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  1. Chun S, Choi Y, Chang Y, Cho J, Zhang Y, Rampal S, et al.
    Am Heart J, 2016 07;177:17-24.
    PMID: 27297845 DOI: 10.1016/j.ahj.2016.03.018
    BACKGROUND: Sugar-sweetened carbonated beverage consumption has been linked to obesity, metabolic syndrome, type 2 diabetes, and clinically manifest coronary heart disease, but its association with subclinical coronary heart disease remains unclear. We investigated the relationship between sugar-sweetened carbonated beverage consumption and coronary artery calcium (CAC) in a large study of asymptomatic men and women.

    METHODS: This was a cross-sectional study of 22,210 adult men and women who underwent a comprehensive health screening examination between 2011 and 2013 (median age 40 years). Sugar-sweetened carbonated beverage consumption was assessed using a validated food frequency questionnaire, and CAC was measured by cardiac computed tomography. Multivariable-adjusted CAC score ratios and 95% CIs were estimated from robust Tobit regression models for the natural logarithm (CAC score +1).

    RESULTS: The prevalence of detectable CAC (CAC score >0) was 11.7% (n = 2,604). After adjustment for age; sex; center; year of screening examination; education level; physical activity; smoking; alcohol intake; family history of cardiovascular disease; history of hypertension; history of hypercholesterolemia; and intake of total energy, fruits, vegetables, and red and processed meats, only the highest category of sugar-sweetened carbonated beverage consumption was associated with an increased CAC score compared with the lowest consumption category. The multivariable-adjusted CAC ratio comparing participants who consumed ≥5 sugar-sweetened carbonated beverages per week with nondrinkers was 1.70 (95% CI, 1.03-2.81). This association did not differ by clinical subgroup, including participants at low cardiovascular risk.

    CONCLUSION: Our findings suggest that high levels of sugar-sweetened carbonated beverage consumption are associated with a higher prevalence and degree of CAC in asymptomatic adults without a history of cardiovascular disease, cancer, or diabetes.

  2. Ong TK, Chin SP, Liew CK, Chan WL, Seyfarth MT, Liew HB, et al.
    Am Heart J, 2006 Jun;151(6):1323.e1-6.
    PMID: 16781246
    The new 64-row multidetector computed tomography (CT)-assisted angiography can now detect coronary artery disease with shorter breath-hold time and at faster heart rates for symptomatic patients. We aim to determine if the 64-row scanner can also overcome limitations due to mild to moderate calcification.
  3. Zangrillo A, Alvaro G, Pisano A, Guarracino F, Lobreglio R, Bradic N, et al.
    Am Heart J, 2016 Jul;177:66-73.
    PMID: 27297851 DOI: 10.1016/j.ahj.2016.03.021
    OBJECTIVE: Patients undergoing cardiac surgery are at risk of perioperative low cardiac output syndrome due to postoperative myocardial dysfunction. Myocardial dysfunction in patients undergoing cardiac surgery is a potential indication for the use of levosimendan, a calcium sensitizer with 3 beneficial cardiovascular effects (inotropic, vasodilatory, and anti-inflammatory), which appears effective in improving clinically relevant outcomes.

    DESIGN: Double-blind, placebo-controlled, multicenter randomized trial.

    SETTING: Tertiary care hospitals.

    INTERVENTIONS: Cardiac surgery patients (n = 1,000) with postoperative myocardial dysfunction (defined as patients with intraaortic balloon pump and/or high-dose standard inotropic support) will be randomized to receive a continuous infusion of either levosimendan (0.05-0.2 μg/[kg min]) or placebo for 24-48 hours.

    MEASUREMENTS AND MAIN RESULTS: The primary end point will be 30-day mortality. Secondary end points will be mortality at 1 year, time on mechanical ventilation, acute kidney injury, decision to stop the study drug due to adverse events or to start open-label levosimendan, and length of intensive care unit and hospital stay. We will test the hypothesis that levosimendan reduces 30-day mortality in cardiac surgery patients with postoperative myocardial dysfunction.

    CONCLUSIONS: This trial is planned to determine whether levosimendan could improve survival in patients with postoperative low cardiac output syndrome. The results of this double-blind, placebo-controlled randomized trial may provide important insights into the management of low cardiac output in cardiac surgery.

  4. Luo N, Teng TK, Tay WT, Anand IS, Kraus WE, Liew HB, et al.
    Am Heart J, 2017 Sep;191:75-81.
    PMID: 28888273 DOI: 10.1016/j.ahj.2017.06.016
    BACKGROUND: Assessing health-related quality of life (HRQoL) in patients with heart failure (HF) is an important goal of clinical care and HF research. We sought to investigate ethnic differences in perceived HRQoL and its association with mortality among patients with HF and left ventricular ejection fraction ≤35%, controlling for demographic characteristics and HF severity.

    METHODS AND RESULTS: We compared 5697 chronic HF patients of Indian (26%), white (23%), Chinese (17%), Japanese/Koreans (12%), black (12%), and Malay (10%) ethnicities from the HF-ACTION and ASIAN-HF multinational studies using the Kansas City Cardiomyopathy Questionnaire (KCCQ; range 0-100; higher scores reflect better health status). KCCQ scores were lowest in Malay (58±22) and Chinese (60±23), intermediate in black (64±21) and Indian (65±23), and highest in white (67±20) and Japanese or Korean patients (67±22) after adjusting for age, sex, educational status, HF severity, and risk factors. Self-efficacy, which measures confidence in the ability to manage symptoms, was lower in all Asian ethnicities (especially Japanese/Koreans [60±26], Malay [66±23], and Chinese [64±28]) compared to black (80±21) and white (82±19) patients, even after multivariable adjustment (P

  5. Schwalm JR, McCready T, Lamelas P, Musa H, Lopez-Jaramillo P, Yusoff K, et al.
    Am Heart J, 2018 09;203:57-66.
    PMID: 30015069 DOI: 10.1016/j.ahj.2018.06.004
    BACKGROUND: Cardiovascular disease is the leading cause of death throughout the world, with the majority of deaths occurring in low- and middle-income countries. Despite clear evidence for the benefits of blood pressure reduction and availability of safe and low-cost medications, most individuals are either unaware of their condition or not adequately treated.

    OBJECTIVE: The primary objective of this study is to evaluate whether a community-based, multifaceted intervention package primarily provided by nonphysician health workers can improve long-term cardiovascular risk in people with hypertension by addressing identified barriers at the patient, health care provider, and health system levels.

    METHODS/DESIGN: HOPE-4 is a community-based, parallel-group, cluster randomized controlled trial involving 30 communities (1,376 participants) in Colombia and Malaysia. Participants ≥50 years old and with newly diagnosed or poorly controlled hypertension were included. Communities were randomized to usual care or to a multifaceted intervention package that entails (1) detection, treatment, and control of cardiovascular risk factors by nonphysician health workers in the community, who use tablet-based simplified management algorithms, decision support, and counseling programs; (2) free dispensation of combination antihypertensive and cholesterol-lowering medications, supervised by local physicians; and (3) support from a participant-nominated treatment supporter (either a friend or family member). The primary outcome is the change in Framingham Risk Score after 12 months between the intervention and control communities. Secondary outcomes including change in blood pressure, lipid levels, and Interheart Risk Score will be evaluated.

    SIGNIFICANCE: If successful, the study could serve as a model to develop low-cost, effective, and scalable strategies to reduce cardiovascular risk in people with hypertension.

  6. Apprill PG, Ashton J, Guerrero J, Glas-Greenwalt P, Buja LM, Willerson JT
    Am Heart J, 1987 Apr;113(4):898-906.
    PMID: 3565240
    The potential use of ancrod, a purified isolate from the venom of the Malaysian pit viper, Agkistrodon rhodostoma, in decreasing the frequency of cyclic flow variations in severely stenosed canine coronary arteries and causing thrombolysis of an acute coronary thrombus induced by a copper coil was evaluated. Open-chest, anesthetized dogs were used. Ancrod was given intravenously (8 U/kg) over 1 hour and caused a significant reduction in the frequency of cyclic flow variations (5.8 +/- 0.7 to 3.6 +/- 0.8 cyclic flow variations per 30 minutes, p less than 0.05), whereas control animals failed to decrease the frequency of their cyclic flow variations over the same time period (5.3 +/- 0.3 to 5.0 +/- 0.4 cyclic flow variations per 30-minute period). Twenty-seven dogs had a coronary thrombus induced by a copper coil positioned directly in a major coronary artery; of these, four died of ventricular fibrillation prior to treatment, eight received an infusion of saline and showed no thrombolysis over 5 hours, and three died of ventricular fibrillation during the initial part of an intravenous infusion of ancrod. The remaining 12 dogs received ancrod intravenously (16 U/kg); six demonstrated lysis of the coronary thrombus (mean time to lysis, 65 +/- 20 minutes). The concentrations of ancrod used in these studies produced a severe decrease in systemic fibrinogen concentration and a significant decrease in the inhibitor of plasminogen activator levels. Thus, ancrod decreases the frequency of cyclic flow variations in stenosed canine coronary arteries and may cause coronary thrombolysis in approximately 50% of animals within 65 +/- 20 minutes of its intravenous administration.
  7. Conen D, Popova E, Wang MK, Chan MTV, Landoni G, Reimer C, et al.
    Am Heart J, 2023 May;259:87-96.
    PMID: 36754105 DOI: 10.1016/j.ahj.2023.01.018
    BACKGROUND: Perioperative atrial fibrillation (AF) and myocardial injury after noncardiac surgery (MINS) are common complications after noncardiac surgery. Inflammation has been implicated in the pathogenesis of both disorders. The COP-AF trial tests the hypothesis that colchicine reduces the incidence of perioperative AF and MINS in patients undergoing major noncardiac thoracic surgery.

    METHODS AND RESULTS: The 'COlchicine for the Prevention of Perioperative Atrial Fibrillation' (COP-AF) trial is an international, blinded, randomized trial that compares colchicine to placebo in patients aged at least 55 years and undergoing major noncardiac thoracic surgery with general anesthesia. Exclusion criteria include a history of AF and a contraindication to colchicine (eg, severe renal dysfunction). Oral colchicine at a dose of 0.5 mg or matching placebo is given within 4 hours before surgery. Thereafter, patients receive colchicine 0.5 mg or placebo twice daily for a total of 10 days. The 2 independent co-primary outcomes are clinically important perioperative AF (including atrial flutter) and MINS during 14 days of follow-up. The main safety outcomes are sepsis or infection and non-infectious diarrhea. We aim to enroll 3,200 patients from approximately 40 sites across 11 countries to have at least 80% power for the independent evaluation of the 2 co-primary outcomes. The COP-AF main results are expected in 2023.

    CONCLUSIONS: COP-AF is a large randomized and blinded trial designed to determine whether colchicine reduces the risk of perioperative AF or MINS in patients who have major noncardiac thoracic surgery.

  8. Joseph P, Pais P, Dans AL, Bosch J, Xavier D, Lopez-Jaramillo P, et al.
    Am Heart J, 2018 Dec;206:72-79.
    PMID: 30342297 DOI: 10.1016/j.ahj.2018.07.012
    BACKGROUND: It is hypothesized that in individuals without clinical cardiovascular disease (CVD), but at increased CVD risk, a 50% to 60% reduction in CVD risk could be achieved using fixed dose combination (FDC) therapy (usually comprised of multiple blood-pressure agents and a statin [with or without aspirin]) in a single "polypill". However, the impact of a polypill in preventing clinical CV events has not been evaluated in a large randomized controlled trial.

    METHODS: TIPS-3 is a 2x2x2 factorial randomized controlled trial that will examine the effect of a FDC polypill on major CV outcomes in a primary prevention population. This study aims to determine whether the Polycap (comprised of atenolol, ramipril, hydrochlorothiazide, and a statin) reduces CV events in persons without a history of CVD, but who are at least at intermediate CVD risk. Additional interventions in the factorial design of the study will compare the effect of (1) aspirin versus placebo on CV events (and cancer), (2) vitamin D versus placebo on the risk of fractures, and (3) the combined effect of aspirin and the Polycap on CV events.

    RESULTS: The study has randomized 5713 participants across 9 countries. Mean age of the study population is 63.9 years, and 53% are female. Mean INTERHEART risk score is 16.8, which is consistent with a study population at intermediate CVD risk.

    CONCLUSION: Results of the TIP-3 study will be key to determining the appropriateness of FDC therapy as a strategy in the global prevention of CVD.

  9. Borges FK, Sessler DI, Tiboni M, Patel A, LeManach Y, Heels-Ansdell D, et al.
    Am Heart J, 2024 Sep;275:45-52.
    PMID: 38851520 DOI: 10.1016/j.ahj.2024.05.020
    INTRODUCTION: Troponin elevation after noncardiac surgery is associated with an elevated risk of 30-day mortality. Little is known about relative merit of using a high-sensitivity Troponin T (hsTnT), the fifth-generation assay, vs the nonhigh sensitivity Troponin T (non-hsTnT), the fourth-generation assay, in the noncardiac surgery setting. We aimed to identify whether hsTnT can identify additional patients at risk that would have gone undetected with non-hsTnT measurement.

    METHODS: The VISION Study included 40,004 noncardiac surgery patients with postoperative troponin measurements. Among them, 1,806 patients had both fourth-generation non-hsTnT and fifth-generation hsTnT concomitant measurements (4,451 paired results). We compared the absolute concentrations, the timing, and the impact of different thresholds on predicting 30-day major cardiovascular complications (composite of death, nonfatal cardiac arrest, coronary revascularization, and congestive heart failure).

    RESULTS: Based on the manufacturers' threshold of 14 ng/L, 580 (32.1%) patients had postoperative hsTnT concentrations greater than the threshold, while their non-hsTnT concentrations were below the manufacturer's threshold. These 580 patients had higher risk of major cardiovascular events (OR 2.33; CI 95% 1.04-5.23; P = .049) than patients with hsTnT concentrations below the manufacturer threshold. Among patients with myocardial injury after noncardiac surgery, only 50% would be detected by the fourth-generation non-hsTnT assay at 6 to 12 hours postoperative as compared to 85% with the fifth-generation hsTnT assay (P-value < .001).

    CONCLUSIONS: Within the first 3 postoperative days, fifth-generation hsTnT identified at least 1 in 3 patients with troponin elevation that would have gone undetected by fourth-generation non-hsTnT using published thresholds in this setting. Furthermore, fifth-generation hsTnT identified patients with an elevation earlier than fourth-generation non-hsTnT, indicating potential to improve postoperative risk stratification.

  10. Munhoz D, Collet C, Mizukami T, Yong A, Leone AM, Eftekhari A, et al.
    Am Heart J, 2023 Nov;265:170-179.
    PMID: 37611857 DOI: 10.1016/j.ahj.2023.07.016
    INTRODUCTION: Diffuse disease has been identified as one of the main reasons leading to low post-PCI fractional flow reserve (FFR) and residual angina after PCI. Coronary pressure pullbacks allow for the evaluation of hemodynamic coronary artery disease (CAD) patterns. The pullback pressure gradient (PPG) is a novel metric that quantifies the distribution and magnitude of pressure losses along the coronary artery in a focal-to-diffuse continuum.

    AIM: The primary objective is to determine the predictive capacity of the PPG for post-PCI FFR.

    METHODS: This prospective, large-scale, controlled, investigator-initiated, multicenter study is enrolling patients with at least 1 lesion in a major epicardial vessel with a distal FFR ≤ 0.80 intended to be treated by PCI. The study will include 982 subjects. A standardized physiological assessment will be performed pre-PCI, including the online calculation of PPG from FFR pullbacks performed manually. PPG quantifies the CAD pattern by combining several parameters from the FFR pullback curve. Post-PCI physiology will be recorded using a standardized protocol with FFR pullbacks. We hypothesize that PPG will predict optimal PCI results (post-PCI FFR ≥ 0.88) with an area under the ROC curve (AUC) ≥ 0.80. Secondary objectives include patient-reported and clinical outcomes in patients with focal vs. diffuse CAD defined by the PPG. Clinical follow-up will be collected for up to 36 months, and an independent clinical event committee will adjudicate events.

    RESULTS: Recruitment is ongoing and is expected to be completed in the second half of 2023.

    CONCLUSION: This international, large-scale, prospective study with pre-specified powered hypotheses will determine the ability of the preprocedural PPG index to predict optimal revascularization assessed by post-PCI FFR. In addition, it will evaluate the impact of PPG on treatment decisions and the predictive performance of PPG for angina relief and clinical outcomes.

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