Pathophysiology of Takotsubo Cardiomyopathy: Reopened Debate.

Takotsubo cardiomyopathy (TTC), a persistently obscure dysfunctional condition of the left ventricle, is uniquely transient but nevertheless dangerous. It features variable ventricular patterns and is predominant in women. For 30 years, pathophysiologic investigations have progressed only slowly and with inadequate focus. It was initially proposed that sudden-onset spastic obliteration of coronary flow induced myocardial ischemia with residual stunning and thus TTC. Later, it was generally accepted without proof that, in the presence of pain or emotional stress, the dominant mechanism for TTC onset was a catecholamine surge that had a direct, toxic myocardial effect. We think that the manifestations of TTC are more dynamic and complex than can be assumed from catecholamine effects alone. In addition, after reviewing the recent medical literature and considering our own clinical observations, especially on spasm, we theorize that atherosclerotic coronary artery disease modulates and physically opposes obstruction during spasm. This phenomenon may explain the midventricular variant of TTC and the lower incidence of TTC in men. We continue to recommend and perform acetylcholine testing to reproduce TTC and to confirm our theory that coronary spasm is its initial pathophysiologic factor. An improved understanding of TTC is especially important because of the condition's markedly increased incidence during the ongoing COVID-19 pandemic.

Association between blood pressure categories and cardiovascular disease mortality in China.

BACKGROUND: Blood pressure (BP) categories are useful to simplify preventions in public health, and diagnostic and treatment approaches in clinical practice. Updated evidence about the associations of BP categories with cardiovascular diseases (CVDs) and its subtypes is warranted. METHODS AND FINDINGS: About 0.5 million adults aged 30 to 79 years were recruited from 10 areas in China during 2004-2008. The present study included 430 977 participants without antihypertension treatment, cancer, or CVD at baseline. BP was measured at least twice in a single visit at baseline and CVD deaths during follow-up were collected via registries and the national health insurance databases. Multivariable Cox regression was used to estimate the associations between BP categories and CVD mortality. Overall, 16.3% had prehypertension-low, 25.1% had prehypertension-high, 14.1% had isolated systolic hypertension (ISH), 1.9% had isolated diastolic hypertension (IDH), and 9.1% had systolic-diastolic hypertension (SDH). During a median 10-year follow-up, 9660 CVD deaths were documented. Compared with normal, the hazard ratios (95% CI) of prehypertension-low, prehypertension-high, ISH, IDH, SDH for CVD were 1.10 (1.01-1.19), 1.32 (1.23-1.42), 2.04 (1.91-2.19), 2.20 (1.85-2.61), and 3.81 (3.54-4.09), respectively. All hypertension subtypes were related to the increased risk of CVD subtypes, with a stronger association for hemorrhagic stroke than for ischemic heart disease. The associations were stronger in younger than older adults. CONCLUSIONS: Prehypertension-high should be considered in CVD primary prevention given its high prevalence and increased CVD risk. All hypertension subtypes were independently associated with CVD and its subtypes mortality, though the strength of associations varied substantially.

Improving translational research in sex-specific effects of comorbidities and risk factors in ischaemic heart disease and cardioprotection: position paper and recommendations of the ESC Working Group on Cellular Biology of the Heart.

Ischaemic heart disease (IHD) is a complex disorder and a leading cause of death and morbidity in both men and women. Sex, however, affects several aspects of IHD, including pathophysiology, incidence, clinical presentation, diagnosis as well as treatment and outcome. Several diseases or risk factors frequently associated with IHD can modify cellular signalling cascades, thus affecting ischaemia/reperfusion injury as well as responses to cardioprotective interventions. Importantly, the prevalence and impact of risk factors and several comorbidities differ between males and females, and their effects on IHD development and prognosis might differ according to sex. The cellular and molecular mechanisms underlying these differences are still poorly understood, and their identification might have important translational implications in the prediction or prevention of risk of IHD in men and women. Despite this, most experimental studies on IHD are still undertaken in animal models in the absence of risk factors and comorbidities, and assessment of potential sex-specific differences are largely missing. This ESC WG Position Paper will discuss: (i) the importance of sex as a biological variable in cardiovascular research, (ii) major biological mechanisms underlying sex-related differences relevant to IHD risk factors and comorbidities, (iii) prospects and pitfalls of preclinical models to investigate these associations, and finally (iv) will provide recommendations to guide future research. Although gender differences also affect IHD risk in the clinical setting, they will not be discussed in detail here.

Long COVID-19: A Primer for Cardiovascular Health Professionals, on Behalf of the CCS Rapid Response Team.

It is now widely recognized that COVID-19 illness can be associated with significant intermediate and potentially longer-term physical limitations. The term, "long COVID-19" is used to define any patient with persistent symptoms after acute COVID-19 infection (ie, after 4 weeks). It is postulated that cardiac injury might be linked to symptoms that persist after resolution of acute infection, as part of this syndrome. The Canadian Cardiovascular Society Rapid Response Team has generated this document to provide guidance to health care providers on the optimal management of patients with suspected cardiac complications of long COVID-19.

SARS-CoV 2 Infection (Covid-19) and Cardiovascular Disease in Africa: Health Care and Socio-Economic Implications.

The current pandemic of SARS-COV 2 infection (Covid-19) is challenging health systems and communities worldwide. At the individual level, the main biological system involved in Covid-19 is the respiratory system. Respiratory complications range from mild flu-like illness symptoms to a fatal respiratory distress syndrome or a severe and fulminant pneumonia. Critically, the presence of a pre-existing cardiovascular disease or its risk factors, such as hypertension or type II diabetes mellitus, increases the chance of having severe complications (including death) if infected by the virus. In addition, the infection can worsen an existing cardiovascular disease or precipitate new ones. This paper presents a contemporary review of cardiovascular complications of Covid-19. It also specifically examines the impact of the disease on those already vulnerable and on the poorly resourced health systems of Africa as well as the potential broader consequences on the socio-economic health of this region.

Exercise testing in COVID-19 era: Clinical profile, results and feasibility wearing a facemask.

BACKGROUND: No data are available about whether Coronavirus disease 2019 (COVID-19) pandemic have led to changes in clinical profiles or results of exercise testing once the usual activity was reassumed, as well as if wearing a facemask has any impact on the tests. The aim of this study is to evaluate differences in the patients referred to exercise stress testing in the context of COVID-19 pandemic and analyse the feasibility and results of these tests wearing a facemask. METHODS: We included all patients referred for an exercise test from 1 June to 30 September 2020 and compared them with the patients attended within the same period in 2019 before and after propensity score matching. All patients referred in 2020 wore a facemask. RESULTS: A total of 854 patients were included: 398 in the 2020 group and 456 in 2019. No significant differences in baseline characteristics of the patients were observed, with the exception of dyspnoea, which was nearly twice as high in 2020 as compared with 2019. Regarding the results of the tests, no differences were observed, with almost 80% of maximal tests, similar functional capacity and over a 20% of positive exercise tests in both groups. These results remained after propensity score matching. CONCLUSION: COVID-19 pandemic has not changed the clinical profile of patients referred to exercise testing. In addition, performing exercise testing wearing a facemask is feasible, with no influence in functional capacity and clinical results.

Quantifying and reporting cardiac findings in imaging of COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to be a public health emergency and a pandemic of international concern. As of April 31st,  the reported cases of COVID-19 are three million in 186 countries. Reported case fatality has crossed 200 thousand among which more than fifty thousand has been in the USA. Most patients present with symptoms of fever, cough, and shortness of breath following exposure to other COVID-19 patients. Respiratory manifestations predominate in patients with mild, moderate, severe illness. Imaging of patients with COVID-19 consistently reports various pulmonary parenchymal involvement. In this article we wanted to reinforce and review the various reported imaging patterns of cardiac and mediastinal involvement in COVID-19 patients. Among patients with COVID 19 who underwent various imaging of chest various cardiac findings including pericardial effusion, myocarditis, cardiomegaly has been reported. Most of these findings have been consistently reported in patients with significant acute myocardial injury, and fulminant myocarditis. Acute biventricular dysfunction has also been reported with subsequent improvement of the same following clinical improvement. Details of cardiac MRI is rather limited. In a patient with clinical presentation of acute myocarditis, biventricular myocardial interstitial edema, diffuse biventricular hypokinesia, increased ventricular wall thickness, and severe LV dysfunction has been reported. Among patients with significant clinical improvement in LV structure and function has also been documented. With increasing number of clinical cases, future imaging studies will be instrumental in identifying the various cardiac manifestations, and their relation to clinical outcome.

Potential Therapeutic Role of Purinergic Receptors in Cardiovascular Disease Mediated by SARS-CoV-2.

Novel coronavirus disease 2019 (COVID-19) causes pulmonary and cardiovascular disorders and has become a worldwide emergency. Myocardial injury can be caused by direct or indirect damage, particularly mediated by a cytokine storm, a disordered immune response that can cause myocarditis, abnormal coagulation, arrhythmia, acute coronary syndrome, and myocardial infarction. The present review focuses on the mechanisms of this viral infection, cardiac biomarkers, consequences, and the possible therapeutic role of purinergic and adenosinergic signalling systems. In particular, we focus on the interaction of the extracellular nucleotide adenosine triphosphate (ATP) with its receptors P2X1, P2X4, P2X7, P2Y1, and P2Y2 and of adenosine (Ado) with A2A and A3 receptors, as well as their roles in host immune responses. We suggest that receptors of purinergic signalling could be ideal candidates for pharmacological targeting to protect against myocardial injury caused by a cytokine storm in COVID-19, in order to reduce systemic inflammatory damage to cells and tissues, preventing the progression of the disease by modulating the immune response and improving patient quality of life.