Olivia Y. Hung

Myocardial bridging: contemporary understanding of pathophysiology with implications for diagnostic and therapeutic strategies.

Patients with myocardial bridging are often asymptomatic, but this anomaly may be associated with exertional angina, acute coronary syndromes, cardiac arrhythmias, syncope, or even sudden cardiac death. This review presents our understanding of the pathophysiology of myocardial bridging and describes prevailing diagnostic modalities and therapeutic options for this challenging clinical entity.

Favorable Bed Utilization and Readmission Rates for Emergency Department Observation Unit Heart Failure Patients

OBJECTIVES The objective was to compare readmission rates and hospital bed-days between acute decompensated heart failure (AHF) patients admitted or discharged following accelerated treatment protocol (ATP)-driven care in an emergency department observation unit (OU). METHODS This was a retrospective cohort study conducted at two urban university-affiliated hospitals. A total of 358 selected AHF patients received treatment on an ATP in the OU between October 1, 2007, and June 30, 2011. The comparison of interest was admission or discharge following OU treatment. The outcome of interest was readmission within 30 and 90 days of hospital discharge following care in the OU. We also examined resource use (inpatient, inpatient plus outpatient-days) between the admitted and discharged groups. Time to readmission analysis was performed with Cox proportional hazards regression. RESULTS Discharged and admitted patients were similar with respect to age, race, sex, ED length of stay (LOS), and OU LOS. Patients admitted from the OU had a higher median B-type natriuretic peptide (BNP; 1,063 pg/mL [interquartile range {IQR} = 552 to 2,067 pg/mL] vs. 708 pg/mL [IQR = 254 to 1,683 pg/mL]; p = 0.002) and blood urea nitrogen (BUN; 19 mg/dL [IQR = 14 to 26 mg/dL] vs. 17 mg/dL [IQR = 13 to 23 mg/dL]) than those discharged (p = 0.04) and a lower median ejection fraction (EF; 22.5% [15% to 43%] vs. 35% [IQR 20% to 55%]; p = 0.002). In models controlling for age, race, sex, clinical site, BNP, BUN, creatinine, and EF, the 30-day readmission rate (13.8% in the study population as a whole) was not significantly different between the patients discharged or admitted following OU care (hazard ratio [HR] = 0.99; 95% confidence interval [CI] = 0.47 to 2.10). The readmission rates were also not significantly different at 90 days (HR = 1.07; 95% CI = 0.65 to 1.77). Within 30 days of discharge from the OU, patients spent a median of 1.7 days (IQR = 0.0 to 5.1 days) as inpatients, compared to 3.5 days (IQR = 2.3 to 5.8 days) among patients admitted from the OU (p < 0.0001). Among readmitted patients, the total median inpatient time was not significantly different between the comparison groups at both 30 and 90 days of follow-up. CONCLUSIONS Selected acute heart failure (HF) patients managed by a rapid treatment protocol in the OU demonstrated favorable hospital use, with discharged patients using fewer bed-days and demonstrating readmission rates that were not higher than admitted patients.

An assessment of intra-patient variability on observed relationships between wall shear stress and plaque progression in coronary arteries.

BackgroundWall shear stress (WSS) has been associated with sites of plaque localization and with changes in plaque composition in human coronary arteries. Different values have been suggested for categorizing WSS as low, physiologic or high; however, uncertainties in flow rates, both across subjects and within a given individual, can affect the classification of WSS and thus influence the observed relationships between local hemodynamics and plaque changes over time. This study examines the effects of uncertainties in flow rate boundary conditions upon WSS values and investigates the influence of this variability on the observed associations of WSS with changes in VH-IVUS derived plaque components.MethodsThree patients with coronary artery disease underwent baseline and 12 month follow-up angiography and virtual histology-intravascular ultrasound (VH-IVUS) measurements. Coronary artery models were reconstructed from the data and models with and without side-branches were created. Patient-specific Doppler ultrasound (DUS) data were employed as inflow boundary conditions and computational fluid dynamics was used to calculate the WSS in each model. Further, the influence of representative coronary artery flow waveforms upon WSS values was investigated and the concept of treating WSS using relative, rather than actual, values was explored.ResultsModels that included side-branch outflows and subject-specific DUS velocities were considered to be the reference cases. Hemodynamic differences were caused by the exclusion of side-branches and by imposing alternative velocity waveforms. One patient with fewer side-branches and a scaled generic waveform had little deviation from the reference case, while another patient with several side-branches excluded showed much larger departures from the reference situation. Differences between models and the respective reference cases were reduced when data were analyzed using relative, rather than actual, WSS.ConclusionsWhen considering individual subjects, large variations in patient-specific flow rates and exclusion of multiple side-branches in computational models can cause significant differences in observed associations between plaque evolution and ranges of computed WSS. These differences may contribute to the large variability typically found among subjects in pooled populations. Relative WSS may be more useful than actual WSS as a correlative variable when there is a large degree of uncertainty in flow rate data.

High wall shear stress and high-risk plaque: an emerging concept.

In recent years, there has been a significant effort to identify high-risk plaques in vivo prior to acute events. While number of imaging modalities have been developed to identify morphologic characteristics of high-risk plaques, prospective natural-history observational studies suggest that vulnerability is not solely dependent on plaque morphology and likely involves additional contributing mechanisms. High wall shear stress (WSS) has recently been proposed as one possible causative factor, promoting the development of high-risk plaques. High WSS has been shown to induce specific changes in endothelial cell behavior, exacerbating inflammation and stimulating progression of the atherosclerotic lipid core. In line with experimental and autopsy studies, several human studies have shown associations between high WSS and known morphological features of high-risk plaques. However, despite increasing evidence, there is still no longitudinal data linking high WSS to clinical events. As the interplay between atherosclerotic plaque, artery, and WSS is highly dynamic, large natural history studies of atherosclerosis that include WSS measurements are now warranted. This review will summarize the available clinical evidence on high WSS as a possible etiological mechanism underlying high-risk plaque development.

Appropriate Use Criteria: Lessons From Japan

Professional societies, including the American College of Cardiology, have for many years developed and periodically updated formal guidelines that attempt to provide a comprehensive review of available evidence for management of certain clinical conditions. These guidelines are distinctly

Vasomotor Function Comparative Assessment at 1 and 2 Years Following Implantation of the Absorb Everolimus-Eluting Bioresorbable Vascular Scaffold and the Xience V Everolimus-Eluting Metallic Stent in Porcine Coronary Arteries: Insights From In Vivo Angiography, Ex Vivo Assessment, and Gene Analysis at the Stented/Scaffolded Segments and the Proximal and Distal Edges

OBJECTIVES The purpose of this study was to assess and compare in vivo the restoration of vasomotor function following Absorb bioresorbable vascular scaffold (BVS) (Abbott Vascular, Santa Clara, California) and metallic Xience V (XV) (Abbott Vascular, Santa Clara, California) stent implantations in porcine coronary arteries at 1 and 2 years. BACKGROUND Drug-eluting metallic coronary stents induce sustained vasomotor dysfunction, and preliminary observations from arteries with bioresorbable scaffolds have indicated partially restored vasoreactivity. METHODS A total of 15 Absorb BVS (3.0 × 18.0 mm) and 14 XV (3.0 × 18.0 mm or 3.0 × 12.0 mm) stents were randomly implanted in the main coronaries of 12 nonatherosclerotic swine. The effect of implant on vasomotor performance (constrictive and expansive) was measured in the stented/scaffolded segments and the 5-mm proximal and distal adjacent segments in vivo by angiography assessing mean luminal diameter changes following infusion of vasoactive agents at 1 year (n = 6) and 2 years (n = 6) as well as ex vivo at 2 years using a tissue chamber apparatus. Endothelial cell function and smooth muscle cell phenotype gene marker levels were evaluated with quantitative real-time polymerase chain reaction. RESULTS The scaffolded Absorb BVS segments showed fully restored constrictive response compared with XV implanted vessels at 1 year: -24.30 ± 14.31% versus -1.79 ± 6.57% (p < 0.004) and at 2 years: -28.13 ± 14.60% versus -3.90 ± 6.44% (p < 0.004). The early restoration of vasomotor function within the scaffolded segments reached a peak at 1 year and did not significantly change up to 2 years. The vasoactive responses of Absorb BVS-implanted vessels within the scaffolded segments were similar to those observed within the proximal and distal edge segments at both time points. Conversely, the stented XV segments demonstrated significantly impaired constrictive response compared with the distal XV edges at 1 year: -1.79 ± 6.57% versus -21.89 ± 7.17% (p < 0.0002) and at 2 years: -3.90 ± 6.44% versus -21.93 ± 15.60% (p < 0.03). Ex vivo assessment of contraction induced by PGF2α and relaxation induced by substance P of isolated BVS segments compared with XV-treated segments generated greater contraction force of 3.94 ± 0.97 g versus 1.83 ± 1.03 g (p < 0.05), and endothelial-dependent relaxation reached 35.91 ± 24.74% versus 1.20 ± 3.79% (p < 0.01). Quantitative real-time polymerase chain reaction gene analysis at 2 years demonstrated increased Connexin 43 messenger ribonucleic acid levels of Absorb BVS-treated vessels compared with XV-treated vessels: 1.92 ± 0.23 versus 0.77 ± 12 (p < 0.05). CONCLUSIONS Absorb BVS-implanted coronary arteries demonstrate early functional restoration of the scaffolded and adjacent segments at 1 year, which is preserved up to 2 years.

Comprehensive Assessment of Coronary Plaque Progression With Advanced Intravascular Imaging, Physiological Measures, and Wall Shear Stress: A Pilot Double‐Blinded Randomized Controlled Clinical Trial of Nebivolol Versus Atenolol in Nonobstructive Coronary Artery Disease

Background We hypothesized that nebivolol, a β‐blocker with nitric oxide–mediated activity, compared with atenolol, a β‐blocker without such activity, would decrease oxidative stress and improve the effects of endothelial dysfunction and wall shear stress (WSS), thereby reducing atherosclerosis progression and vulnerability in patients with nonobstructive coronary artery disease. Methods and Results In this pilot double‐blinded randomized controlled trial, 24 patients treated for 1 year with nebivolol 10 mg versus atenolol 100 mg plus standard medical therapy underwent baseline and follow‐up coronary angiography with assessments of inflammatory and oxidative stress biomarkers, microvascular function, endothelial function, and virtual histology intravascular ultrasound. WSS was calculated from computational fluid dynamics. Virtual histology intravascular ultrasound segments were assessed for vessel volumetrics and remodeling. There was a trend toward more low‐WSS segments in the nebivolol cohort (P=0.06). Low‐WSS regions were associated with greater plaque progression (P<0.0001) and constrictive remodeling (P=0.04); conversely, high‐WSS segments demonstrated plaque regression and excessive expansive remodeling. Nebivolol patients had decreased lumen and vessel areas along with increased plaque area, resulting in more constrictive remodeling (P=0.002). There were no significant differences in biomarker levels, microvascular function, endothelial function, or number of thin‐capped fibroatheromas per vessel. Importantly, after adjusting for β‐blocker, low‐WSS segments remained significantly associated with lumen loss and plaque progression. Conclusion Nebivolol, compared with atenolol, was associated with greater plaque progression and constrictive remodeling, likely driven by more low‐WSS segments in the nebivolol arm. Both β‐blockers had similar effects on oxidative stress, microvascular function, and endothelial function. Clinical Trial Registration URL: https://clinicaltrials.gov/. Unique identifier: NCT01230892.

Association of Wall Shear Stress with Coronary Plaque Progression and Transformation

Coronary endothelial function regulation by wall shear stress (WSS), the frictional force of blood exerted against the vessel wall, can help explain the focal propensity of plaque development in an environment of systemic atherosclerosis risk factors. Sustained abnormal pathologic WSS leads to a proatherogenic endothelial cell phenotype, plaque progression and transformation, and adaptive vascular remodeling in site-specific areas. Assessing dynamic coronary plaque compositional changes in vivo remains challenging; however, recent advances in intravascular image acquisition and processing may provide swifter WSS calculations and make possible larger prospective investigations on the prognostic value of WSS in patients with coronary atherosclerosis.

Elevated Levels of Serum Fibrin and Fibrinogen Degradation Products Are Independent Predictors of Larger Coronary Plaques and Greater Plaque Necrotic Core

BACKGROUND Co-existence of vulnerable plaque and pro-thrombotic state may provoke acute coronary events. It was hypothesized that elevated serum levels of fibrin and fibrinogen degradation products (FDP) are associated with larger total plaque and necrotic core (NC) areas. METHODSANDRESULTS Seventy-five patients presenting with stable anginal symptoms (69%) or stabilized acute coronary syndrome (ACS; 31%), and found to have non-obstructive coronary artery disease (CAD) with a fractional flow reserve >0.8, were studied. Invasive virtual histology intravascular ultrasound (VH-IVUS) was performed in 68 LAD arteries, 6 circumflex arteries, and 1 right coronary artery. Serum FDP levels were measured using ELISA technique. Plaque volumetrics and composition were assessed in each VH-IVUS frame and averaged. The median age of patients was 56 (47-63) years; 52% were men and 23% had diabetes. The average length of coronary artery studied was 62 mm. After adjustment for systemic risk factors, medications, CRP levels and ACS, male gender (P<0.001) and serum FDP levels (P=0.02) were independent predictors of a larger NC area. Older age (P<0.001), male gender (P<0.0001) and increased serum FDP level (P=0.03) were associated with a larger plaque area. CONCLUSIONS In patients with CAD, a higher serum level of FDP is independently associated with larger plaques and greater plaque NC.

Pattern of cardiac surveillance among patients with lymphoma receiving anthracycline-based chemotherapy

Objective Anthracyclines are potent antineoplastic agents in the treatment of lymphoid malignancies, but their therapeutic benefit is limited by cardiotoxicity. The American Heart Association (AHA) recommends routine surveillance, early diagnosis and treatment of anthracycline-based chemotherapy (AC) induced cardiomyopathy (AC-CMP). We aimed to assess the prevalence of AC-CMP in patients with lymphoma, surveillance patterns of left ventricular ejection fraction (LVEF) in those receiving AC and management of patients with AC-CMP at an academic medical centre prior to the development of a comprehensive cardio-oncology programme. Methods We performed a retrospective cohort study examining 218 patients with aggressive B cell non-Hodgkins lymphomas (B-NHL) who received AC 1992–2012 and had serial follow-up. AC-CMP was defined as LVEF decrease ≥10% with final LVEF≤50% or LVEF reduction ≥15% regardless of final LVEF. Results Of 218 patients treated with AC, 73 (34%) had LVEF assessment both prior to and after receiving AC. Of these 73 patients, 24 developed AC-CMP and had higher cumulative all-cause mortality than those without AC-CMP (HR 2.35, p=0.03). Coronary artery disease (CAD) was an independent predictor of AC-CMP (p=0.048). Mean post-AC LVEF was lower in patients with CAD compared with those without CAD when their baseline LVEF was 45% (p=0.0009) or 55% (p=0.001) but was similar at 65% (p=0.33). Less than half of patients with AC-CMP received recommended heart failure medication therapy. Conclusions Historically, one-third of patients with B-NHL treated with AC underwent surveillance according to AHA guidelines. There is substantial opportunity for collaboration between oncologists and cardiologists to improve the care of patients with lymphoma receiving AC.