Assessment of Small-bowel and Colonic Transit on Routine Gastric Emptying Scintigraphy: Establishment of Reference Values.

Purpose of the Study: The primary objective was to establish the reference values for small-bowel and colonic transit within the context of the routine standard solid meal gastric emptying scintigraphy (GES). The secondary objective was to compare the small-bowel and colonic transit between the anterior view and geometric mean methods. Materials and Methods: Twenty-nine healthy controls underwent routine GES, with additional imaging at 24 h if feasible. Small-bowel transit was assessed using the index of small-bowel transit (ISBT), calculated as the ratio of terminal ileal reservoir counts to total abdominal counts at 4 h. Colonic transit was evaluated using the colonic geometric center (CGC) by dividing the large bowel into four segments, with an additional fifth segment accounting for the eliminated counts. Reference values were established based on the fifth percentile or mean ± 1.96 standard deviations. Rapid small-bowel transit was visually determined. Paired Samples t-test or Wilcoxon signed-rank test, as applicable, was used to compare the small-bowel and colonic transit between the anterior view and geometric mean methods. For comparing small-bowel and colonic transit between females and males, the Independent samples t-test or Mann-Whitney U-test was applied, as appropriate. The correlation between age and small-bowel and colonic transit was assessed using Spearman's rank correlation analysis. Results: The reference value for small-bowel transit using the geometric mean method was established as ISBT >37% at 4 h, whereas rapid small-bowel transit was defined as the first visualization of activity in the cecum-ascending colon within 2 h. For colonic transit, the reference range was established as CGC 2.8-4.4 at 24 h. Comparing the anterior view and geometric mean methods, there were no significant differences in ISBT and CGC values (P ≥ 0.125). Gender did not affect small-bowel and colonic transit in both methods (P ≥ 0.378), and age showed no significant correlations (P ≥ 0.053). Conclusion: This study determined the reference values for small-bowel and colonic transit in the Indian population using routine GES, avoiding the need for additional complex procedures. The results may be generalized to the Indian population, emphasizing the importance of assessing small-bowel and colonic transit in patients with normal gastric emptying parameters to enhance gastrointestinal transit evaluation.

Epidemiology, management, and clinical outcomes of extrapulmonary Mycobacterium abscessus complex infections in heart transplant and ventricular assist device recipients.

Nontuberculous mycobacteria are emerging pathogens, yet data on the epidemiology and management of extrapulmonary nontuberculous mycobacteria infections in orthotopic heart transplantation (OHT) and ventricular assist device (VAD) recipients are scarce. We retrospectively reviewed records of OHT and VAD recipients who underwent cardiac surgery at our hospital and developed Mycobacterium abscessus complex (MABC) infection from 2013 to 2016 during a hospital outbreak of MABC linked to heater-cooler units. We analyzed patient characteristics, medical and surgical management, and long-term outcomes. Ten OHT patients and 7 patients with VAD developed extrapulmonary M. abscessus subspecies abscessus infection. The median time from presumed inoculation during cardiac surgery to the first positive culture was 106 days in OHT and 29 days in VAD recipients. The most common sites of positive cultures were blood (n = 12), sternum/mediastinum (n = 8), and the VAD driveline exit site (n = 7). The 14 patients diagnosed when alive received combination antimicrobial therapy for a median of 21 weeks, developed 28 antibiotic-related adverse events, and underwent 27 surgeries. Only 8 (47%) patients survived longer than 12 weeks after diagnosis, including 2 patients with VAD who experienced long-term survival after an explantation of infected VADs and OHT. Despite aggressive medical and surgical management, OHT and VAD patients with MABC infection experienced substantial morbidity and mortality.

Investigation of Immune Responses to Oxidation, Deamidation, And Isomerization in Therapeutic Antibodies using Preclinical Immunogenicity Risk Assessment Assays.

Product- and process- related critical quality attributes have the potential to impact pharmacokinetics, immunogenicity, potency, and safety of biotherapeutics. Among these critical quality attributes are chemical degradations, specifically oxidation, deamidation, and isomerization. These degradations can be induced by stressors such as light, pH, or temperature; they can also occur naturally under normal conditions. The immunogenicity risk of chemical degradations, particularly in the absence of aggregation, has not been thoroughly understood. In this study, model antibodies with known labile residues were stressed to induce each of the three chemical degradation classes. Aggregate-free and chemically modified antibody species were fractionalized and characterized, followed by testing in standardized and qualified preclinical immunogenicity risk assessment assays for dendritic cell internalization and presentation, monocyte activation, and pre-existing reactivity. Preclinical immunogenicity risk was assessed holistically in vitro based on changes in innate activation risk, CD4 T cell risk, and B cell risk compared to corresponding native antibody. The results of this study suggest an overall moderate increase in immune activation potential for the antibody with isomerization, with only slight increases observed in oxidized and deamidated antibodies. These findings could lend understanding to the immunogenicity risk of chemical degradations in therapeutic antibodies and therefore inform optimization engineering at particular labile residues and risk assessment under the Quality by Design framework.

Assessment of myocardial sympathetic innervation with 18F-FDOPA-PET/CT in patients with autonomic dysfunction: feasibility study in IPD patients.

BACKGROUND: Dysfunction and denervation of myocardial nor-adrenergic sympathetic neurons has been documented in IPD patients with dysautonomia. The aim of this study was to evaluate the feasibility of single tracer imaging of myocardial sympathetic and cerebral striatal involvement in these patients. METHODS: Twenty-two controls (mean-age 59.09 ± 12.39 years, 15 men) with no clinical autonomic-dysfunction and normal striatal-uptake in 18F-FDOPA-PET/CT; and 28 patients (mean-age 58.18 ± 8.25 years, 18 men) with autonomic-dysfunction (in Autonomic Function Tests) and striatal dopaminergic-dysfunction were enrolled. Both cardiac-PET/CT (40 minutes post IV-injection of 185-259MBq 18F-FDOPA) and Brain-PET/CT (60 minutes post-IV) were acquired in same session. ROIs were drawn over the entire left ventricular myocardium, individual walls and mediastinum for quantification. Patients and controls were followed-up for 26.93 ± 5.43 months and 37.91 ± 8.63 months, respectively. RESULTS: Striatal and myocardial-parameters were significantly lower in patients compared to controls; with Myocardium/mediastinal ratio (MwMR) yielding the area-under-the-curve of .941 (P < .001). MwMR correlated negatively with the drop in systolic blood pressure (SBP) during AFTs {Pearson-coefficient (-).565, P = .002}. Mean MwMR in patients with abnormal-AFTs was significantly lower than patients with borderline-AFTs (1.39 ± .12 vs 1.55 ± .10; P = .002). 9/20 patients with abnormal-AFTs showed functional worsening during follow-up, compared to 2/8 with borderline-AFTs. CONCLUSION: Single tracer, single session imaging of striatal and cardiac sympathetic dysfunction in patients with advanced IPD is feasible with use of 18F-FDOPA. Significantly reduced 18F-FDOPA uptake is seen in the myocardium of the IPD patients with sympathetic dysfunction.

New method to measure interbreath intervals in infants for the assessment of apnoea and respiration.

BACKGROUND: Respiratory disorders, including apnoea, are common in preterm infants due to their immature respiratory control compared with term-born infants. However, our inability to accurately measure respiratory rate in hospitalised infants results in unreported episodes of apnoea and an incomplete picture of respiratory activity. METHODS: We develop, validate and use a novel algorithm to identify interbreath intervals (IBIs) and apnoeas in preterm infants. In 42 preterm infants (1600 hours of recordings), we assess IBIs from the chest electrical impedance pneumograph using an adaptive amplitude threshold for the detection of breaths. The algorithm is refined by comparing its accuracy with clinically observed breaths and pauses in breathing. We develop an automated classifier to differentiate periods of true apnoea from artefactually low amplitude signal. We assess the performance of this algorithm in the detection of morphine-induced respiratory depression. Finally, we use the algorithm to investigate whether retinopathy of prematurity (ROP) screening alters the IBI distribution. RESULTS: Individual breaths were detected with a false-positive rate of 13% and a false-negative rate of 12%. The classifier identified true apnoeas with an accuracy of 93%. As expected, morphine caused a significant shift in the IBI distribution towards longer IBIs. Following ROP screening, there was a significant increase in pauses in breathing that lasted more than 10 s (t-statistic=1.82, p=0.023). This was not reflected by changes in the monitor-derived respiratory rate and no episodes of apnoea were recorded in the medical records. CONCLUSIONS: We show that our algorithm offers an improved method for the identification of IBIs and apnoeas in preterm infants. Following ROP screening, increased respiratory instability can occur even in the absence of clinically significant apnoeas. Accurate assessment of infant respiratory activity is essential to inform clinical practice.

Diastolic dyssynchrony assessment by gated myocardial perfusion-SPECT in subjects who underwent cardiac resynchronization therapy.

BACKGROUND: Left ventricular diastolic dyssynchrony (LVDD) can be assessed by gated myocardial perfusion single-photon emission computed tomography (GMP-SPECT). LVDD is an area of interest in subjects who underwent cardiac resynchronization therapy (CRT). The aim of this post hoc analysis was to assess the role of LVDD in subjects with CRT who were followed up at 6-month period. MATERIAL & METHODS: Left ventricular diastolic dyssynchrony was assessed by GMP-SPECT at baseline and after CRT procedure in 160 subjects from 10 different cardiological centers. CRT procedure was performed as per current guidelines. Outcomes were defined as improvement in ≥1 New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF) by 5%, and reduction in end-systolic volume (ESV) by 15% and 5% points in Minnesota Living with Heart Failure Questionnaire. LVDD was defined as diastolic phase standard deviation ≥40 ± 14°. RESULTS: Improvement in NYHA functional class occurred in 105 (65.6%), LVEF in 74 (46.3%), decrease in ESV in 86 (53.8%), and Minnesota score in 85 (53.1%) cases. Baseline LV diastolic standard deviation was 53.53° ± 20.85 and at follow-up 40.44° ± 26.1283; (P < 0.001). LVDD was not associated with improvement in clinical outcomes at follow-up. CONCLUSION: CRT improves both systolic and diastolic dyssynchrony values at 6-month follow-up. LVDD at baseline is correlated with cardiac functionality at follow-up, but not with overall favorable clinical outcomes.

Value of intraventricular dyssynchrony assessment by gated-SPECT myocardial perfusion imaging in the management of heart failure patients undergoing cardiac resynchronization therapy (VISION-CRT).

BACKGROUND: Placing the left ventricular (LV) lead in a viable segment with the latest mechanical activation (vSOLA) may be associated with optimal cardiac resynchronization therapy (CRT) response. We assessed the role of gated SPECT myocardial perfusion imaging (gSPECT MPI) in predicting clinical outcomes at 6 months in patients submitted to CRT. METHODS: Ten centers from 8 countries enrolled 195 consecutive patients. All underwent gSPECT MPI before and 6 months after CRT. The procedure was performed as per current guidelines, the operators being unaware of gSPECT MPI results. Regional LV dyssynchrony (Phase SD) and vSOLA were automatically determined using a 17 segment model. The lead was considered on-target if placed in vSOLA. The primary outcome was improvement in ≥1 of the following: ≥1 NYHA class, left ventricular ejection fraction (LVEF) by ≥5%, reduction in end-systolic volume by ≥15%, and ≥5 points in Minnesota Living With Heart Failure Questionnaire (MLHFQ). RESULTS: Sixteen patients died before the follow-up gSPECT MPI. The primary outcome occurred in 152 out of 179 (84.9%) cases. Mean change in LV phase standard deviation (PSD) at 6 months was 10.5°. Baseline dyssynchrony was not associated with the primary outcome. However, change in LV PSD from baseline was associated with the primary outcome (OR 1.04, 95% CI 1.01-1.07, P = .007). Change in LV PSD had an AUC of 0.78 (0.66-0.90) for the primary outcome. Improvement in LV PSD of 4° resulted in the highest positive likelihood ratio of 7.4 for a favorable outcome. In 23% of the patients, the CRT lead was placed in the vSOLA, and in 42% in either this segment or in a segment within 10° of it. On-target lead placement was not significantly associated with the primary outcome (OR 1.53, 95% CI 0.71-3.28). CONCLUSION: LV dyssynchrony improvement by gSPECT MPI, but not on-target lead placement, predicts clinical outcomes in patients undergoing CRT.

Assessment of Limitations to Optimization of Guideline-Directed Medical Therapy in Heart Failure From the GUIDE-IT Trial: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Despite evidence that guideline-directed medical therapy (GDMT) improves outcomes in patients with heart failure (HF) and reduced ejection fraction, many patients are undertreated. The Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment (GUIDE-IT) trial tested whether a strategy of using target concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) to guide optimization of GDMT could improve outcomes. Objective: To examine medical therapy for HF in GUIDE-IT and potential reasons why the intervention did not produce improvements in medical therapy. Design, Setting, and Participants: GUIDE-IT, a randomized clinical trial performed at 45 sites in the United States and Canada, was conducted from January 16, 2013, to September 20, 2016. A total of 894 patients with HF and reduced ejection fraction (≤40%) were randomized to NT-proBNP-guided treatment with a goal to suppress NT-proBNP concentrations to less than 1000 pg/mL vs usual care. This secondary analysis examined the medical therapy titration and reasons why the intervention did not produce improvements in care and outcomes. Data were analyzed March 27 to June 28, 2019. Main Outcomes and Measures: For each encounter, medication titrations were captured. A reason was requested if a modification was not made. A Cox proportional hazards regression model was used to assess the independent association of drug class with outcomes. Results: Among the 838 patients available for analysis (566 men [67.5%]; median age, 62.0 years), 6223 visits occurred during 24 months. Adjustments of HF medication were made during 2847 of 5218 qualified visits (54.6%) (all usual care visits and all guided care visits with NT-proBNP level ≥1000 pg/mL) in 862 patients (96.4%). Most adjustments occurred within the first 6 months, primarily within the first 6 weeks. The most common reasons for not adjusting were "clinically stable" and "already at maximally tolerated therapy." Only 130 patients (15.5%) achieved optimal GDMT (≥50% of the target dose of ß-blockers or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers or any dose of mineralocorticoid antagonists) at 6 months, an increase from the baseline (79 of 891 [8.9%]) but not different by treatment arm. Higher doses of ß-blockers were associated with reduced risk of the composite outcome of HF hospitalization and cardiovascular death (hazard ratio [HR], 0.98; 95% CI, 0.97-1.00; P = .008) and of all-cause death (HR, 0.97; 95% CI, 0.95-0.99; P = .01). Higher doses of angiotensin-converting enzyme inhibitors (HR, 0.84; 95% CI, 0.75-0.93; P < .001) and angiotensin receptor blockers (HR, 0.84; 95% CI, 0.71-0.99; P = .04) were associated with reduced risk of all-cause death. Increasing doses of mineralocorticoid antagonists did not appear to be associated with improved outcomes. Conclusions and Relevance: Despite a protocol-driven approach, many patients in GUIDE-IT did not receive medication adjustments and did not achieve optimal GDMT, including those with known elevated NT-proBNP concentrations. These results suggest that opportunities exist to titrate medications for maximal benefit in HF. GUIDE-IT may have failed to achieve treatment benefit because of therapeutic inertia in clinical practice, or current GDMT goals may be unrealistic. Trial Registration: ClinicalTrials.gov Identifier: NCT01685840.

Sex Differences in Quality of Life and Clinical Outcomes in Patients With Advanced Heart Failure: Insights From the PAL-HF Trial.

BACKGROUND: Palliative care improves quality of life in patients with heart failure. Whether men and women with heart failure derive similar benefit from palliative care interventions remains unknown. METHODS: In a secondary analysis of the PAL-HF trial (Palliative Care in Heart Failure), we analyzed differences in quality of life among men and women with heart failure and assessed for differential effects of the palliative care intervention by sex. Differences in clinical characteristics and quality-of-life metrics were compared between men and women at serial time points. The primary outcome was change in Kansas City Cardiomyopathy Questionnaire score between baseline and 24 weeks. RESULTS: Among the 71 women and 79 men, there was a significant difference in baseline Kansas City Cardiomyopathy Questionnaire (24.5 versus 36.2, respectively; P=0.04) but not Functional Assessment of Chronic Illness Therapy-Palliative Care scale (115.7 versus 120.3; P=0.27) scores. Among those who received the palliative care intervention (33 women and 42 men), women's quality-of-life score remained lower than that of men after enrollment. Treated men's scores were significantly higher than those untreated (6-month Kansas City Cardiomyopathy Questionnaire, 68.0 [interquartile range, 52.6-85.7] versus 41.1[interquartile range, 32.0-78.3]; P=0.047), whereas the difference between treated and untreated women was not significantly different (P=0.39). Rates of death and rehospitalization, as well as the composite end point, were similar between treated and untreated women and men. CONCLUSIONS: In the PAL-HF trial, women with heart failure experienced a greater symptom burden and poorer quality of life as compared with men. The change in treated men's Kansas City Cardiomyopathy Questionnaire score between baseline and 24 weeks was significantly higher than those untreated; this trend was not observed in women. Thus, there may be a sex disparity in response to palliative care intervention, suggesting that sex-specific approaches to palliative care may be needed to improve outcomes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT0158960.

Nationwide outcomes and costs of laparoscopic and robotic vs. open hepatectomy.

The safety of hepatectomy continues to improve and it holds a key role in the management of benign and malignant hepatic lesions. Laparoscopic and robotic approaches to hepatectomy are increasingly utilized. The purpose of this study was to compare outcomes and costs of laparoscopic and robotic vs. open approaches to hepatectomy and to determine the national nonelective postoperative readmission rate, including readmission to other hospitals. The Nationwide Readmission Database from 2013 to 2014 was queried for all patients undergoing hepatectomy. Patients undergoing laparoscopic and robotic hepatectomies were compared to patients undergoing open hepatectomy. Multivariate logistic regression was implemented to determine the odds ratios (OR) for non-elective readmission within 45 days. There were 10,870 patients who underwent hepatectomy from 2013 to 2014 and 724 (6.7%) were approached with laparoscopic or robotic technique. The robotic cohort had lower mean cost of the index admission ($24,983 ± $18,329 vs. open $32,391 ± $31,983, p < 0.001, 95% CI - 18,292 to 534), shorter LOS (4.5 ± 3.8 vs. lap 6.8 ± 6.0 vs. open 7.6 ± 7.7 days, p < 0.01), and were less likely to be readmitted within 45 days (7.9% vs. 13.0% lap vs. 13.8% open, p = 0.05). The robotic cohort was slightly younger (mean age 57.5 ± 13.5 vs. lap 60.1 ± 13.8 vs. open 58.9 ± 13.7, p < 0.05), and no significant differences were seen by Charlson Comorbidity Index. Anastomosis of hepatic duct to GI tract carried higher odds of mortality (OR 2.87, p < 0.01) and higher odds of readmission (OR 1.40, p < 0.01). LOS above 7 days increased odds of readmission (OR 2.24, p < 0.01). Nearly one-fifth of patients readmitted after hepatectomy present to a different hospital. Robotic hepatectomy was associated with favorable cost and readmission outcomes compared to laparoscopic and open hepatectomy patients, despite similar patient comorbid burdens and patient's age. Length of stay over 7 days and anastomosis of hepatic duct to GI tract are strong risk factors for readmission and mortality.

Assessment of asymptomatic ischemic heart disease using stress myocardial perfusion imaging in patients with type 2 diabetes mellitus.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of death in patients with type 2 diabetes mellitus (T2DM) and may be asymptomatic. OBJECTIVE: The objective of this study was to assess the prevalence of asymptomatic myocardial ischemia in patients with T2DM using stress myocardial perfusion imaging. METHODS: We evaluated 97 consecutive patients with T2DM without clinical evidence of CAD presenting to Cardiology and Endocrinology clinics using Tc-99m MIBI gated single-photon emission-computed tomography (SPECT) myocardial perfusion imaging for the presence of asymptomatic CAD. RESULTS: Abnormal myocardial perfusion was observed in 10 patients (10.3%). Of these, one half of patients had reversible myocardial perfusion defects suggestive of inducible myocardial ischemia. The other half had fixed perfusion defects suggestive of previous silent myocardial infarctions. Small and moderate reversible perfusion defects were observed in 3 and 2 patients, respectively. The fixed perfusion defects observed in 5 patients were medium sized. The presence of asymptomatic ischemia was significantly associated with age and smoking but not with other traditional cardiac risk factors. CONCLUSION: Ten percent of patients with T2DM with no clinical evidence of CAD were found to have evidence of asymptomatic ischemia or infarction.

Assessment of cardiac allograft systolic function by global longitudinal strain: From donor to recipient.

BACKGROUND: Cardiac allografts are routinely evaluated by left ventricular ejection fraction (LVEF) before and after transplantation. However, myocardial deformation analyses with LV global longitudinal strain (GLS) are more sensitive for detecting impaired LV myocardial systolic performance compared with LVEF. METHODS: We analyzed echocardiograms in 34 heart donor-recipient pairs transplanted at Duke University from 2000 to 2013. Assessments of allograft LV systolic function by LVEF and/or LV GLS were performed on echocardiograms obtained pre-explanation in donors and serially in corresponding recipients. RESULTS: Donors had a median LVEF of 55% (25th, 75th percentile, 54% to 60%). Median donor LV GLS was -14.6% (-13.7 to -17.3%); LV GLS was abnormal (ie, >-16%) in 68% of donors. Post-transplantation, LV GLS was further impaired at 6 weeks (median -11.8%; -11.0 to -13.4%) and 3 months (median -11.4%; -10.3 to -13.9%) before recovering to pretransplant levels in follow-up. Median LVEF remained ≥50% throughout follow-up. We found no association between donor LV GLS and post-transplant outcomes, including all-cause hospitalization and mortality. CONCLUSIONS: GLS demonstrates allograft LV systolic dysfunction in donors and recipients not detected by LVEF. The clinical implications of subclinical allograft dysfunction detected by LV GLS require further study.

Quantitative assessment of cardiac mechanical dyssynchrony and prediction of response to cardiac resynchronization therapy in patients with non-ischaemic dilated cardiomyopathy using equilibrium radionuclide angiography.

AIMS: The aim of this study was to evaluate equilibrium radionuclide angiography (ERNA) in prediction of response to cardiac resynchronization therapy (CRT) in non-ischaemic dilated cardiomyopathy (DCM) patients. METHODS AND RESULTS: Thirty-two patients (23 males, 57.5 ± 12.1 years) were prospectively included. Equilibrium radionuclide angiography and clinical evaluation were performed before and 3 months after CRT implantation. Standard deviation of left ventricle mean phase angle (SD LVmPA) and difference between LV and right ventricle mPA (LV-RVmPA) expressed in degrees (°) were used to quantify left intraventricular synchrony and interventricular synchrony, respectively. Left ventricular ejection fraction (LVEF) was also evaluated. At the baseline, mean NYHA class was 3.3 ± 0.5, LVEF 22.5 ± 5.6%, mean QRS duration 150.3 ± 18.2 ms, SD LVmPA 43.5 ± 18°, and LV-RVmPA 30.4 ± 15.6°. At 3-month follow-up, 22 patients responded to CRT with improvement in NYHA class ≥1 and EF >5%. Responders had significantly larger SD LVmPA (51.2 ± 13.9 vs. 26.5 ± 14°) and LV-RVmPA (35.8 ± 13.7 vs. 18.4 ± 13°) than non-responders. Receiver-operating characteristic curve analysis demonstrated 95% sensitivity and 80% specificity at a cut-off value of 30° for SD LVmPA, and 81% sensitivity and 80% specificity at a cut-off value of 23° for LV-RVmPA in prediction of response to CRT. CONCLUSION: Baseline SD LVmPA and LV-RVmPA derived from ERNA are useful for prediction of response to CRT in non-ischaemic DCM patients.

Development of a conversion program to make SIMIND-generated SPECT data interfile acceptable to Xeleris.

The Monte Carlo code SIMIND is used in nuclear medicine for research purposes, and also for testing the validity of various applications. Conversion of a SIMIND-generated interfile (header and image data file) is required to process the simulated image data on a Xeleris workstation. Currently there is no conversion program provided with SIMIND to convert its interfile, which is acceptable in any nuclear medicine workstation. Manual editing of the header file is possible with any standard text editor but it is time-consuming (requiring ∼1 h) and stressful. To alleviate this, we have developed a conversion program using FreeMat V4.0 (an open source software similar to MATLAB from MathWorks). It takes an average of 0.04404 s to convert a SIMIND SPECT data interfile and make it acceptable to Xeleris.

Quantitative assessment of cardiac mechanical dyssynchrony and prediction of response to cardiac resynchronization therapy in patients with nonischaemic dilated cardiomyopathy using gated myocardial perfusion SPECT.

OBJECTIVE: The aim of the study was to evaluate gated myocardial perfusion SPECT (GMPS) in the prediction of response to cardiac resynchronization therapy (CRT) in nonischaemic dilated cardiomyopathy patients. PATIENTS AND METHODS: Thirty-two patients (23 men, mean age 57.5±12.1 years) with severe heart failure, who were selected for CRT implantation, were prospectively included in this study. Patients with coronary heart disease and structural heart diseases were excluded. 99mTc-MIBI GMPS and clinical evaluation were performed at baseline and 3 months after CRT implantation. In GMPS, first-harmonic fast Fourier transform was used to extract a phase array using commercially available software. Phase standard deviation (PSD) and phase histogram bandwidth (PHB) were used to quantify cardiac mechanical dyssynchrony (CMD). Left ventricular ejection fraction was evaluated. RESULTS: At baseline evaluation the mean NYHA class was 3.3±0.5, left ventricular ejection fraction was 23.2±5.3% and mean QRS duration was 150.3±18.2 ms. PSD was 55.8±19.2° and PHB was 182.1±75.8°. At 3-month follow-up, 22 patients responded to CRT with improvement in NYHA class by more than 1 grade and in ejection fraction by more than 5%. Responders had significantly larger PSD (63.6±16.6 vs. 38.7±12.7°) and PHB (214.8±63.9 vs. 110.2±43.5°) compared with nonresponders. Receiver-operating characteristic curve analysis demonstrated 86% sensitivity and 80% specificity at a cutoff value of 43° for PSD and 86% sensitivity and 80% specificity at a cutoff value of 128° for PHB in the prediction of response to CRT. CONCLUSION: Baseline PSD and PHB derived from GMPS are useful for prediction of response to CRT in nonischaemic dilated cardiomyopathy patients.

The palliative care in heart failure trial: rationale and design.

BACKGROUND: The progressive nature of heart failure (HF) coupled with high mortality and poor quality of life mandates greater attention to palliative care as a routine component of advanced HF management. Limited evidence exists from randomized, controlled trials supporting the use of interdisciplinary palliative care in HF. METHODS: PAL-HF is a prospective, controlled, unblinded, single-center study of an interdisciplinary palliative care intervention in 200 patients with advanced HF estimated to have a high likelihood of mortality or rehospitalization in the ensuing 6 months. The 6-month PAL-HF intervention focuses on physical and psychosocial symptom relief, attention to spiritual concerns, and advanced care planning. The primary end point is health-related quality of life measured by the Kansas City Cardiomyopathy Questionnaire and the Functional Assessment of Chronic Illness Therapy with Palliative Care Subscale score at 6 months. Secondary end points include changes in anxiety/depression, spiritual well-being, caregiver satisfaction, cost and resource utilization, and a composite of death, HF hospitalization, and quality of life. CONCLUSIONS: PAL-HF is a randomized, controlled clinical trial that will help evaluate the efficacy and cost effectiveness of palliative care in advanced HF using a patient-centered outcome as well as clinical and economic end points.

Trends in the use and outcomes of ventricular assist devices among medicare beneficiaries, 2006 through 2011.

OBJECTIVES: This study sought to examine trends in mortality, readmission, and costs among Medicare beneficiaries receiving ventricular assist devices (VADs) and associations between hospital-level procedure volume and outcomes. BACKGROUND: VADs are an option for patients with advanced heart failure, but temporal changes in outcomes and associations between facility-level volume and outcomes are poorly understood. METHODS: This is a population-based, retrospective cohort study of all fee-for-service Medicare beneficiaries with heart failure who received an implantable VAD between 2006 and 2011. We used Cox proportional hazards models to examine temporal changes in mortality, readmission, and hospital-level procedure volume. RESULTS: Among 2,507 patients who received a VAD at 103 centers during the study period, the in-hospital mortality decreased from 30% to 10% (p < 0.001), the 1-year mortality decreased from 42% to 26% (p < 0.001), and the all-cause readmission was frequent (82% and 81%; p = 0.70). After covariate adjustment, in-hospital and 1-year mortality decreased (p < 0.001 for both), but the all-cause readmission did not change (p = 0.82). Hospitals with a low procedure volume had higher risks of in-hospital mortality (risk ratio: 1.72; 95% confidence interval [CI]: 1.28 to 2.33) and 1-year mortality (risk ratio: 1.55; 95% CI: 1.24 to 1.93) than high-volume hospitals. Procedure volume was not associated with risk of readmission. The greatest cost was from the index hospitalization and remained unchanged ($204,020 in 2006 and $201,026 in 2011; p = 0.21). CONCLUSIONS: Short- and long-term mortality after VAD implantation among Medicare beneficiaries improved, but readmission remained similar over time. A higher volume of VAD implants was associated with lower risk of mortality but not readmission. Costs to Medicare have not changed in recent years.

Quantitative assessment of cardiac mechanical synchrony using equilibrium radionuclide angiography.

BACKGROUND: Data on normal parameters of cardiac mechanical synchrony is limited, variable and obtained from small cohorts till date. In most studies, software used for such assessment has not been mentioned. The aim of study is to establish normal values of mechanical synchrony with equilibrium radionuclide angiography (ERNA) in a larger population using commercially available software. METHODS: We retrospectively analysed ERNA studies of 108 patients having low pretest likelihood of coronary artery disease, no known history of cardiac disease, normal electrocardiogram and whose ERNA studies were considered normal by experienced observers. In addition, ten patients diagnosed with dilated cardiomyopathy (DCM) and having LVEF ≤ 40% underwent ERNA. Fourier first harmonic analysis of phase images was used to quantify synchrony parameters using commercially available software (XT-ERNA). Intraventricular synchrony for each ventricle was measured as the standard deviation of the LV and RV mean phase angles (SD LVmPA and SD RVmPA, respectively). Interventricular synchrony was measured as LV-RVmPA. Absolute interventricular delay was calculated as absolute difference between LV and RVmPA (without considering ± sign). All variables were expressed in milliseconds (ms) and degree (°). Intra-observer and inter-observer variabilities were assessed. Cut-off values for parameters were calculated from the normal database, and validated against patient group. RESULTS: On phase analysis, LVmPA was observed to be 343 ± 48.5 milliseconds (174.7° ± 18.5°), SD LVmPA was 16.3 ± 5.4 milliseconds (8.2° ± 2.5°), RVmPA was 339 ± 50.4 milliseconds (171.8° ± 18.5°) and SD RVmPA was 37.3 ± 15.7 milliseconds (18.7° ± 7.2°). LV-RVmPA was observed to be 3.9 ± 21.7 milliseconds (2.9° ± 9.6°) and absolute interventricular delay was 16.3 ± 14.8 milliseconds (7.9° ± 6.1°). The cut-off values for the presence of dyssynchrony were estimated as SD LVmPA > 27.1 milliseconds (>13.2°), SD RVmPA > 68.7 milliseconds (>33.1°) and LV-RVmPA > 47.3 milliseconds (>22.1°). There was no statistically significant intra-observer or inter-observer variability. Using these cut offs, 9 patients with DCM showed the presence of left intraventricular dyssynchrony, 5 had right intraventricular dyssynchrony and 2 had interventricular dyssynchrony. CONCLUSIONS: ERNA phase analysis offers an objective and reproducible tool to quantify cardiac mechanical synchrony using commercially available software and can be used in routine clinical practice to assess mechanical dyssynchrony.