Abdelmoneim, Sahar S.

Background: Skin substitutes play a crucial role in wound care by actively modulating the wound healing process, promoting angiogenesis, and protecting the integrity of the native extracellular matrix. Consequently, surgeons have increasingly recognized these resources as excellent complements to improve reconstructive outcomes. This review focuses on the author’s experience using these biomaterials in complex cases, highlighting the benefits they bring to patient care. Methods: A literature review was conducted to evaluate the regenerative properties of skin substitutes and their applicability in head and neck, upper and lower extremities, and trunk reconstruction. Results: The reviewed literature, along with the authors’ experience, supports the adjunct use of skin substitutes in various reconstructive situations. Combining them with skin grafts improves resulting skin quality and may also enhance donor site healing. They have proven to be effective in addressing chronic venous ulcers, traumatic wounds with limited donor tissues for coverage, extensive burns, diabetic foot ulcers, and oncological resections in the face and scalp. Furthermore, combining them with autologous tissue shows promising results in achieving stable closure. Conclusions: Incorporating skin substitutes in complex reconstructive scenarios offers multiple benefits. Their regenerative properties and ability to modulate the healing process contribute to enhanced outcomes and reduced overall costs.

Background: Regadenoson is a selective A2A receptor agonist that is administered as a fixed dose bolus with rapid onset (∼30 sec), and short duration (∼2-4 min) of action. The aim of this study was to evaluate the feasibility of real-time myocardial contrast echocardiography (MCE) for quantification of coronary flow reserve (CFR) in healthy humans during regadenoson vasodilator stress. Methods: Fifteen subjects [3 males, age: 45.8±5.2 years, BMI 23.8±2.3 kg/m2] with normal LV wall motion and no CAD underwent real-time MCE. Three standard apical LV views were acquired during a continuous intravenous (IV) infusion of Definity (1.3 ml in 60 cc 0.9% saline at 200 ml/hr) at rest and during vasodilator stress (regadenoson 400 ug IV bolus). Following transient microbubble destruction, microbubble velocity (β, sec -1 ), myocardial blood volume (A, dB) and myocardial blood flow (MBF, dB/sec) were determined. Videodensitometric quantification using a 16-segment model at end-systole was performed off-line. Results: Quantification of reserve parameters was feasible in all (15/15) patients, 188/240 segments (78%)[82%, 80% and 70% of 4-, 2-, 3-chambers apical views] and 43/45 (95%) coronary territories [one each of Cx and RCA territories were not feasible]. Augmentation from baseline to vasodilator stress was observed for both ß (s -1 ) [0.65± 0.25 vs 0.79± 0.21, P=0.031] and MBF (dB/sec) [2.85± 1.43 vs 4.65± 2.06, P= 0.002], however A (dB) did not change [06.62± 2.57 vs 6.79±2.1, P=0.463]. CFR measurements from all views were similar (Fig 1). There was no significant difference between CFR measured in the 3 coronary territories, although some heterogeneity was noted in the posterior circulation CFR (Fig 2). Conclusion: Real-time MCE during Regadenoson vasodilator stress is feasible, and is a useful technique for the rapid noninvasive quantification of CFR in healthy humans.

Introduction: Hospitalization for acute decompensated heart failure (ADHF) remains a major source of morbidity and mortality. While previous studies have shown outpatient intravenous (IV) diuretic therapy to be safe and cost-effective, there have been no randomized controlled trials to evaluate the utilization of continued outpatient IV furosemide diuretic maintenance treatment in patients with HF following hospitalization for ADHF. Hypothesis: We hypothesized that 30-day hospital readmission from ADHF would be lower with routine, standardized outpatient IV diuretic treatment along with a comprehensive HF care approach vs standard treatment. Methods: In a single center, prospective, randomized, double-blind study, 100 patients were randomized to receive standard of care (Group 1), IV placebo infusion (Group 2), or IV furosemide infusion (Group 3) over 3 hours, biweekly for a one-month period following hospitalization for ADHF. Patients in Groups 2 and 3 also received a comprehensive HF care protocol including bi-weekly clinic visits for dose-adjusted IV-diuretics, medication adjustment, laboratory, weight, and blood pressure-monitoring, and education during infusion visits. Echocardiography, Kansas City Cardiomyopathy Questionnaire (KCCQ) and depression questionnaires were performed at baseline and 30-day follow-up. The primary outcome was 30-day re-hospitalization for ADHF. Results: Overall, a total of 94 patients were included in the study (mean age 64 years, 56% males, 69% African American, 70% HF reduced ejection fraction). There were a total of 14 (15%) readmissions for ADHF at 30 days, 6 (17.1%) in Group 1, 7 (22.6%) in Group 2, and 1 (3.7%) in Group 3 (overall p=0.11; p=0.037 comparing Group 2 and Group 3). Patients receiving IV furosemide infusion experienced significantly greater urine output and weight loss compared to those receiving placebo without any significant increase creatinine and no significant between group differences in echocardiography parameters, KCCQ or depression scores. Conclusions: The use of a standardized protocol of outpatient IV furosemide infusion for a one-month period following hospitalization for ADHF was found to be safe and efficacious in reducing 30-day re-hospitalization.

Background: In women with low to intermediate risk of coronary artery disease (CAD), prognostic detection strategies have been controversial. We present the follow-up data of the SMART trial in peri/postmenopausal women at low to intermediate risk of CAD. Objectives: To determine the value of contrast stress echocardiography (CSE), stress electrocardiogram (sECG), and serum biomarkers for prediction of cardiovascular events (CE) in peri/postmenopausal women at low to intermediate risk of CAD. Materials and Methods: From January 2004 to August 2007, 400 peri/postmenopausal women were prospectively enrolled. All women had detailed risk factor assessment, and underwent simultaneous CSE (Definity ® , Lantheus Medical Imaging) and sECG. Laboratories included brain natriuretic peptide (BNP), atrial natriuretic peptide, endothelin, and high sensitivity C-reactive protein. Wall motion score index was based on a 16-segment model. Abnormal CSE was defined as new or worsening wall motion abnormality at stress, while abnormal sECG was ≥1 mm horizontal/downsloping ST segment depression/elevation (80 mseconds duration). Self-reported outcome data were collected from a mailed Women's Heart Clinic Questionnaire. CE outcomes included all-cause mortality, nonfatal myocardial infarction (MI), heart failure, chest pain hospitalization or development of typical angina (CP), and revascularization (REVASC). Adjusted Cox proportional hazard ratios (HR; 95% confidence intervals) were reported. Results: A total of 366 women (54.4 ± 5.5 years, Framingham risk 6.5% ± 4.4%) completed simultaneous CSE and sECG. Forty-two (11.5%) had abnormal CSE, while sECG was abnormal in 22 (6%) women. Follow-up (4.4 ± 1.2 years) was available in 315/366 (86%) women (78% exercise-CSE, 22% dobutamine-CSE). In those who completed follow-up, CSE was abnormal in 33 women (10.5%) and sECG was abnormal in 21 (6.7%). In 33 women with abnormal CSE, sECG was abnormal in 7 (21.2%) and normal in 26 (79%), p = 0.0004. CE occurred in 27 (8.6%) women: 8 all-cause mortality, 2 nonfatal MI, 13 CP, and 4 REVASC. CE occurred in 21% versus 7% of women with abnormal versus normal CSE, p = 0.014 and 38% versus 6% of women with abnormal versus normal sECG, p < 0.0001. Rest BNP was higher in women with CE versus those without ( p = 0.018). Abnormal sECG and abnormal CSE were associated with CE, while only abnormal sECG was an independent predictor of CE (adjusted HR 10.3 [1.9–61.4], p = 0.007). Of the laboratory results, only BNP was associated with CE (adjusted HR 2.9 [1.1–7.3], p = 0.028). Conclusions: sECG and rest BNP were independent predictors of subsequent CE within 5 years in peri/postmenopausal women at low to intermediate risk of CAD.

Background— Afterload reduction is a cornerstone in the management of patients with heart failure (HF) and reduced ejection fraction. However, arterial load and the effect of HF therapies on afterload might vary between individuals. Tailoring vasoactive medicines to patients with HF based upon better understanding of arterial afterload may enable better individualization of therapy. Methods and Results— Subjects with HF and reduced ejection fraction underwent aggressive titration of vasoactive HF therapies with assessment of central aortic waveforms analyzed using pulse wave, wave separation, and arterial reservoir models. Clinical response to treatment was assessed using the 6-minute walk test distance, which increased in 25 subjects and decreased or remained unchanged in 13. Subjects with improvement on therapy displayed higher aortic pressure wave pulsatility (central pulse pressure [PP], reflected pressure wave, and reservoir pressure) at study entry compared with subjects without improvement (all P <0.05). Parameters derived by the arterial analysis methods were strongly correlated with one another and displayed similar ability to predict improvement. Aortic pressure pulsatility significantly decreased in subjects with functional improvement, whereas no change was observed in patients without functional improvement ( P for interaction <0.05). These differences in arterial load at baseline and on therapy were not apparent from conventional brachial artery cuff pressure assessments. Conclusions— Increased aortic pressure wave pulsatility and greater decrease in pulsatility on treatment are associated with functional improvement in patients with HF and reduced ejection fraction receiving aggressive vasodilator titration. These differences are not identifiable using brachial cuff pressures. Central aortic waveform analysis may enable better individualization of vasoactive therapies in chronic HF and reduced ejection fraction. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00588692.

PurposeInfarct mass as assessed by myocardial‐delayed enhancement imaging on cardiac magnetic resonance (CMR) and myocardial blood flow as assessed by real time myocardial perfusion echocardiography (RT‐MPE) have been shown to predict adverse events following ST elevation myocardial infarction (STEMI). There has been no published comparison of quantitative assessment using these modalities as predictors of clinical outcomes to date. We compared RT‐MPE with CMR for prediction of cardiac events in reperfused STEMI patients.Materials and MethodsConsecutive STEMI patients with early reperfusion were studied. RT‐MPE and CMR were performed. Perfusion score indices (PSIRT‐MPE and PSICMR) were calculated [sum of segmental perfusion scores/number of segments]. CMR infarct mass (g) and RT‐MPE myocardial blood flow (MBF dB/s) were quantified. Patients were followed for cardiac events (death, nonfatal MI, revascularization, angina, and heart failure).ResultsAll 27 patients (age 62±14; follow‐up 3.5±2.6 years) had thrombolysis in myocardial infarction (TIMI) grade 3 flow of infarct vessel. Cardiac events occurred in 17 (63%). Cardiac event patients had higher PSIRT‐MPE, PSICMR, infarct mass, and lower MBF. PSIRT‐MPE cutoff of 0.3 had an AUC of 0.856 (82% sensitivity, 70% specificity), while a PSICMR cutoff of 0.2 had an AUC of 0.765 (76% sensitivity, 60% specificity). Infarct mass and MBF were independent predictors of cardiac events after adjusting for risk factors (hazard ratios: 20.9 [95% CI 1.8–256] P=.02 and 8.1 [95% CI 1.5–78] P=.01, respectively).ConclusionsQuantitative RT‐MPE performed comparably to CMR for prediction of MACE in STEMI patients supporting a prognostic role for this noninvasive, bedside imaging method.

Background— The CoreValve US High-Risk Clinical Study compared clinical outcomes and serial echocardiographic findings in patients with severe aortic valve stenosis after transcatheter aortic valve replacement (TAVR) with a self-expanding bioprosthesis or surgical aortic valve replacement (SAVR). Methods and Results— Eligible patients were randomly assigned 1:1 to TAVR with a self-expanding bioprosthesis or SAVR (N=747). Echocardiograms were obtained at baseline, discharge, 30 days, 6 months, and 1 year after the procedure and were analyzed at a central core laboratory. Compared with SAVR patients (N=357), TAVR patients (N=390) had a lower mean aortic valve gradient, larger valve area, and less patient–prosthesis mismatch (all P <0.001), but more paravalvular regurgitation at discharge, which decreased at 1 year. SAVR patients experienced significant right ventricular systolic dysfunction at discharge and 1 month with normal right ventricular function at 1 year. One-year all-cause mortality was 14.2% for TAVR and 19.1% for SAVR patients. Preimplantation aortic regurgitation ≥mild was associated with reduced mortality hazard for both the TAVR (hazard ratio 0.48, 95% confidence interval 0.27–0.85; P =0.01) and the SAVR groups (hazard ratio 0.53, 95% confidence interval 0.32–0.87; P =0.01). Aortic regurgitation ≥mild after TAVR was associated with increased risk for all-cause mortality (hazard ratio 1.95, 95% confidence interval 1.08–3.53; P =0.03). Conclusions— In patients with severe aortic stenosis at increased surgical risk, TAVR was associated with better systolic valve performance, similar left ventricular remodeling, more paravalvular regurgitation, and less right ventricular systolic dysfunction compared with SAVR. Despite an overall mortality reduction for the TAVR group, ≥mild aortic valve regurgitation after TAVR was associated with an increased mortality hazard. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01240902.

Introduction: We aim to describe changes in exercise habits and barriers to physical activity over 5 years in menopausal women at low–intermediate risk for cardiovascular disease. Materials and Methods: Women in the Stress Echocardiography in Menopausal Women at Risk for Coronary Artery Disease trial were prospectively enrolled in a multisite study from 2004 to 2007. Inclusion criteria were as follows: peri- and postmenopausal women with symptoms and/or risk factors for cardiovascular disease resulting in referral for stress echocardiography. A questionnaire, which assessed details of medical history, physical activity, and body mass index (BMI), was administered at baseline and 5 years. Results: 216 menopausal women (62.5% hypertensive, 15.3% diabetic, 52.3% prior or current smokers) were studied. At baseline, age was 54.9 ± 4.8 years, BMI was 30.7 ± 6.4 kg/m 2 , and Framingham risk score was 4.05% ± 3.76%. One hundred women (46.3%) were obese, 79 (36.6%) overweight, and 37 (17.1%) had a normal BMI. Women changed their self-reported aerobic exercise patterns in similar patterns regardless of their BMI at baseline. There was low participation in strength training among all women. Mean BMI decreased by 0.12 kg/m 2 in obese women and increased by 1.63 kg/m 2 in normal BMI women at 5 years ( p < 0.0001). Conclusion: These data suggest that women can increase their level of physical activity regardless of BMI and that overweight or obese status is not a barrier to initiating an aerobic, nonaerobic, or strength training exercise routine.

Background: A women-based formula for calculation of age-predicted maximum heart rate [age-predicted maximum heart rate=206−(0.88×age)] was established in asymptomatic volunteer women undergoing treadmill exercise tolerance testing (ETT). We sought to perform a comparison of the performance of this women-based formula for prediction of peak heart rate to the traditional formula [220−age] and our own database-generated prediction formula in a large database of women undergoing ETT. Methods: We performed a retrospective analysis of all consecutive women who underwent symptom-limited Bruce protocol ETT at the Mayo Clinic from 1994 to 2010. Women with known cardiovascular disease or those using beta blockers, calcium channel blockers, or digitalis were excluded. Separate analyses were performed according to symptomatic status. Results: The study included 11,029 women (89.4% Caucasian) with a mean age 52±12 years; 3,632 (33%) were referred specifically for evaluation of symptoms. Age-predicted maximum heart rate calculated by the traditional formula was achieved by 49.7% of women versus 69.9% by the women-based formula with most of the underestimation observed in older women. Average absolute deviation between achieved and predicted peak heart rate (HR) was 10.85±9.18 bpm for traditional versus 11.98±9.00 for women-based formulas (dependent t =−16.64, p <0.0001). The linear regression line calculated from our population [HR=201−(0.67×age)] was closer to the women-based formula, both in terms of intercept and slope than the traditional formula. Peak HR was shown to be slightly affected (−2.5 bpm) by symptom status at referral, whereas smoking and diabetes more significantly reduced achieved peak HR. Conclusions: The women-based formula underestimated peak HR, especially in older women, but was observed to be closer in both intercept and slope to the regression line determined from our study in this large population of female patients. These sex-unique observations should be taken into account when determining adequacy and targets for ETT in women.

To study the relationship between glycosylated hemoglobin (HgbA1c) and myocardial perfusion in type 2 diabetes mellitus (T2DM) patients, we prospectively enrolled 24 patients with known or suspected coronary artery disease (CAD) who underwent adenosine stress by real-time myocardial perfusion echocardiography (RTMPE). HgbA1c was measured at time of RTMPE. Microbubble velocity (β min−1), myocardial blood flow (MBF, mL/min/g), and myocardial blood flow reserve (MBFR) were quantified. Quantitative MCE analysis was feasible in all patients (272/384 segments, 71%). Those with HgbA1c > 7.1% had significantly lowerβreserveand MBFR than those with HgbA1c ≤ 7.1%(P<0.05). In patients with suspected CAD, there was a significant inverse correlation between MBFR and HgbA1c (r=-0.279,P=0.01); however, in those with known CAD, this relationship was not significant (r=-0.117,P=0.129). Using a MBFR cutoff value > 2 as normal, HgbA1c > 7.1% significantly increased the risk for abnormal MBFR, (adjusted odds ratio: 1.92, 95% CI: 1.12–3.35,P=0.02). Optimal glycemic control is associated with preservation of MBFR as determined by RTMPE, in T2DM patients at risk for CAD.