Immature Platelet Fraction Predicts Adverse Events in Patients With Acute Coronary Syndrome: the ISAR-REACT 5 Reticulated Platelet Substudy.

BACKGROUND: Immature or reticulated platelets are associated with impaired efficacy of antiplatelet drugs and adverse events in cardiovascular patients. Their role as a predictive biomarker in patients with acute coronary syndrome treated with potent P2Y12 receptor inhibitors is not fully understood. We aimed to prospectively evaluate reticulated platelets as a predictor of the primary end point of the ISAR-REACT 5 trial consisting of death, myocardial infarction, or stroke at 1 year in patients with acute coronary syndrome randomized to prasugrel or ticagrelor. METHODS: Immature platelet fraction (IPF) was assessed within 48 hours after randomization. Patients were divided based on the IPF median values: the IPFhigh group included patients with IPF>median and the IPFlow group included patients with IPF≤median. Platelet aggregation was assessed using the Multiplate Analyzer and was correlated to IPF. RESULTS: Five hundred seventy-seven patients were included in the study. IPF values in % (median [interquartile range]) within the first 48 hours did not differ between the two study groups: 3.6 (2.5-5.2)% in the prasugrel group and 3.6 (2.5-5.4)% in the ticagrelor group (P=0.882). The incidence of the primary end point was significantly higher in the IPFhigh (IPF>3.6%) group compared with the IPFlow (IPF≤3.6%) group: 13.0% versus 7.2% (HRadj, 1.74 [1.02-3.00]; P=0.044), independently from the assigned drug (Pint=0.159). No significant association between IPF and BARC 3 to 5 bleeding was observed. ADP-induced platelet aggregation correlated significantly with IPF in patients treated with prasugrel (r=0.22; P=0.005) while no correlation was detected in patients treated with ticagrelor (r=0.09; P=0.257). CONCLUSIONS: Independently from drug treatment, IPF was associated with the primary end point and therefore is a promising biomarker for the prediction of adverse cardiovascular events in patients with acute coronary syndrome treated with prasugrel or ticagrelor. REGISTRATION: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01944800.

Exercise for Primary and Secondary Prevention of Cardiovascular Disease: JACC Focus Seminar 1/4.

Regular exercise that meets or exceeds the current physical activity guidelines is associated with a reduced risk of cardiovascular disease (CVD) and mortality. Therefore, exercise training plays an important role in primary and secondary prevention of CVD. In this part 1 of a 4-part focus seminar series, we highlight the mechanisms and physiological adaptations responsible for the cardioprotective effects of exercise. This includes an increase in cardiorespiratory fitness secondary to cardiac, vascular, and skeletal muscle adaptations and an improvement in traditional and nontraditional CVD risk factors by exercise training. This extends to the role of exercise and its prescription in patients with CVDs (eg, coronary artery disease, chronic heart failure, peripheral artery disease, or atrial fibrillation) with special focus on the optimal mode, dosage, duration, and intensity of exercise to reduce CVD risk and improve clinical outcomes in these patients.

Cardiovascular risk factors, exercise capacity and health literacy in patients with chronic ischaemic heart disease and type 2 diabetes mellitus in Germany: Baseline characteristics of the Lifestyle Intervention in Chronic Ischaemic Heart Disease and Type 2 Diabetes study.

BACKGROUND: Lifestyle interventions are a cornerstone in the treatment of chronic ischaemic heart disease (CIHD) and type 2 diabetes mellitus (T2DM). This study aimed at identifying differences in clinical characteristics between categories of the common lifestyle intervention targets BMI, exercise capacity (peak V̇O2) and health literacy (HL). METHODS: Cross-sectional baseline characteristics of patients enrolled in the LeIKD trial (Clinicaltrials.gov NCT03835923) are presented in total, grouped by BMI, %-predicted peak V̇O2 and HL (HLS-EU-Q16), and compared to other clinical trials with similar populations. RESULTS: Among 499 patients (68.3±7.7 years; 16.2% female; HbA1c, 6.9±0.9%), baseline characteristics were similar to other trials and revealed insufficient treatment of several risk factors (LDL-C 92±34 mg/dl; BMI, 30.1±4.8 kg/m2; 69.6% with peak V̇O2<90% predicted). Patients with lower peak V̇O2 showed significantly higher (p < 0.05) CIHD and T2DM disease severity (HbA1c, CIHD symptoms, coronary artery bypass graft). Obese patients had a significantly higher prevalence of hypertension and higher triglyceride levels, whereas in patients with low HL both quality of life components (physical, mental) were significantly reduced. CONCLUSIONS: In patients with CIHD and T2DM, peak V̇O2, BMI and HL are important indicators of disease severity, risk factor burden and quality of life, which reinforces the relevance of lifestyle interventions.

Peak O2 -pulse predicts exercise training-induced changes in peak V̇O2 in heart failure with preserved ejection fraction.

AIMS: Exercise training (ET) has been consistently shown to increase peak oxygen consumption (V̇O2 ) in patients with heart failure with preserved ejection fraction (HFpEF); however, inter-individual responses vary significantly. Because it is unlikely that ET-induced improvements in peak V̇O2 are significantly mediated by an increase in peak heart rate (HR), we aimed to investigate whether baseline peak O2 -pulse (V̇O2  × HR-1 , reflecting the product of stroke volume and arteriovenous oxygen difference), not baseline peak V̇O2 , is inversely associated with the change in peak V̇O2 (adjusted by body weight) following ET versus guideline control (CON) in patients with HFpEF. METHODS AND RESULTS: This was a secondary analysis of the OptimEx-Clin (Optimizing Exercise Training in Prevention and Treatment of Diastolic Heart Failure, NCT02078947) trial, including all 158 patients with complete baseline and 3 month cardiopulmonary exercise testing measurements (106 ET, 52 CON). Change in peak V̇O2 (%) was analysed as a function of baseline peak V̇O2 and its determinants (absolute peak V̇O2 , peak O2 -pulse, peak HR, weight, haemoglobin) using robust linear regression analyses. Mediating effects on change in peak V̇O2 through changes in peak O2 -pulse, peak HR and weight were analysed by a causal mediation analysis with multiple correlated mediators. Change in submaximal exercise tolerance (V̇O2 at the ventilatory threshold, VT1) was analysed as a secondary endpoint. Among 158 patients with HFpEF (66% female; mean age, 70 ± 8 years), changes in peak O2 -pulse explained approximately 72% of the difference in changes in peak V̇O2 between ET and CON [10.0% (95% CI, 4.1 to 15.9), P = 0.001]. There was a significant interaction between the groups for the influence of baseline peak O2 -pulse on change in peak V̇O2 (interaction P = 0.04). In the ET group, every 1 mL/beat higher baseline peak O2 -pulse was associated with a decreased mean change in peak V̇O2 of -1.45% (95% CI, -2.30 to -0.60, P = 0.001) compared with a mean change of -0.08% (95% CI, -1.11 to 0.96, P = 0.88) following CON. None of the other factors showed significant interactions with study groups for the change in peak V̇O2 (P > 0.05). Change in V̇O2 at VT1 was not associated with any of the investigated factors (P > 0.05). CONCLUSIONS: In patients with HFpEF, the easily measurable peak O2 -pulse seems to be a good indicator of the potential for improving peak V̇O2 through exercise training. While changes in submaximal exercise tolerance were independent of baseline peak O2 -pulse, patients with high O2 -pulse may need to use additional therapies to significantly increase peak V̇O2 .

Prediction of Successful Pharmacological Cardioversion in Acute Symptomatic Atrial Fibrillation: The Successful Intravenous Cardioversion for Atrial Fibrillation (SIC-AF) Score.

Background: Modern personalised medicine requires patient-tailored decisions. This is particularly important when considering pharmacological cardioversion for the acute treatment of haemodynamically stable atrial fibrillation and atrial flutter in a shared decision-making process. We aimed to develop and validate a predictive model to estimate the individual probability of successful pharmacological cardioversion using different intravenous antiarrhythmic agents. Methods: We analysed data from a prospective atrial fibrillation registry comprising 3053 cases of first-detected or recurrent haemodynamically stable, non-permanent, symptomatic atrial fibrillation presenting to an Austrian academic emergency department between January 2012 and December 2017. Using multivariable analysis, a prediction score was developed and externally validated. The clinical utility of the score was assessed using decision curve analysis. Results: A total of 1528 cases were included in the development cohort (median age 69 years, IQR 58−76; 43.9% female), and 1525 cases were included in the validation cohort (median age 68 years, IQR (58−75); 39.5% female). Finally, 421 cases were available for score development and 330 cases for score validation The weighted score included atrial flutter (8 points), duration of symptoms associated with AF (<24 h; 8 points), absence of previous electrical cardioversion (10 points), and the specific intravenous antiarrhythmic drug (amiodarone 10 points, vernakalant 11 points, ibutilide 13 points). The final score, the "Successful Intravenous Cardioversion for Atrial Fibrillation (SIC-AF) score," showed good calibration (R2 = 0.955 and R2 = 0.954) and discrimination in both sets (c-indices: 0.68 and 0.66) and net clinical benefit. Conclusions: A predictive model was developed to estimate the success of intravenous pharmacological cardioversion using different antiarrhythmic agents in a cohort of patients with haemodynamically stable, non-permanent, symptomatic atrial fibrillation. External temporal validation confirmed good calibration, discrimination, and clinical usefulness. The SIC-AF score may help patients and physicians jointly decide on the appropriate treatment strategy for acute symptomatic atrial fibrillation. Registration: NCT03272620.

Comparison of American and European Guidelines for Primary Prevention of Cardiovascular Disease: JACC Guideline Comparison.

This review compares the primary prevention recommendations of the recent 2021 European Society of Cardiology (ESC) and 2019 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines on cardiovascular disease (CVD) prevention. Although the 2019 ACC/AHA guideline represents its inaugural version, the ESC guideline is an update to its 2016 statement. Both guidelines address prevention using a holistic approach and agree on the importance of lifestyle optimization and intensified risk factor management. Cardiovascular (CV) risk assessment tools differ, reflecting the unique populations being screened as well as philosophical differences to their approach. Conventional risk factors are used to estimate CV risk, but each guideline acknowledges the role of risk modifiers to refine risk calculation. The ESC guideline recognizes the importance of nonclassical risk factors, including environmental issues, that impact CV health at the population level and calls for legislative action at the local, regional, and national levels.

[The new ESC guidelines 2021 on prevention of cardiovascular diseases : Appeal for prevention]. / Neue ESC-Leitlinien 2021 zur Prävention von kardiovaskulären Erkrankungen : Aufruf zur Prävention.

This article summarizes the innovations and most important points of the recently published and updated ESC guidelines 2021 on the prevention of cardiovascular diseases. Developments in risk stratification and further developments with respect to targets and options for the treatment of risk factors necessitated an update of the guidelines from 2016. The innovations incorporate a staged and individualized approach to the prevention targets, an implementation of the systematic coronary risk evaluation 2 (SCORE 2 update) and the SCORE 2­older persons (OP) systems on risk stratification, including age-dependent estimations for young (<50 years old) and older people (≥70 years old) as well as for patients with diabetes mellitus and atherosclerotic cardiovascular diseases. Furthermore, specific recommendations are given for coronary heart disease, heart failure and chronic kidney insufficiency. In addition to recommendations on individualized treatment, the relevance of cardiovascular prevention at the population level, including environmental protection is underlined.