Rationale and design of the REgistry of Fast Myocardial Perfusion Imaging with NExt generation SPECT (REFINE SPECT).

BACKGROUND: We aim to establish a multicenter registry collecting clinical, imaging, and follow-up data for patients who undergo myocardial perfusion imaging (MPI) with the latest generation SPECT scanners. METHODS: REFINE SPECT (REgistry of Fast Myocardial Perfusion Imaging with NExt generation SPECT) uses a collaborative design with multicenter contribution of clinical data and images into a comprehensive clinical-imaging database. All images are processed by quantitative software. Over 290 individual imaging variables are automatically extracted from each image dataset and merged with clinical variables. In the prognostic cohort, patient follow-up is performed for major adverse cardiac events. In the diagnostic cohort (patients with correlating invasive angiography), angiography and revascularization results within 6 months are obtained. RESULTS: To date, collected prognostic data include scans from 20,418 patients in 5 centers (57% male, 64.0 ± 12.1 years) who underwent exercise (48%) or pharmacologic stress (52%). Diagnostic data include 2079 patients in 9 centers (67% male, 64.7 ± 11.2 years) who underwent exercise (39%) or pharmacologic stress (61%). CONCLUSION: The REFINE SPECT registry will provide a resource for collaborative projects related to the latest generation SPECT-MPI. It will aid in the development of new artificial intelligence tools for automated diagnosis and prediction of prognostic outcomes.

Upper reference limits of transient ischemic dilation ratio for different protocols on new-generation cadmium zinc telluride cameras: A report from REFINE SPECT registry.

BACKGROUND: Upper reference limits for transient ischemic dilation (TID) have not been rigorously established for cadmium-zinc-telluride (CZT) camera systems. We aimed to derive TID limits for common myocardial perfusion imaging protocols utilizing a large, multicenter registry (REFINE SPECT). METHODS: One thousand six hundred and seventy-two patients with low likelihood of coronary artery disease with normal perfusion findings were identified. Images were processed with Quantitative Perfusion SPECT software (Cedars-Sinai Medical Center, Los Angeles, CA). Non-attenuation-corrected, camera-, radiotracer-, and stress protocol-specific TID limits in supine position were derived from 97.5th percentile and mean + 2 standard deviations (SD). Reference limits were compared for different solid-state cameras (D-SPECT vs. Discovery), radiotracers (technetium-99m-sestamibi vs. tetrofosmin), different types of stress (exercise vs. four different vasodilator-based protocols), and different vasodilator-based protocols. RESULTS: TID measurements did not follow Gaussian distribution in six out of eight subgroups. TID limits ranged from 1.18 to 1.52 (97.5th percentile) and 1.18 to 1.39 (mean + 2SD). No difference was noted between D-SPECT and Discovery cameras (P = 0.71) while differences between exercise and vasodilator-based protocols (adenosine, regadenoson, or regadenoson-walk) were noted (all P < 0.05). CONCLUSIONS: We used a multicenter registry to establish camera-, radiotracer-, and protocol-specific upper reference limits of TID for supine position on CZT camera systems. Reference limits did not differ between D-SPECT and Discovery camera.

Risk factors and prognosis for clot formation on cardiac device leads.

BACKGROUND: Clot formation on cardiac device leads is poorly understood. We sought to determine how often clot is seen on device leads by transthoracic echo (TTE), identify risk factors, and to describe the natural history of this phenomenon. METHODS: We reviewed 71,888 echocardiographic studies performed at the University of California, San Francisco from 2005 to 2011. We searched for cases where clot was found adhered to a device lead with no diagnosis of endocarditis. For every case, three age-matched controls with a device but no clot were selected from the echo database. RESULTS: We found 15 cases with clot adhered to a device lead among 1,086 patients with devices who had TTE (1.4%). In univariate analysis, females had more than four times greater odds of having a clot on their device lead and patients with a history of atrial fibrillation (AF) had an eight times greater odds. Percentage mode switch was also associated with clot formation. Only AF was still associated with clot formation after multivariate analysis. Follow-up data were available for nine of 15 patients. All nine patients had intensification of their anticoagulant/antiplatelet regimen following clot discovery. Complete resolution or shrinkage of clot was observed in eight of nine patients. The one case with no change was a patient who continued taking only aspirin (higher dose) after clot discovery. None of the nine patients had embolic phenomenon. CONCLUSION: Patients with AF are at higher risk for clot formation on device leads. After clot detection, treatment with anticoagulants usually results in resolution of the clot without embolic phenomenon.

Funding source and author affiliation in TASER research are strongly associated with a conclusion of device safety.

BACKGROUND: Controversy exists regarding the safety of electrical stun guns (TASERs). Much of the research on TASERs is funded by the maker of the device and, therefore, could be biased. We sought to determine if funding source or author affiliation is associated with TASER research conclusions. METHODS: MEDLINE was searched for TASER or electrical stun gun to identify relevant studies. All human and animal studies published up to September 01, 2010, were included. Reviews, editorials, letters, and case reports were excluded from the analysis. Two independent reviewers blinded to this study hypothesis evaluated each article with regard to conclusions of TASER safety. RESULTS: Fifty studies were reviewed: 32 (64%) were human studies and 18 (36%) were animal studies. Twenty-three (46%) studies were funded by TASER International or written by an author affiliated with the company. Of these, 22 (96%) concluded that TASERs are unlikely harmful (26%) or not harmful (70%). In contrast, of the 22 studies not affiliated with TASER, 15 (55%) concluded that TASERs are unlikely harmful (29%) or not harmful (26%). A study with any affiliation with TASER International had nearly 18 times higher odds to conclude that the TASER is likely safe as compared with studies without such affiliation (odds ratio 17.6, 95% CI 2.1-150.1, P = .001). CONCLUSIONS: Studies funded by TASER and/or written by an author affiliated with the company are substantially more likely to conclude that TASERs are safe. Research supported by TASER International may thus be significantly biased in favor of TASER safety.

Predictors of axillary vein location for vascular access during pacemaker and defibrillator lead implantation.

BACKGROUND: The axillary vein is a commonly used extrathoracic access site for cardiac rhythm device lead implantation. We sought to describe variation in axillary vein location and identify predictors of a more cranial or caudal radiographic location to facilitate blind venous cannulation. METHODS: This was a single-center, retrospective study of patients undergoing lead implantation between 2006 and 2010. The cranial-caudal location of the axillary vein lateral and medial to the rib cage border was determined by reviewing peripheral contrast venograms. Multivariate linear regression was performed. RESULTS: Of 155 patients, the majority were men (62%) and White (53%). The most frequent position of the lateral and medial axillary vein was over the third rib (40%) and top of the third rib (15%), respectively. In multivariate analysis, whites had a more caudal location of both the lateral (0.56 rib spaces lower, 95% confidence interval [CI] 0.22-0.91, P = 0.002) and medial axillary vein (0.50 rib spaces lower, 95% CI 0.85-0.91, P = 0.019). Other independent predictors included an approximate 3-4% higher rib space location for every digit increase in body mass index (BMI) (P = 0.049 for the lateral location and P = 0.016 for the medial location) and an approximate half rib space higher location for males (P = 0.015 for the lateral location and P = 0.013 for the medial location). CONCLUSIONS: The most common radiographic position of the axillary vein was over the third rib. Whites have a more caudal axillary vein location while men and patients with higher BMI have a more cranial position of the axillary vein.

Impact of Early Revascularization on Major Adverse Cardiovascular Events in Relation to Automatically Quantified Ischemia.

OBJECTIVES: Using a contemporary, multicenter international single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) registry, this study characterized the potential major adverse cardiovascular event(s) (MACE) benefit of early revascularization based on automatic quantification of ischemia. BACKGROUND: Prior single-center data reported an association between moderate to severe ischemia SPECT-MPI and reduced cardiac death with early revascularization. METHODS: Consecutive patients from a multicenter, international registry who underwent 99mTc SPECT-MPI between 2009 and 2014 with solid-state scanners were included. Ischemia was quantified automatically as ischemic total perfusion deficit (TPD). Early revascularization was defined as within 90 days. The primary outcome was MACE (death, myocardial infarction, and unstable angina). A propensity score was developed to adjust for nonrandomization of revascularization; then, multivariable Cox modeling adjusted for propensity score and demographics was used to predict MACE. RESULTS: In total, 19,088 patients were included, with a mean follow-up of 4.7 ± 1.6 years, during which MACE occurred in 1,836 (9.6%) patients. There was a significant interaction between ischemic TPD modeled as a continuous variable and early revascularization (interaction p value: 0.012). In this model, there was a trend toward reduced MACE in patients with >5.4% ischemic TPD and a significant association with reduced MACE in patients with >10.2% ischemic TPD. CONCLUSIONS: In this large, international, multicenter study reflecting contemporary cardiology practice, early revascularization of patients with >10.2% ischemia on SPECT-MPI, quantified automatically, was associated with reduced MACE.

5-Year Prognostic Value of Quantitative Versus Visual MPI in Subtle Perfusion Defects: Results From REFINE SPECT.

OBJECTIVES: This study compared the ability of automated myocardial perfusion imaging analysis to predict major adverse cardiac events (MACE) to that of visual analysis. BACKGROUND: Quantitative analysis has not been compared with clinical visual analysis in prognostic studies. METHODS: A total of 19,495 patients from the multicenter REFINE SPECT (REgistry of Fast Myocardial Perfusion Imaging with NExt generation SPECT) study (64 ± 12 years of age, 56% males) undergoing stress Tc-99m-labeled single-photon emission computed tomography (SPECT) myocardial perfusion imaging were followed for 4.5 ± 1.7 years for MACE. Perfusion abnormalities were assessed visually and categorized as normal, probably normal, equivocal, or abnormal. Stress total perfusion deficit (TPD), quantified automatically, was categorized as TPD = 0%, TPD >0% to <1%, ≤1% to <3%, ≤3% to <5%, ≤5% to ≤10%, or TPD >10%. MACE consisted of death, nonfatal myocardial infarction, unstable angina, or late revascularization (>90 days). Kaplan-Meier and Cox proportional hazards analyses were performed to test the performance of visual and quantitative assessments in predicting MACE. RESULTS: During follow-up examinations, 2,760 (14.2%) MACE occurred. MACE rates increased with worsening of visual assessments, that is, the rate for normal MACE was 2.0%, 3.2% for probably normal, 4.2% for equivocal, and 7.4% for abnormal (all p < 0.001). MACE rates increased with increasing stress TPD from 1.3% for the TPD category of 0% to 7.8% for the TPD category of >10% (p < 0.0001). The adjusted hazard ratio (HR) for MACE increased even in equivocal assessment (HR: 1.56; 95% confidence interval [CI]: 1.37 to 1.78) and in the TPD category of ≤3% to <5% (HR: 1.74; 95% CI: 1.41 to 2.14; all p < 0.001). The rate of MACE in patients visually assessed as normal still increased from 1.3% (TPD = 0%) to 3.4% (TPD ≥5%) (p < 0.0001). CONCLUSIONS: Quantitative analysis allows precise granular risk stratification in comparison to visual reading, even for cases with normal clinical reading.

Valve thrombosis following transcatheter aortic valve replacement: significance of blood stasis on the leaflets.

OBJECTIVES: Leaflet thrombosis following transcatheter aortic valve replacement (TAVR) and valve-in-valve (ViV) procedures has been increasingly recognized. However, the factors affecting the post-TAVR/ViV thrombosis are not fully understood. This study aimed to investigate the effect of the geometric confinement of transcatheter aortic valve (TAV) on blood residence time (BRT) on the TAV leaflets and in turn on the post-TAVR valve thrombosis. METHODS: Two computational models, representing a surgical bioprosthesis and a TAV, were developed to study the effect of the geometric confinement on BRT on the leaflets in ViV setting/TAVR Intra-annular positioning. 3D flow fields were obtained via a one-way fluid-solid interaction modelling approach validated by experimental testing. BRT was compared between the two models by quantification and statistical analysis of the residence time of randomly distributed particles in close proximity of the leaflets. RESULTS: Significantly longer BRT on the leaflets was observed in the TAV compared to the surgical valve during different stages of the cardiac cycle. During forward flow, the mean value of BRT was found to be 39% higher in the TAV compared to the surgical bioprosthesis ( P < 0.0001). During diastole, specifically from end-systole to mid-diastole and from mid-diastole to the beginning of systole, the amount by which the mean BRT was higher for TAV compared to the surgical valve was 150% and 40%, respectively ( P < 0.0005). CONCLUSIONS: The geometric confinement of TAV by the failed bioprosthesis or the calcified native valve increases the BRT on the TAV leaflets. This may act as a permissive factor in valve thrombosis.

Effect of reduced cardiac output on blood stasis on transcatheter aortic valve leaflets: implications for valve thrombosis.

AIMS: There is an increasing awareness of leaflet thrombosis following transcatheter aortic valve implantation (TAVI) and valve-in-valve (ViV) procedures. Nevertheless, the predisposing factors affecting transcatheter aortic valve (TAV) thrombosis have remained unclear. This study aimed to quantify the effects of reduced cardiac output (CO) on blood stasis on the TAV leaflets as a permissive factor for valve thrombosis. METHODS AND RESULTS: An idealised computational model representing a TAV was developed in a patient-specific geometry. Three-dimensional flow fields were obtained via a fluid-solid interaction modelling approach at different COs: 5.0, 3.5, 2.0 L/min. Blood residence time (BRT) was subsequently calculated on the leaflets. An association between reduced CO and increased blood stasis on the TAV leaflets was observed. At the end of diastole, larger areas of high BRT (>1.2 s) were observed at the leaflet's fixed edge at low COs. Such areas were calculated to be 2, 8, and 11% of the total surface area of leaflets at CO=5.0, 3.5, and 2.0 L/min, respectively, indicating a ~sixfold increase of BRT on the leaflets from the highest to the lowest CO. CONCLUSIONS: This study indicates an association between reduced CO and increased blood stasis on the TAV leaflets which can be regarded as a precursor of valve thrombosis.

Blood Stasis on Transcatheter Valve Leaflets and Implications for Valve-in-Valve Leaflet Thrombosis.

BACKGROUND: Leaflet thrombosis after valve-in-valve (ViV) procedure has been increasingly recognized. This study aimed to investigate the flow dynamics aspect of leaflet thrombosis by quantifying the blood stasis on the noncoronary and coronary leaflets of a surgical aortic valve (SAV) and a transcatheter aortic valve (TAV) in a ViV setting. METHODS: Two computational models, representing a SAV and a TAV in ViV setting, were developed in a patient-specific geometry. Three-dimensional flow fields were obtained through a fluid-solid interaction modeling approach to study the difference in blood residence time (BRT) on the coronary and noncoronary leaflets. RESULTS: Longer BRT was observed on the TAV leaflets compared with the SAV, specifically near the leaflet fixed boundary. Particularly, at the end of diastole, the areas of high BRT (≥1.2 seconds) on the surface of the TAV model leaflets were four times larger than those of the SAV model. The distribution of BRT on the three leaflets exhibited a similar pattern in the model for the TAV in ViV setting. That was in contrast to the SAV model where large areas of high BRT were observed on the noncoronary leaflet. CONCLUSIONS: Geometric confinement of the TAV by the leaflets and the frame of the degenerated bioprosthesis that circumferentially surround the TAV stent increases the BRT on the leaflets, which may act as a permissive factor in the TAV leaflet thrombosis after ViV procedure. A similar distribution pattern of BRT observed on the TAV leaflets may explain the similar rate of occurrence of thrombosis on the three leaflets.

Left Atrial Fibrosis and Risk of Cerebrovascular and Cardiovascular Events in Patients With Atrial Fibrillation.

BACKGROUND: Severity of left atrial (LA) fibrosis is a strong predictor of atrial fibrillation (AF) ablation success and has been associated with a history of stroke, hypertension, and heart failure (HF). However, it is unclear whether more severe LA fibrosis independently increases the risk of major adverse cardiovascular and cerebrovascular events (MACCE) among those with AF. OBJECTIVES: The goal of this study was to evaluate the occurrence and frequency of MACCE by strata of LA fibrosis severity in patients with AF. METHODS: This was a retrospective cohort study of 1,228 patients with AF who underwent late gadolinium enhancement (LGE)-cardiac magnetic resonance imaging to quantify LA fibrosis severity between January 2007 and June 2015. Patients were stratified according to Utah stage of LA LGE criteria, and observed for the occurrence of MACCE, which included a composite of stroke or transient ischemic attack (TIA), myocardial infarction, acute decompensated HF, or cardiovascular death. Disease risk score (DRS) stratification was used to control for between-group differences in baseline characteristics and risk. RESULTS: During follow-up, 62 strokes or TIAs, 42 myocardial infarctions, 156 HF events, and 38 cardiovascular deaths occurred. In DRS stratified analysis, the hazard ratio comparing patients with stage IV versus stage I LA LGE was 1.67 (95% confidence interval: 1.01 to 2.76) for the composite MACCE outcome. The only individual component of the MACCE outcome to remain significantly associated with advanced LGE following DRS stratification was stroke or TIA (hazard ratio: 3.94; 95% confidence interval: 1.72 to 8.98). CONCLUSIONS: This retrospective analysis demonstrated that more severe LA LGE is associated with increased MACCE risk, driven primarily by increased risk of stroke or TIA.

Trainee inexperience is associated with longer procedure times but no increase in complications for cardiac device implantation.

BACKGROUND: The "July phenomenon" describes poor patient outcomes in teaching hospitals at the beginning of a new academic year when trainees begin. Whether this phenomenon truly exists is unclear. OBJECTIVE: The purpose of this study was to identify whether trainee and attending inexperience is associated with cardiac electrophysiologic procedural outcomes including total procedure time, fluoroscopy time, and complications. METHODS: We retrospectively reviewed the available electronic records of 488 consecutive patients undergoing initial dual-chamber pacemaker (PM) or cardiac resynchronization therapy (CRT) device implantation performed at University of California, San Francisco from February 2004 through November 2011. We calculated physician's year of experience using the procedure date and the physician's job start date. Patients were stratified into two subgroups based on their device type. Procedural outcomes including procedure length, fluoroscopy time, and complications were retrieved from electronic databases. RESULTS: After multivariate analysis, fellow experience was associated with decreased procedure time (19% less procedure time/year of experience, 95% confidence interval [CI] 13%-25%, P <.001 in the PM subgroup; and 15% less procedure time/year of experience, 95% CI 7%-23%, P <.001 in the CRT subgroup). Fellow experience was associated with decreased fluoroscopy time in the CRT subgroup (19% less fluoroscopy time/experience years, 95% CI 5%-34%, P = .009). Neither fellow nor attending experience was associated with complications. CONCLUSION: Each year of fellow experience is associated with a decrease in cardiac device implantation procedure time and a decrease in fluoroscopy time during CRT implantation. No associations between fellow experience and in-hospital complications were observed.

Asymptomatic Left Bundle Branch Block Predicts New-Onset Congestive Heart Failure and Death From Cardiovascular Diseases.

BACKGROUND: Left bundle branch block (LBBB) has been proposed as a risk factor for cardiovascular morbidity and mortality. We sought to characterize the strength of these associations in a population without preexisting clinical heart disease. METHODS: The association between LBBB and new-onset congestive heart failure (CHF) or death from cardiovascular diseases was examined in 1,688 participants enrolled in the SPPARCS study who were free of known CHF or previous myocardial infarction. SPPARCS is a community-based cohort study in residents of Sonoma, California that are > 55 years. Medical history and 12-lead ECGs were obtained every 2 years for up to 6 years of follow-up. LBBB at enrollment or year 2 was considered "baseline" and assessed as a predictor of CHF and cardiovascular death ascertained at years 4 and 6. RESULTS: The prevalence of LBBB at baseline was 2.5% (n = 42). During 6 years of follow-up, 70 (4.8%) people developed new CHF. Incidence of CHF was higher in patients with LBBB than in participants without LBBB. This association persisted after controlling for potential confounders (odds ratio (OR): 2.85; 95% confidence interval (CI): 1.01 - 8.02; P = 0.047). A higher mortality from cardiovascular diseases was also found in participants with LBBB after adjusting for potential confounders (OR: 2.35, 95%CI: 1.02 - 5.41; P = 0.044). CONCLUSIONS: LBBB in the absence of a clinically detectable heart disease is associated with new-onset CHF and death from cardiovascular diseases. Further study is warranted to determine if additional diagnostic testing or earlier treatment in patients with asymptomatic LBBB can decrease cardiovascular morbidity or mortality.

Frequency of atrial flutter after adult lung transplantation.

Lung transplantation, which involves an anastomosis of the graft to the native left atrium, may increase the risk of left-side atrial flutter (AFL). Our aim was to evaluate the incidence, predisposing conditions, and course of AFL after lung transplantation in adults. Two hundred sixty-nine consecutive patients who underwent lung transplantation were studied retrospectively. All patients received a preoperative echocardiogram and postoperative electrocardiographic monitoring. All 12-lead electrocardiograms were reviewed. Typical or atypical AFL was diagnosed by 2 independent reviewers based on accepted criteria. Predictors of AFL were investigated separately using univariate and multivariate logistic regression analyses. AFL occurred in 35 of 269 patients (13%) over a mean of 12 days after transplantation. All patients who developed AFL had no previous atrial arrhythmia. Of these 35 patients, 24 (68.6%) had atypical AFL by electrocardiographic criteria. In multivariate logistic regression analysis, patients with idiopathic pulmonary fibrosis (IPF) were 2.9 times more likely to have AFL than those patients with lung transplant without IPF (p = 0.009). Other independent risk factors for AFL were advanced age and preoperative left atrial enlargement. Only 3 of 35 patients (8.6%) with AFL had persistent atrial arrhythmia and needed electrophysiologic study and ablation. In conclusion, AFL is common soon after lung transplantation. Those with IPF, advanced age, or left atrial enlargement are at increased risk. In most cases, AFL is a self-limited arrhythmia that resolves spontaneously with no need for ablation.