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The exact interaction of factors leading to myocardial dysfunction and fibrosis of the systemic right ventricle (SRV) is not completely understood. Myocardial ischemia and injury associated with a supply-demand mismatch of the pressure overloaded SRV are thought to play an important role, however studies confirming this are lacking. Adult SRV patients were included in this single centre cohort study. All patients underwent a comprehensive diagnostic and imaging workup. A two-day stress-rest SPECT was performed to assess myocardial perfusion. SRV ischemia was defined as decreased segmental tracer uptake during exercise with significant improvement at rest. Contrast enhanced cardiac magnetic resonance imaging (CMR) was also performed in a subgroup of patients without contraindication, to assess focal myocardial fibrosis. Differences between patients with and without SRV ischemia were assessed. Twenty-three SRV patients (15 with transposition of the great arteries after atrial switch procedure and 8 with congenitally corrected transposition of the great arteries; 5 (22%) females; mean age 38 ± 11 years) were included. Seven (30%) patients had SRV ischemia on SPECT. Late gadolinium enhancement on CMR was more common in patients with SRV ischemia (p = 0.002). However, there was no association between SRV ischemia and different echocardiographic or CMR parameters of SRV systolic function, laboratory markers (high-sensitivity troponin I and NT-proBNP) and exercise capacity. Our multimodality study showed that SRV ischemia in adult SRV patients was associated with more focal myocardial fibrosis, but not with functional or imaging markers of SRV function. • The role of myocardial ischemia in dysfunction of the systemic right ventricle is unknown. • Myocardial ischemia of the systemic right ventricle was evident in 30% of adult patients with systemic right ventricle. • Patients with ischemia more commonly had focal myocardial fibrosis. • Myocardial ischemia had no impact on functional or imaging markers of systemic right ventricular function. [ABSTRACT FROM AUTHOR]

The usefulness of preoperative measurement of left ventricular global longitudinal strain (LVGLS) for predicting prognosis in patients undergoing non-cardiac surgery has not been evaluated. We analyzed the prognostic value of LVGLS in predicting postoperative 30-day cardiovascular events and myocardial injury after non-cardiac surgery (MINS). This prospective cohort study was conducted in two referral hospitals and included 871 patients who underwent non-cardiac surgery <1 month after preoperative echocardiography. Those with ejection fraction <40%, valvular heart disease, and regional wall motion abnormality were excluded. The co-primary endpoints were the (1) composite incidence of all-cause death, acute coronary syndrome (ACS), and MINS and (2) composite incidence of all-cause death and ACS. Among the 871 participants enrolled (mean age: 72.9 years; female: 60.8%), there were 43 cases of the primary endpoint (4.9%): 10 deaths, 3 ACS, and 37 MINS. Participants with impaired LVGLS (≤16.6%) had a higher incidence of the co-primary endpoints (log-rank P < 0.001 and 0.015) than those without. The result was similar after adjustment with clinical variables and preoperative troponin T levels (hazard ratio = 1.30, 95% confidence interval [CI] = 1.03–1.65; P = 0.027). In sequential Cox analysis and net reclassification index, LVGLS had an incremental value for predicting the co-primary endpoints after non-cardiac surgery. Among the 538 (61.8%) participants who underwent serial troponin assay, LVGLS predicted MINS independently from the traditional risk factors (odds ratio = 3.54, 95% CI = 1.70–7.36; P = 0.001). Preoperative LVGLS has an independent and incremental prognostic value in predicting early postoperative cardiovascular events and MINS. Clinical Trial Registration : URL: https://trialsearch.who.int/. Unique identifiers: KCT0005147. • LVGLS is independently associated with the early postoperative outcomes. • Preoperative LVGLS has incremental value in predicting cardiovascular events. • LVGLS had good diagnostic performance on myocardial injury after noncardiac surgery • Assessing LVGLS may be useful in predicting cardiovascular events and MINS [ABSTRACT FROM AUTHOR]

Positron Emission Tomography (PET) Myocardial Perfusion Imaging (MPI) is a robust diagnostic and prognostic test in patients with suspected or known coronary artery disease (CAD). We aimed to assess the incremental prognostic value of myocardial flow reserve (MFR) using the latest generation of digital PET scanners. Consecutive patients with clinically indicated PET MPI for suspected or known CAD were included. Myocardial blood flow (MBF) in ml/min/g was obtained from dynamic images at rest and peak hyperemia, and the myocardial flow reserve (MFR) was calculated as the ratio of stress to rest MBF. Patients were followed from the date of PET imaging for the occurrence of the primary outcome (composite of all-cause death, myocardial infarction, and Percutaneous Coronary Intervention or Coronary Artery Bypass Graft occurring >90 days after imaging). Nested multivariable Cox regression models were used to assess the incremental prognostic role of MFR over traditional risk factors and PET relative perfusion parameters. The final cohort consisted of 3534 patients (mean age 67 ± 12 years, 48% female, 67% Caucasian, 53% obese, 55% hypertension, 32% diabetes, 42% dyslipidemia). During a median follow-up of 8.5 (3.0–15.4) months, 229 patients (6.5%, 6.4 per 1000 person-years) experienced the primary outcome. In nested multivariable Cox models, impaired MFR (MFR < 2) was significantly associated with the primary outcome (HR 2.9, 95% CI 2.0–4.1, p < 0.001) and significantly improved discrimination (Harrell's C 0.77, p = 0.002). MFR derived from digital PET scanners has an independent and incremental prognostic role in patients with suspected or known CAD. • PET MPI is a robust diagnostic and prognostic test for managing patients with suspected or established CAD. • Digital PET MPI has higher sensitivity at a lower radiotracer dose, radiation exposure (below 1milisilvert), and cost. • We aimed to assess the incremental prognostic value of MFR using the latest generation of digital PET scanners. • We found digital PET MFR has an independent and incremental prognostic role in patients with suspected or known CAD. [ABSTRACT FROM AUTHOR]

Both the latest European guidelines on chronic coronary syndromes and the American guidelines on chest pain have underlined the importance of noninvasive imaging to select patients to be referred to invasive angiography. Nevertheless, although coronary stenosis has long been considered the main determinant of inducible ischemia and symptoms, growing evidence has demonstrated the importance of other underlying mechanisms (e.g., vasospasm, microvascular disease, energetic inefficiency). The search for a pathophysiology-driven treatment of these patients has therefore emerged as an important objective of multimodality imaging, integrating "anatomical" and "functional" information. We here provide an up-to-date guide for the choice and the interpretation of the currently available noninvasive anatomical and/or functional tests, focusing on emerging techniques (e.g., coronary flow velocity reserve, stress-cardiac magnetic resonance, hybrid imaging, functional-coronary computed tomography angiography, etc.), which could provide deeper pathophysiological insights to refine diagnostic and therapeutic pathways in the next future. CCTA allows a comprehensive assessment of CAD, while traditional functional imaging is aimed to assess myocardial ischemia. Since ischemia may be secondary either to epicardial coronary obstructive or to other conditions (e.g., vasospasm, microvascular dysfunction, energetic mismatch), the use of more modern techniques such as FFR CT , stress-CTP, CFVR, stress-CMR, and hybrid imaging may provide further information to tailor therapeutic choices to each patient. CAD: coronary atherosclerotic disease; CCTA: coronary computed tomography angiography; CFVR: coronary flow velocity reserve; CMR: cardiac magnetic resonance; CTP, computed tomography perfusion imaging; FFR, fractional flow reserve; MPI, myocardial perfusion imaging. [Display omitted] • Both the latest European guidelines on chronic coronary syndromes and the American guidelines on chest pain have underlined the importance of noninvasive imaging. • Other mechanisms than coronary stenosis (e.g., vasospasm, microvascular disease, energetic inefficiency) may underly inducible ischemia and symptoms. • The search for a pathophysiology-driven treatment of these patients is an important objective of multimodality imaging, integrating "anatomical" and "functional" information. [ABSTRACT FROM AUTHOR]

Coronary computed tomographic angiography (CCTA) and Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) provide comprehensive anatomic and functional assessment of the coronary arteries useful in the diagnosis and prognosis of patients with coronary artery disease (CAD). We aimed to assess the incremental prognostic role of SPECT physiologic assessment to CCTA in patients with suspected CAD. Consecutive patients with suspected CAD undergoing clinically indicated CCTA within 180 days of undergoing SPECT were included. Patients were followed for major adverse cardiovascular events (MACE, inclusive of all-cause death, non-fatal myocardial infarction, and percutaneous coronary intervention or coronary artery bypass grafting 90-days after imaging test.) The cohort consisted of 956 patients (mean age 61.1 ± 14.2 years, 54% men, 89% hypertension, 81% diabetes, 84% dyslipidemia). Obstructive stenosis was found in 14% of patients, while scar (fixed perfusion defect), ischemia and left ventricular ejection fraction <40% were found in 17, 14 and 9% of patients, respectively. In nested multivariable cox regression models, perfusion and left ventricular function when added to a model with CCTA obstructive stenosis significantly improved model risk prediction (Harrell's C = 0.73, p = 0.037) and risk reclassification on a continuous scale (P < 0.001). We have shown that a combined assessment of perfusion burden and left ventricular function added incremental value over and above a CCTA based anatomic assessment in patients with suspected CAD. • CCTA-based anatomic assessment in patients with suspected CAD lacks information on physiologic significance of a lesion. • SPECT MPI has long been established as a powerful diagnostic and prognostic test in patients with CAD. • We analyzed the incremental prognostic value of SPECT functional assessment over CCTA anatomic assessment. • We have shown that perfusion defect and LVEF on SPECT showed incremental prognostic value over stenosis on CCTA. [ABSTRACT FROM AUTHOR]

Whether a coronary lesion with discordant fractional flow reserve (FFR) and non-hyperemic pressure ratios (NHPRs) causes myocardial ischemia remains unclear. This study investigates the prevalence of myocardial ischemia as assessed by myocardial perfusion scintigraphy (MPS) in coronary lesions with discordant FFR and instantaneous wave-free ratio (iFR), and, additionally, other NHPRs: resting full-cycle ratio (RFR), diastolic pressure ratio (dPR), and resting Pd/Pa. A total of 484 coronary arteries in 295 patients with stable coronary artery disease that underwent MPS and invasive physiological pressure measurements were categorized into four groups (FFR+/NHPR+, FFR+/NHPR-, FFR-/NHPR+, and FFR-/NHPR-) using the respective cut-off values of FFR ≤ 0.80, iFR ≤ 0.89, RFR ≤ 0.89, dPR < 0.89, and Pd/Pa ≤ 0.92. The proportions of MPS-derived myocardial ischemia in a relevant myocardial territory were compared between the four groups. In total, 175 (36%), 61(13%), 35(7%) and 213(44%) vessels were classified into FFR+/iFR+, FFR+/iFR-, FFR-/iFR+ and FFR-/iFR- groups, respectively. The FFR+/iFR+ group had the highest proportion of MPS-derived ischemia (70%), followed by the FFR+/iFR- group (38%), the FFR-/iFR+ group (23%), and the FFR-/iFR- group (10%) (P < 0.001). Similar proportions of MPS-derived ischemia were found when RFR. (70%, 34%, 24%, and 10%, P < 0.001), dPR (70%, 38%, 26%, and 10%, P < 0.001), and Pd/Pa (70%, 31%, 22%, and 10%, P < 0.001) were used in place of iFR. The prevalence of MPS-derived myocardial ischemia in coronary lesions with discordance between FFR and NHPRs is lower than those with concordantly positive FFR and NHPRs, but higher than those with concordantly negative FFR and NHPRs. • FFR and NHPR individually agree well with ischemia on myocardial perfusion imaging. • Highest prevalence of ischemia was found when FFR and NHPR were concordantly positive. • Prevalence of ischemia was the lowest when FFR and NHPR were concordantly negative. • Discordant FFR and NHPR were associated with intermediate prevalence of ischemia. • Similar trends were seen in the prevalence of myocardial ischemia whether MVD or SVD. [ABSTRACT FROM AUTHOR]

Remote ischemic postconditioning (RIPostC) has recently emerged as a potential novel therapeutic strategy to achieve protection against acute myocardial infarction (AMI) injury. We aimed to evaluate the longitudinal cardioprotective effects of RIPostC on AMI using 99mTc-MIBI SPECT myocardial perfusion imaging (MPI) and gated 18F-FDG PET (GPET) in pigs. MI was induced in 12 Chinese pigs. RIPostC was conducted by four 5 min cycles of blood pressure cuff inflation applied to the lower limb immediately after AMI. MPI and GPET were performed longitudinally at baseline, 3rd, 14th, 28th, and 56th days after AMI. Total perfusion defect (TPD), hibernating myocardium (HM), scar, left ventricular (LV) remodeling (End diastolic volume, EDV), and bone marrow (BM) metabolic activity were analyzed, and inflammation biomarkers were measured. In outcome evaluation, there was a significant attenuation in TPD (Δ value, at 14th, 28th and 56th days), HM (Δ value, at 14th, 56th days) and Scar (Δ value, at 14th, 28th days) in the RIPostC group compared with the control group (P < 0.05). Additionally, RIPostC attenuated LV enlargement (ΔEDV, at 14th day) (P < 0.05) in comparison to controls. BM 18F-FDG uptake activity in the RIPostC group was lower than the control group (P < 0.05) at the 3rd day after AMI. There was a non-statistically significant trend of decreased MMP-2 levels in the RIPostC group post-AMI (P > 0.05). RIPostC presented the longitudinal cardioprotective effects by preserving myocardial viability, reducing infarct size, attenuating LV remodeling at early stage post-AMI, and may also have an anti-inflammatory effect at the acute phase. • RIPostC presented cardioprotective effects by preserving HM, attenuating infarct size and remodeling at early stage post-MI. • RIPostC presented the putative role of anti-inflammatory signaling for cardioprotection. • These data might provide practical evidence that RIPostC served as an adjuvant approach in patients with AMI. [ABSTRACT FROM AUTHOR]

Detection of obstructive coronary artery disease (CAD) by stress myocardial perfusion imaging (MPI) is conventionally based on relative differences in perfusion. This may lead to either underestimation of the extent of myocardial ischemia, or the ischemia might be completely missed in case of balanced perfusion reduction. Using absolute quantification of myocardial blood flow (MBF) by positron emission tomography (PET), we evaluated how common are extensive and balanced myocardial perfusion abnormalities in symptomatic patients with suspected obstructive CAD. Among 758 consecutive symptomatic patients undergone coronary computed tomography angiography (CTA), 286 patients subsequently underwent quantitative 15O-water adenosine-stress PET MPI to assess the hemodynamic significance of suspected obstructive stenosis. Out of these, 46 (16%) patients had reduced (≤2.3 ml/g/min) absolute stress MBF in all three standard coronary territories (LAD, LCX, RCA). Subsequently, relative stress MBF in each coronary territory was calculated, considering a territory with the highest absolute stress MBF as a reference region. Among the 46 patients, 72% had significant regional heterogeneity in myocardial perfusion (defined as having ≥1 territory with relative stress MBF <80%) while the remaining 28% (4.5% of the whole MPI cohort) showed balanced perfusion reduction (all relative MBF values ≥80%). Among symptomatic patients with suspected obstructive stenosis on coronary CTA, quantitative PET revealed that 16% of patients had reduced stress MBF involving all three coronary artery territories, of whom approximately one third showed balanced reduction. Thus, in 4.5% of the patients the perfusion abnormalities could have been missed by conventional relative MPI analysis. • Absolute quantification may reveal extensive reduction of myocardial blood flow. • Small proportion of real-life patients shows balanced reduction of blood flow. • Also other mechanisms than obstructive coronary artery disease cause flow reduction. [ABSTRACT FROM AUTHOR]

Ischemia with non-obstructive coronary arteries (INOCA) is not uncommon in clinical practice. However, the incidence and imaging characteristics of INOCA on dynamic CT myocardial perfusion imaging (CT-MPI) remains unclear. We aimed to investigate the prevalence and disease features of INOCA as evaluated by dynamic CT-MPI + coronary CT angiography (CCTA). Patients with suspected chronic coronary syndrome and intermediate-to-high pre-test probability of obstructive CAD (according to updated Diamond and Forrester Chest Pain Prediction Rule) were referred for dynamic CT-MPI + CCTA and retrospectively included. Various parameters, including myocardial blood flow (MBF) and high-risk plaque (HRP) features, were measured. INOCA was diagnosed if patients were revealed to have myocardial ischemia and absence of obstructive stenosis. 314 patients were finally included. 20 patients (6.4%) were observed to have myocardial ischemia without obstructive stenosis. In addition, 138 patients (43.9%) had normal or near normal findings, 101 patients (32.2%) had obstructive stenosis without myocardial ischemia and 55 patients (17.5%) had obstructive stenosis with myocardial ischemia. Compared with patients with normal/near normal findings, patients with INOCA showed a higher prevalence of positive remodeling (40.0% vs. 17.4%, p = 0.04). In patients with obstructive stenosis, the mean age, calcium score and incidence of spotty calcification, positive remodeling as well as HRPs were significantly higher than those in patients with INOCA (p < 0.05 for all). The overall prevalence of INOCA was low in patients with suspected chronic coronary syndrome. HRPs were less frequently presented in patients with INOCA, compared with patients having obstructive coronary stenosis. • The overall prevalence of INOCA was low (6.4%) in patients with stable angina. • HRPs were less frequently presented in patients with INOCA. • Dynamic CT-MPI + CCTA was helpful for accurate "one-stop shop" imaging of INOCA. [ABSTRACT FROM AUTHOR]

Coronary microvascular dysfunction is a powerful prognostic factor in patients with coronary artery disease. We investigated the role of reactive digital hyperemia peripheral arterial tonometry (RH-PAT) as a non-invasive tool to identify patients with impaired coronary microvasculature. Patients undergoing elective coronary angiography were consecutively assessed for peripheral microvascular endothelial function before coronary angiography: both the Reactive Hyperemic Index (RHI) and the Framingham reactive hyperemic index (Endoscore) were measured. During coronary angiography, the Index of microvascular resistance (IMR) was measured in all patients, and an IMR value > 25 identified patients with coronary microvascular impairment. A total of 47 patients with chronic coronary syndromes candidate to coronary angiography were included. Those with coronary microvascular impairment (n = 18 [38%]) presented with significantly lower RHI (1.68 ± 0.38 vs. 1.94 ± 0.93, p = 0.04) and Endoscore 0.50 ± 0.23 vs. 0.64 ± 0.23, p = 0.04) values as compared with patients with preserved coronary microvasculature. A significant relationship was observed between IMR with both RHI (r = 0.35, p = 0.02) and Endoscore (r = 0.34, p = 0.02). At the multivariable analysis, RHI and Endoscore were the only independent predictors of an IMR > 25. Our study demonstrates that digital reactive hyperemia indexes are lower in patients with high IMR values, suggesting a role for RH-PAT as non-invasive tool for identifying patients with coronary microvascular impairment. • The invasive IMR identifies patients with coronary microcirculatory dysfunction. • The non-invasive RH-PAT identifies patients with peripheral endothelial dysfunction. • An inverse correlation between IMR and RH-PAT measures has been showed. • Patients with coronary microvascular dysfunction have lower Endoscore values. • RH-PAT might be useful to identify patients with coronary microvascular dysfunction. [ABSTRACT FROM AUTHOR]

The impact of a non-dominant right coronary artery (NDRCA), on single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI)has not been clarified. We compared SPECT-MPI results of consecutive patients without significant (diameter stenosis ≥50%)coronary artery disease (CAD) and a NDRCA (Group-1), with those of patients from our database without CAD and a dominant RCA (Group-2). All patients were subjected to SPECT-MPI with I.V. infusion of adenosine, and TC99-tetrofosmin. Group-1 included 69 patients (55 men, 79.7%), mean age 66.8 ± 9.8 years. Group-2 consisted of 79 patients (56 men, 70.9%), mean age 62.7 ± 11.5. There was no difference in demographics and CAD risk factors between the two groups. The SPECT-MPI revealed inferior wall ischemia, in 35 patients (50.7%), in Group-1 and 27 patients (34.1%), in Group-2 (P = 0.041). A relatively high rate of reversible SPECT-MPI perfusion defects may be anticipated in patients with an unobstructed NDRCA compared to patients with a dominant RCA. • A non-dominant right coronary artery (NDRCA) is found in approximately 7–9% of the general population. Its impact –if any- on single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), has not been studied prospectively. • We compared SPECT-MPI results between 69 consecutive patients without significant, coronary artery disease (CAD) and 79 patients with a dominant-RCA, also without significant CAD. There was no difference in demographics between the two groups. The SPECT-MPI revealed ischemia in 50.7%, patients with NDRCA and 34.2%, in patients with a dominant RCA, P = 0.041. • The semiquantitive segmental analysis of radiotracer uptake in the inferior wall revealed that the difference between the perfusion score at stress and rest (SDS), was significantly higher (1.25 ± 1.45 vs. 0.77 ± 1.08, P = 0.028), in patients with NDRCA compared to the rest. • In summary this study shows that a relatively high rate of reversible SPECT-MPI perfusion defects may be anticipated in patients with an unobstructed NDRCA compared to patients with a dominant RCA. [ABSTRACT FROM AUTHOR]

Assessment of both coronary artery calcium(CAC) scores and myocardial perfusion imaging(MPI) in patients suspected of coronary artery disease(CAD) provides incremental prognostic information. We used an automated method to determine CAC scores on low-dose attenuation correction CT(LDACT) images gathered during MPI in one single assessment. The prognostic value of this automated CAC score is unknown, we therefore investigated the association of this automated CAC scores and major adverse cardiovascular events(MACE) in a large chest-pain cohort. We analyzed 747 symptomatic patients referred for 82RubidiumPET/CT, without a history of coronary revascularization. Ischemia was defined as a summed difference score≥2. We used a validated deep learning(DL) method to determine CAC scores. For survival analysis CAC scores were dichotomized as low(<400) and high(≥400). MACE was defined as all cause death, late revascularization (>90 days after scanning) or nonfatal myocardial infarction. Cox proportional hazard analysis were performed to identify predictors of MACE. During 4 years follow-up, 115 MACEs were observed. High CAC scores showed higher cumulative event rates, irrespective of ischemia (nonischemic: 25.8% vs 11.9% and ischemic: 57.6% vs 23.4%, P -values <0.001). Multivariable cox regression revealed both high CAC scores (HR 2.19 95%CI 1.43–3.35) and ischemia (HR 2.56 95%CI 1.71–3.35) as independent predictors of MACE. Addition of automated CAC scores showed a net reclassification improvement of 0.13(0.022–0.245). Automatically derived CAC scores determined during a single imaging session are independently associated with MACE. This validated DL method could improve risk stratification and subsequently lead to more personalized treatment in patients suspected of CAD. • Combined assessment of CAC scores and perfusion data provide additional information. • We show a validated DL-method to determine CAC scores on CT images required during MPI. • No additional radiation exposure and manual scoring of a physician is needed. • We showed that this automated CAC score was independently associated with MACE. • If confirmed externally this could lead to better risk stratification in patients suspected of CCS. [ABSTRACT FROM AUTHOR]

In patients with normal left ventricular ejection fraction, it may be difficult to distinguish between the normal and diseased heart. Novel assessments of ventricular function, such as extracellular volume imaging, myocardial perfusion imaging and myocardial contraction fraction are emerging to better assess disease burden in these cases. This study endeavored to determine whether the ratio of myocardial volume in systole to myocardial volume in diastole (MVs/MVd), differs between normal hearts and those with disease states characterized by normal ejection fraction. Consecutive patients from 2008 to 2018 with hypertrophic cardiomyopathy (HCM), cardiac amyloidosis, and heart failure with preserved ejection fraction (HFpEF) who underwent cardiac magnetic resonance imaging (MRI) were selected for inclusion, along with a sex- and age-matched cohort of normal volunteers who also underwent cardiac MRI. Manual tracings were performed on each MRI to calculate MVs/MVd, which was then compared across subgroups. Included were 50 patients with HCM, 50 patients with cardiac amyloidosis, 26 patients with HFpEF, and 30 normal subjects. Age was 54.1 years (SD 16.7); mean MVs/MVd was 0.88 (SD 0.04) in the normal subgroup, 1.03 (SD 0.06) in HCM patients, 1.03 (SD 0.06) in cardiac amyloidosis patients, and 0.97 (SD 0.02) in HFpEF patients, with all pathology subgroups different from the normal subgroup (p <.0001 for each). The ratio of MVs/MVd discriminated diseased from normal with c statistic 0.989 (p <.001). This study suggests that a novel and easily-captured metric of ventricular function, MVs/MVd, can differentiate normal ventricular function from multiple cardiomyopathies with normal ejection fractions. • MVs/MVd differentiates HCM, cardiac amyloidosis and HFpEF from normal. • MVs/MVd is easily-captured and may provide new information on cardiac physiology. • Further study of the diagnostic and prognostic utility of MVs/MVd is warranted. [ABSTRACT FROM AUTHOR]

We aim to describe the feasibility, challenges, success rates and techniques utilized in coronary angiography (CA) and percutaneous coronary intervention (PCI) in patients post transcatheter aortic valve replacement (TAVR). CA and PCI after TAVR are becoming increasingly encountered in clinical practice. There have been technical difficulties reported in re-accessing the coronary arteries through the self-expanding CoreValve prosthesis. From January 2012 to November 2017, 672 patients who underwent TAVR with a self-expanding prosthesis were retrospectively reviewed and those who had a CA and/or PCI post TAVR were analysed. Clinical characteristics, angiographic and procedural details were obtained. A subgroup of patients had computed tomographic angiography (CTA) post TAVR to evaluate positions of the coronary ostia relative to the self-expanding prosthesis. Study endpoint was successful selective engagement of coronary ostia for CA and PCI. Thirty-two patients (4.8%) had attempted 46 CA and 26 PCI after TAVR with a self-expanding valve. Mean age was 85.2 years and 41% were females. Selective left and right coronary angiography using standard catheters could be achieved in 50% and 28% of cases respectively. Successful PCI was performed in 25 cases (96%); however, significant technique modification was required in 64% of cases. CTA in 9 patients confirmed the difficulty in coronary re-access was due to a combination of the sealing skirt relationship to coronary ostia and sinotubular junction as well as commissural post orientation and significant native leaflet calcification. CA and PCI post TAVR with self-expanding CoreValve is technically challenging but feasible with modification of standard techniques. • Out of 672 patients who underwent TAVR with a self-expanding prosthesis, 32 patients (4.8%) had attempted 46 CA and 26 PCI • Diagnostic angiography was done in 96% of cases; selective left and right coronary angiography was achieved in 50% and 28% of cases. • Successful PCI was performed in 96% of the cases with significant technique modification required in 64% of cases. • Computed tomographic angiography allowed to establish the anatomical factors associated with difficult coronary engagement. [ABSTRACT FROM AUTHOR]

Quantitative flow ratio (QFR) is a novel, adenosine-free method for functional lesion interrogation based on 3-dimensional quantitative coronary angiography and computational algorithms. We sought to investigate the diagnostic performance of QFR versus myocardial perfusion imaging positron emission tomography (MPI-PET), which yields the highest accuracy for detection of myocardial ischemia. Diagnostic performance of QFR versus MPI-PET was assessed in consecutive patients undergoing both clinically indicated coronary angiography and 13N-ammonia MPI-PET within a six-month period. Out of 176 patients (439 coronary arteries), 19.3% were women. Percent area stenosis was 45 [32–58] %. Myocardial ischemia on 13N-ammonia MPI-PET was detected in 106 (24.1%) vessel territories and hemodynamic significance defined as contrast-flow vessel QFR ≤ 0.80 was observed in 83 (18.9%) vessels. Diagnostic accuracy, sensitivity, and specificity of contrast-flow vessel QFR for the prediction of myocardial ischemia on 13N-ammonia MPI-PET were 92.5 (95% CI 89.6–94.7) %, 73.6 (95% CI 64.1–81.7) %, and 98.5 (95% CI 96.5–99.5) %, respectively. The AUCs for contrast-flow vessel QFR, percent diameter stenosis, and percent area stenosis were 0.85 (95% CI 0.81–0.88, p < 0.001), 0.76 (95% CI 0.71–0.79, p < 0.001) and 0.75 (95% CI 0.70–0.79, p < 0.001), respectively. QFR, a novel diagnostic tool for functional coronary lesion assessment, provides good diagnostic agreement with MPI-PET and superior diagnostic accuracy for the detection of myocardial ischemia as compared to anatomic indices. Future studies will have to determine the non-inferiority of QFR to fractional flow reserve with respect to clinical outcomes. • Quantitative flow ratio (QFR) allows for functional lesion assessment. • QFR provides good diagnostic agreement with positron emission tomography. • Future studies compare QFR with fractional flow reserve with respect to outcomes. [ABSTRACT FROM AUTHOR]

Accurate risk stratification in patients with known coronary artery disease (CAD) is critical for patient management. Prior myocardial infarction (MI) or revascularization without MI are often equated as known CAD. We compared the prognostic significance of prior MI and previous revascularization in patients undergoing single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). Consecutive patients undergoing SPECT MPI at Cedars-Sinai Medical Center between 1992 and 2012 were included. Medical history, including history of MI or revascularization, was collected prospectively. Association with all-cause mortality was assessed with multivariable Cox analysis, adjusted for patient demographics, medical history, medications, and SPECT MPI results. In total, 50,121 patients were identified including 7428 (14.8%) with a history of previous MI and 3608 (7.2%) with a history of revascularization without prior MI. During a median follow-up of 8.0 years, 19,696 (39.3%) patients died including 4467 (60.1%) with a history of MI and 1880 (52.1%) with a history of revascularization. Prior MI (adjusted HR 1.12, p =0.001) and prior revascularization without MI (adjusted HR 1.15, p <0.001) were independently associated with increased all-cause mortality. Previous MI (adjusted HR 1.27, p <0.001) and previous revascularization without MI (adjusted HR 1.21, p<0.001) were significantly associated with increased all-cause mortality only in patients without ischemia. In this large cohort of patients undergoing SPECT MPI, previous MI and previous revascularization without MI were independent predictors of all-cause mortality, with no significant difference in associated risk. History of CAD may be particularly important for risk stratification in patients without ischemia. • Previous MI and revascularization without MI were associated with all-cause mortality. • No difference in risk associated previous MI compared to revascularization without MI. • Prior MI or revascularization were more significant in patients without ischemia. [ABSTRACT FROM AUTHOR]

Coronary microvascular dysfunction before percutaneous coronary intervention (PCI) predicts PCI-related myocardial injury in patients with stable coronary artery disease (CAD). Whether the dynamic changes of the microcirculation during PCI might be associated with the occurrence of procedure-related myocardial injury and infarction is still unclear. We aimed to investigate the impact of pre- and post-PCI microvascular function, evaluated with the index of microvascular resistance (IMR) on the occurrence of PCI-related myocardial injury and infarction. In consecutive patients with stable CAD referred for elective PCI, coronary physiological indexes, including IMR, were measured before and after revascularization. High sensitivity Troponin T (hs-TnT) was assessed up to 24 h after PCI, and PCI-related myocardial injury and type 4a myocardial infarction (MI) were defined according to the fourth universal definition of myocardial infarction. In the 50 patients enrolled, a significant correlation was found between maximum post-PCI hs-Tn and IMR, both at baseline (rho = 0.309, p =0.029) and post-PCI (rho = 0.378, p =0.007). Patients who developed type 4a MI, compared with patients who did not, presented significantly higher IMR levels, both at baseline (28.3 ± 12.2 vs. 19.6 ± 8.8, p =0.020) and post-PCI (45.4 ± 21.3 vs. 21.6 ± 11.2, p <0.0001). Patients with post-PCI IMR > 38 showed significantly higher maximum post-PCI hs-Tn levels (105.4 [49.4–126.9] vs. 22.4 [11.7–38.6] ng/ml, p <0.0001), and developed type 4a MI more frequently (66.8% vs. 4.9%, p<0.0001). Dynamic changes of microvascular resistance post-PCI are strongly correlated with PCI-related myocardial injury and post-PCI IMR is a strong predictor of type 4a MI in patients with stable CAD undergoing elective PCI. • Microvascular resistance, as assessed with IMR, significantly increases after elective PCI in patients with stable CAD. • There is a significant correlation between baseline and post-PCI IMR values. • Post-PCI IMR is a stronger and independent predictor of the occurrence of type 4a MI. [ABSTRACT FROM AUTHOR]

Iron deficiency (ID) is a known co-morbidity and a potential therapeutic target in heart failure. Whether ID is frequent also in ST-segment elevation acute myocardial infarction (STEMI) patients and is associated with worse in-hospital outcomes has never been evaluated. We defined ID as a serum ferritin < 100 μg/L or transferrin saturation < 20% at hospital admission. We assessed the association between ID and the primary endpoint (a composite of in-hospital mortality and Killip class ≥ 3). We explored the potential association between ID, circulating cell-free mitochondrial DNA (mtDNA), and cardiac magnetic resonance (CMR) parameters. Four-hundred-twenty STEMI patients undergoing primary percutaneous coronary intervention (pPCI) were included. Of them, 237 (56%) had ID. They had significantly higher admission high-sensitivity troponin and mtDNA levels as compared to non-ID patients (145 ± 35 vs. 231 ± 66 ng/L, P < 0.001; 917 [404–1748] vs. 1368 [908–4260] copies/μL; P < 0.003, respectively). A lower incidence of the primary endpoint (10% vs. 18%, P = 0.01) was observed in ID patients (adjusted OR 0.50 [95% CI 0.27–0.93]; P = 0.02). At CMR (n = 192), ID patients had a similar infarct size (21 ± 18 vs. 21 ± 19 g; P = 0.95), but a higher myocardial salvage index (0.56 ± 0.30 vs. 0.43 ± 0.27; P = 0.002), and a smaller microvascular obstruction extent (3.6 ± 2.2 vs. 6.9 ± 3.9 g; P < 0.001). Iron deficiency is frequent in STEMI patients, it is coupled with mitochondrial injury, and, paradoxically, with a better in-hospital outcome. This unexpected clinical result seems to be associated with a smaller myocardial reperfusion injury. The mechanisms underlying our findings and their potential clinical implications warrant further investigation. • Iron deficiency (ID) is a frequent condition in patients with STEMI. • It is associated with mitochondrial injury, as reflected by higher levels of mitochondrial DNA. • ID is paradoxically associated with a better in-hospital outcome. • This result is associated with a lower myocardial reperfusion injury, as assessed by CMR. [ABSTRACT FROM AUTHOR]

Despite widespread use of ETT and vasodilator-stress with myocardial perfusion imaging (MPI) for noninvasive detection of flow-limiting coronary artery disease, there is continued need to improve diagnostic accuracy. We examined whether measurement of interlead T-wave heterogeneity (TWH) during exercise tolerance testing (ETT) or pharmacologic stress testing improves detection of stenoses in large epicardial coronary arteries. All 137 patients at our institution who underwent diagnostic coronary angiography within 0 to 5 days after ETT (N = 81) or dipyridamole IV infusion (N = 58) in 2016 were studied, including 2 patients with both tests. Cases (N = 93) had angiographically significant stenosis (≥50% of left main or ≥ 70% of an epicardial coronary artery ≥2 mm in diameter); controls (N = 44) did not. TWH, i.e., interlead splay of T waves, was determined by second central moment analysis from precordial leads by an investigator blinded to angiographic results. At rest, TWH levels were similar for cases and controls. ETT and dipyridamole stress testing increased TWH by 69% (p < 0.0001) and 27% (p < 0.0001), respectively, in cases. In controls, TWH did not change. Areas under the ROC curves for TWH increase for any flow-limiting coronary artery stenosis were 0.737 (p < 0.0001) for ETT and 0.818 (p < 0.0001) for dipyridamole stress testing. By contrast, neither ST-segment changes during ETT (p = 0.12) nor MPI during dipyridamole stress testing (p = 0.60) discriminated cases from controls. TWH measurement is a novel method that improves detection of angiographically confirmed flow-limiting stenoses in large epicardial coronary arteries during both ETT and MPI during pharmacologic stress testing with dipyridamole. • T-wave heterogeneity (TWH) is a novel measure of interlead splay of ECG waveforms. • TWH detects flow-limiting stenoses during ETT (AUC, 0.737, p < 0.0001) and MPI (AUC, 0.818, p < 0.0001). • ST-segment changes during ETT (p = 0.12) and MPI (p = 0.60) did not detect CAD. • Combining TWH with MPI improves specificity (to 95%), odds ratio (to 36.54), and positive likelihood ratio (to 13.16). • TWH testing is performed using standard protocols, equipment, and electrodes. [ABSTRACT FROM AUTHOR]

This study aimed to compare the diagnostic accuracy of stress myocardial perfusion imaging between cardiac magnetic resonance (CMR) and nuclear medical imaging, including single-photon emission computed tomography (SPECT) and positron emission tomography (PET), for the diagnosis of hemodynamically significant coronary artery disease (CAD) with fractional flow reserve (FFR) as the reference standard. We searched PubMed and Embase for all published studies that evaluated the diagnostic accuracy of stress myocardial perfusion imaging modalities, including CMR, SPECT, and PET, to diagnose hemodynamically significant CAD with FFR as the reference standard. A total of 28 articles met the inclusion criteria and were included in the meta-analysis: 14 CMR, 13 SPECT, and 5 PET articles. The results demonstrated a pooled sensitivity of 0.88 (95% confidence interval [CI]: 0.80–0.93), 0.69 (95% CI: 0.56–0.79), and 0.83 (95% CI: 0.70–0.91), and a pooled specificity of 0.89 (95% CI: 0.85–0.93), 0.85 (95% CI, 0.80–0.89), and 0.89 (95% CI, 0.86–0.91) for CMR, SPECT, and PET, respectively. The area under the curve (AUC) of CMR, PET, and SPECT was 0.94 (95% CI, 0.92–0.96), 0.92 (95% CI, 0.89–0.94), and 0.87 (95% CI, 0.83–0.89), respectively. CMR and PET both have high accuracy and SPECT has moderate accuracy to detect hemodynamically significant CAD with FFR as the reference standard. Furthermore, the diagnostic accuracy of CMR at 3.0 T is superior to 1.5 T. • CMR and PET both have high accuracy to detect hemodynamically significant CAD. • The diagnostic accuracy of CMR at 3.0 T is superior to 1.5 T. • SPECT has stable specificity in different percentage of patients with MVD. • SPECT has a trend towards decreasing sensitivity with increasing percentage of MVD. • CMR may have higher sensitivity compared with SPECT in patients with MVD. [ABSTRACT FROM AUTHOR]

CT myocardial perfusion imaging (CTP) represents one of the newly developed CT-based techniques but its cost-effectiveness in the clinical pathway is undefined. The aim of the study is to evaluate the usefulness of combined evaluation of coronary anatomy and myocardial perfusion in intermediate to high-risk patients for suspected CAD or with known disease in terms of clinical decision-making, resource utilization and outcomes in a broad variety of geographic areas and patient subgroups. CTP-PRO study is a cooperative, international, multicentre, prospective, open-label, randomized controlled study evaluating the cost-effectiveness of a CCTA+CTP strategy (Group A) versus usual care (Group B) in intermediate-high risk patients with suspected or known CAD who undergo clinically indicated diagnostic evaluation. A total sample size of 2000 subjects will be enrolled and followed up for 24 months. The primary endpoint is the reclassification rate of CCTA in group A due to the addition of CTP. The secondary endpoint will be the comparison between groups in terms of non-invasive and invasive downstream testing, prevalence of obstructive CAD at ICA, revascularization, cumulative ED and overall cost during the follow-up at 1- and 2-years. The tertiary endpoint will be the comparison between each group in terms of MACE and cost-effectiveness at 1- and 2-years. The study will provide information to patients, health care providers and other stakeholders about which strategy could be more effective in the diagnosis of suspected CAD in intermediate to high-risk patients or in the symptomatic patients with known CAD and previous history of revascularization. • CTP-PRO study is a prospective, randomized study evaluating the cost-effectiveness of a CCTA+CTP strategy (Group A) versus usual care (Group B). • A total sample size of 2000 subjects will be enrolled and followed up for 24 months. • •Primary endpoint: reclassification rate of CCTA in group B due to the addition of CTP. • Secondary endpoint: comparison of downstream testing, prevalence of obstructive CAD, revascularization, cumulative ED and overall cost. • Tertiary endpoint: comparison between each group in terms of MACE and cost-effectiveness at 1- and 2-years. [ABSTRACT FROM AUTHOR]

Amongst patients with coronary artery disease (CAD), women experience relatively worse outcomes as compared to men. Evidence to date has failed to explore unique female imaging targets as major determinants of cardiovascular risk. We sought to assess the prognostic value of epicardial (EFV) and intrathoracic fat volume (IFV) quantification in women and men with suspected and known CAD. Intrathoracic fat volume and EFV were calculated from non-contrast CT and analyzed in a propensity-matched cohort of 190 patients (95 women, mean age 62.5 ± 11.3 years) undergoing myocardial perfusion imaging (MPI) and coronary computed tomography angiography (CCTA) for evaluation of CAD. IFV and EFV were significantly lower in women as compared to men (198.2 ± 78.4 vs 293.2 ± 114.7 cm3 and 105.6 ± 48.9 vs 135.8 ± 60.9 cm3, p < 0.001) and showed a strong association with coronary artery calcium score (CACS) and obstructive CAD in women (p < 0.05), but not in men. Fat volumes were not related to abnormal MPI in either population (p = NS). During a median follow-up of 2.8 years, high IFV was associated with reduced event free survival (log rank = 0.019 vs low IFV) in women, but not in men. Accordingly, a multivariate Cox regression model adjusted for cardiovascular risk factors, CACS, CCTA, and MPI findings selected IFV as a significant predictor of major adverse cardiovascular events (MACE) in women (HR 1.32, 95%CI 1.18–1.55, p = 0.001). Quantification of IFV provides incremental prognostic value for MACE in women, beyond that provided by traditional risk factors and imaging findings. • IFV provides incremental prognostic value for MACE in women. • IFV values are significantly higher in women who experience adverse outcome. • EFV and IFV are associated with CACS and obstructive CAD in women and men. [ABSTRACT FROM AUTHOR]

Aortic stenosis (AS) is frequently associated with coronary artery disease (CAD). However, the best tool to functionally assess CAD in AS remains undetermined. Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) have never been validated in AS. FFR, iFR and stress single photon emission computed tomography (SPECT) were performed in a consecutive series of 28 patients with severe AS and 41 borderline coronary lesions during the work-up for valve replacement. Both FFR and iFR were correlated with an abnormal SPECT. At ROC analysis, FFR yielded an AUC = 0.91 with negative predictive value (NPV) = 95% in detecting ischemia according to SPECT. iFR showed significant worse agreement with myocardial perfusion imaging compared to FFR (59% vs 85%, p = 0.014). Specifically, a significant larger proportion of false positive measurements (negative SPECT and iFR < 0.89) was observed using iFR vs FFR: 39% vs 12%, p = 0.011. Using a pre-specified 0.82 cut-off, the iFR agreement with SPECT increased to 73%. FFR yielded a good correlation with SPECT and a high NPV in detecting ischemia-provoking lesions. iFR diagnostic metrics were inferior compared with FFR and improved adopting a lower ischemic threshold. • FFR and iFR have not been validated in patients with severe aortic stenosis (AS). • The role of physiology in guiding revascularization in AS remains controversial. • FFR demonstrated substantial agreement with myocardial perfusion imaging. • iFR agreement with myocardial perfusion imaging was inferior compared with FFR. • iFR diagnostic performance increased using a prespecified lower cut-off (0.82). [ABSTRACT FROM AUTHOR]

Abstract Background We aimed to compare the myocardial ischemic burden assessed using semi-quantitative and quantitative analysis of computed tomography-myocardial perfusion imaging (CT-MPI) with that of single-photon emission computed tomography (SPECT). Methods From 2011 to 2013, 97 patients who underwent CT-MPI and SPECT were evaluated. The extent and severity of perfusion defects were assessed on a 5-point scale using a standard 16-segment model, and were expressed as summed stress score (SSS) and summed difference score (SDS). Receiver operating characteristic (ROC) curves for quantitative parameters were generated for the diagnosis of abnormal perfusion defect (SSS ≥ 4) and presence of ischemia (SDS ≥ 2) on SPECT. Results On CT-MPI, 298 (19.2%) of the 1552 segments showed perfusion abnormalities during stress, whereas perfusion abnormalities were shown in 179 (11.5%) segments on SPECT-MPI. On a per-person basis, there was good agreement, with intraclass correlation coefficients of 0.78 for SSS and 0.72 for SDS. A significant reduction of attenuation in stress and myocardial perfusion reserve index, along with an increase in % defect volume of CT-MPI, were demonstrated as the degree of perfusion defect or ischemia on SPECT increased. On the ROC curves, % defect volume on CT-MPI demonstrated the highest area under the curve: 0.91 for abnormal perfusion defect and 0.89 (all p < 0.001) for the presence of ischemia on SPECT. Conclusions Semi-quantitative analysis of CT-MPI showed good accordance with SPECT. A quantitative approach for CT-MPI, especially % defect volume, may provide additional value in the identification of myocardial perfusion abnormalities. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01696006. Highlights • CT-MPI showed good agreement with SPECT by a semi-quantitative approach. • The % defect volume demonstrated excellent accuracy in the detection of perfusion abnormality on SPECT. • The % defect volume may play an additional role to identify myocardial perfusion defect and ischemia. [ABSTRACT FROM AUTHOR]

Abstract Purpose To evaluate gender-related differences in diagnostic accuracy of cadmium‑zinc-telluride (CZT) myocardial perfusion imaging in detecting single- and multi-vessel coronary artery disease (CAD). Methods We prospectively enrolled 1161 consecutive patients with known or suspected coronary artery disease (288, 25% women and 873, 75% men) who had been referred to our laboratory for stress–rest myocardial perfusion imaging (single-day stress–rest protocol, mean radiation dose: 4 mSv). All patients underwent coronary angiography within 30 days; significant CAD was defined in the presence of a coronary stenosis >70%. Summed stress scores (SSS), summed rest scores (SRS) and summed difference scores (SDS) were obtained. Image quality was graded "good" or better in >90% of patients. Results On coronary angiography, left main trunk, left anterior descending artery, left circumflex artery and right coronary artery obstructive stenosis were seen in 13, 486, 393 and 499 patients, respectively. Global SSS was the best predictor of CAD in women (AUC = 0.866, 81% sensitivity and 79% specificity) and in men (AUC = 0.871, 76% sensitivity and 84% specificity). Interestingly, its accuracy was maintained also in patients with two-vessel (women: AUC = 0.842, p < 0.001; men: AUC 0.839, p < 0.001) or three-vessel disease (women: AUC = 0.800, p < 0.001; men: AUC 0.804, p < 0.001). There was no gender-related difference in terms of diagnostic accuracy. Conclusions Evaluation of multivessel disease can be obtained by CZT camera in men as well as in women, with high accuracy at a lower radiation exposure. Highlights • Evaluation of multivessel disease can be obtained by CZT camera with high accuracy. • No difference in diagnostic accuracy between men and women was described. • CZT-based perfusion imaging allows a lower radiation exposure than standard SPECT. • CZT provides a thorough morpho-functional analysis to further discriminate patients. [ABSTRACT FROM AUTHOR]

Abstract Background Coronary computed tomography angiography (cCTA) has limited diagnostic accuracy in patients with intermediate to high pre-test likelihood of coronary artery disease (CAD) that may have large amounts of coronary calcium. Stress computed tomography myocardial perfusion (CTP) has emerged as a valuable strategy, combining anatomical and functional assessment of CAD. Purpose of the study is to evaluate the diagnostic accuracy of combining coronary artery imaging and myocardial perfusion in a single stress dataset versus invasive coronary angiography (ICA) and invasive fractional flow reserve (FFR) as reference standard. Methods One-hundred-thirty consecutive symptomatic patients (age: 65 ± 9 years; men: 70%) scheduled for clinically indicated ICA plus invasive FFR were prospectively enrolled. cCTA + CTP were simultaneously evaluated in a single stress-dataset by blinded readers and compared to ICA and invasive FFR findings. Results CTP was successfully performed in all patients. The most common artifacts observed in the stress dataset for coronary artery imaging were blooming effect and motion effect related. Overall evaluability of coronary arteries by using cCTA stress dataset was 93%. In a vessel and patient-based model, stress cCTA + stress CTP showed sensitivity, specificity, negative predictive value, positive predictive value and diagnostic accuracy of 93%, 94%, 97%, 85%, 94%, and 98%, 86%, 98%, 85%, 92%, respectively. The overall effective dose (ED) of stress protocol acquisition alone was 2.5 ± 1.1 mSv. Conclusions Simultaneous evaluation of coronary arteries and myocardial perfusion with single stress acquisition is feasible and it has diagnostic accuracy and low ED to identify functionally significant stenosis in patients with intermediate to high risk for CAD. Highlights • Single stress acquisition for simultaneous evaluation of coronary arteries and myocardial perfusion has high accuracy • It is possible to obtain anatomical and functional data with a single acquisition with less than 3 mSv. • Only a minority of patients may need a second rest-scan deriving a benefit in terms of radiation exposure and contrast load. [ABSTRACT FROM AUTHOR]

The three major techniques for clinically diagnosing coronary heart disease, including angina associated with myocardial ischemia, are coronary angiography, myocardial perfusion imaging, and drug stress echocardiography. Compared to the first two methods, which are invasive or involve the use of radionuclides, drug stress echocardiography is increasingly used in clinical practice due to its non-invasive, low-risk, and controllable nature, and wide applicability. We developed a novel methodology to demonstrate knowledge graph-based efficacy analysis of drug stress echocardiography as a complement to traditional meta-analysis. By measuring coronary flow reserve (CFR), we discovered that regional ventricular wall abnormalities (RVWA) and drug-loaded cardiac ultrasound can be used to detect coronary artery disease. Additionally, drug-loaded cardiac ultrasound can be used to identify areas of cardiac ischemia, stratify risks, and determine prognosis. Furthermore, adenosine stress echocardiography(ASE) can determine atypical symptoms of coronary heart disease with associated cardiac events through CFR and related quantitative indices for risk stratification. Using a knowledge graph-based approach, we investigated the positive and negative effects of three drugs - Dipyridamole, Dobutamine, and Adenosine - for coronary artery disease analysis. Our findings show that Adenosine has the highest positive effect and the lowest negative effect among the three drugs. Due to its minimal and controlled side effects, and high sensitivity for diagnosing coronary microcirculation disorders and multiple lesions, adenosine is frequently used in clinical practice. • Drug stress echocardiography is a low-risk, non-invasive diagnostic method for coronary artery disease. • ASE is highly sensitive, specific, and accurate in diagnosing multi-branch coronary artery lesions. • CFR values have important clinical value in prognostic assessment and functional evaluation. • ASE can determine atypical symptoms of coronary heart disease and associated cardiac events through CFR. • ASE is widely used in clinical practice due to its non-invasive nature, low adverse effects, and high sensitivity. [ABSTRACT FROM AUTHOR]

Abstract Background It has recently been shown that magnetic resonance (MR) “native T1” mapping is capable of characterizing abnormal microcirculation in patients with obstructive coronary artery disease (CAD). In studies involving women with signs and symptoms of ischemia and no obstructive CAD (INOCA), however, the potential role of native T1 as an imaging marker and its association with indices of diastolic function or vasodilator-induced myocardial ischemia have not been explored. We investigated whether native T1 in INOCA is associated with reduced myocardial perfusion reserve index (MPRI) or with diastolic dysfunction. Methods Twenty-two female patients with INOCA and twelve female reference controls with matching age and body-mass index were studied. The patients had evidence of vasodilator-induced ischemia without obstructive CAD or any prior infarction. All 34 subjects underwent stress/rest MR including native T1 mapping (MOLLI 5(3)3) at 1.5-Tesla. Results Compared with controls, patients had similar morphology/function. As expected, MPRI was significantly reduced in patients compared to controls (1.78 ± 0.39 vs. 2.49 ± 0.41, p < 0.0001). Native T1 was significantly elevated in patients (1040.1 ± 29.3 ms vs. 1003.8 ± 18.5 ms, p < 0.001) and the increased T1 showed a significant inverse correlation with MPRI (r = −0.481, p = 0.004), but was not correlated with reduced diastolic strain rate. Conclusions Symptomatic women with INOCA have elevated native T1 compared to matched reference controls and there is a significant association between elevated native T1 and impaired MPRI, considered a surrogate measure of ischemia severity in this cohort. Future studies in a larger cohort are needed to elucidate the mechanism underlying this inverse relationship. Highlights • Women with signs and symptoms of myocardial ischemia and no obstructive coronary artery disease (INOCA) often have coronary microvascular dysfunction. • In this pilot study, native T1 was significantly elevated in INOCA patients compared to matched reference controls. • The increased native T1 showed a significant inverse correlation with myocardial perfusion reserve index. • Native myocardial T1 may evolve as a useful imaging marker in serial studies of INOCA patients. [ABSTRACT FROM AUTHOR]

Aim Whether myocardial ischemia identified using myocardial perfusion imaging (MPI) can be an alternative target of coronary revascularization to reduce the incidence of cardiac events remains unclear. Methods and results This multicenter, prospective cohort study aimed to clarify the prognostic impact of reducing myocardial ischemia. Among 494 registered patients with possible or definite coronary artery disease (CAD), 298 underwent initial pharmacological stress 99m Tc-tetrofosmin MPI before, and eight months after revascularization or medical therapy, and were followed up for at least one year. Among these, 114 with at least 5% ischemia at initial MPI were investigated. The primary endpoints were cardiac death, non-fatal myocardial infarction and hospitalization for heart failure. Ischemia was reduced ≥5% in 92 patients. Coronary revascularization reduced ischemia ( n  = 89) more effectively than medical therapy ( n  = 25). Post-stress cardiac function also improved after coronary revascularization. Ejection fraction significantly improved at stress (61.0% ± 10.7% vs. 65.4% ± 11.3%; p  < 0.001) but not at rest (67.1% ± 11.3% vs. 68.3% ± 11.6%; p  = 0.144), among patients who underwent revascularization. Rates of coronary revascularization and cardiac events among the 114 patients were significantly higher (13.6%, p  = 0.035) and lower (1.1% p  = 0.0053), respectively, in patients with, than without ≥5% ischemia reduction. Moreover, patients with complete resolution of ischemia at the time of the second MPI had a significantly better prognosis. Conclusions Reducing ischemia by ≥5% and the complete resolution of ischemia could improve the prognosis of patients with stable CAD. [ABSTRACT FROM AUTHOR]

Purpose In a pig model of acute myocardial infarction (AMI), we validated a functional computed tomography (CT) technique for concomitant assessment of myocardial edema and ischemia through extravscualar contrast distribution volume (ECDV) and myocardial perfusion (MP) measurements from a single dynamic imaging session using a single contrast bolus injection. Methods In seven pigs, balloon catheter was used to occlude the distal left anterior descending artery for one hour followed by reperfusion. CT and cardiac magnetic resonance (CMR) imaging studies were acquired on 3 days and 12 ± 3 day post ischemic insult. In each CT study, 0.7 ml/kg of iodinated contrast was intravenously injected at 3–4 ml/s before dynamic contrast-enhanced (DCE) cardiac images were acquired with breath-hold using a 64-row CT scanner. DCE cardiac images were analyzed with a model-based deconvolution to generate ECDV and MP maps. ECDV as an imaging marker of edema was validated against CMR T2 weighted imaging in normal and infarcted myocardium delineated from ex-vivo histological staining. Results ECDV in infarcted myocardium was significantly higher (p < 0.05) than that in normal myocardium on both days post AMI and was in agreement with the findings of CMR T2 weighted imaging. MP was significantly lower (p < 0.05) in the infarcted region compared to normal on both days post AMI. Conclusion This imaging technique can rapidly and simultaneously assess myocardial edema and ischemia through ECDV and MP measurements, and may be useful for delineation of salvageable tissue within at-risk myocardium to guide reperfusion therapy. [ABSTRACT FROM AUTHOR]

Background In patients with angina undergoing invasive management, no obstructive coronary artery disease (NOCAD) is a common finding, and angina may persist following percutaneous coronary intervention (PCI). Coronary microvascular dysfunction may be relevant. We aimed to assess the proportion of patients presenting with suspected CAD who had coronary microvascular dysfunction. Methods Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 (CE-MARC 2) was a prospective multicenter randomised controlled trial of functional imaging versus guideline-based management in patients with suspected CAD. Invasive coronary angiography was protocol-directed. Fractional flow reserve (FFR) and parameters of microvascular function (coronary flow reserve (CFR), index of microcirculatory resistance (IMR), resistance reserve ratio (RRR)) were measured in major epicardial coronary arteries with ≥40–≤90% diameter stenosis. An FFR value ≤0.80 indicated the presence of obstructive CAD. Results 267/1202 (22.2%) patients underwent angiography and 81 (30%) patients had FFR measured. 63 (78%) of these patients had microvascular function assessed in 85 arteries (mean age 58.5 ± 8.2 years; 47 (75%) male). 25/63 (40%) patients had NOCAD, and of these, 17 (68%) had an abnormality ≥1 parameter of microvascular function (abnormal IMR (≥25), abnormal CFR (<2.0), and abnormal RRR (<2.0) occurred in 10 (40%), 12 (48%), and 11 (44%), respectively). 38/63 (60%) patients had obstructive epicardial CAD. Of these patients, 15/38 (39%), 20/38 (53%), and 12/38 (32%) had an abnormal IMR, CFR and RRR, respectively. Conclusions Coronary microvascular dysfunction is common in patients with angina. Invasive assessment of microvascular function may be informative and relevant for decision-making in patients with both NOCAD and obstructive epicardial CAD. Clinical trial registration ClinicalTrials.gov Identifier: NCT01664858 [ABSTRACT FROM AUTHOR]

Background There is growing concern about radiation exposure from nuclear myocardial perfusion imaging (MPI), particularly among younger patients who are more prone to develop untoward effects of ionizing radiation, and hence US and European professional society guidelines recommend age as a consideration in weighing radiation risk from MPI. We aimed to determine how patient radiation doses from MPI vary across age groups in a large contemporary international cohort. Methods Data were collected as part of a global cross-sectional study of centers performing MPI coordinated by the International Atomic Energy Agency (IAEA). Sites provided information on each MPI study completed during a single week in March–April 2013. We compared across age groups laboratory adherence to pre-specified radiation-related best practices, radiation effective dose (ED; a whole-body measure reflecting the amount of radiation to each organ and its relative sensitivity to radiation's deleterious effects), and the proportion of patients with ED ≤ 9 mSv, a target level specified in guidelines. Results Among 7911 patients undergoing MPI in 308 laboratories in 65 countries, mean ED was 10.0 ± 4.5 mSv with slightly higher exposure among younger age groups (trend p value < 0.001). There was no difference in the proportion of patients with ED ≤ 9 mSv across age groups, or in adherence to best practices based on the median age of patients in a laboratory. Conclusions In contemporary nuclear cardiology practice, the age of the patient appears not to impact protocol selection and radiation dose, contrary to professional society guidelines. [ABSTRACT FROM AUTHOR]

Background Comparing to SPECT and MRI, with higher temporal and spatial resolution and development of radiation dose reduction, myocardial computed tomography perfusion has emerged as a potential method for evaluation of hemodynamic myocardial ischemia. This meta-analysis systematically analyzed the performance of dynamic CT myocardial perfusion (DCTMP) to diagnose myocardial ischemia (MI) with clinically established reference methods [MR/SPECT/PET perfusion and fractional flow reserve (FFR)] as the reference standard. Methods We searched PubMed, Embase and web of science databases for all published studies that evaluated the accuracy of DCTMP to diagnose MI met our inclusion criteria. An exact binomial rendition of the bivariate mixed-effects regression model with test type as a random-effects covariate was performed to synthesize the available data. Results The search revealed 13 eligible studies including 482 patients. The pooled sensitivity and specificity of myocardial blood flow (MBF) were 0.83 (95% CI: 0.80 to 0.86) and 0.90 (95% CI: 0.88 to 0.91) at the segment level, 0.85 (95% CI: 0.80 to 0.88) and 0.81 (95% CI: 0.78 to 0.84) at the artery level, and 0.93 (95% CI: 0.82 to 0.98) and 0.82 (95% CI: 0.70 to 0.91), at the patient level, respectively. The high area under the sROC curves of MBF were 0.944 at segment level, 0.911 at vessel level and 0.949 at patient level, respectively. Conclusions DCTMP has a high diagnostic accuracy in detecting myocardial ischemia and it may increase significantly at segment level in combined use of coronary CTA. [ABSTRACT FROM AUTHOR]

Background Full body scintigraphy using bone tracers plays an important role in defining the type of amyloidosis and in diagnosing the heart involvement (cardiac amyloidosis, CA). No study has been conducted to explore lung retention (LR) in CA and its correlation to heart retention (HR).We evaluated LR in patients undergoing 99mTc-HMDP scintigraphy during evaluation for suspected CA. Methods and results We enrolled 93 suspected CA patients. Patients underwent a complete diagnostic work up. After diagnostic process 82 patients resulted affected by certain CA (20 AL and 62 TTR), while 11 subjects showed left ventricular hypertrophy (LVH) not caused by CA. 99mTc-HMDP cardiac uptake was evaluated using the Perugini visual score while the modified Janssen score was used for LR estimation (grade 0 no uptake, grade 1 less than ribs, grade 2 more than ribs). Results 99mTc-HMDP LR was observed in 1/20 AL patient (5%), while 36/62 (58%) TTR patients showed LR with 29 grade 1 (47%) and 7 grade 2 (11%). No LR was observed in patients with LVH and no CA. LR was not evident in patients without HR, present in 1/3 (33%) of the patients with Perugini 1 HR and 11/24 (46%) and 26/36 (72%) of the patients showing respectively a Perugini 2 and a Perugini 3. Conclusion 99mTc-HMDP scintigraphy shows LR in about 60% of TTR subjects, related to the grade of HR. In AL amyloidosis LR is less frequent than in TTR amyloidosis suggesting an aetiological tropism that seems comparable to the already known TTR related cardiac tropism. [ABSTRACT FROM AUTHOR]

Purpose We implemented and validated a compressed sensing (CS) based algorithm for reconstructing dynamic contrast-enhanced (DCE) CT images of the heart from sparsely sampled X-ray projections. Methods DCE CT imaging of the heart was performed on five normal and ischemic pigs after contrast injection. DCE images were reconstructed with filtered backprojection (FBP) and CS from all projections (984-view) and 1/3 of all projections (328-view), and with CS from 1/4 of all projections (246-view). Myocardial perfusion (MP) measurements with each protocol were compared to those with the reference 984-view FBP protocol. Results Both the 984-view CS and 328-view CS protocols were in good agreements with the reference protocol. The Pearson correlation coefficients of 984-view CS and 328-view CS determined from linear regression analyses were 0.98 and 0.99 respectively. The corresponding mean biases of MP measurement determined from Bland-Altman analyses were 2.7 and 1.2 ml/min/100 g. When only 328 projections were used for image reconstruction, CS was more accurate than FBP for MP measurement with respect to 984-view FBP. However, CS failed to generate MP maps comparable to those with 984-view FBP when only 246 projections were used for image reconstruction. Conclusion DCE heart images reconstructed from one-third of a full projection set with CS were minimally affected by aliasing artifacts, leading to accurate MP measurements with the effective dose reduced to just 33% of conventional full-view FBP method. The proposed CS sparse-view image reconstruction method could facilitate the implementation of sparse-view dynamic acquisition for ultra-low dose CT MP imaging. [ABSTRACT FROM AUTHOR]

Peripheral arterial disease (PAD), is a major health problem. Many studies have been focused on the possibilities of treatment offered by vascular regeneration. Human adipose-derived stem cells (HASCs), multipotent CD34 + stem cells found in the stromal-vascular fraction of adipose tissues, which are capable to differentiate into multiple mesenchymal cell types. The High mobility group box 1 protein (HMGB1) is a nuclear protein involved in angiogenesis. The aim of the study was to define the role of HMGB1 in cell therapy with HASCs, in an animal model of PAD. We induced unilateral ischemia in mice and we treated them with HASCs, with the specific HMGB1-inihibitor BoxA, with HMGB1 protein, and with the specific VEGF inhibitor sFlt1, alternately or concurrently. We measured the blood flow recovery in all mice. Immunohistochemical and ELISA analyses was performed to evaluate the number of vessels and the VEGF tissue content. None auto-amputation occurred and there have been no rejection reactions to the administration of HASCs. Animals co-treated with HASCs and HMGB1 protein had an improved blood flow recovery, compared to HASCs-treated mice. The post-ischemic angiogenesis was reduced when the HMGB1 pathway was blocked or when the VEGF activity was inhibited, in mice co-treated with HASCs and HMGB1. In conclusion, the HASCs treatment can be used in a mouse model of PAD to induce post-ischemic angiogenesis, modulating angiogenesis by HMGB1. This effect is mediated by VEGF activity. Although further data are needed, these findings shed light on possible new cell treatments for patients with PAD. [ABSTRACT FROM AUTHOR]

Background Quantitative assessment of myocardial flow reserve (MFR) by single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is challenging but may facilitate evaluation of multi-vessel coronary artery disease (CAD). Methods We enrolled 153 patients with suspected or known CAD, referred for pharmacological stress MPI. They underwent a 99m Tc-perfusion stress/rest SPECT with an ultrafast cadmium-zinc-telluride (CZT) camera. Dynamic data were acquired and time-activity curves fitted to a 1-tissue compartment analysis with input function. K1 was assigned for stress and rest data. The MFR index (MFR i ) was calculated as K1 stress/K1 at-rest. The findings were validated by invasive coronary angiography in 69 consecutive patients. Results The global MFR i was 1.46 (1.16–1.76), 1.33 (1.12–1.54), and 1.18 (1.01–1.35), for 1-vessel disease (VD), 2-VD, and 3-VD, respectively. In the 3-VD, global MFR i was lower than that in 0-VD (1.63 [1.22–2.04], P < 0.0001) and 1-VD (P = 0.003). Multivariate logistic regression analysis for 3-VD showed significant associations with smoking history (odds ratio [OR]: 4.4 [0.4–8.4]), left ventricular ejection fraction (OR: 61.6 [57.5–66.0]), and global MFR i (OR: 119.6 [111.5–127.7], P = 0.002). A cut-off value of 1.3 yielded 93.3% sensitivity and 75.9% specificity for diagnosing 3-VD. Fractional flow reserve positively correlated with regional MFR i (r = 0.62, P = 0.008), and the SYNTAX score correlated negatively with global MFR i (r = 0.567, P = 0.0003). Conclusion We developed and validated a clinically available method for MFR quantification by dynamic 99m Tc-perfusion SPECT utilizing a CZT camera, which improves the detectability of multi-vessel CAD. [ABSTRACT FROM AUTHOR]

Aims Evaluation of predictors of silent coronary artery disease (SCAD) in high-risk asymptomatic diabetic patients and to evaluate their two-year outcome. Methods and results Four hundred diabetic patients without prior CAD but at high CAD risk underwent myocardial perfusion scintigraphy (MPS) in this prospective multicentre outcome trial. MPS were abnormal in 22% of patients. Male sex (OR 2.223, 1.152–4.290; p = 0.017), diabetes duration (OR 1.049,1.015–1.085; p = 0·005), peripheral artery disease (OR 2.134, 1·150–3.961; p = 0.016), smoking (OR 2.064, 1.109–3.839; p = 0·022), systolic blood pressure (OR 1.014, 1.00–1.03, p = 0·056), brain natriuretic peptide (OR 1.002, 1.001–1.004, p = 0·005) independently predicted an abnormal MPS: if < 2 and > 3 predictors were present, 3.2% and 47% patients had an abnormal MPS, respectively (p < 0·001). Two-year major adverse cardiac event rates increased from 2·9% to 14·6%, cardiac death rates from 0·6% to 4·1% in patients with summed stress scores ≤ 10 and > 10%, respectively (each p < 0.045). Conclusions Male sex, diabetes duration, peripheral artery disease, smoking, elevated systolic blood pressure and increased brain-natriuretic peptides independently predicted SCAD. In presence of > 3 predictors, almost 50% of patients had an abnormal MPS. They may benefit from screening by MPS since the extent of the MPS abnormality discriminated clearly between a favourable compared to a bad 2-year outcome. However, even highest risk patients without objective evidence of CAD had a benign prognosis without need for specific evaluation or therapy. Trial Registration Number: ISRCTN87953632. [ABSTRACT FROM AUTHOR]

Background Exercise ECG stress testing is the most widely available method for evaluation of patients with suspected myocardial ischemia. Its major limitation is the relatively poor accuracy of ST-segment changes regarding ischemia detection. Little is known about the optimal method to assess ST-deviations. Methods A total of 1558 consecutive patients undergoing bicycle exercise stress myocardial perfusion imaging (MPI) were enrolled. Presence of inducible myocardial ischemia was adjudicated using MPI results. The diagnostic value of ST-deviations for detection of exercise-induced myocardial ischemia was systematically analyzed 1) for each individual lead, 2) at three different intervals after the J-point (J + 40 ms, J + 60 ms, J + 80 ms), and 3) at different time points during the test (baseline, maximal workload, 2 min into recovery). Results Exercise-induced ischemia was detected in 481 (31%) patients. The diagnostic accuracy of ST-deviations was highest at + 80 ms after the J-point, and at 2 min into recovery. At this point, ST-amplitude showed an AUC of 0.63 (95% CI 0.59–0.66) for the best-performing lead I. The combination of ST-amplitude and ST-slope in lead I did not increase the AUC. Lead I reached a sensitivity of 37% and a specificity of 83%, with similar sensitivity to manual ECG analysis (34%, p = 0.31) but lower specificity (90%, p < 0.001). Conclusion When using ECG stress testing for evaluation of patients with suspected myocardial ischemia, the diagnostic accuracy of ST-deviations is highest when evaluated at + 80 ms after the J-point, and at 2 min into recovery. [ABSTRACT FROM AUTHOR]

Background Peripheral Raynaud's phenomenon (RP) is either primary (PRP), without any coexisting disease or secondary (SRP), due to connective tissue diseases (CTD). We hypothesized that adenosine stress cardiovascular magnetic resonance (CMR) can assess myocardial perfusion in a population of PRP and SRP. Patients-methods Twenty CTDs, aged 30.6 ± 7.5 yrs., 16F/4M, including 9 systemic sclerosis (SSc), 4 systemic lupus erythematosus (SLE), 3 mixed connective tissue disease (MCTD), 2 polymyositis (PM) and 2 rheumatoid arthritis (RA), with SRP, under treatment with calcium blockers, were evaluated by stress CMR and compared with age-sex matched PRP and controls. All RP patients were under treatment with calcium blockers. Stress perfusion CMR was performed by 1.5 T system using 140 mg/kg/min adenosine for 4 min and 0.05 mmol/kg Gd-DTPA for first-pass perfusion. A rest perfusion was performed with the same protocol. Late gadolinium enhanced (LGE) images were acquired after another dose of Gd-DTPA. Results In both PRP, SRP, the myocardial perfusion reserve index (MPRI) was significantly reduced compared with the controls (1.7 ± 0.6 vs 3.5 ± 0.4, p < 0.001 and 0.7 ± 0.2 vs 3.5 ± 0.4, p < 0.001, respectively). Furthermore, in SRP, MPRI was significantly reduced, compared with PRP (0.7 ± 0.2 vs 1.7 ± 0.6, p < 0.001). Subendo-cardial LGE = 8.2 ± 1.7 of LV mass was revealed in 1 SLE, 1MCTD and 2 SSc, but in none of PR patients. Conclusions MPRI reduction is common in both PRP and SRP, but it is more severe in SRP, even if RP patients are under treatment with calcium blockers. Occult fibrosis may coexist with the reduced MPRI in SRP but not in PRP. [ABSTRACT FROM AUTHOR]

Background Morphine is frequently used in ST-segment elevation myocardial infarction (STEMI) patients, even if recently it has been associated with a delayed onset of action of the oral antiplatelet agents. There are no data regarding the impact of morphine on myocardial reperfusion after primary percutaneous coronary intervention (PPCI). Objective This study sought to assess myocardial reperfusion by early ST-segment resolution (≥ 50% at 30 minutes) according to morphine use in STEMI patients undergoing PPCI. Methods 182 STEMI patients undergoing PPCI and receiving either prasugrel (n = 51) or ticagrelor (n = 131), who were antiplatelet and anticoagulant therapies naïve, were included in the study. All patients had serial ST-segment elevation evaluations by ECG and residual platelet reactivity assessments by VerifyNow P2Y12 Reactivity Units (PRU). Results Overall, 74 (41%) patients received morphine according to the attending physician's preference and showed lower ST-segment resolution rate as compared with patients without morphine (76% vs 87%, p = 0.047). Higher baseline TIMI flow < 2 rate (79% vs 64%, p = 0.036) and peak CPK values (1821 [924–3283] U/L vs 1483 [718–2327] U/L, p = 0.034) were observed in morphine patients. Moreover, a delayed response to oral antiplatelet (PRU area under the curve [AOU0–8]: 1448 ± 448 vs 686 ± 292, p = 0.001) was documented in patients with morphine as compared with those without. The independent predictors of early ST-segment elevation resolution failure were PRU ≥ 208 after antiplatelet loading (OR 2.78, 95% CI 1.08–7.14; p = 0.034) and TIMI flow grade < 3 after PPCI (OR 5.89, 95% CI 1.64–21.12; p = 0.009), but not morphine use. Conclusions In STEMI patients undergoing PPCI, morphine use is associated with a higher residual platelet reactivity and a poorer myocardial reperfusion. Independent predictors of impaired myocardial reperfusion were high residual platelet reactivity and TIMI flow grade after PPCI but not morphine use, questioning the direct relationship between morphine and worse myocardial reperfusion. [ABSTRACT FROM AUTHOR]

Background To analyse prognosis according to different clinical, electrocardiographic and scintigraphic responses on stress myocardial perfusion scintigraphy. Methods 3579 consecutive patients (age 63.1 ± 12; women: 46.8%) without known coronary artery disease were evaluated with a stress-rest myocardial perfusion single photon emission computed tomography (SPECT). In accordance with clinical (chest pain: ChP), electrocardiographic (ST +) and scintigraphic (SPECT +) ischemia criteria, patients were divided into 5 groups: Group 1 (n = 1902; with normal exercise test and SPECT without ChP); Group 2 (n = 456): ChP −, ST + and SPECT −; Group 3 (n = 594): ChP − and SPECT +; Group 4 (n = 444): ChP + and SPECT −; and Group 5 (n = 183): ChP + and SPECT +. Results During a follow-up of 5.1 ± 3.4 years, cardiac events (CE: cardiac mortality or nonfatal myocardial infarction) were significantly higher in groups 2 to 5 than in group 1 (p < 0.001). There was a trend to increased CE in patients with silent myocardial ischemia (SMI: Groups 2 and 3) vs symptomatic ischemia (Groups 4 and 5). Predictive value for CE of patients with SMI was HR: 3.1 (95%CI:2.1–4.4), and HR: 2.4 (95%CI:1.5–3.7) of patients with symptomatic ischemia. SMI was observed in 34.6% of diabetic patients vs 28.1% in nondiabetic patients (p = 0.001). Prognosis of patients with ST + plus SPECT + was significantly worse than patients with only ST + or only SPECT + (HR: 1.7, p = 0.026). Conclusions SMI has incremental prognostic value over clinical variables and symptomatic ischemia. In the context of SMI, a similar prognosis was observed between patients with only ST + and patients with only SPECT +, but significant worse prognosis was observed in patients with ST + plus SPECT +. [ABSTRACT FROM AUTHOR]