Varicella zoster virus and cardiovascular diseases.

Varicella zoster virus (VZV) is a Herpesviridae family double-stranded DNA virus that only affects humans. The first clinical manifestation appears to be varicella, typical of childhood. VZV, on the other hand, becomes latent in ganglion neurons throughout the neuroaxis after primary infection. The VZV reactivates and travels along peripheral nerve fibers in the elderly and immunocompromised individuals, resulting in Zoster. It can, however, spread centrally and infect cerebral and extracranial arteries, resulting in vasculopathy, which can lead to transient ischemic attacks, strokes, aneurysms, cavernous sinus thrombosis, giant cell arteritis, and granulomatous aortitis. Although the mechanisms of virus-induced pathological vascular remodeling are not fully understood, recent research indicates that inflammation and dysregulation of ligand-1 programmed death play a significant role. Few studies, on the other hand, have looked into the role of VZV in cardiovascular disease. As a result, the purpose of this review is to examine the relationship between VZV and cardiovascular disease, the efficacy of the vaccine as a protective mechanism, and the target population of heart disease patients who could benefit from vaccination.

Cardiac biomarkers and mortality in COVID-19 infection: A review.

Lots of meta-analysis emphasize that a great number of hospitalized patients with moderate and severe forms of COVID-19 developed acute myocardial damage, defined as an increase of cardiac biomarkers, such N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), creatine kinase-myocardial band (CK-MB) and of all type of troponins. The highest mortality rate is related with progressively increasing biomarkers levels and with a history of cardiovascular disease. In fact, the biomarkers dosage should be considered as a prognostic marker in all patients with COVID-19 disease at admission, during hospitalization and in the case of clinical deterioration. The purpose of this review is to evaluate cardiovascular prognostic factors in COVID-19 disease throughout the analysis of cardiac biomarkers to early identify the most serious patients and to optimize their outcomes.

Endothelial dysfunction in COVID-19 patients assessed with Endo-PAT2000.

It has been widely reported that the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) attaches human cells by using the Angiotensin Converting Enzyme 2 (ACE2) receptor, but vascular impairment described during coronavirus disease 2019 (COVID-19) infection is primarily due to the direct involvement of the endothelial cells by the virus or secondarily to the inflammatory host response is currently unknown. We therefore aimed to demonstrate in vivo the presence of endothelial dysfunction in six COVID-19 patients without cardiovascular risk factors or pre-existing cardiac condition, using the Endo-PAT 2000, a device able to measure endothelial vasodilation function in a rapid and non-invasive way. Four patients were positive for endothelial dysfunction, with RHI values between 1.13-1.56 (average value 1.32, normal values >1.67); in one of the two negative patients the reported RHI value was slightly above the cutoff (1.72). Our findings confirm that COVID-19 patients are at higher risk of developing endothelial dysfunction. In addition, our results demonstrate that endothelial impairment may occur even in the absence of cardiovascular risk factors.

Thrombotic risk in patients with COVID-19.

Emerging evidences prove that the ongoing pandemic of coronavirus disease 2019 (COVID-19) is strictly linked to coagulopathy even if pneumonia appears as the major clinical manifestation. The exact incidence of thromboembolic events is largely unknown, so that a relative significant number of studies have been performed in order to explore thrombotic risk in COVID-19 patients. Cytokine storm, mediated by pro-inflammatory interleukins, tumor necrosis factor α and elevated acute phase reactants, is primarily responsible for COVID-19-associated hypercoagulopathy. Also comorbidities, promoting endothelial dysfunction, contribute to a higher thromboembolic risk. In this review we aim to investigate epidemiology and clarify the pathophysiological pathways underlying hypercoagulability in COVID-19 patients, providing indications on the prevention of thromboembolic events in COVID-19. Furthermore we aim to reassume the pathophysiological paths involved in COVID-19 infection.

Vericiguat for Heart Failure with Reduced Ejection Fraction.

PURPOSE OF REVIEW: The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway plays an important role in the regulation of cardiovascular function, and it is disrupted in heart failure (HF), resulting in decreased protection against myocardial injury. Impaired NO-sGC-cGMP signaling in HF is secondary to reduced NO bioavailability and altered redox state of sGC, which becomes less responsive to NO. The sGC activator cinaciguat increases cGMP levels by direct NO-independent activation of sGC and may be particularly effective in conditions of increased oxidative stress and endothelial dysfunction, and therefore reduced NO levels, at the expense of a greater risk of hypotension. Conversely, sGC stimulators (riociguat and vericiguat) enhance sGC sensitivity to endogenous NO, thus exerting a more physiological action. RECENT FINDINGS: Clinical trials have suggested the benefit of vericiguat in patients with high-risk HF; in particular, a lower incidence of death from cardiovascular causes or HF hospitalization. Adding vericiguat may be considered in individual patients with HF, and reduced left ventricular ejection fraction (HFrEF) particularly those at higher risk of HF hospitalization.

Congestion in Patients with Advanced Heart Failure: Assessment and Treatment.

Heart failure (HF) is characterized by frequent hospital admissions due to acute decompensation and shortened life span with a progressive clinical course leading to an advanced stage where traditional therapies become ineffective. Due to aging of the population and improved therapies, only a small of proportion of patients with advanced HF are candidates for surgical treatments, such as mechanical circulatory support or heart transplantation. In most cases, prompt identification and management of congestion is paramount to improving symptoms and quality of life and avoiding progression to severe multiorgan dysfunction and death.

Obesity, heart failure with preserved ejection fraction, and the role of glucagon-like peptide-1 receptor agonists.

Heart failure with preserved ejection fraction (HFpEF) has a high prevalence, affecting more than 50% of patients with heart failure. HFpEF is associated with multiple comorbidities, and obesity is one of the most common. A distinct phenotype has been proposed for obese patients with HFpEF. Recent data show the beneficial role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for weight loss in diabetic and non-diabetic patients with obesity or overweight when given as adjunctive therapy to diet and exercise. The mechanisms of action are related to paracrine and endocrine signalling pathways within the gastrointestinal tract, pancreas, and central nervous system that delay gastric emptying, decrease appetite, augment pancreatic beta-cell insulin secretion, and suppress pancreatic glucagon release. These drugs are therefore potentially indicated for treatment of patients with HFpEF and obesity or overweight. Efficacy and safety need to be shown by clinical trials with a first one, Semaglutide Treatment Effect in People with obesity and heart failure with preserved ejection fraction (STEP HFpEF), recently concluded. The aim of the present review is to provide the pathophysiological and pharmacological rationale for GLP-1 RA administration to obese patients with HFpEF.

Impact and predictors of device-related thrombus after percutaneous left atrial appendage closure.

Device-related thrombus (DRT) is a known complication occurring in up to 7% of patients undergoing percutaneous left atrial appendage closure (LAAC). Since the target population of LAAC is generally ineligible for oral anticoagulant therapies, DRT raises important concerns. The aim of this review will be to summarize available evidence on DRT after LAAC focusing on its possible impact on outcomes. Recent findings showed a tighter association between DRT and neurological ischemic events. Antithrombotic regimen adopted after LAAC may have a protective effect against DRT. Many patient-related and procedural factors have been identified as possible predictors of DRT. A tailored approach, which takes into account DRT, is needed in the patient selection for LAAC and in the postprocedural follow-up.

Prognostic value of right ventricular longitudinal strain in patients with secondary mitral regurgitation undergoing transcatheter edge-to-edge mitral valve repair.

AIMS: To evaluate the prognostic impact of pre-procedural right ventricular longitudinal strain (RVLS) in patients with secondary mitral regurgitation (SMR) undergoing transcatheter edge-to-edge repair (TEER) in comparison with conventional echocardiographic parameters of RV function. METHODS AND RESULTS: This is a retrospective study including 142 patients with SMR undergoing TEER at two Italian centres. At 1-year follow-up 45 patients reached the composite endpoint of all-cause death or heart failure hospitalization. The best cut-off value of RV free-wall longitudinal strain (RVFWLS) to predict outcome was -18% [sensitivity 72%, specificity of 71%, area under curve (AUC) 0.78, P < 0.001], whereas the best cut-off value of RV global longitudinal strain (RVGLS) was -15% (sensitivity 56%, specificity 76%, AUC 0.69, P < 0.001). Prognostic performance was suboptimal for tricuspid annular plane systolic excursion, Doppler tissue imaging-derived tricuspid lateral annular systolic velocity and fractional area change (FAC). Cumulative survival free from events was lower in patients with RVFWLS ≥ -18% vs. RVFWLS < -18% (44.0% vs. 85.4%; < 0.001) as well as in patients with RVGLS ≥ -15% vs. RVGLS < -15% (54.9% vs. 81.7%; P < 0.001). At multivariable analysis FAC, RVGLS and RVFWLS were independent predictors of events. The identified cut-off of RVFWLS and RVGLS both resulted independently associated with outcomes. CONCLUSION: RVLS is a useful and reliable tool to identify patients with SMR undergoing TEER at high risk of mortality and HF hospitalization, on top of other clinical and echocardiographic parameters, with RVFWLS offering the best prognostic performance.

Updates in heart failure: sodium glucose co-transporter 2 inhibitors and beyond - major changes are coming.

Prevalence of heart failure is increasing worldwide mainly due to the ageing of the population and the improvement in diagnosis and treatment. In recent years, huge progress has been made in the management of heart failure patients. A new definition of chronic heart failure based on left ventricular ejection fraction and its possible trajectories has been reported. New drug classes have been introduced for the treatment of chronic heart failure. In particular, the prognostic benefit of sodium glucose co-transporter 2 inhibitors was demonstrated across all the heart failure phenotypes. Therapies for patients with advanced heart failure (long-term mechanical circulatory supports and heart transplantation) are now indicated also in the case of mild-to-moderate symptoms but with high risk of progression. In patients with acute heart failure, monitoring of urinary sodium and the use of acetazolamide may lead to better decongestion. Importantly, pre- and postdischarge assessment should lead to optimal treatment. Devices and telemonitoring can also be of help. Cardiovascular and noncardiovascular comorbidities are major determinants of the clinical course and need proper management. This review will summarize these important advances.

[Advances in heart failure treatment: a summary of 50 years of evolution]. / Progressi nella terapia dello scompenso cardiaco: la continua evoluzione degli ultimi 50 anni.

Management of heart failure is one of the most important challenges of modern medicine. Heart failure affects a large number of patients worldwide and its prevalence is increasing. The adoption of the methodology of randomized controlled trials has led to the identification of drugs and devices that prolong life and, in many cases, also yield a better quality of life. Improvement in the diagnostic techniques and devices has also led to better treatment of most major comorbidities, another strong driver of patient's symptoms and natural history. This article aims to provide an overview of the key events that have led to such improvement.

Endothelial function evaluation in idiopathic vs. ischemic dilated cardiomyopathy.

AIMS: In the latest years an emerging interest has risen towards the role of endothelial dysfunction (ED) in the pathogenesis of heart failure (HF) since the very first steps of the disease. Since the prevalent etiology of HF is ischemic cardiomyopathy (ICM), it is still not clear whether the connection with ED is linked to HF itself or to atherosclerosis. The aim is to determine the presence of ED in subjects with idiopathic dilated cardiomyopathy (IDCM) compared to ICM. METHODS: In this observational study 107 patients were enrolled, 65 of them suffering from IDCM and 42 from ICM. ED was assessed as peripheral arterial tonometry by means of EndoPAT device. The Reactive Hyperaemia Index (RHI) was calculated, ED being established with RHI values ≤1.67 and normal endothelial function >2.00 (grey area between 1.67 and 2.00). RESULTS: ED, expressed both as RHI ≤1.67 and RHI ≤2.00, showed a similar prevalence in the two groups. However, they differed as regards sex, dyslipidemia and statin use. CONCLUSION: Endothelial function, evaluated through peripheral artery tonometry, seems equally compromised in patients with IDCM and ICM.

Study of endothelial function and vascular stiffness in patients affected by dilated cardiomyopathy on treatment with sacubitril/valsartan.

BACKGROUND: The multiple beneficial effects of sacubitril/valsartan in the treatment of heart failure with reduced ejection fraction are vastly known, but still no or few mentions have been made regarding its effects on endothelial dysfunction and arterial stiffness. PATIENTS AND METHODS: To understand more deeply if sacubitril/valsartan may have a role on endothelial function and arterial stiffness, 15 patients with dilated cardiomyopathy with reduced left ventricular ejection fraction (LVEF) were evaluated through transthoracic echocardiography, peripheral arterial tonometry (EndoPAT®) and applanation tonometry (SphygmoCor® Px system). These noninvasive exams were performed at the beginning of the study and after 6 months of sacubitril/valsartan treatment. RESULTS: Aortic stiffness parameters didn't differ after 6 months of treatment. Augmentation pressure (P=0.889), augmentation index (P=0.906) and sphygmic wave velocity (P=0.263) increased slightly, but they weren't found to be statistically significant. Systolic, diastolic, and differential central arterial pressure didn't differ at the beginning and at the end of the study. RHI (reactive hyperemia index) increased significantly after 6 months (P=0.001) as well as augmentation index corrected for 75 bpm. Ejection fraction (32.21% ± 5.7 to 38.43% ± 8.4; P=0.010) and diastolic dysfunction degree (P=0.021) improved. There was an improvement in mitral regurgitation that wasn't statistically significant (P=0.116). TAPSE didn't change while pulmonary systolic arterial pressure increased, although not significantly (22.83 mmHg ± 4 to 27.33 mmHg ± 6; P=0.068) and within the normal range values. CONCLUSIONS: Even though in a study with a limited number of patients, sacubitril/valsartan improved endothelial function, left ventricular function, MR, and diastolic function significantly in patients with dilated cardiomyopathy and reduced LVEF. It showed no effects on vascular stiffness.

Unusual intracardiac thrombosis in two patients with coronavirus disease 2019 (COVID-19): case series.

BACKGROUND: COVID-19 may induce a coagulation dysregulation resulting in a prothrombotic state with a higher risk of arterial and venous thrombosis. This abnormal thrombotic diathesis can lead to pulmonary embolism, stroke, and intracardiac thrombosis. CASE SUMMARY: We present two cases of unusual intracardiac thrombosis in patients hospitalized for COVID-19. In both cases, imaging tests (such as transthoracic echocardiography (TTE), computed tomography scan of the chest, and cardiac magnetic resonance imaging) showed evidence of unusual intracardiac thrombosis with thrombi adherent to regularly contracting walls. DISCUSSION: This evidence confirms that COVID-19 induces a hypercoagulable state which can result in intracardiac thrombosis. Therefore, TTE is indicated in all COVID-19 patients for early diagnosis, and prompt anticoagulant therapy is to be considered as a thromboprophylaxis strategy.

Sinus Node Dysfunction in a Young Patient With COVID-19.

A 34-year-old man was admitted with acute lung injury and COVID-19 pneumonia. In the intensive care unit, he experienced episodes of prolonged asystole accompanied by hypotension without loss of consciousness. Once reversible causes were excluded, symptoms were related to dysfunction of the sinus node, and the patient underwent implantation of a pacemaker. (Level of Difficulty: Beginner.).

COVID-19 Pneumonia, Takotsubo Syndrome, and Left Ventricle Thrombi.

Left ventricle thrombus is considered a rare complication of Takotsubo syndrome. However, both a stress condition predisposing to Takotsubo syndrome and coagulation abnormalities coexist in COVID-19. We describe a case of a patient with COVID-19 with Takotsubo syndrome. (Level of Difficulty: Intermediate.).

Cardiogenic Shock due to COVID-19-Related Myocarditis in a 19-Year-Old Autistic Patient.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mainly responsible for respiratory involvement but cardiac complications are also reported. Nevertheless, potential life-threatening conditions in young people have not been described. A 19-year-old male autistic patient was admitted with fever and cough. The chest radiography showed viral pneumonia and the nasopharyngeal swab detected SARS-CoV-2. He rapidly developed hypotension, oliguria and increased myocardial injury markers and was treated with adrenaline, antiviral drugs and mechanical ventilation. Echocardiography revealed diffuse myocardial hypo-akinesia and decreased left ventricular ejection fraction (LVEF). After several days of treatment, the patient was weaned off mechanical ventilation, LVEF recovered to 50% and laboratory tests showed a decrease of markers of myocardial injury. Coronavirus disease 2019 (COVID-19) can therefore severely affect myocardium with life-threatening complications and even young people can be involved.

Recurrent in-stent restenosis, certainty of its origin, uncertainty about treatment.

Treatment of recurrent in-stent restenosis is a real brainteaser for the interventional cardiologist who cannot resort to the guidelines to have indications about the type of treatment to be preferred. The use of intracoronary imaging may provide insights into the underlying mechanisms of this complication and use of drug-coated balloons may be a valid alternative and especially a thoughtful treatment when the repeated and perseverant use of drug-eluting stents clearly fails. In this setting, we present a review of the literature about this interesting topic, going deep into the heart of the problem, its origin and possible treatment options.