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 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 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.

Cardiovascular implications and complications of the coronavirus disease-2019 pandemic: a world upside down.

PURPOSE OF REVIEW: The new pandemic of coronavirus disease-2019 (COVID-19) has produced a global tumult and has overburdened national health systems. We herein discuss the cardiovascular implications and complications of this pandemic analyzing the most recent data clustered over the last several months. RECENT FINDINGS: COVID-19 afflicts the cardiovascular system producing acute cardiac injury in 10-20% of cases with mild disease but in greater than 50-60% in severe cases, contributing to patients' demise. Other cardiovascular complications include arrhythmias, heart failure, pulmonary embolism and shock. Off-label therapies are being trialed with their own inherent cardiovascular risks, while supportive therapies currently dominate, until more specific and effective antiviral therapies and vaccinations become available. A controversial issue relates to the safety of drugs blocking the renin--angiotensin system as an angiotensin-converting enzyme (ACE) homologue, ACE2, serves as the receptor for viral entry into host cells. However, to-date, no harm has been proven for these drugs. SUMMARY: In the cardiovascular system, COVID-19 can induce acute cardiac injury, arrhythmias, heart failure, pulmonary embolism, shock and death, whereas anti-COVID therapies also confer serious cardiovascular side-effects. Ongoing extensive efforts focus on specific vaccines and antivirals. Meanwhile, cardiovascular risk factors and diseases should be jointly controlled according to current evidence-based guidelines.

COVID-19 Infection: Viral Macro- and Micro-Vascular Coagulopathy and Thromboembolism/Prophylactic and Therapeutic Management.

Coronavirus-2019 (COVID-19) predisposes patients to arterial and venous thrombosis commonly complicating the clinical course of hospitalized patients and attributed to the inflammatory state, endothelial dysfunction, platelet activation and blood stasis. This viral coagulopathy may occur despite thromboprophylaxis and raises mortality; the risk appears highest among critically ill inpatients monitored in the intensive care unit. The prevalence of venous thromboembolism in COVID-19 patients has been reported to reach ∼10-35%, while autopsies raise it to nearly 60%. The most common thrombotic complication is pulmonary embolism, which though may occur in the absence of a recognizable deep venous thrombosis and may be due to pulmonary arterial thrombosis rather than embolism, resulting in thrombotic occlusion of small- to mid-sized pulmonary arteries and subsequent infarction of lung parenchyma. This micro-thrombotic pattern seems more specific for COVID-19 and is associated with an intense immuno-inflammatory reaction that results in diffuse occlusive thrombotic micro-angiopathy with alveolar damage and vascular angiogenesis. Furthermore, thrombosis has also been observed in various arterial sites, including coronary, cerebral and peripheral arteries. Biomarkers related to coagulation, platelet activation and inflammation have been suggested as useful diagnostic and prognostic tools for COVID-19-associated coagulopathy; among them, D-dimer remains a key biomarker employed in clinical practice. Various medical societies have issued guidelines or consensus statements regarding thromboprophylaxis and treatment of these thrombotic complications specifically adapted to COVID-19 patients. All these issues are detailed in this review, data from meta-analyses and current guidelines are tabulated, while the relevant mechanisms of this virus-associated coagulopathy are pictorially illustrated.

COVID-19 infection and cardiac arrhythmias.

As the coronavirus 2019 (COVID-19) pandemic marches unrelentingly, more patients with cardiac arrhythmias are emerging due to the effects of the virus on the respiratory and cardiovascular (CV) systems and the systemic inflammation that it incurs, and also as a result of the proarrhythmic effects of COVID-19 pharmacotherapies and other drug interactions and the associated autonomic imbalance that enhance arrhythmogenicity. The most worrisome of all arrhythmogenic mechanisms is the QT prolonging effect of various anti-COVID pharmacotherapies that can lead to polymorphic ventricular tachycardia in the form of torsade des pointes and sudden cardiac death. It is therefore imperative to monitor the QT interval during treatment; however, conventional approaches to such monitoring increase the transmission risk for the staff and strain the health system. Hence, there is dire need for contactless monitoring and telemetry for inpatients, especially those admitted to the intensive care unit, as well as for outpatients needing continued management. In this context, recent technological advances have ushered in a new era in implementing digital health monitoring tools that circumvent these obstacles. All these issues are herein discussed and a large body of recent relevant data are reviewed.

The Controversy of Renin-Angiotensin-System Blocker Facilitation Versus Countering COVID-19 Infection.

The ongoing COVID-19 pandemic has produced serious turmoil world-wide. Lung injury causing acute respiratory distress syndrome seems to be a most dreaded complication occurring in ∼30%. Older patients with cardiovascular comorbidities and acute respiratory distress syndrome have an increased mortality. Although the precise mechanisms involved in the development of lung injury have not been fully elucidated, the role of the extended renin-angiotensin system seems to be pivotal. In this context, angiotensin-converting enzyme 2 (ACE2), an angiotensin-converting enzyme homologue, has been recognized as a facilitator of viral entry into the host, albeit its involvement in other counter-regulatory effects, such as converting angiotensin (Ang) II into Ang 1-7 with its known protective actions. Thus, concern was raised that the use of renin-angiotensin system inhibitors by increasing ACE2 expression may enhance patient susceptibility to the COVID-19 virus. However, current data have appeased such concerns because there has been no clinical evidence of a harmful effect of these agents as based on observational studies. However, properly designed future studies will be needed to further confirm or refute current evidence. Furthermore, other pathways may also play important roles in COVID-19 transmission and pathogenesis; spike (S) protein proteases facilitate viral transmission by cleaving S protein that promotes viral entry into the host; neprilysin (NEP), a neutral endopeptidase known to cleave natriuretic peptides, degrades Ang I into Ang 1-7; NEP can also catabolize bradykinin and thus mitigate bradykinin's role in inflammation, whereas, in the same context, specific bradykinin inhibitors may also negate bradykinin's harmful effects. Based on these intricate mechanisms, various preventive and therapeutic strategies may be devised, such as upregulating ACE2 and/or using recombinant ACE2, and exploiting the NEP, bradykinin and serine protease pathways, in addition to anti-inflammatory and antiviral therapies. These issues are herein reviewed, available studies are tabulated and pathogenetic mechanisms are pictorially illustrated.