Mechanical Valves: Past, Present, and Future-A Review.

The mechanical valve was first invented in the 1950s, and since then, a wide variety of prostheses have been developed. Although mechanical valves have outstanding durability, their use necessitates life-long treatment with anticoagulants, which increases the risk of bleeding and thromboembolic events. The current guidelines recommend a mechanical prosthetic valve in patients under 50-60 years; however, for patients aged 50-70 years, the data are conflicting and there is not a clear-cut recommendation. In recent decades, progress has been made in several areas. First, the On-X mechanical valve was introduced; this valve has a lower anticoagulant requirement in the aortic position. Second, a potential alternative to vitamin K-antagonist treatment, rivaroxaban, has shown encouraging results in small-scale trials and is currently being tested in a large randomized clinical trial. Lastly, an innovative mechanical valve that eliminates the need for anticoagulant therapy is under development. We attempted to review the current literature on the subject with special emphasis on the role of mechanical valves in the current era and discuss alternatives and future innovations.

Minimal Learning Curve for Minimally Invasive Aortic Valve Replacement.

BACKGROUND: Minimally invasive aortic valve replacement (MiAVR) is an established technique for surgical aortic valve replacement (AVR). Although MiAVR was first described in 1993 and has shown good results compared with full sternotomy AVR (FSAVR) only a minority of patients undergo MiAVR. We recently started using MiAVR via an upper hemisternotomy. We aimed to examine the early results of our initial experience with this technique. METHODS: We compared 55 MiAVR patients with a historical cohort of 142 isolated FSAVR patients (December 2016-December 2022). The primary outcome was in-hospital mortality. Secondary outcomes included cardiopulmonary bypass (CPB) and cross-clamp times, blood product intake, in-hospital morbidity, and length of intensive care unit and hospital stay. RESULTS: There was no significant difference in preoperative characteristics, including age, laboratory values, and comorbidities. There was no significant difference between the groups regarding in-hospital mortality (FSAVR 3.52 vs. MiAVR 1.82%). There was no significant difference in CPB time (FSAVR 103.5 [interquartile range: 82-119.5] vs. MiAVR 107 min [92.5-120]), aortic cross-clamp time (FSAVR 81 [66-92] vs. MiAVR 90 min [73-99]), and valve size (FSAVR 23 [21-25] vs. MiAVR 23 [21-25]). The incidence of intraoperative blood products transfusion was significantly lower in the MiAVR group (10.91%) compared with the FSAVR group (25.35%, p = 0.03). CONCLUSION: Our findings further establish the possibility of reducing invasiveness of AVR without compromising patient safety and clinical outcomes. This is true even in the learning curve period and without requiring any significant change in the operative technique and dedicated equipment.

Transient time flow measurement in arterial grafts.

Coronary artery bypass grafting (CABG) is one of the foundations of treatment for coronary artery disease. While it has improved substantially since its inception more than 50 years ago, including a rising use of multiple arterial grafting, intraoperative quality assessment is yet to be disseminated as an integral part of the procedure. Herein we review the fundamentals of intraoperative quality assessment in CABG using transient time flow measurement (TTFM) with a focus on its use in arterial grafting.

The effect of COVID-19 vaccination on 30-day mortality after cardiac surgery - Insights from the Israel national registries.

Background: We compared the effect of perioperative COVID-19, before and after vaccination, on 30-day mortality after cardiac surgery. Methods: Data was extracted from several national registries. The study period was March 1st, 2020-March 31st, 2022. Results: 2594 adult patients underwent cardiac surgery before the availability of a universal COVID-19 vaccine. 33 patients were diagnosed with COVID-19 prior to surgery (mean age 58.3±10.0, mean length of time 73.6±60.1 days) and 7 patients were diagnosed with COVID-19 0-14 days after surgery (age 66.4±7.6). These were compared to 4426 patients who underwent cardiac surgery after the availability of a universal vaccine: 469 patients were diagnosed with COVID-19 prior to surgery (age 62.1±10.1, length of time 175.8±158.2) and 32 patients diagnosed with COVID-19 0-14 days after surgery (age 60.8±14.5). In patients diagnosed with COVID-19 prior to surgery, there was no excess 30-day mortality either before or after vaccination (1 (3.0%) vs. 57 (2.2%), respectively, P<0.8, and 8 (1.7%) vs. 87 (2.2%), respectively, P<0.5). Patients diagnosed with COVID-19 after surgery, but before vaccination, had significantly higher 30-day mortality compared to COVID-19 negative patients (2 (28.6%) vs. 56 (2.2%) respectively, P<0.0001). This excess mortality disappeared after universal vaccination (1 (3.1%) vs. 94 (2.1%) respectively, P<0.7). Conclusions: COVID-19, when diagnosed in the early post-operative period, was a risk factor for mortality before available vaccinations, but not after vaccination was widely available. Pre-surgery screening and post-surgical isolation is essential until vaccines are available. This data may be useful for patient management in future respiratory pandemics.

Implementation of a Short-term Treatment Protocol in Anemic Patients before Cardiac Surgery.

BACKGROUND: We assessed whether implementation of an immediate preoperative treatment in anemic patients could result in fewer perioperative packed red blood cell (PRBC) transfusions and improved outcomes in a real-world setting. METHODS: From January 1, 2020, to November 31, 2022, we implemented a perioperative protocol for anemic patients (hemoglobin (Hb) level in women <11.5 g/dL, men <12.5 g/dL), which included subcutaneous erythropoietin α, intravenous Iron, and intramuscular vitamin B12 (all given preoperatively) and per os iron and folic acid given once a day postoperatively. We retrospectively compared all patients receiving the protocol to all eligible patients who were operated upon in the 4 years prior to implementation of the protocol. Primary outcome was amount of PRBC transfusions during surgery and index admission. RESULTS: In the months after protocol implementation, 114 patients who received the treatment protocol were compared with 236 anemic patients in the 4 years prior to who did not receive the protocol. The treatment reduced total PRBC use (control group median 4 [2-7] units vs. treatment 2 [1-3] units, p < 0.0001) and the incidence of postoperative blood products transfusions (treatment group 58 patients, 50.88% vs. control group 177 patients, 75%, p < 0.0001). Hb prior to discharge was higher among the protocol group (treatment median 9 g/dL [8.3-9.5 g/dL] vs. control 8.6 g/dL [8.1-9.1 g/dL], p = 0.0081). CONCLUSION: Despite some differences compared with previously described protocols, the implementation of a perioperative treatment protocol for anemic patients was associated with a reduction in PRBC transfusion in a real-world setting.

Predictors and Long-Term Prognostic Significance of Acute Renal Function Change in Patients Who Underwent Surgical Aortic Valve Replacement.

There are few reports on short-term changes in renal function after surgical aortic valve replacement, and data are scarce regarding its impact on long-term outcomes. This is a retrospective study of patients who underwent isolated aortic valve replacement between 2009 and 2020 in four medical centers. Patients with end-stage renal disease were excluded. Renal function was assessed based on short-term changes. Multivariable regression models were used to identify predictors of improvement/deterioration. Cox proportional hazard models were used to assess survival trends. The study included 2402 patients, with a mean age of 69.3 years and a mean eGFR of 82.3 mL/min/1.73 m2. Short-term improvement rates were highest in stage 4 (24.4%) and stage 3 (16.8%) patients. Deterioration rates were highest in stage 1 (38.1%) and stage 2 (34.8%) patients. Deterioration in the chronic kidney disease stage was associated with a higher ten-year mortality (p < 0.001, HR 1.46); an improved stage trended toward improved survival (p = 0.14, HR 0.722). Patients with stage 3 and 4 kidney disease tended to remain stable or improve in the short term after aortic valve replacement while patients at stages 1 and 2 were at increased risk of deteriorating.

High sensitivity troponin-I threshold to predict perioperative myocardial infarction.

BACKGROUND: High-sensitivity Troponin I (hs-cTnI) has largely replaced conventional troponin assays in an effort to improve detection of myocardial infarction. However, the mean displacement of hs-cTnI following coronary artery bypass graft (CABG) and the optimal threshold to detect perioperative myocardial infarction (MI) is unclear. Our objective is to describe mean hs-cTnI values at 6-12 h post-CABG and to determine the highest specificity while maintaining 100% sensitivity hs-cTnI cut-off values for diagnosis of perioperative or type-5 MI. METHODS: Between 2016 and 2018, 374 patients underwent non-emergent, isolated CABG. Pre-operative and 6 h post-operative hs-cTnI values were recorded as well as ECG, echocardiographic and angiographic data. RESULTS: Of 374 patients, 151 (40.3%) had normal and 224 (59.7%) had elevated preoperative hs-cTnI. Patients with normal preoperative hs-cTnI had a mean 6 h hs-cTnI of 9193 ng/l or 270X the upper normal value. Eleven patients (7.3%) presented with post-operative MI with a mean 6 h hs-cTnI of 50,218 ng/l or 1477X the upper normal value. Patients with elevated preoperative hs-cTnI had a mean 6 h hs-cTnI of 9449 ng/l or 292X the upper normal value. Eleven patients (4.9%) who presented with post-operative MI had a mean 6 h hs-cTnI of 26,823 ng/l or 789X the upper normal value. CONCLUSIONS: We suggest hs-cTnI threshold of 80-fold in patients with normal pre-operative hs-cTnI and 2.7-fold in patients with elevated pre-operative hs-cTnI. These results have important implications for perioperative care and for surgical trial reporting.

Prognostic role of endocarditis in isolated tricuspid valve surgery. A propensity-weighted study.

OBJECTIVES: The role of the underlying etiology in isolated tricuspid valve surgery has not been investigated extensively in current literature. Aim of this study was to analyse outcomes of patients undergoing surgery due to endocarditis compared to other pathologies. METHODS: The SURTRI study is a multicenter study enrolling adult patients who underwent isolated tricuspid valve surgery (n = 406, 55 ± 16 y.o.; 56% female) at 13 international sites. Propensity weighted analysis was performed to compare groups (IE group n = 107 vs Not-IE group n = 299). RESULTS: No difference was found regarding the 30-day mortality (Group IE: 2.8% vs Group Not-IE = 6.8%; OR = 0.45) and major adverse events. Weighted cumulative incidence of cardiac death was significantly higher for patients with endocarditis (p = 0.01). The composite endpoint of cardiac death and reoperation at 6 years was reduced in the Group IE (63.2 ± 6.8% vs 78.9 ± 3.1%; p = 0.022). Repair strategy resulted in an increased late survival even in IE cases. CONCLUSIONS: Data from SURTRI study report acceptable 30-day results but significantly reduced late survival in the setting of endocarditis of the tricuspid valve. Multi-disciplinary approach, repair strategy and earlier treatment may improve outcomes.

Outcome of patients undergoing isolated tricuspid repair or replacement surgery.

OBJECTIVES: The interest in isolated tricuspid valve disease has rapidly increased recently. However, clinical trials and registry data are rare in the surgical literature. This study aimed to describe the early and long-term outcomes of a real-world experience in isolated tricuspid procedures comparing repair and replacement strategies. METHODS: The Surgical-Tricuspid study is a multicentre retrospective study that enrolled adult patients who had undergone isolated tricuspid valve surgery at 13 international sites. Propensity score-matched analysis was used to compare repair versus replacement. RESULTS: A cohort of 426 patients was enrolled [mean age: 55 (16) years; 56% female]. After matching, 175 comparable pairs were analysed. Preoperative left ventricular ejection fraction was 55(9) vs 56(9) (P = 0.8) while moderate-severe tricuspid regurgitation was present in 95% of cases. The 30-day mortality rate was 4.0% vs 8.0% in the repair and replacement groups, respectively (P = 0.115). The rates of re-exploration for bleeding (6.9% vs 13.1% P = 0.050), permanent pacemaker implantation (5.1% vs 12.0%; P = 0.022) and blood transfusion (46% vs 62%; P = 0.002) were higher in the replacement group. Cumulative survival rates at 3, 5 and 7 years in the repair group were 84 (3)%, 75 (4)% and 56 (9)% vs 71 (4)%, 66 (5)% and 58 (5)% in the replacement group (P = 0.001) while cumulative incidence for reoperation at 10 years did not differ between groups [repair 10 (1)% vs replacement 9 (1)%; P = 0.469]. CONCLUSIONS: The data from the Surgical-Tricuspid study reported a high risk for patients undergoing tricuspid surgery. Isolated valve repair offered reduced early and late mortality with no difference regarding reoperation rate when compared with replacement.

Biological or mechanical mitral valve replacement in patients 50-70 years of age-a propensity-adjusted analysis.

OBJECTIVES: The choice of a bioprosthetic valve (BV) over a mechanical valve (MV) in middle-aged adults in the mitral position is still under debate. Each valve type has benefits and drawbacks. We examined the mid-term survival of patients aged 50-70 years after BV versus MV mitral valve replacement (MVR). METHODS: We conducted a multicentre, retrospective analysis of patients aged 50-70 years undergoing MVR from 2005 to December 2018 in 4 medical centres in Israel. To control for between-group differences, we used propensity-adjusted analysis. The primary end point was all-cause mortality. Secondary end points included reoperation, cerebrovascular accident and bleeding. RESULTS: During the study period, 2125 MVR procedures were performed. Of these, 796 were eligible for inclusion [539 (67.8%) MV replacement and 257 (32.2%) BV]. The mean age was 61.0 ± 5.4. There were 287 deaths during 4890 person-years of follow-up. The adjusted hazard ratio was (1.13 [0.85-1.49], P = 0.672). There was also no difference in the secondary end points. Subgroup analysis of patients aged 50-64 years showed a higher risk of mortality with BV (hazard ratio = 1.50 [1.07-2.1], P = 0.018). Reoperation was a strong predictor of mortality during the study period (72.2%). CONCLUSIONS: In patients aged 50-70 years, we found an interaction between age and MV or BV outcomes-those younger than 65 years gained a mortality advantage with MV, while outcomes were similar in the 65-70 age group. this supports the current guidelines recommending using MV in patients <65 years of age.

Outcomes of cardiac surgery in patients with end-stage renal disease: Insights from the Israel national registries.

BACKGROUND: End-stage renal disease (ESRD) has been shown to be associated with increased mortality in patients undergoing cardiac surgery. We aimed to compare the short- and mid-term mortality after cardiac surgery of patients with dialysis-dependent ESRD (DD-ESRD) to patients with normal renal function (NRF), using national registries: the ESRD registry, the adult cardiac surgery registry (ACSR), and the National Mortality Registry. METHODS: The study population comprised 8207 adult patients who underwent either isolated coronary artery bypass grafting (CABG), isolated aortic valve replacement (AVR), isolated mitral valve replacement (MVR), or CABG + valve-related procedure, between January 2017 and April 2019. Data were retrospectively extracted and reported to the ACSR by the department of medical records of each medical center. RESULTS: One hundred and four DD-ESRD patients (mean age 63.2 ± 8.8 years, 83.7% males) were compared with 8103 NRF patients (mean age 64.9 ± 9.8 years, 77.6% males). Median follow-up for the total cohort was of 32.0 months (IQR; 25.0, 40.0). In DD-ESRD compared to NRF patients, 30-day mortality was higher (14.4% vs. 2.3%, respectively, p = 0.0001) and 4-year survival was significantly lower (44% ± 0.06 vs. 91% ± 0.04, respectively, p = 0.0001). Fifty-three percent of DD-ESRD 30-day mortality was caused by sepsis. Risk factors associated with reduced midterm survival included: DD-ESRD patients (HR = 4.7, 95% CI; 1.2-18.2), MVR procedure (HR = 1.5, 95% CI; 1.04-2.1) and combined CABG + valve-related procedure (HR = 1.6, 95% CI; 1.2-2.04). CONCLUSIONS: Preoperative DD-ESRD was associated with a significant increase in 30-day and mid-term mortality after cardiac surgery. The highest mortality rate was observed in valvular and combined procedures.

Leadless pacemaker implantation under direct visualization during valve surgery.

OBJECTIVE: The leadless cardiac pacemaker is typically implanted percutaneously and has been widely used for patients who have already undergone valve surgery. We sought to determine the feasibility and safety of implanting the leadless pacemaker under direct visualization during valve surgery. METHODS: We performed a retrospective analysis of consecutive adult patients (n = 15) who underwent implantation of a leadless pacemaker under direct visualization at the time of valve surgery. Indications for single-chamber pacing were sick sinus syndrome with pauses (53.3%), atrial fibrillation with slow ventricular rates (13.3%) or complete heart block (6.6%), and elevated risk for postoperative heart block (26.6%). Leadless pacemaker performance and pacing percentage were assessed. RESULTS: Patients' age was 67.5 ± 17 years, 6 patients (40%) were male, and 14 patients (93%) had atrial fibrillation. Isolated tricuspid valve replacement was performed in 5 patients (33.3%), and the remainder underwent multivalve surgery that included concomitant tricuspid valve repair/replacement. In 93% of the patients (n = 14), the immediate post-cardiopulmonary bypass pacing thresholds were normal (≤2.0 V at 0.24 ms) and normalized in the remaining patient by the next morning. The impedance/sensing values were normal and stable through follow-up (151 ± 119 days) in all patients. Reliable leadless pacemaker performance allowed for deferral of temporary epicardial wires in 11 patients (73%). There were no procedural complications or device malfunction. CONCLUSIONS: Leadless cardiac pacemaker implantation during valve surgery is feasible and safe. This hybrid approach to pacing may simplify the perioperative management of patients undergoing valve surgery who have an indication for single-chamber pacing.

Beating Versus Arrested Heart Isolated Tricuspid Valve Surgery: Long-term Outcomes.

BACKGROUND: Isolated tricuspid valve (TV) surgery is a rare procedure generally considered at high risk for perioperative mortality and poor long-term outcomes. Surgical treatment can be performed with either an arrested heart (AH) or beating heart (BH) technique. The aim of this study was to compare the outcomes of isolated tricuspid surgery with 2 different approaches. METHODS: The Surgical-Tricuspid Study is a multicenter international retrospective study enrolling adult patients who underwent isolated TV procedures (n = 406; age 56 ± 16 years; 56% female) at 13 international sites. The AH and BH strategies were performed in 253 and 153 patients, respectively. Propensity score-matched analysis was used to compare groups. RESULTS: After matching, 129 pairs were obtained and analyzed. The 30-day mortality rate was 6.2% versus 5.0% in the AH and BH groups, respectively (P = .9). The rates of acute renal failure requiring replacement therapy (10% versus 3%; P = .02) and stroke (1.6% versus 0%; P = .08) were numerically higher in the AH group. The 6-year survival rate was 67% ± 6% versus 78% ± 5% in the AH and BH groups, respectively (P = .18), whereas freedom from cardiac death was 75% ± 5% versus 84% ± 4% (P = .21). The 6-year composite cardiac end point of cardiac death and reoperation rate was 60% ± 9% versus 86% ± 5% (P = .024) comparing AH-TV replacement and BH-TV repair groups. CONCLUSIONS: Isolated TV surgery performed with a BH strategy is a safe option and resulted in a trend of increased long-term survival and freedom from reoperation compared with the standard AH technique. Patients undergoing BH valve repair had the best long-term outcome.

Midterm Results of Isolated Tricuspid Valve Replacement-Implications for Clinical Decision Making.

BACKGROUND: Isolated tricuspid valve replacement (TVR) is considered high-risk surgery. We investigated our outcomes of TVR with the aim of identifying variables that may influence morbidity and mortality of isolated TVR compared with combined TVR and left-sided valve surgery. METHODS: Retrospective analysis of patients undergoing TVR surgery. The primary endpoint was long-term mortality. The association of postoperative outcomes with isolated compared with combined replacement was analyzed. The association between type of surgery and mortality over time was evaluated using Cox proportional hazards regression models to estimate the hazard ratio. RESULTS: Overall, 70 patients underwent TVR. Mean age was 61 ± 12 years and 74% (52 of 70) were women. About two thirds (61%) of the study population had a diagnosis of rheumatic heart disease and 8% (6 of 70) had previous infectious endocarditis. Atrial fibrillation was prevalent (86%, 60 of 70). Comorbidities were similar between groups. Tricuspid valve replacement combined with left-sided valvular surgery was performed in 37 patients (53%), and isolated replacement in 33 patients (47%). Previous cardiac surgery was common (40 patients, 57%). One-month survival rate was 94.3% (66 of 70). During a median follow-up period of 3.6 years, 12 patients (17%) died. The cumulative 5-year survival tended to be lower among patients with isolated TVR compared with patients having combined surgery. CONCLUSIONS: We showed that TVR can be performed with good outcomes. Isolated TVR did not increase morbidity and mortality when patients are referred for surgery early, including after previous sternotomy. This finding should perhaps lead to a more aggressive approach toward patients requiring isolated replacement.

Surgical ablation in rheumatic heart disease-Uncharted territory.

BACKGROUND: Atrial fibrillation is a common arrhythmia with a large impact on society and on patients. Rheumatic valve disease is still prevalent in low- and medium-income countries. Performing surgical ablation during surgery for mitral valve disease has been shown to restore sinus rhythm in most patients. AIMS, MATERIALS AND METHODS: In this issue of the Journal of Cardiac Surgery, Ma et al., publish a meta-analysis of surgical ablation in patients with rheumatic heart disease (RHD). RESULTS: They found no difference in short-term outcomes with a higher incidence of restoration to sinus rhythm. In mid- to long-term follow-up, there was no difference in mortality with a signal towards more permanent pacemaker implantation. DISCUSSION AND CONCLUSION: Despite some inherent limitations and some methodological flows, this meta-analysis has important insights and is valuable for surgeons taking care of patients with RHD.

Mechanical vs Bioprosthetic Aortic Valve Replacement in Patients Younger Than 70 Years of Age: A Hazard Ratio Meta-analysis.

BACKGROUND: The choice between mechanical valves (MVs) and bioprosthetic valves (BVs) in patients undergoing aortic valve surgery is complex, requiring a balance between the inferior durability of BV and the indicated long-term anticoagulation therapy with MV. This is especially challenging in the middle age group (< 70 years), which has seen an increased use of BV over recent years. METHODS: A meta-analysis of randomised controlled trials (RCTs), observational studies using propensity score matching (PSM) and inverse probability weighting (IPW) was conducted to examine the clinical outcomes of patients < 70 years of age undergoing aortic valve replacement. The primary outcome was overall long-term mortality. Secondary outcomes included bleeding events, reoperation, systemic thromboembolism, and cerebrovascular accident. RESULTS: Fifteen studies (1 RCT, 12 PSM studies, and 2 IPW studies; aggregated sample size 16,876 patients) were included. Median follow-up was 7.8 years. Mortality was higher with BVs vs MVs (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.00-1.49), as was reoperation (HR 3.05, 95% CI 2.22-4.19). Bleeding risk was lower with BVs (HR 0.58, 95% CI 0.48-0.69), and the risk of stroke was similar in both valve types (HR 0.96, 95% CI 0.83-1.11) CONCLUSIONS: This broadest meta-analysis comparing BV and MV suggests a survival benefit for MVs in patients < 70 years of age. This should lead to reassessment of current patterns used in the choice of valves for patients < 70 among the cardiothoracic surgery community.

Pericardial constriction with calcified cystic mass compressing the right ventricle and right coronary artery.

Constrictive pericarditis is characterized by fibrosis and calcification of the pericardium that progressively impair the diastolic filling of the heart, causing heart failure. Uncommonly, pericardial constriction may be localized leading to a focal cystic mass formation that may compress nearby cardiac structures. We describe a unique case of a patient presenting with right heart failure due to idiopathic calcific constrictive pericarditis that was associated with a large pericardial cystic mass compressing the right ventricular free wall. This led to reduced cardiac output and possibly severe focal stenosis of the proximal right coronary artery that was resolved after pericardiectomy, the only definitive treatment for chronic progressive constrictive pericarditis. .

Transit time flow measurement of coronary bypass grafts before and after protamine administration.

BACKGROUND: Intraoperative graft assessment with tools like Transit Time Flow Measurement (TTFM) is imperative for quality control in coronary surgery. We investigated the variation of TTFM parameters before and after protamine administration to identify new benchmark parameters for graft quality assessment. METHODS: The database of the REQUEST ("REgistry for QUality AssESsmenT with Ultrasound Imaging and TTFM in Cardiac Bypass Surgery") study was retrospectively reviewed. A per graft analysis was performed. Only single grafts (i.e., no sequential nor composite grafts) where both pre- and post-protamine TTFM values were recorded with an acoustical coupling index > 30% were included. Grafts with incomplete data and mixed grafts (arterio-venous) were excluded. A second analysis was performed including single grafts only in the same MAP range pre- and post- protamine administration. RESULTS: After adjusting for MAP, we found a small increase in MGF (29 mL/min to 30 mL/min, p = 0.009) and decrease in PI (2.3 to 2.2, p <  0.001) were observed after the administration of protamine. These changes were especially notable for venous conduits and for CABG procedures performed on-pump. CONCLUSION: The small changes in TTFM parameters observed before and after protamine administration seem to be clinically irrelevant, despite being statistically significant in aggregate. Our data do not support a need to perform TTFM measurements both before and after protamine administration. A single TTFM measurement taken either before or after protamine may suffice to achieve reliable data on each graft's performance. Depending on the specific clinical situation and intraoperative changes, more measurements may be informative. TRIAL REGISTRATION: Clinical Trials Number: NCT02385344 , registered February 17th, 2015.