Rationale and design of the Clinical Evaluation of Magnetic Resonance Imaging in Coronary heart disease 2 trial (CE-MARC 2): a prospective, multicenter, randomized trial of diagnostic strategies in suspected coronary heart disease

Background: A number of investigative strategies exist for the diagnosis of coronary heart disease (CHD). Despite the widespread availability of noninvasive imaging, invasive angiography is commonly used early in the diagnostic pathway. Consequently, approximately 60% of angiograms reveal no evidence of obstructive coronary disease. Reducing unnecessary angiography has potential financial savings and avoids exposing the patient to unnecessary risk. There are no large-scale comparative effectiveness trials of the different diagnostic strategies recommended in international guidelines and none that have evaluated the safety and efficacy of cardiovascular magnetic resonance.<p></p> Trial Design: CE-MARC 2 is a prospective, multicenter, 3-arm parallel group, randomized controlled trial of patients with suspected CHD (pretest likelihood 10%-90%) requiring further investigation. A total of 1,200 patients will be randomized on a 2:2:1 basis to receive 3.0-T cardiovascular magnetic resonance–guided care, single-photon emission computed tomography–guided care (according to American College of Cardiology/American Heart Association appropriate-use criteria), or National Institute for Health and Care Excellence guidelines–based management. The primary (efficacy) end point is the occurrence of unnecessary angiography as defined by a normal (>0.8) invasive fractional flow reserve. Safety of each strategy will be assessed by 3-year major adverse cardiovascular event rates. Cost-effectiveness and health-related quality-of-life measures will be performed.<p></p> Conclusions: The CE-MARC 2 trial will provide comparative efficacy and safety evidence for 3 different strategies of investigating patients with suspected CHD, with the intension of reducing unnecessary invasive angiography rates. Evaluation of these management strategies has the potential to improve patient care, health-related quality of life, and the cost-effectiveness of CHD investigation

Combined anatomical and clinical factors for the long-term risk stratification of patients undergoing percutaneous coronary intervention: the Logistic Clinical SYNTAX score

Background The SYNTAX score (SXscore), an anatomical-based scoring tool reflecting the complexity of coronary anatomy, has established itself as an important long-term prognostic factor in patients undergoing percutaneous coronary intervention (PCI). The incorporation of clinical factors may further augment the utility of the SXscore to longer-term risk stratify the individual patient for clinical outcomes. Methods and results Patient-level merged data from >6000 patients in seven contemporary coronary stent trials was used to develop a logistic regression model—the Logistic Clinical SXscore—to predict 1-year risk for all-cause death and major adverse cardiac events (MACE). A core model (composed of the SXscore, age, creatinine clearance, and left ventricular ejection fraction) and an extended model [incorporating the core model and six additional (best performing) clinical variables] were developed and validated in a cross-validation procedure. The core model demonstrated a substantial improvement in predictive ability for 1-year all-cause death compared with the SXscore in isolation [area under the receiver operator curve (AUC): core model: 0.753, SXscore: 0.660]. A minor incremental benefit of the extended model was shown (AUC: 0.791). Consequently the core model alone was retained in the final the Logistic Clinical SXscore model. Validation plots confirmed the model predictions to be well calibrated. For 1-year MACE, the addition of clinical variables did not improve the predictive ability of the SXscore, secondary to the SXscore being the predominant determinant of all-cause revascularization. Conclusion The Logistic Clinical SXscore substantially enhances the prediction of 1-year mortality after PCI compared with the SXscore, and allows for an accurate personalized assessment of patient ris

Novel Imaging Approaches for the Detection of Hemodynamically Significant Coronary Artery Disease: Quantitative Flow Ratio and Artificial Intelligence-Based Ischemia Algorithm

ABSTRACT In coronary artery disease (CAD), the decision on revascularization is based on the hemodynamic significance of stenoses. However, this cannot directly be determined from the first-line anatomical imaging methods coronary computed tomography angiography (CCTA) in chronic coronary syndrome (CCS) or invasive coronary angiography (ICA) in acute coronary syndrome (ACS). The aim of this thesis was to investigate the prognostic value of two novel approaches to determine functionally significant CAD according to impaired invasive fractional flow reserve (FFR) directly from CCTA in CCS and ICA in ACS. Quantitative flow ratio (QFR) is a novel computational fluid dynamic-based technique to estimate the presence of impaired FFR from biplane ICA. In this study, QFR from untreated non-culprit lesions showed incremental 5-year prognostic value for major adverse cardiac events among ST-elevation myocardial infarction patients undergoing angiography-guided complete revascularization. However, non-culprit QFR did not independently predict non-target-vessel related events prior to planned staged percutaneous coronary intervention (PCI) in ACS patients, and the study does not provide conceptual evidence that QFR could be useful to refine the timing of staged PCI on top of clinical judgement. AI-QCTischemia is an artificial intelligence-based method to predict the probability of an impaired invasive FFR using 37 morphological features from CCTA. Among symptomatic patients with suspected CAD undergoing CCTA, AI-QCTischemia showed incremental prognostic value for the composite of death, myocardial infarction, or unstable angina pectoris throughout a median of 7 years follow-up. This risk stratification pertained especially to patients with no/non-obstructive disease. Patients with obstructive disease on CCTA were referred for downstream myocardial perfusion imaging with positron emission tomography (PET), and among those, AI-QCTischemia showed incremental risk stratification among patients with normal PET perfusion, but not among those with abnormal PET perfusion. KEYWORDS: coronary artery disease, quantitative flow ratio, coronary computed tomography angiography, artificial intelligence, prognosisTIIVISTELMÄ Sepelvaltimotaudissa revaskularisaatiopäätös perustuu hemodynaamisesti merkittävän ahtauman osoitukseen. Tätä ei voida kuitenkaan suoraan määrittää kaikilla kuvantamismenetelmillä, kuten sepelvaltimoiden tietokonetomografialla (TT) kroonisessa sepelvaltimo-oireyhtymässä tai kajoavalla angiografialla akuutissa sepelvaltimotautikohtauksessa. Tämän väitöskirjan tavoitteena oli tutkia kahden uuden sepelvaltimoahtauman hemodynaamisen merkityksen arvioimiseen käytettävän menetelmän ennusteellista arvoa: kajoavaan angiografiaan pohjautuva menetelmä akuutissa sepelvaltimotautikohtauksessa ja TT:aan pohjautuva menetelmä kroonisessa sepelvaltimo-oireyhtymässä. Kvantitatiivinen virtaussuhde (KVS) on uusi laskennalliseen virtausdynamiikkaan perustuva menetelmä, jolla kajoavaan painevaijerimittaukseen perustuvaa sydänlihas-iskemiaa pyritään arvioimaan suoraan tavanomaisista angiografiakuvista. Ei-revaskularisoidun non-culprit-ahtauman KVS:n määrityksellä osoitettiin ennusteellista lisäarvoa 5 vuoden sydän- ja verisuonitautitapahtumien suhteen ST-nousuinfarkti-potilailla, joille oli tehty angiografiaohjattu täydellinen revaskularisaatio. Non-culprit-ahtauman KVS ei kuitenkaan ennustanut kyseiseen suoneen liittyviä tapahtumia ennen suunniteltua viivästettyä non-culprit-ahtauman perkutaanista sepelvaltimotoimenpidettä, joten tämän tutkimuksen perusteella KVS ei vaikuta hyödylliseltä menetelmältä viivästetyn sepelvaltimotoimenpiteen ajoituksen optimoimiseksi. AI-QCTischemia on tekoälyyn perustuva menetelmä, jolla arvioidaan kajoavaan painevaijerimittaukseen perustuvan sydänlihasiskemian todennäköisyyttä käyttäen 37 morfologista sepelvaltimoiden TT:aan pohjautuvaa muuttujaa. Oireisilla potilailla, joille tehtiin TT-tutkimus sepelvaltimotaudin epäilyn vuoksi, AI-QCTischemia tarjosi ennusteellista lisäarvoa yhdistelmätapahtumalle (kuolema, sydäninfarkti tai epävakaa angina pectoris) 7 vuoden seurannan aikana. Tämä riskiluokittelu koski erityisesti potilaita, joilla ei todettu ahtauttavaa sepelvaltimotautia TT:ssa. Potilaat, joilla todettiin TT:n perusteella ahtauttava sepelvaltimotauti, ohjattiin sydänlihasperfuusion kuvantamiseen positroniemissiotomografialla (PET). Tässä joukossa AI-QCTischemia antoi ennusteellista lisätietoa potilailla, joilla oli normaali sydänlihasperfuusio, mutta ei niillä, joilla perfuusio oli alentunut. AVAINSANAT: sepelvaltimotauti, kvantitatiivinen virtaussuhde, tietokonetomografia, tekoäly, ennust

Clinical outcomes of percutaneous coronary intervention in patients turned down for surgical revascularization

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137727/1/ccd26781_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137727/2/ccd26781.pd

Risk scores of bleeding complications in patients on dual antiplatelet therapy. how to optimize identification of patients at risk of bleeding after percutaneous coronary intervention

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor in patients undergoing percutaneous coronary intervention (PCI) reduces the risk of ischemic events but reduces the risk of ischemic events but increases the risk of bleeding, which in turn is associated with increased morbidity and mortality. With the aim to offer personalized treatment regimens to patients undergoing PCI, much effort has been devoted in the last decade to improve the identification of patients at increased risk of bleeding complications. Several clinical scores have been developed and validated in large populations of patients with coronary artery disease (CAD) and are currently recommended by guidelines to evaluate bleeding risk and individualize the type and duration of antithrombotic therapy after PCI. In clinical practice, these risk scores are conventionally computed at the time of PCI using baseline features and risk factors. Yet, bleeding risk is dynamic and can change over time after PCI, since patients can worsen or improve their clinical status and accumulate comorbidities. Indeed, evidence now exists that the estimated risk of bleeding after PCI can change over time. This concept is relevant, as the inappropriate estimation of bleeding risk, either at the time of revascularization or subsequent follow-up visits, might lead to erroneous therapeutic management. Serial evaluation and recalculation of bleeding risk scores during follow-up can be important in clinical practice to improve the identification of patients at higher risk of bleeding while on DAPT after PCI

Optimization of treatment in patients undergoing coronary revascularization:From subgroup analysis to heterogeneity of treatment effect

Randomized controlled trial is the gold standard to evaluate the efficacy and safety of one treatment over another. While randomization ensures the comparability of treatment groups, randomized clinical trials usually provide average treatment effect as a summary result, which is less meaningful to physicians who treat individual patients. Alternatively, predictive approaches to treatment effect heterogeneity (PATH) are recommended to estimate heterogeneity of treatment effect across individuals. This method can predict risks of adverse events after treatment and thereby to stratify patients at a low to high risk for adverse events. In this thesis, we found that the SYNTAX score and its variants (the CABG SYNTAX score and residual SYNTAX score) could identify patients at higher risk of mortality after myocardial revascularization, who require more intensive pharmacological treatments for secondary prevention and need to be closely monitored during follow-up. Another strength of predictive models is to estimate which of two treatments will be preferred for individual patients when multiple patient characteristics that affect benefits or harms of treatments are taken into consideration simultaneously. In this thesis, we redeveloped the SYNTAX score II for the optimal mode of myocardial revascularization in patients with complex coronary artery disease, and we described the risks of a purely data-driven approach to discover a statistically significant predictive factor when developing models. The PATH can help the heart team provide patients and their families with a more transparent and shared decision-making process by providing objective, evidence-based information prior to treatments

Coronary revascularization strategies and the effects of diabetes complications on poor health

Objectives: This research assessed the effect of comorbid diabetes complications on short-term adverse outcomes: in-hospital mortality, postoperative stroke, postoperative renal failure and readmissions within 30 days of discharge after coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) among patients age 45 and older who have diabetes. The analysis compared differences in outcomes for CABG and PCI and for off-pump and on-pump CABG. The analysis also focused on assessing associations between structure and process factors and the study outcomes. Specifically for readmissions, the effect of discharge disposition was evaluated, including discharge to home without home health care (HHC), to home with HHC, and to a transitional care facility. Methods: In-hospital mortality, postoperative stroke, and postoperative renal failure were assessed using the 2007 Nationwide Inpatient Sample (NIS) database. Readmission was categorized into early (=10 days) and late (11 to 30 days), and assessed using the 2007 State Inpatient Databases (SIDs) for Arizona, California, and Florida. Analyses included chi-square, t-test, propensity adjusted multivariate logistic regression, multilevel regression, and Cox proportional hazard regression. Analyses using the NIS data accounted for the survey design and were weighted for national representation. Covariates included age, race/ethnicity, health insurance, median household income, gender, 30 comorbidities, illness acuity measure, procedure volume and hospital characteristics. Results: In adjusted analyses, patients with comorbid diabetes complications were more likely to have in-hospital mortality with both CABG (Odds Ratio, OR 1.60; 95% Confidence Interval, CI 1.22-2.10) and PCI (OR 1.59, CI 1.27-1.99) than those without diabetes complications. Their odds of renal failure were higher with PCI than CABG (OR 4.27 vs. 2.25, p<0.05). Further, they were more likely to have postoperative stroke with off-pump CABG (OR 1.69, CI 1.10-2.60). For readmissions, the adjusted hazard of early (Hazard Ratio, HR 1.24, CI 1.08-1.42) and late (HR 1.27, CI 1.11-1.39) readmissions for those with comorbid diabetes complications and early (HR 4.16, CI 3.53-4.91) and late (HR 1.88, CI 1.69-2.10) readmissions for patients discharged to a transitional care facility were higher. Discharge to home with HHC (HR 1.24, CI 1.12-1.36) was associated only with late readmission. Discussion: Regardless of the revascularization strategy, patients with comorbid diabetes complications may have higher risks of in-hospital death after coronary revascularization. Effects of comorbid diabetes complications on poor outcomes should be considered when making clinical decisions about CABG and PCI for patients with diabetes. Comprehensive discharge planning may be needed to identify potential vulnerabilities, such as a predisposition to poor diabetes management for patients with comorbid diabetes, to reduce their risk for readmission. Further research should examine the association between termination of HHC services and late readmission for patients using HHC services after discharge