Heart Transplants: PVR No Magic Number for Ruling Out Candidates

PHOENIX — High pulmonary vascular resistance (PVR) alone should not disqualify a person for heart transplantation, research suggested.

Based on data from the Organ Procurement and Transplantation Network, an elevated PVR was not actually predictive of excess 1-year mortality after heart transplantation, whereas a high transpulmonary gradient (TPG) was, reported Ahmed Zayed, MBBCh, of Staten Island University Hospital, Northwell Health, New York City.

Compared with transplant recipients who’d had low PVR and low TPG, the excess risk was observed in peers who had elevated TPG, whether with a low PVR (adjusted HR 1.15, 95% CI 1.04-1.28) or a high PVR (adjusted HR 1.18, 95% CI 1.08-1.28). A high PVR with low TPG was not significantly tied to greater post-transplant mortality (adjusted HR 1.06, 95% CI 0.92-1.23).

Similarly, as continuous variables, rising PVR did not correlate with rising deaths (adjusted HR 1.00 at 3 Wood Units, adjusted HR 0.94 at 8 Wood Units), while rising TPG did (adjusted HR 1.13 at 12 mmHg, adjusted HR 1.23 at 18 mmHg).

Zayed presented these findings during a poster session here at the Heart Failure Society of America annual meeting. The study manuscript was simultaneously published in JACC: Heart Failure.

“The high PVR/low TPG phenotype was defined by low cardiac output and high filling pressures, indicating that its PVR elevation is a flow-dependent, mathematical artifact rather than fixed pulmonary vascular disease, so the donor right ventricle is not exposed to a high gradient,” the authors wrote.

“The practical message for clinicians is simple and I think reassuring: a candidate with a high calculated PVR but a normal TPG probably shouldn’t be turned down on the PVR number alone. Conversely, a normal PVR in a high-output or LVAD [left ventricular assist device]-supported patient can be falsely reassuring, and an elevated gradient in that setting deserves real attention to reversibility and to protecting the donor right ventricle around the time of transplant,” according to Zayed.

“The goal isn’t to discard PVR, it’s to stop reading it in isolation,” he told MedPage Today.

Zayed explained that TPG and PVR are two related hemodynamic measures that help gauge the risk of donor right ventricular failure: TPG is the direct measurement of pressure drop across the lungs (mean pulmonary artery [PA] pressure minus pulmonary capillary wedge pressure), whereas PVR is derived from TPG divided by cardiac output.

PVR has been the preferred metric for decades due to history and convention, according to Zayed. “It’s the number clinicians are trained to look at and the one that appears on every right-heart-cath report. It’s also intuitively appealing as it packages pressure and flow into a single value.”

But TPG is flow-independent, whereas a reduced cardiac output alone, in low-output heart failure, can yield a mathematically elevated PVR despite a normal gradient. A high PVR in this case does not reflect true pulmonary vascular disease, Zayed said. “PVR is least reliable when flow is high or pulsatility is low: LVAD-driven high output mathematically lowers calculated PVR, and on venoarterial extracorporeal membrane oxygenation, a reassuring PVR may reflect the right ventricle’s inability to generate pulmonary pressure rather than a healthy vascular bed.”

Maya Guglin, MD, of Rutgers Health and The Robert Wood Johnson Transplant Center in New Brunswick, New Jersey, agreed with considering PVR and TPG together as complements. She was unswayed by the present report, however, as it lacked absolute numbers of pulmonary pressures.

“PA pressure is always taken in consideration even with current practice. No surgeon would go to transplant a patient with systolic PA pressure above 60-65 [mmHg], regardless of what the PVR calculation brings,” she told MedPage Today. “We never decide on transplant only based on the PVR. At the same time, there is whole literature, far more than one paper, on disadvantage of transplanting someone with PVR>3.”

“Without the raw number of PA pressure, this paper, although thought provoking, doesn’t provide enough evidence to change the current practice,” she commented.

Zayed’s group had for the study 42,845 adult recipients of primary, isolated heart transplants in 2005-2025 with complete pretransplant hemodynamic records. The investigators had excluded records with missing or implausible hemodynamics following calculation of PVR and TPG.

Of these patients, 65.3% had low PVR/low TPG, 10.0% low PVR/high TPG, 6.1% high PVR/low TPG, and 18.5% high PVR/high TPG.

Neither PVR nor TPG, or any other hemodynamic variable, performed well at predicting 1-year mortality, early mechanical support, and primary graft dysfunction. Only small between-group differences could be gleaned regarding post-transplant dialysis and graft failure (lowest in high PVR/low TPG and highest in low PVR/high TPG).

Of note, the retrospective registry analysis was potentially subject to residual confounding and selection bias, Zayed and colleagues acknowledged, and the database used also lacked information on cardiac output calculation method, right ventricular function, and perioperative management.

“Our planned next steps include looking at body-size-indexed PVR, incorporating vasodilator-challenge reversibility, and ultimately prospective, multicenter confirmation,” Zayed said.