Abstract Background Many patients receiving amiodarone therapy are male. The long-term risk for amiodarone-induced thyroid dysfunction in these patients has not been systematically and prospectively ...investigated. The purpose of this study was to determine the extent of amiodarone-induced thyroid dysfunction in a large male cohort. Methods This is a substudy of a prospective randomized controlled trial (SAFE-Trial) in which amiodarone, sotalol, and placebo for persistent atrial fibrillation were evaluated. For the purpose of this substudy, sotalol and placebo groups were combined into a control group. Serial thyroid function tests were performed over 1-4.5 years. Of the 665 patients enrolled in the SAFE-Trial, 612 patients were included in this sub-study. Results Subclinical hypothyroidism, thyroid-stimulating hormone (TSH) level 4.5-10 mU/L, was seen among 25.8% of the amiodarone-treated patients and only 6.6% of controls ( P <.0001). Overt hypothyroidism, TSH level >10 mU/L, was seen among 5.0% of the amiodarone-treated patients, and only 0.3% of controls ( P <.001). By 6 months, 93.8% of the patients who developed TSH elevations above 10 mU/L on amiodarone had been detected. There was a trend toward a greater proportion of hyperthyroidism, defined as a TSH <0.35 mU/L, in the amiodarone group compared with the control group (5.3% vs 2.4%, P = .07). Conclusions Hypothyroidism developed in 30.8% of older males treated with amiodarone and in only 6.9% of the controls. Hypothyroidism presented at an early stage of therapy. Hyperthyroidism occurred in 5.3% of amiodarone treated patients, and was a subclinical entity in all but 1 case.
Background Therapy for chronic atrial fibrillation (AF) focuses on rate versus rhythm control, but little is known about the effects of common therapeutic interventions on exercise tolerance in AF. ...Methods Six hundred fifty-five patients with chronic AF underwent maximal exercise testing at baseline and 8 weeks, 6 months, and 1 year after randomization to sotalol, amiodarone, or placebo therapy and attempted direct current cardioversion. Analyses of baseline determinants of exercise capacity, predictors of change in exercise capacity at 6 months and 1 year, and the short- and long-term effects of cardioversion on exercise capacity were made. Results Age, obesity, and presence of symptoms accompanying AF were inversely associated with baseline exercise capacity, but these factors accounted for only 10% of the variance in exercise capacity. Patients most likely to benefit from cardioversion were those most limited initially, younger, not obese or hypertensive, and with an uncontrolled ventricular rate at baseline. Conversion to sinus rhythm (SR) resulted in significant reductions in resting (≈25 beat/min) and peak exercise (≈40 beat/min) heart rates at 6 months and 1 year ( P < .001). Successful cardioversion improved exercise capacity by 15% at 8 weeks, and these improvements were maintained throughout the year. This improvement was observed both among those who maintained SR and those with intermittent AF. Conclusion Cardioversion resulted in a sustained improvement in exercise capacity over the course of 1 year, and this improvement was similar between those in SR and those with SR and recurrent AF. Patients most likely to improve with treatment tended to be younger and nonobese and have the greatest limitations initially.
Background The Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study profiled patients with mild, moderate, and severe asthma and nonatopic healthy control subjects. Objective We ...explored this data set to define type 2 inflammation based on airway mucosal IL-13–driven gene expression and how this related to clinically accessible biomarkers. Methods IL-13–driven gene expression was evaluated in several human cell lines. We then defined type 2 status in 25 healthy subjects, 28 patients with mild asthma, 29 patients with moderate asthma, and 26 patients with severe asthma based on airway mucosal expression of (1) CCL26 (the most differentially expressed gene), (2) periostin, or (3) a multigene IL-13 in vitro signature (IVS). Clinically accessible biomarkers included fraction of exhaled nitric oxide (F eno ) values, blood eosinophil (bEOS) counts, serum CCL26 expression, and serum CCL17 expression. Results Expression of airway mucosal CCL26, periostin, and IL-13–IVS all facilitated segregation of subjects into type 2–high and type 2–low asthmatic groups, but in the ADEPT study population CCL26 expression was optimal. All subjects with high airway mucosal CCL26 expression and moderate-to-severe asthma had F eno values (≥35 ppb) and/or high bEOS counts (≥300 cells/mm3 ) compared with a minority (36%) of subjects with low airway mucosal CCL26 expression. A combination of F eno values, bEOS counts, and serum CCL17 and CCL26 expression had 100% positive predictive value and 87% negative predictive value for airway mucosal CCL26–high status. Clinical variables did not differ between subjects with type 2–high and type 2–low status. Eosinophilic inflammation was associated with but not limited to airway mucosal type 2 gene expression. Conclusion A panel of clinical biomarkers accurately classified type 2 status based on airway mucosal CCL26, periostin, or IL-13–IVS gene expression. Use of F eno values, bEOS counts, and serum marker levels (eg, CCL26 and CCL17) in combination might allow patient selection for novel type 2 therapeutics.
Energy levels for electrocardioversion in atrial fibrillation (AF) have been empiric, and the influence of antiarrhythmic therapy compared with placebo is largely unknown.
The purpose of this study ...was to determine systematically the energy levels for electrocardioversion in patients with persistent AF and to define the influence of antiarrhythmic therapy.
Patients (n = 665) with persistent AF were randomized to amiodarone, sotalol, or placebo. Rate control, if necessary, was achieved with digoxin, diltiazem, or verapamil. Among the 665 patients, 504 who did not achieve sinus rhythm at day 28 had electrocardioversion systematically by a prespecified four-step protocol as follows: monophasic shocks-100, 200, 360, 360 J; or biphasic shocks-150, 175, 200, 200 J sequentially. Energy levels and shock waveforms (monophasic/biphasic) for successful electrocardioversion (sinus rhythm for at least 1 minute) and use of antiarrhythmic therapy and calcium channel blockers were recorded.
Electrocardioversion was successful in 371 (71.6%) of 504 patients: 72%, 73.5%, and 67.9% for patients assigned to amiodarone, sotalol, and placebo, respectively. Overall, after adjustments for age, body mass index (BMI), history of AF, shock waveforms, left atrial size, and ejection fraction, both amiodarone (odds ratio OR: 2.16, 95% confidence interval CI: 1.24-3.77, P <.01) and sotalol (OR: 1.92, 95% CI: 1.11-3.33, P = .02) significantly facilitated successful electrocardioversion compared with placebo. Calcium channel blockers had no effect on the success rate of electrocardioversion. Success of electrocardioversion was associated with lower BMI, AF history < or =1 year, and older age. Compared with placebo, patients taking amiodarone were significantly more likely to achieve successful electrocardioversion in step 1 (OR: 2.73, 95% CI: 1.11-6.74, P = .03) and step 3 (OR: 1.86, 95% CI: 1.00-3.44, P = .05) but not in steps 2 and 4. Sotalol was superior to placebo in step 4 (OR: 2.58, 95% CI: 1.02-6.52, P = .05) and trended in step 2 (OR: 1.7, 95% CI: 0.98-3.07, P = .06). Successful electrocardioversion was seen in 11%, 29%, 38%, and 29% in steps 1, 2, 3, and 4, respectively. Compared with monophasic shocks, biphasic shocks achieved higher success rates for step 1 (P <.001) and step 2 (P <.01), respectively. Antiarrhythmic therapy did not influence the total number of energy steps used for the patients with successful electrocardioversion. However, biphasic shocks, lower BMI, and AF duration < or =1 year were associated with less energy step used for successful cardioversion.
Amiodarone and sotalol facilitated successful electrocardioversion, which could be achieved in a stepwise fashion. Upon achievement of successful electrocardioversion, amiodarone is superior to placebo, and sotalol has a lesser effect. Antiarrhythmic drugs had no effect on the total number of energy step use in patients who had successful electrocardioversion. Calcium channel blockers had no influence on the success rate in achieving sinus rhythm. Successful electrocardioversion was associated with lower BMI and AF history < or =1 year. Lower energy use was associated with biphasic shocks, lower BMI, and AF duration < or =1 year.
Controlled clinical trial data are lacking for cardiac resynchronization therapy (CRT) outcomes in patients with advanced heart failure (HF) from reduced left ventricular ejection fraction (HFrEF) ...and intermittent atrial fibrillation or flutter (IAF/AFL).
The purpose of this study was to describe CRT outcomes in patients with IAF/AFL and advanced HF.
HF outcomes in patients in the COMPANION (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure) trial with New York Heart Association class III or IV HFrEF, left ventricular ejection fraction ≤0.35, sinus rhythm at randomization, and no history of baseline arrhythmia were compared with those with a history of IAF/AFL.
In those with no history of baseline arrhythmia (n = 887), compared with optimal pharmacological therapy (OPT) with no CRT, the CRT + OPT arms exhibited a significant reduction in the end points of death or any hospitalization (hazard ratio HR 0.73 95% Confidence Interval (CI): 0.60 to 0.89; P = .002) and death or HF hospitalization (HR 0.53 95% CI: 0.41 to 0.68; P < .001). In contrast, in the IAF/AFL subgroup (n = 293), CRT did not result in improved outcomes compared with OPT (death or any hospitalization: HR 1.16 95% CI: 0.83 to 1.63; P = .38; death or HF hospitalization: HR 0.97 95% CI: 0.64 to 1.46; P = .88). The interaction between history of AF/AFL and CRT was statistically significant for both outcomes (P < .05).
In the COMPANION trial, patients with moderate to severe HFrEF and a history of IAF/AFL had no benefit from CRT.
Objectives The scientific understanding of aortic dilation associated with bicuspid aortic valve (BAV) has evolved during the past 2 decades, along with improvements in diagnostic technology and ...surgical management. We aimed to evaluate secular trends and predictors of thoracic aortic surgery among patients with BAV in the United States. Methods We used the 1998-2009 Nationwide Inpatient Sample, an administrative dataset representative of US hospital admissions, to identify hospitalizations for adults aged 18 years or more with BAV and aortic valve or thoracic aortic surgery. Covariates included age, gender, year, aortic dissection, endocarditis, thoracic aortic aneurysm, number of comorbidities, hospital teaching status and region, primary insurance, and concomitant coronary artery bypass surgery. Results Between 1998 and 2009, 48,736 ± 3555 patients with BAV underwent aortic valve repair or replacement and 1679 ± 120 patients with BAV underwent isolated thoracic aortic surgery. The overall number of surgeries increased more than 3-fold, from 4556 ± 571 in 1998/1999 to 14,960 ± 2107 in 2008/2009 ( P < .0001). The proportion of aortic valve repair or replacement including concomitant thoracic aortic surgery increased from 12.8% ± 1.4% in 1998/1999 to 28.5% ± 1.6% in 2008/2009, which mirrored an increasing proportion of patients with a diagnosis of thoracic aortic aneurysm. Mortality was equivalent for patients undergoing aortic valve repair or replacement with thoracic aortic surgery and those undergoing isolated aortic valve repair or replacement (1.8% ± 0.3% vs 1.5% ± 0.2%; multivariable odds ratio, 1.02; 95% confidence interval, 0.67-1.57), with decreasing mortality over the study period (from 2.5% ± 0.6% in 1998/1999 to 1.5% ± 0.2% in 2008/2009; multivariable odds ratio per 2-year increment, 0.89; 95% confidence interval, 0.81-0.99; P = .03). Total charges for BAV surgical hospitalizations increased more than 7.5-fold from approximately $156 million in 1998 to $1.2 billion in 2009 (inflation-adjusted 2009 dollars). Conclusions There was a marked increase in the use of thoracic aortic surgery among patients with BAV.
Background:
The meniscal roots are essential for preserving the structural and biomechanical properties of the tibiofemoral joint. Posterior meniscal root avulsions can cause meniscal extrusion, ...joint space narrowing, and progressive knee arthritis. Iatrogenic avulsions after malpositioning of the transtibial tunnels during anterior cruciate ligament (ACL) reconstruction have previously been reported in the literature to account for poor long-term outcomes seen in some patients following ACL reconstruction. Therefore, correct transtibial tunnel placement during ACL reconstruction is essential to avoid iatrogenic meniscal damage.
Indication:
Patients are indicated for surgery when presenting with a verified, symptomatic, complete meniscal root tear seen on advanced imaging or diagnostic arthroscopy. Contraindications for a root repair include the development of advanced osteoarthritis in the ipsilateral compartment, older age, and malalignment in the affected compartment.
Technique Description:
The ACL graft was appreciated and noted to be vertical and posterior relative to its native anatomical position, violating the lateral posterior horn root attachment. A full lateral posterior meniscal root avulsion was then confirmed directly adjacent to the graft tunnel. A curette was used to prepare the footprint of the lateral meniscal root on the posterolateral tibia for the 2-tunnel transtibial pull-out tunnels, and a grasper was used to position the torn meniscal root back into its anatomical site. Two ultrabraided sutures were passed through the posterior horn of the lateral meniscus using a suture passer. These were then passed through the tunnels into the body of the meniscal root and reduced to its native anatomical position. The suture repair was then secured over an Endobutton Fixation Device at 90° of knee flexion through each tunnel into its native anatomical position while confirming its adequate tension by viewing arthroscopically.
Results:
Within 2 years postoperatively, patients are expected to have improved overall knee-specific quality of life, reduced pain, and a successful return to activities.
Discussion/Conclusion:
This injury underscores the importance of an accurate tibial tunnel placement during ACL reconstruction to avoid posterior meniscal root injuries and other associated complications. Physicians should consider such pathology in the differential diagnosis of patients presenting with persistent pain and instability following a primary ACL reconstruction.
Patient Consent Disclosure Statement:
The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
Graphical Abstract
This is a visual representation of the abstract.
Abstract Background context Recent reports of postoperative radiculitis, bone osteolysis, and symptomatic ectopic bone formation after recombinant human bone morphogenetic protein-2 (rhBMP-2) use in ...transforaminal lumbar interbody fusions (TLIFs) are a cause for concern. Purpose To determine the clinical and radiographic complications associated with BMP utilization in a minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) environment. Study design/setting Retrospective clinical case series at a single institution. Patient sample Five hundred seventy-three consecutive patients undergoing an MIS-TLIF. Outcome measures Reoperation rates and total costs associated with complications of rhBMP-2 use and pseudarthrosis. Methods A retrospective review of 610 consecutive patients undergoing an MIS-TLIF (2007–2010) by a single surgeon at our institution was performed (mean age 48.7 years, range 26–82 years). All patients underwent an MIS laminectomy with bilateral facetectomy, single TLIF cage, unilateral pedicle screw fixation, and 12 mg (large kit) or 4.2 mg (small kit) of rhBMP-2. The BMP-2 collagen-soaked sponge was placed anteriorly in the disc space, followed by local bone graft, and then the cage was filled only with local bone and no BMP-2. Patients were evaluated at 6 months and 1 year with computed tomography (CT) scan. Those demonstrating neuroforaminal bone growth, osteolysis/cage migration, or pseudarthrosis were reviewed, and cost data including direct cost/procedure for both index and revision surgeries were collected. Results Of the 573 patients, 10 (1.7%) underwent 15 additional procedures based on recalcitrant radiculopathy and CT evidence of neuroforaminal bone growth, vertebral body osteolysis, and/or cage migration. Thirty-nine patients (6.8%) underwent reoperation for clinically symptomatic pseudarthrosis. Bone overgrowth was associated with nerve impingement and radiculopathy in all 10 patients (small kit, n=9; large kit, n=1). Osteolysis and cage migration occurred in 2 (20%) of these same 10 patients. Average total costs were calculated per procedure ($19,224), and the costs for reoperation equaled $14,785 per encounter for neuroforaminal bone growth and $20,267 for pseudarthrosis. Conclusions Symptomatic ectopic bone formation, vertebral osteolysis, and pseudarthrosis are recognized complications with the use of rhBMP-2 in MIS-TLIFs. Potential causes include improper dosage and a closed space that prevents the egress of the postoperative BMP-2 fluid collection. Management of these complications has a substantial cost for the patient and the surgeon and needs to be considered with the off-label use of rhBMP-2.
Most transplant centers perform serial cardiac biopsies for rejection surveillance in pediatric heart transplant (HT) recipients. We sought to assess tissue Doppler imaging (TDI) findings during ...biopsy specimen-proven rejection in pediatric HT recipients and to develop TDI criteria for absence of rejection with high predictive accuracy.
We included the 122 HT recipients in follow-up at our center (median age at HT, 8.7 years). We identified all echocardiograms with adequate TDI data performed within 24 hours of a cardiac biopsy during 2005 to 2011. Rejection was defined as Grade ≥ 2R cellular rejection or antibody-mediated rejection. Paired comparisons of TDI velocities were made using patients' baseline velocities as the control.
Overall, 647 specimen-pairs were identified where there was no rejection at baseline. In 24 of these, the second biopsy specimen demonstrated rejection. Using receiver operating characteristic curve analysis of percentage change from baseline, we identified < 15% decline in left ventricular (LV) S' velocity and < 5% decline in LV A' velocity to individually predict non-rejection with > 99% accuracy. When joint criteria were used, the predictive accuracy was 100%, and no rejection event was misclassified. More than 75% of TDI pairs met these criteria for non-rejection.
Biopsy specimen-proven rejection is associated with a significant decline in biventricular TDI velocities from baseline in pediatric HT recipients. By using well-defined TDI criteria to predict non-rejection, a substantial proportion of planned biopsies may be deferred or avoided at minimal risk to pediatric HT recipients.
Background Orthotopic liver transplantation (OLT) is the gold standard treatment for patients with early hepatocellular carcinoma (HCC). There are concerns about the efficacy of OLT for HCC in older ...patients, who we hypothesized might have poorer outcomes. Therefore, we sought to examine advanced age and its impact on OLT outcomes. Study Design The United Network for Organ Sharing database was queried for patients who underwent OLT for HCC from 1987 to 2009. Patients were divided into 3 age groups: 35 to 49 years old, 50 to 64 years old, and 65 years or older, and patient characteristics were compared. Univariate and multivariate analyses were performed to assess the impact of age on OLT outcomes. Results Of 10,238 patients with OLT for HCC, 16.5% (n = 1,688) of patients were 35 to 49 years old, 67.8% (n = 6,937) were 35 to 49 years old, and 15.8% (n = 1,613) were 65 years and older. By Kaplan-Meier method, the 50- to 64-year-old age group had the highest overall survival, despite having one of the highest rates of hepatitis C positivity (70%), but this group also had the lowest rate of diabetes mellitus (8.7%). The lowest overall survival was observed in the 65-year or older age group (p < 0.001). Finally, there was no difference in disease-specific survival among the age groups (p = 0.858), and patients aged 65 years and older had the highest rate of death from nonhepatic causes (17.5%). Conclusions Although OS was prolonged in younger patients who underwent OLT for HCC, there was no observed difference in disease-specific survival among the age groups. Our results suggest that carefully selected patients 65 years of age and older can derive equal benefit from OLT for HCC when compared with their younger counterparts.
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