BACKGROUND AND AIMS:The randomized CENTURY trial tested the hypothesis that a comprehensive strategy integrating intense lifestyle modification and aggressive medical management to goals with revascularization reserved for severely reduced coronary flow capacity (CFC) by positron emission tomography (PET) would reduce risk factors, subsequent revascularization, death and myocardial infarction (MI) compared with standard of care in chronic stable coronary artery disease (CAD). METHODS:Participants were randomly assigned to standard or comprehensive care groups. Rest-stress PET quantified CFC for physiological CAD severity at baseline, 2, 5, and up to 11 years. The comprehensive care group reviewed PET results with frequent clinic visits and open 24/7 phone/email support. Standard care lacked supportive contact with blinded PET results that were unblinded only for severely reduced CFC with high mortality risk for potential revascularization. RESULTS:Between 2009-2017, 515 patients were assigned to comprehensive care and 513 to standard care and followed for 5 or more years. Comprehensive vs standard care decreased risk factors and summed 5-year risk score (Δ-1.1 vs + 0.33; 95% confidence interval -1.84 to -0.97; P < .0001), decreased cumulative 11-year all-cause death (4.7% vs 8.2%; P = .023), death or MI (7.0% vs 11.1%; P = .024) late revascularization (9.5% vs 14.8%; P = .021) and major adverse cardiac events (20.5% vs 29.9%; P = .0006). Only 56 of 1028 (5.4%) CENTURY patients with chronic CAD had revascularization within 90 days predominantly guided by CFC severity. CONCLUSIONS:The randomized CENTURY trial demonstrates that comprehensive integrated lifestyle modification and medical management towards goals with revascularization reserved for severely reduced CFC, significantly reduced risk factor scores, death, death or MI, and revascularization. CLINICALTRIALS.GOV:NCT00756379.

Background and Aims Coronary flow capacity (CFC) is associated with an observed 10-year survival probability for individual patients before and after actual revascularization for comparison to virtual hypothetical ideal complete revascularization.Methods Stress myocardial perfusion (mL/min/g) and coronary flow reserve (CFR) per pixel were quantified in 6979 coronary artery disease (CAD) subjects using Rb-82 positron emission tomography (PET) for CFC maps of artery-specific size-severity abnormalities expressed as percent left ventricle with prospective follow-up to define survival probability per-decade as fraction of 1.0.Results Severely reduced CFC in 6979 subjects predicted low survival probability that improved by 42% after revascularization compared with no revascularization for comparable severity (P = .0015). For 283 pre-and-post-procedure PET pairs, severely reduced regional CFC-associated survival probability improved heterogeneously after revascularization (P < .001), more so after bypass surgery than percutaneous coronary interventions (P < .001) but normalized in only 5.7%; non-severe baseline CFC or survival probability did not improve compared with severe CFC (P = .00001). Observed CFC-associated survival probability after actual revascularization was lower than virtual ideal hypothetical complete post-revascularization survival probability due to residual CAD or failed revascularization (P < .001) unrelated to gender or microvascular dysfunction. Severely reduced CFC in 2552 post-revascularization subjects associated with low survival probability also improved after repeat revascularization compared with no repeat procedures (P = .025).Conclusions Severely reduced CFC and associated observed survival probability improved after first and repeat revascularization compared with no revascularization for comparable CFC severity. Non-severe CFC showed no benefit. Discordance between observed actual and virtual hypothetical post-revascularization survival probability revealed residual CAD or failed revascularization.

BACKGROUND:The literature reports no randomized trial in chronic coronary artery disease (CAD) of a comprehensive management strategy integrating intense lifestyle management, maximal medical treatment to specific goals and high precision quantitative cardiac positron emission tomography (PET) for identifying high mortality risk patients needing essential invasive procedures. We hypothesize that this comprehensive strategy achieves greater risk factor reduction, lower major adverse cardiovascular events and fewer invasive procedures than standard practice. METHODS:The CENTURY Study (NCT00756379) is a randomized-controlled-trial study in patients with stable or at high risk for CAD. Patients are randomized to standard of care (Standard group) or intense comprehensive lifestyle-medical treatment to targets and PET guided interventions (Comprehensive group). Comprehensive Group patients are regularly consulted by the CENTURY team implementing diet/lifestyle/exercise program and medical treatment to target risk modification. Cardiac PET at baseline, 24-, and 60-months quantify the physiologic severity of CAD and guide interventions in the Comprehensive group while patients and referring physicians of the Standard group are blinded to PET results. The primary end-point is the CENTURY risk score reduction during 5 years follow-up. The secondary endpoint is a composite of death, non-fatal myocardial infarction, stroke, and coronary revascularization. CONCLUSIONS:The CENTURY Study is the first study in stable CAD to test the incremental benefit of a comprehensive strategy integrating intense lifestyle modification, medical treatment to specific goals, and high-precision quantitative myocardial perfusion imaging to guide revascularization. A total of 1028 patients have been randomized, and the 5 years follow-up will conclude in 2022.

Because randomized coronary revascularization trials in stable coronary artery disease (CAD) have shown no reduced myocardial infarction (MI) or mortality, the threshold of quantitative myocardial perfusion severity was analyzed for association with reduced death, MI, or stroke after revascularization within 90 d after PET. Methods: In a prospective long-term cohort of stable CAD, regional, artery-specific, quantitative myocardial perfusion by PET, coronary revascularization within 90 d after PET, and all-cause death, MI, and stroke (DMS) at 9-y follow-up (mean ± SD, 3.0 ± 2.3 y) were analyzed by multivariate Cox regression models and propensity analysis. Results: For 3,774 sequential rest–stress PET scans, regional, artery-specific, severely reduced coronary flow capacity (CFC) (coronary flow reserve ≤ 1.27 and stress perfusion ≤ 0.83 cc/min/g) associated with 60% increased hazard ratio for major adverse cardiovascular events and 30% increased hazard of DMS that was significantly reduced by 54% associated with revascularization within 90 d after PET (P = 0.0369), compared with moderate or mild CFC, coronary flow reserve, other PET metrics or medical treatment alone. Depending on severity threshold for statistical certainty, up to 19% of this clinical cohort had CFC severity associated with reduced DMS after revascularization. Conclusion: CFC by PET provides objective, regional, artery-specific, size–severity physiologic quantification of CAD severity associated with high risk of DMS that is significantly reduced after revascularization within 90 d after PET, an association not seen for moderate to mild perfusion abnormalities or medical treatment alone.

We investigated whether prehospital, reduced dose fibrinolysis coupled with urgent percutaneous coronary intervention (FAST‐PCI) reduces mortality and cardiac magnetic resonance (CMR) measures of infarct size, compared with primary percutaneous coronary intervention (PPCI), in patients with ST‐elevation myocardial infarction (STEMI).

Cardiac positron emission tomography (PET) has evolved rapidly from a relatively esoteric research tool into clinical applications providing unique, quantitative information on myocardial perfusion, metabolism, and cell membrane function and having a potentially significant impact on cardiovascular medicine. Although there are many different positron radionuclides for imaging diverse myocardial behavior, three radionuclides have reached accepted clinical utility. Cardiac PET using nitrogen-13-ammonia, rubidium-82, and fluoro-18-deoxyglucose has proved accurate and definitive in multiple university and private-practice sites for diagnosing and assessing severity and location of coronary artery disease in symptomatic or asymptomatic patients, for identifying injured but viable myocardium potentially salvageable by revascularization, and for ruling out clinically significant coronary artery stenosis with a high specificity in patients who might otherwise undergo coronary arteriography to document the absence of significant disease.

As stated in American College of Cardiology/American Heart Association Guidelines, randomized trials have not demonstrated that elective percutaneous coronary intervention (PCI) reduces myocardial infarction (MI) or mortality over medical treatment. Even the Fractional Flow Reserve Guided PCI Versus Medical Therapy in Stable Coronary Disease (FAME 2) trial showed no statistically significant benefit of PCI over the deferred group by traditional intention-to-treat, nonbenchmark analysis starting at randomization that includes procedure-related events. Benchmark analysis in FAME 2 beginning 1 week after PCI removed procedure-related events that counterbalanced subsequent reduced MI and mortality compared with the deferred group. Meta-analysis of the literature on risk of events related to fractional flow reserve (FFR), including FFR Versus Angiography in Multivessel Evaluation (FAME), and other physiological measures of severity reveal an underappreciated, powerful interdependence among physiological severity of stenosis, diffuse coronary artery disease (CAD), event rates, sample size, and statistical certainty of differences. This analytic review synthesizes an evidenced-based, quantitative hypothesis and potential solution to this issue based on hard data from the literature by coauthors of diverse cardiovascular disciplines in trial design, biostatistics, invasive procedures, coronary physiology, fluid dynamics, coronary pathology, and quantitative imaging. Our synthesis elucidates a dual hypothesis for failure of elective PCI in stable CAD to reduce MI or mortality and novel trial design for selecting patients for whom PCI will likely reduce these events. First, a large burden of global diffuse CAD carries a high risk of coronary events unmitigated by PCI of a focal stenosis. Second, focal stenosis severity in previous randomized revascularization trials has been too modest without objectively quantified sufficient severity to observe benefit of PCI. In previous trials, mixture of diffuse coronary disease and intermediate stenosis may not incur high enough risk for potential benefit by PCI for sample size of reported trials. Greater quantitative severity with …

SPECT and PET myocardial perfusion images show greater myocardial intensity and homogeneity in systole than diastole because of greater systolic myocardial thickness, less partial volume loss, and enhanced activity recovery. Consequently, conventional myocardial perfusion images obtained from whole cardiac cycles have lower myocardial intensity and greater heterogeneity than systolic images. Considering relative activity distribution on SPECT systolic images may add clinical utility to whole-cycle images and wall motion. Methods: Patients undergoing coronary angiogram within 4 mo after SPECT myocardial perfusion imaging were reviewed. Images were interpreted by 2 masked interpreters using a 17-segment, 5-point scale to determine summed rest scores (SSS), summed stress scores, and summed difference scores on conventional and systolic images in 603 patients (55.6% no coronary artery disease [ no-CAD] and 44.4% CAD). Studies were considered normal when the SSS was less than 4 and summed difference score was less than 2. Results: In the no-CAD group, systolic SSS was lower than SSS from conventional images (2 +/- 2.3 vs. 3 +/- 2.6, P < 0.001). In contrast, SSS derived from systolic and conventional images were not different in the obstructive CAD group (9.1 +/- 7.6 vs. 9.2 +/- 7.4, P 5 0.559). When systolic images were considered, true-negative studies increased from 27.2% to 43.3% (P < 0.001) whereas false-positive studies decreased from 28.4% to 12.3% (P < 0.001). True-positive (38% vs. 37.2%, P = 0.505) and false-negative studies (6.5% vs. 7%, P = 0.450) were not significantly changed. Diagnostic accuracy increased from 65.2% to 80.8% (P < 0.001). Conclusion: For gated SPECT myocardial perfusion imaging, when relative activity distribution on systolic images was considered, false-positive studies were reduced and diagnostic accuracy was improved.

Introduction: The current standard treatment for ST-elevation myocardial infarction (STEMI) is primary percutaneous coronary intervention (PPCI). Early reperfusion results in shorter ischemic time (IT) which reduces mortality. In general, fibrinolysis can be initiated earlier than PPCI. For over 7 years we have used a strategy of field evaluation for STEMI using 12 lead ECGs obtained and transmitted by emergency services personnel with over-read by emergency center physicians. Appropriate STEMI patients receive pre-hospital reduced dose fibrinolytic (10 units reteplase) along with aspirin, clopidogrel, and heparin, and are transported to our center for urgent PCI (termed FAST-PCI strategy). Hypothesis: Patients with STEMI in FAST-PCI group have lower 30-day mortality rate compared with those in PPCI group. Methods: Patients with STEMI at our tertiary center were prospectively included for retrospective analysis. Demographic, clinical, angiographic data and outcomes were investigated. Ischemic time was defined as time from onset of pain to device activation. Patients were divided into groups based on IT (<120, 120-179, 180-239, ≥ 240 minutes). Within each IT group, patients were compared by PPCI and FAST-PCI groups. The primary endpoint was 30-day mortality. Results: Between 02/2007 and 12/2013, we treated 1112 STEMI patients of which 551 (49.5%) underwent FAST-PCI and 561 (50.4%) had PPCI. The two treatment groups in each IT interval were well matched for age, cardiac risk factors, left main and left anterior descending artery infarct. Data are shown in the table. Conclusions: For STEMI patients who presented with IT < 180 minutes, FAST-PCI had reduced 30-day mortality rate compared to PPCI. However, a mortality difference was not seen in patients with IT ≥ 180 minutes between the two treatment groups. This suggests that in patients presenting within 3 hours of onset of symptoms FAST-PCI may confer an advantage over PPCI.

A coordinated system of care for patients with ST-segment elevation myocardial infarctions that includes prehospital administration of reduced-dose fibrinolytic agents coupled with urgent percutaneous coronary intervention (PCI), termed FAST-PCI, has been shown to be at least as effective as primary PCI (PPCI) alone. However, this reduced-dose fibrinolytic strategy could be associated with increased bleeding risk, especially in elderly patients. The purpose of this study was to examine 30-day outcomes in patients aged ≥75 years with ST-segment elevation myocardial infarctions treated with either strategy. Data from 120 patients aged ≥75 years treated with FAST-PCI were compared with those of 94 patients aged ≥75 years treated with PPCI. The primary comparator was mortality at 30 days. Stroke, reinfarction, and major bleeding were also compared. The groups were well matched for age, cardiac risk factors, and ischemic times. At 30 days, mortality was lower with FAST-PCI than with PPCI (4.2% vs 18.1%, p <0.01). Rates of stroke, reinfarction, and major bleeding (4% vs 2%) were similar in the 2 groups. The FAST-PCI cohort had lower rates of cardiogenic shock on hospital arrival (15% vs 26%, p = 0.05) and completely occluded infarct arteries (Thrombolysis In Myocardial Infarction [TIMI] grade 0 flow, 35% vs 61%, p <0.01). In conclusion, for patients aged ≥75 years with ST-segment elevation myocardial infarctions, a FAST-PCI strategy in a coordinated system of care was associated with reduced 30-day mortality, earlier infarct artery patency, and lower incidence of cardiogenic shock at arrival compared with PPCI, without apparent bleeding, stroke, or reinfarction penalties.

Cardiogenic shock (CS) occurs in up to 25% of patients with ST elevation myocardial infarction (STEMI). Use of peripheral ventricular assist device (p-VAD) such as intra aortic balloon pump (IABP) is recommended in these patients. However, there is conflicting evidence regarding the timing of

We present a preliminary cost analysis of a combination intervention using PET and comprehensive lifestyle modification to reverse atherosclerosis. With a sensitivity of 92%–95% and specificity of 85%–95%, PET is an essential tool for high-precision diagnosis of coronary artery disease, accurately guiding optimal treatment for both symptomatic and asymptomatic patients. PET imaging provides a powerful visual and educational aid for helping patients identify and adopt appropriate treatments. However, little is known about the operational cost of using the technology for this purpose. Methods: The analysis was done in the context of the Century Health Study for Cardiovascular Medicine (Century Trial), a 1,300-patient, randomized study combining PET imaging with lifestyle changes. Our methodology included a microcosting and time study focusing on estimating average direct and indirect costs. Results: The total cost of the Century Trial in present-value terms is $9.2 million, which is equal to $7,058 per patient. Sensitivity analysis indicates that the present value of total costs is likely to range between $8.8 and $9.7 million, which is equivalent to $6,655–$7,606 per patient. Conclusion: The clinical relevance of the Century Trial is significant since it is, to our knowledge, the first randomized controlled trial to combine high-precision imaging with lifestyle strategies. The Century Trial is in its second year of a 5-y protocol, and we present preliminary findings. The results of this cost study, however, provide policy makers with an early estimate of the costs of implementing, at large scale, a combined intervention such as the Century Trial. Further, we believe that imaging-guided lifestyle management may have considerable potential for improving outcomes and reducing health-care costs by eliminating unnecessary invasive procedures.

Introduction: In STEMI, early reperfusion is imperative to preserve viability. The interval between steady ischemic symptom onset to first medical contact time (ST1) is a component of total ischemic time (IT) that has a large margin for improvement. Hypothesis: We hypothesized that ST1 is the main contributor to IT and can be influenced by specific patient demographics, characteristics and socio-economical status. Methods: We queried the database from an experienced urban-based STEMI accredited receiving center in Houston, TX from 2011 to 2014. We included only patients with STEMI who presented directly from the community to our hospital via EMS. IT was defined as the sum of ST1, first medical contact (FMC) to hospital arrival and arrival to first device activation (FDA) times. Patients transferred from outside facilities or without documented symptom onset, FMC or FDA times were excluded. Results: 263 patients met the inclusion criteria: 52% White, 28% Black and 17% Hispanic. 48% had private insurance, 38% Medicare and 8% Medicaid. Mean ST1 was 117, FMC to arrival 49 and arrival to FDA 58 min. Mean ST1 comprised 41.7% of IT. Compared to other groups, the Black race was independently associated with the longest ST1 time at 156 ± 234 min (p = 0.05), Similarly, Medicaid insurance status showed the highest ST1 time at 283 ± 396 min (p Conclusions: 1. Symptoms onset to first medical contact time (ST1) has the largest impact on total ischemic time in STEMI. 2. Black race and Medicaid insurance status are associated with a longer ST1 time. 3. Continued public education regarding prolonged myocardial ischemia is needed.

a large atherosclerotic plaque burden and severe luminal stenosis are associated with unfavorable outcomes in coronary artery disease (cad). On the one hand, critical luminal obstruction has remained the gold standard for clinical decisions on coronary revascularization. On the other hand, expansion

In patients with acute ST-elevation myocardial infarction (STEMI), a strategy of pre-hospital reduced dose fibrinolytic administration coupled with urgent percutaneous coronary intervention (PCI), termed FAST-PCI strategy, has been found to be superior to primary PCI (PPCI) alone. A coordinated STEMI system of care that includes FAST-PCI should offer better outcomes than a system in which prehospital diagnosis of STEMI is followed by PPCI alone. The aim of this study was to compare the in-hospital outcomes for patients treated with the FAST-PCI approach with outcomes for patients treated with the PPCI approach in a common system. The in-hospital data for 253 STEMI patients (March 2003 December 2009) treated with a FAST-PCI protocol were compared with 124 patients (January 2010 August 2011) treated with PPCI strategy alone. In-hospital mortality was the primary comparator. Stroke, major bleeding, and reinfarction during index hospitalization were also compared. The in-hospital mortality was significantly lower with FAST-PCI than with PPCI (2.77% vs 10.48%, p = 0.0017). Rates of stroke, reinfarction, and major bleeding were similar in the 2 groups. There was a lower frequency of pre-PCI Thrombolysis In Myocardial Infarction 0 flow (no patency) seen in patients treated with FAST-PCI compared with the PPCI patients (26.7% vs 62.7%, p<0.0001). Earlier infarct artery patency in the FAST-PCI group had a favorable impact on the incidence of cardiogenic shock on hospital arrival (3.1% vs 20.9%, p<0.0001). In conclusion, compared with a PPCI strategy in a common STEMI system of care, the FAST-PCI strategy was associated with earlier infarct artery patency and lower incidence of cardiogenic shock, as well as with reduced in-hospital mortality. (C) 2013 Elsevier Inc. All rights reserved.

In September 2011, a 55 year old active man, ex-smoker with previous history of squamous cell cancer of the lung, presented to the hospital with frontal headache of > 12 hours duration and low grade fever. Headache was severe and not accompanied by nausea, vomiting or sensitivity to light. His lung cancer was treated with surgery and radiation therapy, which was completed in 2010. His treatment was complicated by post radiation pneumonitis. He was very active, bicycling regularly up to 10 miles, three times per week. His main reason for hospital visit was headache, but on arrival he also reported atypical right sided pleuritic chest pain, which was attributed to his radiation pneumonitis.

Background: The ultimate treatment goal in ST-elevation myocardial infarction (STEMI) is rapid restoration of coronary blood flow. In general, fibrinolysis can be initiated earlier than primary percutaneous coronary intervention (PPCI) but it could be associated with bleeding risk, especially in elderly patients. For over 7 years we have used a strategy of field evaluation for STEMI using 12 lead EKGs obtained and transmitted by emergency services (EMS) personnel with over-read by emergency center physicians. Appropriate STEMI patients receive pre-hospital reduced dose fibrinolytic (10 units reteplase) along with aspirin, clopidogrel, and heparin, and are transported to our STEMI center for urgent PCI (termed FAST-PCI strategy). Methods: We examined the data for elderly patients (≥ 75 years) treated by either a FAST-PCI strategy or conventional PPCI. We compared demographic, clinical, angiographic data and outcomes. Ischemic time was defined as time from onset of pain to device activation. Bleeding was assessed using GUSTO criteria. Results: Between February 2006 and April 2013, we treated 1323 STEMI patients of which 214 (16.2%) were ≥75 years. FAST-PCI was employed in 120 (56%) and PPCI in 94 (44%) patients. The groups were well matched for age, cardiac risk factors and ischemic time. Data are shown in the table. Conclusions: In the elderly patients, compared with a PPCI strategy, the FAST-PCI strategy was associated with earlier infarct artery patency (Less TIMI 0 flow) and reduced 30 day mortality, as well as with lower incidence of cardiogenic shock at presentation without a bleeding penalty.

Angiographic severity of coronary artery stenosis has historically been the primary guide to revascularization or medical management of coronary artery disease. However, physiologic severity defined by coronary pressure and/or flow has resurged into clinical prominence as a potential, fundamental change from anatomically to physiologically guided management. This review addresses clinical coronary physiology-pressure and flow-as clinical tools for treating patients. We clarify the basic concepts that hold true for whatever technology measures coronary physiology directly and reliably, here focusing on positron emission tomography and its interplay with intracoronary measurements.