Concomitant Tricuspid Repair in Patients with Degenerative Mitral Regurgitation.

BACKGROUND: Tricuspid regurgitation is common in patients with severe degenerative mitral regurgitation. However, the evidence base is insufficient to inform a decision about whether to perform tricuspid-valve repair during mitral-valve surgery in patients who have moderate tricuspid regurgitation or less-than-moderate regurgitation with annular dilatation. METHODS: We randomly assigned 401 patients who were undergoing mitral-valve surgery for degenerative mitral regurgitation to receive a procedure with or without tricuspid annuloplasty (TA). The primary 2-year end point was a composite of reoperation for tricuspid regurgitation, progression of tricuspid regurgitation by two grades from baseline or the presence of severe tricuspid regurgitation, or death. RESULTS: Patients who underwent mitral-valve surgery plus TA had fewer primary-end-point events than those who underwent mitral-valve surgery alone (3.9% vs. 10.2%) (relative risk, 0.37; 95% confidence interval [CI], 0.16 to 0.86; P = 0.02). Two-year mortality was 3.2% in the surgery-plus-TA group and 4.5% in the surgery-alone group (relative risk, 0.69; 95% CI, 0.25 to 1.88). The 2-year prevalence of progression of tricuspid regurgitation was lower in the surgery-plus-TA group than in the surgery-alone group (0.6% vs. 6.1%; relative risk, 0.09; 95% CI, 0.01 to 0.69). The frequencies of major adverse cardiac and cerebrovascular events, functional status, and quality of life were similar in the two groups at 2 years, although the incidence of permanent pacemaker implantation was higher in the surgery-plus-TA group than in the surgery-alone group (14.1% vs. 2.5%; rate ratio, 5.75; 95% CI, 2.27 to 14.60). CONCLUSIONS: Among patients undergoing mitral-valve surgery, those who also received TA had a lower incidence of a primary-end-point event than those who underwent mitral-valve surgery alone at 2 years, a reduction that was driven by less frequent progression to severe tricuspid regurgitation. Tricuspid repair resulted in more frequent permanent pacemaker implantation. Whether reduced progression of tricuspid regurgitation results in long-term clinical benefit can be determined only with longer follow-up. (Funded by the National Heart, Lung, and Blood Institute and the German Center for Cardiovascular Research; ClinicalTrials.gov number, NCT02675244.).

Locoregional Versus General Anesthesia for Carotid Artery Stenting in the American College of Surgeons National Surgical Quality Improvement Project.

OBJECTIVES: Carotid artery stenting (CAS) may be performed by transfemoral or transcervical (TCAR) approaches and with a variety of anesthetic techniques. No current literature clearly supports one anesthetic method over another. We therefore sought to evaluate the outcomes of CAS procedures based on anesthetic approach. DESIGN: Retrospective cohort study. SETTING: American College of Surgeons National Surgical Quality Improvement Program database from 2011 to 2018. PARTICIPANTS: All individuals undergoing CAS during the study period. INTERVENTIONS: Anesthetic type (locoregional versus general [GA]). MEASUREMENTS AND MAIN RESULTS: Locoregional anesthesia for CAS was used for 754 (65.5%) patients, with the remainder under GA. Demographic variables were comparable, as were the incidence of symptomatic presentation, high-risk anatomy or physiology, severity of the stenosis, and presence/severity of contralateral carotid disease. There was no difference in composite outcome (stroke, myocardial infarction [MI], and death) (7.0% v 6.1%, p = 0.53). The GA group had lower odds ratio of MI (0.12, p = 0.0362) but higher odds ratio of death (3.33, p = 0.008) and postoperative pneumonia (3.87, p = 0.0083), although on multivariable analysis the risk of death appeared confounded by respiratory variables. Multivariable and propensity score-weighted analyses did not identify a significant association of GA with the composite outcome. CONCLUSIONS: In patients undergoing CAS in the National Surgical Quality Improvement Program, GA was not associated with the composite outcome but was associated with increased rates of postoperative pneumonia and decreased rates of MI. Further investigation should attempt to better clarify these relationships.

Does the Hospital Day of Surgery for Endovascular Repair of Symptomatic Abdominal Aortic Aneurysms Affect Outcomes?

OBJECTIVE: Symptomatic abdominal aortic aneurysms (sAAA) are considered surgically urgent. Recent data suggest delaying surgery allows for medical optimization without affecting outcomes. We investigated the association of the hospital day of surgery with 30 day outcomes. METHODS: Patients with infrarenal sAAA undergoing endovascular aortic repair (EVAR) between 2011 and 2018 in the American College of Surgeons National Surgery Quality Improvement Project database were included. The primary outcome was 30 day mortality. Additional outcomes included myocardial infarction, pulmonary complications, length of stay, and discharge disposition. Days-to-surgery were classified as the day of presentation (D0), day 1, day 2, days 3 and 4, days 5 to 7 (D5), and day 8 or more (D8). RESULTS: A total of 804 patients were identified. D8 patients had higher proportions of dyspnea on exertion, chronic obstructive pulmonary disease, congestive heart failure, and history of dialysis. D0 surgery appeared protective of mortality (odds ratio [OR] 0.34, p=0.0132). Each additional day increased the mortality risk (OR 1.23, p<0.001) although not within the first 4 days. There was increased mortality for patients having surgery at D5 (7.7%) and D8 (23.8%) compared with repair earlier (1%-4%, p=0.03). Bivariable analysis revealed no significant differences in secondary outcomes. Multivariable modeling revealed increased mortality for D8 versus D0 (adjusted OR of 6.8, 95% confidence interval 1.7-26.5). CONCLUSIONS: While D0 appears to have the lowest risk of mortality, EVAR for sAAA up to 4 days may not be associated with increased mortality. Further research should determine delay etiologies and whether they improve operative planning and optimization without impacting morbidity and mortality.

The order of surgery and chemotherapy matters: Multimodality therapy and stage-specific differences in survival in gastric cancer.

BACKGROUND AND OBJECTIVES: Multimodality treatment improves survival for gastric cancer (GC). However, the effect of treatment sequence by stage remains unclear. We aim to compare outcomes between patients receiving neoadjuvant(neoadj) and adjuvant chemotherapy (adj). METHODS: Nonmetastatic GC patients with clinical stage ≥ T2N0 who underwent both resection and neoadj or adj were identified using the National Cancer Database (2005-2014). Multivariable Cox regression analyses were performed on propensity score-matched (PSM) cohorts stratified by stage to compare overall survival (OS). RESULTS: We identified 11 984 patients; 55% stage I (SI), 76% stage II (SII) and 57% stage III (SIII) received neoadj. Unadjusted analysis showed worse survival among SI neoadj patients (hazard ratio [HR] 1.195, confidence interval [CI] 1.04-1.38) and improved survival for SII (HR 0.93 CI 0.87-0.998) and SIII (HR 0.75, CI 0.68-0.84). After PSM, SI patients with neoadj had worse OS with increased risk of death compared to Adj (HR 1.186, CI 1.004-1.402). SII patients had no difference in OS (HR 0.98, CI 0.91-1.07) and SIII patients had improved OS (HR 0.78, CI 0.69-0.90). CONCLUSIONS: In patients who received surgery and chemotherapy, the benefit of neoadj was limited to SIII with worse survival for SI. A clinical trial to examine the optimal sequence of chemotherapy is warranted.

Novel Arthrometer for Quantifying In Vivo Knee Laxity in Three Planes Following Total Knee Arthroplasty.

BACKGROUND: Knee instability is a leading cause of dissatisfaction following total knee arthroplasty (TKA). Instability can involve abnormal laxity in multiple directions including varus-valgus (VV) angulation, anterior-posterior (AP) translation, and internal-external rotation (IER). No existing arthrometer objectively quantifies knee laxity in all three of these directions. The study objectives were to verify the safety and assess reliability of a novel multiplanar arthrometer. METHODS: The arthrometer utilized a five degree-of-freedom instrumented linkage. Two examiners each conducted two tests on the leg that had received a TKA of 20 patients (mean age 65 years (range, 53-75); 9 men, 11 women), with nine and eleven distinct patients tested at 3-month and 1-year postoperative time points, respectively. AP forces from -10 to 30 Newtons, VV moments of ±3 Newton-meters, and IER moments of ±2.5 Newton-meters were applied to each subject's replaced knee. Severity and location of knee pain during testing were assessed using a visual analog scale. Intraexaminer and interexaminer reliabilities were characterized using intraclass correlation coefficients. RESULTS: All subjects successfully completed testing. Pain during testing averaged 0.7 (out of possible 10; range, 0-2.5). Intraexaminer reliability was >0.77 for all loading directions and examiners. Interexaminer reliability and 95% confidence intervals were 0.85 (0.66-0.94), 0.67 (0.35-0.85), and 0.54 (0.16-0.79) in the VV, IER, and AP directions, respectively. CONCLUSION: The novel arthrometer was safe for evaluating AP, VV, and IER laxities in subjects who had received TKA. This device could be used to examine relationships between laxity and patient perceptions of knee instability.

Perioperative outcomes of carotid endarterectomy and transfemoral and transcervical carotid artery stenting in radiation-induced carotid lesions.

OBJECTIVE: Limited data are available to guide the choice of intervention for patients with radiation-induced carotid stenosis (RICS), either transcarotid artery revascularization (TCAR), transfemoral carotid artery stenting (TFCAS), or carotid endarterectomy (CEA). The purpose of the present study was to evaluate patients who had undergone these carotid artery interventions for RICS and the associated outcomes. METHODS: Patients in the Society for Vascular Surgery (SVS) Vascular Quality Initiative (VQI) carotid artery stenting surveillance project registry and the SVS VQI CEA modules who had undergone carotid artery intervention (TCAR, TFCAS, or CEA) for RICS were included. Those aged >90 years and those with concomitant interventions (eg, coronary bypass) were excluded. A composite of death, myocardial infarction (MI), and stroke was the primary outcome. The secondary outcomes included death, MI, stroke, cranial nerve injury (CNI), and other local and systemic complications. Multivariable logistic regression controlling for presenting symptomatic status and comorbid medical conditions was conducted for the outcome variables, except for death, which was analyzed using Cox regression modeling. RESULTS: A total of 1927 patients with RICS had undergone CEA (n = 1172), TCAR (n = 253), or TFCAS (n = 502). The CEA group had a higher rate of diabetes (31% vs 25% for TCAR and 25% for TFCAS; P = .01), hypertension (85% vs 82% for TCAR and 79% for TFCAS; P < .01), and peripheral vascular disease (8% vs 4% for TCAR and 4% for TFCAS; P < .01). The TCAR and TFCAS groups had higher rates of coronary artery disease (21% for CEA vs 30% for TCAR and 29% for TFCAS; P < .01). The patients who had undergone TFCAS were more likely to have had symptomatic lesions (57% for TFCAS vs 47% for CEA and 41% for TCAR; P < .01) and prior stroke (55% for TFCAS vs 47% for CEA and 40% for TCAR; P < .001). The composite outcome occurred in 3.2% of TCAR patients, 11.2% of TFCAS patients, and 11.1% of CEA patients (P < .01) with an odds ratio of 0.27 for TCAR, 0.91 for TFCAS, and 1.00 for CEA. However, no differences in the individual outcomes were noted for any procedure. TCAR exhibited the lowest odds ratio for CNI (0.15) compared with TFCAS at 0.9, both relative to CEA (P = .03). CONCLUSIONS: RICS patients treated by TCAR in the SVS VQI had the lowest risk of the composite of stroke, death, and MI and CNI. Therefore, TCAR might be the preferred treatment modality. Further comparative studies are needed to evaluate the long-term outcomes in this population and to elucidate the relationship of these procedures to the individual outcomes of stroke, MI, and death.

De Novo Renal Failure and Clinical Outcomes of Patients With Critical Coronavirus Disease 2019.

OBJECTIVES: To describe the characteristics and outcomes associated with concomitant renal and respiratory failure in patients with critical coronavirus disease 2019. DESIGN, SETTING, AND PATIENTS: This is a case series of patients from a U.S. healthcare system in New York City. All adult patients (≥ 18 yr) admitted to the hospital with positive coronavirus disease 2019 testing between March 10, 2020, and March 31, 2020, who required mechanical ventilatory support were included. Patients who remained hospitalized were followed through May 1, 2020. INTERVENTIONS: Renal replacement therapy included at least one session of dialysis, continued venovenous hemofiltration, or peritoneal dialysis. MEASUREMENTS AND MAIN RESULTS: Baseline characteristics, laboratory markers, 30-day in-hospital outcomes, ventilator days, and survival to discharge were included. Multivariate predictors for mortality and need for renal replacement therapy were identified. A total of 330 patients were included in this analysis and were most commonly greater than or equal to 70 years (40%), male (61%), Black or African American (41%), and Hispanic or Latino (38%). Renal replacement therapy was required in 101 patients (29%), most commonly among Blacks or African Americans (50%). Elevated d-dimer, C-reactive protein, and procalcitonin were associated with renal replacement therapy, compared with the nondialysis cohort. Overall, 243 patients (74%) died and 56 (17%) were discharged from the hospital, of which 9 (3%) required renal replacement therapy. Male sex (odds ratio, 2.0; 1.1-3.5; p = 0.020), Black race (odds ratio, 1.8; 1.0-3.1; p = 0.453), and history of hypertension (odds ratio, 2.7; 1.3-5.4; p = 0.005) were predictors for requiring renal replacement therapy. Risk factors for in-hospital mortality included age greater than or equal to 60 years (odds ratio, 6.2; 3.0-13.0; p < 0.0001), male sex (odds ratio, 3.0; 1.4-6.4; p = 0.004), and body mass index greater than or equal to 30 kg/m2 (odds ratio, 2.1; 1.0-4.4; p = 0.039). Concomitant renal failure in critical coronavirus disease 2019 was not a significant predictor of death (odds ratio, 2.3; 0.98-5.5; p = 0.057). CONCLUSIONS: This case series concludes that respiratory failure conveys significant mortality risk in patients with coronavirus disease 2019 and that survival with concomitant renal failure is rare.

Clinical Stage of Cancer Affects Perioperative Mortality for Gastrointestinal Cancer Surgeries.

BACKGROUND: The impact of the stage of cancer on perioperative mortality remains obscure. The purpose of this study was to investigate whether cancer stage influences 30-d mortality for gastric, pancreatic, and colorectal cancers. METHODS: Data were collected from the National Cancer Database for patients undergoing resections for cancers of the stomach, pancreas, colon, or rectum between 2004 and 2015. The main analysis was conducted among patients with cancer stages 1-3. A sensitivity analysis also included cancer stage 4. Descriptive statistics were used to compare the patients' baseline characteristics. Generalized linear mixed models were used to evaluate the relationship between stage and 30-d mortality, controlling for other disease-, patient- and hospital-level factors. Pseudo R2 statistics (%Δ pseudo R2) were used to quantify the relative explanatory capacity of the variables to the model for 30-d mortality. All analyses were performed using SAS 9.4. RESULTS: The cohort included 24,468, 28,078, 176,285, and 64,947 patients with stomach, pancreas, colon, and rectal cancers, respectively. After adjusting for other variables, 30-d mortality was different by stage for all cancer types examined. The factor most strongly associated with 30-d mortality was age (%Δ pseudo R2 range 14%-39%). The prognostic impact of cancer stage (Stages 1, 2, or 3) on 30-d mortality was comparable to that of the Charlson comorbidity index. CONCLUSIONS: Cancer stage contributes to explaining differences observed in short-term mortality for gastrointestinal cancers. Short-term mortality models would benefit by including more granular cancer stage, beyond disseminated status alone.

The Utility of Hepatobiliary Scintigraphy Scans in the Tokyo Guidelines Era for Acute Cholecystitis.

BACKGROUND: Hepatobiliary Scintigraphy (HIDA) aids the diagnosis of acute cholecystitis (AC) but has limitations. We sought to design a model based on the Tokyo Guidelines 2018 (TG18) to predict HIDA results. METHODS: A retrospective review of patients who underwent a HIDA scan during the evaluation of AC was performed. Using logistic regression techniques incorporating the TG18 criterion and additional readily available patient characteristics, a prediction model was created to identify patients likely to test negative for acute cholecystitis by HIDA scan. RESULTS: In 235 patients with suspected AC, a HIDA scan was performed. Variables associated with positive HIDA results were male gender (RR 2.0 (CI 1.33-2.99), age (OR 1.02 (CI 1.01-1.04), right upper quadrant tenderness (RR 1.7 (CI 1.1-2.8)), clinical Murphy's sign (RR 2.2 (CI 1.5-3.4)), ultrasound findings suggestive of AC by any of its components (RR 3.2 (CI 1.6-6.5)), gallbladder wall thickening (RR 2.0 (CI 1.3-3.1)), and gallbladder distention (RR 1.9 (CI 1.3-2.9)). These variables allowed for creation of a model to predict HIDA results. The model predicted HIDA results in 36.9% of patients with an area under the curve of 0.81. CONCLUSIONS: In the era of TG18, HIDA is probably over utilized. We developed an accurate, simple model based on TG18 that identifies a group of patients for whom a HIDA scan is unnecessary to establish the diagnosis of AC.

Outcomes of Adrenalectomy and the Aldosteronoma Resolution Score in the Black and Hispanic Population.

BACKGROUND: Outcomes after adrenalectomy in patients with primary aldosteronism (PA) are variable. The aldosteronoma resolution score (ARS) uses preoperative variables to calculate a score that identifies those patients that are more likely to have resolution of hypertension after adrenalectomy. We aim to determine the efficacy of adrenalectomy and whether the ARS accurately predicts clinical success in a Black and Hispanic population. METHODS: We reviewed patients who underwent adrenalectomy for PA from 2004 to 2018 at two academic centers treating primarily Hispanic and Black patients. Postoperative outcomes were evaluated based on the primary aldosteronism surgical outcome consensus criterion. Retrospectively, the accuracy of ARS was determined by a receiver operating characteristic curve and the area under the curve (AUC). RESULTS: Forty-three Hispanic and 10 Black patients underwent adrenalectomy for PA. Twenty-two patients (41.5%) had complete clinical success. Variables associated with complete clinical success in the univariate analysis were female gender (p = 0.026), younger age (p = 0.001), lower preoperative aldosterone (p = 0.035), lower preoperative systolic blood pressure (p = 0.001), fewer number of preoperative antihypertensive medications (p = 0.007) and a higher ARS (p = 0.003). On multivariate analysis, only fewer number of preoperative antihypertensive medications was independently associated with complete clinical success (p = 0.026). The AUC of the ARS was 0.746. CONCLUSION: The rate of clinical success from adrenalectomy is good for Hispanic and Black patients with PA. Our analysis shows that the ARS is an accurate test of clinical success in Hispanic and Black patients. The ARS may be utilized preoperatively to frame expectations after adrenalectomy in these populations.

COVID-19 infection in kidney transplant recipients at the epicenter of pandemics.

We investigated the prevalence and clinical outcomes of COVID-19 in recipients of kidney transplants in the Bronx, New York, one of the epicenters of the pandemic. Between March 16 and June 2, 2020, 132 kidney transplant recipients tested positive by SARS-CoV-2 RT-PCR. From May 3 to July 29, 2020, 912 kidney transplant recipients were screened for SARS-CoV-2 IgG antibodies during routine clinic visits, of which 16.6% tested positive. Fifty-five of the 152 patients had previously tested positive by RT-PCR, while the remaining 97 did not have significant symptoms and had not been previously tested by RT-PCR. The prevalence of SARS-CoV-2 infection was 23.4% in the 975 patients tested by either RT-PCR or SARS-CoV-2 IgG. Older patients and patients with higher serum creatinine levels were more likely diagnosed by RT-PCR compared to SARS-CoV-2 IgG. Sixty-nine RT-PCR positive patients were screened for SARS-CoV-2 IgG antibodies at a median of 44 days post-diagnosis (Inter Quartile Range 31-58) and 80% were positive. Overall mortality was 20.5% but significantly higher (37.8%) in the patients who required hospitalization. Twenty-three percent of the hospitalized patients required kidney replacement therapy and 6.3% lost their allografts. In multivariable analysis, older age, receipt of deceased-donor transplantation, lack of influenza vaccination in the previous year and higher serum interleukine-6 levels were associated with mortality. Thus, 42% of patients with a kidney transplant and with COVID-19 were diagnosed on antibody testing without significant clinical symptoms; 80% of patients with positive RT-PCR developed SARS-CoV-2 IgG and mortality was high among patients requiring hospitalization.

The effect of COVID-19 on stroke hospitalizations in New York City.

BACKGROUND: Little is known about the effect of the Coronavirus disease 2019 pandemic on stroke care and the impact of the epidemic on acute stroke hospitalizations has not been described. METHODS: We analyze the stroke admission rate in three hospitals in New York City from January 1, 2020 through April 17, 2020, identifying all cases of acute ischemic stroke, intraparenchymal hemorrhage and subarachnoid hemorrhage. RESULTS: We confirmed 518 cases of out-of-hospital stroke. During the baseline period up to February 25, 2020, the daily stroke admission rate was stable, with the slope of the regression describing the number of admissions over time equal to -0.33 (se = 1.21), not significantly different from 0 (p = 0.79), with daily admissions averaging 41. During the pandemic period, the slope was -4.4 (se = 1.00); i.e., the number of stroke admissions decreased an average of 4.4 per week, (p = 0.005), with weekly admissions averaging 23, a reduction of 44% versus baseline. This general result was not different by patient age, sex, or race/ethnicity. CONCLUSIONS: The weekly stroke admission rate started declining two weeks prior to the local surge of coronavirus admissions. The consequences of lack of diagnosis and treatment of a large proportion of acute stroke patients are likely severe and lasting.

Two-Year Outcomes of Surgical Treatment of Severe Ischemic Mitral Regurgitation.

BACKGROUND: In a randomized trial comparing mitral-valve repair with mitral-valve replacement in patients with severe ischemic mitral regurgitation, we found no significant difference in the left ventricular end-systolic volume index (LVESVI), survival, or adverse events at 1 year after surgery. However, patients in the repair group had significantly more recurrences of moderate or severe mitral regurgitation. We now report the 2-year outcomes of this trial. METHODS: We randomly assigned 251 patients to mitral-valve repair or replacement. Patients were followed for 2 years, and clinical and echocardiographic outcomes were assessed. RESULTS: Among surviving patients, the mean (±SD) 2-year LVESVI was 52.6±27.7 ml per square meter of body-surface area with mitral-valve repair and 60.6±39.0 ml per square meter with mitral-valve replacement (mean changes from baseline, -9.0 ml per square meter and -6.5 ml per square meter, respectively). Two-year mortality was 19.0% in the repair group and 23.2% in the replacement group (hazard ratio in the repair group, 0.79; 95% confidence interval, 0.46 to 1.35; P=0.39). The rank-based assessment of LVESVI at 2 years (incorporating deaths) showed no significant between-group difference (z score=-1.32, P=0.19). The rate of recurrence of moderate or severe mitral regurgitation over 2 years was higher in the repair group than in the replacement group (58.8% vs. 3.8%, P<0.001). There were no significant between-group differences in rates of serious adverse events and overall readmissions, but patients in the repair group had more serious adverse events related to heart failure (P=0.05) and cardiovascular readmissions (P=0.01). On the Minnesota Living with Heart Failure questionnaire, there was a trend toward greater improvement in the replacement group (P=0.07). CONCLUSIONS: In patients undergoing mitral-valve repair or replacement for severe ischemic mitral regurgitation, we observed no significant between-group difference in left ventricular reverse remodeling or survival at 2 years. Mitral regurgitation recurred more frequently in the repair group, resulting in more heart-failure-related adverse events and cardiovascular admissions. (Funded by the National Institutes of Health and Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00807040.).

Rate Control versus Rhythm Control for Atrial Fibrillation after Cardiac Surgery.

BACKGROUND: Atrial fibrillation after cardiac surgery is associated with increased rates of death, complications, and hospitalizations. In patients with postoperative atrial fibrillation who are in stable condition, the best initial treatment strategy--heart-rate control or rhythm control--remains controversial. METHODS: Patients with new-onset postoperative atrial fibrillation were randomly assigned to undergo either rate control or rhythm control. The primary end point was the total number of days of hospitalization within 60 days after randomization, as assessed by the Wilcoxon rank-sum test. RESULTS: Postoperative atrial fibrillation occurred in 695 of the 2109 patients (33.0%) who were enrolled preoperatively; of these patients, 523 underwent randomization. The total numbers of hospital days in the rate-control group and the rhythm-control group were similar (median, 5.1 days and 5.0 days, respectively; P=0.76). There were no significant between-group differences in the rates of death (P=0.64) or overall serious adverse events (24.8 per 100 patient-months in the rate-control group and 26.4 per 100 patient-months in the rhythm-control group, P=0.61), including thromboembolic and bleeding events. About 25% of the patients in each group deviated from the assigned therapy, mainly because of drug ineffectiveness (in the rate-control group) or amiodarone side effects or adverse drug reactions (in the rhythm-control group). At 60 days, 93.8% of the patients in the rate-control group and 97.9% of those in the rhythm-control group had had a stable heart rhythm without atrial fibrillation for the previous 30 days (P=0.02), and 84.2% and 86.9%, respectively, had been free from atrial fibrillation from discharge to 60 days (P=0.41). CONCLUSIONS: Strategies for rate control and rhythm control to treat postoperative atrial fibrillation were associated with equal numbers of days of hospitalization, similar complication rates, and similarly low rates of persistent atrial fibrillation 60 days after onset. Neither treatment strategy showed a net clinical advantage over the other. (Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT02132767.).

Two-Year Outcomes of Surgical Treatment of Moderate Ischemic Mitral Regurgitation.

BACKGROUND: In a trial comparing coronary-artery bypass grafting (CABG) alone with CABG plus mitral-valve repair in patients with moderate ischemic mitral regurgitation, we found no significant difference in the left ventricular end-systolic volume index (LVESVI) or survival after 1 year. Concomitant mitral-valve repair was associated with a reduced prevalence of moderate or severe mitral regurgitation, but patients had more adverse events. We now report 2-year outcomes. METHODS: We randomly assigned 301 patients to undergo either CABG alone or the combined procedure. Patients were followed for 2 years for clinical and echocardiographic outcomes. RESULTS: At 2 years, the mean (±SD) LVESVI was 41.2±20.0 ml per square meter of body-surface area in the CABG-alone group and 43.2±20.6 ml per square meter in the combined-procedure group (mean improvement over baseline, -14.1 ml per square meter and -14.6 ml per square meter, respectively). The rate of death was 10.6% in the CABG-alone group and 10.0% in the combined-procedure group (hazard ratio in the combined-procedure group, 0.90; 95% confidence interval, 0.45 to 1.83; P=0.78). There was no significant between-group difference in the rank-based assessment of the LVESVI (including death) at 2 years (z score, 0.38; P=0.71). The 2-year rate of moderate or severe residual mitral regurgitation was higher in the CABG-alone group than in the combined-procedure group (32.3% vs. 11.2%, P<0.001). Overall rates of hospital readmission and serious adverse events were similar in the two groups, but neurologic events and supraventricular arrhythmias remained more frequent in the combined-procedure group. CONCLUSIONS: In patients with moderate ischemic mitral regurgitation undergoing CABG, the addition of mitral-valve repair did not lead to significant differences in left ventricular reverse remodeling at 2 years. Mitral-valve repair provided a more durable correction of mitral regurgitation but did not significantly improve survival or reduce overall adverse events or readmissions and was associated with an early hazard of increased neurologic events and supraventricular arrhythmias. (Funded by the National Institutes of Health and Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00806988.).

Proposed Standardized Neurological Endpoints for Cardiovascular Clinical Trials: An Academic Research Consortium Initiative.

Surgical and catheter-based cardiovascular procedures and adjunctive pharmacology have an inherent risk of neurological complications. The current diversity of neurological endpoint definitions and ascertainment methods in clinical trials has led to uncertainties in the neurological risk attributable to cardiovascular procedures and inconsistent evaluation of therapies intended to prevent or mitigate neurological injury. Benefit-risk assessment of such procedures should be on the basis of an evaluation of well-defined neurological outcomes that are ascertained with consistent methods and capture the full spectrum of neurovascular injury and its clinical effect. The Neurologic Academic Research Consortium is an international collaboration intended to establish consensus on the definition, classification, and assessment of neurological endpoints applicable to clinical trials of a broad range of cardiovascular interventions. Systematic application of the proposed definitions and assessments will improve our ability to evaluate the risks of cardiovascular procedures and the safety and effectiveness of preventive therapies.

Intramyocardial Injection of Mesenchymal Precursor Cells and Successful Temporary Weaning From Left Ventricular Assist Device Support in Patients With Advanced Heart Failure: A Randomized Clinical Trial.

Importance: Left ventricular assist device (LVAD) therapy improves myocardial function, but few patients recover sufficiently for explant, which has focused attention on stem cells to augment cardiac recovery. Objective: To assess efficacy and adverse effects of intramyocardial injections of mesenchymal precursor cells (MPCs) during LVAD implant. Design, Setting, and Participants: A randomized phase 2 clinical trial involving patients with advanced heart failure, undergoing LVAD implant, at 19 North American centers (July 2015-August 2017). The 1-year follow-up ended August 2018. Interventions: Intramyocardial injections of 150 million allogeneic MPCs or cryoprotective medium as a sham treatment in a 2:1 ratio (n = 106 vs n = 53). Main Outcomes and Measures: The primary efficacy end point was the proportion of successful temporary weans (of 3 planned assessments) from LVAD support within 6 months of randomization. This end point was assessed using a Bayesian analysis with a predefined threshold of a posterior probability of 80% to indicate success. The 1-year primary safety end point was the incidence of intervention-related adverse events (myocarditis, myocardial rupture, neoplasm, hypersensitivity reactions, and immune sensitization). Secondary end points included readmissions and adverse events at 6 months and 1-year survival. Results: Of 159 patients (mean age, 56 years; 11.3% women), 155 (97.5%) completed 1-year of follow-up. The posterior probability that MPCs increased the likelihood of successful weaning was 69%; below the predefined threshold for success. The mean proportion of successful temporary weaning from LVAD support over 6 months was 61% in the MPC group and 58% in the control group (rate ratio [RR], 1.08; 95% CI, 0.83-1.41; P = .55). No patient experienced a primary safety end point. Of 10 prespecified secondary end points reported, 9 did not reach statistical significance. One-year mortality was not significantly different between the MPC group and the control group (14.2% vs 15.1%; hazard ratio [HR], 0.89; 95%, CI, 0.38-2.11; P = .80). The rate of serious adverse events was not significantly different between groups (70.9 vs 78.7 per 100 patient-months; difference, -7.89; 95% CI, -39.95 to 24.17; P = .63) nor was the rate of readmissions (0.68 vs 0.75 per 100 patient-months; difference, -0.07; 95% CI, -0.41 to 0.27; P = .68). Conclusions and Relevance: Among patients with advanced heart failure, intramyocardial injections of mesenchymal precursor cells, compared with injections of a cryoprotective medium as sham treatment, did not improve successful temporary weaning from left ventricular assist device support at 6 months. The findings do not support the use of intramyocardial mesenchymal stem cells to promote cardiac recovery as measured by temporary weaning from device support. Trial Registration: clinicaltrials.gov Identifier: NCT02362646.

Surgical ablation of atrial fibrillation during mitral-valve surgery.

BACKGROUND: Among patients undergoing mitral-valve surgery, 30 to 50% present with atrial fibrillation, which is associated with reduced survival and increased risk of stroke. Surgical ablation of atrial fibrillation has been widely adopted, but evidence regarding its safety and effectiveness is limited. METHODS: We randomly assigned 260 patients with persistent or long-standing persistent atrial fibrillation who required mitral-valve surgery to undergo either surgical ablation (ablation group) or no ablation (control group) during the mitral-valve operation. Patients in the ablation group underwent further randomization to pulmonary-vein isolation or a biatrial maze procedure. All patients underwent closure of the left atrial appendage. The primary end point was freedom from atrial fibrillation at both 6 months and 12 months (as assessed by means of 3-day Holter monitoring). RESULTS: More patients in the ablation group than in the control group were free from atrial fibrillation at both 6 and 12 months (63.2% vs. 29.4%, P<0.001). There was no significant difference in the rate of freedom from atrial fibrillation between patients who underwent pulmonary-vein isolation and those who underwent the biatrial maze procedure (61.0% and 66.0%, respectively; P=0.60). One-year mortality was 6.8% in the ablation group and 8.7% in the control group (hazard ratio with ablation, 0.76; 95% confidence interval, 0.32 to 1.84; P=0.55). Ablation was associated with more implantations of a permanent pacemaker than was no ablation (21.5 vs. 8.1 per 100 patient-years, P=0.01). There were no significant between-group differences in major cardiac or cerebrovascular adverse events, overall serious adverse events, or hospital readmissions. CONCLUSIONS: The addition of atrial fibrillation ablation to mitral-valve surgery significantly increased the rate of freedom from atrial fibrillation at 1 year among patients with persistent or long-standing persistent atrial fibrillation, but the risk of implantation of a permanent pacemaker was also increased. (Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00903370.).

A Randomized Dose-Ranging Study of Neuropeptide Y in Patients with Posttraumatic Stress Disorder.

Background: Anxiety and trauma-related disorders are among the most prevalent and disabling medical conditions in the United States, and posttraumatic stress disorder in particular exacts a tremendous public health toll. We examined the tolerability and anxiolytic efficacy of neuropeptide Y administered via an intranasal route in patients with posttraumatic stress disorder. Methods: Twenty-six individuals were randomized in a cross-over, single ascending dose study into 1 of 5 cohorts: 1.4 mg (n=3), 2.8 mg (n=6), 4.6 mg (n=5), 6.8 mg (n=6), and 9.6 mg (n=6). Each individual was dosed with neuropeptide Y or placebo on separate treatment days 1 week apart in random order under double-blind conditions. Assessments were conducted at baseline and following a trauma script symptom provocation procedure subsequent to dosing. Occurrence of adverse events represented the primary tolerability outcome. The difference between treatment conditions on anxiety as measured by the Beck Anxiety Inventory and the State-Trait Anxiety Inventory immediately following the trauma script represented efficacy outcomes. Results: Twenty-four individuals completed both treatment days. Neuropeptide Y was well tolerated up to and including the highest dose. There was a significant interaction between treatment and dose; higher doses of neuropeptide Y were associated with a greater treatment effect, favoring neuropeptide Y over placebo on Beck Anxiety Inventory score (F1,20=4.95, P=.038). There was no significant interaction for State-Trait Anxiety Inventory score. Conclusions: Our study suggests that a single dose of neuropeptide Y is well tolerated up to 9.6 mg and may be associated with anxiolytic effects. Future studies exploring the safety and efficacy of neuropeptide Y in stress-related disorders are warranted. The reported study is registered at: http://clinicaltrials.gov (ID: NCT01533519).