Germline predictors for bevacizumab induced hypertensive crisis in ECOG-ACRIN 5103 and BEATRICE.

BACKGROUND: Bevacizumab is a beneficial therapy in several advanced cancer types. Predictive biomarkers to better understand which patients are destined to benefit or experience toxicity are needed. Associations between bevacizumab induced hypertension and survival have been reported but with conflicting conclusions. METHODS: We performed post-hoc analyses to evaluate the association in 3124 patients from two phase III adjuvant breast cancer trials, E5103 and BEATRICE. Differences in invasive disease-free survival (IDFS) and overall survival (OS) between patients with hypertension and those without were compared. Hypertension was defined as systolic blood pressure (SBP) ≥ 160 mmHg (n = 346) and SBP ≥ 180 mmHg (hypertensive crisis) (n = 69). Genomic analyses were performed to evaluate germline genetic predictors for the hypertensive crisis. RESULTS: Hypertensive crisis was significantly associated with superior IDFS (p = 0.015) and OS (p = 0.042), but only IDFS (p = 0.029; HR = 0.28) remained significant after correction for prognostic factors. SBP ≥ 160 mmHg was not associated with either IDFS or OS. A common single-nucleotide polymorphism, rs6486785, was significantly associated with hypertensive crisis (p = 8.4 × 10-9; OR = 5.2). CONCLUSION: Bevacizumab-induced hypertensive crisis is associated with superior outcomes and rs6486785 predicted an increased risk of this key toxicity.

Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure.

BACKGROUND: The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS: We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS: During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS: Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016-002299-28.).

The effect of intravenous tranexamic acid on visual clarity in arthroscopic shoulder surgery compared to epinephrine and a placebo: a double-blinded, randomized controlled trial.

BACKGROUND: The addition of epinephrine in irrigation fluid and the intravenous or local administration of tranexamic acid have independently been reported to decrease bleeding, thereby improving surgeons' visualization during arthroscopic shoulder procedures. No study has compared the effect of intravenous tranexamic acid, epinephrine in the irrigation fluid, or the combination of both tranexamic acid and epinephrine on visual clarity during shoulder arthroscopy with a placebo group. We hypothesized that intravenous tranexamic acid is more effective than epinephrine mixed in the irrigation fluid in improving visualization during shoulder arthroscopy, with no additive effect when both are used. METHODS: Patients aged ≥18 years undergoing shoulder arthroscopy were randomized into one of 4 study arms: (1) saline irrigation fluid (placebo); (2) epinephrine (0.33 mL of 1:1000 per liter) mixed in irrigation fluid (EPI); (3) 1 g intravenous tranexamic acid (TXA); and (4) epinephrine and tranexamic acid combined (TXA + EPI). Visualization was rated intraoperatively on a scale from 0, indicating poor clarity, to 3, indicating excellent clarity, every 15 minutes and overall. The primary outcome measure was the overall rating of visualization. A stepwise linear regression was performed using visualization as the dependent variable and independent variables including presence or absence of epinephrine and tranexamic acid, surgery duration, complexity, mean arterial pressure, increase in pump pressure, and volume of irrigation fluid. RESULTS: One hundred twenty-eight patients (mean age 56 years) were randomized. Mean visual clarity for the placebo, TXA, EPI, and TXA + EPI groups were 2.0 (±0.6), 2.0 (±0.6), 2.6 (±0.5), and 2.7 (±0.5), respectively (P < .001). The presence or absence of epinephrine was the most significant predictor of visual clarity (P < .001). Tranexamic acid presence or absence had no effect. No adverse events were recorded in any of the groups. CONCLUSION: Intravenous tranexamic acid is not an effective alternative to epinephrine in irrigation fluid to improve visualization during routine arthroscopic shoulder surgeries, and there is no additive effect when both are used.

Incidental detection of malignancy during preprocedural workup for transcatheter aortic valve implantation: A longitudinal cohort study.

The aim of this retrospective analysis was to investigate the prevalence and prognostic importance of incidental malignancy detected during pre-TAVI computed tomography. Among 579 patients, CT-work-up for TAVI exposed previously undetected malignancy in 4.5% of patients. TAVI patients with a new malignancy had a 2.9-fold increased risk of death at 1 year, and a 16 month shorter mean survival time compared to patients with no malignancy.

Influence of atrial fibrillation on efficacy and safety of omecamtiv mecarbil in heart failure: the GALACTIC-HF trial.

AIMS: In GALACTIC-HF, the cardiac myosin activator omecamtiv mecarbil compared with placebo reduced the risk of heart failure events or cardiovascular death in patients with heart failure with reduced ejection fraction. We explored the influence of atrial fibrillation or flutter (AFF) on the effectiveness of omecamtiv mecarbil. METHODS AND RESULTS: GALACTIC-HF enrolled patients with New York Heart Association (NYHA) Class II-IV heart failure, left ventricular ejection fraction ≤35%, and elevated natriuretic peptides. We assessed whether the presence or absence of AFF, a pre-specified subgroup, modified the treatment effect for the primary and secondary outcomes, and additionally explored effect modification in patients who were or were not receiving digoxin. Patients with AFF (n = 2245, 27%) were older, more likely to be randomized as an inpatient, less likely to have a history of ischaemic aetiology or myocardial infarction, had a worse NYHA class, worse quality of life, lower estimated glomerular filtration rate, and higher N-terminal pro-B-type natriuretic peptide. The treatment effect of omecamtiv mecarbil was modified by baseline AFF (interaction P = 0.012), with patients without AFF at baseline deriving greater benefit. The worsening of the treatment effect by baseline AFF was significantly more pronounced in digoxin users than in non-users (interaction P = 0.007); there was minimal evidence of effect modification in those patients not using digoxin (P = 0.47) or in digoxin users not in AFF. CONCLUSION: Patients in AFF at baseline were less likely to benefit from omecamtiv mecarbil than patients without AFF, although the attenuation of the treatment effect was disproportionally concentrated in patients with AFF who were also receiving digoxin.Clinical Trial Registration: NCT02929329.

Open anatomical glenoid reconstruction with an iliac crest bone autograft effectively resolves off-track Hill-Sachs lesions to on-track lesions.

INTRODUCTION: The purpose of this study was to determine if "off-track" Hill-Sachs lesions in patients with dynamic anteroinferior instability were transformed into "on-track" lesions using iliac bone autografts with screw fixation. The secondary purpose was to observe if postoperative bony remodeling would occur over time, resulting in recurrent "off-track" Hill-Sachs lesions with corresponding instability. MATERIALS AND METHODS: We retrospectively reviewed clinical and CT records of 8 patients with an "off-track" Hill-Sachs lesion who underwent open anatomical glenoid reconstruction with an iliac crest bone autograft. Hill-Sachs lesions, glenoid track widths, and glenoid surface areas were measured on a preoperative and two postoperative (6 weeks, ≥ 2 years) 3D-CT models to determine graft resorption over time. All patients were available for postoperative clinical and CT final follow-up 3 years (2-4 years) postoperatively. RESULTS: In all patients, the Hill-Sachs lesions were "on-track" 6 weeks postoperatively and remained "on-track" at final-follow-up. Compared to preoperative values, the glenoid track width and glenoid surface area both were higher 6 weeks postoperatively (p < 0.001 and p = 0.023, respectively) and at final follow-up (p < 0.001 and p = 0.023, respectively). Whereas the glenoid track width between 6 weeks and final follow-up showed no decrease (p = 0.234), glenoid surface area tended to decrease (p = 0.055). The median SSV was 93 points (85-95 points), the Rowe score 90 points (80-100 points) and the WOSI 1980 points (1783-2067 points) at final follow-up. No recurrent dislocations or subluxations were observed. CONCLUSIONS: An open anatomical glenoid reconstruction with an iliac crest bone autograft technique using screw fixation effectively transformed "off-track" Hill-Sachs lesions to "on-track" lesions, resulting in good short-term clinical outcomes. Whereas glenoid surface area tended to be reduced by bony remodeling processes over time, the glenoid track width did not decrease at final follow-up and consequently no recurrence of "off-track" lesions occurred. LEVEL OF EVIDENCE: Case series; Level of evidence, IV.

Accuracy of free-hand humeral head resection planned on 3D-CT models in shoulder arthroplasty: an in vitro analysis.

INTRODUCTION: Three-dimensional planning of humeral head osteotomy in shoulder arthroplasty (SA) is understudied. This study evaluated whether a standard osteotomy technique along the anterosuperior anatomic neck (ASOT) could be surgically reproduced as pre-operatively planned on 3D-CT models. MATERIAL AND METHODS: Pre-operative planning in 12 cadaver shoulders was performed on a 3D-CT model of the humerus to calculate the planned osteotomy plane (planned OP). The osteotomy was then performed using a free-hand technique, and a post-operative CT scan was obtained for analysis (performed OP). Planes were compared with regards to inclination, retroversion, and resected humeral head thickness so the accuracy could be quantified. RESULTS: The absolute errors between the performed and planned OP were 2° (0-10°), 5° (0-14°), and 4 mm (1-7 mm) for inclination, retroversion, and resected head thickness, respectively. Deviation < 10° for inclination and retroversion and < 5 mm for resected humeral head thickness between planned and performed OP was achieved in 92%, 83%, 58% of cases, respectively. No differences were found for inclination (p = 0.289), whereas retroversion and resected head thickness were smaller than planned (p ≤ 0.027). CONCLUSIONS: Pre-operative planning of the ASOT using a 3D-CT model is accurate within a threshold of 10° when using a free-hand technique in 92% of cases for inclination. Retroversion and resected head thickness differed from the pre-operative plan, thereby limiting the unrestricted use of humeral head osteotomy planning from 3D-CT models in SA. These findings are a reference for further studies to develop and quantify the accuracy of pre-operative planning software including cutting guides for SA using 3D-CT models. LEVEL OF EVIDENCE: Basic science article.

Editorial Commentary: Is Your Critical Shoulder Angle Accurate? Only If You Can Verify That You Have the Correct Images.

The critical shoulder angle (CSA) has been the focus of significant research related to the etiology and prognosis of rotator cuff tears in recent years, but the accuracy of CSA measurements on plain anteroposterior (Grashey) radiographs has been questioned. Research to better understand what qualifies as a "tolerable" radiograph for reliable measurement of the CSA can inform best practices for obtaining plain radiographs. Optimal measurements rely on optimal images, and knowing how much room for error there is regarding malrotation provides surgeons with unbiased criteria to rule out inadequate images.

Long-term cardiac outcomes of patients with HER2-positive breast cancer treated in the adjuvant lapatinib and/or trastuzumab Treatment Optimization Trial.

BACKGROUND: Cardiotoxicity is the most significant adverse event associated with trastuzumab (T), the main component of HER2-positive breast cancer (BC) treatment. Less is known about the cardiotoxicity of dual HER2 blockade with T plus lapatinib (L), although this regimen is used in the metastatic setting. METHODS: This is a sub-analysis of the ALTTO trial comparing adjuvant treatment options for patients with early HER2-positive BC. Patients randomised to either T or concomitant T + L were eligible. Cardiac events (CEs) rates were compared according to treatment arm. RESULTS: With 6.9 years of median follow-up (FU) and 4190 patients, CE were observed in 363 (8.6%): 166 (7.9%) of patient in T + L arm vs. 197 (9.3%) in T arm (OR = 0.85 [95% CI, 0.68-1.05]). During anti-HER2 treatment 270 CE (6.4%) occurred while 93 (2.2%) were during FU (median time to onset = 6.6 months [IQR = 3.4-11.7]). While 265 CEs were asymptomatic (73%), 94 were symptomatic (26%) and four were cardiac deaths (1%). Recovery was observed in 301 cases (83.8%). Identified cardiac risk factors were: baseline LVEF < 55% (vs > 64%, OR 3.1 [95% CI 1.54-6.25]), diabetes mellitus (OR 1.85 [95% CI 1.25-2.75]), BMI > 30 kg/m2 (vs < 25 mg/kg2, OR 2.21 [95% CI 1.40-3.49]), cumulative dose of doxorubicin ≥240 mg/m2 (OR 1.36 [95% CI 1.01-1.82]) and of epirubicin≥ 480 mg/m2 (OR 2.33 [95% CI 1.55-3.51]). CONCLUSIONS: Dual HER2 blockade with T + L is a safe regimen from a cardiac perspective, but cardiac-focused history for proper patient selection is crucial. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT00490139 (registration date: 22/06/2007); EudraCT Number: 2006-000562-36 (registration date: 04/05/2007); Sponsor Protocol Number: BIG2-06 /EGF106708/N063D.

Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer.

BACKGROUND: Pertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. In this trial, we investigated whether pertuzumab, when added to adjuvant trastuzumab and chemotherapy, improves outcomes among patients with HER2-positive early breast cancer. METHODS: We randomly assigned patients with node-positive or high-risk node-negative HER2-positive, operable breast cancer to receive either pertuzumab or placebo added to standard adjuvant chemotherapy plus 1 year of treatment with trastuzumab. We assumed a 3-year invasive-disease-free survival rate of 91.8% with pertuzumab and 89.2% with placebo. RESULTS: In the trial population, 63% of the patients who were randomly assigned to receive pertuzumab (2400 patients) or placebo (2405 patients) had node-positive disease and 36% had hormone-receptor-negative disease. Disease recurrence occurred in 171 patients (7.1%) in the pertuzumab group and 210 patients (8.7%) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.66 to 1.00; P=0.045). The estimates of the 3-year rates of invasive-disease-free survival were 94.1% in the pertuzumab group and 93.2% in the placebo group. In the cohort of patients with node-positive disease, the 3-year rate of invasive-disease-free survival was 92.0% in the pertuzumab group, as compared with 90.2% in the placebo group (hazard ratio for an invasive-disease event, 0.77; 95% CI, 0.62 to 0.96; P=0.02). In the cohort of patients with node-negative disease, the 3-year rate of invasive-disease-free survival was 97.5% in the pertuzumab group and 98.4% in the placebo group (hazard ratio for an invasive-disease event, 1.13; 95% CI, 0.68 to 1.86; P=0.64). Heart failure, cardiac death, and cardiac dysfunction were infrequent in both treatment groups. Diarrhea of grade 3 or higher occurred almost exclusively during chemotherapy and was more frequent with pertuzumab than with placebo (9.8% vs. 3.7%). CONCLUSIONS: Pertuzumab significantly improved the rates of invasive-disease-free survival among patients with HER2-positive, operable breast cancer when it was added to trastuzumab and chemotherapy. Diarrhea was more common with pertuzumab than with placebo. (Funded by F. Hoffmann-La Roche/Genentech; APHINITY ClinicalTrials.gov number, NCT01358877 .).

A pooled analysis of the cardiac events in the trastuzumab adjuvant trials.

BACKGROUND: Trastuzumab-associated cardiotoxicity remains an issue for patients with HER2-positive breast cancer. This pooled analysis of 3 adjuvant trials investigated the incidence, timing, impact on treatment completion, and risk factors for trastuzumab-associated cardiotoxicity. METHODS: This is an individual patient data level pooled analysis of HERA, NSBAP B-31, and NCCTG 9831 (Alliance Trials). Definitions of cardiac events were as per each individual study. RESULTS: A total of 7445 patients enrolled in the 3 trials were included in the analysis, of which 4017 were in the trastuzumab and 3428 in the control (observation) arms, respectively. Median follow-up exceeded 10 years (119.2-137.2 months). Nearly all patients (97.4%) in the trastuzumab arms received anthracycline-based chemotherapy. In total, 452 patients in the trastuzumab arms experienced a cardiac event (11.3%), with most being mildly symptomatic or asymptomatic left ventricular ejection fraction (LVEF) decrease (351 patients, 8.7%). Severe congestive heart failure was more common in the trastuzumab arm (2.3%) than in the control arm (0.8%). Most cardiac events occurred during trastuzumab treatment (78.1%) and cardiac events were the main cause of discontinuation across the sample (10.0%); nevertheless, a large majority of patients completed trastuzumab treatment (76.2%). Baseline risk factors that were significantly associated with the development of cardiac events were baseline LVEF < 60%, hypertension, body mass index > 25, age ≥ 60 and, non-Caucasian ethnicity. CONCLUSION: One year of trastuzumab increases the risk of cardiac events, though most consist of asymptomatic or mildly symptomatic LVEF drops. Adjuvant trastuzumab should be considered a safe treatment from a cardiac standpoint for most patients. Trastuzumab-associated cardiotoxicity is the main cause of discontinuation and further research is needed to individualize prevention and management.

Cardio-Oncology Services: rationale, organization, and implementation.

AIMS: Anticancer therapies have extended the lives of millions of patients with malignancies, but for some this benefit is tempered by adverse cardiovascular (CV) effects. Cardiotoxicity may occur early or late after treatment initiation or termination. The extent of this cardiotoxicity is variable, depending on the type of drug used, combination with other drugs, mediastinal radiotherapy, the presence of CV risk factors, and comorbidities. A recent position paper from the European Society of Cardiology addressed the management of CV monitoring and management of patients treated for cancer. METHODS AND RESULTS: The current document is focused on the basis of the Cardio-Oncology (C-O) Services, presenting their rationale, organization, and implementation. C-O Services address the spectrum of prevention, detection, monitoring, and treatment of cancer patients at risk of cardiotoxicity and/or with concomitant CV diseases. These services require a multidisciplinary approach, with the aims of promoting CV health and facilitating the most effective cancer therapy. CONCLUSION: The expected growing volume of patients with cancer at risk of developing/worsening CV disease, the advent of new technological opportunities to refine diagnosis, and the necessity of early recognition of cancer therapy-related toxicity mandate an integrative multidisciplinary approach and care in a specialized environment. This document from the ESC Cardio-Oncology council proposes the grounds for creating C-O Services in Europe based on expert opinion.

Viewing perspective malrotation influences angular measurements on lateral radiographs of the scapula.

BACKGROUND: Accurate and reliable assessment of acromial tilt (ATA) and slope (ASA) angles have been important in the clinical evaluation of degenerative and traumatic rotator cuff tears. This study analyzed the influence of radiographic viewing perspective on the ATA and ASA and developed criteria to identify true lateral (TL) view radiographs. METHODS: Three-dimensional computed tomographic (CT) reconstructions of 52 scapulae without rotator cuff tears or osteoarthritis were studied. Digitally reconstructed radiographs (DRRs) were aligned to obtain a TL view. In 10 random scapulae, incremental ante- and retroversion and up- and downward rotation views were generated (10° increments, ±30°), and ATA and ASA were measured by 2 observers. Clinically applicable criteria were developed and validated to identify TL views. RESULTS: The mean ATA and ASA on TL views were 33°±4° (range 23°-42°) and 22°±7° (8°-43°), respectively. Mixed effect models showed that DRRs malpositioned in 20° and 30° anteversion and downward rotation decreased the ATA (P ≤ .030). DRRs malpositioned in anteversion and >10° of up- and downward rotation demonstrated a significantly decreased ASA (P ≤ .047). Intra- and interobserver reliability was excellent for TL views (intraclass correlation coefficient ≥ 0.95) but decreased with increasing viewing angle. Anatomic landmark criteria were capable of identifying TL-view radiographs with sensitivity of 81% and specificity of 82%. CONCLUSION: Both ATA and ASA were significantly affected by malposition in anteversion and downward rotation of the scapula. Reliable ASA measurement was more susceptible in up- and downward rotation than the ATA. New visual criteria can identify TL-view radiographs and should be used in future studies to ensure consistency in ATA and ASA measurement.

Cardiac biomarkers for early detection and prediction of trastuzumab and/or lapatinib-induced cardiotoxicity in patients with HER2-positive early-stage breast cancer: a NeoALTTO sub-study (BIG 1-06).

BACKGROUND: Biomarkers of cardiac damages, such as troponin T (TnT) and the amino-terminal fragment of brain natriuretic peptide (NT-proBNP), may be useful as early predictors of cardiac dysfunction. The role of these biomarkers in patients receiving lapatinib and/or trastuzumab before anthracyclines is unknown. This study explores TnT and NT-proBNP as predictors of early cardiac toxicity in neoadjuvant breast cancer patients. METHODS: This sub-study of the NEOALTTO trial tested if changes in the levels of TnT and NT-proBNP occurred after 2 weeks of anti-HER2 therapy (lapatinib, trastuzumab or their combination) alone and/or after 18 weeks of anti-HER2 therapy plus weekly paclitaxel. RESULTS: 173 and 172 were tested at all three timepoints for NT-proBNP and TnT, respectively. The incidence of biomarker elevation was overall low at all timepoints for all the three treatment arms. A total of 13 CEs in 11 patients occurred. Biomarker elevations in patients with CEs were very rare; only one patient with subsequent CE had a NT-proBNP elevation at baseline and at week 2. CONCLUSION: These results suggest that TnT and proBNP may not be useful as early predictors of cardiac toxicity in anthracycline-naïve patients receiving trastuzumab and/or lapatinib.

[Pharmacological therapy of heart failure with reduced ejection fraction]. / Medikamentöse Therapie der Herzinsuffizienz mit verminderter Auswurffraktion.

Pharmacological therapy of heart failure with reduced ejection fraction Abstract. Pharmacological therapy for heart failure has made great progress over the last three decades and evidence-based therapies have significantly improved survival and quality of life. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and beta-blockers are the cornerstone of the heart failure therapy; indicated in virtually every patient with heart failure and reduced ejection fraction. As soon as the left ventricular ejection fraction decreases below 35 % and / or symptoms are still present (NYHA II-IV), a mineralocorticoid receptor antagonist should be added. A rather recent addition to current heart failure therapy with convincing data is the substance combination sacubitril / valsartan. It is indicated for patients with persistent symptomatic heart failure despite optimal medical therapy with ACE inhibitors or ARBs, beta-blockers, and MRAs. Crucial for all mentioned substances is to aim for the maximal tolerated dose. Various additional therapies have no proven survival benefit but are important for symptom control in everyday life. Above all the diuretics, where loop diuretics show a better effect profile compared to thiazide diuretics. Furthermore, achieving an optimal iron status (the limit to start a substitution is significantly higher than in patients without heart failure), decreasing the heart frequency with Ivabradine (if heart rate persists above 70 / min despite fully dosed betablocker) and «lifestyle changes¼ can add to the success of the medical treatment. The importance of digoxin has been steadily decreasing. The previously advocated therapeutic anticoagulation in patients with severely reduced LVEF is not propagated anymore. Significant arrhythmias (especially atrial fibrillation and ventricular arrhythmias) are common in advanced diseases. In addition to beta-blockers, amiodarone is clearly the antiarrhythmic drug of choice. According to latest data, an early interventional treatment of atrial fibrillation by pulmonary vein ablation may be beneficial and has the potential to reduce mortality in special subgroups of patients. New developments in the field of antidiabetic drugs seem to be promising for reduction of mortality and hospitalization in patients with heart failure.

High-Sensitivity Troponin T and NT-proBNP Kinetics in Breast Cancer Chemotherapy.

BACKGROUND/AIMS: Doxorubicin (DOX) and trastuzumab (TRA) are associated with cardiac dysfunction. METHOD: High-sensitivity troponin T (hs-TnT) and brain natriuretic peptide attached to the amino acid N-terminal fragment in the prohormone (NT-proBNP) were measured before and on days +1, +2, +3, and +7 during cycles 1 and 2 of therapy with DOX or TRA in breast cancer patients. RESULTS: Five of eleven DOX-treated women, compared with 2/11 TRA-treated women, had undetectable baseline hs-TnT. By day +1 of cycle 2, all the DOX-treated women (p = 0.03) but only 7/11 TRA-treated women (p = ns) had detectible hs-TnT. Time to peak was 1-2 days for both groups. In the DOX-treated women, hs-TnT showed significant peaks from precycle baseline, increases in precycle 1 to precycle 2 levels, and a cycle 1 to cycle 2 peak and area under the curve (AUC). hs-TnT increased from precycle (1, 4.6 ± 6.3 pg/mL) to a cycle 2 peak of 16.1 ± 15.0 pg/mL (p < 0.002). No increases were seen with the TRA treatment. Transient posttreatment increases in NT-proBNP were seen after both therapies. CONCLUSION: DOX was associated with increased pretreatment baseline, peak, and AUC hs-TnT levels. Both DOX and TRA acutely perturb NT-proBNP. Assessment of pre- and posttreatment hs-TnT could be a means of quantifying cumulative myocardial injury in the course of chemotherapy.

Humeral head osteotomy in shoulder arthroplasty: a comparison between anterosuperior and inferoanterior resection techniques.

BACKGROUND: The best chance that a shoulder arthroplasty will restore motion and muscle balance across the glenohumeral joint is by closely replicating natural articular morphology. Defining the humeral osteotomy plane along clear landmarks at the anatomic neck is critical. We hypothesized that a new osteotomy, based on alternative landmarks on the anatomic neck, would restore 3-dimensional humeral head morphology more reliably than the traditional osteotomy. METHODS: The anatomic neck was digitized in 30 human cadaver shoulders and compared with its 3-dimensional computed tomography reconstruction. Two different osteotomy techniques were virtually performed: the traditional, following the anterosuperior anatomic neck; and a new technique, defined by the inferoanterior anatomic neck. The length-width difference and orientation (retroversion, inclination) of the resection area were compared between the techniques and with native anatomy. RESULTS: Length-width difference of the anterosuperior resection area was higher than in the inferoanterior osteotomy (6 ± 2 mm vs. 3 ± 1 mm; P < .001). Retroversion of the anterosuperior resection plane was higher than the native head (50° ± 12° vs. 37° ± 11°; P < .001), whereas retroversion after the inferoanterior osteotomy (32° ± 12°) did not differ from native (P = .057). Inclination differed after the anterosuperior osteotomy (129° ± 5°) and the inferoanterior osteotomy (127° ± 4°) compared with the native head (134° ± 4°; P ≤ .001). CONCLUSION: The inferoanterior referenced osteotomy generated a more circular resection area, matching the native humeral head retroversion more closely than in the anterosuperior technique. This study suggests that in shoulder arthroplasty, the humeral resection level should be referenced at the inferoanterior rather than the anterosuperior anatomic neck. Further studies should investigate the biomechanical effects of this alternative resection plane.

The influence of radiographic viewing perspective and demographics on the critical shoulder angle.

BACKGROUND: Accurate assessment of the critical shoulder angle (CSA) is important in clinical evaluation of degenerative rotator cuff tears. This study analyzed the influence of radiographic viewing perspective on the CSA, developed a classification system to identify malpositioned radiographs, and assessed the relationship between the CSA and demographic factors. METHODS: Glenoid height, width, and retroversion were measured on 3-dimensional computed tomography reconstructions of 68 cadaver scapulae. A digitally reconstructed radiograph was aligned perpendicular to the scapular plane, and retroversion was corrected to obtain a true anteroposterior (AP) view. In 10 scapulae, incremental anteversion/retroversion and flexion/extension views were generated. The CSA was measured, and a clinically applicable classification system was developed to detect views with >2° change in CSA vs. true AP view. RESULTS: The average CSA was 33° ± 4°. Intraobserver and interobserver reliability was high (intraclass correlation coefficient ≥ 0.81) but decreased with increasing viewing angle. Views beyond 5° anteversion, 8° retroversion, 15° flexion, and 26° extension resulted in >2° deviation of the CSA compared with the true AP view. The classification system was capable of detecting aberrant viewing perspectives with sensitivity of 95% and specificity of 53%. Correlations between glenoid size and CSA were small (R ≤ 0.3), and CSA did not vary by gender (P = .426) or side (P = .821). CONCLUSIONS: The CSA was most susceptible to malposition in anteversion/retroversion. Deviations as little as 5° in anteversion resulted in a CSA >2° from true AP view. A new classification system refines the ability to collect true AP radiographs of the scapula. The CSA was unaffected by demographic factors.