Ketone Bodies and Cardiovascular Disease: An Alternate Fuel Source to the Rescue.

The increased metabolic activity of the heart as a pump involves a high demand of mitochondrial adenosine triphosphate (ATP) production for its mechanical and electrical activities accomplished mainly via oxidative phosphorylation, supplying up to 95% of the necessary ATP production, with the rest attained by substrate-level phosphorylation in glycolysis. In the normal human heart, fatty acids provide the principal fuel (40-70%) for ATP generation, followed mainly by glucose (20-30%), and to a lesser degree (<5%) by other substrates (lactate, ketones, pyruvate and amino acids). Although ketones contribute 4-15% under normal situations, the rate of glucose use is drastically diminished in the hypertrophied and failing heart which switches to ketone bodies as an alternate fuel which are oxidized in lieu of glucose, and if adequately abundant, they reduce myocardial fat delivery and usage. Increasing cardiac ketone body oxidation appears beneficial in the context of heart failure (HF) and other pathological cardiovascular (CV) conditions. Also, an enhanced expression of genes crucial for ketone break down facilitates fat or ketone usage which averts or slows down HF, potentially by avoiding the use of glucose-derived carbon needed for anabolic processes. These issues of ketone body utilization in HF and other CV diseases are herein reviewed and pictorially illustrated.

Takotsubo Syndrome and Sudden Cardiac Death.

Takotsubo syndrome (TTS), triggered by intense emotional or physical stress, occurring most commonly in post-menopausal women, presents as an ST-elevation myocardial infarction (MI). Cardiovascular complications occur in almost half the patients with TTS, and the inpatient mortality is comparable to MI (4-5%) owing to cardiogenic shock, myocardial rupture, or life-threatening arrhythmias. Thus, its prognosis is not as benign as previously thought, as it may cause mechanical complications (cardiac rupture) and potentially lethal arrhythmias and sudden cardiac death (SCD). Similar to MI, some patients may perish before reaching the hospital due to out-of-hospital cardiac arrest; this may lead to underestimation of the actual SCD risk. Furthermore, after discharge, some patients may develop late SCD and/or TTS recurrence that may result in SCD. There are risk factors for SCD in TTS patients, such as severe/persistent QT-interval prolongation inciting torsade-de-pointes, other ECG abnormalities (diffuse giant negative T-waves, widened QRS-complex), bradyarrhythmias, comorbidities, concurrent obstructive coronary artery disease or vasospasm, male gender, older age, severe left ventricular dysfunction, and use of sympathomimetic drugs. All these issues are herein reviewed, case reports/series and data from large cohort studies and meta-analyses are analyzed, risk factors are tabulated, and proarrhythmic effects and management strategies are discussed and pictorially illustrated.

Low serum albumin: A neglected predictor in patients with cardiovascular disease.

Albumin, the most abundant circulating protein in blood, is an essential protein which binds and transports various drugs and substances, maintains the oncotic pressure of blood and influences the physiological function of the circulatory system. Albumin also has anti-inflammatory, antioxidant, and antithrombotic properties. Evidence supports albumin's role as a strong predictor of cardiovascular (CV) risk in several patient groups. Its protective role extends to those with coronary artery disease, heart failure, hypertension, atrial fibrillation, peripheral artery disease or ischemic stroke, as well as those undergoing revascularization procedures or with aortic stenosis undergoing transcatheter aortic valve replacement, and patients with congenital heart disease and/or endocarditis. Hypoalbuminemia is a strong prognosticator of increased all-cause and CV mortality according to several cohort studies and meta-analyses in hospitalized and non-hospitalized patients with or without comorbidities. Normalization of albumin levels before discharge lowers mortality risk, compared with hypoalbuminemia before discharge. Modified forms of albumin, such as ischemia modified albumin, also has prognostic value in patients with coronary or peripheral artery disease. When albumin is combined with other risk factors, such as uric acid or C-reactive protein, the prognostic value is enhanced. Although albumin supplementation may be a plausible approach, its efficacy has not been established and in patients with hypoalbuminemia, priority is focused on diagnosing and managing the underlying condition. The CV effects of hypoalbuminemia and relevant issues are considered in this review. Large cohort studies and meta-analyses are tabulated and the physiologic effects of albumin and the deleterious effects of low albumin are pictorially illustrated.

COVID-19 Re-Infections: More Common with the Omicron Variant / COVID-19 Pandemic: Is There Light at the End of the Tunnel?

A recent surge of COVID-19 reinfections has been ascribed to new variants of concern (VOCs) with increased transmissibility, such as the Omicron variant, but also to laxity in compliance with measures of prophylaxis, incomplete or lack of vaccination, the Peltzman effect where people tend to increase their risky behavior when safety measures are mandated, weaker antibody responses after booster immunization in some individuals and/or immunocompromised patients, and increased antigen variability in VOCs. The latter impairs humoral and cellular immunity post-infection rendering COVID-19 convalescents more vulnerable and at risk of re-infection with VOCs. Unfortunately, COVID-19 disease is here to stay demanding observance of measures of prophylaxis, expansion of vaccination programs and continued vigilance;there is still a dire need for the development of durably effective vaccines against SARS-CoV-2 but also against its emerging variants. [ FROM AUTHOR] Copyright of Rhythmos is the property of Evagelismos General Hospital of Athens and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

COVID-19 Related Myocarditis: Diagnosis and Management

A comprehensive review of current data on COVID-19 related myocarditis is herein presented. [ FROM AUTHOR] Copyright of Rhythmos is the property of Evagelismos General Hospital of Athens and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

COVID-19 infection and body weight: A deleterious liaison in a J-curve relationship.

During the course of the COVID-19 pandemic, obesity has been shown to be an independent risk factor for high morbidity and mortality. Obesity confers poor outcomes in younger (<60 years) patients, an age-group considered low-risk for complications, a privilege that is negated by obesity. Findings are consistent, the higher the body mass index (BMI) the worse the outcomes. Ectopic (visceral) obesity also promotes proinflammatory, prothrombotic, and vasoconstrictive states, thus enhancing the deleterious effects of COVID-19 disease. Less, albeit robust, evidence also exists for a higher risk of COVID-19 infection incurred with underweight. Thus, the relationship of COVID-19 and BMI has a J-curve pattern, where patients with both overweight/obesity and underweight are more susceptible to the ailments of COVID-19. The pathophysiology underlying this link is multifactorial, mostly relating to the inflammatory state characterizing obesity, the impaired immune response to infectious agents coupled with increased viral load, the overexpression in adipose tissue of the receptors and proteases for viral entry, an increased sympathetic activity, limited cardiorespiratory reserve, a prothrombotic milieu, and the associated comorbidities. All these issues are herein reviewed, the results of large studies and meta-analyses are tabulated and the pathogenetic mechanisms and the BMI relationship with COVID-19 are pictorially illustrated.

COVID-19 Infection: A Neuropsychiatric Perspective.

As a potentially life-threatening disease with no definitive treatment and without fully implemented population-wide vaccination, COVID-19 has created unprecedented turmoil in socioeconomic life worldwide. In addition to physical signs from the respiratory and many other systems, the SARS-CoV-2 virus produces a broad range of neurological and neuropsychiatric problems, including olfactory and gustatory impairments, encephalopathy and delirium, stroke and neuromuscular complications, stress reactions, and psychoses. Moreover, the psychosocial impact of the pandemic and its indirect effects on neuropsychiatric health in noninfected individuals in the general public and among health care workers are similarly far-ranging. In addition to acute neuropsychiatric manifestations, COVID-19 may also produce late neuropsychiatric sequelae as a function of the psychoneuroimmunological cascade that it provokes. The present article presents a state-of-the-science review of these issues through an integrative review and synthesis of case series, large-cohort studies, and relevant meta-analyses. Heuristics for evaluation and further study of the neuropsychiatric manifestations of SARS-CoV-2 infection are offered.

COVID-19 Genetics: Current Status

Interindividual clinical variability characterizes COVID-19 infection SARS-CoV-2 infection, ranging from no or mild symptoms in >95% of individuals to severe and life-threatening acute respiratory distress syndrome with bilateral pneumonia requiring intensive care unit monitoring in <0.5% of infected individuals. The host genetic background seems to determine the susceptibility and outcome in COVID-19 patients. Several relevant genetic variants and risk genes have been identified, relating to blood type, HLA system, angiotensin converting enzyme and other proteins, cytokines, and other host genetic signals and immune system's specific response. On the other hand, emerging new variants of the COVID-19 virus with enhanced transmissibility/infectivity and immune escape ability pose new risks, especially if they are going to have an impact on the efficacy of currently available vaccines. All these issues relating to the impact of genetics on COVID-19 selectivity are herein reviewed. [ABSTRACT FROM AUTHOR] Copyright of Rhythmos is the property of Evagelismos General Hospital of Athens and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

COVID-19 and Acute Myocardial Injury and Infarction: Related Mechanisms and Emerging Challenges.

In the era of the coronavirus disease 2019 (COVID-19) pandemic, acute cardiac injury (ACI), as reflected by elevated cardiac troponin above the 99th percentile, has been observed in 8%-62% of patients with COVID-19 infection with highest incidence and mortality recorded in patients with severe infection. Apart from the clinically and electrocardiographically discernible causes of ACI, such as acute myocardial infarction (MI), other cardiac causes need to be considered such as myocarditis, Takotsubo syndrome, and direct injury from COVID-19, together with noncardiac conditions, such as pulmonary embolism, critical illness, and sepsis. Acute coronary syndromes (ACS) with normal or near-normal coronary arteries (ACS-NNOCA) appear to have a higher prevalence in both COVID-19 positive and negative patients in the pandemic compared to the pre-pandemic era. Echocardiography, coronary angiography, chest computed tomography and/or cardiac magnetic resonance imaging may render a correct diagnosis, obviating the need for endomyocardial biopsy. Importantly, a significant delay has been recorded in patients with ACS seeking advice for their symptoms, while their routine care has been sharply disrupted with fewer urgent coronary angiographies and/or primary percutaneous coronary interventions performed in the case of ST-elevation MI (STEMI) with an inappropriate shift toward thrombolysis, all contributing to a higher complication rate in these patients. Thus, new challenges have emerged in rendering a diagnosis and delivering treatment in patients with ACI/ACS in the pandemic era. These issues, the various mechanisms involved in the development of ACI/ACS, and relevant current guidelines are herein reviewed.

Deep Neural Networks Can Predict New-Onset AF from the 12-Lead ECG and Help Identify Those at Risk of AF-Related Stroke

Similarly, within the prospective, genetic heart disease-enriched dataset, the difference between DNNpredicted QTc values derived from mECG tracings and those annotated from 12-lead ECGs by a QT expert (-0.45±24.73 ms) and a commercial core ECG laboratory (10.52±25.64 ms) was nominal. Compared with patients with ARDS without COVID-19, patients with COVID-19 were older and had higher creatinine levels and less favorable vital signs. This model predicted patients at high risk for new-onset AF in 62% of all patients who experienced an AF-related stroke within 3 years of the index ECG (Raghunath S et al, Circulation 2021;143: 1287-98). [Extracted from the article] Copyright of Rhythmos is the property of Evagelismos General Hospital of Athens and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

COVID-19 Vaccines: Cardiovascular Perspectives

The accelerated development of COVID-19 vaccines has ushered in new hope for the beginning of the end of this unprecedented pandemic with the heaviest toll on global health and economy. The goal of vaccination is to achieve "herd immunity" which helps interrupt the chain of transmission with the threshold of such immunity estimated at 60-70%. There are four main types of COVID-19 vaccines: messenger RNA (mRNA);viral vector;protein-based;and whole virus. mRNA vaccines and most of the COVID-19 vaccines are using various versions of the spike (S) protein as their vaccine antigen component, while a few vaccines employ the whole virion. Local reactions and mild symptoms are the most common adverse reactions to vaccination;however, anaphylaxis is a potentially life-threatening adverse effect and needs to be monitored and promptly managed. Deaths with temporal association with vaccination have also been reported, but not causally linked to vaccination. Thrombotic events have also been reported, particularly with two brands, and have caused alarm but apparently remain extremely rare, nevertheless authorities remain watchful. One is considered fully vaccinated for COVID-19 ≥2 weeks after one has received the last dose. Unfortunately, new strains of COVID-19 are emerging fast, for which the current vaccines may be less effective. Thus, it is still crucial to continue wearing facemasks, apply hand washing, and social distancing in order to slow viral spread and to protect everybody from infection. Several unknowns still remain about COVID-19 vaccines that relate to the safety and efficacy of the vaccines in "special" populations, the degree and duration that these vaccines protect against infection and transmission. and possible long-term adverse effects of vaccination, not yet encountered in phase 3 trials. [ABSTRACT FROM AUTHOR] Copyright of Rhythmos is the property of Evagelismos General Hospital of Athens and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)