Dysregulation of the endogenous lipid mediators endocannabinoids and their G-protein-coupled cannabinoid receptors 1 and 2 (CB
R and CB
R) has been implicated in a variety of cardiovascular ...pathologies. Activation of CB
R facilitates the development of cardiometabolic disease, whereas activation of CB
R (expressed primarily in immune cells) exerts anti-inflammatory effects. The psychoactive constituent of marijuana, Δ
-tetrahydrocannabinol (THC), is an agonist of both CB
R and CB
R, and exerts its psychoactive and adverse cardiovascular effects through the activation of CB
R in the central nervous and cardiovascular systems. The past decade has seen a nearly tenfold increase in the THC content of marijuana as well as the increased availability of highly potent synthetic cannabinoids for recreational use. These changes have been accompanied by the emergence of serious adverse cardiovascular events, including myocardial infarction, cardiomyopathy, arrhythmias, stroke, and cardiac arrest. In this Review, we summarize the role of the endocannabinoid system in cardiovascular disease, and critically discuss the cardiovascular consequences of marijuana and synthetic cannabinoid use. With the legalization of marijuana for medicinal purposes and/or recreational use in many countries, physicians should be alert to the possibility that the use of marijuana or its potent synthetic analogues might be the underlying cause of severe cardiovascular events and pathologies.
Chest pain in patients without obstructive coronary artery disease has been realized as a frequent problem encountered in clinical practice. Invasive flow investigations have suggested that up to ...two-thirds of patients with nonobstructive coronary atherosclerosis may have microvascular dysfunction (MVD). Positron emission tomography myocardial perfusion imaging in conjunction with tracer-kinetic modeling enables the concurrent quantification of myocardial blood flow (MBF) in milliliters per minute per gram of tissue. This allows the assessment of hyperemic MBFs and myocardial flow reserve for the noninvasive identification and characterization of MVD as an important functional substrate for angina symptoms amenable to intensified and individualized medical intervention with nitrates, calcium-channel blockers, statins, angiotensin-converting enzyme inhibitors, and/or angiotensin II type 1 receptor blockers. Recent investigations suggest that cardiac magnetic resonance and computed tomography may also be suitable for the noninvasive detection of MVD. Whether intensified and individualized treatment related improvement or even normalization of hyperemic MBF and/or myocardial flow reserve may lead to a persistent reduction in angina symptoms and/or improved cardiovascular outcome as compared to standard care, deserves further testing in large-scale randomized clinical trials.
Despite major advances in mechanical and pharmacological reperfusion strategies to improve acute myocardial infarction (MI) injury, substantial mortality, morbidity, and socioeconomic burden still ...exists. To further reduce infarct size and thus ameliorate clinical outcome, the focus has also shifted towards early detection of MI with high-sensitive troponin assays, imaging, cardioprotection against pathophysiological targets of myocardial reperfusion injury with mechanical (ischaemic post-conditioning, remote ischaemic pre-conditioning, therapeutic hypothermia, and hypoxemia) and newer pharmacological interventions (atrial natriuretic peptide, cyclosporine A, and exenatide). Evidence from animal models of myocardial ischaemia and reperfusion also demonstrated promising results on more selective anti-inflammatory compounds that require additional validation in humans. Cardiac stem cell treatment also hold promise to reduce infarct size and negative remodelling of the left ventricle that may further improves symptoms and prognosis in these patients. This review focuses on the pathophysiology, detection, and reperfusion strategies of ST-segment elevation MI as well as current and future challenges to reduce ischaemia/reperfusion injury and infarct size that may result in a further improved outcome in these patients.
Positron emission tomography (PET) myocardial perfusion imaging in concert with tracer-kinetic modeling affords the assessment of regional myocardial blood flow (MBF) of the left ventricle in ...absolute terms (milliliters per gram per minute). Assessment of MBF both at rest and during various forms of vasomotor stress provides insight into early and subclinical abnormalities in coronary arterial vascular function and/or structure, noninvasively. The noninvasive evaluation and quantification of MBF and myocardial flow reserve (MFR) extend the scope of conventional myocardial perfusion imaging from detection of end-stage, advanced, and flow-limiting, epicardial coronary artery disease (CAD) to early stages of atherosclerosis or microvascular dysfunction. Recent studies have shown that impaired hyperemic MBF or MFR with PET, with or without accompanying CAD, is predictive of increased relative risk of death or progression of heart failure. Quantitative approaches that measure MBF with PET identify multivessel CAD and offer the opportunity to monitor responses to lifestyle and/or risk factor modification and to therapeutic interventions. Whether improvement or normalization of hyperemic MBF and/or the MFR will translate to improvement in long-term cardiovascular outcome remains clinically untested. In the meantime, absolute measures of MBF with PET can be used as a surrogate marker for coronary vascular health, and to monitor therapeutic interventions. Although the assessment of myocardial perfusion with PET has become an indispensable tool in cardiac research, it remains underutilized in clinical practice. Individualized, image-guided cardiovascular therapy may likely change this paradigm in the near future.
In cardiotoxicity, PET/MR affords an accurate evaluation of cardiovascular morphology, function, and also multi-parametric tissue characterization. A composite of several cardiac imaging parameters ...provided by the PET/MR scanner is likely to outperform a single parameter or imaging modality in the assessment and prediction of the severity and progression of cardiotoxicity but needing clinical investigations. Of particular interest, a heterogeneity map of single PET and CMR parameters could be perfectly correlated with the PET/MR scanner likely emerging as a promising marker of cardiotoxicity to monitor treatment response. While such functional and structural multiparametric imaging approach with cardiac PET/MR in the assessment and characterization of cardiotoxicity holds much promise, its validity and value in cancer patients treated with chemotherapy and/or radiation still needs to be assessed. The multi-parametric imaging approach with PET/MR, however, is likely to set new standards to develop predictive constellations of parameters for the severity and potential progression of cardiotoxicity that should afford timely and individualized treatment intervention to ascertain myocardial recovery and improved clinical outcome in these high-risk patients.
•In cardiotoxicity, PET/MR affords an accurate evaluation of cardiovascular morphology, function, and also multi-parametric tissue characterization•A composite of several cardiac imaging parameters provided by the PET/MR scanner is likely to outperform a single parameter or imaging modality in the assessment and prediction of the severity and progression of cardiotoxicity but needing clinical investigations•Heterogeneity map of single PET and CMR parameters could be perfectly correlated with the PET/MR scanner likely emerging as a promising marker of cardiotoxicity to monitor treatment response
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