A rare case of isolated persistent left superior vena cava diagnosed by echocardiography.

BACKGROUND: The persistent left superior vena cava (PLSVC) is an infrequent vascular variant. PLSVC with absent right superior vena cava, also known as isolated PLSVC, is an exceptionally rare entity. In this case we present a patient with isolated PLSVC draining to coronary sinus, diagnosed incidentally during echocardiography. CASE PRESENTATION: A 35-year-old man underwent a transthoracic echocardiography which showed an enormously dilated coronary sinus. Hand-agitated saline was injected via peripheral intravenous cannulas. The contrast appeared firstly in the coronary sinus before it opacified the right atrium. Since this was also visible by the right antecubital saline injection, it indicated an extremely rare case of PLSVC with the absence of right superior vena cava which was confirmed by cardiac magnetic resonance. CONCLUSIONS: The finding of a distinctively dilated coronary sinus in echocardiography led us to further investigation using agitated saline that revealed an infrequent anomaly termed isolated PLSVC. The in-depth diagnosis of this vascular variant is crucial considering that it may lead to important clinical implications, such as difficulties with central venous access, especially in the current era of a rapid development of cardiac device therapies.

Red Blood Cell Adenylate Energetics Is Related to Endothelial and Microvascular Function in Long COVID.

Adenine nucleotides play a critical role in maintaining essential functions of red blood cells (RBCs), including energy metabolism, redox status, shape fluctuations and RBC-dependent endothelial and microvascular functions. Recently, it has been shown that infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) might lead to morphological and metabolic alterations in erythrocytes in both mild and severe cases of coronavirus disease (COVID-19). However, little is known about the effects of COVID-19 on the nucleotide energetics of RBCs nor about the potential contribution of nucleotide metabolism to the long COVID syndrome. This study aimed to analyze the levels of adenine nucleotides in RBCs isolated from patients 12 weeks after mild SARS-CoV-2 infection who suffered from long COVID symptoms and to relate them with the endothelial and microvascular function parameters as well as the rate of peripheral tissue oxygen supply. Although the absolute quantities of adenine nucleotides in RBCs were rather slightly changed in long COVID individuals, many parameters related to the endothelial and microcirculatory function showed significant correlations with RBC adenosine triphosphate (ATP) and total adenine nucleotide (TAN) concentration. A particularly strong relationship was observed between ATP in RBCs and the serum ratio of arginine to asymmetric dimethylarginine-an indicator of endothelial function. Consistently, a positive correlation was also observed between the ATP/ADP ratio and diminished reactive hyperemic response in long COVID patients, assessed by the flow-mediated skin fluorescence (FMSF) technique, which reflected decreased vascular nitric oxide bioavailability. In addition, we have shown that patients after COVID-19 have significantly impaired ischemic response parameters (IR max and IR index), examined by FMSF, which revealed diminished residual bioavailability of oxygen in epidermal keratinocytes after brachial artery occlusion. These ischemic response parameters revealed a strong positive correlation with the RBC ATP/ADP ratio, confirming a key role of RBC bioenergetics in peripheral tissue oxygen supply. Taken together, the outcomes of this study indicate that dysregulation of metabolic processes in erythrocytes with the co-occurring endothelial and microvascular dysfunction is associated with diminished intracellular oxygen delivery, which may partly explain long COVID-specific symptoms such as physical impairment and fatigue.

The usefulness of speckle tracking echocardiography for the prediction of cardiac involvement in patients with biopsy-proven sarcoidosis.

INTRODUCTION: Cardiac sarcoidosis (CS) is commonly diagnosed based on clinical criteria and abnormalities in noninvasive imaging reported in patients with biopsy-proven extracardiac sarcoidosis. Electrocardiogram and two-dimensional echocardiography have a low sensitivity for CS detection. Cardiovascular magnetic resonance imaging (CMR) and positron emission tomography (PET) have limitations in terms of cost and availability. OBJECTIVES: This study aimed to assess the usefulness of left ventricular longitudinal strain, measured using two-dimensional speckle tracking echocardiography (STE), for the prediction of late gadolinium enhancement (LGE) presence in CMR in patients with biopsy-proven sarcoidosis. PATIENTS AND METHODS: A total of 119 patients with biopsy-proven extracardiac sarcoidosis were divided, according to the clinical criteria proposed by the 2014 Heart Rhythm Society expert consensus statement (HRS 2014), into two groups: 43 individuals with "probable cardiac sarcoidosis", CS(+) and 76 individuals without cardiac sarcoidosis, CS (-). Data from echocardiography, CMR, 12-lead ECG and 24 h Holter monitoring were analyzed. RESULTS: Left ventricular global longitudinal strain (LV-GLS) was slightly reduced in the entire sarcoidosis group (-18.61± 2.96), no difference between the CS (+) and CS (-) subgroups was found (-18.0% ± 3.2% and -18.9% ± 2.8%, respectively; p = .223). No cut-off value for LV-GLS was identified that could predict the presence of LGE. Segmental longitudinal strain impairment partially correlated with the presence of LGE on CMR. CONCLUSIONS: In our cohort of sarcoidosis patients, segmental longitudinal strain proved more helpful in the diagnostic process than LV-GLS. The ultimate role of STE in the diagnosis of CS remains to be established.

Mechanisms of Vascular Inflammation and Potential Therapeutic Targets: A Position Paper From the ESH Working Group on Small Arteries.

Inflammatory responses in small vessels play an important role in the development of cardiovascular diseases, including hypertension, stroke, and small vessel disease. This involves various complex molecular processes including oxidative stress, inflammasome activation, immune-mediated responses, and protein misfolding, which together contribute to microvascular damage. In addition, epigenetic factors, including DNA methylation, histone modifications, and microRNAs influence vascular inflammation and injury. These phenomena may be acquired during the aging process or due to environmental factors. Activation of proinflammatory signaling pathways and molecular events induce low-grade and chronic inflammation with consequent cardiovascular damage. Identifying mechanism-specific targets might provide opportunities in the development of novel therapeutic approaches. Monoclonal antibodies targeting inflammatory cytokines and epigenetic drugs, show promise in reducing microvascular inflammation and associated cardiovascular diseases. In this article, we provide a comprehensive discussion of the complex mechanisms underlying microvascular inflammation and offer insights into innovative therapeutic strategies that may ameliorate vascular injury in cardiovascular disease.

Changes in Adenosine Deaminase Activity and Endothelial Dysfunction after Mild Coronavirus Disease-2019.

Endothelial cells are a preferential target for SARS-CoV-2 infection. Previously, we have reported that vascular adenosine deaminase 1 (ADA1) may serve as a biomarker of endothelial activation and vascular inflammation, while ADA2 plays a critical role in monocyte and macrophage function. In this study, we investigated the activities of circulating ADA isoenzymes in patients 8 weeks after mild COVID-19 and related them to the parameters of inflammation and microvascular/endothelial function. Post-COVID patients revealed microvascular dysfunction associated with the changes in circulating parameters of endothelial dysfunction and inflammatory activation. Interestingly, serum total ADA and ADA2 activities were diminished in post-COVID patients, while ADA1 remained unchanged in comparison to healthy controls without a prior diagnosis of SARS-CoV-2 infection. While serum ADA1 activity tended to positively correspond with the parameters of endothelial activation and inflammation, sICAM-1 and TNFα, serum ADA2 activity correlated with IL-10. Simultaneously, post-COVID patients had lower circulating levels of ADA1-anchoring protein, CD26, that may serve as an alternative receptor for virus binding. This suggests that after the infection CD26 is rather maintained in cell-attached form, enabling ADA1 complexing. This study points to the possible role of ADA isoenzymes in cardiovascular complications after mild COVID-19.

The importance of microvascular inflammation in ageing and age-related diseases: a position paper from the ESH working group on small arteries, section of microvascular inflammation.

Microcirculation is pervasive and orchestrates a profound regulatory cross-talk with the surrounding tissue and organs. Similarly, it is one of the earliest biological systems targeted by environmental stressors and consequently involved in the development and progression of ageing and age-related disease. Microvascular dysfunction, if not targeted, leads to a steady derangement of the phenotype, which cumulates comorbidities and eventually results in a nonrescuable, very high-cardiovascular risk. Along the broad spectrum of pathologies, both shared and distinct molecular pathways and pathophysiological alteration are involved in the disruption of microvascular homeostasis, all pointing to microvascular inflammation as the putative primary culprit. This position paper explores the presence and the detrimental contribution of microvascular inflammation across the whole spectrum of chronic age-related diseases, which characterise the 21st-century healthcare landscape. The manuscript aims to strongly affirm the centrality of microvascular inflammation by recapitulating the current evidence and providing a clear synoptic view of the whole cardiometabolic derangement. Indeed, there is an urgent need for further mechanistic exploration to identify clear, very early or disease-specific molecular targets to provide an effective therapeutic strategy against the otherwise unstoppable rising prevalence of age-related diseases.

Speckle-tracking echocardiographic evaluation of the right ventricle in patients with ischemic left ventricular dysfunction.

BACKGROUND: The comprehensive assessment of right ventricular (RV) performance is of paramount importance because it is has been recognized as a strong prognostic factor in a variety of clinical settings. The aim herein was to evaluate the usefulness of RV longitudinal strain imaging by speckle-tracking echocardiography (STE) in daily clinical practice, especially in the context of RV systolic function and its changes after acute coronary syndrome (ACS). METHODS: This prospective study enrolled 63 patients with ischemic injury (left ventricular ejection fraction [LVEF] ≤ 45%). Additionally, a subgroup was created: patients with ACS treated with successful percutaneous coronary intervention. The clinical and echocardiographic parameters, including STE, were analyzed. RESULTS: Significant correlations for both RV free-wall (RVFWSL) and four-chamber (RV4CSL) longitudinal strain evaluated by STE with New York Heart Association class, LVEF, E/E' ratio, as well as conventional parameters of RV function were found. RVFWSL was able to detect subtle RV functional abnormalities, unreachable for traditional indices. RV recovery after ACS was not related to higher LVEF but better contractility of the interventricular septum (IVS) assessed by STE. CONCLUSIONS: Right ventricular strain proved to be a useful two-dimensional echocardiographic method to detect impaired RV performance, which showed a significant relationship with clinical and other echocardiographic indices. The IVS played a vital role in RV recovery among ACS survivors.

Vascular Aging and Damage in Patients with Iron Metabolism Disorders.

Vascular aging is a physiological, multifactorial process that involves every type of vessel, from large arteries to microcirculation. This manifests itself as impaired vasomotor function, altered secretory phenotype, deteriorated intercellular transport function, structural remodeling, and aggravated barrier function between the blood and the vascular smooth muscle layer. Iron disorders, particularly iron overload, may lead to oxidative stress and, among other effects, vascular aging. The elevated transferrin saturation and serum iron levels observed in iron overload lead to the formation of a non-transferrin-bound iron (NTBI) fraction with high pro-oxidant activity. NTBI can induce the production of reactive oxygen species (ROS), which induce lipid peroxidation and mediate iron-related damage as the elements of oxidative stress in many tissues, including heart and vessels' mitochondria. However, the available data make it difficult to precisely determine the impact of iron metabolism disorders on vascular aging; therefore, the relationship requires further investigation. Our study aims to present the current state of knowledge on vascular aging in patients with deteriorated iron metabolism.

Novel Targets for a Combination of Mechanical Unloading with Pharmacotherapy in Advanced Heart Failure.

LVAD therapy is an effective rescue in acute and especially chronic cardiac failure. In several scenarios, it provides a platform for regeneration and sustained myocardial recovery. While unloading seems to be a key element, pharmacotherapy may provide powerful tools to enhance effective cardiac regeneration. The synergy between LVAD support and medical agents may ensure satisfying outcomes on cardiomyocyte recovery followed by improved quality and quantity of patient life. This review summarizes the previous and contemporary strategies for combining LVAD with pharmacotherapy and proposes new therapeutic targets. Regulation of metabolic pathways, enhancing mitochondrial biogenesis and function, immunomodulating treatment, and stem-cell therapies represent therapeutic areas that require further experimental and clinical studies on their effectiveness in combination with mechanical unloading.

Assessment of microvascular function and pharmacological regulation in genetically confirmed familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is a genetic lipid disorder leading to accelerated atherosclerosis, premature cardiovascular disease and death. Microvascular endothelial dysfunction is one of the earliest vascular pathology manifestations and may precede symptomatic atherosclerosis. METHODS: In this paper, microvascular endothelial function was assessed in FH patients and healthy controls using flow mediated skin fluorescence (FMSF), based on measurements of nicotinamide adenine dinucleotide fluorescence intensity during brachial artery occlusion (ischemic response, IR) and immediately after occlusion (hyperemic response, HR). Low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were used to assess its relation with microvascular parameters evaluated in vivo. RESULTS: LDL-C levels were significantly correlated to both HRmax (r = -0.548, p = 0.001) and HRindex (r = -0.514, p = 0.003). Similarly, there was a significant inverse correlation of TC levels and both HRmax (r = -0.538, p = 0.002) and HRindex (r = -0.512, p = 0.003). All FMSF parameters were found lower in FH patients compared to age- and sex-matched healthy controls. Hyperemic response (HRmax) was significantly higher in FH patients examined on statins compared to those without any lipid-lowering treatment (19.9 ± 3.1 vs. 16.4 ± 4.2 respectively, p = 0.022). CONCLUSIONS: This study shows that, in patients with FH, microvascular endothelial-dependent hyperemic response is impaired and inversely correlated to plasma cholesterol levels. Microvascular function was found better in FH patients receiving statins.

Invasive Assessment of the Myocardial Microcirculation during Beating Heart Coronary Artery Bypass Grafting.

Coronary artery bypass grafting may be associated with several cardiac complications, including ischemia, acute myocardial infarction, arrhythmias, or hemodynamic instability. Accumulating evidence suggests that well-developed coronary collateral circulation may protect against adverse effects, including myocardial ischemia. Assessment of myocardial microvascular perfusion is, therefore, of great clinical interest in beating heart surgery. In this paper, myocardial microvascular perfusion is continuously assessed on the beating heart using laser Doppler flowmetry in consecutive patients who underwent coronary artery bypass grafting procedures. No significant (p = 0.110) differences were found between the averaged perfusion signal (n = 42) at the baseline, during artery occlusion, or after reperfusion (732.4 ± 148.0 vs. 711.4 ± 144.1 vs. 737.0 ± 141.2, respectively). In contrast, significantly different (p < 0.001) mean perfusion signals (n = 12) were found (805.4 ± 200.1 vs. 577.2 ± 212.8 vs. 649.3 ± 220.8) in a subset of patients who presented with hemodynamic instability and myocardial ischemia. Additionally, a strong positive correlation between the plasma levels of high-sensitivity troponin I and perfusion decrease level after artery occlusion was found (r = 0.854, p < 0.001). This study argues that myocardial microvascular perfusion remains constant during coronary artery bypass grafting on the beating heart in advanced coronary artery disease. This phenomenon is most likely due to an extensive coronary collateral circulation.