TakoTsubo Syndrome: A Well-Known Disease but Not Everything Is Clear Yet.

TakoTsubo Syndrome (TTS) is a stress-induced cardiac disease characterized by temporary and segmental left ventricle dysfunction, typically involving the apex. Post-menopause women are more frequently affected. ECG and clinical features at presentation may be similar to those observed in acute coronary syndrome (ACS). However underlying pathomechanisms are completely different and, for what concerns TTS, extremely debated and not yet completely understood. Some hypotheses have been proposed during years, mostly regarding catecholamine-induced cardiotoxicity and microvascular dysfunction, usually following a trigger event which may be either "emotional" (primary TTS) or "physical" (secondary TTS). Additional modulators like neuroendocrine disorders (particularly hypothalamic-pituitary-adrenal axis dysfunction and estrogen drop in menopause) may play a crucial role in TTS onset. Despite being originally considered more benign than ACS, several studies have enlightened that TTS and STEMI are burdened by the same in-hospital mortality and complications. However, TTS and ACS complications somehow differ for what concerns incidence, the underlying mechanisms, and both long- and short-term outcomes. Full recovery in TTS requires weeks to months and cases of recurrences have been described, but no single clinical feature seems to predict subsequent episodes so far. By now, apart from inhibitors of the Renin-Angiotensin-Aldosterone System (RAASi), no drug has proved to be effective either in the acute or chronic phase in reducing mortality, improving outcome, or preventing recurrences.

Low- vs high-dose ARNI effects on clinical status, exercise performance and cardiac function in real-life HFrEF patients.

PURPOSE: Only a few studies are available on dose-related effects of sacubitril/valsartan (angiotensin receptor neprilysin inhibition (ARNI)) in real-life patients with heart failure and reduced ejection fraction (HFrEF). We sought to investigate clinical and functional effects in real-life HFrEF patients receiving ARNI at a different cumulative dose. METHODS: This was an observational study in consecutive outpatients admitted for HFrEF from October 2017 to June 2019. The PARADIGM criteria were needed for enrolment. ARNI was uptitrated according to blood pressure, drug tolerability, renal function and kaliemia. At least 10-month follow-up was required in each patient. Clinical assessment, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, 6-min walk test and strain echocardiography were performed in each patient on a regular basis during the observational period. At the end of the study, patients were divided into two groups based on the median yearly dose of the ARNI medication. RESULTS: A total of 90 patients, 64 ± 11 years, 82% males, were enrolled. The cut-off dose was established in 75 mg BID, and the study population was divided into group A (≤ 75 mg), 52 patients (58%), and group B (> 75 mg), 38 patients (42%). The follow-up duration was 12 months (range 11-13). NYHA class, KCCQ score and 6MWT performance ameliorated in both groups, with a quicker time to benefit in group B. The proportion of patients walking > 350 m increased from 21 to 58% in group A (p < 0.001), and from 29 to 82% in group B (p < 0.001). A positive effect was also disclosed in the left ventricular remodelling, strain deformation and diastolic function. CONCLUSION: One-year ARNI treatment was effective in our real-life HFrEF patient population, leading to clinical and functional improvement in both study groups, slightly greater and with a shorter time to benefit in group B.

Prognostic value of two-dimensional strain in early ischemic heart disease: A 5-year follow-up study.

INTRODUCTION: Two-dimensional strain echocardiography (2D-SE) is a reliable method for measuring deformation of the left ventricle. AIM OF THE STUDY: Aim of the study was to determine changes in 2D-SE parameters over time collected during dipyridamole stress echo-cardiography (dipy-stress) and prognosis of patients with non-diagnostic dipy-stress results. METHODS: In the first phase of the study, assessment of a prospective enrolled population with a non-diagnostic dipy-stress test result was conducted, checking through coronary CT angiography (CCTA) the presence of coronary artery disease (CAD). In the follow-up phase, an echocardiographic re-evaluation and outcome analysis during a mean follow-up of 78 months was carried out. RESULTS: In the first phase, Global Circumferential Strain (GCS) values were similar in the CCTA positive and CCTA negative groups at rest and after stress. For Global Longitudinal Strain (GLS), there was a significant reduction (p < .0001) in the CCTA positive group compared to the CCTA negative group. After 78 ± 9 months none of the enrolled patients experimented cardiac events. Values of GCS, both at rest and after stress, did not differ statistically comparing follow-up values with baseline ones. No statistically significant changes were seen in the same analysis for GLS rest and stress values, between baseline and follow-up in the two groups. CONCLUSIONS: Performing 2D-SE during dipy-stress can detect mild CAD that conventional stress-tests miss. Patients with mild coronary stenosis may have a favorable mid-term prognosis, but efforts should be made to investigate the decrease trend in GLS, at rest and after stress, reported in this patient group.

Pharmacologic Rate versus Rhythm Control for Atrial Fibrillation in Heart Failure Patients.

Atrial fibrillation (AF) and Heart failure (HF) constitute two frequently coexisting cardiovascular diseases, with a great volume of the scientific research referring to strategies and guidelines associated with the best management of patients suffering from either of the two or both of these entities. The common pathophysiological paths, the adverse outcomes, the hospitalization rates, and the mortality rates that occur from various reports and trials indicate that a targeted therapy to the common background of these cardiovascular conditions may reverse the progression of their interrelating development. Among other optimal treatments concerning the prevalence of both AF and HF, the introduction of rhythm and rate control strategies in the guidelines has underlined the importance of sinus rhythm and heart rate control in the prevention of deleterious complications. The use of these strategies in the clinical practice has led to a debate about the superiority of rhythm versus rate control. The current guidelines as well as the published randomized trials and studies have not proved that rhythm control is more beneficial than the rate control treatments in the terms of survival, all-cause mortality, hospitalization rates, and quality of life. Therefore, the current therapeutic strategy is based on the therapy guidelines and the clinical judgment and experience. The aim of this review was to elucidate the endpoints of pharmacologic randomized clinical trials and the clinical data of each antiarrhythmic or rate-limiting medication, so as to promote their effective, individualized, evidence-based clinical use.

Malignant right coronary artery origin from the left sinus of Valsalva: Complementary role for transesophageal echocardiography upon the cath-lab diagnosis.

Anomalous origin of the right coronary artery (RCA) from the left sinus of Valsalva is a rare but clinically relevant congenital anomaly, since the RCA may be subjected to cyclical compression due to its interarterial course. At least in the past, most patients experienced bad outcomes before being diagnosed with a malignant variant. Chronic (often subclinical) myocardial ischemia and possible arrhythmias are common complications. Once symptoms or electrocardiographic signs of myocardial ischemia become apparent, a quick diagnosis is mandatory. We report the case of a late symptomatic woman in whom RCA originated from the opposite sinus of Valsalva. The malignant variant was confirmed at transesophageal echocardiography directly in the catheterization laboratory, soon after angiographic diagnosis of aberrant origin.

Dynamic right ventricular outflow tract obstruction by cardiac hydatic cysts: A multimodality imaging study.

We report the case of massive hydatic heart disease in a 50-year-old male patient referred to hospital for recent-onset dyspnea, atypical chest, and hypotension. Right ventricular outflow tract obstruction was demonstrated to be caused by hypoechogenic formations at Doppler-echocardiography and confirmed to be hydatic cysts at cardiac magnetic resonance. These cysts developed within the right ventricular wall and the septum, and caused hemodynamic instability.

Pathophysiological and clinical implications of high intramural coronary blood flow velocity in aortic stenosis.

We sought to recognize the blood flow velocity (BFV) through the left anterior descending (LAD) coronary artery and its small intramyocardial (IM) branches by transthoracic Doppler-echocardiography in patients with aortic stenosis (AS). Sixty-two patients, aged 74.0 ± 9.6 years, 37 women, with preserved left ventricular (LV) function, apparently free of active ischemic disease, were enrolled and classified into 3 groups according to the mean gradient (MG) across the aortic valve: 13 patients (21%) entered the group A (MG ≤ 20 mmHg), 29 (48%) group B (MG 21-40 mmHg) and 20 (31%) group C (MG > 40 mmHg). Peak and mean coronary BFVs were demonstrated to gradually increase according to AV gradient, especially through the IM arteries. Peak IM-BFV was 58.9 cm/s (95% CI 46.4-71.4) in group A, 73.2 cm/s (95% CI 64.8-81.6) in group B, and 96.4 cm/s (95% CI 86.3-106.5) in group C (p < 0.001), whereas peak LAD-BFV was 38.1 cm/s (95% CI 32.8-43.3), 44.4 cm/s (95% CI 40.9-47.9) and 47.3 cm/s (95% CI 43.1-52.5), respectively (p = 0.03). Also, 34 patients complaining with unspecific symptoms showed much higher IM-BFV than those who were not. High values were also recognized in patients with LV ejection fraction/velocity ratio (EFVR) ≤ 0.90 (IM-BFV 91 ± 26 cm/s vs. 72 ± 24 cm/s in those with EFVR > 0.90, p = 0.001). In conclusion, AS patients in the present study showed gradually higher coronary BFVs according to AS gradient, especially through the IM vessels, and both peak and mean velocities were discriminating specific patient subsets. Pathophysiological mechanisms and potential clinical implications are discussed.

Echocardiographic Findings in Cardiac Amyloidosis: Inside Two-Dimensional, Doppler, and Strain Imaging.

PURPOSE OF REVIEW: The aim is to provide a description of the most important echocardiographic features in systemic amyloidosis. RECENT FINDINGS: Amyloidosis is a heterogeneous group of multisystem disorders, characterized by an extracellular deposition of amyloid fibrils. Several imaging tests are available for the diagnosis; however, echocardiography is the cornerstone of the non-invasive imaging modality for cardiac amyloidosis. So far, little is known about the diagnosis of cardiac amyloidosis through imaging modalities. We summarized the most important echocardiographic findings in cardiac amyloidosis. Hence, we offered a systematic report of the diagnostic performance of cardiac amyloidosis using echocardiography.

Left ventricular endocardial longitudinal dysfunction persists after acute myocarditis with preserved ejection fraction.

BACKGROUND: The aim of present study was to assess left ventricular (LV) myocardial deformation and changes over time in patients with acute myocarditis (AM) with preserved ejection fraction detected by late gadolinium enhancement (LGE) magnetic resonance imaging. METHODS: Thirty-five male patients with AM diagnoses and preserved systolic function based on cardiac magnetic resonance imaging (MRI) were prospectively enrolled. On admission, echocardiography with measurements of global and segmental longitudinal (LS) strains was performed both at the endocardial (ENDO) and epicardial (EPI) levels. Findings were compared to 25 control subjects. Twenty-six patients were also monitored over a 22-month follow-up (FU group). RESULTS: On admission, global ENDO-LS was poorer in magnitude in AM (-19.2 ± 3.1) than in controls (-24.0 ± 1.05) (P < 0.0001), whereas EPI-LS was not different (-20.6 ± 3.4 vs -19.7 ± 6 P = NS). A functional increase in magnitude in both ENDO-LS (-20.8 ± 5.4, P = NS) and EPI-LS (-22.6 ± 4.6, P = 0.02) was found in FU vs AM patients. CONCLUSIONS: The present study demonstrates a steady ENDO-LS impairment in infarct-like AM during a 2-year follow-up period, despite a preserved LV ejection fraction.

Physical Training and Cardiac Rehabilitation in Heart Failure Patients.

Regardless of advances in medical and interventional treatment of cardiovascular disease (CVD), a limited number of patients attend a cardiac rehabilitation (CR) programme on a regular basis. Due to modern therapies more individuals will be surviving an acute cardiovascular event, but the expected burden of chronic heart failure will be increasing worldwide.However, both in high- and low-income countries, secondary prevention after an acute myocardial infarction or stroke has been implemented in less than a half of eligible patients.Combined interventions are still needed to reduce decompensations, hospitalizations and mortality in heart failure patients from any origin. In addition to medical treatments, regular exercise has been demonstrated to improve metabolic and hemodynamic conditions in both asymptomatic risk factor carriers and cardiac patients. Risk factor control and exercise should gather together for an effective management of patients.Exercise-based training is a core component of primary and secondary prevention. It should involve healthy carriers of cardiovascular risk factors, and patients with cardiomyopathy as well. The supposed attenuated effect of CR in the era of advanced revascularization and structural interventions is due to the heterogeneity of training models and physical training in the literature. Moreover, lifestyle modification, psycho-social challenges and patient's compliance are potential confounders.In this chapter the most recent evidences about training modalities and potential benefit of CR in heart failure patients are discussed.

Athlete's Heart and Left Heart Disease.

Physical activity comprises all muscular activities that require energy expenditure. Regular sequence of structured and organized exercise with the specific purpose of improving wellness and athletic performance is defined as a sports activity.Exercise can be performed at various levels of intensity and duration. According to the social context and pathways, it can be recreational, occupational, and competitive. Therefore, the training burden varies inherently and the heart adaptation is challenging.Although a general agreement on the fact that sports practice leads to metabolic, functional and physical benefits, there is evidence that some athletes may be subjected to adverse outcomes. Sudden cardiac death can occur in apparently healthy individuals with unrecognized cardiovascular disease.Thus, panels of experts in sports medicine have promoted important pre-participation screening programmes aimed at determining sports eligibility and differentiating between physiological remodeling and cardiac disease.In this review, the most important pathophysiological and diagnostic issues are discussed.

Advanced Non-invasive Imaging Techniques in Chronic Heart Failure and Cardiomyopathies : Focus on Cardiac Magnetic Resonance Imaging and Computed Tomographic.

Cardiomyopathies (Cs) are a heterogeneous group of myocardial diseases with structural and/or functional abnormalities.The aetiology is due to genetic-family substrate in most cases, however, the correct and detailed analysis of morphofunctional abnormalities (severity and distribution of hypertrophy, ventricular dilatation, ventricular dysfunction) and tissue characteristics (myocardial fibrosis, myocardial infiltration) are a crucial element for a definite diagnosis.Among the different diagnostic imaging modalities applied in clinical practice (echocardiography, nuclear medicine), cardiac magnetic resonance (CMR) has emerged as a non-invasive diagnostic tool having high ability to quantify systolic function and tissue abnormalities that represent the substrates of many Cs.The main added value of CMR is the ability to identify cardiomyopathies with respect to ischemic heart disease and, above all, to discriminate the major types of cardiomyopathies based on morpho-functional presentation patterns and the presence and location of myocardial fibrosis.Many CMR elements allow increasing diagnostic accuracy but CMR data should be integrated with an appropriate clinical and instrumental context.Computed Tomographic (CT) scan technology has showed a complementary role in patients having Cs and HF.In this chapter, the diagnostic, pathophysiologic and prognostic value of CMR and CT in heart failure due to the most common cardiomyopathies will be discussed.

Left Atrial Morphology, Size and Function in Patients With Transthyretin Cardiac Amyloidosis and Primary Hypertrophic Cardiomyopathy　- Comparative Strain Imaging Study.

BACKGROUND: We sought to assess left atrial (LA) morphology and function in patients with transthyretin cardiac amyloidosis (TTR-CA) and hypertrophic cardiomyopathy (HCM). Primarily, longitudinal deformation (reservoir) and pump function were the focus of vector-velocity strain echocardiography imaging. METHODS AND RESULTS: The study group comprised 32 patients (mean age 57.7±15.4 years, 16 in each group), and 15 healthy controls. Diagnosis of TTR-CA was based on echocardiography and either gadolinium-enhanced (LGE) cardiac magnetic resonance (cMRI) or radionuclide imaging. At baseline, there were no differences in age, body surface area, blood pressure and risk factors among the groups. Left ventricular (LV) mass was greater in patients than in controls, and slight LA dilatation was found in the TTR-CA group. LA reservoir was 14.1±4.7% in TTR-CA, 20.0±5.6% in HCM, and 34.0±11.8% in controls (<0.001). In addition, LA pump function chiefly was impaired in the former group, irrespective of LA chamber size and LV ejection fraction. LGE in the atrial wall was seen in 9/10 TTR-CA versus 0/8 HCM patients undergoing cMRI (P<0.001). LA reservoir ≤19% and pump function ≤-1.1% best discriminated TTR-CA from HCM patients in the receiver-operating characteristic analysis. CONCLUSIONS: LA reservoir and pump function were significantly impaired in both TTR-CA and HCM patients compared with controls, but mainly in the former group, irrespective of LA volume and LV ejection fraction, likely caused by a more altered LA wall structure. (Circ J 2016; 80: 1830-1837).

Extrinsic pulmonary stenosis in primary mediastinal B-cellular lymphoma.

We describe the case of a 34-year-old man with a history of asthenia and excessive fatigability. Transthoracic echocardiography showed a mass in the right ventricular outflow tract with a peak systolic gradient of 52 mmHg. Contrast-enhanced CT confirmed the presence of a lobulated mass, which extensively filled the anterior mediastinum, infiltrating the pulmonary artery trunk up to occupying the right ventricular outflow tract. CT-guided biopsy revealed primary mediastinal B-cellular lymphoma. The patient underwent chemotherapy, achieving complete remission of the disease at the 12-month follow-up, while the gradient across the pulmonary artery dropped from 52 mmHg to 14 mmHg.

The long-term cardiovascular impairment of COVID 19: need for clarity in definition and terminology.

Clinical experience and several large studies in the field have found that SARS-CoV-2 infection can cause long-term persistent cardiovascular (CV) impairment beyond the acute phase of the disease. This has resulted in a major public health concern worldwide. Regarding COVID-related long-term involvement of various organs and systems, using specific definitions and terminology is crucial to point out time relationships, lingering damage, and outcome, mostly when symptoms and signs of CV disease persist beyond the acute phase. Due to a lack of a common standardized definition, investigators have used interchangeable terms such as "long COVID," "post-COVID," or "post-acute sequelae of COVID-19" to describe CV involvement, thus causing some confusion. For the sake of clarity, the aim of this paper is to discuss the definition and terminology used in defining sequelae after the acute phase of COVID-19, thus pointing out the meaning of definitions like acute cardiac injury, post-acute sequelae of COVID-19, long COVID syndrome, and increased risk of atherosclerotic cardiovascular disease.

Transient Left Ventricular Dysfunction from Cardiomyopathies to Myocardial Viability: When and Why Cardiac Function Recovers.

Transient left ventricular dysfunction (TLVD), a temporary condition marked by reversible impairment of ventricular function, remains an underdiagnosed yet significant contributor to morbidity and mortality in clinical practice. Unlike the well-explored atherosclerotic disease of the epicardial coronary arteries, the diverse etiologies of TLVD require greater attention for proper diagnosis and management. The spectrum of disorders associated with TLVD includes stress-induced cardiomyopathy, central nervous system injuries, histaminergic syndromes, various inflammatory diseases, pregnancy-related conditions, and genetically determined syndromes. Furthermore, myocardial infarction with non-obstructive coronary arteries (MINOCA) origins such as coronary artery spasm, coronary thromboembolism, and spontaneous coronary artery dissection (SCAD) may also manifest as TLVD, eventually showing recovery. This review highlights the range of ischemic and non-ischemic clinical situations that lead to TLVD, gathering conditions like Tako-Tsubo Syndrome (TTS), Kounis syndrome (KS), Myocarditis, Peripartum Cardiomyopathy (PPCM), and Tachycardia-induced cardiomyopathy (TIC). Differentiation amongst these causes is crucial, as they involve distinct clinical, instrumental, and genetic predictors that bode different outcomes and recovery potential for left ventricular function. The purpose of this review is to improve everyday clinical approaches to treating these diseases by providing an extensive survey of conditions linked with TLVD and the elements impacting prognosis and outcomes.

The enigma of the 'smoker's paradox': Results from a single-center registry of patients with STEMI undergoing primary percutaneous coronary intervention.

BACKGROUND: Smoker's paradox usually refers to the observation of a favorable outcome of smoking patients in acute myocardial infarction. METHODS: From April 2006 to December 2018 a population of 2456 patients with ST segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI) were prospectively enrolled in the MATRIX registry. Ischemic time, clinical, demographics, angiographic data, and 1-year follow-up were collected. RESULTS: Among 2546 patients admitted with STEMI, 1007 (41 %) were current smokers. Smokers were 10 years younger and had lower crude in-hospital and 1-year mortality (1.5 % vs 6 %, p < 0.0001 and 5 % vs 11 %, p < 0.0001), shorter ischemic time (203 [147-299] vs 220 [154-334] minutes, p = 0.002) and shorter decision time (60 [30-135] vs 70 [36-170] minutes, p = 0.0063). Smoking habit [OR:0.37(95 % CI:0.18-0.75)-p < 0.01], younger age [OR 1.06 (95%CI:1.04-1.09)-p < 0.001] and shorter ischemic time [OR:1.01(95%CI:1.01-1.02)-p < 0.05] were associated to lower in-hospital mortality. Only smoking habit [HR:0.65(95 % CI: 0.44-0.9)-p = 0.03] and younger age [HR:1.08 (95%CI:1.06-1.09)-p < 0.001] were also independently associated to lower all-cause death at 1-year follow-up. After propensity matching, age, cardiogenic shock and TIMI flow <3 were associated with in-hospital mortality, while smoking habit was still associated with reduced mortality. Smoking was also associated with reduced mortality at 1-year follow-up (HR 0.54, 95 % CI [0.37-0.78]; p < 0.001). CONCLUSIONS: Smoking patients show better outcome after PCI for STEMI at 1-year follow-up. Although "Smoking paradox" could be explained by younger age of patients, other factors may have a role in the explanation of the phenomenon.

Cardio-Oncoimmunology: Cardiac Toxicity, Cardiovascular Hypersensitivity, and Kounis Syndrome.

Cancer therapy can result in acute cardiac events, such as coronary artery spasm, acute myocardial infarction, thromboembolism, myocarditis, bradycardia, tachyarrhythmias, atrio-ventricular blocks, QT prolongation, torsades de pointes, pericardial effusion, and hypotension, as well as chronic conditions, such as hypertension, and systolic and diastolic left ventricular dysfunction presenting clinically as heart failure or cardiomyopathy. In cardio-oncology, when referring to cardiac toxicity and cardiovascular hypersensitivity, there is a great deal of misunderstanding. When a dose-related cardiovascular side effect continues even after the causative medication is stopped, it is referred to as a cardiotoxicity. A fibrotic response is the ultimate outcome of cardiac toxicity, which is defined as a dose-related cardiovascular adverse impact that lasts even after the causative treatment is stopped. Cardiotoxicity can occur after a single or brief exposure. On the other hand, the term cardiac or cardiovascular hypersensitivity describes an inflammatory reaction that is not dose-dependent, can occur at any point during therapy, even at very low medication dosages, and can present as Kounis syndrome. It may also be accompanied by anti-drug antibodies and tryptase levels. In this comprehensive review, we present the current views on cardiac toxicity and cardiovascular hypersensitivity, together with the reviewed cardiac literature on the chemotherapeutic agents inducing hypersensitivity reactions. Cardiac hypersensitivity seems to be the pathophysiologic basis of coronary artery spasm, acute coronary syndromes such as Kounis syndrome, and myocarditis caused by cancer therapy.

Systemic Vascular Resistance and Myocardial Work Analysis in Hypertrophic Cardiomyopathy and Transthyretin Cardiac Amyloidosis with Preserved Left Ventricular Ejection Fraction.

Background: The pathophysiological impact of systemic vascular resistance (SVR) and pressure-strain loop-derived global myocardial work index (GWI) in hypertrophic cardiomyopathy (HCM) and transthyretin cardiac amyloidosis (ATTR) has been randomly investigated. Methods: Both SVR and GWI were assessed in outpatients consecutively referred at two Italian cardiology departments for heart failure with preserved left ventricular ejection fraction (LVEF), affected by either nonobstructive HCM or wild-type ATTR. Based on relevant cross-tabulations, the patients were gathered into 4 functional classes according to cut-off values of 1440 dyne/s/cm-5 for SVR, and 1576 mm Hg% for GWI, as suggested by previous studies. Results: A total of 60 patients, 30 in each group, aged 61 ± 16 years, with 78% males, were studied. HCM patients were younger than those with ATTR and in a better clinical condition (23% HCM vs. 77% ATTR were NYHA class II-III, p < 0.001). Overall, 51 patients (85%) showed a high SVR, 21/30 HCM (70%), and 30 ATTR (100%) (p < 0.005). Both SVR and GWI (expressions of ventricular-arterial coupling) were impaired in 43% of HCM patients (showing greater LV concentric hypertrophy) and 93% of ATTR patients (in advanced NYHA functional class) (p < 0.001). Conclusions: A substantial percentage of present study population showed impaired SVR and/or GWI, despite preserved LVEF. The proposed classification may shed further light on the pathophysiological and clinical characteristics of such hypertrophic phenotypes.

"When," "Where," and "How" of SARS-CoV-2 Infection Affects the Human Cardiovascular System: A Narrative Review.

Coronavirus disease 2019 (COVID-19) is caused by the novel severe acute respiratory coronavirus-2 (SARS-CoV-2). Several explanations for the development of cardiovascular complications during and after acute COVID-19 infection have been hypothesized. The COVID-19 pandemic, caused by SARS-CoV-2, has emerged as one of the deadliest pandemics in modern history. The myocardial injury in COVID-19 patients has been associated with coronary spasm, microthrombi formation, plaque rupture, hypoxic injury, or cytokine storm, which have the same pathophysiology as the three clinical variants of Kounis syndrome. The angiotensin-converting enzyme 2 (ACE2), reninaldosterone system (RAAS), and kinin-kallikrein system are the main proposed mechanisms contributing to cardiovascular complications with the COVID-19 infection. ACE receptors can be found in the heart, blood vessels, endothelium, lungs, intestines, testes, neurons, and other human body parts. SARS-CoV-2 directly invades the endothelial cells with ACE2 receptors and constitutes the main pathway through which the virus enters the endothelial cells. This causes angiotensin II accumulation downregulation of the ACE2 receptors, resulting in prothrombotic effects, such as hemostatic imbalance via activation of the coagulation cascade, impaired fibrinolysis, thrombin generation, vasoconstriction, endothelial and platelet activation, and pro-inflammatory cytokine release. The KKS system typically causes vasodilation and regulates tissue repair, inflammation, cell proliferation, and platelet aggregation, but SARS-CoV-2 infection impairs such counterbalancing effects. This cascade results in cardiac arrhythmias, cardiac arrest, cardiomyopathy, cytokine storm, heart failure, ischemic myocardial injuries, microvascular disease, Kounis syndrome, prolonged COVID, myocardial fibrosis, myocarditis, new-onset hypertension, pericarditis, postural orthostatic tachycardia syndrome, pulmonary hypertension, stroke, Takotsubo syndrome, venous thromboembolism, and thrombocytopenia. In this narrative review, we describe and elucidate when, where, and how COVID-19 affects the human cardiovascular system in various parts of the human body that are vulnerable in every patient category, including children and athletes.