Heart failure and vascular responsiveness are closely linked during cardiac surgery, but a low arterial pressure does not explain which part of the circulation is failing. A prospective study by Papazisi and colleagues examined how patients with chronic heart failure respond to phenylephrine before and after cardiopulmonary bypass (CPB), alongside laboratory testing of small resistance vessels. The findings suggest reduced responsiveness through the α1-adrenergic pathway, while the potential benefit of alternative vasopressors remains a question for clinical trials.
What the Study Examined
The VASOR study was conducted at Leiden University Medical Center and enrolled adults undergoing elective or urgent cardiac surgery with CPB. Patients with chronic heart failure and a left ventricular ejection fraction of 35% or less were compared with controls without heart failure whose ejection fraction exceeded 50%. Emergency surgery, acute heart failure, active infection, and preoperative vasopressor or mechanical support were among the exclusions.
The bedside analysis included 36 patients: 18 with heart failure and 18 controls. Investigators measured the proportional change in systemic vascular resistance (SVR) after a standardized phenylephrine challenge at baseline, after anesthesia induction, shortly after separation from CPB, and on the first postoperative day. Nitroglycerin testing assessed vasodilator responsiveness at baseline and on postoperative day one. Testing was performed only when clinically safe.
A separate laboratory component examined resistance arterioles from fat collected before CPB. Forty biopsies were processed, but only 13 produced usable experiments: 10 controls and three heart-failure patients. These are the relevant numbers for interpreting the ex vivo findings; 40 biopsies should not be mistaken for 40 successful vascular experiments.
Heart Failure and Vascular Responsiveness: Main Findings
Before anesthesia, the estimated SVR increase following phenylephrine was 26% in the heart-failure group, compared with 51% in controls. The corresponding 95% confidence intervals were 16–35% and 38–64%, with a between-group p value of 0.002. This supports an attenuated response already present before surgery, rather than a difference arising solely after bypass.
| Measurement point | Heart failure: SVR increase | Controls: SVR increase |
|---|---|---|
| Baseline | 26% | 51% |
| After anesthesia induction | 42% | 66% |
| After separation from CPB | 17% | 60% |
| First postoperative day | 12% | 29% |
These values are estimated mean changes from each patient’s SVR immediately before the drug challenge, not absolute SVR measurements or treatment targets. The postoperative decline occurred in both groups, but responsiveness remained lower in patients with heart failure. The tests surrounding CPB were performed after induction and after bypass cessation; the study does not establish a response measured during pump support itself.
A smaller SVR response after CPB was associated with greater norepinephrine use over the first postoperative day. The association persisted after adjustment for heart-failure status and norepinephrine dose at the measurement time, although the small cohort limited further adjustment. This relationship does not establish that a phenylephrine challenge can reliably predict individual treatment needs.
What the Vasopressin Findings Mean
The usable heart-failure arterioles showed markedly reduced phenylephrine-induced contraction in the laboratory, while their responses to vasopressin appeared greater than those of controls. Nitroglycerin responses in the bedside study were broadly similar between groups. Together, these observations are compatible with a pathway-specific alteration in adrenergic responsiveness rather than a complete inability of vascular smooth muscle to contract.
However, the laboratory heart-failure group contained only three patients, and formal between-group statistical testing of these experiments was not performed. Receptor downregulation and receptor desensitization were not directly distinguished. Greater contraction in an isolated arteriole also does not demonstrate that earlier vasopressin improves organ perfusion, reduces complications, or saves lives after surgery.
The authors propose a physiological rationale for studying non-adrenergic vasopressor strategies in selected heart-failure patients. This was an observational mechanistic study, not a randomized comparison of phenylephrine, norepinephrine, and vasopressin, and it does not establish a preferred first-line agent.
Relevance for Perfusion and Cardiac Surgical Teams
The findings help explain why patients with chronic ventricular dysfunction may have different pressure responses to the same adrenergic stimulus. They also reinforce the importance of interpreting pressure alongside flow, ventricular function, and the broader hemodynamic picture when separating from bypass. A reduced pressor response alone cannot identify the cause of postoperative hypotension.
Only one patient, a control, met the study’s specified postoperative vasoplegia definition. That definition required sustained vasopressor support with a cardiac index of at least 2.2 L/min/m² and may have missed mixed low-output and vasodilatory states. Accordingly, this cohort demonstrates differences in vascular reactivity more clearly than it establishes differences in clinically defined vasoplegia or patient outcomes.
Limitations and Disclosures
This was a small, single-center, nonrandomized study with heterogeneous operations and substantial differences in medication use. Residual confounding from procedures, inotropes, and other therapies remains possible. Some bedside measurements were omitted for safety, and many collected vessel samples could not be analyzed. Baseline cardiac-output calibration, pulse-contour measurements in LVAD recipients, and unrecorded differences in postoperative testing or tissue-storage timing introduce additional uncertainty.
The findings therefore warrant confirmation in larger cohorts and adequately powered treatment trials. The study was funded by Stichting Zabawas, grant G2012/026. The authors declared no conflicts of interest and reported that the funder had no role in study design, analysis, interpretation, or publication.
Original Article
Papazisi O, van Vessem ME, Beeres SLMA, et al. Impact of Chronic Heart Failure on Vascular Responsiveness: A Prospective Observational In Vivo and Ex Vivo Study in Patients Undergoing Cardiac Surgery. Journal of Clinical Medicine. 2026;15:8179. doi:10.3390/jcm15208179.
This original educational summary accompanies the unchanged source article, published under a Creative Commons Attribution license. The cover is a conceptual editorial illustration, not an anatomical or treatment guide.
