Kirklin Clinic

BACKGROUND: Since the initial utilization of heart transplantation as therapy for end-stage pediatric heart disease, improvements have occurred in outcomes with heart transplantation and surgical therapies for congenital heart disease along with the application of medical therapies to pediatric heart failure that have improved outcomes in adults. These events justify a reevaluation of the indications for heart transplantation in congenital heart disease and other causes of pediatric heart failure. METHODS AND RESULTS: A working group was commissioned to review accumulated experience with pediatric heart transplantation and its use in patients with unrepaired and/or previously repaired or palliated congenital heart disease (children and adults), in patients with pediatric cardiomyopathies, and in pediatric patients with prior heart transplantation. Evidence-based guidelines for the indications for heart transplantation or retransplantation for these conditions were developed. CONCLUSIONS: This evaluation has led to the development and refinement of indications for heart transplantation for patients with congenital heart disease and pediatric cardiomyopathies in addition to indications for pediatric heart retransplantation.

BACKGROUND: The value of transesophageal echocardiography in the assessment of patients with aortic dissection was studied. METHODS AND RESULTS: Group 1 (34 patients) represented all patients studied at our institution with this technique in whom aortic dissection was proven by aortography, surgery, or autopsy. Group 2 (27 patients) represented all patients studied with this technique at our institution in whom aortic dissection was excluded by aortography. Transesophageal echocardiography made a correct diagnosis of aortic dissection in 33 of 34 patients (sensitivity, 97%; specificity, 100%). It also correctly demonstrated the type of dissection in all 29 patients with aortographic or surgical proof. On the other hand, computed tomography scanning, performed in 24 of 34 patients in group 1, made a correct diagnosis in only 67% of patients and misclassified the type of dissection in 33%. Transesophageal echocardiography correctly identified involvement of the coronary arteries by aortic dissection in six of seven patients as well as absence of both left and right coronary artery involvement in 10 patients with aortic dissection. This technique was also useful in detecting communications between the true and false lumens, presence of thrombi in the false lumen, and, in two patients, localized dissection rupture with formation of a false aneurysm. In both groups 1 and 2, transesophageal echocardiography correctly identified patients with moderate to severe aortic regurgitation. CONCLUSIONS: Transesophageal echocardiography is very useful in the assessment of aortic dissection.

Heart transplantation has become a standard therapy option for advanced heart failure. The translation of heart transplantation from innovative experiments to long-term clinical success has married prescient insights with discipline and organization in the domains of surgical techniques, organ preservation, immunosuppression, organ donation and transplantation logistics, infection control, and long-term graft surveillance. This review explores the key milestones of the past 50 years of heart transplantation and discusses current challenges and promising innovations on the clinical horizon.

OBJECTIVE: To compare the safety and efficacy of insulin aspart (IAsp), buffered regular insulin (BR), and insulin lispro administered by continuous subcutaneous insulin infusion (CSII) in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: After completing a 4-week run-in period with BR, 146 adult patients with type 1 diabetes (with pretrial CSII experience) were randomly assigned (2:2:1) to CSII treatment with IAsp, BR, or lispro for 16 weeks in a multicenter, open-label, randomized, parallel-group study. Bolus insulin doses were administered 30 min before meals (BR) or immediately before meals (IAsp or lispro). RESULTS: Treatment groups had similar baseline HbA(1c) (7.3% +/- 0.7 for IAsp, 7.5% +/- 0.8 for BR, and 7.3% +/- 0.7 for lispro). After 16 weeks of treatment, HbA1c values were relatively unchanged from baseline, and the mean changes in baseline HbA1c values were not significantly different between the three groups (0.00 +/- 0.51, 0.15 +/- 0.63, and 0.18 +/- 0.84 for the IAsp, BR, and lispro groups, respectively). The rates of hypoglycemic episodes (blood glucose <50 mg/dl) per patient per month were similar (3.7, 4.8, and 4.4 for the IAsp, BR, and lispro groups, respectively). Clogs/blockages in pumps or infusion sets were infrequent; most subjects (76, 83, and 75% in the IAsp, BR, and lispro groups, respectively) had < or = 1 clog or blockage per 4 weeks during the trial. CONCLUSIONS: Insulin aspart in CSII was as efficacious and well tolerated as BR and lispro and is a suitable insulin for continuous subcutaneous insulin infusion using external pumps.

PURPOSE: We describe the first-in-human dose-escalation trial for ALRN-6924, a stabilized, cell-permeating peptide that disrupts p53 inhibition by mouse double minute 2 (MDM2) and MDMX to induce cell-cycle arrest or apoptosis in TP53-wild-type (WT) tumors. PATIENTS AND METHODS: Two schedules were evaluated for safety, pharmacokinetics, pharmacodynamics, and antitumor effects in patients with solid tumors or lymphomas. In arm A, patients received ALRN-6924 by intravenous infusion once-weekly for 3 weeks every 28 days; arm B was twice-weekly for 2 weeks every 21 days. RESULTS: Seventy-one patients were enrolled: 41 in arm A (0.16-4.4 mg/kg) and 30 in arm B (0.32-2.7 mg/kg). ALRN-6924 showed dose-dependent pharmacokinetics and increased serum levels of MIC-1, a biomarker of p53 activation. The most frequent treatment-related adverse events were gastrointestinal side effects, fatigue, anemia, and headache. In arm A, at 4.4 mg/kg, dose-limiting toxicities (DLT) were grade 3 (G3) hypotension, G3 alkaline phosphatase elevation, G3 anemia, and G4 neutropenia in one patient each. At the MTD in arm A of 3.1 mg/kg, G3 fatigue was observed in one patient. No DLTs were observed in arm B. No G3/G4 thrombocytopenia was observed in any patient. Seven patients had infusion-related reactions; 3 discontinued treatment. In 41 efficacy-evaluable patients with TP53-WT disease across both schedules the disease control rate was 59%. Two patients had confirmed complete responses, 2 had confirmed partial responses, and 20 had stable disease. Six patients were treated for >1 year. The recommended phase 2 dose was schedule A, 3.1 mg/kg. CONCLUSIONS: ALRN-6924 was well tolerated and demonstrated antitumor activity.

PURPOSE The ATEMPT trial was designed to determine if treatment with trastuzumab emtansine (T-DM1) caused less toxicity than paclitaxel plus trastuzumab (TH) and yielded clinically acceptable invasive disease-free survival (iDFS) among patients with stage I human epidermal growth factor receptor 2–positive (HER2+) breast cancer (BC). METHODS Patients with stage I centrally confirmed HER2+ BC were randomly assigned 3:1 to T-DM1 or TH and received T-DM1 3.6 mg/kg IV every 3 weeks for 17 cycles or T 80 mg/m 2 IV with H once every week × 12 weeks (4 mg/kg load →2 mg/kg), followed by H × 39 weeks (6 mg/kg once every 3 weeks). The co-primary objectives were to compare the incidence of clinically relevant toxicities (CRTs) in patients treated with T-DM1 versus TH and to evaluate iDFS in patients receiving T-DM1. RESULTS The analysis population includes all 497 patients who initiated protocol therapy (383 T-DM1 and 114 TH). CRTs were experienced by 46% of patients on T-DM1 and 47% of patients on TH ( P = .83). The 3-year iDFS for T-DM1 was 97.8% (95% CI, 96.3 to 99.3), which rejected the null hypothesis ( P &lt; .0001). Serially collected patient-reported outcomes indicated that patients treated with T-DM1 had less neuropathy and alopecia and better work productivity compared with patients on TH. CONCLUSION Among patients with stage I HER2+ BC, one year of adjuvant T-DM1 was associated with excellent 3-year iDFS, but was not associated with fewer CRT compared with TH.

Background. The aims of this study were to evaluate the efficacy of US Food and Drug Administration-approved drugs in genetically engineered pig-to-baboon kidney xenotransplantation and compare the results with those using an anti-CD40 monoclonal antibody (mAb)-based regimen. Methods. Ten life-supporting kidney transplants were carried out in baboons using α1,3-galactosyltransferase gene-knockout/CD46 pigs with various other genetic manipulations aimed at controlling coagulation dysregulation. Eight transplants resulted in informative data. Immunosuppressive therapy consisted of induction with antithymocyte globulin and anti-CD20mAb, and maintenance based on either (1) CTLA4-Ig and/or tacrolimus (+rapamycin or mycophenolate mofetil) ( GroupA [US Food and Drug Administration-approved regimens], n = 4) or (2) anti-CD40mAb + rapamycin ( GroupB , n = 4). All baboons received corticosteroids, interleukin-6R blockade, and tumor necrosis factor-α blockade. Baboons were followed by clinical and laboratory monitoring of kidney function, coagulation, and immune parameters. At euthanasia, morphological and immunohistochemical studies were performed on the kidney grafts. Results. The median survival in GroupB was 186 days (range 90–260), which was significantly longer than in GroupA ; median 14 days (range 12–32) ( P &lt; 0.01). Only GroupA baboons developed consumptive coagulopathy and the histopathological features of thrombotic microangiopathic glomerulopathy and interstitial arterial vasculitis. Conclusions. Recognizing that the pig donors in each group differed in some genetic modifications, these data indicate that maintenance immunosuppression including anti-CD40mAb may be important to prevent pig kidney graft failure.

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OBJECTIVE: Considerable research indicates that both high levels of anxiety and female sex are associated with increased sensitivity to experimental pain and greater experience of clinical pain. In general, however, previous research has not investigated the joint effects of sex and anxiety on pain responses. A single previous laboratory-based study indicated that anxiety was inversely related to pain thresholds among men but not among women. The present study examined the relation between pain-related anxiety and adjustment to chronic pain in a sex-dependent manner. DESIGN AND SETTING: A total of 215 (114 women, 101 men) chronic pain patients referred to a multidisciplinary treatment center completed questionnaires assessing anxiety and adjustment to chronic pain. RESULTS: Results generally supported the previous laboratory-based finding indicating that an inverse relation between anxiety and adjustment to chronic pain was present only among male patients. Although male patients with high pain-related anxiety reported greater pain severity, greater interference of pain, and lower levels of daily activity than male patients with low anxiety, this effect was not present among female patients. Moreover, the effects of pain-related anxiety on adjustment to chronic pain were not attributable to either hypervigilance or use of passive coping strategies. Potential explanations and implications for the present findings are discussed.

Thrombotic and bleeding complications have historically been major causes of morbidity and mortality in pediatric ventricular assist device (VAD) support. Standard anticoagulation with unfractionated heparin is fraught with problems related to its heterogeneous biochemical composition and unpredictable pharmacokinetics. We sought to describe the utilization and outcomes in children with paracorporeal VAD support who are treated with direct thrombin inhibitors (DTIs) antithrombosis therapy. Retrospective multicenter review of all pediatric patients (aged <19 years) treated with a DTI (bivalirudin or argatroban) on paracorporeal VAD support, examining bleeding and thrombotic adverse events. From May 2012 to 2018, 43 children (21 females) at 10 centers in North America, median age 9.5 months (0.1-215 months) weighing 8.6 kg (2.8-150 kg), were implanted with paracorporeal VADs and treated with a DTI. Diagnoses included cardiomyopathy 40% (n = 17), congenital heart disease 37% (n = 16; single ventricle n = 5), graft vasculopathy 9% (n = 4), and other 14% (n = 6). First device implanted included Berlin Heart EXCOR 49% (n = 21), paracorporeal continuous flow device 44% (n = 19), and combination of devices in 7% (n = 3). Adverse events on DTI therapy included; major bleeding in 16% (n = 7) (2.6 events per 1,000 patient days of support on DTI), and stroke 12% (n = 5) (1.7 events per 1,000 patient days of support on DTI). Overall survival to transplantation (n = 30) or explantation (n = 8) was 88%. This is the largest multicenter experience of DTI use for anticoagulation therapy in pediatric VAD support. Outcomes are encouraging with lower major bleeding and stroke event rate than that reported in literature using other anticoagulation agents in pediatric VAD support.

OBJECTIVE: To determine whether a significant number of patients with hyperparathyroidism remain undiagnosed and untreated. BACKGROUND: Failure to diagnose primary hyperparathyroidism and refer patients to surgeons leads to impaired quality of life and increased costs. We hypothesized that many patients with hyperparathyroidism would be untreated due to not considering the diagnosis, inadequate evaluation of hypercalcemia, and under-referral to surgeons. METHODS: We reviewed administrative data on 682,704 patients from a tertiary referral center between 2011 and 2015, and identified hypercalcemia (>10.5 mg/dL) in 10,432 patients. We evaluated whether hypercalcemic patients underwent measurement of parathyroid hormone (PTH), had documentation of hypercalcemia/hyperparathyroidism, or were referred to surgeons. RESULTS: The mean age of our cohort was 54 years, with 61% females, and 56% whites. Only 3200 (31%) hypercalcemic patients had PTH levels measured, 2914 (28%) had a documented diagnosis of hypercalcemia, and 880 (8%) had a diagnosis of hyperparathyroidism in the medical record. Only 592 (22%) out of 2666 patients with classic hyperparathyroidism (abnormal calcium and PTH) were referred to surgeons. CONCLUSIONS: A significant proportion of patients with hyperparathyroidism do not undergo appropriate evaluation and surgical referral. System-level interventions which prompt further evaluation of hypercalcemia and raise physician awareness about hyperparathyroidism could improve outcomes and produce long-term cost savings.

Background: Our current understanding of right heart failure (RHF) post-left ventricular assist device (LVAD) is lacking. Recently, a new Interagency Registry for Mechanically Assisted Circulatory Support definition of RHF was introduced. Based on this definition, we investigated natural history, risk factors, and outcomes of post-LVAD RHF. Methods: Patients implanted with continuous flow LVAD between June 2, 2014, and June 30, 2016 and registered in the Interagency Registry for Mechanically Assisted Circulatory Support/Society of Thoracic Surgeons Database were included. RHF incidence and predictors, and survival after RHF were assessed. The manifestations of RHF which were separately analyzed were elevated central venous pressure, peripheral edema, ascites, and use of inotropes. Results: Among 5537 LVAD recipients (mean 57±13 years, 49% destination therapy, support 18.9 months) prevalence of 1-month RHF was 24%. Of these, RHF persisted at 12 months in 5.3%. In contrast, de novo RHF, first identified at 3 months, occurred in 5.1% and persisted at 12 months in 17% of these, and at 6 months occurred in 4.8% and persisted at 12 months in 25%. Higher preimplant blood urea nitrogen (ORs,1.03–1.09 per 5 mg/dL increase; P &lt;0.0001), previous tricuspid valve repair/replacement (ORs, 2.01–10.09; P &lt;0.001), severely depressed right ventricular systolic function (ORs,1.17–2.20; P =0.004); and centrifugal versus axial LVAD (ORs,1.15–1.78; P =0.001) represented risk factors for RHC incidence at 3 months. Patients with persistent RHF at 3 months had the lowest 2-year survival (57%) while patients with de novo RHF or RHF which resolved by 3 months had more favorable survival outcomes (75% and 78% at 2 years, respectively; P &lt;0.001). Conclusions: RHF at 1 or 3 months post-LVAD was a common and frequently transient condition, which, if resolved, was associated with relatively favorable prognosis. Conversely, de novo, late RHF post-LVAD (&gt;6 months) was more frequently a persistent disorder and associated with increased mortality. The 1-, 3-, and 6-month time points may be used for RHF assessment and risk stratification in LVAD recipients.

2505 Background: ALRN-6924 is a cell-penetrating stapled alpha-helical peptide designed to equipotently disrupt the interaction between the p53 tumor suppressor protein and its endogenous inhibitors, murine double minute X (MDMX) and 2 (MDM2). For TP53 wild-type (WT) tumors, pharmacological disruption of this interaction offers a means to restore p53-dependent cell cycle arrest and apoptosis, resulting in antitumor efficacy via a novel mechanism. Methods: The study evaluated safety, PK, PD and anti-tumor effects of ALRN-6924 in patients (pts) with advanced solid tumors or lymphomas in a standard 3+3 design. Pts received ALRN-6924 IV once weekly for 3 consecutive wks on a 28-day cycle (arm A), or 2/wk for 2 consecutive wks on a 21-day cycle (arm B). Results: As of Dec 2016, 69 pts were enrolled with median age 61 yrs (25-78). Pts received a median of 2 (1-19) cycles in arm A [0.16-4.4 mg/kg] and 3 (1-19) cycles in arm B [0.32-2.7 mg/kg]. ALRN-6924 showed a t 1/2 of 5.5 hours, dose-dependent PK, and an increase in serum macrophage inhibitory cytokine-1. Treatment-related AEs seen in 96% of pts were primarily grade 1 and 2; most frequent were GI side effects, fatigue, anemia, and headache. DLTs were G3 fatigue at 3.1 mg/kg, and G3 hypotension, G3 alkaline phosphatase elevation, G3 anemia and G4 neutropenia at 4.4 mg/kg all in 5 pts in arm A. No G3/4 thrombocytopenia was observed. All DLTs resolved with dose hold. Infusion-related reactions were seen in 7 pts, with 3 treatment discontinuations. The RP2D was determined to be at MTD: 3.1 mg/kg QW for 3 wks every 28 days. In 55 pts evaluable for efficacy, disease control rate (DCR) was 45%, including 2 CR (Peripheral T-cell Lymphoma [PTCL], Merkel Cell Carcinoma), 2 PRs (Colorectal Cancer, Liposarcoma) and 21 pts with SD. In WT TP53 pts who initiated ALRN-6924 at ≥0.8 mg/kg, DCR was 57%. 9 pts remain on treatment post data cutoff including 3 pts exceeding 1 year of treatment. Conclusions: ALRN-6924 was well tolerated and demonstrated intriguing anti-tumor activity in this first-in-human phase I trial. An expansion phase IIa cohort in PTCL opened in August 2016 using 3.1 mg/kg (arm A) and is currently enrolling. Clinical trial information: NCT02264613.

Background: Ischemic and hemorrhagic cerebrovascular accidents remain common among patients with centrifugal-flow left ventricular assist devices, despite improvements in survival and device longevity. We compared the incidence of neurologic adverse events (NAEs) associated with 2 contemporary centrifugal-flow left ventricular assist devices: the Abbott HeartMate3 (HM3) and the Medtronic HeartWare HVAD (HVAD). Methods: Using the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs), we collected data on adult patients who received a centrifugal-flow left ventricular assist device as a primary isolated implant between January 1, 2017, and September 30, 2019. Major NAEs were defined as transient ischemic attack, ischemic cerebrovascular accident, or hemorrhagic cerebrovascular accident. The association of HVAD with risk of NAE in the first year after implant was evaluated using propensity score matching to balance for preimplant risk factors. After matching, freedom from first major NAE in the HM3 and HVAD cohorts was compared with Kaplan-Meier curves. A secondary analysis using multivariable multiphase hazard models was used to identify predictors of NAE, which uses a data-driven parametric fit of the early declining and constant phase hazards and the associations of risk factor with either phase. Results: Of 6205 included patients, 3129 (50.4%) received the HM3 and 3076 (49.6%) received the HVAD. Median follow-up was 9 and 12 months (HM3 and HVAD, respectively). Patients receiving HVAD had more major NAEs (16.4% versus 6.4%, P &lt;0.001) as well as each subtype (transient ischemic attack: 3.3% versus 1.0%, P &lt;0.001; ischemic cerebrovascular accident: 7.7% versus 3.4%, P &lt;0.001; hemorrhagic cerebrovascular accident: 7.2% versus 2.0%, P &lt;0.001) than did patients receiving HM3. A propensity-matched cohort balanced for preimplant risk factors showed that HVAD was associated with higher probabilities of major NAEs (% freedom from NAE 82% versus 92%, P &lt;0.001). Device type was not significantly associated with NAEs in the early hazard phase, but HVAD was associated with higher incidence of major NAEs during the constant hazard phase (hazard ratio, 5.71 [CI, 3.90–8.36]). Conclusions: HM3 is associated with lower hazard of major NAEs than is HVAD beyond the early postimplantation period and during the constant hazard phase. Defining the explanation for this observation will inform device selection for individual patients.

STUDY DESIGN: An in vitro biomechanical study of reconstruction techniques used after multilevel cervical corpectomy. OBJECTIVES: To determine the biomechanical behavior of the cervical spine after a multilevel corpectomy and reconstruction with a strut graft and supplementation of the graft with anterior and posterior plates. SUMMARY OF BACKGROUND DATA: Reconstruction of the spine after multilevel corpectomy represents a significant challenge, with nonunion or graft dislodgment being relatively common. Anterior and posterior plate fixation have increased the possibilities for supplemental stabilization. Although some clinical studies have been performed to examine multilevel corpectomies reconstructed with plates, biomechanical studies are few and are limited to single-segment models. METHODS: Flexibility testing was performed on 11 intact cervical spine preparations. Flexibility testing was also conducted on the spine preparations after reconstruction with a strut graft, after supplementation of the graft with an anterior plate, and after supplementation of the graft with lateral mass plates. Physiologic moments were applied dynamically, and the three-dimensional motion of the specimen was recorded with stereophoto-grammetry. Failure testing was performed on the plated specimens in compression. Load displacement curves and failure modes were analyzed. RESULTS: The range of motion after reconstruction compared with the control was decreased 24% after strut grafting, 43% after application of an anterior plate, and 62% after application of posterior plates. Similarly, flexibility coefficients showed that the posterior plate technique was the least flexible, followed by the anterior plate technique, with the graft alone being the most flexible reconstruction construct. Load to initial failure tended to be higher in posterior than in anterior plate specimens, and screw pullout was the predominant failure mode. CONCLUSIONS: The application of plates to the cervical spine as an adjunct to bone graft may improve the surgeon's ability to stabilize the spine after multilevel corpectomy. Understanding the biomechanics of these devices and the potential mode of failure is important in their use.

Little is known about out-of-pocket (OOP) costs incurred for medical and health needs by rural breast cancer survivors and what factors may be associated with higher OOP costs and the associated economic burden. Data were examined for 432 survivors participating in the Rural Breast Cancer Survivor Intervention trial. OOP costs were collected using the Work and Finances Inventory survey at baseline and four assessments every 3 months. Mean and median OOP costs and burden (percent of monthly income spent on OOP costs) were reported and factors associated with OOP costs and burden identified with generalized linear models fitted with over-dispersed gamma distributions and logarithmic links (OOP costs) and with beta distributions with logit link (OOP burden). OOP costs per month since the end of treatment were on average $232.7 (median $95.6), declined at the next assessment point to $186.5 (median $89.1), and thereafter remained at that level. Mean OOP burden was 9% at baseline and between 7% and 8% at the next assessments. Factors suggestive of contributing to higher OOP costs and OOP burden were the following: younger age, lower income, time in survivorship from diagnosis, and use of supportive services. OOP costs burden rural breast cancer survivors, particularly those who are younger and low income. Research should investigate the impact of OOP costs and interventions to reduce economic burden.

High-resolution computed tomograms (HRCT) reveal strikingly little variation in the dimensions of inner ear structures among people with normal hearing. However, a subgroup of people exist who have a sensorineural hearing loss (SNHL) and morphologically normal HRCT scans, yet have subtle radiographic aberrations based on measurements of inner ear dimensions. These changes might have resulted from teratogenic influences during the late first to mid second trimester, a time when the inner ear has achieved adult form, yet continues to enlarge to adult size. A retrospective study of HRCTs on three groups of ears was performed to determine inner ear structure dimensions. Group I, the control group, consisted of 50 ears with no SNHL and no discernible abnormalities on HRCT. In group II, there were 70 ears with SNHL and obvious abnormalities on HRCT. Group III, the test group, was composed of 140 ears with SNHL and "normal" HRCTs. Groups II and III were analyzed, applying the normal dimensions derived from group I. When compared to the control group (I), all of the ears in group II were abnormal. Moreover, 75% of the ears in group III had subtle differences not apparent unless measurements were made. Two or more abnormal dimensions were found in 32%. Findings and implications are thoroughly discussed.

BACKGROUND: Although the necessity of long-term follow-up after total knee arthroplasty is unquestioned, this task may become burdensome as greater numbers of total knee arthroplasties are performed. We sought to use comparisons with clinician-assessed values to determine whether patients could reliably assess their own outcome with use of a combination of American Knee Society Score and Oxford Knee Score questionnaires and self-reported knee motion. We hypothesized that patients would self-report worse pain and function and a similar range of knee motion than clinicians would. METHODS: One hundred and forty patients (181 knees) scheduled for routine follow-up at two centers after primary total knee arthroplasty were mailed American Knee Society Score and Oxford Knee Score questionnaires, a set of photographs illustrating knee motion in 5° increments for comparison with the patient's range of knee motion, and a goniometer with instructions. The patient's American Knee Society Score, Oxford Knee Score, and knee motion were then independently assessed within two weeks of the self-evaluation by one of three clinicians who had not been involved with the surgery. Patient-reported and clinician-assessed measures were compared with use of a paired-sample t test and the Spearman correlation coefficient. RESULTS: The mean patient-reported American Knee Society pain subscore was 4 points worse than the clinician-assessed score, and the function subscore was 10 points worse (p < 0.001 for both). The mean Oxford Knee Score did not differ significantly between the patient self-assessment and the clinician assessment (p = 0.05). The mean maximum flexion reported by the patient with use of the photographs differed by <1° from the mean value reported by the patient with use of the goniometer or the mean value measured by the clinician; these differences were not clinically important. CONCLUSIONS: Patients' self-reported American Knee Society pain and function subscores were worse than the corresponding clinician assessments, but the two Oxford Knee Scores were similar. Range of knee motion may reasonably be self-assessed by comparison with photographs. Long-term follow-up of patients after total knee arthroplasty may be possible with use of patient-reported measures, alleviating the burden of clinic visits yet maintaining contact, but further studies involving other validated instruments is warranted.

Twenty-two consecutive severely symptomatic infants and small children less than 4 years of age (mean age 25.5 months, range 3½ to 48 months) have presented for initial surgical treatment of the tetralogy of Fallot at the University of Alabama Medical Center between September 1, 1971 and January 31, 1973. One was considered unsuitable for complete repair because of massive thrombosis of the inferior vena cava, and was successfully treated by a right Blalock-Taus-sig operation. Twenty-one were treated by primary intracardiac repair. One patient (age 24 months) died, a hospital mortality rate of 4.8%. Mean value for the RV/LV peak pressure ratio immediately after repair was 0.55. An outflow patch was placed across the valve ring in one patient, and should have been placed in one other. Heart block has not occurred. Profound hypothermia and circulatory arrest (Kyoto-Barratt-Boyes technique) was used in 9 patients, and cardiopulmonary bypass with profound hypothermia in 12. We discuss the controversy concerning initial management of infants and small children severely symptomatic from the tetralogy of Fallot, and conclude that primary intracardiac repair is advisable in centers prepared for infant intracardiac surgery.

Background Early right heart failure (RHF) occurs commonly in left ventricular assist device (LVAD) recipients, and increased right ventricular (RV) afterload may contribute. Selective pulmonary vasodilators, like phosphodiesterase-5 inhibitors (PDE5i), are used off-label to reduce RV afterload before LVAD implantation, but the association between preoperative PDE5i use and early RHF after LVAD is unknown. Methods and Results We analyzed adult patients from the INTERMACS registry (Interagency Registry for Mechanically Assisted Circulatory Support) who received a continuous flow LVAD after 2012. Patients on PDE5i were propensity-matched 1:1 to controls. The primary outcome was the incidence of severe early RHF, defined as the composite of death from RHF within 30 days, need for RV assist device support within 30 days, or use of inotropes beyond 14 days. Of 11 544 continuous flow LVAD recipients, 1199 (10.4%) received preoperative PDE5i. Compared to controls, patients on PDE5i had higher pulmonary artery systolic pressure (53.4 mm Hg versus 49.5 mm Hg) and pulmonary vascular resistance (2.6 WU versus 2.3 WU; P<0.001 for both). Before propensity matching, the incidence of severe early RHF was higher among patients on PDE5i than in controls (29.4% versus 23.1%; unadjusted odds ratio (OR), 1.32; 95% CI, 1.17-1.50). This association persisted after propensity matching (PDE5i, 28.9% versus control 23.7%; OR, 1.31; 95% CI, 1.09-1.57), driven by a higher incidence of prolonged inotropic support. Similar results were observed across a wide range of subgroups stratified by markers of pulmonary vascular disease and RV dysfunction. Conclusions Patients treated with preoperative PDE5i had markers of increased RV afterload and HF severity compared to unmatched controls. Even after propensity matching, patients receiving preimplant PDE5i therapy had higher rates of post-LVAD RHF.