The incidence of ST segment elevation myocardial infarction (STEMI) has decreased over the last two decades in developed countries, but mortality from STEMI despite widespread access to reperfusion ...therapy is still substantial as is the development of heart failure, particularly among an expanding older population. In developing countries, the incidence of STEMI is increasing and interventional reperfusion is often not available. We here review the pathophysiology of acute myocardial infarction and reperfusion, notably the temporal and spatial evolution of ischaemic and reperfusion injury, the different modes of cell death, and the resulting coronary microvascular dysfunction. We then go on to briefly characterize the cardioprotective phenomena of ischaemic preconditioning, ischaemic postconditioning, and remote ischaemic conditioning and their underlying signal transduction pathways. We discuss in detail the attempts to translate conditioning strategies and drug therapy into the clinical setting. Most attempts have failed so far to reduce infarct size and improve clinical outcomes in STEMI patients, and we discuss potential reasons for such failure. Currently, it appears that remote ischaemic conditioning and a few drugs (atrial natriuretic peptide, exenatide, metoprolol, and esmolol) reduce infarct size, but studies with clinical outcome as primary endpoint are still underway.
Abstract Background Dose reduction of non–vitamin K antagonist oral anticoagulants (NOACs) is indicated in patients with atrial fibrillation (AF) with renal impairment. Failure to reduce the dose in ...patients with severe kidney disease may increase bleeding risk, whereas dose reductions without a firm indication may decrease the effectiveness of stroke prevention. Objectives The goal of this study was to investigate NOAC dosing patterns and associated outcomes, i.e., stroke (ischemic stroke and systemic embolism) and major bleeding in patients treated in routine clinical practice. Methods Using a large U.S. administrative database, 14,865 patients with AF were identified who initiated apixaban, dabigatran, or rivaroxaban between October 1, 2010, and September 30, 2015. We examined use of a standard dose in patients with a renal indication for dose reduction (potential overdosing) and use of a reduced dose when the renal indication is not present (potential underdosing). Cox proportional hazards regression was performed in propensity score–matched cohorts to investigate the outcomes. Results Among the 1,473 patients with a renal indication for dose reduction, 43.0% were potentially overdosed, which was associated with a higher risk of major bleeding (hazard ratio: 2.19; 95% confidence interval: 1.07 to 4.46) but no statistically significant difference in stroke (3 NOACs pooled). Among the 13,392 patients with no renal indication for dose reduction, 13.3% were potentially underdosed. This underdosing was associated with a higher risk of stroke (hazard ratio: 4.87; 95% confidence interval: 1.30 to 18.26) but no statistically significant difference in major bleeding in apixaban-treated patients. There were no statistically significant relationships in dabigatran- or rivaroxaban-treated patients without a renal indication. Conclusions In routine clinical practice, prescribed NOAC doses are often inconsistent with drug labeling. These prescribing patterns may be associated with worse safety with no benefit in effectiveness in patients with severe kidney disease and worse effectiveness with no benefit in safety in apixaban-treated patients with normal or mildly impaired renal function.
The importance of the left atrium in cardiovascular performance has long been acknowledged. Quantitative assessment of left atrial (LA) function is laborious, requiring invasive pressure-volume loops ...and thus precluding its routine clinical use. In recent years, novel postprocessing imaging methodologies have emerged, providing a complementary approach for the assessment of the left atrium. Atrial strain and strain rate obtained using either Doppler tissue imaging or two-dimensional speckle-tracking echocardiography have proved to be feasible and reproducible techniques to evaluate LA mechanics. It is essential to fully understand the clinical applications, advantages, and limitations of LA strain and strain rate analysis. Furthermore, the technique's prognostic value and utility in therapeutic decisions also need further elucidation. The aim of this review is to provide a critical appraisal of LA mechanics. The authors describe the fundamental concepts and methodology of LA strain and strain rate analysis, the reference values reported with different imaging techniques, and the clinical implications.
In recent years, it has become apparent that coronary microvascular dysfunction plays a pivotal pathogenic role in angina pectoris. Functional and structural mechanisms can affect the physiological ...function of the coronary microvasculature and lead to myocardial ischemia in people without coronary atheromatous disease and also in individuals with obstructive coronary artery disease. Abnormal dilatory responses of the coronary microvessels, coronary microvascular spasm, and extravascular compressive forces have been identified as pathogenic mechanisms in both chronic and acute forms of ischemic heart disease. The condition characterized by anginal symptoms and evidence of myocardial ischemia triggered by coronary microvascular dysfunction, in the absence of obstructive coronary disease, is known as microvascular angina. The concept of microvascular angina, however, may extend further to include patients with obstructive coronary artery disease and individuals with angina after coronary revascularization or heart transplantation because coronary microvascular dysfunction contributes to myocardial ischemia in many such patients. Patients with microvascular angina constitute a sizeable proportion of all cases of stable angina undergoing diagnostic coronary angiography and of those with persisting angina after successful coronary revascularization. Coronary microvascular dysfunction is also often responsible for angina in individuals with cardiomyopathy and heart valve disease as well as acute coronary syndrome cases such as Takotsubo syndrome and myocardial infarction with no obstructive coronary artery disease. Patients with stable microvascular angina present typically with effort or rest chest pain and a reduced coronary flow reserve or microvascular spasm. This condition, which affects women and men, can markedly impair quality of life and prognosis and represents a substantial cost burden to healthcare systems and individuals alike. In recent years, progress in the diagnosis of myocardial ischemia and the use of tests to investigate functional and structural causes for a reduced coronary flow reserve and microvascular spasm have allowed the identification of an increased number of cases of microvascular angina in everyday clinical practice. Although some of the available anti-anginal drugs may be helpful, treatment of coronary microvascular dysfunction remains a major challenge. The present article discusses the fundamental role that coronary microvascular dysfunction plays in the pathogenesis of ischemic heart disease, the clinical characteristics of patients presenting with microvascular angina, and possible diagnostic and therapeutic strategies.
The global impetus to identify curative therapies has been fuelled by the unmet needs of patients in the context of a growing heart failure pandemic. To date, regeneration trials in patients with ...cardiovascular disease have used stem-cell-based therapy in the period immediately after myocardial injury, in an attempt to halt progression towards ischaemic cardiomyopathy, or in the setting of congestive heart failure, to target the disease process and prevent organ decompensation. Worldwide, several thousand patients have now been treated using autologous cell-based therapy; the safety and feasibility of this approach has been established, pitfalls have been identified, and optimization procedures envisioned. Furthermore, the initiation of phase III trials to further validate the therapeutic value of cell-based regenerative medicine and address the barriers to successful clinical implementation has led to resurgence in the enthusiasm for such treatments among patients and health-care providers. In particular, poor definition of cell types used, diversity in cell-handling procedures, and functional variability intrinsic to autologously-derived cells have been identified as the main factors limiting adoption of cell-based therapies. In this Review, we summarize the experience obtained from trials of 'first-generation' cell-based therapy, and emphasize the advances in the purification and lineage specification of stem cells that have enabled the development of 'next-generation' stem-cell-based therapies targeting cardiovascular disease.
Hypertrophic cardiomyopathy (HCM) is an uncommon but important cause of sudden cardiac death.
This study sought to develop an artificial intelligence approach for the detection of HCM based on ...12-lead electrocardiography (ECG).
A convolutional neural network (CNN) was trained and validated using digital 12-lead ECG from 2,448 patients with a verified HCM diagnosis and 51,153 non-HCM age- and sex-matched control subjects. The ability of the CNN to detect HCM was then tested on a different dataset of 612 HCM and 12,788 control subjects.
In the combined datasets, mean age was 54.8 ± 15.9 years for the HCM group and 57.5 ± 15.5 years for the control group. After training and validation, the area under the curve (AUC) of the CNN in the validation dataset was 0.95 (95% confidence interval CI: 0.94 to 0.97) at the optimal probability threshold of 11% for having HCM. When applying this probability threshold to the testing dataset, the CNN’s AUC was 0.96 (95% CI: 0.95 to 0.96) with sensitivity 87% and specificity 90%. In subgroup analyses, the AUC was 0.95 (95% CI: 0.94 to 0.97) among patients with left ventricular hypertrophy by ECG criteria and 0.95 (95% CI: 0.90 to 1.00) among patients with a normal ECG. The model performed particularly well in younger patients (sensitivity 95%, specificity 92%). In patients with HCM with and without sarcomeric mutations, the model-derived median probabilities for having HCM were 97% and 96%, respectively.
ECG-based detection of HCM by an artificial intelligence algorithm can be achieved with high diagnostic performance, particularly in younger patients. This model requires further refinement and external validation, but it may hold promise for HCM screening.
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Coronary Artery Disease in Patients ≥80 Years of Age Madhavan, Mahesh V.; Gersh, Bernard J.; Alexander, Karen P. ...
Journal of the American College of Cardiology,
05/2018, Letnik:
71, Številka:
18
Journal Article
Recenzirano
Odprti dostop
Coronary artery disease (CAD) is a major cause of morbidity and mortality in patients ≥80 years of age. Nonetheless, older patients have typically been under-represented in cardiovascular clinical ...trials. Understanding the pathophysiology, epidemiology, and optimal means of diagnosis and treatment of CAD in older adults is crucial to improving outcomes in this high-risk population. A patient-centered approach, taking into account health status, functional ability and frailty, cognitive skills, and patient preferences is essential when caring for older adults with CAD. The present systematic review focuses on the current knowledge base, gaps in understanding, and directions for future investigation pertaining to CAD in patients ≥80 years of age.
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