Cardiovascular involvement during COVID-19 and clinical implications in elderly patients. A review.

SARS-CoV-2 betacoronavirus is responsible for the Corona Virus Disease 2019 (COVID-19) which has relevant pathogenic implications for the cardiovascular system. Incidence and severity of COVID-19 are higher in the elderly population (65 years and older). This may be due to higher frequency of comorbidities, but increased frailty and immunosenescence linked with aging may also contribute. Moreover, in elderly individuals, SARS-CoV-2 may adopt different molecular strategies to strongly impact on cardiac aging that culminate in exacerbating a pro-inflammatory state (cytokine storm activation), which, in turn, may lead to pulmonary vascular endothelialitis, microangiopathy, diffuse thrombosis, myocarditis, heart failure, cardiac arrhythmias, and acute coronary syndromes. All these events are particularly relevant in elderly patients, and deserve targeted cardiovascular treatments and specific management of repurposed drugs against COVID-19. We discuss current evidence about the cardiovascular involvement during COVID-19, and elaborate on clinical implications in elderly patients.

Therapy against reperfusion-induced microvascular injury.

No-reflow, i.e., the lack of distal myocardial perfusion to fully recover following recanalization of an acutely occluded coronary artery, is not only a mere consequence of ischemic injury, as substantial microvascular alterations may also develop subsequently, after initial restoration of perfusion. Since part of perfusion impairment is secondary to events set in motion by reperfusion, this gives way to the possibility of preventing it through adequate interventions. Duration and severity of ischemia influence the occurrence of reperfusion-mediated no-reflow, since severity of ischemic injury sets the stage for events which actually unfold after restoration of blood flow. Proposed mechanisms of no-reflow are impaired vasodilation, intravascular thrombosis, and accumulation of neutrophils in the microvasculature, orchestrated by activation of vascular endothelium. Experimental studies have unraveled much of mechanisms of noreflow, and delineated possible ways of intervention. Despite successful experimental data, in the clinical setting results have been much less encouraging, and no drug can be currently recommended for routine use to prevent or treat microvascular injury and no-reflow in patients. Reperfusion-mediated impairment of microcirculation in postischemic hearts remains a challenges for investigators and clinicians alike. Large multicenter studies, specifically aimed at evaluating the effects of the more promising interventions (adenosine, nicorandil, statins, ACE inhibitors or angiotensin II receptor blockers) need to be designed and performed, to test the effect of these promising interventions on microvascular alterations during postischemic reflow, and their ability to improve tissue perfusion, myocardial function and prognosis in patients with acute myocardial infarction.

Relationship between oxidative stress, lipid peroxidation, and ultrastructural damage in patients with coronary artery disease undergoing cardioplegic arrest/reperfusion.

OBJECTIVE: In animal models, formation of oxidants during postischemic reperfusion may exert deleterious effects ("oxidative stress"). Cardioplegic arrest/reperfusion during cardiac surgery might similarly induce oxidative stress. However, the phenomenon has not been precisely characterized in patients, and therefore the role of antioxidant therapy at cardiac surgery is a matter of debate. Thus, we wanted to ascertain whether the relationship between oxidant formation and development of myocardial injury also translates to the situation of patients subjected to cardioplegic arrest. METHODS: In 24 patients undergoing coronary artery bypass, trans-cardiac blood samples and myocardial biopsies were taken before cardioplegic arrest and again following reperfusion. RESULTS: Cardiac glutathione release (marker of oxidant production) was negligible at baseline (0.02+/-0.04 micromol/L), but it increased 15 min into reperfusion (1.10+/-0.40 micromol/L; p<0.05); concomitantly, myocardial concentration of the antioxidant ubiquinol decreased from 144.5+/-52.0 to 97.6+/-82.0 nmol/g (p<0.05). Although these changes document cardiac exposure to oxidants, they were not accompanied by evidence of injury. Neither coronary sinus blood nor cardiac biopsies showed increased lipid peroxide concentrations. Furthermore, electron microscopy showed no major ultrastructural alterations. Finally, full recovery of left ventricular systolic and diastolic function was observed. CONCLUSIONS: Careful investigation reveals that while oxidant production does occur during cardiac surgery in patients with chronic ischemic heart disease, cardiac oxidative stress may not progress through membrane damage and irreversible injury.

Lipoperoxidación de membranas y daño ultraestructural por estrés oxidativo en isquemia-reperfusión miocárdica / Formation of reactive oxygen species during post ischemic reperfusion: ultrastructural damage

Introducción: En modelos experimentales, la formación de especies reactivas del oxígeno durante la reperfusión posisquémica induce ôestrés oxidativoõ que afecta al miocardio. Dado que los pacientes sometidos a cardioplejía sufren isquemia-reperfusión, se sugirió que en ellos habría estrés oxidativo. Sin embargo, este fenómeno aún no se ha caracterizado correctamente. Objetivo: El propósito del presente trabajo fue correlacionar la liberación de glutatión (el paso inicial de estrés oxidativo) con marcadores de progresión del daño oxidativo, como peroxidación de lípidos de membrana y desarrollo de alteraciones ultraestructurales. Material y métodos: En 24 pacientes sometidos a cirugía de puente aortocoronario se investigaron cambios en varios marcadores de estrés oxidativo y daño tisular durante la reperfusión posisquémica. Se obtuvieron muestras de sangre y biopsias cardíacas basales y luego de la reperfusión a 40,9 ± 11,9 minutos de la cardioplejía. La liberación de glutatión basal fue insignificante (0,02 ± 0,04 µmol/L), pero aumentó a los 15 minutos de la reperfusión (1,10 ± 0,40 µmol/L; p < 0,05); también disminuyeron los niveles tisulares de ubiquinol, de 144,5 ± 52 a 97,6 ± 82 nmol/g (p < 0,05). Aunque estos cambios documentan el estrés oxidativo cardíaco, no hubo alteraciones bioquímicas indicativas de daño celular, ya que no se produjo un incremento de marcadores de peroxidación lipídica, tanto en sangre del seno coronario como en las biopsias cardíacas. Tampoco se observaron alteraciones ultraestructurales importantes. Conclusiones: A pesar de observarse estrés oxidativo en pacientes sometidos a cirugía cardíaca, en las condiciones descriptas, no induce lesiones progresivas de membranas ni daño celular irreversible.

Radiation-induced ostial stenosis of the coronary artery as a cause of acute coronary syndromes: a novel mechanism of thrombus formation?

Mediastinal irradiation can induce coronary artery disease characterized by fibrous lesions developing in the absence of lipid/foam cell accumulation. We document several consecutive cases of acute coronary artery occlusion developing over radiation-induced lesions in patients who were relatively young, without evidence of classical risk factors for atherosclerosis, and in whom the coronary vasculature was otherwise apparently free of disease. The finding of acute coronary artery occlusion at the site of a fibrous lesion lends further support to the hypothesis that acute coronary syndromes may not necessarily be identifiable with ulceration/disruption of the atherosclerotic plaque as the underlying mechanism of acute thrombus formation.