Domeier TL, Emter CA. Length and PKA Dependence of Force Generation and Loaded Shortening in Porcine Cardiac Myocytes. Biochem. Res. Int. 2012, 2012, 371415. DOI:10.1155/2012/371415

[27] Schmitt B, Steendijk P, Lunze K, Ovroutski S, Falkenberg J, Rahmanzadeh P, et al. Integrated assessment of diastolic and systolic ventricular function using diagnostic cardiac magnetic resonance catheterization: validation in pigs and application in a clinical pilot study. JACC Cardiovasc. Imaging 2009, 2, 1271-1281. DOI:10.1016/j.jcmg.2009.09.007

[28] Miranda DR, Klompe L, Cademartiri F, Haitsma JJ, Palumbo A, Takkenberg JJ, et al. The effect of open lung ventilation on right ventricular and left ventricular function in lung-lavaged pigs. Crit. Care 2006, 10, R86. DOI:10.1186/cc4944

[29] Lambermont B, Ghuysen A, Kolh P, Tchana-Sato V, Segers P, Gérard P, et al. Effects of endotoxic shock on right ventricular systolic function and mechanical efficiency. Cardiovasc. Res. 2003, 59, 412-418. DOI:10.1016/s0008-6363(03)00368-7

[30] Haney MF, Johansson G, Häggmark S, Biber B. Method of preload reduction during LVPVR analysis of systolic function: Airway pressure elevation and vena cava occlusion. Anesthesiology 2002, 97, 436-446. DOI:10.1097/00000542-200208000-00022

[31] Lewis ME, Al-Khalidi AH, Bonser RS, Clutton-Brock T, Morton D, Paterson D, et al. Vagus nerve stimulation decreases left ventricular contractility in vivo in the human and pig heart. J. Physiol. 2001, 534 Pt 2, 547-552. DOI:10.1111/j.1469-7793.2001.00547.x

[32] Tayama M, Solomon SB, Glantz SA. Effect of lidocaine on left ventricular pressure-volume curves during demand ischemia in pigs. Am. J. Physiol. 1998, 274, H2100-H2109. DOI:10.1152/ajpheart.1998.274.6.H2100

[33] Cassidy SC, Chan DP, Allen HD. Left ventricular systolic function, arterial elastance, and ventricular-vascular coupling: A developmental study in piglets. Pediatr. Res. 1997, 42, 273-281. DOI:10.1203/00006450-199709000-00005

[34] Brunel L, Williams ZA, Yata M, Robinson BM, Wise IK, Paterson HS, et al. Incorporating the anterior mitral leaflet to the annulus impairs left ventricular function in an ovine model. JTCVS Open 2021, 7, 111-120. DOI:10.1016/j.xjon.2021.03.010

[35] Giao DM, Wang Y, Rojas R, Takaba K, Badathala A, Spaulding KA, et al. Left ventricular geometry during unloading and the end-systolic pressure volume relationship: Measurement with a modified real-time MRI-based method in normal sheep. PLoS ONE 2020, 15, e0234896. DOI:10.1371/journal.pone.0234896

[36] Wo N, Rajagopal V, Cheung MMH, Smolich JJ, Mynard JP. Assessment of single beat end-systolic elastance methods for quantifying ventricular contractility. Heart Vessels 2019, 34, 716-723. DOI:10.1007/s00380-018-1303-5

[37] Mau J, Menzie S, Huang Y, Ward M, Hunyor S. Nonsurround, nonuniform, biventricular-capable direct cardiac compression provides Frank-Starling recruitment independent of left ventricular septal damage. J. Thorac. Cardiovasc. Surg. 2011, 142, 209-215. DOI:10.1016/j.jtcvs.2010.05.057

[38] Yerebakan C, Klopsch C, Prietz S, Boltze J, Vollmar B, Liebold A, et al. Pressure-volume loops: Feasible for the evaluation of right ventricular function in an experimental model of acute pulmonary regurgitation? Interact. Cardiovasc. Thorac. Surg. 2009, 9, 163-168. DOI:10.1510/icvts.2008.198275

[39] Grignola JC, Ginés F, Guzzo D. Comparison of the Tei index with invasive measurements of right ventricular function. Int. J. Cardiol. 2006, 113, 25-33. DOI:10.1016/j.ijcard.2005.10.012

[40] Leeuwenburgh BP, Helbing WA, Steendijk P, Schoof PH, Baan J. Effects of acute left ventricular unloading on right ventricular function in normal and chronic right ventricular pressure-overloaded lambs. J. Thorac. Cardiovasc. Surg. 2003, 125, 481-490. DOI:10.1067/mtc.2003.28

[41] Ramanathan T, Shirota K, Morita S, Nishimura T, Huang Y, Zheng X, et al. Left ventricular oxygen utilization efficiency is impaired in chronic streptozotocin-diabetic sheep. Cardiovasc. Res. 2002, 55, 749-756. DOI:10.1016/s0008-6363(02)00497-2

[42] Cardozo RH, de Vroomen M, van Bel F, Baan J, Steendijk P. Simultaneous measurement of right and left ventricular volume by the conductance catheter technique in the newborn lamb. Neth. Heart J. 2003, 11, 203-209.

[43] Hon JK, Steendijk P, Khan H, Wong K, Yacoub M. Acute effects of pulmonary artery banding in sheep on right ventricle pressure-volume relations: Relevance to the arterial switch operation. Acta Physiol. Scand. 2001, 172, 97-106. DOI:10.1046/j.1365-201X.2001.00844.x

[44] Lewinsky RM, Szwarc RS, Benson LN, Ritchie JW. The effects of hypoxic acidemia on left ventricular end-systolic elastance in fetal sheep. Pediatr. Res. 1993, 34, 38-43. DOI:10.1203/00006450-199307000-00010

[45] Gupta KB, Bavaria JE, Ratcliffe MB, Edmunds LH, Jr., Bogen DK. Measurement of end-systolic pressure-volume relations by intra-aortic balloon occlusion. Circulation 1989, 80, 1016-1028. DOI:10.1161/01.cir.80.4.1016

[46] Ahmadian M, Williams AM, Mannozzi J, Konecny F, Hoiland RL, Wainman L, et al. A cross-species validation of single-beat metrics of cardiac contractility. J. Physiol. 2022, 600, 4779-4806. DOI:10.1113/JP283319

[47] Gruslova AB, Cabe AG, Kottam A, Walmsley J, Porterfield JE, Sako EY, et al. Smart Drain for Post-Cardiac Surgery Left Ventricular Volumes Evaluated in Large Animal Models. Ann. Thorac. Surg. 2022, 114, 2270-2279. DOI:10.1016/j.athoracsur.2021.10.044

[48] Mathieu M, El Oumeiri B, Touihri K, Hadad I, Mahmoudabady M, Thoma P, et al. Ventricular-arterial uncoupling in heart failure with preserved ejection fraction after myocardial infarction in dogs—Invasive versus echocardiographic evaluation. BMC Cardiovasc. Disord. 2010, 10, 32. DOI:10.1186/1471-2261-10-32

[49] Iwade M, Nomura M, Uezono S, Ashikari E, Ozaki M. Effects of dopamine and olprinone on ventricular energetics in sevoflurane-induced acute left ventricular depression in dogs. J. Cardiothorac. Vasc. Anesth. 2006, 20, 358-363. DOI:10.1053/j.jvca.2005.05.021

[50] Sun Y, Belenkie I, Wang JJ, Tyberg JV. Assessment of right ventricular diastolic suction in dogs with the use of wave intensity analysis. Am. J. Physiol. Heart Circ. Physiol. 2006, 291, H3114-H3121. DOI:10.1152/ajpheart.00853.2005

[51] Munagala VK, Hart CY, Burnett JC, Jr., Meyer DM, Redfield MM. Ventricular structure and function in aged dogs with renal hypertension: A model of experimental diastolic heart failure. Circulation 2005, 111, 1128-1135. DOI:10.1161/01.CIR.0000157183.21404.63

[52] Karunanithi MK, Feneley MP. Single-beat determination of preload recruitable stroke work relationship: Derivation and evaluation in conscious dogs. J. Am. Coll. Cardiol. 2000, 35, 502-513. DOI:10.1016/s0735-1097(99)00566-5

[53] Leather HA, Segers P, Sun YY, De Ruyter HA, Vandermeersch E, Wouters PF. The limitations of preload-adjusted maximal power as an index of right ventricular contractility. Anesth. Analg. 2002, 95, 798-804. DOI:10.1097/00000539-200210000-00003

[54] Denault AY, Gorcsan J, III, Pinsky MR. Dynamic effects of positive-pressure ventilation on canine left ventricular pressure-volume relations. J. Appl. Physiol. 2001, 91, 298-308. DOI:10.1152/jappl.2001.91.1.298

[55] Atkins BZ, Silvestry SC, Davis JW, Kisslo JA, Glower DD, Jr. Means for load variation during echocardiographic assessment of the Frank-Starling relationship. J. Am. Soc. Echocardiogr. 1999, 12, 792-800. DOI:10.1016/s0894-7317(99)70183-5

[56] Hettrick DA, Pagel PS, Warltier DC. Desflurane, sevoflurane, and isoflurane impair canine left ventricular-arterial coupling and mechanical efficiency. Anesthesiology 1996, 85, 403-413. DOI:10.1097/00000542-199608000-00023

[57] Regan CP, Stump GL, Detwiler TJ, Chen L, Regan HK, Gilberto DB, et al. Characterization of an investigative safety pharmacology model to assess comprehensive cardiac function and structure in chronically instrumented conscious beagle dogs. J. Pharmacol. Toxicol. Methods 2016, 81, 107-114. DOI:10.1016/j.vascn.2016.05.002

[58] McKay RG, Miller MJ, Ferguson JJ, Momomura S, Sahagian P, Grossman W, et al. Assessment of left ventricular end-systolic pressure-volume relations with an impedance catheter and transient inferior vena cava occlusion: use of this system in the evaluation of the cardiotonic effects of dobutamine, milrinone, Posicor and epinephrine. J. Am. Coll. Cardiol. 1986, 8, 1152-1160. DOI:10.1016/s0735-1097(86)80395-3

[59] Kass DA, Yamazaki T, Burkhoff D, Maughan WL, Sagawa K. Determination of left ventricular end-systolic pressure-volume relationships by the conductance (volume) catheter technique. Circulation 1986, 73, 586-595. DOI:10.1161/01.cir.73.3.586

[60] Pilz PM, Ward JE, Chang WT, Kiss A, Bateh E, Jha A, et al. Large and Small Animal Models of Heart Failure with Reduced Ejection Fraction. Circ. Res. 2022, 130, 1888-1905. DOI:10.1161/CIRCRESAHA.122.320246

[61] Charles CJ, Rademaker MT, Scott NJA, Richards AM. Large Animal Models of Heart Failure: Reduced vs. Preserved Ejection Fraction. Animals 2020, 10, 1906. DOI:10.3390/ani10101906

[62] Kapur NK, Reyelt L, Crowley P, Richey L, McCarthy J, Annamalai S, et al. Intermittent Occlusion of the Superior Vena Cava Reduces Cardiac Filling Pressures in Preclinical Models of Heart Failure. J. Cardiovasc. Transl. Res. 2020, 13, 151-157. DOI:10.1007/s12265-019-09916-y

[63] Lohmeier TE, Iliescu R. Chronic lowering of blood pressure by carotid baroreflex activation: mechanisms and potential for hypertension therapy. Hypertension 2011, 57, 880-886. DOI:10.1161/HYPERTENSIONAHA.108.119859