Prospective Comparison of Urinary Measured Creatinine Clearance With eGFR and Cystatin C Based Cis-eGFR, Including Kinetic eGFR in the Immediate Post-transplant Period With Prompt Allograft Function.

BACKGROUND: The estimated glomerular filtration rate (eGFR) and kinetic estimated glomerular filtration rate (KeGFR) have not been compared, with urinary measured creatinine clearance (mCrCl) or serum cystatin C (CysC) eGFR, soon after kidney transplantation (KTx) with prompt primary function. This study aims to compare post-KTx, urinary mCrCl, and eGFR CysC with eGFR and KeGFR. METHODS: Post-KTx, urine was collected every 12 hours from 25 of the 34 consenting subjects to calculate mCrCl and compare with Modification of Diet in Renal Disease (MDRD)-4, Jelliffe eGFR, Cockcroft-Gault creatinine clearance (CrCl), and KeGFR by Chen and Brater formulae. Serum CysC levels were also measured in the last 14 subjects to compare with creatinine, mCrCl, and eGFR CysC. RESULTS: At 12 to 96 hours post-KTx (n = 25), mCrCl was 55.8% to 13.6% higher than MDRD-4 eGFR. The mean CysC level (n = 14) was 58% to 14% lower than creatinine for up to 3.0 days post-KTx, with higher MDRD-4 eGFR CysC. Chen and Brater KeGFR were significantly lower than mCrCl and eGFR (Fig 1B, Table 1). Within 3 days post-KTx, a 50% decrease in creatinine provided ≥ 50 mL/min CrCl in 90% of cases (mean mCrCl 61.7 ± 22.8). This difference was greater when the initial creatinine was higher with the rapid decrease in creatinine. CONCLUSIONS: (1) Post-KTx eGFR/KeGFR formulae underestimated mCrCl. (2) Serum CysC levels were lower than creatinine, corresponding with higher eGFR CysC. (3) A 50% decrease from initial serum creatinine; mean mCrCl was 61.7 ± 22.8 mL/min, and 90% of them have mCrCl > 50 mL/min. Post-KTx, until creatinine is stabilized, recipients are often receiving subtherapeutic dosing of renally adjusted medications. More prospective studies are necessary, including radioisotope clearance.

Review of Sarcopenia and Testosterone Deficiency With Chronic Liver Disease and Postoperative Liver Transplant Utility of Short-Term Testosterone Replacement Therapy.

OBJECTIVES: Chronic liver disease is often associated with testosterone deficiency. However, testosterone replacement does not improve hepatic function or survival with diseased liver. So far, to our knowledge, testosterone replacement therapy after successful livertransplantforfunctional sarcopenia has not been studied. We had 3 goals: (1) define postoperative functional sarcopenia afterlivertransplant with serum testosterone level; (2) examine the role of short-term testosterone replacement therapy with active in-bed exercise of upper and lower extremity joints; and (3) correlate functional sarcopenia with skeletal muscle index and skeletal muscle density in relation to ascites, pleural effusion subtracted body mass index. MATERIALS AND METHODS: We evaluated 16 liver transplant recipients who had been receiving posttransplanttestosterone replacementtherapy with functional sarcopenia. Preoperative and postoperative demographics and laboratory and radiological data were retrieved; body mass index, skeletal muscle index, and skeletal muscle density were calculated. For this retrospective study, institutional review board approval was obtained before the electronic database was reviewed and analyzed. RESULTS: Mean testosterone level was 28.3 ng/dL (<5% of expected). Twelve patients received 1 dose, and the remaining 4 patients received >1 dose oftestosterone cypionate, 200 mg. Mean hospital stay was 26 days. Seven patients were discharged home, with the remaining patients to a rehabilitation facility or nursing home. One patient died from a cardiac event, and another patient died from recurrent metastatic malignancy. The 1-year and 5-year actuarial patient and graft survival rates were 93.8% and 87.5%, respectively. Overall, 5 patients were sarcopenic by skeletal muscle index, and 6 patients had poor muscle quality by skeletal muscle density. CONCLUSIONS: Testosterone deficiency after liver transplant exists with functional sarcopenia. Two- thirds of such recipients have low skeletal muscle index and/or have low skeletal muscle density. Short- term testosterone replacement therapy with in-bed active exercise provides 5-year patient and graft survival of 87.5%.

Review of Standardized Incidence Ratios (SIR) of non-lymphoid de novo malignancies after liver transplantation: Structured analysis of global differences.

INTRODUCTION: De Novo malignancy after liver transplantation (LTx) is the second most common cause of death in adult LTx recipients. The current report identifies differences in Standardized Incidence Ratios (SIR) for various non-lymphoid de novo malignancies by comparing and analyzing post LTx SIR for non-lymphoid de novo malignancies. MATERIAL AND METHODS: A thorough search of PubMed and Web of Science databases was conducted; 25 publications describing de novo malignancies post-LTx with SIR were identified. RESULTS: Overall SIR varied from 1.4 to 11.6 (median 2.4). Oropharyngeal/larynx (OPL), lung, colo-rectal, and kidney malignancies were more prevalent with higher SIR (median = 4.4, 1.9, 2.67, 2.5, respectively). Breast and prostate malignancies were also more prevalent with lower SIR (median = 0.9, 1.0, respectively). Pancreatic, central nervous system (CNS), melanoma, rare cancers and Kaposi's sarcoma were less prevalent (except in Italy and Sweden) but had much higher SIR (median = 2.6, 2.4, 2.02, 22.5 and 53.6, respectively). The overall higher SIR values are related to the age of the recipient, length of follow-up, the grouping of different organ systems, inclusion or exclusion of epidermal non-malacotic skin cancers, lymphoid malignancy, and occurrence of rare malignancies including Kaposi's sarcoma. CONCLUSION: OPL, lung, gastrointestinal, kidney, and bladder malignancies were more prevalent with higher SIR. Breast and prostate cancers were more prevalent with lower SIR. Pancreatic, CNS, melanoma, rare cancers and Kaposi's sarcoma were less prevalent with higher SIR. Age of the recipients, length of follow-up, and rare cancer types influence overall SIR values with some global differences.

Steroid-free maintenance immunosuppression using alemtuzumab in pediatric kidney transplantation: Long-term longitudinal follow-up.

BACKGROUND: There is a scarcity of long-term data on steroid-free immunosuppression using alemtuzumab in pediatric kidney transplantation (KTx). This study examines long-term outcomes with alemtuzumab without steroid maintenance therapy in pediatric KTx. METHODS: From July 2005 to June 2015, 71 pediatric KTx recipients received alemtuzumab without steroid maintenance. They were followed from 4.1 to 14.1 years post KTx. RESULTS: Patient survival: One child expired with a functioning graft from post-transplant lymphoproliferative disorder (PTLD). Patient survival was 98.6%. Graft survival: Eighteen grafts were lost (16 from chronic rejection). Graft survival at 5 and 10 years was 92.3% and 61.3%, respectively. Rejection: Twenty-three (32.4%) patients were free from T-cell-mediated rejection (TCMR), 16 (22.5%) had >3 episodes. Sixteen (22.5%) were treated for antibody-mediated rejection (AMR). Infection: Twenty-three children developed Epstein-Barr virus (EBV), 5 developed cytomegalovirus (CMV), and 20 developed BK virus infection. Four (5.6%) developed PTLD. Twenty-two (31.0%) required treatment for neutropenia. Growth parameters: Mean height and weight increased by 0.56 and 0.69 SDS (standard deviation score), respectively. Body mass index increased by 5.1 kg/m2 at 10 years. Less than 40% required antihypertensive medications at all-time points. CONCLUSION: Alemtuzumab, without corticosteroid maintenance, offers 98.6% patient survival at 14 years with five and 10-year graft survival of 92.3% and 61.3%, respectively. TCMR and AMR requiring treatment were 67.4% and 22.5%, respectively. CMV, EBV, and BK viremia rates were 7.0%, 32.4%, and 28.2%, respectively. Thirty-one percent were treated for neutropenia; 5.6% developed PTLD. There were improvements in growth parameters and blood pressure.

Renal Protective Effect of Everolimus in Liver Transplantation: A Prospective Randomized Open-Label Trial.

Renal dysfunction is associated with poor long-term outcomes after liver transplantation. We examined the renal sparing effect of everolimus (EVR) compared to standard calcineurin inhibitor (CNI) immunosuppression with direct measurements of renal function over 24 months. METHODS: This was a prospective, randomized, open-label trial comparing EVR and mycophenolic acid (MPA) with CNI and MPA immunosuppression. An Investigational New Drug Application (IND # 113882) was obtained with the Food and Drug Administration as EVR is only approved for use with low-dose tacrolimus. Serum creatinine, 24-hour urine creatinine clearance, iothalamate clearance, Cockcroft-Gault creatinine clearance (CrCl), and Modification of Diet in Renal Disease estimated glomerular filtration rate were prospectively measured at 4 study visits. Nonparametric statistical tests were used for analyses, including the Mann-Whitney U test for continuous outcomes and Pearson's chi-square test for binary outcomes. Effect size was measured using Cohen's d. Patients also completed quality of life surveys using the FACT-Hep instrument at each study visit. Comparison between the 2 groups was performed using the Student t test. RESULTS: Each arm had 12 subjects; 4 patients dropped out in the EVR arm and 1 in the CNI arm by 24 months. Serum creatinine (P = 0.015), Modification of Diet in Renal Disease estimated glomerular filtration rate (P = 0.013), and 24-hour urine CrCL (P = 0.032) were significantly better at 24 months with EVR. Iothalamate clearance showed significant improvement at 12 months (P = 0.049) and a trend toward better renal function (P = 0.099) at 24 months. There was no statistical significance with Cockcroft-Gault CrCl. Adverse events were not significantly different between the 2 arms. The EVR group also showed significantly better physical, functional, and overall self-reported quality of life (P = 0.01) at 24 months. CONCLUSIONS: EVR with MPA resulted in significant long-term improvement in renal function and quality of life at 24 months after liver transplantation compared with standard CNI with MPA immunosuppression.

Navigating Kidney Transplantation in the Early Phase of Coronavirus Disease 2019: Screening Patients With Reverse Transcriptase Polymerase Chain Reaction and Low-Radiation-Dose Chest Computed Tomography.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic of 2020 changed organ transplantation. All elective cases at our institution were postponed for approximately 3 months. Centers for Medicare and Medicaid Services considers organ transplant surgery a Tier 3b case, along with other high acuity procedures, recommending no postponement. Our transplant program collaborated with our transplant infectious disease colleagues to create a protocol that would ensure both patient and staff safety during these unprecedented times. METHODS: The living donor program was electively placed on hold until we had the proper protocols in place. Preoperative COVID-19 testing was required for all recipients and living donors. All patients underwent a rapid nasopharyngeal swab test. After testing negative by nasopharyngeal swab, recipients also underwent a low-radiation-dose computed tomography scan to rule out any radiographic changes suggestive of a COVID-19 infection. RESULTS: We performed 8 living donor and 9 deceased donor kidney transplants. In comparison, we performed 10 living donor and 4 deceased donor transplants during the same time period in the previous year. Our testing protocol enabled efficient use of all suitable organs offered during the viral pandemic. No recipients or living donors tested positive or developed COVID-19. CONCLUSIONS: Creation of a viral testing protocol, developed in conjunction with our infectious disease team, permitted kidney transplantation to be performed safely, and the number of deceased donor transplants increased considerably without adversely affecting our outcomes.

Liver Allografts From Older Donors With or Without Recovery of Thoracic Organs and Their Impact on Hepatic Graft and Patient Survival.

OBJECTIVES: Multiorgan procurement involving thoracic organs prolongs the liver recovery cross-clamp time. This may impact the outcome of hepatic allograft, more so in older donors (age > 60 years). We compared the outcomes of liver allografts from older donors with and without recovery of thoracic organs. MATERIALS AND METHODS: Using the Scientific Registry of Transplant Recipients database, we compared survival outcomes of 258 adults who received a liver allograft from older donors with thoracic organ recovery (group A) with 6006 patients who received liver allografts from older donor without thoracic organ recovery (group B). Furthermore, we performed a subgroup analysis matched for recipient and donor risk factors including presence of hypertension, diabetes mellitus, renal function, donor age, and use of inotropes. For the final analyses, there were 159 patients in group A and 468 in group B. RESULTS: The 1-month, 1-year, 3-year, and 5-year patient survival rates in group A were 95%, 91.6%, 70.1%, and 65.5% compared with 95%, 92%, 70%, and 57.7% in group B, respectively (P = .695). Graft survival rates for group A at the same time points were 91.5%, 81.0%, 71.7%, and 57.4% compared with 91.3%, 81.1%, 61.9%, and 50.4% in group B, respectively (P = .791). In the matched population, patient survival rates at 1 month, 1 year, 3 years, and 5 years were 95%, 83.1%, 77.1%, and 68.8% compared with 94.4%, 81.6%, 72.2%, and 66.8% in group B, respectively (P = .69). Graft survival rates at the same time points were 88.7%, 76.8%, 71.5%, and 63.1% in group A and 90.0%, 77.5%, 70.4%, and 62.5% in group B, respectively (P = .956). CONCLUSIONS: Liver procurement with or without recovery of thoracic organs from donors > 60 years old does not affect liver grafts and recipient outcomes in the short-term or long-term and should be encouraged.

Incidence of Post-Liver Transplant Hepatic Dysfunction After Sustained Virologic Response Following Direct-Acting Anti-Hepatitis C Therapy.

OBJECTIVES: Newly developed, direct-acting antiviral therapy is effective in over 90% of cases to eradicate hepatitis C virus infection. Direct-acting antiviral therapy is also effective in liver transplant recipients with recurrent hepatitis C virus infection. However, hepatic function after sustained virologic response in transplant recipients is unknown. Here, we aimed to uncover the incidence of hepatic dysfunction in this patient group at our center. MATERIALS AND METHODS: Our study included 40 consecutive (January 2014 to February 2016) and compliant posttransplant recipients who achieved sustained viral response from direct-acting antiviral therapy. Patients were investigated for incidence and causes of hepatic dysfunction. RESULTS: In our patient group, 4 (10%) experienced hepatic dysfunction with stable baseline immunosuppression, with 2 having drastic increases in alanine aminotransferase at 15 and 32 weeks after direct-acting antiviral therapy. Biopsies showed hepatitis, and both patients were treated with hydrocortisone, which increased their baseline immunosuppression. The 3rd patient had an increase in bilirubin at 21 weeks posttherapy, with biopsy showing macrovascular steatosis. The 4th patient had a rapid increase in bilirubin at 7 weeks after direct-acting antiviral therapy, with biopsy showing significant duct loss. CONCLUSIONS: During the study period, 10% of patients experienced hepatic dysfunction after sustained viral response. Presumed causative factors included partial immune reconstitution and nonalcoholic fatty liver disease.

Assessing cardiovascular risk in the prerenal transplant population: Comparison of myocardial perfusion imaging and coronary angiography with risk factor stratification.

INTRODUCTION: Patients with end-stage renal disease (ESRD) have a higher incidence of coronary artery disease (CAD). Hence, it is crucial to evaluate CAD before renal transplantation. This study compares the utility of pharmacologic single-photon emission computed-tomography (SPECT) imaging directly to coronary angiography for diagnosis of CAD with correlation to cardiovascular risk factors. METHOD: Retrospective review of asymptomatic renal failure patients who underwent both SPECT and coronary angiography to identify obstructive CAD between the years 2008-2016. Ninety-four ESRD subjects were evaluated. RESULTS: Myocardial perfusion SPECT study found, when compared to coronary angiography demonstrated for CAD, the sensitivity of 93.3% with a specificity of 73.4%. Importantly, the negative predictive value for coronary artery disease was 96%. With seven or more cardiac risk factors, 66.7% of patients had obstructive coronary artery disease. Among all the risk factors examined, patients with a previous history of coronary artery disease had a 68% risk of obstructive coronary artery disease. CONCLUSION: Comparing myocardial perfusion imaging SPECT findings with coronary angiography in patients with ESRD, a sensitivity of 93.3% and a specificity of 73% were observed. Of all the risk factors examined, patient with the previous history of CAD was the single most significant risk factor for CAD in 68% of cases.

Is there increased risk of hepatocellular carcinoma recurrence in liver transplant patients with direct-acting antiviral therapy?

BACKGROUND: Recently, a controversy has emerged: is the rate of recurrence of hepatocellular carcinoma (HCC) higher following treatment of hepatitis C virus (HCV) with direct-acting antiviral (DAA) therapy? However, the risk of HCC recurrence has not been studied in liver transplant (LTx) recipients who received DAA therapy. The aim of the present study is to compare the rate of HCC recurrence in LTx recipients who did or did not receive DAA therapy. PATIENTS AND METHODS: Sixty-three patients received LTx with HCC. Twenty-seven (42.9%) with HCV received DAA therapy (Group A), 20 (31.7%) with HCV did not receive DAA therapy (Group B), and 16 (25.4%) did not have HCV (Group C). RESULTS: In group A, three (11%), in group B, one (5%), and in group C, none had recurrence of HCC. Actuarial 4-year recurrence-free survival was 88.9, 95, and 100% in group A, B, and C, respectively (p = 0.37). Group A was subdivided into two groups for comparison with Group B: A1 included five patients who had end of treatment response (ETR) without sustained virological response (SVR), and A2 included 20 patients who achieved SVR. Three patients from A1 had HCC recurrence and no patients from A2 had HCC recurrence. (p = 0.0038; group A1, A2, and B). CONCLUSIONS: The rate of HCC recurrence in LTx patients with DAA therapy was significantly higher with ETR, without SVR, after DAA therapy compared to patients with SVR or patients who did not receive DAA therapy. LTx recipients with HCC receiving DAA therapy requires further studies.

Hepatitis C virus (HCV) RNA level in plasma and kidney tissue in HCV antibody-positive donors: Quantitative comparison.

Kidney transplant from donors with hepatitis C virus (HCV) antibody has been limited to HCV viremic recipients only, due to concern of the HCV transmission. However, the new antiviral medications provide an opportunity to expand the utilization of these donors. To study the risk of HCV transmission in kidney transplantation, we used discarded donor kidneys and determined HCV RNA levels by quantitative real-time PCR in bilateral (right and left) kidney biopsies and plasma from 14 HCV antibody-positive donors (sensitivity: 15 international unit (IU)/mL plasma; 1.8 IU/50 nL kidney). In three NAT-negative donors, HCV RNA was negative in plasma and kidney. In all 11 NAT-positive donors, HCV RNA was positive in plasma (range: 5807-19 134 177 IU/mL) but negative in six kidneys from four donors with plasma HCV RNA <1.5 million IU/µL. HCV RNA correlated between right and left kidneys (P = 0.75) and between kidney and plasma (r = 0.86). When normalized by volume, HCV RNA median (range) was 49 (0-957) IU/50 nL plasma and 1.0 (0-103) IU/50 nL kidney, significantly lower in kidney (P = 0.005) than in plasma (14-fold). Plasma HCV RNA can be used to predict the kidney HCV load. Future studies are needed if plasma/kidney HCV levels can be used to stratify donors for transmission risk and recipients for post-transplant management in extended utilization of HCV antibody-positive donors.

Axilloaxillary Arteriovenous Fistula Caused by Previous Penetrating Trauma.

BACKGROUND: Traumatic axilloaxillary arteriovenous (AV) fistulas are rare occurrences, with the predominance of AV fistulas in this region occurring as an alternative surgical intervention in patients who are undergoing hemodialysis. CASE REPORT: We describe the case of a young man with this condition caused by a previous penetrating trauma who had a delayed diagnosis primarily because of the infrequency of the clinical presentation. This is one of a few documented cases of axilloaxillary AV fistulas in the setting of trauma. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Axilloaxillary AV fistulas present with loud machinery like cardiac murmurs that can be similar to patients with coarctation of the aorta and patent ductus arteriosus; however, important clinical examination features can help distinguish the two conditions. Diagnosis is important in avoiding late-stage complications and more technically difficult surgical repairs.

Portal Hypertension: An Underestimated Entity?

OBJECTIVE: The aim of this study is to evaluate portal hypertension as an independent risk factor in general surgical procedures. BACKGROUND: Data on the impact of portal hypertension in general surgical outcomes has been limited. Published literature has focused mainly on its effect in liver surgery. The Child Pugh score and Model for End Stage Liver Disease are utilized for surgical risk assessment in liver disease but they do not accurately reflect degree of portal hypertension. METHODS: From 2005 to 2012, patients with esophageal varices (EV) in the National Surgical Quality Improvement Program (NSQIP) formed the portal hypertension cohort, and were case matched to patients without esophageal varices (NEV) based on sex, age, surgery type, and year of operation. Thirty day mortality and morbidity were analyzed using generalized estimating equations for binary outcomes. EV patients were also dichotomized by Model for End Stage Liver Disease (MELD) score (≤15 vs >15) and compared with NEV patients. RESULTS: One thousand five hundred and seventy-four EV patients were matched to 3148 NEV patients. In multivariable analysis, EV patients had a 3.01 higher odds of 30 day mortality (P < 0.001) and 1.28 higher odds of complications (P < 0.001) compared with NEV patients. EV patients with MELD >15 had 4.64 higher odds of death within 30 days (P < 0.001) and had 1.75 higher odds of complications within 30 days (P < 0.001) compared with NEV patients; EV patients with MELD 15 or less had 1.95 higher odds of 30 day mortality (P < 0.001) compared with NEV patients. CONCLUSIONS: Portal hypertension is associated with a significant mortality and morbidity risk in general surgery, and should not be underestimated even in patients with MELD 15 or less where the early mortality risk remained significant.

Donor-specific antibody to trans-encoded donor HLA-DQ heterodimer.

The majority of de novo donor specific HLA antibodies (DSAs) in transplant patients are directed to HLA-DQ antigens, which consist of a heterodimer of alpha and beta chains. Although a heterodimer can theoretically be cis- or trans-encoded, the sensitizing forms generally appear to be forms. DSA to DQ trans-heterodimer has never been reported. We reviewed 360 post-kidney transplant recipients (transplant: 2002-2013; follow-up: 5.6±3.3years). DQ DSA was detected in 46 of 57 patients who developed DSA. DSA specificity was consistent with donor mismatched DQ trans-heterodimers in three patients: DQ2.5 (DQB1*02, DQA1*05), DQ2.3 (DQB1*02, DQA1*03), and DQ4.3 (DQB1*04, DQA1*03). Two of them eventually lost grafts (2 and 5years later) with allograft nephropathy. In conclusion, post-transplant patients may develop DSA to donor DQ trans-heterodimers. Further studies are warranted to determine the clinical significance of such DSAs.

Do postliver transplant patients need thromboprophylactic anticoagulation?

Postoperative thromboprophylactic anticoagulation against Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) is standard of care with current evidence-based guidelines. However, majority of liver transplant (LT) patients have thrombocytopenia and/or prolonged INR before surgery. Studies or guidelines regarding role of prophylactic anticoagulation after LT are lacking. There is a need to balance the risk of thrombosis with significant hemorrhage, implying those needing transfusion or return to OR due to bleeding. We conclude that after LT, anticoagulation is not required routinely for DVT/PE prophylaxis. Rather, it is indicated in specific circumstances, chiefly for prophylaxis of hepatic artery thrombosis or portal vein thrombosis in cases with use of grafts, pediatric cases, small size vessels, Budd Chiari syndrome, amongst others.

Chronotropic incompetence on dobutamine stress echocardiography in candidates for a liver transplant.

OBJECTIVES: We evaluated dobutamine stress echocardiography as an initial screening test for a cardiac evaluation before a liver transplant. MATERIALS AND METHODS: We retrospectively examined 111 liver transplant candidates who had undergone previous cardiac evaluation; 30 of whom had undergone a liver transplant. RESULTS: Eighty patients (72.1%) completed a dobutamine stress echocardiography (41 chronotropically competent, 39 incompetent), while 31 patients (27.9%) required us to terminate early. Overall, 68 patients (61%) were on ß-blockers (21 required early dobutamine stress echocardiography termination, 30 chronotropically incompetent, and 17 competent). Patient results were normal. Thirty patients underwent a liver transplant. Among candidates requiring termination of early dobutamine stress echocardiography, posttransplant cardiac events included 1 fatal acute myocardial infarction, 1 nonfatal acute myocardial infarction, and 1 idiopathic cardiomyopathy. Among chronotropically incompetent patients, 2 patients had transient bradycardia, and among those who were chronotropically competent, 1 had refractory atrial fibrillation, and 1 had transient bradycardia. CONCLUSIONS: Nearly 50% of patients with end-stage liver disease may not reach the target heart rate. Early termination of dobutamine stress echocardiography because of cardiac symptoms or significant echocardiographic changes have more effect in predicting postoperative cardiac events, but further evaluation is required even if their target heart rate is close to that desired. Lower target heart rate may be acceptable in chronotropically incompetent individuals provided they are asymptomatic, have no echocardiographic changes, or cardiovascular risk factors, especially if they are on ß-blockers.