The Prognostic Utility of Heart Rate and Blood Pressure Response to Regadenoson Stress.

BACKGROUND: Although heart rate response (HRR) to regadenoson stress has been shown to be a strong predictor of outcome, it has not been investigated in a large all-comers cohort. The prognostic utility of systolic blood pressure response (SBPR) has not been investigated in comparison to HRR. METHODS AND RESULTS: In a retrospective cohort of 10,227 patients undergoing regadenoson stress SPECT myocardial perfusion imaging (MPI), HRR, and SBPR were calculated as 100*(Peak hyperemia value-Baseline value)/Baseline value. During 35±21 months follow-up, 921 (8.8%) deaths were observed. The median HRR was 35% (Interquartile range [IQR], 21% to 51%). The median SBPR was -9% (IQR, -17% to -2%). HRR and SBPR were independently associated with all-cause mortality with adjusted hazard ratio [HR] of 0.980 per 1% increment in HRR (CI, 0.977-0.984) and 0.994 per 1% increment in SBPR (CI, 0.988-0.999). Mortality rates increased with decreasing HRR quartile and SBPR tertile. HRR provided incremental prognostic value for all-cause mortality beyond clinical and imaging parameters (area under the curve [AUC] increase, 0.03; P<0.001) and SBPR data (AUC increase, 0.11; P<0001). SBPR did not provide significant incremental prognostic value beyond clinical and imaging parameters or HRR data. We derived and validated HRR of < 20% as a cutoff that can improve risk stratification beyond clinical and MPI findings. CONCLUSION: Among patients undergoing stress MPI, impaired HRR to regadenoson provided independent and incremental prognostic value for all-cause mortality beyond clinical, imaging, and SBPR data. SBPR positively correlates with HRR, but it does not provide incremental prognostic utility. HRR, but not SBPR, should be routinely reported and considered in assessing patients' overall risk. An abnormal HRR threshold of < 20% can improve risk stratification.

Impact of change of ischemic burden on the outcomes of ESRD patients awaiting kidney transplantation.

BACKGROUND: In asymptomatic patients with end-stage renal disease (ESRD) wait-listed for kidney transplantation (KT), it is unclear whether a change in ischemic burden on serial surveillance SPECT myocardial perfusion imaging (MPI) impacts outcome. METHODS AND RESULTS: In a retrospective cohort of 700 asymptomatic KT candidates with ≥ 2 sequential SPECT-MPI studies, we defined a significant change in ischemic burden between MPIs as ΔSDS of ≥ 2 points. Patients were followed for mean 19 ± 12 months after MPI2 for cardiac death or myocardial infarction. Between MPIs, 29 (4%) subjects received coronary revascularization which was associated with a greater incidence of reduction in ischemic burden on MPI2 (31% vs. 17%, P = 0.049). Among 514 patients with no ischemia on MPI1 (SDS ≤ 1), 15% had new ischemia on MPI2 which was associated with increased MACE (adjusted HR 1.75; CI 1.02-3.01; P = 0.041). Among 186 patients with ischemia on MPI1 (SDS ≥ 2), 66% had improvement of ischemic burden on MPI2 which was associated with significantly lower MACE (adjusted HR 0.46; CI 0.25-0.82; P = 0.009). There was no significant interaction between coronary revascularization and improvement in ischemic burden impacting outcome (interaction P = 0.845). CONCLUSION: Among KT candidates who underwent serial MPI for CAD surveillance, new ischemia was associated with increased MACE risk. Improvement in ischemic burden was associated with lower MACE risk irrespective of coronary revascularization status.

The prognostic and diagnostic implications of surveillance serial myocardial perfusion imaging in asymptomatic renal transplant candidates.

BACKGROUND: The utility of serial SPECT myocardial perfusion imaging (MPI) for CAD surveillance in asymptomatic ESRD patients awaiting kidney transplantation (KT) is uncertain. METHODS AND RESULTS: We retrospectively investigated 700 asymptomatic KT candidates with ≥ 2 pre-transplant SPECT-MPIs (mean interval, 20 ± 13 months). Worsening MPI was defined as total perfusion deficit increase (ΔTPD) > 5%. High clinical risk was defined as ≥ 3 AHA/ACC KT risk factors. The primary outcome was major adverse cardiac events (MACE) of cardiac death or myocardial infarction. The initial MPI was normal in 462 (66%) subjects. On repeat MPI, ΔTPD > 5% was observed in 82 (12%) subjects, and the incidence increased with increasing time gap between MPIs (P = .006). During a mean follow-up of 16 ± 8 months, there were 119 (17%) MACEs. In the entire cohort, ΔTPD > 5% was not significantly associated with MACE (HR = 1.38; P = .210). ΔTPD > 5% was associated with increased MACE rate among patients with normal initial MPI (HR = 2.30; P = .005), but not among those with abnormal initial MPI (P = .260). There was a significant interaction between ΔTPD > 5% and initial MPI normalcy status in predicting MACE (interaction P = .018), such that the predictive value of ΔTPD is dependent on the initial MPI normalcy. Among subjects with normal initial MPI, ΔTPD > 5% was significantly associated with MACE only if the sum of KT risk factors was ≥ 3 (HR = 2.26; P = .016). Among 123 patients who underwent coronary angiography, ΔTPD > 5% was associated with a higher prevalence of obstructive CAD when the initial MPI was normal and the sum of KT risk factors was ≥ 3. CONCLUSION: Among patients with ESRD waitlisted for KT, new/worsening MPI abnormalities are expected. On serial surveillance, ΔTPD > 5% is associated with MACE and obstructive CAD among those with a normal initial MPI and ≥ 3 AHA/ACC KT risk factors.

Prevalence and predictors of Twiddler's syndrome.

BACKGROUND: Twiddler's syndrome is a poorly understood clinical phenomenon when patients either consciously or subconsciously rotate their cardiac device resulting in lead dislodgement. We aimed to determine the true prevalence and risk factors associated with Twiddler's syndrome in a real-world population. METHODS: A retrospective chart review was performed on all patients who underwent cardiac device implantation from January 1st 2017 until Jan 1st 2022. We specifically searched for the terms "Twiddler" or "Twiddler's" imbedded within the text of the medical chart. Demographic and clinical variables were collected from the electronic medical record system. We utilized multivariable logistic regression analysis as well as Kaplan-Meier prediction models to determine independent clinical predictors of Twiddler's syndrome as well as associated mortality, respectively. RESULTS: Twenty one out of 1793 patients (1.2%) were identified as having Twiddler's syndrome after chart review. Independent variables associated with Twiddler's syndrome were female sex (OR 3.76; 95% CI 1.29-10.95), antidepressant medications (OR 3.58; 95% CI 1.07-11.99), and BMI (OR 1.08; 95% CI 1.03-1.31). There was no increased six-month mortality via Kaplan-Meier analysis. CONCLUSION: Our study shows that 1.2% of patients in our real-world population had evidence of Twiddler's syndrome. Independent predictors of Twiddler's syndrome include female sex, antidepressant medications as well as BMI.

Feasibility and safety of laser balloon pulmonary vein isolation in patients with prior left atrial appendage occlusion device implantation.

INTRODUCTION: With the increasing adoption of left atrial appendage occlusion (LAAO) procedures and the eligibility of patients for pulmonary vein isolation (PVI) post device placement, we examined the feasibility and safety of laser balloon (LB) for PVI in patients with prior LAAO. METHODS: We retrospectively examined consecutive patients with paroxysmal or persistent, drug-resistant atrial fibrillation (AF) who underwent LB PVI, after Watchman FLX device implantation at Rush University Medical Center between January 2020 and December 2021. RESULTS: Seven patients (four persistent and three paroxysmal) with a mean age of 64 ± 11 years, predominantly male sex (86%), were included in the study. Two (29%) patients had prior cryoablation PVI with recurrence of AF. The mean CHA2 DS2 VASc is 2.6 ± 0.5 and the mean HAS-BLED score is 3.4 ± 0.8. The mean follow-up duration was 10 ± 7 months. The mean duration between Watchman FLX device implantation and LB PVI was 592 days. Acute first pass left pulmonary vein (PV) isolation was achieved in 100% of the procedures. There were no periprocedural complications such as death, pericardial tamponade or effusion, phrenic nerve injury, PV stenosis, device perforation or embolization, or worsening peri-device leak in any of the patients. None of the patients had AF recurrence after the blanking period. CONCLUSION: LB PVI was safe and effective with 100% acute isolation of left-sided veins in patients with prior LAAO device.

Novel oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation after transcatheter aortic valve replacement: A systematic review and meta-analysis.

BACKGROUND: The efficacy and safety of novel oral anticoagulants (NOACs) compared to the current guideline-recommended vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients undergoing transcatheter aortic valve replacement (TAVR) has not been well established. We pooled evidence from all available studies to assess the risks and benefits of this drug class. METHODS: We queried electronic databases (MEDLINE, Scopus, and Cochrane central) up until January 28th, 2022 for studies comparing NOACs to VKAs in AF patients undergoing TAVR. Results from studies were presented as risk ratios (RR) and pooled using a random-effects model. Subgroup analysis by study design and meta-regression analysis were performed to explore heterogeneity. RESULTS: A total of 12 studies (3 RCTs and 9 observational) containing 12,203 patients (mean age 81.2 years; 50.5% men) were identified and included in the analysis. Pooled analysis revealed no significant difference between NOACs and VKAs in terms of stroke or systemic embolism (RR: 0.78; p = 0.18), major bleeding (RR: 0.84; p = 0.32), intracranial hemorrhage (RR 0.61; p = 0.06), all-cause mortality (RR: 0.69; p = 0.07), and myocardial infarction (RR: 1.60; p = 0.24) at a mean length of follow-up of 15.1 months. RCTs and observational studies did not significantly differ across outcomes on subgroup analysis. Meta-regression analysis found heterogeneity in all-cause mortality to be significantly explained by percentage of males (coefficient: 0.049, p = 0.007), mean age (coefficient: 0.221, p < 0.001), and CHA2DS2-VASc score (coefficient: -1.657, p < 0.001). CONCLUSIONS: This meta-analysis suggests that outcomes with NOACs do not significantly differ compared to VKAs following TAVR in patients with AF.

Cardiac imaging for the assessment of patients being evaluated for liver transplantation.

Cardiac risk assessment prior to liver transplantation has become widely accepted. With the emergence of nonalcoholic steatohepatitis among the leading causes of end-stage liver disease and the steady rise of the age of liver transplant recipients, the burden of cardiovascular diseases has markedly increased in this population. Selecting appropriate liver transplant candidates is crucial due to the increasing demand for scarce donor organs. The use of noninvasive cardiac imaging for pre-operative assessment of the cardiovascular status of liver transplant recipients has been on the rise, yet the optimal assessment strategy remains an area of active debate. In this review, we examine the relevant literature pertaining to the diagnostic and prognostic applications of noninvasive cardiac imaging in this population. We also propose a simple literature-based evaluation algorithm for CAD surveillance in liver transplant candidates.

Cardiac imaging for the assessment of patients being evaluated for kidney transplantation.

Cardiac risk assessment before kidney transplantation has become widely accepted. However, the optimal patient selection and screening tool for cardiac assessment remain controversial. Clinicians face several challenges in this process, including the ever-growing pre-transplant population, aging transplant candidates, increasing prevalence of coronary artery disease, and scarcity of donor organs. Optimizing the cardiovascular risk profile in kidney transplant candidates is necessary to better appropriate limited donor organs and improve patient outcomes. Increasing waiting times from the initial evaluation for transplant candidacy to the actual transplant raises questions regarding re-testing and re-stratification of risk. In this review, we summarize and discuss the current literature on cardiac evaluation prior to kidney transplantation. We also propose simple evidence-based evaluation algorithms for initial and follow-up CAD surveillance in patients being wait-listed for kidney transplantation.

The prognostic implications of ST-segment and T-wave abnormalities in patients undergoing regadenoson stress SPECT myocardial perfusion imaging.

BACKGROUND: The prognostic implications of ST-segment and T-wave (ST/T) abnormalities in patients undergoing stress SPECT-myocardial perfusion imaging (MPI) are not well defined. METHODS AND RESULTS: This was a single-center, retrospective cohort study of consecutive patients who underwent regadenoson stress SPECT-MPI. Patients with baseline electrocardiogram (ECG) abnormalities that impede ST/T analysis or those with known coronary artery disease were excluded. Patients were categorized as having primary ST abnormalities, secondary ST/T abnormalities due to ventricular hypertrophy or right bundle branch block, T-wave abnormalities, or normal ECG. The primary outcome was major adverse cardiovascular events (MACE) defined as the composite of cardiac death or myocardial infarction. Among 6,059 subjects, 1912 (32%) had baseline ST/T abnormalities. During a mean follow-up of 2.3 ± 1.9 years, the incidence of MACE was significantly higher among patients with secondary ST/T abnormalities compared to those with normal ECG (HR 2.05; 95% confidence interval [CI], 1.04-4.05; P = 0.039). No significant difference in MACE was observed among patients with primary ST abnormalities (HR 1.64; CI 0.87-3.06; P = 0.124) or T-wave abnormalities (HR 1.15; CI 0.62-2.16; P = 0.658) compared with patients who had normal ECG. Among patients with secondary ST/T changes, abnormal MPI was not associated with a significant increase in MACE rates compared to normal MPI (HR 1.18; CI 0.31-4.58; P = 0.808). However, abnormal MPI was associated with higher MACE rates among patients with primary ST abnormalities (HR 4.50; CI 1.44-14.10; P = 0.005) and T-wave abnormalities (HR 3.74; CI 1.20-11.68; P = 0.015). Similarly, myocardial ischemia on regadenoson stress SPECT-MPI was not associated with a significant increase in MACE rates in patients with secondary ST/T abnormalities (HR 1.45; CI 0.38-5.61; P = 0.588), while it was associated with a higher incidence of MACE in patients with primary ST abnormalities (HR 3.012; CI 0.95-9.53; P = 0.049) and T-wave abnormalities (HR 5.06; CI 1.60-15.96; P = 0.002). CONCLUSION: While patients with secondary ST/T abnormalities had significantly higher MACE risk, abnormal MPI or presence of myocardial ischemia on regadenoson SPECT-MPI in this group does not add prognostic information. Patients with primary ST abnormalities and T-wave abnormalities do not seem to have a significantly higher MACE risk compared to those with normal ECG; however, abnormal MPI or presence of myocardial ischemia, in these groups, correlates with higher MACE rates.

The prognostic utility of regadenoson SPECT myocardial perfusion imaging in patients with end-stage renal disease: The largest cohort to date.

BACKGROUND: There are limited data on the prognostic utility of regadenoson SPECT myocardial perfusion imaging (MPI) in patients with end-stage renal disease (ESRD). METHODS AND RESULTS: In a single-center, retrospective study, we analyzed consecutive ESRD patients who underwent regadenoson SPECT-MPI. The severity of MPI abnormalities and ischemic burden were determined quantitatively. The primary endpoint was major adverse cardiac events (MACE), defined as the composite of cardiac death or myocardial infarction. Among 1,227 subjects (mean age 54 ± 13 years, 47% men), 60 (5%) MACE were observed during a mean follow-up of 2.5 ± 1.8 years. The presence and severity of MPI abnormalities and ischemic burden were associated with a stepwise increase in MACE risk. Abnormal MPI (SSS ≥ 4) was associated with increased MACE risk, independent and incremental to relevant clinical covariates; adjusted hazard ratio, 1.95; 95% confidence interval, 1.15-3.32; Δχ2 = 5.97; P = .013. Myocardial ischemia (SDS ≥ 2) was associated with a trend towards increased MACE risk; adjusted hazard ratio, 1.63; 95% confidence interval, 0.96-2.77; Δχ2 = 3.12; P = .072. CONCLUSION: In the largest cohort to date, we demonstrated the incremental prognostic value of abnormal MPI in predicting MACE risk in ESRD patients. Given its size, our study provides improved risk estimates in this population compared to previous reports.

The diagnostic and prognostic value of near-normal perfusion or borderline ischemia on stress myocardial perfusion imaging.

BACKGROUND: Data on the diagnostic and prognostic value of subtle abnormalities on myocardial perfusion imaging (MPI) are limited. METHODS AND RESULTS: In a retrospective single-center cohort of patients who underwent regadenoson SPECT-MPI, near-normal MPI was defined as normal left ventricular ejection fraction (LVEF ≥ 50%) and a summed stress score (SSS) of 1-3 vs SSS = 0 in normal MPI. Borderline ischemia was defined as normal LVEF, SSS = 1-3, and a summed difference score (SDS) of 1 vs SDS = 0 in the absence of ischemia. Coronary angiography data within 6 months from MPI were tabulated. Patients were followed for cardiac death (CD), myocardial infarction (MI), coronary revascularization (CR), and Late CR (LCR) [> 90 days post MPI]. Among 6,802 patients (mean age, 62 ± 13 years; 42% men), followed for a mean of 2.5 ± 2.1 years, 4,398 had normal MPI, 2,404 had near-normal MPI, and 972 had borderline ischemia. Among patients who underwent angiography within 6 months, obstructive (≥ 70% or left main ≥ 50%) CAD was observed at higher rates among subjects with near-normal MPI (33.5% vs 25.5%; P = .049) and those with borderline ischemia (40.5% vs 25.8%; P = .004). During follow-up, 158 (2.3%) CD/MI, 246 (3.6%) CR, and 150 (2.2%) LCR were observed. Near-normal MPI (SSS = 1-3), compared to normal MPI (SSS = 0), was not associated with a significant difference in the risk of the composite endpoint of CD/MI (Hazard ratio [HR], 1.21; 95% confidence interval [CI], .88-1.66; P = .243) or LCR (HR 1.28; CI .93-1.78; P = .130), but was associated with a significant increase in the risk of CR (HR 1.91; CI 1.49-2.46; P < .001). Borderline ischemia (SDS = 1), compared to no ischemia (SDS = 0), was not associated with a significant difference in the risk of CD/MI [HR 1.09; CI .70-1.69; P = .693], but was associated with a significant increase in the risk of CR (HR 5.62; CI 3.08-10.25; P < .001) and LCR (HR 2.98; CI 1.36-6.53; P = .006). CONCLUSION: Near-normal MPI and borderline ischemia on SPECT-MPI provide no significant prognostic information in predicting hard cardiac events but are associated with higher rates of obstructive angiographic CAD and coronary revascularizations.

Right ventricle assessment in patients with pulmonary embolism at low risk for death based on clinical models: an individual patient data meta-analysis.

AIMS: Patients with acute pulmonary embolism (PE) at low risk for short-term death are candidates for home treatment or short-hospital stay. We aimed at determining whether the assessment of right ventricle dysfunction (RVD) or elevated troponin improves identification of low-risk patients over clinical models alone. METHODS AND RESULTS: Individual patient data meta-analysis of studies assessing the relationship between RVD or elevated troponin and short-term mortality in patients with acute PE at low risk for death based on clinical models (Pulmonary Embolism Severity Index, simplified Pulmonary Embolism Severity Index or Hestia). The primary study outcome was short-term death defined as death occurring in hospital or within 30 days. Individual data of 5010 low-risk patients from 18 studies were pooled. Short-term mortality was 0.7% [95% confidence interval (CI) 0.4-1.3]. RVD at echocardiography, computed tomography or B-type natriuretic peptide (BNP)/N-terminal pro BNP (NT-proBNP) was associated with increased risk for short-term death (1.5 vs. 0.3%; OR 4.81, 95% CI 1.98-11.68), death within 3 months (1.6 vs. 0.4%; OR 4.03, 95% CI 2.01-8.08), and PE-related death (1.1 vs. 0.04%; OR 22.9, 95% CI 2.89-181). Elevated troponin was associated with short-term death (OR 2.78, 95% CI 1.06-7.26) and death within 3 months (OR 3.68, 95% CI 1.75-7.74). CONCLUSION: RVD assessed by echocardiography, computed tomography, or elevated BNP/NT-proBNP levels and increased troponin are associated with short-term death in patients with acute PE at low risk based on clinical models. RVD assessment, mainly by BNP/NT-proBNP or echocardiography, should be considered to improve identification of low-risk patients that may be candidates for outpatient management or short hospital stay.

Prognostic value of regadenoson stress myocardial perfusion imaging in patients with left bundle branch block or ventricular paced rhythm.

BACKGROUND: Vasodilator stress myocardial perfusion imaging (MPI) is the provocative test of choice in patients with left bundle branch block (LBBB) or ventricular paced (V-paced) rhythm. The prognostic value of regadenoson SPECT myocardial perfusion imaging (MPI) in these patients has not been studied. METHODS AND RESULTS: We conducted a retrospective cohort study of 562 patients [mean age, 69 ± 11 years; men, 53.3%] with LBBB (50.7%) or V-paced rhythm (49.3%) who underwent regadenoson stress SPECT-MPI. There were 321 (57.1%) subjects with abnormal MPI and 192 (34.2%) with myocardial ischemia. During a mean follow-up of 2.5 ± 1.9 years, 39 (6.9%) patients had a major adverse cardiac event (MACE), defined as cardiac death or myocardial infarction. The annualized MACE rate in patients with normal MPI was 0.9% (LBBB, 0.8%; V-paced, 1.0%). There was a significant stepwise increase in MACE rates with increasing burdens of perfusion abnormality (P < 0.001) and myocardial ischemia (P = 0.001). Increased risk with abnormal MPI [adjusted hazard ratio, 4.26; P = 0.001] and myocardial ischemia [adjusted hazard ratio, 2.70; P = 0.003] was independent of and incremental to important clinical covariates. Abnormal MPI and myocardial ischemia predicted MACE similarly in both LBBB and V-paced subgroups (interaction P values > 0.05). CONCLUSION: In patients with LBBB and V-paced rhythm, regadenoson stress SPECT-MPI provides independent and incremental prognostic value in predicting adverse cardiac events.

Comparison of planar with tomographic pyrophosphate scintigraphy for transthyretin cardiac amyloidosis: Perils and pitfalls.

BACKGROUND: Tc-99m pyrophosphate (PYP) SPECT is recommended for indeterminate findings on planar imaging. We aimed to compare the findings on planar PYP scintigraphy alone to that of routinely performed PYP SPECT. METHODS: PYP scintigraphy data of 133 patients (53% men; mean age 76 years) were evaluated. SPECT was routinely performed following 1-hour planar imaging, in all cases. Semiquantitative visual score and heart-to-contralateral (H/CL) ratio were determined in all patients as recommended. RESULTS: PYP images from 35 patients (26%) were considered to be positive based on SPECT myocardial uptake. Among them, 20 (57%) had a H/CL ratio ≥1.5 and 34 had a visual score ≥ 2. SPECT identified myocardial uptake in one patient with a visual score < 2 and refuted the presence of myocardial uptake in two patients with a visual score ≥ 2. Visual score correlated well with SPECT (r = 0.94; P < .0001) and had an accuracy of 98% for tomographic myocardial uptake. Addition of H/CL ratio reduced the diagnostic performance of visual score. CONCLUSIONS: Planar-derived visual score has an excellent accuracy for tomographic myocardial uptake, though it misclassifies a small proportion of patients. H/CL ratio decreases the diagnostic certainty of planar imaging. Tomographic imaging prevents misdiagnoses and should always be performed.

The prognostic value of regadenoson SPECT myocardial perfusion imaging: The largest cohort to date.

BACKGROUND: Data on the prognostic value of regadenoson SPECT myocardial perfusion imaging (MPI) is limited and based on small cohorts. METHODS AND RESULTS: We conducted a single-center, retrospective cohort study of 10,275 consecutive patients who underwent regadenoson SPECT-MPI. Among the study subjects, 28.7% had abnormal MPI and 25.5% had myocardial ischemia. Patients were followed for a mean of 2.4 ± 2.2 years for major adverse cardiac events (MACE), defined as cardiac death or myocardial infarction. There was a significant stepwise increase in MACE with an increasing burden of perfusion abnormality (P < .001) and myocardial ischemia (P < .001). Abnormal MPI (adjusted HR 1.52; 95% CI 1.21 to 1.91) and myocardial ischemia (adjusted HR 1.53; 95% CI 1.25 to 1.89) were associated with MACE, independent of and incremental to clinical covariates and left ventricular ejection fraction (LVEF). Moreover, post-stress LVEF, LVEF reserve, and left ventricular end-diastolic volume added significant prognostic information. Transient ischemic dilation ≥ 1.31 did not provide incremental prognostic value (adjusted HR 1.02; P = .906). CONCLUSION: In the largest cohort to date, we demonstrated that the presence and severity of perfusion abnormality and myocardial ischemia on regadenoson stress SPECT-MPI are associated with an independent increase in MACE.

Contribution of individual components to composite end points in contemporary cardiovascular randomized controlled trials.

Cardiovascular randomized controlled trials (RCTs) typically set composite end points as the primary outcome to enhance statistical power. However, influence of individual component end points on overall composite outcomes remains understudied. METHODS: We searched MEDLINE for RCTs published in 6 high-impact journals (The Lancet, the New England Journal of Medicine, Journal of the American Medical Association, Circulation, Journal of the American College of Cardiology and the European Heart Journal) from 2011 to 2017. Two-armed, parallel-design cardiovascular RCTs which reported composite outcomes were included. All-cause or cardiovascular mortality, myocardial infarction, heart failure, and stroke were deemed "hard" end points, whereas hospitalization, angina, and revascularization were identified as "soft" end points. Type of outcome (primary or secondary), event rates in treatment and control groups for the composite outcome and of its components according to predefined criteria. RESULTS: Of the 45.8% (316/689) cardiovascular RCTs which used a composite outcome, 79.4% set the composite as the primary outcome. Death was the most common component (89.8%) followed by myocardial infarction (66.1%). About 80% of the trials reported complete data for each component. One hundred forty-seven trials (46.5%) incorporated a "soft" end point as part of their composite. Death contributed the least to the estimate of effects (R2 change = 0.005) of the composite, whereas revascularization contributed the most (R2 change = 0.423). CONCLUSIONS: Cardiovascular RCTs frequently use composite end points, which include "soft" end points, as components in nearly 50% of studies. Higher event rates in composite end points may create a misleading interpretation of treatment impact due to large contributions from end points with less clinical significance.

Impact of chronic thrombocytopenia on in-hospital outcomes and healthcare resource utilization after transcatheter aortic valve replacement.

BACKGROUND: There is little data on the impact of chronic thrombocytopenia (CTP) on outcomes after transcatheter aortic valve repair (TAVR). Most studies are from single centers and mostly focused on postprocedure thrombocytopenia. OBJECTIVES: This study sought to report on the impact of CTP (>1 year) on in-hospital outcomes and healthcare resource utilization after TAVR. METHODS: From the National Inpatient Sample (NIS) between 2012 and 2015, we identified patients with CTP who underwent TAVR. A 1:1 propensity-matched cohort was created to examine in-hospital outcomes in patients with and without CTP. The primary outcome was in-hospital mortality. Secondary outcomes included postprocedure complications, length of stay, total cost, and discharge disposition. RESULTS: A matched pair of 4,300 patients with and without CTP were identified. Patients with CTP had higher in-hospital mortality as compared to no CTP patients (6.0 vs. 3.3%, p-value .007), increased postprocedure hemorrhage, platelet and blood transfusion, vascular complications, postop sepsis, and acute kidney injury. With regards to resource utilization, CTP patients had a longer length of stay, higher total cost and were more likely to be discharged to a facility (34.1 vs. 27.6%) other than home (All, p-value <.001). Subanalysis, however, revealed this difference in resource utilization was seen when patients developed postprocedure complications. CONCLUSION: This study demonstrated higher risk of in-hospital mortality, perioperative complications, and healthcare resource utilization in patients with baseline CTP undergoing TAVR. Further studies are required to investigate ways to improve the management of these patients.

Impact of pretransplant mitral annular calcification on the incidence of cardiac events after renal transplantation.

BACKGROUND: Mitral annular calcification (MAC) is associated with increased risk of major adverse cardiac events. We hypothesized that MAC, identified on a pretransplant transthoracic echocardiography (TTE), is predictive of cardiac events following renal transplantation (RT). METHODS: In a retrospective cohort of consecutive RT recipients, pretransplant MAC presence and severity were determined on TTE performed within 1 year prior to transplant. MAC severity was quantified based on the circumferential MAC extension relative to the mitral valve annulus. Post-transplant cardiac risk was assessed using the sum of risk factors (range: 0-8) set forth by the American Heart Association/American College of Cardiology Foundation consensus statement on the assessment of RT candidates. Subjects underwent pretransplant stress single-photon emission computed tomography myocardial perfusion imaging and followed for post-transplant composite outcome of cardiac death or myocardial infarction (CD/MI). RESULTS: Among 336 subjects (60.5% men; mean age 52 ± 12 years), MAC was present in 78 (23%) patients. During a mean follow-up of 3.1 ± 1.9 years, a total of 70 events were observed. Patients with MAC had a higher event rate compared with those without MAC (34.6% versus 17.8%, log-rank P = 0.001). There was a stepwise increase in CD/MI risk with increasing MAC severity (P for trend = 0.002). MAC-associated risk remained significant after adjusting for sex, duration of dialysis, sum of risk factors, ejection fraction and perfusion abnormality burden, providing an incremental prognostic value to these parameters (Δχ2 =4.63; P = 0.031). CONCLUSION: Among RT recipients, the burden of pretransplant MAC is an independent predictor of post-transplant risk of CD/MI. MAC should be considered in the preoperative assessment of RT candidates.

Prognostic significance of ischemic electrocardiographic changes with regadenoson stress myocardial perfusion imaging.

BACKGROUND: In patients undergoing regadenoson SPECT myocardial perfusion imaging (MPI), the prognostic value of ischemic ST-segment depression (ST↓) and the optimal ST↓ threshold have not been studied. METHODS: A retrospective cohort study of consecutive patients referred for regadenoson stress MPI was conducted. Patients with uninterpretable ECG were excluded. Two diagnostic thresholds of horizontal or downsloping ST↓ were studied, ≥ 0.5 mm and ≥ 1.0 mm. The primary endpoint was the composite major adverse cardiac events (MACE) of cardiac death, myocardial infarction, or coronary revascularization. RESULTS: Among 8615 subjects (mean age 62 ± 13 years; 55% women), 89 (1.0%) had ST↓ ≥ 1.0 mm and 133 (1.5%) had ST↓ ≥ 0.5 mm. Regadenoson-induced ST↓ was more common in women (P < .001). Mean follow-up was 2.5 ± 2.2 years. After multivariate adjustment, ST↓ ≥ 1.0 mm was associated with a non-significant increase in MACE risk (P = .069), irrespective to whether MPI was abnormal (P = .162) or normal (P = .214). Ischemic ST↓ ≥ 0.5 mm was independently associated with MACE in the entire cohort (HR 2.14; CI 1.38-3.32; P = .001), whether MPI is normal (HR 2.07; CI 1.07-4.04; P = .032) or abnormal (HR 2.24; CI 1.23-4.00; P = .007), after adjusting for clinical and imaging covariates. An ST↓ threshold of ≥ 0.5 mm provided greater incremental prognostic value beyond clinical and imaging parameters (Δχ2 = 12.78; P < .001) than ≥ 1.0 mm threshold (Δχ2 = 3.72; P = .093). CONCLUSION: Regadenoson-induced ischemic ST↓ is more common in women and it provides a modest independent prognostic value beyond MPI and clinical parameters. ST↓ ≥ 0.5 mm is a better threshold than ≥ 1.0 mm to define ECG evidence for regadenoson-induced myocardial ischemia.

Ischemia and Viability Testing in New-Onset Heart Failure.

PURPOSE OF REVIEW: To examine the utility and methods of coronary artery disease (CAD) assessment in patients with new-onset heart failure with reduced ejection fraction (HFrEF) of unclear etiology. Moreover, we sought to review the role and techniques of assessing myocardial viability to guide coronary revascularization in patients with established ischemic cardiomyopathy. RECENT FINDINGS: Data indicates that surgical coronary revascularization in patients with HFrEF due to ischemic cardiomyopathy leads to lower long-term all-cause mortality and cardiovascular hospitalizations. Thus, identifying ischemic heart disease in patients with new-onset HFrEF is essential. In addition to invasive coronary angiography (ICA), radionuclide myocardial perfusion imaging, coronary CT angiography (CCTA), and cardiac magnetic resonance (CMR) imaging have emerged as effective non-invasive tools in the assessment of CAD in this population. Viability testing remains an area of particular interest and debate and its full potential has not been fully addressed. We propose stepwise algorithms for CAD and viability assessment in this patient population. Non-invasive testing with radionuclide myocardial perfusion imaging, CCTA, and CMR is an alternative to ICA for CAD assessment in patients with new-onset HFrEF of unclear etiology. Several non-invasive imaging modalities have proved to be effective in detecting viable myocardium in patients with ischemic cardiomyopathy. The use of viability imaging to guide coronary revascularization should be individualized.