Background: While uncommon, normal stress SPECT myocardial perfusion imaging (MPI) can be seen in... more Background: While uncommon, normal stress SPECT myocardial perfusion imaging (MPI) can be seen in patients with high-risk coronary artery disease (CAD) by invasive coronary angiography (ICA). The predictors of high risk CAD in patients with normal SPECT-MPI have not been described. Methods: We studied 580 patients (age 64±12 years, 49% men) without known CAD who underwent stress gated SPECT-MPI [exercise (41%) or vasodilator (59%)] <2 months before ICA and had summed stress score (SSS) <4. High risk CAD was defined as 3 vessels with ≥70% stenosis, 2 vessels with ≥70% stenosis including proximal left anterior descending, or left main with ≥50% stenosis. Obstructive non-high risk CAD was defined by the presence of a ≥70% stenosis but without having other high risk criteria. Tenfold cross-validated receiver operating characteristic (ROC) estimates were obtained to assess the predictors of high risk CAD. Results: Forty-two subjects (7.2%) had high-risk CAD and 162 had obstructive non-high risk CAD. Variables associated with high risk CAD were pretest probability of CAD ≥66% (Odds ratio [OR] 3.63, 95% CI1.6-8.3, p=0.002), SSS>0 (OR7.46, 95% CI2.6-21.1, p<0.001) and abnormal TID (OR2.16, 95% CI1.0-4.5, p=0.044). When substituted for TID, EF change was also predictive of high risk CAD (OR0.93, 95% CI0.9-1.0, p=0.023). The prevalence of high risk CAD increased as the number of these predictors increased. In a sub-analysis of patients in whom quantitative
Journal of Pharmacology and Experimental Therapeutics, Oct 10, 2012
Background: Selective pharmacological activation of adenosine 1 receptor (A 1 R) is a promising n... more Background: Selective pharmacological activation of adenosine 1 receptor (A 1 R) is a promising new approach to achieve potent block of AV-nodal conduction without significant cardiovascular side effects. The purpose of the present study was to evaluate the cardiovascular profile of INO-8875, a highly-selective A 1 R agonist and to compare its properties with CVT-510 that has already been shown to induce negative dromotropic effect with minimal cardiovascular side effects in animals and in clinical studies. Methods: Dose-response experiments in the isolatedheart of rats were used to evaluate the functional selectivity of INO-8875 for slowing of AVnodal conduction. In vivo, ventilated adult rats were used to study the effects of INO-8875 on arterial blood pressure as well as on supraventricular electrophysiology (EP). Results: Ex vivo, INO-8875 (100nM-3μM) progressively prolonged AV-nodal conduction without reducing left ventricular function or coronary resistance. In vivo, INO-8875 up to a dose of 50 μg/Kg did not reduce the carotid arterial blood pressure (n=4). INO-8875 (1-50 μg/Kg) and CVT-510 (20 and 50 μg/Kg) both induced dose-dependent decrease of heart rate and atrial refractoriness, as well as slowing of AV-nodal conduction. However, compared to CVT-510 the activity of INO-8875 was more pronounced on AV-nodal function. INO-8875 exhibited a greater duration of action, lasting up to 2.5 hours post-dosing, whereas the effects of CV-510 dissipated over 1 hour (p<0.01). CONCLUSIONS: INO-8875 demonstrates functional properties of a highly selective A 1 R agonist. INO-8875 exhibits increased dromotropic effect and greater duration of action compared to CV-510.
Journal of the American College of Cardiology, Mar 1, 2013
Imaging predicTors of high risk coronary arTery disease in suBjecTs wiTh normal sTress myocardial... more Imaging predicTors of high risk coronary arTery disease in suBjecTs wiTh normal sTress myocardial perfusion specT Poster Contributions
Journal of the American College of Cardiology, Apr 1, 2014
We aimed to develop an objective method to predict which patients will undergo revascularization ... more We aimed to develop an objective method to predict which patients will undergo revascularization after myocardial perfusion SPECT (MPS) by integrating clinical data and quantitative image features by machine learning (ML). 713 rest 201Thallium/stress 99mTechnetium MPS studies with correlating
Objective-We aimed to improve the diagnostic accuracy of myocardial perfusion SPECT (MPS) by inte... more Objective-We aimed to improve the diagnostic accuracy of myocardial perfusion SPECT (MPS) by integrating clinical data and quantitative image features with machine learning (ML) algorithms. Methods-1,181 rest 201 Tl/stress 99m Tc-sestamibi dual-isotope MPS studies [713 consecutive cases with correlating invasive coronary angiography (ICA) and suspected coronary artery disease (CAD) and 468 with low likelihood (LLk) of CAD <5%] were considered. Cases with stenosis <70% by ICA and LLk of CAD were considered normal. Total stress perfusion deficit (TPD) for supine/prone data, stress/rest perfusion change, and transient ischemic dilatation were derived by automated perfusion quantification software and were combined with age, sex, and postelectrocardiogram CAD probability by a boosted ensemble ML algorithm (Logit-Boost). The diagnostic accuracy of the model for prediction of obstructive CAD ≥70% was compared to standard prone/supine quantification and to visual analysis by two experienced readers utilizing all imaging, quantitative, and clinical data. Tenfold stratified cross-validation was performed. Results-The diagnostic accuracy of ML (87.3% ± 2.1%) was similar to Expert 1 (86.0% ± 2.1%), but superior to combined supine/prone TPD (82.8% ± 2.2%) and Expert 2 (82.1% ± 2.2%) (P <.01). The receiver operator characteristic areas under curve for ML algorithm (0.94 ± 0.01) were higher than those for TPD and both visual readers (P <.001). The sensitivity of ML algorithm (78.9% ± 4.2%) was similar to TPD (75.6% ± 4.4%) and Expert 1 (76.3% ± 4.3%), but higher than that of Expert 2 (71.1% ± 4.6%), (P <.01). The specificity of ML algorithm (92.1% ± 2.2%) was similar to Expert 1 (91.4% ± 2.2%) and Expert 2 (88.3% ± 2.5%), but higher than TPD (86.8% ± 2.6%), (P <.01). Conclusion-ML significantly improves diagnostic performance of MPS by computational integration of quantitative perfusion and clinical data to the level rivaling expert analysis.
Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main fu... more Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): (1) the Deutsche Forschungsgemeinschaft; (2) Israel Ministry of Health Background Increased proximal aortic stiffness (PAS) is directly associated with cardiovascular risk. Likewise, metabolic syndrome (MS) and abdominal obesity are associated with cardiovascular risk. The direct association between MS determinants and PAS among a healthy population with abdominal obesity remains to be examined. Purpose To examine the association between MS determinants and PAS among healthy participants with abdominal obesity. Methods We utilized the cross-sectional baseline data of the DIRECT-PLUS study (clinicaltrials.gov NCT03020186), where we recruited healthy participants with abdominal obesity/dyslipidemia. Along with anthropometric measurements and blood tests, all participants underwent magnetic-resonance-imaging from which PAS we assessed by calculating the aortic arch pulse-wa...
European Heart Journal - Cardiovascular Imaging, 2019
The ventriculoarterial coupling (VAC) ratio, the ratio of arterial and ventricular elastance, is ... more The ventriculoarterial coupling (VAC) ratio, the ratio of arterial and ventricular elastance, is a measure of cardiovascular efficiency, and can be estimated non-invasively as the ratio of end-systolic volume to stroke volume. Little is known about the potential relationship between VAC and myocardial deformation. We used a previously-described cardiac magnetic resonance (CMR) method to assess VAC in a cohort of patients with functional mitral regurgitation (FMR), examined its relation to myocardial deformation variables, and compared with controls. Purpose: To calculate VAC and myocardial deformation variables in a cohort of patients with FMR, as compared with normal controls, using CMR, and assess for correlation. Methods: We analysed CMR data from a cohort of patients with FMR with a mitral regurgitation fraction >10% (n = 41), as well as controls with normal cardiac anatomy and function (n = 49). All subjects underwent CMR studies for clinical indications. 2D myocardial-tracking analyses were conducted using commercially available software. We calculated VAC (end-systolic volume/stroke volume), peak apical displacement (PAD), peak basal displacement (PBD), global longitudinal strain (GLS), longitudinal displacement (GLD) and ventricular twist. Results: The median age of the control cohort was 42.5 years, range 16-78 years, and 63% were male. The median age of the FMR cohort was 57 years old, range 23-84 years, and 66% were male (p = 0.0005 for age). Patients with FMR had significantly increased median VAC as compared to controls (1.85 vs 0.59, p < 0.0001, figure A), with a "dose-dependent" increase in VAC observed with increasing regurgitation fraction (p = 0.0145, R²=0.144, figure B). Twist, GLD and GLS correlated negatively with VAC in the FMR cohort, with GLS showing the strongest correlation (p < 0.0001, R²=0.59, figure C), but only GLS correlated with VAC in the control cohort. There was no significant correlation between VAC and PAD or PBD, and there was no significant correlation between VAC and age. Conclusion: Although the control cohort was significantly younger, the absence of a correlation between VAC and age in this study suggest that the results should not be affected by this. We found that patients with FMR demonstrate cardiovascular inefficiency as evidenced by increased VAC ratio and this correlates with myocardial deformation parameters, in particular GLS. We found a relationship between GLS and VAC in both FMR and control subjects. Further study into the relationship between these parameters is warranted, in particular to assess the possible prognostic implications.
In severe AS patients, the heart remodels to adapt to the increased afterload leading to LV hyper... more In severe AS patients, the heart remodels to adapt to the increased afterload leading to LV hypertrophy, ultimately resulting in myocardial fibrosis. Timeless AVR prevents replacement fibrosis progression, but how the quantity of myocardial fibrosis affects the remodelling after surgery limiting its potential benefits is unknown. Objectives: To evaluate the impact of late-gadolinium enhancement (LGE) by CMR imaging on indexed LV mass (LVMi) regression 6 months after AVR. Methods: Prospective cohort of 62 severe AS patients with preserved LVEF referred for AVR that underwent CMR at baseline. We performed a paired analysis with those who also undergone CMR at 6-months after AVR. LGE scan protocol was performed to identify segments of replacement fibrosis. LVMi regression was defined as reduction of LVMi measured by CMR above 10% at 6-month follow-up (FUP). Comparisons were made between patients with and without LVMi regression. Results: 32 patients had paired CMR at baseline and at 6-month follow-up (age 70±8.3 years; 66%males). Overall obstructive CAD (more than 1 stenosis higher than 70%) was observed in 9 patients (28.1%). A bioprosthesis was implanted in 25 patients (78.1%). An additional CABG was performed in 7 (21.9%) patients. After surgery, a significant reduction in the mean transvalvular gradient was observed (49.4±11.6mmHg to 9.6±4.0mmHg; p<0.001). LVMi decreased from91±22.0 g/m 2 at baseline to 70±15.9 g/m 2 at 6 months FUP (P<0.001),as mass/volume ratio from1.09±0.28 to 0.98±0.19 (p=0.037). LV volumes decreased after surgery (LVEDVi 86.0±25.6 mL/m 2 vs. 73.3±16.3 mL/m 2 , P=0.009; LVESVi 32.5±17.5 mL/m 2 vs. 27.0±10.6 mL/m 2 , p=0.076), and no change was observed in LVEF (62.4±8.0%to 62.4±7.1%, p=0.986). LVMi regression occurred in 78% of patients. Patients with LVMi regression had higher baseline LVMi (95.2±22.18 vs. 74.0±11.4, p=0.022), lower LV volumes at FUP (LVEDVi 69.8±15.1 vs. 85.8±14.8mL/m 2 , p=0.019; LVESV46.4±16.8 vs. 63.7±22.0mL/m 2 , p=0.032), higher LVEF (63.7±6.5 vs. 57.5±7.1, p=0.040). No differences were found in the distribution or number of segments affected by LGE at baseline and the occurrence of the endpoint LVMi regression (mean 1.13 (6.6%) vs. 1.00 (5.9%), P=0.830). At 6 months after surgery, the extension of late enhancement remained unchanged (p=0.180). After adjustment for age, gender, presence of CAD, baseline LVMi and gradient change after surgery, the number of segments with LGE was not associated with LVMi regression (OR0.39, 95% CI 0.10-1.47, p=0.167). The only factor associated with LVMi regression was baseline LVMi. Conclusions: After 6 months from aortic valve replacement for severe aortic stenosis, significant LVM regression occurs. The extension and pattern of distribution of baseline LGE remained unchanged at follow up. Importantly, the presence of LGE was not associated with a negative impact in preventing LV mass regression.
Background: Peripartum cardiomyopathy (PPCM) is a rare but potentially devastating complication o... more Background: Peripartum cardiomyopathy (PPCM) is a rare but potentially devastating complication of pregnancy. Although the pathophysiology of PPCM is not fully understood, there are known risk factors for developing PPCM, which are maternal and gestation related. In the first wave of the coronavirus disease 2019 (COVID-19) pandemic, we witnessed an elevated incidence of PPCM among COVID-19 survivors. Objectives: To present a single-center case series of three patients diagnosed with peripartum cardiomyopathy after recovered from COVID-19 during the index pregnancy. Methods: In this single center case study, all patients diagnosed with PPCM at our institute during the examined time frame were included. Electronic medical records were studied. Results: Three patients previously diagnosed with asymptomatic or mildly symptomatic COVID-19 disease during pregnancy presented with PPCM before or shortly after delivery. Patients underwent testing to rule out residual COVID-19 myocarditis, were treated pharmacologically and with wearable defibrillators as needed, and were examined in follow-up 1-9 months after delivery. Conclusions: Residual endothelial damage due to COVID-19 disease, even if originally mild in presentation, could predispose pregnant patients to PPCM and should be considered as a risk factor when assessing patients with new onset symptoms of heart failure. Further research is needed to confirm this hypothesis and fully determine the underlying pathophysiology. These preliminary findings warrant a high index of suspicion for PPCM in COVID-19 recoverers.
Objective We evaluated the performance of manual measures of coronary plaque volumes and atherosc... more Objective We evaluated the performance of manual measures of coronary plaque volumes and atherosclerotic plaque features from coronary CT angiography (CTA), using intravascular ultrasound (IVUS) as the reference. Methods Thirty individual coronary plaques with suitable fiduciary markers were identified. Plaque volumes on coronary CTA were manually quantified by two observers and compared to IVUS plaque volumes as interpreted by an independent laboratory. The presence of adverse plaque characteristics-low attenuation plaque (LAP), positive remodelling (PR) and spotty calcification (SC)-on coronary CTA was evaluated and compared to IVUS. Results High correlation in plaque volumes was detected between observers (r=0.94, P<0.0001; 95 % limits of agreement <48.7 mm 3 , bias 6.6 mm 3). Excellent correlation (r=0.95, P<0.0001) was noted in plaque volume between independent observers and IVUS (95 % limits of agreement <40.6 mm 3 , bias −4.4 mm 3) and did not differ from IVUS (105.0±56.7 vs. 109.4±60.7 mm 3 , P= 0.2). The frequency of LAP (10 % vs. 17 %), PR (7 % vs. 10 %) and SC (27 % vs. 33 %) was similar between coronary CTA and IVUS (all P=NS). Conclusions Plaque volume on coronary CTA determined by manual methods demonstrates high correlation and modest agreement to IVUS. Further, coronary CTA demonstrates high accuracy for the identification of adverse plaque characteristics, including LAP, PR and SC. Key Points • Coronary CT angiography is a non-invasive test that enables coronary plaque assessment • Plaque quantification by coronary CT angiography correlates well with intravascular ultrasound findings • Coronary CT angiography can identify adverse plaque characteristics Keywords Coronary plaque. Coronary CT angiography. Intravascular ultrasound. Quantification. Coronary artery disease Abbreviations Coronary CTA Coronary computed tomographic angiography ICA Invasive coronary angiography Electronic supplementary material The online version of this article
Journal of Cardiovascular Pharmacology and Therapeutics, 2022
Introduction: Studies suggest that non-alcoholic fatty liver disease (NAFLD) is associated with a... more Introduction: Studies suggest that non-alcoholic fatty liver disease (NAFLD) is associated with an independent risk of cardiovascular disease (CVD). We utilized a large cohort of patients undergoing myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) to determine the association between alanine aminotransferase (ALT) as a surrogate marker for presumed NAFLD, and the presence of myocardial ischemia and mortality. Methods: We retrospectively assessed SPECT-MPI results and medical records of individuals evaluated between 1997 and 2008. We excluded patients with known non-NAFLD liver diseases, ALT values <17 or >340 U/L and absent liver tests. Elevated ALT cases were classified as presumed NAFLD. The primary endpoint was abnormal SPECT-MPI. Secondary endpoints included cardiac death, acute myocardial infarction and all-cause mortality. Results: Of 26,034 patients who underwent SPECT-MPI, 11,324 met inclusion criteria. 1635 (14.4%) patients ha...
AIM To evaluate insufficient rotational movement of the left ventricle (LV) as a potential novel ... more AIM To evaluate insufficient rotational movement of the left ventricle (LV) as a potential novel mechanism for functional regurgitation of the mitral valve (FMR). METHODS AND RESULTS We compared reference subjects and patients with LV dysfunction (LVD, ejection fraction EF < 50%) with and without FMR (regurgitant volume RVol>10 mL). Subjects without structural mitral valve pathology undergoing cardiac MRI were evaluated. Delayed enhancement, global LV remodeling parameters, systolic twist and torsion were measured (using manual and novel automated cardiac MRI tissue-tracking). The study included 117 subjects with mean ± SD age 50.4 ± 17.8 years, of which 30.8% were female. Compared to subjects with LVD without FMR (n = 31), those with FMR (n = 37) had similar clinical characteristics, diagnoses, delayed enhancement, EF, and longitudinal strain. Subjects with FMR had significantly larger left ventricles (EDVi:136.6 ± 41.8 vs 97.5 ± 26.2 mL/m, p < 0.0001) with wider separation between papillary muscles (21.1 ± 7.6 vs 17.2 ± 5.7 mm, p = 0.023). Notably, they had lower apical (p < 0.0001) but not basal rotation and lower peak systolic twist (3.1 ± 2.4° vs 5.5 ± 2.5°, p < 0.0001) and torsion (0.56 ± 0.38°/cm vs 0.88 ± 0.52°/cm, p = 0.004). In a multivariate model for RVol including age, gender, twist, LV end-diastolic volume, sphericity index and separation between papillary muscles, only gender, volume and twist were significant. Twist was the most powerful correlate (beta -2.23, CI -3.26 to -1.23 p < 0.001). In patients with FMR, peak systolic twist negatively correlates with RVol (r = -0.73, p < 0.0001). CONCLUSION Reduced rotational systolic LV motion is significantly and independently associated with RVol among patients with FMR, suggesting a novel pathophysiological mechanism and a potential therapeutic target.
This file contains supplementary material of the manuscript "Diet-induced fasting ghrelin el... more This file contains supplementary material of the manuscript "Diet-induced fasting ghrelin elevation reflects the recovery of insulin sensitivity and visceral adiposity regression"
Supplemental Material, sj-tiff-1-cpt-10.1177_10742484221074585 for The Association of Alanine Ami... more Supplemental Material, sj-tiff-1-cpt-10.1177_10742484221074585 for The Association of Alanine Aminotransferase Levels With Myocardial Perfusion Imaging and Cardiovascular Morbidity by David Yardeni, Ronen Toledano, Victor Novack, Aryeh Shalev, Arik Wolak, Yaron Rotman and Ohad Etzion in Journal of Cardiovascular Pharmacology and Therapeutics
Supplemental Material, sj-tiff-2-cpt-10.1177_10742484221074585 for The Association of Alanine Ami... more Supplemental Material, sj-tiff-2-cpt-10.1177_10742484221074585 for The Association of Alanine Aminotransferase Levels With Myocardial Perfusion Imaging and Cardiovascular Morbidity by David Yardeni, Ronen Toledano, Victor Novack, Aryeh Shalev, Arik Wolak, Yaron Rotman and Ohad Etzion in Journal of Cardiovascular Pharmacology and Therapeutics
Background: While uncommon, normal stress SPECT myocardial perfusion imaging (MPI) can be seen in... more Background: While uncommon, normal stress SPECT myocardial perfusion imaging (MPI) can be seen in patients with high-risk coronary artery disease (CAD) by invasive coronary angiography (ICA). The predictors of high risk CAD in patients with normal SPECT-MPI have not been described. Methods: We studied 580 patients (age 64±12 years, 49% men) without known CAD who underwent stress gated SPECT-MPI [exercise (41%) or vasodilator (59%)] <2 months before ICA and had summed stress score (SSS) <4. High risk CAD was defined as 3 vessels with ≥70% stenosis, 2 vessels with ≥70% stenosis including proximal left anterior descending, or left main with ≥50% stenosis. Obstructive non-high risk CAD was defined by the presence of a ≥70% stenosis but without having other high risk criteria. Tenfold cross-validated receiver operating characteristic (ROC) estimates were obtained to assess the predictors of high risk CAD. Results: Forty-two subjects (7.2%) had high-risk CAD and 162 had obstructive non-high risk CAD. Variables associated with high risk CAD were pretest probability of CAD ≥66% (Odds ratio [OR] 3.63, 95% CI1.6-8.3, p=0.002), SSS>0 (OR7.46, 95% CI2.6-21.1, p<0.001) and abnormal TID (OR2.16, 95% CI1.0-4.5, p=0.044). When substituted for TID, EF change was also predictive of high risk CAD (OR0.93, 95% CI0.9-1.0, p=0.023). The prevalence of high risk CAD increased as the number of these predictors increased. In a sub-analysis of patients in whom quantitative
Journal of Pharmacology and Experimental Therapeutics, Oct 10, 2012
Background: Selective pharmacological activation of adenosine 1 receptor (A 1 R) is a promising n... more Background: Selective pharmacological activation of adenosine 1 receptor (A 1 R) is a promising new approach to achieve potent block of AV-nodal conduction without significant cardiovascular side effects. The purpose of the present study was to evaluate the cardiovascular profile of INO-8875, a highly-selective A 1 R agonist and to compare its properties with CVT-510 that has already been shown to induce negative dromotropic effect with minimal cardiovascular side effects in animals and in clinical studies. Methods: Dose-response experiments in the isolatedheart of rats were used to evaluate the functional selectivity of INO-8875 for slowing of AVnodal conduction. In vivo, ventilated adult rats were used to study the effects of INO-8875 on arterial blood pressure as well as on supraventricular electrophysiology (EP). Results: Ex vivo, INO-8875 (100nM-3μM) progressively prolonged AV-nodal conduction without reducing left ventricular function or coronary resistance. In vivo, INO-8875 up to a dose of 50 μg/Kg did not reduce the carotid arterial blood pressure (n=4). INO-8875 (1-50 μg/Kg) and CVT-510 (20 and 50 μg/Kg) both induced dose-dependent decrease of heart rate and atrial refractoriness, as well as slowing of AV-nodal conduction. However, compared to CVT-510 the activity of INO-8875 was more pronounced on AV-nodal function. INO-8875 exhibited a greater duration of action, lasting up to 2.5 hours post-dosing, whereas the effects of CV-510 dissipated over 1 hour (p<0.01). CONCLUSIONS: INO-8875 demonstrates functional properties of a highly selective A 1 R agonist. INO-8875 exhibits increased dromotropic effect and greater duration of action compared to CV-510.
Journal of the American College of Cardiology, Mar 1, 2013
Imaging predicTors of high risk coronary arTery disease in suBjecTs wiTh normal sTress myocardial... more Imaging predicTors of high risk coronary arTery disease in suBjecTs wiTh normal sTress myocardial perfusion specT Poster Contributions
Journal of the American College of Cardiology, Apr 1, 2014
We aimed to develop an objective method to predict which patients will undergo revascularization ... more We aimed to develop an objective method to predict which patients will undergo revascularization after myocardial perfusion SPECT (MPS) by integrating clinical data and quantitative image features by machine learning (ML). 713 rest 201Thallium/stress 99mTechnetium MPS studies with correlating
Objective-We aimed to improve the diagnostic accuracy of myocardial perfusion SPECT (MPS) by inte... more Objective-We aimed to improve the diagnostic accuracy of myocardial perfusion SPECT (MPS) by integrating clinical data and quantitative image features with machine learning (ML) algorithms. Methods-1,181 rest 201 Tl/stress 99m Tc-sestamibi dual-isotope MPS studies [713 consecutive cases with correlating invasive coronary angiography (ICA) and suspected coronary artery disease (CAD) and 468 with low likelihood (LLk) of CAD <5%] were considered. Cases with stenosis <70% by ICA and LLk of CAD were considered normal. Total stress perfusion deficit (TPD) for supine/prone data, stress/rest perfusion change, and transient ischemic dilatation were derived by automated perfusion quantification software and were combined with age, sex, and postelectrocardiogram CAD probability by a boosted ensemble ML algorithm (Logit-Boost). The diagnostic accuracy of the model for prediction of obstructive CAD ≥70% was compared to standard prone/supine quantification and to visual analysis by two experienced readers utilizing all imaging, quantitative, and clinical data. Tenfold stratified cross-validation was performed. Results-The diagnostic accuracy of ML (87.3% ± 2.1%) was similar to Expert 1 (86.0% ± 2.1%), but superior to combined supine/prone TPD (82.8% ± 2.2%) and Expert 2 (82.1% ± 2.2%) (P <.01). The receiver operator characteristic areas under curve for ML algorithm (0.94 ± 0.01) were higher than those for TPD and both visual readers (P <.001). The sensitivity of ML algorithm (78.9% ± 4.2%) was similar to TPD (75.6% ± 4.4%) and Expert 1 (76.3% ± 4.3%), but higher than that of Expert 2 (71.1% ± 4.6%), (P <.01). The specificity of ML algorithm (92.1% ± 2.2%) was similar to Expert 1 (91.4% ± 2.2%) and Expert 2 (88.3% ± 2.5%), but higher than TPD (86.8% ± 2.6%), (P <.01). Conclusion-ML significantly improves diagnostic performance of MPS by computational integration of quantitative perfusion and clinical data to the level rivaling expert analysis.
Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main fu... more Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): (1) the Deutsche Forschungsgemeinschaft; (2) Israel Ministry of Health Background Increased proximal aortic stiffness (PAS) is directly associated with cardiovascular risk. Likewise, metabolic syndrome (MS) and abdominal obesity are associated with cardiovascular risk. The direct association between MS determinants and PAS among a healthy population with abdominal obesity remains to be examined. Purpose To examine the association between MS determinants and PAS among healthy participants with abdominal obesity. Methods We utilized the cross-sectional baseline data of the DIRECT-PLUS study (clinicaltrials.gov NCT03020186), where we recruited healthy participants with abdominal obesity/dyslipidemia. Along with anthropometric measurements and blood tests, all participants underwent magnetic-resonance-imaging from which PAS we assessed by calculating the aortic arch pulse-wa...
European Heart Journal - Cardiovascular Imaging, 2019
The ventriculoarterial coupling (VAC) ratio, the ratio of arterial and ventricular elastance, is ... more The ventriculoarterial coupling (VAC) ratio, the ratio of arterial and ventricular elastance, is a measure of cardiovascular efficiency, and can be estimated non-invasively as the ratio of end-systolic volume to stroke volume. Little is known about the potential relationship between VAC and myocardial deformation. We used a previously-described cardiac magnetic resonance (CMR) method to assess VAC in a cohort of patients with functional mitral regurgitation (FMR), examined its relation to myocardial deformation variables, and compared with controls. Purpose: To calculate VAC and myocardial deformation variables in a cohort of patients with FMR, as compared with normal controls, using CMR, and assess for correlation. Methods: We analysed CMR data from a cohort of patients with FMR with a mitral regurgitation fraction >10% (n = 41), as well as controls with normal cardiac anatomy and function (n = 49). All subjects underwent CMR studies for clinical indications. 2D myocardial-tracking analyses were conducted using commercially available software. We calculated VAC (end-systolic volume/stroke volume), peak apical displacement (PAD), peak basal displacement (PBD), global longitudinal strain (GLS), longitudinal displacement (GLD) and ventricular twist. Results: The median age of the control cohort was 42.5 years, range 16-78 years, and 63% were male. The median age of the FMR cohort was 57 years old, range 23-84 years, and 66% were male (p = 0.0005 for age). Patients with FMR had significantly increased median VAC as compared to controls (1.85 vs 0.59, p < 0.0001, figure A), with a "dose-dependent" increase in VAC observed with increasing regurgitation fraction (p = 0.0145, R²=0.144, figure B). Twist, GLD and GLS correlated negatively with VAC in the FMR cohort, with GLS showing the strongest correlation (p < 0.0001, R²=0.59, figure C), but only GLS correlated with VAC in the control cohort. There was no significant correlation between VAC and PAD or PBD, and there was no significant correlation between VAC and age. Conclusion: Although the control cohort was significantly younger, the absence of a correlation between VAC and age in this study suggest that the results should not be affected by this. We found that patients with FMR demonstrate cardiovascular inefficiency as evidenced by increased VAC ratio and this correlates with myocardial deformation parameters, in particular GLS. We found a relationship between GLS and VAC in both FMR and control subjects. Further study into the relationship between these parameters is warranted, in particular to assess the possible prognostic implications.
In severe AS patients, the heart remodels to adapt to the increased afterload leading to LV hyper... more In severe AS patients, the heart remodels to adapt to the increased afterload leading to LV hypertrophy, ultimately resulting in myocardial fibrosis. Timeless AVR prevents replacement fibrosis progression, but how the quantity of myocardial fibrosis affects the remodelling after surgery limiting its potential benefits is unknown. Objectives: To evaluate the impact of late-gadolinium enhancement (LGE) by CMR imaging on indexed LV mass (LVMi) regression 6 months after AVR. Methods: Prospective cohort of 62 severe AS patients with preserved LVEF referred for AVR that underwent CMR at baseline. We performed a paired analysis with those who also undergone CMR at 6-months after AVR. LGE scan protocol was performed to identify segments of replacement fibrosis. LVMi regression was defined as reduction of LVMi measured by CMR above 10% at 6-month follow-up (FUP). Comparisons were made between patients with and without LVMi regression. Results: 32 patients had paired CMR at baseline and at 6-month follow-up (age 70±8.3 years; 66%males). Overall obstructive CAD (more than 1 stenosis higher than 70%) was observed in 9 patients (28.1%). A bioprosthesis was implanted in 25 patients (78.1%). An additional CABG was performed in 7 (21.9%) patients. After surgery, a significant reduction in the mean transvalvular gradient was observed (49.4±11.6mmHg to 9.6±4.0mmHg; p<0.001). LVMi decreased from91±22.0 g/m 2 at baseline to 70±15.9 g/m 2 at 6 months FUP (P<0.001),as mass/volume ratio from1.09±0.28 to 0.98±0.19 (p=0.037). LV volumes decreased after surgery (LVEDVi 86.0±25.6 mL/m 2 vs. 73.3±16.3 mL/m 2 , P=0.009; LVESVi 32.5±17.5 mL/m 2 vs. 27.0±10.6 mL/m 2 , p=0.076), and no change was observed in LVEF (62.4±8.0%to 62.4±7.1%, p=0.986). LVMi regression occurred in 78% of patients. Patients with LVMi regression had higher baseline LVMi (95.2±22.18 vs. 74.0±11.4, p=0.022), lower LV volumes at FUP (LVEDVi 69.8±15.1 vs. 85.8±14.8mL/m 2 , p=0.019; LVESV46.4±16.8 vs. 63.7±22.0mL/m 2 , p=0.032), higher LVEF (63.7±6.5 vs. 57.5±7.1, p=0.040). No differences were found in the distribution or number of segments affected by LGE at baseline and the occurrence of the endpoint LVMi regression (mean 1.13 (6.6%) vs. 1.00 (5.9%), P=0.830). At 6 months after surgery, the extension of late enhancement remained unchanged (p=0.180). After adjustment for age, gender, presence of CAD, baseline LVMi and gradient change after surgery, the number of segments with LGE was not associated with LVMi regression (OR0.39, 95% CI 0.10-1.47, p=0.167). The only factor associated with LVMi regression was baseline LVMi. Conclusions: After 6 months from aortic valve replacement for severe aortic stenosis, significant LVM regression occurs. The extension and pattern of distribution of baseline LGE remained unchanged at follow up. Importantly, the presence of LGE was not associated with a negative impact in preventing LV mass regression.
Background: Peripartum cardiomyopathy (PPCM) is a rare but potentially devastating complication o... more Background: Peripartum cardiomyopathy (PPCM) is a rare but potentially devastating complication of pregnancy. Although the pathophysiology of PPCM is not fully understood, there are known risk factors for developing PPCM, which are maternal and gestation related. In the first wave of the coronavirus disease 2019 (COVID-19) pandemic, we witnessed an elevated incidence of PPCM among COVID-19 survivors. Objectives: To present a single-center case series of three patients diagnosed with peripartum cardiomyopathy after recovered from COVID-19 during the index pregnancy. Methods: In this single center case study, all patients diagnosed with PPCM at our institute during the examined time frame were included. Electronic medical records were studied. Results: Three patients previously diagnosed with asymptomatic or mildly symptomatic COVID-19 disease during pregnancy presented with PPCM before or shortly after delivery. Patients underwent testing to rule out residual COVID-19 myocarditis, were treated pharmacologically and with wearable defibrillators as needed, and were examined in follow-up 1-9 months after delivery. Conclusions: Residual endothelial damage due to COVID-19 disease, even if originally mild in presentation, could predispose pregnant patients to PPCM and should be considered as a risk factor when assessing patients with new onset symptoms of heart failure. Further research is needed to confirm this hypothesis and fully determine the underlying pathophysiology. These preliminary findings warrant a high index of suspicion for PPCM in COVID-19 recoverers.
Objective We evaluated the performance of manual measures of coronary plaque volumes and atherosc... more Objective We evaluated the performance of manual measures of coronary plaque volumes and atherosclerotic plaque features from coronary CT angiography (CTA), using intravascular ultrasound (IVUS) as the reference. Methods Thirty individual coronary plaques with suitable fiduciary markers were identified. Plaque volumes on coronary CTA were manually quantified by two observers and compared to IVUS plaque volumes as interpreted by an independent laboratory. The presence of adverse plaque characteristics-low attenuation plaque (LAP), positive remodelling (PR) and spotty calcification (SC)-on coronary CTA was evaluated and compared to IVUS. Results High correlation in plaque volumes was detected between observers (r=0.94, P<0.0001; 95 % limits of agreement <48.7 mm 3 , bias 6.6 mm 3). Excellent correlation (r=0.95, P<0.0001) was noted in plaque volume between independent observers and IVUS (95 % limits of agreement <40.6 mm 3 , bias −4.4 mm 3) and did not differ from IVUS (105.0±56.7 vs. 109.4±60.7 mm 3 , P= 0.2). The frequency of LAP (10 % vs. 17 %), PR (7 % vs. 10 %) and SC (27 % vs. 33 %) was similar between coronary CTA and IVUS (all P=NS). Conclusions Plaque volume on coronary CTA determined by manual methods demonstrates high correlation and modest agreement to IVUS. Further, coronary CTA demonstrates high accuracy for the identification of adverse plaque characteristics, including LAP, PR and SC. Key Points • Coronary CT angiography is a non-invasive test that enables coronary plaque assessment • Plaque quantification by coronary CT angiography correlates well with intravascular ultrasound findings • Coronary CT angiography can identify adverse plaque characteristics Keywords Coronary plaque. Coronary CT angiography. Intravascular ultrasound. Quantification. Coronary artery disease Abbreviations Coronary CTA Coronary computed tomographic angiography ICA Invasive coronary angiography Electronic supplementary material The online version of this article
Journal of Cardiovascular Pharmacology and Therapeutics, 2022
Introduction: Studies suggest that non-alcoholic fatty liver disease (NAFLD) is associated with a... more Introduction: Studies suggest that non-alcoholic fatty liver disease (NAFLD) is associated with an independent risk of cardiovascular disease (CVD). We utilized a large cohort of patients undergoing myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) to determine the association between alanine aminotransferase (ALT) as a surrogate marker for presumed NAFLD, and the presence of myocardial ischemia and mortality. Methods: We retrospectively assessed SPECT-MPI results and medical records of individuals evaluated between 1997 and 2008. We excluded patients with known non-NAFLD liver diseases, ALT values <17 or >340 U/L and absent liver tests. Elevated ALT cases were classified as presumed NAFLD. The primary endpoint was abnormal SPECT-MPI. Secondary endpoints included cardiac death, acute myocardial infarction and all-cause mortality. Results: Of 26,034 patients who underwent SPECT-MPI, 11,324 met inclusion criteria. 1635 (14.4%) patients ha...
AIM To evaluate insufficient rotational movement of the left ventricle (LV) as a potential novel ... more AIM To evaluate insufficient rotational movement of the left ventricle (LV) as a potential novel mechanism for functional regurgitation of the mitral valve (FMR). METHODS AND RESULTS We compared reference subjects and patients with LV dysfunction (LVD, ejection fraction EF < 50%) with and without FMR (regurgitant volume RVol>10 mL). Subjects without structural mitral valve pathology undergoing cardiac MRI were evaluated. Delayed enhancement, global LV remodeling parameters, systolic twist and torsion were measured (using manual and novel automated cardiac MRI tissue-tracking). The study included 117 subjects with mean ± SD age 50.4 ± 17.8 years, of which 30.8% were female. Compared to subjects with LVD without FMR (n = 31), those with FMR (n = 37) had similar clinical characteristics, diagnoses, delayed enhancement, EF, and longitudinal strain. Subjects with FMR had significantly larger left ventricles (EDVi:136.6 ± 41.8 vs 97.5 ± 26.2 mL/m, p < 0.0001) with wider separation between papillary muscles (21.1 ± 7.6 vs 17.2 ± 5.7 mm, p = 0.023). Notably, they had lower apical (p < 0.0001) but not basal rotation and lower peak systolic twist (3.1 ± 2.4° vs 5.5 ± 2.5°, p < 0.0001) and torsion (0.56 ± 0.38°/cm vs 0.88 ± 0.52°/cm, p = 0.004). In a multivariate model for RVol including age, gender, twist, LV end-diastolic volume, sphericity index and separation between papillary muscles, only gender, volume and twist were significant. Twist was the most powerful correlate (beta -2.23, CI -3.26 to -1.23 p < 0.001). In patients with FMR, peak systolic twist negatively correlates with RVol (r = -0.73, p < 0.0001). CONCLUSION Reduced rotational systolic LV motion is significantly and independently associated with RVol among patients with FMR, suggesting a novel pathophysiological mechanism and a potential therapeutic target.
This file contains supplementary material of the manuscript "Diet-induced fasting ghrelin el... more This file contains supplementary material of the manuscript "Diet-induced fasting ghrelin elevation reflects the recovery of insulin sensitivity and visceral adiposity regression"
Supplemental Material, sj-tiff-1-cpt-10.1177_10742484221074585 for The Association of Alanine Ami... more Supplemental Material, sj-tiff-1-cpt-10.1177_10742484221074585 for The Association of Alanine Aminotransferase Levels With Myocardial Perfusion Imaging and Cardiovascular Morbidity by David Yardeni, Ronen Toledano, Victor Novack, Aryeh Shalev, Arik Wolak, Yaron Rotman and Ohad Etzion in Journal of Cardiovascular Pharmacology and Therapeutics
Supplemental Material, sj-tiff-2-cpt-10.1177_10742484221074585 for The Association of Alanine Ami... more Supplemental Material, sj-tiff-2-cpt-10.1177_10742484221074585 for The Association of Alanine Aminotransferase Levels With Myocardial Perfusion Imaging and Cardiovascular Morbidity by David Yardeni, Ronen Toledano, Victor Novack, Aryeh Shalev, Arik Wolak, Yaron Rotman and Ohad Etzion in Journal of Cardiovascular Pharmacology and Therapeutics
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