Reactive oxygen species induce a procoagulant state in endothelial cells by inhibiting tissue factor pathway inhibitor.

Tissue factor pathway inhibitor (TFPI) is a serine-protease inhibitor, which modulates coagulation tissue factor-dependent (TF). It binds directly and inhibits the TF-FVII/FVIIa complex as well as FXa. Time to reperfusion of acute ischemic myocardium is essential for tissue salvage. However, reperfusion also results in a unique form of myocardial damage, such as contractile dysfunction, decreased coronary flow and altered vascular reactivity. Oxidants and reactive oxygen species (ROS) formation is increased in the post-ischemic heart and is responsible of post-ischemic injury. It has been reported that ROS promote a procoagulant state via TF expression while no data are available on the effect on TFPI. Endothelial cells were incubated with two different ROS generating systems, xanthine (X)/xanthine oxidase (XO) for 5 min, or H2O2 (500 µM) for 24 h. TFPI activity was measured in supernatants by chromogenic assay and TFPI-mRNA analyzed by RT-PCR 2 h after ROS exposure. Unstimulated cells and cells exposed to either X or XO served as controls. Western blot and ligand dot blot was performed to evaluate ROS effect on TFPI structure and binding to FXa. ROS generated by X/XO as well as H2O2 system resulted in decreased TFPI activity compared to unstimulated cells while X or XO alone had no effect. No differences in TFPI mRNA levels versus controls was observed. A significant degradation of TFPI was induced by ROS exposure, resulting in a decreased ability to bind FXa. ROS induce a procoagulant state in endothelial cells by altering TFPI structure, resulting in inhibition of TFPI binding to Factor Xa and loss of activity. This phenomenon might have important consequences during reperfusion of post-ischemic myocardium.

Pathophysiological Link and Treatment Implication of Heart Failure and Preserved Ejection Fraction in Patients with Chronic Kidney Disease.

Heart failure with preserved ejection fraction (HFpEF) results from a complex interplay of age, genetic, cardiac remodeling, and concomitant comorbidities including hypertension, obesity, diabetes, and chronic kidney disease (CKD). Renal failure is an important comorbidity of HFpEF, as well as a major pathophysiological mechanism for those patients at risk of developing HFpEF. Heart failure (HF) and CKD are intertwined conditions sharing common disease pathways; the so-called "kidney tamponade", explained by an increase in intracapsular pressure caused by fluid retention, is only the latest model to explain renal injury in HF. Recognizing the different phenotypes of HFpEF remains a real challenge; the pathophysiological mechanisms of renal dysfunction may differ across the HF spectrum, as well as the prognostic role. A better understanding of the role of cardiorenal interactions in patients with HF in terms of symptom status, disease progression, and prognosis remains essential in HF management. Historically, patients with HF and CKD have been scarcely represented in clinical trial populations. Current concerns affect the practical approach to HF treatment, and, in this context, physicians are frequently hesitant to prescribe and titrate both new and old treatments. Therefore, the extensive application of HF drugs in diverse HF subtypes with numerous comorbidities and different renal dysfunction etiologies remains a controversial matter of discussion. Numerous recently introduced drugs, such as sodium-glucose-linked transporter 2 inhibitors (SGLT2i), constitute a new therapeutic option for patients with HF and CKD. Because of their protective vascular and hormonal actions, the use of these agents may be safely extended to patients with renal dysfunction in the long term. The present review delves into the phenotype of patients with HFpEF and CKD from a pathophysiological perspective, proposing a treatment approach that suggests a practical stepwise algorithm for the proper application of life-saving therapies in clinical practice.

Myocarditis and Chronic Inflammatory Cardiomyopathy, from Acute Inflammation to Chronic Inflammatory Damage: An Update on Pathophysiology and Diagnosis.

Acute myocarditis covers a wide spectrum of clinical presentations, from uncomplicated myocarditis to severe forms complicated by hemodynamic instability and ventricular arrhythmias; however, all these forms are characterized by acute myocardial inflammation. The term "chronic inflammatory cardiomyopathy" describes a persistent/chronic inflammatory condition with a clinical phenotype of dilated and/or hypokinetic cardiomyopathy associated with symptoms of heart failure and increased risk for arrhythmias. A continuum can be identified between these two conditions. The importance of early diagnosis has grown markedly in the contemporary era with various diagnostic tools available. While cardiac magnetic resonance (CMR) is valid for diagnosis and follow-up, endomyocardial biopsy (EMB) should be considered as a first-line diagnostic modality in all unexplained acute cardiomyopathies complicated by hemodynamic instability and ventricular arrhythmias, considering the local expertise. Genetic counseling should be recommended in those cases where a genotype-phenotype association is suspected, as this has significant implications for patients' and their family members' prognoses. Recognition of the pathophysiological pathway and clinical "red flags" and an early diagnosis may help us understand mechanisms of progression, tailor long-term preventive and therapeutic strategies for this complex disease, and ultimately improve clinical outcomes.

Multimodality Imaging in Sarcomeric Hypertrophic Cardiomyopathy: Get It Right on Time.

Hypertrophic cardiomyopathy (HCM) follows highly variable paradigms and disease-specific patterns of progression towards heart failure, arrhythmias and sudden cardiac death. Therefore, a generalized standard approach, shared with other cardiomyopathies, can be misleading in this setting. A multimodality imaging approach facilitates differential diagnosis of phenocopies and improves clinical and therapeutic management of the disease. However, only a profound knowledge of the progression patterns, including clinical features and imaging data, enables an appropriate use of all these resources in clinical practice. Combinations of various imaging tools and novel techniques of artificial intelligence have a potentially relevant role in diagnosis, clinical management and definition of prognosis. Nonetheless, several barriers persist such as unclear appropriate timing of imaging or universal standardization of measures and normal reference limits. This review provides an overview of the current knowledge on multimodality imaging and potentialities of novel tools, including artificial intelligence, in the management of patients with sarcomeric HCM, highlighting the importance of specific "red alerts" to understand the phenotype-genotype linkage.

Effect of acute CORticosteroids on conduction defects after Transcatheter Aortic Valve Implantation: the CORTAVI study.

AIMS: Conduction abnormalities, requiring a permanent pacemaker (PPM), are the most common electrical complications after transcatheter aortic valve implantation (TAVI). The exact mechanism for conduction system defects is not yet clear. The local inflammatory process and edema are thought to play a role in the development of electrical disorders. Corticosteroids are effective anti-inflammatory and antiedematous agents. We aim to investigate the potential protective effect of corticosteroids on conduction defects after TAVI. METHODS: This is a retrospective study of a single center. We analyzed 96 patients treated with TAVI. Thirty-two patients received oral prednisone 50 mg for 5 days after the procedure. This population was compared with the control group. All patients were followed up after 2 years. RESULTS: Of the 96 patients included, 32 (34%) were exposed to glucocorticoids after TAVI. No differences in age, preexisting right bundle branch block or left bundle branch block, or valve type were seen among patients exposed to glucocorticoids versus those who were unexposed. We observed no significant differences between the two groups in the overall frequency of new PPM implantations during hospitalization (12% vs. 17%, P  = 0.76). The incidence of atrioventricular block (AVB) (STx 9% vs. non-STx 9%, P  = 0.89), right bundle branch block (STx 6% vs. non-STx 11%, P  = 0.71), and left bundle branch block (STx 34% vs. non-STx 31%, P  = 0.9) was not significantly different between the STx and non-STx groups. At 2 years after TAVI, none of the patients had implanted PPM or had severe arrhythmias documented by 24-h Holter ECG or cardiac examination. CONCLUSION: Oral prednisone treatment does not appear to significantly reduce the incidence of AVB requiring acute PPM implantation after TAVI.

Clinical Comparison of a Novel Balloon-Expandable Versus a Self-Expanding Transcatheter Heart Valve for the Treatment of Patients with Severe Aortic Valve Stenosis: The EVAL Registry.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an effective treatment option for patients with severe, symptomatic AS, regardless of the transcatheter heart valve (THV) implanted. Prior studies demonstrated a higher device success with lower paravalvular leak (PVL) using the balloon-expandable (BE) Sapien/XT THV vs. a self-expanding (SE) THV. However, few data are available on the performance of a novel BE THV. PURPOSE: to compare early clinical performance and safety of the newly available BE Myval THV (Myval, Meril Life Sciences Pvt. Ltd., India) vs. the commonly used SE (Evolut R, Medtronic) THV. METHODS:  A single-center, retrospective cohort analysis was performed with 166 consecutive patients undergoing TAVR from March 2019 to March 2021 for severe symptomatic AS treated with either the novel BE Myval or the SE Evolut R (ER) bioprosthesis. The primary endpoint was device success at day 30 according to the Valve Academic Research Consortium-3 (VARC-3). Secondary endpoints included 30-day all-cause mortality, cardiovascular mortality, more than mild PVL, permanent pacemaker implantation (PPI) rates and a composite of all-cause mortality and disabling stroke at 6 months. RESULTS:  Among the 166 included patients, 108 patients received the SE ER THV and 58 patients were treated with the BE Myval THV. At baseline, the two groups showed comparable demographic characteristics. The primary composite endpoint of early device success occurred in 55 patients (94.8%) in the BE Myval group and in 90 patients (83.3%) in the SE ER group (OR 3.667, 95% CI 1.094-12.14; p = 0.048). At day 30, the BE Myval THV group exhibited a significantly lower incidence of more than mild PVL (BE Myval 3.45% vs. SE ER 14.8%, OR 0.2, 95% CI 0.05-0.8; p = 0.0338), along with a lower rate of PPI (BE Myval 11% vs. SE ER 24.2%, OR 0.38, 95% CI 0.15-0.99; p = 0.0535). At the 6-month follow-up, the incidence of all-cause mortality and disabling stroke did not significantly differ between the two groups, while the incidence of PPI (BE Myval 11% vs. SE ER 27.5%, OR 0.32, CI 95% 0.1273-0.8; p = 0.02) and ≥moderate PVL (BE Myval 6.9% vs. SE ER 19.8%, OR 0.31, 95% CI 0.1-0.94; p = 0.0396) was significantly lower in the BE Myval group. CONCLUSIONS: In patients with severe symptomatic AS undergoing TAVR, the novel Myval BE THV provided a comparable performance to the well-known ER SE THV, and it was associated with a lower rate of PPI and ≥moderate PVL within 30 days and 6 months after the procedure. Randomized, head-to-head comparison trials are needed to confirm our results.

Clinical and angiographical features of first episode of acute coronary syndrome in patients with human immunodeficiency virus infection.

BACKGROUND: Patients affected by the human immunodeficiency virus (HIV) show an increased risk of myocardial infarction. Clinical and angiographic features of HIV positive (HIV+) patients presenting with the first episode of an acute coronary syndrome (ACS) are not well defined in previous studies. OBJECTIVE: To demonstrate that HIV + patients with acute coronary syndrome had different features than non-HIV patients. METHODS: We identified 48 HIV + patients without previous cardiovascular events admitted to our Emergency Department with ACS diagnosis between 2012 and 2020. Clinical and angiographic characteristics were compared with a control group of 48 non-HIV consecutive patients affected by ACS as first episode. RESULTS: HIV + patients were most frequently men (87.5% vs 62.5%, p = 0.009) and younger about a decade (mean age 53.8 ± 8.2 vs 63.7 ± 11.9 years old, p < 0.0001); statistically significant hypertriglyceridemia has been found in the HIV group (178,6 ± 59,8 mg/dl vs 142,7 ± 63,7 mg/dl, p = 0.005). HIV(+) patients had a higher rate of anterior ST-elevation myocardial infarction (STEMI) (65% vs 33%, p = 0.03) and significant lesions on left anterior descending (LAD) coronary artery (83% vs 58% p = 0.01). CONCLUSIONS: HIV + patients with the first episode of ACS are generally young men with higher triglycerides and most frequently presenting with anterior STEMI and LAD involvement. The strict control of risk factors and a program for the early identification of coronary artery disease are strongly recommended in this subset of patients.

Progression of Lactobacillus plantarum prosthetic valve endocarditis followed by transesophageal echocardiogram.

Endocarditis due to Lactobacillus species is extremely rare. We report an uncommon case of Lactobacillus plantarum bioprosthetic aortic valve endocarditis, presenting with severe aortic steno-regurgitation, which responded to conventional medical and surgical treatment. This case provides a better understanding of the disease process of L. plantarum and highlights the role of transesophageal echocardiography in following the entire course of endocarditis.

Adipokines, vascular wall, and cardiovascular disease: a focused overview of the role of adipokines in the pathophysiology of cardiovascular disease.

Epidemiological evidence has shown that abdominal obesity is closely associated with the development of cardiovascular (CV) disease, suggesting that it might be considered as an independent CV risk factor. However, the pathophysiological mechanisms responsible for the association between these 2 clinical entities remain largely unknown. Adipocytes are considered able to produce and secrete chemical mediators known as "adipokines" that may exert several biological actions, including those on heart and vessels. Of interest, a different adipokine profile can be observed in the plasma of patients with obesity or metabolic syndrome compared with healthy controls. We consider the main adipokines, focusing on their effects on the vascular wall and analyzing their role in CV pathophysiology.