Tranexamic Acid in Patients Undergoing Liver Resection: The HeLiX Randomized Clinical Trial.

Importance: Tranexamic acid reduces bleeding and blood transfusion in many types of surgery, but its effect in patients undergoing liver resection for a cancer-related indication remains unclear. Objective: To determine whether tranexamic acid reduces red blood cell transfusion within 7 days of liver resection. Design, Setting, and Participants: Multicenter randomized clinical trial of tranexamic acid vs placebo conducted from December 1, 2014, to November 8, 2022, at 10 hepatopancreaticobiliary sites in Canada and 1 site in the United States, with 90-day follow-up. Participants, clinicians, and data collectors were blinded to allocation. A volunteer sample of 1384 patients undergoing liver resection for a cancer-related indication met eligibility criteria and consented to randomization. Interventions: Tranexamic acid (1-g bolus followed by 1-g infusion over 8 hours; n = 619) or matching placebo (n = 626) beginning at induction of anesthesia. Main Outcomes and Measures: The primary outcome was receipt of red blood cell transfusion within 7 days of surgery. Results: The primary analysis included 1245 participants (mean age, 63.2 years; 39.8% female; 56.1% with a diagnosis of colorectal liver metastases). Perioperative characteristics were similar between groups. Red blood cell transfusion occurred in 16.3% of participants (n = 101) in the tranexamic acid group and 14.5% (n = 91) in the placebo group (odds ratio, 1.15 [95% CI, 0.84-1.56]; P = .38; absolute difference, 2% [95% CI, -2% to 6%]). Measured intraoperative blood loss (tranexamic acid, 817.3 mL; placebo, 836.7 mL; P = .75) and total estimated blood loss over 7 days (tranexamic acid, 1504.0 mL; placebo, 1551.2 mL; P = .38) were similar between groups. Participants receiving tranexamic acid experienced significantly more complications compared with placebo (odds ratio, 1.28 [95% CI, 1.02-1.60]; P = .03), with no significant difference in venous thromboembolism (odds ratio, 1.68 [95% CI, 0.95-3.07]; P = .08). Conclusions and Relevance: Among patients undergoing liver resection for a cancer-related indication, tranexamic acid did not reduce bleeding or blood transfusion but increased perioperative complications. Trial Registration: ClinicalTrials.gov Identifier: NCT02261415.

Long-term outcomes following valve-sparing root replacement with concomitant mitral repair.

OBJECTIVES: To examine the late outcomes of valve-sparing root replacement and concomitant mitral valve repair in patients who have been followed prospectively for more than 2 decades. METHODS: From 1992 to 2020, 54 consecutive patients (mean age, 47 ± 16 years; 80% men) underwent valve-sparing root replacement (45 reimplantation and 9 remodeling) with concomitant repair of the mitral valve. Patients were followed prospectively for a median of 9 years (IQR, 3-14 years). RESULTS: No patient experienced perioperative death or stroke. There were 3 late deaths and the 15-year overall survival was 96.0% (95% CI, 74.8%-99.4%), similar to the age- and sex-matched population. Over the follow-up period, 6 patients had reoperation of the aortic valve and 3 on the mitral valve. Of those, 2 had reoperation on both aortic and mitral valves for a total of 7 reoperations in this cohort. The cumulative proportion of reoperation at 10 years of either or both valves were as follows: aortic valve 11.4% (95% CI, 3.9%-33.3%), mitral valve 4.2% (95% CI, 0.6%-28.4%), and both valves 11.4% (95% CI, 3.9%-33.3%). The estimated probability of developing moderate/severe aortic insufficiency at 15 years was 18.5% (95% CI, 9.0%-34.2%). On final echocardiographic follow-up, none of the patients had developed moderate/severe mitral regurgitation. CONCLUSIONS: In this single-center series of concomitant valve-sparing root replacement and mitral valve repair, we observed excellent clinical outcomes with a low risk of death or valve-related complications. Continued surveillance of late valve function is necessary.

Early and mid-term outcomes after aortic valve intervention in patients with previous stentless or stented bioprostheses.

BACKGROUND: Limited data are available concerning comparative outcomes of redo aortic valve interventions, including surgery after aortic valve replacement (AVR) with either stented or stentless bioprostheses. We investigated the comparative outcomes of redo aortic valve interventions, including surgery after AVR with either stented or stentless bioprostheses. METHODS: The cohort consisted of 112 patients who underwent aortic valve intervention for infective endocarditis or structural valve deterioration between 2001 and 2020. One hundred patients received a stented valve (stented group) and 12 patients received a stentless valve (stentless group) during the initial surgery. Early and late outcomes were evaluated. RESULTS: The mean [IQR] ages during the current interventions were 66 [54, 77] years in the stented group and 74 [67, 79] years in the stentless group (P = 0.13). In the stented group, aortic valve interventions included redo AVRs with stented valves (n = 54), mechanical valves (n = 26), stentless valves (n = 16), and transcatheter aortic valve implantations (n = 4). In the stentless group, redo AVRs were performed with stented valves (n = 4), mechanical valves (n = 2), stentless valves (n = 1), and transcatheter valve implantations (n = 5). Hospital mortality was observed in 2 (2%) patients in the stented group and 1 (8%) patients in the stentless group (P = 0.29). The 5-year survival was 80.8% [66.8, 88.5] in the stented group and 91.7% [53.9, 98.8] in stentless group. Statistically significant differences in thromboembolisms were observed between the groups. CONCLUSIONS: No significant differences in early and mid-term outcomes (except thromboembolism) after aortic valve interventions were detected between patients with stented and stentless AVRs.

Platelet preservation in cardiac surgery using minimally invasive extracorporeal circulation versus optimized cardiopulmonary bypass.

BACKGROUND: Minimally invasive extracorporeal circulation (MiECC) is employed as a strategy to attenuate the physiologic disturbance caused by cardiopulmonary bypass. The aim of this study was to compare the coagulation profile of MiECC to an optimized conventional extracorporeal circuit (OpECC) with regards to platelet function, rotational thromboelastometry and blood product usage. METHODS: A retrospective analysis of coronary artery bypass grafting operations using either MiECC or OpECC was performed at a single institution. RESULTS: A total of 112 patients were included, with 61 receiving MiECC and 51 OpECC patients. OpECC patients had a significantly larger BSA (1.95+/- 0.22m2 vs 1.88 +/- 0.18m2, p = 0.034), than those who received MiECC. No difference between groups was observed regarding red blood cell, plasma, and platelet transfusions. Functional platelet count during the warming phase of cardiopulmonary bypass was found to be higher in the MiECC group ((136 (102-171) x109/L vs 109 (94-136) x109/L), p = 0.027), as were functional platelets as a percent of total platelet count ((86 (77-91)% vs 76 (63-82)%), p = 0.003). There were no significant differences between other outcomes such as operative mortality, incidence of stroke, and intensive care unit length of stay. CONCLUSION: While we did not see a difference in blood transfusions, MiECC resulted in a statistically significant advantage over OpECC with regards to preservation of functional platelets.

Outcomes of Reimplantation of the Aortic Valve in Patients With Aortic Cusp Fenestration.

BACKGROUND: Aortic cusp fenestrations are common in patients with aortic root aneurysm, and their management during aortic valve repair remains controversial. We believe that fenestrations in the area of the commissures may rupture after reimplantation of the aortic valve because this operation increases the mechanical stress on the cusps. For this reason we have reinforced the free margin of the aortic cusp with fenestration with fine Gore-Tex sutures (WL Gore). This study examines the outcomes of reimplantation of the aortic valve in patients who had cusp fenestration reinforced with Gore-Tex sutures. METHODS: A review of all patients who had reimplantation of the aortic valve for aortic root aneurysm disclosed 111 patients who had at least 1 cusp fenestration reinforced with a double layer of a fine Gore-Tex suture. The outcomes of these patients were examined and compared with a group of patients without fenestration using propensity score analysis. All patients were followed prospectively with images of the heart. RESULTS: The median follow-up was 8.3 years. Overall the cumulative incidence of aortic valve reintervention at 15 years was 4.8% and the cumulative incidence of aortic insufficiency of moderate or severe degree was 9.2%. Comparison of outcomes of patients with and without fenestrations showed similar results up to 15 years of follow-up. CONCLUSIONS: Reinforcement of the free margins of cusps with fenestrations using Gore-Tex sutures is safe and does not seem to adversely affect the durability of reimplantation of the aortic valve.

Improved Outcomes of Reimplantation vs Remodeling in Marfan Syndrome: A Propensity-Matched Study.

BACKGROUND: Valve-sparing root replacement (VSRR) has excellent outcomes when performed in experienced centers in well-selected patients. It is suggested that reimplantation of the aortic valve may have better durability than remodeling in patients with Marfan syndrome (MFS), although long-term comparative data are limited. METHODS: Between 1988 and 2018, 194 patients with MFS underwent VSRR at our institution. From these, we derived a propensity-matched cohort of 68 patients (44 who underwent reimplantation and 24 who had remodeling). Early outcomes included death and perioperative complications. Late outcomes were survival, probability of aortic insufficiency, and reintervention up to 20 years of follow-up. Median follow-up was 17.8 years (interquartile range, 12.0-20.6 years) for the entire matched cohort. RESULTS: Baseline variables were similar between reimplantation and remodeling patients after matching: age (39 ± 12 vs 40 ± 13 years, P = .75) and male sex (28 [64%] vs 15 [63%], P = 1.0). Similar 20-year survival was observed after reimplantation compared with remodeling (82% vs 72%, P = .20), whereas the probability of developing greater than mild aortic insufficiency at 20 years was increased after remodeling (5.8% vs 13%, P = .013). More patients underwent reoperation on the aortic valve after a remodeling procedure than after reimplantation of the aortic valve (18% vs 0%, P = .018). CONCLUSIONS: VSRR provides excellent long-term survival and freedom from valve-related complications outcomes in patients with MFS. Reimplantation of the aortic valve was associated with a lower risk of aortic valve reoperation and aortic insufficiency than the remodeling procedure after 2 decades of follow-up.

Improved Outcomes Following the Ross Procedure Compared With Bioprosthetic Aortic Valve Replacement.

BACKGROUND: The ideal aortic valve substitute for young and middle-aged adults remains elusive. OBJECTIVES: This study sought to compare the long-term outcomes of patients undergoing the Ross procedure and those receiving bioprosthetic aortic valve replacements (AVRs). METHODS: Consecutive patients aged 16-60 years who underwent a Ross procedure or surgical bioprosthetic AVR at the Toronto General Hospital between 1990 and 2014 were identified. Propensity score matching was used to account for differences in baseline characteristics. The primary outcome was all-cause mortality. Secondary outcomes included valve reintervention, valve deterioration, endocarditis, thromboembolic events, and permanent pacemaker implantation. RESULTS: Propensity score matching yielded 108 pairs of patients. The median age was 41 years (IQR: 34-47 years). Baseline characteristics were similar between the matched groups. There was no operative mortality in either group. Mean follow-up was 14.5 ± 7.2 years. All-cause mortality was lower following the Ross procedure (HR: 0.35; 95% CI: 0.14-0.90; P = 0.028). Using death as a competing risk, the Ross procedure was associated with lower rates of reintervention (HR: 0.21; 95% CI: 0.10-0.41; P < 0.001), valve deterioration (HR: 0.25; 95% CI: 0.14-0.45; P < 0.001), thromboembolic events (HR: 0.15; 95% CI: 0.05-0.50; P = 0.002), and permanent pacemaker implantation (HR: 0.22; 95% CI: 0.07-0.64; P = 0.006). CONCLUSIONS: In this propensity-matched study, the Ross procedure was associated with better long-term survival and freedom from adverse valve-related events compared with bioprosthetic AVR. In specialized centers with sufficient expertise, the Ross procedure should be considered the primary option for young and middle-aged adults undergoing AVR.

Outcomes of combined aortic and mitral valve replacement with reconstruction of the fibrous skeleton of the heart.

OBJECTIVES: The objectives of this study were to examine operative and long-term results of combined aortic and mitral valve replacement when reconstruction of the fibrous skeleton of the heart is needed because of calcification, abscess, previous operations, or patient-prosthesis mismatch. METHODS: From 1985 to 2020, 182 consecutive patients underwent combined aortic and mitral valve replacement with reconstruction of the intervalvular fibrous skeleton in all cases and also the posterior mitral annulus in 63 patients. Bovine pericardium or Dacron grafts were used for the reconstructions. Median follow-up was 7.5 (interquartile range, 2.1-12.6) years and 98% complete. RESULTS: Patient mean age was 62 years; 69% had 1 or more previous valve operations, and 92% were functional class III or IV. The indications for reconstruction were extensive calcification of the fibrous skeleton in 34%, abscess in 13%, tissue damage secondary to previous operations in 39%, and patient-prosthesis mismatch of the mitral valve in 13%. Bovine pericardium was used in two-thirds of cases and Dacron grafts in one-third. Operative mortality was 13.2% and postoperative complications were common. Survival at 1, 10, and 20 years was 81.8%, 51.1%, and 23.7%, respectively. Fourteen patients required reoperation and 3 transcatheter interventions. The cumulative probability of reinterventions at 1, 10, and 20 years were 3.3%, 5.8%, and 9.1%, respectively. Most patients experienced symptomatic improvement postoperatively. CONCLUSIONS: Reconstructions of the fibrous skeleton of the heart are associated with high operative mortality but the long-term results are satisfactory because most patients would not have survived without surgical intervention.

A progress report on reimplantation of the aortic valve.

OBJECTIVE: To examine the late outcomes of reimplantation of the aortic valve (RAV) in patients followed prospectively since surgery. METHODS: All 465 patients who had RAV from 1989 to 2018 were followed prospectively with periodic clinical and echocardiographic assessments. Mean follow-up was 10 ± 6 years and 98% complete. RESULTS: Patients' mean age was 47 ± 5.1 years, and 78% were men. The aortic root aneurysm was associated with Marfan syndrome in 164 patients, Loeys-Dietz syndrome in 13, bicuspid aortic valve (BAV) in 67, and type A aortic dissection in 33. Aortic insufficiency (AI) was greater than mild in 298 patients. Concomitant procedures were performed in 105 patients. There were 5 operative and 51 late deaths. At 20 years, 69.1% of patients were alive and free from aortic valve reoperation, and the cumulative probability of aortic valve reoperation with death as a competing risk was 6.0%, and the cumulative probability of developing moderate or severe AI was 10.2%. Only time per 1-year interval was associated with the development of postoperative AI by multivariable analysis (hazard ratio, 1.06; 95% confidence interval, >1.02-1.10; P = .006). Gradients across preserved BAV increased in 5 patients, and 1 required reoperation for aortic stenosis. Distal aortic dissections occurred in 22 patients, primarily in those with associated genetic syndromes. CONCLUSIONS: RAV provides excellent long-term results, but there is a progressive rate of AI over time, and patients with BAV may develop aortic stenosis. Patients with genetic syndromes have a risk of distal aortic dissections. Continued surveillance after RAV is necessary.

Early outcomes of the Bentall procedure after previous cardiac surgery.

OBJECTIVES: We sought to evaluate the early outcomes of patients undergoing a Bentall procedure after previous cardiac surgery. METHODS: From 1990 to 2014, 473 patients underwent a Bentall procedure after previous cardiac surgery with a composite valve graft at a single institution: composite valve graft with a mechanical prosthesis (n = 256) or composite valve graft with a bioprosthesis (n = 217). Patients were excluded if their index operation was less than 30 days before the reoperation. The primary outcome was 30-day mortality. The secondary outcome was a composite of major morbidity and operative mortality: stroke, renal failure, prolonged mechanical ventilation, deep sternal infection, or reoperation during the same admission. Multivariable logistic regression was used to identify risk factors associated with the primary and secondary outcomes of interest. RESULTS: Median age was 57 (interquartile range, 44-67) years, and 349 patients (74%) were male. Median time between index surgery and reoperation was 13 (interquartile range, 8-21) years. A total of 178 patients (38%) underwent urgent or emergency intervention, 61 patients (13%) had active endocarditis/abscess, 87 patients (19%) had left ventricular ejection fraction less than 40%, and 262 patients (55%) had undergone more than 1 previous operation. Previous operations (not mutually exclusive) included coronary artery bypass grafting (n = 58, 12%), aortic valve/root replacement (n = 376, 80%) or repair (n = 36, 8%), and other surgical interventions (n = 245, 52%). Ninety-six patients (20%) had undergone coronary reimplantation during the previous operation, which consisted of a Bentall procedure in 81 patients, a Ross operation in 8 patients, a valve-sparing root replacement in 4 patients, and an arterial switch in 3 patients. At the time of the reoperative Bentall, both coronary arteries were reimplanted directly in 357 patients (77%), whereas 79 patients (17%) received at least 1 interposition graft. In 26 patients (5%), at least 1 of the native coronary arteries was oversewn and a vein graft bypass was performed. Thirty-day mortality occurred in 37 patients (7.8%), and 152 patients (32%) had major morbidity and operative mortality. On multivariable analysis, risk factors associated with increased 30-day mortality included older age and coronary reimplantation by a technique other than direct anastomosis. Indirect coronary reimplantation was also associated with a higher incidence of major morbidity and operative mortality, as were more than 1 previous cardiac operation and preoperative New York Heart Association functional class III/IV or greater. CONCLUSIONS: In the largest reported cohort of aortic root replacement after previous cardiac surgery, the reoperative Bentall procedure was associated with a significant operative risk. The need for complex coronary reimplantation techniques was an important factor associated with adverse perioperative events.

Comparison of Heart Transplantation Outcomes: Adult Congenital Heart Disease vs Matched Cardiac Patients in a Quaternary Reference Centre.

BACKGROUND: The number of transplantations performed for adult congenital heart disease (ACHD) patients is increasing. We sought to compare survival and post-transplantation complications, including graft failure, rejection, dialysis, and use of a right ventricular assist device, between ACHD and a cohort of dilated (DCM) and ischemic (ICM) cardiomyopathy patients matched by age and year of transplantation. METHODS: We retrospectively reviewed our single-institution heart transplantation database and selected all patients who had surgery from 1988 to 2017. In our primary analysis, we looked at survival and post-transplantation complications across cardiomyopathy groups. Our secondary analysis was matched to mitigate era effects as well as differences in age at transplant. RESULTS: We analyzed a cohort consisting of 303 heart transplant patients with cardiomyopathy due to either 1) ACHD (n = 38), 2) ICM (n = 110), or 3) DCM (n = 155). Kaplan-Meier analysis and a multivariable Cox proportional hazard regression model were used for all-cause mortality, and cause-specific hazard regression for cause-specific mortality and morbidity. There was no statistically significant survival difference across groups. The 1-year survival was 68.5% for ACHD, 85.4% for ICM, and 85.5% for DCM. In multivariable analysis, ICM and DCM patients showed a 66% lower risk of death relative to the ACHD group. The matched analysis showed no significant difference in survival across groups. CONCLUSIONS: ACHD patients represent a growing high-risk patient cohort referred for transplantation. To improve survival outcomes we need to address modifiable risk factors.

Left Ventricular Size and Outcomes in Patients With Left Ventricular Ejection Fraction Less Than 20.

BACKGROUND: The interactive relationship between left ventricular (LV) ejection fraction (LVEF) and LV size in predicting perioperative outcomes after cardiac surgery has not been clarified. METHODS: This study reviewed all patients who underwent cardiac surgery between 2010 and 2016 with either preserved LVEF (>60%; n = 5685) or severely reduced LVEF (<20%; n = 143). LV size was categorized by using either LV end-diastolic or end-systolic diameter or a qualitative assessment, as follows: normal, smaller than 4 cm; mildly enlarged, 4.1 to 5.4 cm moderately enlarged, 5.5 to 6.5 cm; and severely enlarged, larger than 6.5 cm. Using propensity-score analysis, we matched patients with LVEF less than 20% (n = 143) in a 3:1 ratio with patients with LVEF greater than 60% (n = 429). RESULTS: There were significant differences in mortality, major morbidity, and operative mortality and prolonged length of stay between patients with LVEF less than 20% and LVEF greater than 60%. In patients with LVEF less than 20%, there were no significant differences in outcomes between those with an LV size of 5.4 cm or smaller and an LV size of 5.5 cm or larger. In patients undergoing isolated coronary artery bypass grafting (CABG), LV size predicted mortality, major morbidity, and operative mortality (odds ratio, 5.5 [95% confidence interval, 2.0 to 15.7]; P < .001) and prolonged length of stay (odds ratio, 3.4 [95% confidence interval, 1.2 to 10.3]; P = .026), respectively. CONCLUSIONS: LVEF is more important than LV size in predicting outcomes after cardiac surgery. However, in patients undergoing isolated CABG, LV size has an interactive effect with LVEF and can potentially aid the decision-making process. Risk adjustment models using only LVEF may be inaccurate, particularly with respect to isolated CABG procedures.

Long-term outcomes of chordal replacement with expanded polytetrafluoroethylene sutures to repair mitral leaflet prolapse.

OBJECTIVES: This study examines the durability of mitral valve (MV) repair for mitral regurgitation using chordal replacement with expanded polytetrafluoroethylene sutures to correct leaflet prolapse. METHODS: Isolated chordal replacement was used to correct prolapse in 186 (24.9%) patients and combined with leaflet resection in 560 (75.1%). Patients were followed prospectively with periodical clinical and echocardiographic assessments for a median follow-up of 11 years (range, 7-16 years). RESULTS: Patients' median age was 58 years (range, 48-67 years) and 516 (69.2%) were men. Bileaflet prolapse was present in 63% of patients and advanced myxomatous degeneration was present in 32%. The number of neochords per repaired valve increased over time and was not associated with MV reoperation or recurrent mitral regurgitation. The cumulative incidence of MV reoperation with death as a competing risk was 4.2% (95% confidence interval [CI], 2.4-6.0) at 20 years. Multivariable analysis revealed that previous cardiac operations (hazard ratio, 5.70; 95% CI, 1.96-16.53; P = .001), and isolated anterior leaflet prolapse (hazard ratio, 3.92; 95% CI, 1.106-13.91; P = .034) were associated with increased hazard of MV reoperation. The probability of recurrent moderate or severe mitral regurgitation using repeated measures regression models was 14.1% (95% CI, 10.3-19.0) at 20 years. Variables associated with recurrent MR in multivariable regression analysis were left ventricular ejection <40% (hazard ratio, 3.57; 95% CI, 1.37-9.32; P = .009) and preoperative complete heart block (hazard ratio, 5.90; 95% CI, 2.47-14.09; P < .001). CONCLUSIONS: Chordal replacement with expanded polytetrafluoroethylene sutures provides stable MV function in most patients during the first 2 decades of follow-up.

Machine Learning Identifies Clinical and Genetic Factors Associated With Anthracycline Cardiotoxicity in Pediatric Cancer Survivors.

BACKGROUND: Despite known clinical risk factors, predicting anthracycline cardiotoxicity remains challenging. OBJECTIVES: This study sought to develop a clinical and genetic risk prediction model for anthracycline cardiotoxicity in childhood cancer survivors. METHODS: We performed exome sequencing in 289 childhood cancer survivors at least 3 years from anthracycline exposure. In a nested case-control design, 183 case patients with reduced left ventricular ejection fraction despite low-dose doxorubicin (≤250 mg/m2), and 106 control patients with preserved left ventricular ejection fraction despite doxorubicin >250 mg/m2 were selected as extreme phenotypes. Rare/low-frequency variants were collapsed to identify genes differentially enriched for variants between case patients and control patients. The expression levels of 5 top-ranked genes were evaluated in human induced pluripotent stem cell-derived cardiomyocytes, and variant enrichment was confirmed in a replication cohort. Using random forest, a risk prediction model that included genetic and clinical predictors was developed. RESULTS: Thirty-one genes were differentially enriched for variants between case patients and control patients (p < 0.001). Only 42.6% case patients harbored a variant in these genes compared to 89.6% control patients (odds ratio: 0.09; 95% confidence interval: 0.04 to 0.17; p = 3.98 × 10-15). A risk prediction model for cardiotoxicity that included clinical and genetic factors had a higher prediction accuracy and lower misclassification rate compared to the clinical-only model. In vitro inhibition of gene-associated pathways (PI3KR2, ZNF827) provided protection from cardiotoxicity in cardiomyocytes. CONCLUSIONS: Our study identified variants in cardiac injury pathway genes that protect against cardiotoxicity and informed the development of a prediction model for delayed anthracycline cardiotoxicity, and it also provided new targets in autophagy genes for the development of cardio-protective drugs. (Preventing Cardiac Sequelae in Pediatric Cancer Survivors [PCS2]; NCT01805778).

Long-Term Results of Mitral Valve Repair for Regurgitation Due to Leaflet Prolapse.

BACKGROUND: Mitral valve (MV) repair has become the standard therapy for mitral regurgitation (MR) due to degenerative diseases, but information on late outcomes is limited. OBJECTIVES: The purpose of this study was to examine the late results of MV repair for MR in a large cohort of patients. METHODS: A total of 1,234 consecutive patients (median age 59 years; 70.4% men) had MV repair for MR due to leaflet prolapse and were followed prospectively for a median of 13 years (interquartile range: 8 to 34 years) with periodical echocardiographic studies. There were 163 patients still at risk at 20 years. Cumulative incidences of adverse events and associated factors were examined with death as a competing outcome. RESULTS: At 20 years, reoperation-free survival was 60.4% (95% confidence interval: 56.2% to 64.2%) and the cumulative incidence of cardiac and valve-related deaths was 12%, noncardiac deaths 21.3%, reoperation on the MV 4.6%, infective endocarditis 1.1%, thromboembolism 10.3%, and bleeding 6.4%. The probability of recurrent moderate or severe MR was 12.5%, persistent or new moderate or severe tricuspid regurgitation (TR) 20.8%, and new atrial fibrillation (AF) 32.4%. Multivariable analysis identified older age, complete heart block, MV repair without annuloplasty ring, and the degree of myxomatous degeneration of the MV to be associated with recurrent MR. The development of AF and TR was unrelated to recurrent MR. CONCLUSIONS: MV reoperation was uncommon after MV repair, but there was an increasing incidence of recurrent MR, TR, and new AF over time.

Late results of the Ross procedure.

OBJECTIVE: The study objective was to examine the long-term results of the Ross procedure in a cohort of patients followed prospectively for more than 2 decades. METHODS: From 1990 to 2004, 212 consecutive patients with a median age (interquartile range) of 34 years (28-41) underwent the Ross procedure; 82% had congenital aortic valve disease. The technique of aortic root replacement was used in one half of the patients. Patients have been followed prospectively for a median (interquartile range) of 18.0 (14.6-21.2) years. Valve function was assessed by echocardiography. RESULTS: Cumulative mortality at 20 years was 10.8% (95% confidence interval, 6.5-17.8). Thirty patients required Ross-related reoperations and 3 for coronary artery disease. The cumulative probability of Ross-related reoperations at 20 years was 16.8% (95% confidence interval, 11.3-24.5), on the pulmonary autograft was 11.5% (95% confidence interval, 7.2-18.0), and on the pulmonary homograft was 8.2% (4.6-14.7). The implantation technique was not associated with the cumulative incidence of reoperations on the pulmonary autograft. The development of moderate or severe aortic insufficiency and pulmonary homograft dysfunction increased with time. At 20 years, the probability of aortic insufficiency was 13% (95% confidence interval, 8.0-20.3) and of pulmonary homograft dysfunction was 19.7% (95% confidence interval, 13.9-27.2). Preoperative aortic insufficiency was associated with increased odds of postoperative aortic insufficiency. CONCLUSIONS: The long-term results of the Ross procedure are excellent regardless of the implantation technique, but there is a progressive deterioration of function of both semilunar valves.

Evaluation of left ventricular reverse remodeling in patients with severe aortic regurgitation undergoing aortic valve replacement: Comparison between diameters and volumes.

BACKGROUND: In patients with severe aortic regurgitation (AR), the left ventricular ejection fraction (LVEF) and left ventricle (LV) size are crucial for determining clinical prognosis and timing of valve intervention. In clinical practice, LV internal diameters obtained at end-diastole are used to assess the degree of LV dilatation. Whether quantification of LV volumes would provide more robust information as compared to LV linear dimensions is unknown. METHODS: We retrospectively analyzed preoperative and postoperative transthoracic echocardiograms of patients who underwent aortic valve replacement (AVR) for severe AR. Indexed linear LV end-diastolic and end-systolic diameters along with indexed LV end-diastolic and end-systolic volumes were obtained as per current guidelines. Post-AVR LV reverse remodeling, defined as ≥10% reduction in measures of LV volumes (Teichholz and Simpson's methods), was determined. Positive and negative agreement was calculated between the volume- and diameter-based LV reverse remodeling. RESULTS: Sixty-two consecutive patients were included. Nine patients (17%) without LV reverse remodeling based on Teichholz were reclassified as having LV reverse remodeling based on Simpson (positive agreement 0.846 [95% CI 0.772, 0.921], negative agreement 0.200 [95% CI -0.350, 0.435]). Left ventricle (LV) reverse remodeling assessed by the Teichholz method was underestimated by a mean of 31 mL/m2 (ß = -0.65 [95% CI -1.06 to -0.24], P = .003) compared to Simpson method. CONCLUSION: Compared to the volume-based method, diameter-based LV measurement incorrectly identified LV reverse remodeling post-AVR in 17% of patients with severe AR. Left ventricle (LV) volume may be a better measure to assess LV remodeling post-AVR than LV diameter-based measurements.

Adrenergic receptor genotypes influence postoperative outcomes in infants in the Single-Ventricle Reconstruction Trial.

OBJECTIVES: Adrenergic receptor (ADR) genotypes have been associated with adverse outcomes in heart failure. Our objective was to evaluate the association of ADR genotypes with post-Norwood outcomes in infants with hypoplastic left heart syndrome (HLHS). METHODS: Infants with HLHS participating in the Pediatric Heart Network Single-Ventricle Reconstruction Trial underwent genotyping for 4 single-nucleotide polymorphisms in 3 ADR genes: ADRB1_231A/G, ADRB1_1165G/C, ADRB2_5318C/G, and ADRA2A_2790C/T. The association of genotype with freedom from serious adverse events (SAEs) (death, transplant, extracorporeal membrane oxygenation, cardiopulmonary resuscitation, acute shunt failure, unplanned reoperations, or necrotizing enterocolitis) during 14 months' follow-up was assessed with Cox regression and the association with post-Norwood complications was assessed with Poisson regression. Models were adjusted for clinical and surgical factors. RESULTS: The study included 351 eligible patients (62% male; 83% white). The mean age at Norwood procedure was 5.6 ± 3.6 days. A total of 152 patients had SAEs during 14-month follow-up including 84 deaths and 10 transplants. ADRA2A_2790CC genotype had lower SAE-free survival compared with CT/TT genotypes during follow-up (Log rank test, P = .02), and this association was independent of clinical and surgical risk factors (adjusted Cox regression, hazard ratio 1.54 [95% confidence interval 1.04, 2.30] P = .033). Post-Norwood complication rate did not differ by genotype. CONCLUSIONS: Infants with HLHS harboring ADR genotypes that are associated with greater catecholamine release or sensitivity had lower event-free survival after staged palliation. Excess catecholamine activation may adversely affect cardiovascular adaptation after the Norwood procedure. Future studies should explore whether targeting adrenergic activation in those harboring risk genotypes can improve outcomes. (ClinicalTrials.gov number NCT00115934).

High-frequency microstimulation in human globus pallidus and substantia nigra.

Deep brain stimulation of the basal ganglia and other brain regions has been used successfully to treat a variety of neurological disorders. However, the mechanisms by which it works, remain unclear. In a previous study, we showed that locally delivered single current pulses delivered from a nearby microelectrode are sufficient to inhibit firing in the internal globus pallidus for tens of milliseconds. The GPi and the substantia nigra pars reticulata are the output nuclei of the basal ganglia and share many anatomical and physiological features. The goal of the current study was to examine the after-effects of trains of high-frequency microstimulation on neuronal firing in the GPi of Parkinson's disease and dystonia patients as well as in the SNr of PD patients. Microelectrode recordings and microstimulation were performed in a total of 57 patients during stereotactic surgery. We found that firing in the GPi and SNr is inhibited for several hundreds of milliseconds following the end of a short, 200 Hz high-frequency train delivered through the recording electrode (e.g., on average 618 ms when stimulating in the SNr with a 0.5 s train of 4 microA pulses at 200 Hz). Inhibition duration usually increased with increasing current intensity, train frequency and generally peaked for trains of 1-2 s, while it decreased with increasing train durations. Statistical analysis with general linear models revealed a significant linear relationship between current intensity and inhibition duration in all nuclei and patient groups. There was also a significant relationship between train frequency and inhibition duration in the SNr and GPi of PD patients and between train duration and inhibition duration in the GPi of PD patients. There was no significant difference in inhibition duration across patient groups but the current threshold for inhibition was significantly different in the SNr compared to the GPi. The characteristics of the inhibition observed are consistent with stimulation-induced GABA release following activation of the GABAergic afferents in the SNr and GPi. The findings suggest that high-frequency microstimulation of the GPi and SNr depresses local neuronal activity and synaptic transmission, and such mechanisms may contribute to the therapeutic effects of DBS.

Microstimulation-induced inhibition as a tool to aid targeting the ventral border of the subthalamic nucleus.

OBJECT: The aim of the current study was to examine and compare the aftereffects of local high-frequency microstimulation through the recording electrode on the firing of neurons in the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr) in patients undergoing surgery for deep brain stimulation. Deep brain stimulation has been playing an increasing role in the treatment of Parkinson disease, with the subthalamic nucleus (STN) being the preferred implantation target. Changes in cellular activity indicative of the borders of the STN are typically used during surgery to determine the extent of the STN and locate the optimal target, but in some cases borders may be difficult to identify. In this study the authors compared the effects of microstimulation in the SNr and STN. In previous studies they have shown that microstimulation in the internal globus pallidus, which is functionally similar to the SNr, inhibits firing, whereas similar microstimulation in the STN has minimal effect. The presence of inhibition in the SNr but not in the STN could be used as an additional criterion to help identify the location of the border between the STN and SNr. METHODS: Dual microelectrode recordings were performed during stereotactic surgery in 4 patients. Well-isolated high-amplitude units were stimulated extracellularly through the recording microelectrode with 0.5-second trains of high frequency (200 Hz) and low current (