Serial Changes Research Articles

Serial Changes of Coronary Flow Reserve Over One Year After Transcatheter Aortic Valve Implantation in Patients with Severe Aortic Stenosis

Serial Changes of Coronary Flow Reserve Over One Year After Transcatheter Aortic Valve Implantation in Patients with Severe Aortic Stenosis

Impact of Skeletal Muscle Loss and Visceral Obesity Measured Using Serial CT on the Prognosis of Operable Breast Cancers in Asian Patients.

ObjectiveThis study aimed to investigate the impact of baseline values and temporal changes in body composition parameters, including skeletal muscle index (SMI) and visceral adipose tissue area (VAT), measured using serial computed tomography (CT) imaging on the prognosis of operable breast cancers in Asian patients.Materials and MethodsThis study retrospectively included 627 Asian female (mean age ± standard deviation [SD], 53.6 ± 8.3 years) who underwent surgery for stage I–III breast cancer between January 2011 and September 2012. Body composition parameters, including SMI and VAT, were semi-automatically calculated on baseline abdominal CT at the time of diagnosis and follow-up CT for post-treatment surveillance. Serial changes in SMI and VAT were calculated as the delta values. Multivariable Cox regression analysis was used to evaluate the association of baseline and delta SMI and VAT values with disease-free survival.ResultsAmong 627 patients, 56 patients (9.2%) had breast cancer recurrence after a median of 40.5 months. The mean value ± SD of the baseline SMI and baseline VAT were 43.7 ± 5.8 cm2/m2 and 72.0 ± 46.0 cm2, respectively. The mean value of the delta SMI was -0.9 cm2/m2 and the delta VAT was 0.5 cm2. The baseline SMI and VAT were not significantly associated with disease-free survival (adjusted hazard ratio [HR], 0.983; 95% confidence interval [CI], 0.937–1.031; p = 0.475 and adjusted HR, 1.001; 95% CI, 0.995–1.006; p = 0.751, respectively). The delta SMI and VAT were also not significantly associated with disease-free survival (adjusted HR, 0.894; 95% CI, 0.766–1.043; p = 0.155 and adjusted HR, 1.001; 95% CI, 0.989–1.014; p = 0.848, respectively).ConclusionOur study revealed that baseline and early temporal changes in SMI and VAT were not independent prognostic factors regarding disease-free survival in Asian patients undergoing surgery for breast cancer.

Takotsubo cardiomyopathy in a bedridden patient with dementia and communication difficulties due to Alzheimer's disease.

Takotsubo cardiomyopathy is a transient wall motion abnormality of the left ventricular apex, accompanied by emotional or physical stress. Although Takotsubo cardiomyopathy is generally considered a benign disease, severe clinical complications may occur, and early detection of the disease is important. In this report, we present the case of an 86-year-old bedridden woman with a history of bronchial asthma who was transferred to our hospital because of wheezing. She was diagnosed with Alzheimer’s disease and had communication difficulties. After an asthma attack and improvement, Takotsubo cardiomyopathy was identified via electrocardiography. She was unable to complain of any symptoms but showed serial electrocardiographic changes, elevated myocardial markers, and transient left ventricular apical ballooning. The prevalence of dementia increases dramatically with age. This case indicates that Takotsubo cardiomyopathy may occur even in patients with severe dementia, who are bedridden and show communication difficulties in a clinical setting.

Relationship of Serial High-Sensitivity C-Reactive Protein Changes to Long-term Clinical Outcomes in Stabilised Patients After Myocardial Infarction.

Little is known about the association between serial high-sensitivity C-reactive protein (hsCRP) measurements and long-term outcomes in post-myocardial infarction (MI) patients. We aimed to investigate the usefulness of serial hsCRP measurements for risk stratification in stabilised post-MI patients after percutaneous coronary intervention (PCI). A total of 1018 patients who had hsCRP values at both baseline and 1 year after MI were included. High inflammatory status was defined as hsCRP > 2 mg/L. Patients were classified into 4 groups: persistently low, falling (first high then low hsCRP), rising (first low then high hsCRP), and persistently high hsCRP. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE: a composite of all-cause of death, MI, and cerebrovascular accident) within 4 years after the second hsCRP measurement. At 1 year after MI, the numbers of patients in the persistently low, falling, rising, and persistently high hsCRP groups were 394 (38.7%), 358 (35.2%), 69 (6.8%), and 197 (19.4%), respectively. The incidence of MACCE was progressively elevated from the persistently low to the falling, rising, and persistently high hsCRP groups (4.8%, 8.1%, 10.1%, and 13.2%, respectively; P= 0.004). Persistently high hsCRP was an independent predictor of MACCE (adjusted hazard ratio 2.55; 95% confidence interval 1.35-4.81; P= 0.004) and provided incremental prognostic value beyond that of the baseline clinical risk model (net reclassification improvement= 0.397; integrated discrimination improvement= 0.025; all P < 0.001). Among stabilised post-MI patients who underwent PCI, persistently high hsCRP was frequently seen 1 year after MI and was strongly associated with long-term adverse clinical outcomes. Serial measurements of hsCRP during clinical follow-up after MI may help to identify patients at higher risk for mortality and morbidity.

Effect of Supra-Choroidal Triamcinolone Injection on Best-Corrected Visual Acuity and Central Retinal Thickness in Patients with Macular Edema Secondary to Retinal Vein Occlusion

Purpose: To find out the effect of suprachoroidal Triamcinolone injection on best corrected visual acuity (BCVA) and central retinal thickness (CRT) in patients with macular edema secondary to retinal vein occlusion. Study Design: Interventional case series. Place and Duration of Study: College of Ophthalmology and Allied vision Sciences, Ophthalmology department, Unit II Mayo hospital, Lahore, from September 2019 to January 2020. Methods: This study included 45 patients diagnosed with unilateral, retinal vein occlusion associated with macular edema. Patients with previous anti-vascular endothelial growth factor injection or any steroid injection received in the last 3 months or macular edema due to any other cause were excluded from the study. Only one eye of each patient was enrolled. The patients were treated with suprachoroidal triamcinolone injection (4 mg/100µL concentration). Patients with baseline central retinal thickness (CRT) of &gt; 300 µm were included in the study. Serial changes in this parameter were evaluated at 1 week, 1 month and 3?months after suprachoroidal triamcinolone injection. Final CRT and Best-corrected visual acuity (BCVA) was recorded after three months. Results: Out of 45 patients, 26 (57.7%) were males and 19 (42.2%) were females. Majority of the patients (35.4%) were 51–60 years old. During first week the visual acuity was 0.321 ± 0.273 LogMAR, after one month it was 0.468 ± 0.291 and 0.406 ± 0.318 after 03 months with a p value of 0.003. After three months significant decrease in CRT was observed. With a p-value of 0.002. Conclusions: Suprachoroidal injection significantly improves BCVA and decreases CRT in patients with macular edema due to retinal vein Occlusion. Keywords: Retinal vein occlusion, suprachoroidal injection, triamcinolone acetonide.

Weakened Grip Strength Over 40 Years in a Community-Dwelling Cohort in Tanushimaru, Japan.

An epidemiological survey has been periodically performed since 1977 among the adult population in Tanushimaru, a typical farming town in Japan. We aimed in this study to retrospectively investigate changes of grip strength (GS) and its correlates over 40 years in the same cohort of community-dwelling adults. We used pooled data from the survey to deduce essential correlates of GS in community-dwelling adults. We retrospectively compared serial correlates of GS in the adult population in Tanushimaru between a population tested in 1977 and 1979 (Cohort A, n=2,452) and another population tested in 2016 and 2018 (Cohort B, n=1,505), to identify essential correlates of GS for investigating changes in GS during the past 40 years in community-dwelling adults. Age, height, weight, and the occupation of the subjects remained as correlates of GS in both genders during the past 40 years. In males, abdominal circumference also remained as a correlate of GS. Serum albumin levels in males and systolic blood pressure in females were identified as new correlates. GS after adjustment for the above correlates weakened in both genders, and the serial change in GS was particularly remarkable in subjects whose occupations were Class-1 and Class-2, which were defined as moderately hard work. From a periodically-performed epidemiological survey of a community-dwelling cohort in a Japanese typical farming town, age, height, weight, and occupation were deduced as essential correlates of GS. GS in the community dwelling cohort weakened in both genders over 40 years, possibly affected by their occupation.

Real Color Sectioned Images and Correspondence with Ultrasound Images of the Palmar Wrist

The aim of this study was to identify sequential changes in the actual sites and shapes of wrist structures on the high-resolution sectioned images and to compare these with those on ultrasound (US) images. These images of the wrist may yield guidelines for diagnosing various pathological lesions in the wrist. In the sectioned images of a whole cadaver body, and the images including the wrist were selected, and part of the hand was cropped. A wrist of one healthy Korean subject was scanned by ultrasonography to obtain US images of the wrist. Wrist structures were identified and labeled in detail on the sectioned images and the corresponding US images. Serial changes of the sites and shapes of the wrist structures mainly occurred in the bones, median nerve, ulnar artery, ulnar nerve, and the flexor pollicis longus tendon, along with thickening of the thenar and hypothenar muscles. The present results could provide a new guide for anatomy mapping, diagnosing, and detecting various lesions of the wrist. They can also be useful and effective for educational purposes related to interpreting US images.

Progressive left and right heart dysfunction in coronavirus disease-19: Prospective echocardiographic evaluation.

AimsCardiac dysfunction in coronavirus disease-19 (COVID-19) has been reported during acute phase but serial changes have not been well studied. To determine serial changes in type and severity of echocardiographic left and right heart functions we performed a prospective study.Methods and resultsSuccessive COVID-19 patients at discharge from the hospital from June to December 2020 were enrolled. Clinical details were obtained and echocardiography was performed using Philips IE33X-Matrix. Follow-up evaluation was performed after 3 months. In total, 1789 COVID-19 patients were evaluated. Baseline echocardiography was performed in 1000 eligible patients (men 611, women 389). Mean age was 50.2 ± 15 years, hypertension was in 44.0%, diabetes in 49.4%, and coronary disease in 10.8%. COVID-19 was mild in 47.0%, moderate in 39.5%, and severe in 13.5%. Baseline cardiac parameters were more impaired in severe vs. moderate or mild COVID-19. At 3 months, in 632 patients where baseline and follow-up data were available, decline was observed in select left [left ventricular internal diameter in diastole +0.9 ± 0.2 mm, left atrial volume +7.6 ± 0.1 mL/m2, mitral E/e′ +4.8 ± 0.1, and left ventricular ejection fraction (LVEF) −3.7 ± 0.2%] and right [right ventricular internal diameter in diastole +2.1 ± 0.1 mm, right atrial internal dimension +1.6 ± 0.1 mm, tricuspid Vmax +1.0 ± 0.1 cm, and tricuspid annulus plane systolic excursion (TAPSE) −2.7 ± 0.2 mm] heart variables (P < 0.001). Compared to mild COVID-19, decline was significantly greater in moderate/severe disease, LVEF −1.1 ± 0.3 vs. −3.8 ± 0.3%; mitral E/e′ +3.2 ± 0.1 vs. +4.8 ± 0.1, tricuspid Vmax +0.3 ± 0.1 vs. +1.0 ± 0.1 cm, and TAPSE −0.7 ± 0.2 vs. −2.7 ± 0.2 mm (P < 0.001).ConclusionThis study shows impaired cardiac functions in severe and moderate COVID-19 compared to mild at hospital discharge and progressive decline in left and right heart functions at 3 months. Impairment is significantly greater in patients with moderate to severe disease.

Changes in childhood growth after adenotonsillectomy: a population-based cohort study

ObjectivesThis study aimed to investigate the association between adenotonsillectomy (T&A) and serial changes in growth in children through a population-based nationwide study as well as the national health insurance service (NHIS) database. MethodsPropensity score (PS) matched children with and without T&A were selected in NHIS database, which includes all individuals born in Korea in 2008–2009. Serial changes of BMI and height were compared in children with and without T&A, and growth changes depending on the time of operation were also considered. The outcomes were differences in age-/sex-standardized BMI (BMI-z) and height (height-z) between the groups. Changes in BMI-z and height-z were further analyzed according to the timing of operation. ResultsOf 919,707 individuals born in Korea in 2008–2009, 3172 children were included in the operation group and 31,663 PS-matched children were included in the control group. T&A was related to increased weight and height in the operation group than in the control group. At 66–71 months of age, BMI-z and height-z were 0.41 (0.02) and 0.42 (0.02), respectively, in the operation group and 0.18 (0.01) and 0.35 (0.01), respectively, in the control group. On adjustment with preoperative BMI-z, more weight gain was noted in the operation group (p < 0.001). Shortly after T&A, BMI-z increased significantly in the operation group; a significant increase in height-z was observed more than 1 year after T&A. ConclusionsChildren who underwent T&A tended to experience a growth spurt; when surgical intervention such as T&A is required, care should be taken to minimize or reverse the anticipated weight gain.

Maintenance of low driving pressure in patients with early acute respiratory distress syndrome significantly affects outcomes

BackgroundDriving pressure (∆P) is an important factor that predicts mortality in acute respiratory distress syndrome (ARDS). We test the hypothesis that serial changes in daily ΔP rather than Day 1 ΔP would better predict outcomes of patients with ARDS.MethodsThis retrospective cohort study enrolled patients admitted to five intensive care units (ICUs) at a medical center in Taiwan between March 2009 and January 2018 who met the criteria for ARDS and received the lung-protective ventilation strategy. ∆P was recorded daily for 3 consecutive days after the diagnosis of ARDS, and its correlation with 60-day survival was analyzed.ResultsA total of 224 patients were enrolled in the final analysis. The overall ICU and 60-day survival rates were 52.7% and 47.3%, respectively. ∆P on Days 1, 2, and 3 was significantly lower in the survival group than in the nonsurvival group (13.8 ± 3.4 vs. 14.8 ± 3.7, p = 0.0322, 14 ± 3.2 vs. 15 ± 3.5, p = 0.0194, 13.6 ± 3.2 vs. 15.1 ± 3.4, p = 0.0014, respectively). The patients were divided into four groups according to the daily changes in ∆P, namely, the low ∆P group (Day 1 ∆P < 14 cmH2O and Day 3 ∆P < 14 cmH2O), decrement group (Day 1 ∆P ≥ 14 cmH2O and Day 3 ∆P < 14 cmH2O), high ∆P group (Day 1 ∆P ≥ 14 cmH2O and Day 3 ∆P ≥ 14 cmH2O), and increment group (Day 1 ∆P < 14 cmH2O and Day 3 ∆P ≥ 14 cmH2O). The 60-day survival significantly differed among the four groups (log-rank test, p = 0.0271). Compared with the low ΔP group, patients in the decrement group did not have lower 60-day survival (adjusted hazard ratio 0.72; 95% confidence interval [CI] 0.31–1.68; p = 0.4448), while patients in the increment group had significantly lower 60-day survival (adjusted hazard ratio 1.96; 95% CI 1.11–3.44; p = 0.0198).ConclusionsDaily ∆P remains an important predicting factor for survival in patients with ARDS. Serial changes in daily ΔP might be more informative than a single Day 1 ΔP value in predicting survival of patients with ARDS.

QRS duration predicts outcomes in cardiac arrest survivors undergoing therapeutic hypothermia.

Whether the electrocardiography (ECG) serial changes predict outcomes in cardiac arrest survivors undergoing therapeutic hypothermia remains unclear. This retrospective observational study enrolled 366 adult nontraumatic cardiac arrest survivors who underwent therapeutic hypothermia in a tertiary transfer center during 2006-2018. The ECG at return of spontaneous circulation (ROSC), during hypothermia and after rewarming were analyzed. 295 cardiac arrest survivors were included. Compared with the survivors, the non-survivors had longer QRS durations at the ROSC (118.33±32.47ms vs 106.88±29.78ms, p<0.001) and after rewarming (99.26±25.07ms vs 93.03±19.09ms, p=0.008). The enrolled patients were classified into 4 groups based on QRS duration at the ROSC and after rewarming, namely (1) narrow-narrow (narrow QRS at ROSC and narrow QRS after rewarming, n=156), (2) narrow-wide (n=29), (3) wide-narrow (n=87), and (4) wide-wide (n=23) group. The wide-wide group had the worst survival rates [odds ratio (OR)=0.141, p=0.001], followed by the narrow-wide group (OR 0.223, p=0.003) and the wide-narrow group (OR 0.389, p=0.003). In cardiac arrest survivors given therapeutic hypothermia, QRS durations at the ROSC, after rewarming and their changes may predict survival to hospital discharge.

The Overlap Index: A new means for early detection of serial tau PET signal change

AbstractBackgroundIn longitudinal tau (flortaucipir) positron emission tomography (PET), a reliable method to detect a tau accumulation while minimizing a random variability is crucial. Variability can be a problem especially in the early stages of tau pathology in which only small regions and low levels of accumulation may exist relative to the range of random noise fluctuation.MethodWe recruited 76 participants who had serial scans for a total of 234 tau PET scans. In this cohort we tested a PET signal measurement method we developed called the “overlap index” (OI). The OI was calculated by identifying voxels that have elevated tau PET signal that overlap on two successive tau PET scans in the same participant (Figure 1). This analysis procedure tests the hypothesis that voxel‐wise, elevated‐uptake consistency might be more sensitive for early detection of tau tangles than standard ROI based measures. We compared OI to ROI based measures for early detection of increasing tau PET signal and detection clinical progression. A meta ROI used in this analysis included the amygdala, entorhinal cortex, fusiform, parahippocampal, and inferior temporal and middle temporal gyri.ResultOI showed regional progression of tau in the temporal lobe followed by increases throughout the brain at relatively low standardized uptake value ratio (SUVr) levels (Figure 2A and B). The topographical pattern of OI was in agreement in some respects with the sequential appearance of tau aggregation (Figure 2B and C). The high‐OI group (OI&gt;0.5) had a significantly higher ΔSUVr compared to the low‐OI group (OI&lt;0.5) (Figure 3A and B). OI identified subjects that did or didn’t have tau accumulation within meta SUVr subgroups even when below the meta ROI SUVr threshold. OI was associated with early clinical disease stage progression vs meta‐ROI SUVr measures (Figure 3C‐E).ConclusionIn this study, we found that OI tau PET measurement was able to quantify voxel‐wise consistency using a set of serial scans. OI may detect earlier tau tangle accumulation and earlier disease progression than standard SUVr measurements in tau PET.

Serial CT changes in different components of lung cancer associated with cystic airspace in patients treated with neoadjuvant chemotherapy

The aim of this study was to observe changes in different components (solid, cystic airspace, or entire tumor) in lung cancer associated with cystic airspace following treatment with neoadjuvant chemotherapy (NC), using computerized tomography (CT). We analyzed serial (baseline, first-time follow-up, and last-time follow-up) clinical data and CT imaging in six patients treated with NC. The diameters, areas, and volumes of different tumor components (solid, cystic airspace, and entire tumor) were measured. Delta (Δ) was used to represent changes in these parameters between two examinations: Δ1(%) represents the change from baseline to first follow-up after NC, and Δ2(%) represents the change from baseline to last follow-up after NC. We used the intra-group correlation coefficient (ICC) to test for consistency between parameters as measured by two radiologists. The diameter of solid components in all lesions showed a trend of continuous reduction compared with baseline (Δ1 ranged from − 8.3 to − 46.0%, Δ2 from − 30.8 to − 69.2%). For cystic airspace and entire tumors, different lesions showed different trends over the course of treatment. For diameter, area, and volume, Δ1 of changes in the solid component ranged from − 8.3 to − 46.9%, − 19.4 to − 70.8%, and − 19.1 to − 94.7%, respectively; Δ2 ranged from − 30.8 to − 69.2%, − 50.8 to − 92.1%, and − 32.7 to − 99.8% in diameter, area, and volume, respectively. Results were inconsistent between different components of lung cancer associated with cystic airspace that was treated with NC, but the diameter, area, and volume of solid components were continuously reduced during treatment. Furthermore, area and volume measurements showed more-significant variation than diameter measurements.

Serial change in perfusion\u2013metabolism mismatch after coronary artery bypass grafting

ObjectiveMyocardial ischemia is known to suppress fatty acid metabolism and favor glucose metabolism. However, changes in myocardial metabolism after coronary revascularization are not fully elucidated.MethodsThirty-eight patients with coronary artery disease were retrospectively enrolled. These patients had undergone stress perfusion single photon emission computed tomography (SPECT) and 123I-BMIPP SPECT in both the short-term (6.4 ± 4.7 months) and mid-term (29.9 ± 7.2 months) after isolated coronary artery bypass grafting. Tracer uptake was graded using a 17-segment, 5-point scoring model. Serial changes in SRS (summed rest score), SDS (summed difference score), the BMIPP score (total defect score of BMIPP), and the mismatch score (BMIPP score–SRS) were evaluated. In addition, persistent perfusion–metabolism mismatch (PM) was defined as mismatch score minus SDS of 3 or more during the mid-term postoperative period. The clinical parameters associated with PM were examined.ResultsFrom short- to mid-term postoperative period, the extent of infarcted myocardium (SRS) did not change significantly (7.8 ± 8.0 to 7.1 ± 7.0, P = 0.117). The extent of ischemic myocardium (SDS), the BMIPP score and the mismatch score, which reflects perfusion–metabolism mismatch, were significantly improved (2.0 ± 2.8 to 0.7 ± 1.0, P = 0.010; 12.2 ± 9.0 to 9.5 ± 7.9, P < 0.001; 4.4 ± 3.7 to 2.5 ± 2.6, P < 0.001; respectively). Remarkably, perfusion–metabolism mismatch persisted in 13 patients (34%) even in the mid-term postoperative period. eGFR and SYNTAX score were independent predictors of persistent perfusion–metabolic mismatch in multivariable analysis (OR = 0.951, 95% CI 0.898–0.985, P = 0.010 and OR = 1.126, 95% CI 1.011–1.254, P = 0.031, respectively). The mismatch score both in the short- and mid-term significantly correlated with SYNTAX score (r = 0.400 and r = 0.472, respectively).ConclusionsFatty acid metabolism disturbance improved from short- to mid-term postoperative period in patients with successful reperfusion by coronary artery bypass grafting. However, in patients with severe atherosclerosis, impaired fatty acid metabolism was sustained until the mid-term postoperative period, even though ischemia had resolved.

Abstract 11640: Longitudinal Changes in Ventricular Torsion in Adolescents with Single-Ventricle Anatomy: Long Term Follow Up

Background: Ventricular torsion is important in assessment of the systolic and diastolic function especially in single ventricle (SV) but is poorly studied. Objective: We aimed to a) examine serial changes in SV torsion, and b) examine its association with CMR data and exercise performance. Methods: We retrospectively studied SV patients after Fontan completion. Speckle-tracking echocardiography was used to evaluate serial changes in ventricular mechanics; strain, torsion, and untwist. CMR volumetric data and cardiopulmonary exercise data closest to echocardiograms were obtained. The most recent follow up echocardiographic and CMR data were compared to data before Fontan. Results: 45 SV patients (27 LV, 12 RV, and 6 co dominant) were studied. Demographics, echocardiographic, CMR, and exercise data are shown in table 1. Mean time at follow up echo from time of Fontan was 12.8 (10.6-16.6) years. Follow up echocardiograms showed reduced global longitudinal strain [-17.5(-6.5 to-19.5) vs -19.8 (-12 to -23%), p=0.01], circumferential strain [-15.7 (-8.4 to - 20.7) vs [-18.9 (-11.2 to -25.0), p=0.009], reduced torsion [5.5°/cm (-6.1 to 17.8) vs 8.1°/cm (-9.7 to18.5) vs, p=0.03], decreased apical rotation [6.5°/cm (-11.3 to 18.1) vs 5.1°/cm (-21.2 to 19.7), p=0.02] with no significant change in basal rotation compared to the echo at time of Fontan. Single RV had lower net torsion compared to single LV [2.7°/cm (-2.5.1 to 13.1) vs 6.1°/cm (-6.3 to 19.5) vs, p=0.03]. Mean interval between echocardiograms and exercise testing and CMR were 3.5±2.2 and 5.6±1.8 months respectively. Torsion and untwist rates correlated with peak oxygen consumption (r=0.64, -0.41, p=0.01, 0.04 respectively) but did not correlate with ventricular volumes or ejection fractions. Conclusion: In long term follow up post Fontan, SV torsion is decreased due to decreased apical rotation, worse in single RV, and is associated with decreased exercise capacity.

Abstract 12510: Monitoring of Chemotherapy-Induced Vascular Toxicity in Pediatric, Adolescent, and Young Adult Lymphomas Using PET/CT Imaging

Introduction: Lymphoma treatment with chemotherapy, alone or in combination with radiation therapy, can have off-target effects that lead to vascular toxicity, which has recently gained attention in the field of cardio-oncology. Positron emission tomography (PET)/computed tomography (CT) imaging with fluorine-18 ( 18 F)-fluorodeoxyglucose (FDG) is standard of care for monitoring lymphoma treatment responses and is a widely accepted tool for assessing vascular inflammation. We hypothesized that 18 F-FDG PET/CT imaging could detect and quantify chemotherapy-induced increases in vascular inflammation following the first cycle of lymphoma treatment in pediatric, adolescent, and young adult (AYA) patients. Methods: Whole-body 18 F-FDG PET/CT images were retrospectively acquired at initial staging of disease and first treatment follow-up for pediatric and AYA lymphoma patients (n=33). Regions of interest were manually drawn using each axial slice of fused PET/CT images for the femoral and popliteal arteries/veins to quantify serial changes in vascular uptake of 18 F-FDG. The changes in the average maximum standard uptake value (SUV max ) for the femoral-popliteal vessels were calculated. Results and Conclusions: The patient population consisted of Non-Hodgkin (55%) and Hodgkin (45%) lymphoma patients with a mean age of 13 years (SD=4.7). 18 F-FDG PET/CT imaging detected ( Fig. 1A ) and quantified a significant increase in the mean SUV max from baseline (0.94±0.03) to first treatment follow-up (1.06±0.02) for the femoral and popliteal arteries/veins ( Fig. 1B ). Standard of care 18 F-FDG PET/CT imaging can non-invasively quantify chemotherapy-induced vascular inflammation in young cancer patients in response to the first cycle of treatment, thus representing an approach for evaluating vascular toxicity and creating novel opportunities for personalized medicine focused on reducing cardiovascular side effects of chemotherapy.

Abstract 13154: Association of Serial Health Status Measurements With Clinical Events: Insights From the ISCHEMIA Trial

Introduction: The Seattle Angina Questionnaire (SAQ), a disease-specific health status measure, has been shown to predict future clinical outcomes in patients with chronic coronary disease (CCD) at a single point in time. The prognostic value of serial SAQ scores in patients with CCD is unknown. Methods: Serial assessments of the 7-item SAQ were obtained in the ISCHEMIA trial of patients with CCD and moderate/severe ischemia. Using Cox regression, we examined the association of baseline and 3-month SAQ-7 Summary Scores (SAQ7-SS) with CV death, MI or unstable angina hospitalization over a 12 month period (between 3 and 15 months after randomization) in patients randomized to conservative treatment. We fit several models including: (a) baseline score only; (b) 3-month score only; (c) 3-month change only; (d) baseline and 3-month score; (e) 3-month change and score. Results: The mean age was 64.3 years in 2095 patients randomized to conservative care with SAQ scores at 1 and 3 months; 78% were men. Twelve-month event rates were 3.3% overall; 2.9% with a 3-month SAQ7-SS ≥75, and 6.9% in those with 3-month scores &lt;50. In unadjusted analyses, higher scores at baseline, 3 months, and greater 3-month improvement were associated with fewer clinical events (Figure 1a). In landmark analyses combining serial scores, neither baseline nor change were significant after adjustment for 3-month score (Figures 1b and 1c). Conclusions: We found that the most recent SAQ score was more predictive of subsequent clinical events than prior scores or changes. Following patients’ health status not only provides an assessment of their current angina control, but also a continuously updatable insight into their risk for subsequent cardiac events.

Abstract 10767: Therapeutic Effects of Clustered Human Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells for Chronic Hind Limb Ischemia

Introduction: Human induced pluripotent stem cell-derived mesenchymal stem cell (iPS-MSC) is a promising cell source of regeneration therapy for hind limb ischemia (HLI). To date, we have already demonstrated the clustered cell administration has better therapeutic effects for HLI than single-cell administration using autologous myoblast cells. In this study, we administered clustered iPS-MSCs into the chronic HLI mouse and evaluated the regeneration effect. Methods: Human iPS cells were cultured in a serum-free medium containing the transforming growth factor-β pathway inhibitor SB431542 for the differentiation to MSC in vitro . These iPS-MSCs were expanded to form cell patches (10 6 cells/sheet). These iPS-MSC patches were mechanically fragmented and were then administered into HLI mice as clustered cells (CC group, n=10). As control groups, non-clustered single iPS-MSC (SC, n=12) or Hanks’ balanced salt solution (HBSS, n=9) were administered. HLI was induced to the NOD/Shi-scid mouse by resecting the femoral artery and vein. The mice of which blood perfusion, being evaluated with Laser Doppler Perfusion Imaging (LDPI) at day 7, was under 40 % as compared with contralateral leg were included in the further study as the “chronic HLI model”. Serial change of LDPI and histological change of leg muscles were analyzed regarding angiogenesis and skeletal muscle regeneration. Results: Blood perfusion was significantly improved in CC (56.16±20.03%) as compared with HBSS (34.09±12.80%, P=0.0140) and SC (29.04±6.770%, P=0.0010) at day 14. Also, histological analysis showed the number of CD31 + endothelial cells is significantly larger in CC (353.6±59.97/mm 2 ) as compared with HBSS (126.2±22.85/mm 2 , P=0.0004) and SC (103.6±23.81/mm 2 , P=0.0001). The mean diameter of skeletal muscle cells is significantly larger in CC (42.28±4.113μm) as compared with SC (29.02±2.535μm, P=0.0001) and HBSS (29.61±3.103μm, P=0.0007). Conclusions: The clustered iPS-MSC significantly augmented angiogenesis and muscle regeneration in chronic HLI as compared with single-cell administration.

Assessment of thrombocytopenia, sleep apnea, and cardiac involvement in GNE myopathy patients.

We previously identified UDP-N-acetylglucosamine 2-epimerase (GNE) myopathy patients with sleep apnea and a past history of thrombocytopenia, but without disease-specific cardiac involvement. This study aimed to clarify the occurrence, severity, and serial changes of these complications. Thirty-three genetically confirmed GNE myopathy patients who participated in a 5-y longitudinal observational history study underwent platelet count and platelet-associated immunoglobulin G (PA-IgG) measurements, a sleep study, and electrocardiography (ECG), Holter ECG, and echocardiogram examinations. Among the 33 patients, three had low platelet counts and 17 out of 26 were PA-IgG positive. No patient exhibited bleeding tendencies, and 3 out of 28 had low platelet counts. Muscle weakness was more pronounced, and summed MMT and grip power significantly lower, in PA-IgG-positive patients than in PA-IgG-negative patients. Of 19 patients, 7, 4, and 3 who underwent a sleep study had mild, moderate, and severe sleep apnea, respectively, and three started continuous positive airway pressure (CPAP). The respiratory disturbance index was not significantly correlated with physical evaluation items or forced vital capacity. All patients underwent ECG, 32 underwent cardiac ultrasound, and 25 underwent Holter ECG. No disease-specific cardiac involvement was noted, no serial changes during the follow-up period were observed for ECG and echocardiography, and none of the patients required therapy for cardiac abnormalities. PA-IgG is a potential disease biomarker in GNE myopathy patients, although its significance needs to be clarified. While none of the patients in this study experienced cardiomyopathy or arrythmia due to myopathy, sleep apnea was identified as a frequent complication.

The Right Heart Network and Risk Stratification in Pulmonary Arterial Hypertension

BackgroundPrognosis in pulmonary arterial hypertension (PAH) is closely related to indexes of right ventricular function. A better understanding of their relationship may provide important implications for risk stratification in PAH.Research QuestionCan clinical network graphs inform risk stratification in PAH?Study Design and MethodsThe study cohort consisted of 231 patients with PAH followed up for a median of 7.1 years. An undirected, correlation network was used to visualize the relationship between clinical features in PAH. This network was enriched for right heart parameters and included N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP), comprehensive echocardiographic parameters, and hemodynamics, as well as 6-min walk distance (6MWD), vital signs, laboratory data, and diffusing capacity for carbon monoxide (Dlco). Connectivity was assessed by using eigenvector and betweenness centrality to reflect global and regional connectivity, respectively. Cox proportional hazards regression was used to model event-free survival for the combined end point of death or lung transplantation.ResultsA network of closely intertwined features centered around NT-proBNP with 6MWD emerging as a secondary hub were identified. Less connected nodes included Dlco, systolic BP, albumin, and sodium. Over the follow-up period, death or transplantation occurred in 92 patients (39.8%). A strong prognostic model was achieved with a Harrell’s C-index of 0.81 (0.77-0.85) when combining central right heart features (NT-proBNP and right ventricular end-systolic remodeling index) with 6MWD and less connected nodes (Dlco, systolic BP, albumin, sodium, sex, connective tissue disease etiology, and prostanoid therapy). When added to the baseline risk model, serial change in NT-proBNP significantly improved outcome prediction at 5 years (increase in C-statistic of 0.071 ± 0.024; P = .003).InterpretationNT-proBNP emerged as a central hub in the intertwined PAH network. Connectivity analysis provides explainability for feature selection and combination in outcome models.