Lipoprotein(a) and aortic valve stenosis: A casual or causal association?

AIMS: This review aims to provide an update of available methods for imaging calcification activity and potential therapeutic options. DATA SYNTHESIS: Aortic valve calcification represents the most common heart valve condition requiring treatment among adults in Western societies. No medical therapies are proven to be effective in treating symptoms or reducing disease progression. Therefore, surgical or transcatheter aortic valve replacement remains the only available treatment option. Elevated circulating concentrations of lipoprotein(a) is strongly associated with degenerative aortic stenosis. This relationship was first observed in prospective observational studies, and the causal relationship was confirmed in genetic studies. CONCLUSIONS: New therapeutic targets have been identified and new imaging techniques could be used to test the effectiveness of new agents and further clarify the pathophysiology of AVS. No therapy that specifically lowers Lp (a) levels has been approved for clinical use.

Coeliac and cardiovascular disease: a possible relationship between two apparently separate conditions.

Coeliac disease (CD) is an autoimmune condition with a high prevalence among general population and multisystemic involvement: a more complex scene than a merely gastrointestinal disease. Therefore, an early diagnosis and treatment with a gluten-free diet is mainly important to reduce mortality and comorbidities. Together with autoimmune diseases (as Hashimoto thyroiditis, insulin-dependent diabetes mellitus, autoimmune liver disease and connective tissue diseases), also an accelerated progression of atherosclerosis and a higher prevalence of heart disease have been reported in coeliacs. In the present paper we tried to collect from literature the emergent data on the probable relationship between coeliac and cardiovascular disease, focusing on pathophysiological bases of vascular injury. Data and opinions on the development of cardiovascular risk in patients with CD are conflicting. However, the major evidence supports the theory of an increased cardiovascular risk in CD, due to many mechanisms of myocardial injury, such as chronic malabsorption, abnormalities of intestinal permeability, and direct immune response against self-proteins. The conclusions that come from these data suggest the utility of a careful cardiovascular follow up in coeliac patients.

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.

Stage A Heart Failure: Modern Strategies for an Effective Prevention.

Stage A heart failure (HF) patients do not show HF symptoms or any structural heart disease but are at risk of HF development. Cardiovascular risk factors (hypertension, diabetes, metabolic syndrome, sedentary lifestyle, poor diet, and exposure to cardiotoxic agents) characterize subjects affected by stage A HF. It is essential to identify these subjects early and ensure that, despite being asymptomatic, they grasp the importance of undertaking correct lifestyle and therapeutic interventions. A careful stratification of asymptomatic subject's risk profile is needed to adopt proper preventive strategies and to set individualized therapeutic targets that avoid progression to advanced stages of HF.

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.

[Bempedoic acid: clinical data]. / Acido bempedoico: dati clinici.

The efficacy and safety of bempedoic acid, including the occurrence of muscle-related adverse events, have been addressed by phase 2 and phase 3 clinical trials. Phase 3 clinical trials demonstrated that in patients with atherosclerotic cardiovascular disease and/or familial hypercholesterolemia who were treated with statins at maximum tolerated dose, with or without further lipid-lowering drugs, bempedoic acid treatment was associated with a significant reduction in low-density lipoprotein cholesterol in different groups of patients with a favorable safety profile. An ongoing phase 3 study is currently evaluating the effect of longer-term (median duration of 3-4 years) treatment with bempedoic acid on the incidence of cardiovascular events.

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.

Right ventricular deformation and right ventricular-arterial coupling in patients with heart failure due to severe aortic stenosis undergoing TAVI: long-term results.

AIM: To evaluate the long-term prognostic significance of right ventricular (RV) deformation and RV-arterial coupling in a cohort of patients with heart failure (HF) due to severe aortic stenosis (AS) candidate for trans-catheter aortic valve implantation (TAVI). METHODS: The study is a retrospective analysis of 56 patients undergoing echocardiography before TAVI execution. RV function was defined by tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), peak systolic myocardial velocity by tissue Doppler imaging (RVSm) and RV longitudinal strain (RVLS). RV-arterial coupling were defined as TAPSE and RVLS normalized for systolic pulmonary artery pressure (sPAP) to obtain afterload-independent parameters: TAPSE/sPAP and RVLS/sPAP, respectively. All-cause mortality was the primary endpoint of survival analysis; composite of death and hospitalization for HF was the secondary endpoint. RESULTS: All patients underwent TAVI from femoral access. Mean age was 81.6±6.3 years and left ventricular ejection fraction was preserved in most patients (51±15%). At 10 years, using Cox regression analysis adjusted for the parameters related to prognosis at univariate analysis, we found that only pre-procedural RVLS was independently associated with all-cause mortality (aHR 1.53, 95% CI 1.10-2.12, P=0.011). RVLS (aHR 7.542, 95% CI 1.325-42.921, P=0.023), sPAP (aHR 1.421, 95% CI 1.045-1.932, P=0.025), TAPSE/sPAP (aHR 4.977, 95% CI 5.425-21.99, P=0.044) and RVLS/sPAP (aHR 2.333, 95% CI 3.9677-12.999, P=0.046) were independently associated with the secondary endpoint. CONCLUSIONS: Among patients with HF due to severe AS undergoing TAVI, deformation imaging (i.e., RVLS) and RV-arterial coupling (i.e., TAPSE/sPAP and RVLS/sPAP) provide better risk stratification at long-term follow up of 10 years than other RV echocardiographic parameters.

Acute pulmonary embolism in COVID-19 disease: Preliminary report on seven patients.

There is some evidence that Covid 19 pneumonia is associated with prothrombotic status and increased risk of venous thromboembolic events (deep venous thrombosis and pulmonary embolism). Over a two-week period we admitted in our Unit 25 patients with Covid-19 pneumonia, of these pulmonary embolism was diagnosed using computed tomography angiography in 7. We report on clinical and biochemical features of these patients. They were all males, with a mean age of 70.3 years (range 58-84); traditional risk factors for venous thromboembolism were identified in the majority of patients with pulmonary embolism, however not differently from those without pulmonary embolism. Clinical presentation of pulmonary embolism patients was usually characterized by persistence or worsening of respiratory symptoms, with increasing oxygen requirement. D-dimer levels were several fold higher than the upper threshold of normal; in patients in whom PE was recognized during hospital stay, a rapid and relevant increase of D-dimer levels was observed. Computed tomographic findings ranged from massive acute pulmonary embolism to a segmental or sub-segmental pattern; furthermore, thrombosis of sub-segmental pulmonary arteries within lung infiltrates were occasionally seen, suggesting local mechanisms. Six out of 7 patients were treated with unfractionated or low molecular weight heparin with clinical benefit within few days; one patient needed systemic thrombolysis (death from hemorrhagic complication).

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.

Evaluation of systo-diastolic cardiac function and arterial stiffness in subjects with new diagnosis of coeliac disease without cardiovascular risk factors.

In literature, there are conflicting opinions on the development of cardiovascular disease risk in patients with coeliac disease (CD). The aim of the research was to identify in young subjects without cardiovascular risk factor and newly diagnosed CD, alterations in different instrumental parameters that are associated with an augmented cardiovascular risk. Twenty-one consecutive young adults with a new diagnosis of CD and without cardiovascular risk factors were prospectively enrolled and underwent transthoracic echocardiography to analyse ascending aorta elastic properties [including tissue Doppler imaging strain (TDI-ε)] and left ventricular 2D strains (global longitudinal, radial and circumferential), and applanation tonometry by SphygmoCor. Cases were compared with 21 age- and sex-matched healthy controls. Mean age of the cases was 38 ± 9 years and 15 of them (71%) were female. Brachial and central blood pressure was higher in the CD group. Elastic properties of the ascending aorta were all impaired in the CD group: TDI-ε was altered in 57% of cases (0% of controls, p < 0.001). Concentric remodelling and grade I diastolic dysfunction were present in 38% and 24% of cases, respectively (0% of controls, p < 0.001). Global longitudinal strain was normal in all subjects, while radial and circumferential strain were altered in 67% and 35%, respectively (0% of controls, p < 0.001). In young subjects without cardiovascular risk factor, a newly diagnosed CD is associated with altered aortic elastic properties, left ventricular concentric remodelling and diastolic dysfunction and altered radial and circumferential strain.