Stress Left Ventricular Ejection Fraction Research Articles

Artificial Intelligence Predicts Hospitalization for Acute Heart Failure Exacerbation in Patients Undergoing Myocardial Perfusion Imaging.

Heart failure (HF) is a leading cause of morbidity and mortality in the United States and worldwide, with a high associated economic burden. This study aimed to assess whether artificial intelligence models incorporating clinical, stress test, and imaging parameters could predict hospitalization for acute HF exacerbation in patients undergoing SPECT/CT myocardial perfusion imaging. Methods: The HF risk prediction model was developed using data from 4,766 patients who underwent SPECT/CT at a single center (internal cohort). The algorithm used clinical risk factors, stress variables, SPECT imaging parameters, and fully automated deep learning-generated calcium scores from attenuation CT scans. The model was trained and validated using repeated hold-out (10-fold cross-validation). External validation was conducted on a separate cohort of 2,912 patients. During a median follow-up of 1.9 y, 297 patients (6%) in the internal cohort were admitted for HF exacerbation. Results: The final model demonstrated a higher area under the receiver-operating-characteristic curve (0.87 ± 0.03) for predicting HF admissions than did stress left ventricular ejection fraction (0.73 ± 0.05, P < 0.0001) or a model developed using only clinical parameters (0.81 ± 0.04, P < 0.0001). These findings were confirmed in the external validation cohort (area under the receiver-operating-characteristic curve: 0.80 ± 0.04 for final model, 0.70 ± 0.06 for stress left ventricular ejection fraction, 0.72 ± 0.05 for clinical model; P < 0.001 for all). Conclusion: Integrating SPECT myocardial perfusion imaging into an artificial intelligence-based risk assessment algorithm improves the prediction of HF hospitalization. The proposed method could enable early interventions to prevent HF hospitalizations, leading to improved patient care and better outcomes.

Incremental prognostic value of fully automatic LVEF measured at stress using machine learning

Abstract Background Cardiovascular magnetic resonance (CMR) is the gold standard to measure left ventricular ejection fraction (LVEF), and novel artificial intelligence-based automatic analyses have been proposed for less user interaction and time saving. However, whether automatic LVEF delivers similar information for risk stratification remains unknown. Purpose To assess the prognostic value for all-cause mortality of LVEF measured by stress CMR using a fully automatic machine learning algorithm without human correction. Methods Between 2016 and 2018, all consecutive patients referred for vasodilator stress CMR were included and followed for the occurrence of all-cause death. A fully automatic machine learning algorithm was trained on 3,700 scans and validated on 1,719 unseen CMR studies (MAGNETOM Aera and Skyra, Siemens Healthcare, Erlangen, Germany) to identify end-diastolic and end-systolic phases and segment LV volumes from short-axis cine images at stress. The algorithm combines multiple deep learning networks for detection and segmentation with an active contours approach. Manual and automatic LVEF measured at stress were compared with the paired Wilcoxon test, Pearson correlation and Bland-Altman analysis. Cox regressions were performed to determine the prognostic value of automatic LVEF measured at stress. Results Among 9,883 included patients included to this study, the automatic LVEF was successfully computed in 9,712 (98.3%) patients (66.6% male, mean age 66±12 years). The agreement between manual and automatic LVEF was good (bias = -0.01%, 95% limits of agreement, -6.7% to 6.7%; Pearson’s correlation coefficient r=0.94). A total of 504 (5.2%) deaths were observed during a median (IQR) follow-up period of 4.5 (3.7-5.2) years. Both manual and automatic volumetric assessments showed similar impact on outcome in univariate analyses (manual LVEF per 5%: hazard ratio [HR], 0.80 [95% CI 0.77–0.83]; p&amp;lt;0.001; automatic LVEF per 5%: HR, 0.84 [95% CI, 0.81–0.86]; p&amp;lt;0.001) and multivariable analyses (manual LVEF per 5%: HR, 0.81 [95% CI, 0.78–0.84]; p&amp;lt;0.001; automatic LVEF per 5%: HR, 0.84 [95% CI, 0.82–0.87]; p&amp;lt;0.001). Fully automatic stress LVEF showed an incremental prognostic value to predict all-cause mortality above all traditional risk factors, LVEF measured at rest, the presence of inducible ischemia and LGE (C-statistic improvement: 0.04; NRI=0.221; IDI=0.049; all p&amp;lt;0.001). Conclusions Automatic LVEF is equally predictive of all-cause mortality compared to manual LVEF, and has an incremental prognostic value compared to traditional risk factors, and other stress CMR parameters. Figures: Figure 1: Linear regression plots (A) and Bland-Altman plots (B) comparing stress LVEF measured by experts (LVEFexpert) and computed by fully-automated artificial-intelligence algorithms (LVEFAI). Figure 2: Kaplan-Meier curves for MACE stratified by fully-automated LVEF value. Test comparing the three groups is based on the log-rank test.

Impact of Positron Emission Tomographic Myocardial Perfusion Imaging on Patient Selection for Revascularization

BackgroundPositron emission tomography (PET) myocardial perfusion imaging (MPI) quantifies left ventricular ejection fraction (LVEF) at peak stress. PET LVEF reserve (LVEF-R = stress LVEF − rest LVEF) offers diagnostic and prognostic value. ObjectivesThe purpose of this study was to determine if PET LVEF-R identifies patients with survival benefit postrevascularization. MethodsWe followed 14,649 unique consecutive patients undergoing 82Rb rest/stress PET MPI from January 2010 to January 2016 (excluding known cardiomyopathy). Adjusted Cox models were built to predict all-cause death, and the 3-way interaction of known coronary artery disease (CAD) (prior myocardial infarction/revascularization), LVEF-R, and 90-day revascularization was tested. ResultsKnown CAD was present in 4,982 (34.0%). Ischemia was detected in 5,396 (36.8%; ≥10% in 1,909 [13%]). Mean LVEF-R was 4.2% ± 5.7%, and was ≤0, 1 to 5, and >5 in 3,349 (22.9%), 5,266 (35.9%), and 6,034 (41.2%). Over median follow-up of 3.4 years (IQR: 1.9-5.2 years), 1,324 (8.1%) had 90-day revascularization, and there were 2,192 (15.0%) deaths. In multivariable modeling, there was a significant 3-way interaction among known CAD, LVEF-R, and 90-day revascularization (P = 0.025), such that LVEF-R ≤0 identified patients with survival benefit with 90-day revascularization in those without prior CAD (interaction P = 0.005), independently beyond percent ischemia and myocardial flow reserve. Among patients with known CAD, LVEF-R was not prognostic of death (HR: 0.99; 95% CI: 0.98-1.02; P = 0.98). ConclusionsA lack of augmentation or drop in LVEF with vasodilator stress on PET MPI independently identifies patients who have better survival with revascularization within 90 days post-MPI compared with medical therapy, in absence of prior myocardial infarction or revascularization. Multiparametric assessment of ischemia with PET can optimize post-test management.

Incremental prognostic value of fully-automatic LVEF by stress CMR using machine learning

Abstract Funding Acknowledgements Type of funding sources: None. Background Although some recent reports showed that fully automated artificial intelligence (AI)-based left ventricular ejection fraction (LVEF) measured at stress has good performance, its prognostic value during a stress CMR exam to predict outcomes is not well established. Aim To determine in patients undergoing stress CMR whether fully automated AI-based LVEF (LVEF-AI) measured at stress can provide incremental prognostic value to predict death. Methods Between 2016 and 2018, we conducted a longitudinal study including all consecutive patients referred for vasodilator stress CMR. LVEF-AI was assessed using AI-algorithm combines multiple deep learning networks for LV segmentation. The primary outcome was all-cause death defined by the French National Registry of Death. Cox regression was used to evaluate the association of stress LVEF-AI with death after adjustment for traditional risk factors. Results In 9,712 patients (66±15 years, 67% men), there was an excellent correlation between stress LVEF-AI measurement and LVEF measured by expert (LVEF-expert) (r=0.94, p&amp;lt;0.001). Using Bland–Altman analysis, we found that the difference between the mean LVEF-expert and the LVEF-AI group was −0.1% (−0.066–0.067), that was not statistically significant (p = 0.46). Stress LVEF-AI was associated with death (median [IQR] follow-up 4.5 [3.7–5.2] years) before and after adjustment for risk factors (adjusted hazard ratio [HR], 0.84 [95% CI, 0.82–0.87] per 5% increment, p&amp;lt;0.001). Stress LVEF-AI had similar significant association with death occurrence compared with LVEF-expert. After adjustment, a lower stress LVEF-AI showed the greatest improvement in model discrimination and reclassification over and above traditional risk factors and stress CMR findings (C-statistic improvement: 0.11; NRI=0.250; IDI=0.049, all p&amp;lt;0.001; LR-test p&amp;lt;0.001), with a superior additional prognostic value than the LVEF-AI measured at rest. Conclusion AI-based fully automated LVEF measured at stress is independently associated with the occurrence of death in patients undergoing stress CMR, with an additional prognostic value above traditional risk factors, inducible ischemia and LGE.

Prediction of angiographic coronary disease and mortality with a cadmium-zinc-telluride camera: a comparison of upright and supine ejection fractions and left ventricular volumes

IntroductionPerfusion imaging strongly predicts coronary artery disease (CAD), whereas cardiac volumes and left ventricular ejection fraction (LVEF) strongly predict mortality. Compared to conventional Anger single photon emission computed tomography (SPECT) cameras, cadmium-zinc-telluride (CZT) cameras provide higher resolution, resulting in different left ventricular volumes. The cadmium-zinc-telluride D-SPECT camera is commonly used to image in the upright position, which introduces changes in left ventricular loading conditions and potentially alters left ventricular volumes. However, little or no data exist on the predictive value of left ventricular volumes and ejection fraction when acquired in the upright position. We investigated models for the prediction of CAD and mortality, comparing upright and supine imaging.MethodsA retrospective study of patients with upright/supine stress and rest imaging and coronary angiography within 3 months was performed. Univariate and multivariable analyses were performed to predict abnormal angiograms and all-cause mortality.ResultsOf the 392 patients, 210 (53.6%) had significant angiographic CAD; 78 (19.9%) patients died over 75 months. The best multivariable model for CAD included the supine summed stress score and supine stress LVEF, with an area under the receiver operating characteristic of 0.862, a sensitivity of 76.7%, and a specificity of 82.4%, but this model was not statistically superior to the best upright model. The best multivariable models for mortality included age, diabetes, history of cardiovascular disease, and end-systolic volume, with the upright and supine models being equivalent.DiscussionAngiographic CAD was best predicted by the supine summed stress score and LVEF but was not statistically superior to the next-best upright model. Mortality was best predicted by end-systolic volume in combination with age, diabetes status, and cardiovascular disease status, with equivalent results from the upright and supine images.

Utility of gated SPECT parameters in detection of coronary artery disease in patients with normal perfusion images

BackgroundFalse negative myocardial perfusion images on single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is a substantial problem in the interpretation of MPI. To explore possible parameters from gated SPECT that could detected coronary artery disease (CAD) in patients with normal perfusion images, we retrospectively selected patients who underwent a 2-day Tc-99 m MIBI adenosine stress/rest MPI and a subsequent invasive coronary angiography. Gated SPECT parameters, including end systolic volume (ESV), end diastolic volume (EDV), left ventricular ejection fraction (LVEF), and transient ischemic dilation (TID) ratio of patients with and without CAD were compared and assessed for their respective diagnostic performance using receiver operating characteristics (ROC) area under the curve (AUC).ResultsAmong 22 patients with normal perfusion images, 7 patients had CAD. Despite the small number of patients, we found significant differences between the ESV, the EDV, and the LVEF between patients with and without CAD. The analysis of ROC curve showed the stress ESV could excellently detect CAD (AUC = 0.900). The rest ESV, the stress EDV, the rest EDV, the stress LVEF and the rest LVEF could likewise perform well in the detection of CAD (AUC = 0.833, 0.819, 0.790, 0.862, and 0.838, respectively). In contrast, the change in LVEF and the TID ratio (AUC = 0.667 and 0.524, respectively) did not seem as reliable as other parameters. Optimal cutoffs for detection of CAD in patients with normal perfusion images from our study were ≥ 20.0 mL for the stress ESV, ≥ 71.0 mL for the stress EDV, ≤ 66.3 EF units for the stress LVEF, ≥ 18.0 mL for the rest ESV, ≥ 67.0 mL for the rest EDV and ≤ 70.0 EF unit for the rest LVEF.ConclusionsGated SPECT parameters could facilitate detection of CAD in patient with normal perfusion images on Tc-99m MIBI MPI. These parameters should be carefully interpreted to improve diagnostic accuracy and reduce false negative MPI.

Body mass index associated differences in cardiac stress energetics in type 2 diabetes

Abstract Background Patients with T2D and heart disease have normal body mass index (BMI), suggesting that diabetes and obesity mediate cardiovascular change by different mechanisms. Changes in cardiac energy metabolism in lean diabetic patients during exercise stress have not been previously reported. Objectives We aimed to assess if there are BMI-associated differences in cardiac stress metabolism in patients with T2D. Methods Twenty-five overweight T2D patients (O-T2D) and eleven lean T2D patients (LnT2D), age- and ethnicity-matched and with no other comorbidities were studied. Patients were on oral hypoglycaemics only and were free of diabetes complications. Participants underwent rest and dobutamine stress phosphorus magnetic resonance spectroscopy (31P-MRS) and cardiovascular magnetic resonance (CMR) at 3T for the assessment of myocardial phosphocreatine to ATP ratio (PCr/ATP) as a measure of myocardial energetics, biventricular volumes, rest and stress left ventricular (LV) ejection fraction, global longitudinal shortening, and mitral in-flow E/A ratio for assessment of diastolic function and perfusion. Intravenous Dobutamine was administered at a dose of 10μg/kg/min, increasing at 90 second intervals up to a maximum of 40 μg/kg/min to achieve a target heart rate of 65% of the age-predicted maximal heart rate. Mean rate pressure product (RPP) was recorded at rest and stress. Heart rate was maintained at target for the duration of the 31P-MRS and stress CMR cine, mitral in-flow and perfusion acquisitions. Results The cardiac volumes, systolic or diastolic function and LV mass were similar between LnT2D and O-T2D. Although the O-T2D patients had a numerically lower rest and stress PCr/ATP ratio, this did not reach statistical significance. Resting PCr/ATP was reduced in LnT2D and O-T2D patients similarly. However, LnT2D showed a greater reduction in PCr/ATP (stress PCr/ATP LnT2D 1.51±0.2 vs O-T2D 1.41±0.25, p=0.02) despite similar increases in RPP. Stress myocardial blood flow (MBF) was also significantly lower in the O-T2D patients. There were significant correlations of BMI with LV mass (r=0.35, p=0.03); stress LVEF (r=−0.34, p=0.04); stress MBF stress (r=−0.53, p=0.001) and stress E/A (r=0.46, p=0.01) (figure 1). Conclusions Despite their better stress perfusion and similar glycaemic control, LnT2D show worse metabolic reserve characterised by more significant decrements in energetics in response to hemodynamic stress compared to overweight patients with T2D. Higher BMI correlates inversely with stress myocardial blood flow and with stress left ventricular ejection fraction. The presence of these subtle alterations in measures of stress metabolism and perfusion might signify a distinct metabolic phenotype of “lean diabetic cardiomyopathy”. Future studies are needed to further delineate alterations in cardiac energy metabolism in lean and overweight/obese type 2 diabetes patients, and their role in the development of cardiac dysfunction. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Wellcome TrustBHF

Prognostic risk stratification based on left ventricular mechanical dyssynchrony in patients at low or intermediate risk of major cardiac events using the J-ACCESS risk model.

There have been no reports on prognostic prediction and risk stratification based on stress phase bandwidth (SPBW), or a left ventricular (LV) mechanical dyssynchrony index, in patients with known or suspected stable coronary artery disease (CAD) at low or intermediate risk of major cardiac events (MCEs) using the J-ACCESS risk model. We retrospectively investigated 4,996 consecutive patients with known or suspected CAD who underwent rest 201Tl and stress 99mTc-tetrofosmin electrocardiogram (ECG)-gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) and followed up for 3 years to confirm their prognosis. MCE risk over 3 years was estimated using an equation based on that used in the J-ACCESS study. The composite endpoint was the onset of MCEs consisting of cardiac death, non-fatal myocardial infarction (MI), and severe heart failure requiring hospitalization. SPBW was calculated by phase analysis with the Heart Risk View-F software and its normal upper limit was set to 38°. Based on the estimated 3-year incidence of MCEs obtained from the J-ACCESS risk model, 4,123 of the 4,996 consecutive patients were classified as low (n = 2,653) or intermediate risk (n = 1,470) and they were analyzed for follow-up. During the follow-up, 153 patients experienced MCEs: cardiac death (n = 38), non-fatal MI (n = 45), and severe heart failure (n = 70). The results of the multivariate analysis showed age, estimated glomerular filtration rate (eGFR), stress LV ejection fraction, and stress SPBW to be independent predictors of MCEs. The actual 3-year MCE rate in patients at intermediate risk was significantly higher than in those at low risk (6.7% vs. 2.1%, P < 0.0001). However, the actual 3-year MCE rate in patients with abnormal SPBW (> 38°) was 4.0% and 9.2% in low- and intermediate-risk patients, respectively, which corresponded to intermediate and high risk. Kaplan-Meier analysis also showed significant risk stratification by normal SPBW values for both low- and intermediate-risk patients. LV mechanical dyssynchrony assessed with ECG-gated SPECT MPI is useful for risk stratification of known or suspected stable CAD patients at low or intermediate risk of MCEs and may help identify higher risk patients who could not be identified as being at risk based on J-ACCESS risk assessment.

Left ventricular ejection fraction, myocardial blood flow and hemodynamic variables in adenosine and regadenoson vasodilator 82-Rubidium PET

AimsIn most Rubidium-(Rb)-positron emission tomography (PET) studies, dipyridamole was used as vasodilator. The aim was to evaluate vasodilator PET left ventricular ejection fraction (LVEF), myocardial blood flow (MBF), hemodynamics, and the influence of adenosine and regadenoson on these variables. Methods and resultsConsecutive patients (N = 2299) with prior coronary artery disease (CAD) or no prior CAD undergoing adenosine/regadenoson 82Rb-PET were studied and compared according to CAD status and normal/abnormal PET (summed stress score 0-3 vs. ≥4). Rest and stress LVEF differed significantly depending on CAD status and scan results. In patients with no prior CAD, rest/stress LVEF were 68% and 72%, in patients with prior CAD 60% and 63%. LVEF during stress increased 5 ± 6% in normal compared to 1 ± 8% in abnormal PET (P<0.001). Global rest myocardial blood flow(rMBF), stress MBF(sMBF) and myocardial flow reserve (sMBF/rMBF) were significantly higher in no prior CAD patients compared to prior CAD patients(1.3 ± 0.5, 3.3 ± 0.9, 2.6 ± 0.8 and 1.2 ± 0.4, 2.6 ± 0.8, 2.4 ± 0.8 ml/g/min, respectively, P<0.001) and in normal versus abnormal scans, irrespective of CAD status(no prior CAD: 1.4 ± 0.5, 3.5 ± 0.8, 2.8 ± 0.8 and 1.2 ± 0.8, 2.5 ± 0.8, 2.2 ± 0.7; prior CAD: 1.3 ± 0.4, 3.1 ± 0.8, 2.7 ± 0.8 and 1.1 ± 0.4, 2.3 ± 0.7, 2.2 ± 0.7 ml/g/min, respectively, P<0.001). LVEF and hemodynamic values were similar for adenosine and regadenoson stress. Stress LVEF ≥70% excluded relevant ischemia (≥10%) with a negative predictive value (NPV) of 94% (CI 92-95%). ConclusionsRest/stress LVEF, LVEF reserve and MBF values are lower in abnormal compared to normal scans. Adenosine and regadenoson seem to have similar effect on stress LVEF, MBF and hemodynamics. A stress LVEF ≥70% has a high NPV to exclude relevant ischemia.

Optimization of the left ventricle ejection fraction estimate obtained during cardiac adenosine stress 82Rubidium-PET scanning: impact of different reconstruction protocols

BackgroundLeft ventricular ejection fraction (LVEF) estimation using adenosine stress myocardial perfusion imaging (MPI) can be challenging. The short half-life of adenosine and the guideline-recommended adenosine infusion stop during Rubidium-82 acquisition protocol may affect the accuracy and repeatability of the LVEF measures. MethodsThis study comprised 25 healthy volunteers (median age 23 years) who underwent repeat myocardial perfusion imaging (MPI) sessions employing Rubidium-82 PET/CT. A guideline-recommended reconstruction protocol was used for both rest and adenosine stress MPI (150-360 s post-radiotracer injection, standardrecon). For the stress MPI protocol, two additional reconstruction protocols were considered; one was employing 60 seconds data (150-210 seconds, shortfixed) and the other a dynamic frame window based on the bolus arrival of Rubidium-82 in the heart until 210 seconds (x-210 seconds, shortindividual). We report rest and stress LVEF, the LVEF reserve, and the LVEF reserve repeatability. ResultsDifferences in the LVEF assessments were observed between the guideline recommended and alternative reconstruction protocol (LVEF stress MPI: standardrecon = 68 ± 7%, shortfixed = 71 ± 7% (P = .08), shortindividual = 72 ± 7% (P = .04)), and the LVEF reserve was reduced for the guideline-recommended protocol (standardrecon = 7.8 ± 3.5, shortfixed = 10.1 ± 3.7, shortindividual = 10.5 ± 3.6, all P < .001). The best repeatability measures were obtained for the shortindividual protocol (repeatability: standardrecon = 45.3%, shortfixed = 41.2%, shortindividual = 31.7%). ConclusionWe recommend using the shortindividual reconstruction protocol for improved LVEF repeatability and reserve assessment. Alternatively, in centers with limited technical support we recommend the use of the shortfixed protocol.

Prognostic value of the normalization of left ventricular mechanical dyssynchrony after revascularization in patients with coronary artery disease.

There are no reports indicating a prognostic difference based on normalization of left ventricular (LV) mechanical dyssynchrony after revascularization in patients with coronary artery disease (CAD). We retrospectively investigated 596 patients who underwent rest 201Tl and stress 99mTc-tetrofosmin electrocardiogram-gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging. All patients had significant stenosis with ≥ 75% narrowing of the coronary arterial diameter detected by coronary angiography performed after confirmation of ≥ 5% ischemia by the SPECT. Patients underwent revascularization and thereafter were re-evaluated by the SPECT during a chronic phase, and followed-up to confirm their prognosis for ≥ 1year. The composite endpoint was the onset of major cardiac events (MCEs) consisting of cardiac death, non-fatal myocardial infarction (MI), unstable angina pectoris (UAP), and severe heart failure requiring hospitalization. The stress phase bandwidth (SPBW) was calculated by phase analysis with the Heart Risk View-F software and its normal upper limit was set to 38°. During the follow-up, 64 patients experienced MCEs: Cardiac death (n = 11), non-fatal MI (n = 5), UAP (n = 26), and severe heart failure (n = 22). The results of the multivariate analysis showed the ∆summed difference score %, ∆stress LV ejection fraction, and stress SPBW after revascularization to be independent predictors of MCEs. Additionally, the results of the multivariate logistic regression analysis showed the summed rest score%, summed difference score%, stress LV ejection fraction, and perfusion defects in the left circumflex artery region before revascularization to be independent predictors for normalized SPBW after revascularization. The prognosis of patients who normalized SPBW after revascularization was similar to that of patients with a normal SPBW before revascularization, while patients who did not normalize after revascularization had the worst prognosis. In conclusion, normalization of LV dyssynchrony after revascularization assessed with nuclear cardiology may help predict future MCEs and thus a useful indicator for predicting improved prognosis in patients with CAD.

Combination of myocardial perfusion imaging, left ventricle function parameters and coronary artery calcium score in risk evaluation in patients with diabetes mellitus.

Myocardial perfusion imaging (MPI) can be challenging in some cases of multi vessel involvement. Our aim was to examine specific group of patients with diabetes mellitus (DM), who did not have significant reversible ischaemia diagnosed on perfusion study itself, and asses additional value of functional parameters obtained from gated acquisition and added information from coronary artery calcium score (CACS). One hundred and seventy eight patients with a history of DM, with summed difference score (SDS)≤1, were included in the study. All patients underwent gated acquisition with recording of functional parameters and CACS evaluation. During the follow-up, cardiac events (CE) were recorded. During the median follow-up of 20.3 months there were 23 CE encountered. Optimal cut-off value for CACS to predict CE was found at 1427, higher values were significantly related to CE (P<0.001). Low stress left ventricular ejection fraction (LVEF) <45% and induced stress LVEF drop for 5% were also more frequent in CE group (P=0.001, P=0.008). Multivariable Cox analysis revealed low stress LVEF (P=0.001, HR=4.48, 95%CI 1.79-11.22), stress induced LVEF drop (P=0.017, HR 3.13, 95%CI 1.22-8.01) and high CACS (P<0.001, HR 10.52, 95%CI 4.32-25.63) as significant predictors of CE. Low stress LVEF under 45%, post-stress LVEF drop for more than 5% and CACS more than or equal to 1427 are significant predictors of CE in patients with DM, who did not have reversible ischemia detected on MPI single photon emission computed tomography (SPECT).

Abstract 12890: Prognostic Value of Relative Flow Reserve by Hybrid 13 N-ammonia Positron Emission Tomography/Magnetic Resonance Imaging in Coronary Artery Disease

Background: 13 N-ammonia PET has been used to evaluate myocardial blood flow (MBF) and coronary flow reserve (CFR) quantitatively. Relative flow reserve (RFR) was defined as the ratio of hyperemic MBF in a stenotic area to hyperemic MBF in a normal perfused area. The aim of this study was to examine the prognostic value of RFR in patients with coronary artery disease (CAD). Methods: We enrolled consecutive 66 patients with suspected CAD who underwent hybrid 13 N-ammonia PET/MRI. Under vasodilator stress with intravenous injection of adenosine, MBF and CFR were calculated from dynamic acquisition of 13 N-ammonia PET. RFR was calculated as the ratio of hyperemic MBF of a stenotic myocardial area to hyperemic MBF of a non-stenotic reference vascular territory. MRI images were simultaneously acquired with PET. Left ventricular ejection fraction (LVEF) was calculated from cine mode MRI. The end points were defined as composite of all-cause death, sustained ventricular arrhythmia, hospitalization due to decompensated heart failure and coronary artery revascularization. Results: Over the median follow-up of 3.6 ± 1.3 years, there were 22 (33.3%) adverse cardiac events. Kaplan-Meier analysis demonstrated lower event free rates in patients with CFR &lt; 2.0 (P &lt; 0.01, Figure A) and RFR &lt; 0.81 (P = 0.022, Figure B), but not in those with stress MBF &lt; 1.34 (P = 0.295) and stress LVEF &lt; 55% (P = 0.187). Univariate Cox regression analysis showed that abnormal RFR (&lt; 0.81) was significantly associated with adverse events (HR 3.72, 95% CI 1.21-18.01, P = 0.02). Conclusion: RFR is a useful marker to predict cardiac adverse events in patients with CAD. It would be an alternative approach to perform only stress scan without rest scan to reduce radiation exposure and scan time.

Updated results of hybrid transcatheter and minimally invasive left ventricular reconstruction for the treatment of ischemic cardiomyopathy

Abstract Aims Remodelling of the left ventricle (LV) after anterior myocardial infarction can result in a pathological increase in LV volume and reduction in LV ejection fraction (EF). We describe the updated results of an l hybrid transcatheter and minimally invasive surgical technique to reconstruct the negatively remodelled LV by myocardial scar plication and exclusion to rehape and reduce the excess volume, decrease the wall stress and increase LVEF. Methods and results Patients were considered eligible for the procedure when they presented with symptomatic heart failure (NYHA-class ≥II or more) and ischemic cardiomyopathy (EF&amp;lt;40%) after anterior myocardial infarction. All patients had a dilated LV with either a- or dyskinetic scar in the anteroseptal wall and/or apex of ≥50% transmurality. Hybrid transcatheter and minimally technique that relies on micro-anchoring technology is used to reconstruct the LV by plication of the fibrous scar. A series of internal and external micro anchors are brought together over a PEEK (poly-ether-ether-ketone) tether to form a longitudinal line of apposition between the LV free wall and the anterior septum from the mid-ventricle to the apex. Internal anchors are deployed by transcatheter technique on the right side of the ventricular septum through the right internal jugular vein. Paired external anchors are advanced through a left sided mini-thoracotomy and deployed on the LV epicardium (figure 1). A specialized Force Gauge is used to bring these “RV-LV” anchors together under measured compression forces. “LV-LV” anchor pairs through the LV apex beyond the distal tip of the RV complete the reconstruction. Between October 2016 and March 2021 28 patients (23 males, 5 females; mean age 61±12 years) were operated in a single Dutch centre. Procedural success was 100%. On average 2.3±0.8 anchor-pairs were used to reconstruct the LV. Comparing echocardiographic data pre- and directly postoperatively, LVEF increased from 33±8% to 44±10% (change +35%, P&amp;lt;0.0001) and LV-volumes decreased: LVESV 116 ml ± 52 ml to 69±39 ml (change −35%, P&amp;lt;0.0001) and LVEDV 170 ml ± 72 ml to 118±55 ml (change −29%, P&amp;lt;0.0001). Hospital mortality was 0%. Also no strokes occurred. Median duration of ICU–stay was 2 days (IQR 1–48 days) and median length of hospital stay was 7 days (IQR 5–61 days). Survival at 48 months was 84%. At latest follow-up, 9670% of surviving patients were in NYHA-class I-II compared to 18% preoperatively. Conclusions Hybrid transcatheter and minimally invasive LV reconstruction is a promising novel treatment option for patients with symptomatic heart failure and ischemic cardiomyopathy after anteroseptal myocardial infarction. Updated results demonstrate that the procedure is safe and results in significant improvement in EF, reduction in LV volumes and sustained improvement in heart failure symptoms. Funding Acknowledgement Type of funding sources: None. Figure 1

Influence of adenosine and regadenoson on left ventricular ejection fraction, myocardial blood flow and hemodynamics in vasodilator 82-Rubidium PET

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Most 82Rubidium-(Rb)-Positron emission tomography (PET) studies for myocardial perfusion, dipyridamole was used as vasodilator. Less data is available for adenosine and regadenoson. Purpose Therefore, the aim was to evaluate the influence of adenosine and regadenoson on left ventricular ejection fraction (LVEF), myocardial blood flow (MBF) and hemodynamics in vasodilator 82Rb-PET. Methods Consecutive patients (n = 2299) with suspected or known coronary artery disease (CAD) undergoing 82Rb-PET were studied and compared according to CAD status and normal/abnormal PET (abnormal defined as summed stress score ≥4). Differences between stress and rest values (LVEF, MBF, hemodynamics) were calculated. The threshold of stress LVEF able to exclude a relevant ischemia (as defined by ≥10% myocardium ischemic based on SDS score) was assessed. Results Rest and stress LVEF differed significantly depending on CAD status and scan results. In patients with suspected CAD, rest/stress LVEF were 68 ± 12% and 73 ± 12% (p &amp;lt; 0.001), in patients with prior CAD 60 ± 14% and 63 ± 15% (p &amp;lt; 0.001). LVEF during stress increased 5 ± 6% in normal compared to 1 ± 8% in abnormal PET (p &amp;lt; 0.001). Global rest MBF (rMBF), stress MBF (sMBF) and myocardial flow reserve (sMBF/rMBF) were significantly higher in suspected CAD patients compared to prior CAD patients (1.3 ± 0.5, 3.3 ± 0.9, 2.6 ± 0.8 and 1.2 ± 0.4, 2.6 ± 0.8, 2.4 ± 0.8 ml/g/min, respectively, p &amp;lt; 0.001), and in normal versus abnormal scans, irrespective of CAD status (no CAD: 1.4 ± 0.5, 3.5 ± 0.8, 2.8 ± 0.8 and 1.2 ± 0.8, 2.5 ± 0.8, 2.2 ± 0.7; known CAD: 1.3 ± 0.4, 3.1 ± 0.8, 2.7 ± 0.8 and 1.1 ± 0.4, 2.3 ± 0.7, 2.2 ± 0.7 ml/g/min, respectively, p &amp;lt; 0.001). LVEF and hemodynamic values were similar for adenosine and regadenoson stress. Stress LVEF ≥70% excluded relevant ischemia with a negative predictive value (NPV) of 94% (CI 92-95%). Conclusions Rest/stress LVEF, LVEF reserve and MBF values are lower in abnormal compared with normal scans. Adenosine and regadenoson seem to have similar effect on stress LVEF, MBF and hemodynamics. A stress LVEF ≥70% has a high NPV to exclude relevant ischemia.

Implications of transient ischaemic dilatation and impaired left ventricular ejection fraction reserve in patients with normal stress myocardial perfusion imaging and elevated coronary artery calcium

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Stress only (SO) instead of stress/rest single photon emission computed tomography myocardial perfusion imaging (MPI) is encouraged if perfusion and left ventricular ejection fraction (LVEF) are normal on SO images. Concurrent coronary artery calcium (CAC) scoring has also been recommended to assess atherosclerotic burden in ‘normal’ MPIs. However, the safety of SO MPI in high CAC cases is unclear as additional rest imaging may show transient ischaemic dilation (TID) and/or impaired LVEF reserve (iLVEFr) which are markers of severe coronary artery disease (CAD) and indicate ‘balanced ischaemia’. Purpose We aim to assess the incidence and outcomes of TID and iLVEFr in stress/rest MPIs with normal SO images and elevated CAC. Methods Retrospective analysis of all normal stress/rest MPIs performed between 1 March 2016 to 31 January 2017 with concurrently measured CAC &amp;gt;300. A SO protocol was not in place then. Prone post stress images were routinely done. Known CAD cases were excluded. A reader reviewed only the post stress supine/prone images and excluded cases ineligible for SO MPI (non-homogenous perfusion, LVEF ≤50%, abnormal wall motion). The remaining cases were assessed for TID (software derived TID ratio &amp;gt;1.20) and iLVEFr (stress LVEF – rest LVEF ≤-5%). Coronary angiography (CAG) and major adverse cardiac events (MACE, defined as cardiac death, non fatal myocardial infarction, revascularisation) within 24 months post MPI were traced using electronic medical records. Results There were 230 cases included (mean age 71, 56.5% male) of which 43 (18.7%) had TID and/or iLVEFr (9 TID, 22 iLVEFr, 12 both). There were no significant differences in baseline characteristics, CAC and aspirin/statin use between cases with or without TID and/or iLVEFr (Table 1). More patients in the TID and/or iLVEFr group underwent elective CAG [10 (23.3%) vs 10 (5.3%), p = 0.001] although CAG diagnosis of severe CAD (left main, 3-vessel or 2-vessel disease with proximal left anterior descending involvement) was not different [4/6 (40.0%) vs 5/10 (50.0%), p = 1.000). MACE was significantly higher in the TID and/or iLVEFr group [10 (23.3%) vs 16 (8.6%), p = 0.013], driven by higher elective revascularisation [8 (18.6%) vs 8 (4.3%), p = 0.003] with no significant differences in cardiac death or non fatal myocardial infarction (Table 2). Conclusion TID and/or iLVEFr is seen in &amp;lt;20% of cases eligible for SO MPI with high CAC, suggesting that routine rest scan in these cases exposes the majority to unnecessary radiation. Identification of TID and/or iLVEFr is associated with higher 24 month MACE, driven by higher elective revascularisation from more CAG referral. Approximately half of cases in each group had revascularisation for non severe CAD not typically associated with TID and/or impaired LVEFr. Overall cardiac death and non fatal myocardial infarction rates were low and not significantly different between groups with or without TID and/or iLVEFr.

A pilot study of 13N-ammonia cardiac PET imaging to assess subacute cardiotoxicity following adjuvant intensity-modulated radiotherapy for locally advanced breast cancer

Objective(1) Assess the feasibility of 13 N-ammonia cardiac PET (13 N-ammonia-PET) imaging in radiotherapy (RT) treatment position in locally-advanced breast cancer (LABC) patients. (2) Correlate pre−/post-RT changes in myocardial flow reserve (MFR) with the corresponding radiation heart dose. MethodsTen left-sided LABC patients undergoing Volumetric Modulated-Arc-Therapy (VMAT) to chest wall and regional lymph nodes underwent a rest/stress 13 N-ammonia-PET at baseline and (median) 13 months post-RT. Changes in cardiac functions and coronary artery Ca2+ scoring between baseline and follow-up were correlated with average RT dose to the myocardium,3 coronary territories, and 17 myocardial segments. ResultsEight (of 10) patients successfully completed the study. The average rest (stress) global MBF (ml.g-1.min-1) for baseline (follow-up) were 0.83 ± 0.25 (2.4 ± 0.79) and 0.92 ± 0.30 (2.76 ± 0.71), respectively. Differences in MBF, heart rate, blood pressure, and rate-pressure product (RPP) between baseline and follow-up were insignificant (P > 0.1).Strong (R = 0.79; P < 0.01) and moderate (R = 0.53; P = 0.37) correlation existed between MBF Rest and MBF Stress, and RPP respectively. Four patients showed a reduction in MFR of up to ~41% in follow-up studies, increasing to ~52% in myocardial segments close to high-radiation isodose lines in 5/8 patients. Agatston Ca + 2 scoring were zero in both baseline and follow-up in six patients; two patients exhibited mild increase in Ca + 2 on follow-ups (range:10–20).Rest and stress LVEF's were normal (>50) for all patients in both studies. ConclusionThe feasibility of 13 N-ammonia-PET imaging in treatment position of LABC patients was demonstrated. MFR at 1-year post-irradiation of the heart decreased in 50% of the patients. MFR may be a potential index for early detection of cardiotoxicity in BC patients receiving RT to the chest wall.

Risk Stratification of Cardiovascular Events in Very Elderly Patients with Known or Suspected Coronary Artery Disease Who Had Normal Single-photon Emission Computed Tomographic Myocardial Perfusion Imaging Findings

Objective We aimed to stratify the risk of major cardiovascular (MCV) events in Japanese patients with known or suspected coronary artery disease (CAD) who had normal single-photon emission computed tomographic myocardial perfusion imaging (SPECT MPI) findings and to compare the risk by generation. Methods This was a retrospective study. The composite endpoint was the occurrence of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. Patients The study subjects were 2,035 patients with normal SPECT MPI findings at baseline who had been followed up to confirm their prognosis for 3 years. The patients were categorized into 3 age groups: very elderly (≥80 years old, n=311), elderly (65-79 years old, n=1,097), and younger (<65 years old, n=542). Results During the follow-up, 68 patients experienced MCV events: cardiovascular death (n=29), non-fatal myocardial infarction (n=15), and non-fatal stroke (n=24). The MCV event rate was significantly higher in very elderly patients than in other patients. Multivariate predictors were age categories, the estimated glomerular filtration rate, atrial fibrillation, and stress left ventricular ejection fraction. The MCV event rate was 6.1% in very elderly patients. However, the MCV event rate in those with normal cardiac and renal functions without atrial fibrillation was 3.3%, which was similar to that in elderly and younger patients. Conclusion The MCV event rate was high in very elderly patients despite their normal SPECT MPI findings at baseline. Therefore, very elderly patients with multivariate risks should be carefully followed to avoid a poor prognosis.

The assessment of pressure-volume relationship during exercise stress echocardiography predicts left ventricular remodeling and eccentric hypertrophy in patients with chronic heart failure

BackgroundThe contractile response of patients with heart failure (HF) may be assessed by exercise stress echocardiography (ESE)-derived indexes. We sought to test whether ESE parameters are useful to identify the risk of adverse left ventricular (LV) remodeling in patients with chronic HF and reduced or mildly reduced LV ejection fraction (EF).MethodsWe enrolled 155 stabilized patients (age: 62 ± 11 years, 17% female, coronary artery disease 47%) with chronic HF, LV EF ≤50% and LV end-diastolic volume index > 75 ml/m2. All patients underwent a symptom-limited graded bicycle semi-supine ESE, with evaluation of peak stress LV EF, end-systolic pressure-volume relation (ESPVR, i.e. LV elastance) and cardiac power output to LV mass (CPOM). A complete echocardiographic study was performed at baseline and after 6 ± 3 months. Adverse LV remodeling was defined as the association of eccentric LV hypertrophy (LV mass: ≥115 g/m2 for male and ≥ 95 g/m2 for women, and relative wall thickness < 0.32) with an increase in LV end-systolic volume index ≥10% at six months.ResultsAdverse LV remodeling was detected in 34 (22%) patients. After adjustment for clinical, biochemical and echocardiographic data, peak ESPVR resulted in the most powerful independent predictor of adverse LV remodeling (OR: 12.5 [95% CI 4.5–33]; p < 0.0001) followed by ischemic aetiology (OR: 2.64 [95% 1.04–6.73]; p = 0.04).ConclusionIn patients with HF and reduced or mildly reduced EF, a compromised ESE-derived peak ESPVR, that reflects impaired LV contractility, resulted to be the most powerful predictor of adverse LV remodeling.

Risk stratification with vasodilator stress SPECT myocardial perfusion imaging in patients with elevated cardiac biomarkers

BackgroundAlthough the diagnostic accuracy and prognostic utility of vasodilator stress MPI have been well established in the non-acute setting, the efficacy of all of the vasodilator stressors in risk stratifying post-MI patients as well as the evaluation of cardiac troponin elevation of unclear etiology is not established. Accordingly, the aim of the present study was to investigate the prognostic efficacy of vasodilator stress MPI in the setting of elevated cardiac troponin to accurately risk stratify these higher-risk patients. MethodsAll patients from two tertiary centers, from 1/1/2010 through 12/31/2012, with elevated cardiac biomarkers within < 7 days and undergoing stress SPECT MPI testing were studied. Results of stress MPI were scored using a 17-segment model based on semiquantitative scoring as normal or abnormal (mild, moderate, or severe) using a total perfusion defect (TPD) of 0%, 1-10%, 10-20%, and > 20%. Mortality data through the year 2014 were obtained from the National Death Index, and survival analyses were performed. The primary endpoint was all-cause mortality with the secondary endpoint being cardiac mortality. ResultsA total of 503 patients were followed for an average of 33.6 ± 16.2 months, with a mean age of 69.3 years; 53.7% male; and a majority (88.7%) of them undergoing vasodilator stress. A significant increase in all-cause mortality was seen based on the severity of TPD results for all vasodilators (P < .0001) and regadenoson (P < .0001). Similar prognostic ability was seen for all-cause mortality. This association was maintained even after adjustment for cardiac risk factors, previous coronary disease, and troponin quartiles. MPI results (stress TPD and LVEF) added to traditional cardiac risk factors, and troponin values resulted in a significant incremental increase in the ability to predict all-cause and cardiac mortality, and stress TPD remained independently predictive for both all-cause and cardiac mortality in a multivariate model. ConclusionVasodilator stress (including regadenoson) MPI effectively risk stratifies patients with recently elevated cardiac biomarkers, with the increasing risk of mortality with the increasing severity of perfusion defects. It provides incremental prognostic value, in addition to clinical factors and degree of troponin elevation.