Peculiar clinical and diagnostic features of infective endocarditis in Yemen: Comparative analysis with a Western University Hospital.

The aim of this study was to describe the pattern, characteristics, and outcomes of infective endocarditis (IE) in Yemen and compare the results with the findings of a Western university hospital. Patients (pts) with a final diagnosis of IE observed in Al-Thawra Sanaa Cardiac Center were prospectively enrolled in 1-year time period. Clinical and diagnostic findings were compared to clinical and diagnostic data of 50 pts with IE observed at Sapienza University Hospital in Rome, Italy. The mean age was 38 ± 6. Predisposing factors for IE were rheumatic heart disease (RHD) in 34 pts (68%), congenital heart disease in 9 pts (18%), prosthetic valve IE in 4 pts (8%), and previous IE in 3 pts (6%). Transthoracic echocardiography (TTE) was done in 50 pts and transesophageal echocardiography (TEE) in 25. Blood cultures were taken in all pts and were positive in 3 pts (6%) and negative in 47 (94%). TTE was positive in 34/50 pts (68%) and TEE in 20/25 (80%). Compared to Sapienza University pts, Al-Thawra Cardiac Center pts had a younger age (p = 0.003), more predisposing RHD (p = 0.0004), less prosthetic heart valves IE (p = 0.002), and more negative blood cultures (p = 0.0001). IE is still a common disease in Yemen among RHD pts and affects the younger age group. It has severe complications which need early diagnosis and proper management. Echocardiography is of prime diagnostic value in the absence of positive blood cultures. An effort should be made to prevent rheumatic fever and RHD.

Early and prolonged glutathione infusion favorably impacts length of hospital stay in ST-elevation myocardial infarction patients: a subanalysis of the GSH2014 Trial.

BACKGROUND: Developing strategies aimed to shorten the length of stay (LOS) in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) is a healthcare goal to be pursued. We carried out a subanalysis of the GSH 2014 Trial to assess the potentiality of glutathione sodium salt infusion to impact on LOS. METHODS: 100 consecutive patients with STEMI, aged more than 18 years and referred to the three enrolling centers for primary angioplasty (p-PCI), were asked to participate to the GSH 2014 Trial. Fifty patients were randomized to treatment group and fifty to placebo; treatment consisted into an intravenous infusion of glutathione sodium salt over 10 minutes before p-PCI; after interventions, glutathione was infused at the same doses at 24, 48 and 72 h elapsing time. A stepwise linear multivariate model was built in order to assess independent predictors of LOS. RESULTS: Subjects receiving infusion of glutathione sodium salt had a significantly lower LOS than subjects receiving placebo (8.6±3 vs. 10.8±4 days, P=0.006). At multivariate analysis, the randomization to GSH group was negatively associated with length of stay (ß±SEß -1.64±0.74, cumulative R2 0.43, P=0.03) independently from age, sex, cardiovascular risk factors, number of treated vessels, infarct-related coronary artery (left anterior descending artery as reference) and enrolment hospital. CONCLUSIONS: Results from this subanalysis support the hypothesis that an early and prolonged glutathione sodium salt administration, as antioxidant therapy to patients with STEMI, may favorably impact on LOS. Further studies with larger sample size are necessary to confirm these data.

Protective Biomolecular Mechanisms of Glutathione Sodium Salt in Ischemia-Reperfusion Injury in Patients with Acute Coronary Syndrome-ST-Elevation Myocardial Infarction.

Ischemia-Reperfusion Injury (IRI) is responsible for adverse outcomes in patients with ST-Elevation Myocardial Infarction (STEMI). Oxidative stress, resulting from the production of Reactive Oxygen Species (ROS) and low availability of Glutathione (GSH), are the two main mediators of IRI. The effectiveness of exogenous antioxidant therapy in this scenario is still debated, since the encouraging results obtained in animal models have not been fully reproduced in clinical studies. In this review we focus on the role of GSH, specifically on the biomolecular mechanisms that preserve myocardial cells from damage due to reperfusion. In this regard, we provide an extensive discussion about GSH intrinsic antioxidant properties, its current applications in clinical practice, and the future perspectives.

Glutathione Infusion Before and 3 Days After Primary Angioplasty Blunts Ongoing NOX2-Mediated Inflammatory Response.

Background Glutathione is a water-soluble tripeptide with a potent oxidant scavenging activity. We hypothesized that glutathione administration immediately before and after primary angioplasty (primary percutaneous coronary intervention) could be effective in modulating immune cell activation, thereby preventing infarct expansion. Methods and Results One hundred consecutive patients with ST-segment-elevation myocardial infarction, scheduled to undergo primary percutaneous coronary intervention were randomly assigned before the intervention to receive an infusion of glutathione (2500 mg/25 mL over 10 minutes), followed by drug administration at the same doses at 24, 48, and 72 hours elapsing time or placebo. Total leukocytes, NOX2 (nicotinamide adenine dinucleotide phosphate oxidase 2) activation, NO bioavailability, cTpT (serum cardiac troponin T), hsCRP (high-sensitivity C-reactive protein), and TNF-α (tumor necrosis factor α) levels were measured. Left ventricular size and function were assessed within 120 minutes, 5 days, and 6 months from percutaneous coronary intervention. Following reperfusion, a significant reduction of neutrophil to lymphocyte ratio (P<0.0001), hsCRP generation (P<0.0001), NOX2 activation (P<0.0001), TNF-α levels (P<0.001), and cTpT release (P<0.0001) were found in the glutathione group compared with placebo. In treated patients, blunted inflammatory response was linked to better left ventricular size and function at follow-up (r=0.78, P<0.005). Conclusions Early and prolonged glutathione infusion seems able to protect vital myocardial components and endothelial cell function against harmful pro-oxidant and inflammatory environments, thus preventing maladaptive cardiac repair and left ventricular adverse remodeling. Registration URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2014-004486-25.

Glutathione infusion before primary percutaneous coronary intervention: a randomised controlled pilot study.

OBJECTIVE: In the setting of reperfused ST-elevation myocardial infarction (STEMI), increased production of reactive oxygen species (ROS) contributes to reperfusion injury. Among ROS, hydrogen peroxide (H2O2) showed toxic effects on human cardiomyocytes and may induce microcirculatory impairment. Glutathione (GSH) is a water-soluble tripeptide with a potent oxidant scavenging activity. We hypothesised that the infusion of GSH before acute reoxygenation might counteract the deleterious effects of increased H2O2 generation on myocardium. METHODS: Fifty consecutive patients with STEMI, scheduled to undergo primary angioplasty, were randomly assigned, before intervention, to receive an infusion of GSH (2500 mg/25 mL over 10 min), followed by drug administration at the same doses at 24, 48 and 72 hours elapsing time or placebo. Peripheral blood samples were obtained before and at the end of the procedure, as well as after 5 days. H2O2 production, 8-iso-prostaglandin F2α (PGF2α) formation, H2O2 breakdown activity (HBA) and nitric oxide (NO) bioavailability were determined. Serum cardiactroponin T (cTpT) was measured at admission and up to 5 days. RESULTS: Following acute reperfusion, a significant reduction of H2O2 production (p=0.0015) and 8-iso-PGF2α levels (p=0.0003), as well as a significant increase in HBA (p<0.0001)and NO bioavailability (p=0.035), was found in the GSH group as compared with placebo. In treated patients, attenuated production of H2O2 persisted up to 5 days from the index procedure (p=0.009) and these changes was linked to those of the cTpT levels (r=0.41, p=0.023). CONCLUSION: The prophylactic and prolonged infusion of GSH seems to determine a rapid onset and persistent blunting of H2O2 generation improving myocardial cell survival. Nevertheless, a larger trial, adequately powered for evaluation of clinical endpoints, is ongoing to confirm the current finding. TRIAL REGISTRATION NUMBER: EUDRACT 2014-00448625; Pre-results.

Biventricular assessment of light-chain amyloidosis using 3D speckle tracking echocardiography: Differentiation from other forms of myocardial hypertrophy.

BACKGROUND: Given that in patients with cardiac amyloidosis (CA), deposition of amyloid protein is not restricted to the left ventricular (LV) myocardium, it can be hypothesized that the diagnostic value of deformation mechanics would be enhanced by considering right ventricular (RV) strain measures. The aim of the present study was to examine the potential utility of left ventricular (LV) and right ventricular (RV) deformation and rotational parameters derived from three-dimensional speckle-tracking echocardiograph (3DSTE) to diagnose cardiac amyloidosis and differentiate this disease from other forms of myocardial hypertrophy. METHODS: Twenty-three patients with biopsy-proven light-chain (AL) amyloidosis, 23 patients with systemic arterial hypertension (HTN), 23 patients with hypertrophic cardiomyopathy (HCM), 23 athletes and 23 normal controls were prospectively studied by conventional echocardiography and 3DSTE. LV longitudinal strain (LV LS), LV circumferential strain (LV CS), RV global longitudinal strain and RV free-wall longitudinal strain (RV FW LS) were obtained by 3DSTE, as well as LV rotation and rotational velocities. RESULTS: LV and RV longitudinal strains were reduced in cardiac amyloidosis (CA) patients compared to controls. By multivariate analysis, LV basal LS (p = 0.002), LV peak basal rotation (p = 0.003), and RV basal FW LS (p = 0.014) were independently associated with CA in the overall population. A significant improvement in global χ2 value was noted with RV 3D-strain parameters over only LV-3DSTE + conventional indices for detection of CA (p < 0.001). Comparison of ROC curves showed that the AUC using combined LV basal LS, LV basal rotation and RV basal FW LS had a higher discriminative value than the other echocardiographic parameters used for detecting CA (AUC 0.93, 95%CI 0.81-0.97). CONCLUSIONS: Three-dimensional speckle tracking echocardiography reveals regional and global biventricular dysfunction in CA. Assessment of RV ventricular dysfunction has an additive value in differentiating CA from other causes of myocardial wall thickening.

Dataset on the use of 3D speckle tracking echocardiography in light-chain amyloidosis.

The dataset presented in this article is related to the research article entitled "Biventricular assessment of light-chain amyloidosis using 3D speckle tracking echocardiography: Differentiation from other forms of myocardial hypertrophy" (Vitarelli et al., 2018) [1], which examined the potential utility of left ventricular (LV) and right ventricular (RV) deformation and rotational parameters derived from three-dimensional speckle-tracking echocardiography (3DSTE) to diagnose cardiac amyloidosis(CA) and differentiate this disease from other forms of myocardial hypertrophy. The combined assessment of LV basal longitudinal strain, LV basal rotation and RV basal longitudinal strain had a high discriminative power for detecting CA. The data of this study provides more understanding on the value of LV 3DSTE deformation parameters as well as RV parameters in this particular cardiomyopathy.

A novel ultrafast-low-dose computed tomography protocol allows concomitant coronary artery evaluation and lung cancer screening.

BACKGROUND: Cardiac computed tomography (CT) is often performed in patients who are at high risk for lung cancer in whom screening is currently recommended. We tested diagnostic ability and radiation exposure of a novel ultra-low-dose CT protocol that allows concomitant coronary artery evaluation and lung screening. METHODS: We studied 30 current or former heavy smoker subjects with suspected or known coronary artery disease who underwent CT assessment of both coronary arteries and thoracic area (Revolution CT, General Electric). A new ultrafast-low-dose single protocol was used for ECG-gated helical acquisition of the heart and the whole chest. A single IV iodine bolus (70-90 ml) was used. All patients with CT evidence of coronary stenosis underwent also invasive coronary angiography. RESULTS: All the coronary segments were assessable in 28/30 (93%) patients. Only 8 coronary segments were not assessable in 2 patients due to motion artefacts (assessability: 98%; 477/485 segments). In the assessable segments, 20/21 significant stenoses (> 70% reduction of vessel diameter) were correctly diagnosed. Pulmonary nodules were detected in 5 patients, thus requiring to schedule follow-up surveillance CT thorax. Effective dose was 1.3 ± 0.9 mSv (range: 0.8-3.2 mSv). Noteworthy, no contrast or radiation dose increment was required with the new protocol as compared to conventional coronary CT protocol. CONCLUSIONS: The novel ultrafast-low-dose CT protocol allows lung cancer screening at time of coronary artery evaluation. The new approach might enhance the cost-effectiveness of coronary CT in heavy smokers with suspected or known coronary artery disease.

Uric acid and contrast-induced nephropathy: an updated review and meta-regression analysis.

INTRODUCTION: Previous studies have suggested a relationship between serum uric acid and contrast-induced nephropathy (CIN). AIM: We performed an updated review and a meta-regression analysis to assess whether serum uric acid is associated with CIN or there exists any relationship between serum uric acid and other risk factors for CIN. MATERIAL AND METHODS: We searched PubMed, Embase and Cochrane databases and reviewed cited references up to July 31, 2018 to identify relevant studies. RESULTS: A total of 6,705 patients from 10 clinical studies were included. CIN occurred in 774 of the 6,705 (12%) patients. Baseline uric acid levels were significantly higher in those who developed CIN (6.51 vs. 5.67 mg/dl; 95% CI: 0.55-1.22, p = 0.00001). Comparison of clinical features showed that patients with CIN were significantly older (69 vs. 63 years; p < 0.00001) and more often had diabetes (42% vs. 32%; p = 0.002) and hypertension (67% vs. 59%; p = 0.03). Also, patients who developed CIN had lower hemoglobin (12.5 vs. 13.6 mg/dl; p < 0.00001) and higher levels of baseline creatinine (1.27 vs. 1.01 mg/dl; p < 0.0001), but had similar levels of glycemia, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride. Also, they showed a lower ejection fraction (45% vs. 50%; p < 0.00001). Meta-regression analysis revealed that uric acid related only to age (r = 0.13, p = 0.03). CONCLUSIONS: Our investigation indicates that uric acid is significantly associated with CIN. Uric acid correlated significantly with age only, and not with other major predictors of CIN. Further studies are therefore needed to verify the potential of uric acid to improve CIN risk stratification.

[The importance of defining methodology for post-marketing observational studies on cardiovascular therapies]. / L'importanza della metodologia negli studi post-marketing delle terapie cardiovascolari.

In recent years, a growing number of observational studies in cardiology have been carried out following the criticism that rigid design of randomized clinical trials produces information that is not applicable to the general patient. This approach is very common in several branches of medicine, first of all oncology, but has often been considered marginal in cardiology. The recent introduction of new oral anticoagulants (NOACs) on the market, however, has seen a proliferation of "real-life" studies, drawing the attention of cardiologists to the advantages and limitations of post-marketing studies. NOACs have been approved for use on the basis of large randomized clinical trials that have clearly documented their efficacy and safety. Since they have become available, the analysis of phase IV data has been considered crucial and therefore a great amount of information on the use of NOACs in daily practice has become available. It should be considered, however, that the possibility exists that results obtained from "real-world" studies, which do not apply rigid scientific criteria, may lead to incorrect conclusions. Accordingly, it is mandatory to fully define the operational standards of observational studies. All the protagonists of post-marketing analysis (physicians, epidemiologists, pharmacologists, statisticians) should handle the data strictly in order to ensure their reliability and comparability with other studies. To this end, it is crucial that researchers follow rigorous operational protocols for phase IV studies. Briefly, any "real-life" study should be prospective and adhere to what is prespecified by the research protocol - which must illustrate the background and rationale of the study, define its primary endpoint, and detail the methods, i.e. study design, population and variables.

Intravenous versus intracoronary bolus of glycoprotein IIb/IIIa inhibitor administration during primary percutaneous coronary intervention on long-term left ventricular systolic and diastolic function.

BACKGROUND: In primary percutaneous coronary intervention (PCI), glycoprotein (GP) IIb/IIIa inhibitors are often given in order to attain and maintain better myocardial perfusion. We tested the hypothesis that intracoronary (IC) bolus of GP IIb/IIIa inhibitors might produce a greater improvement in left ventricular (LV) systolic and diastolic function than an intravenous(IV) bolus. METHODS AND RESULTS: Seventy seven patients undergoing primary PCI for their first ST elevation myocardial infarction (STEMI) were randomly assigned to either an IC or IV bolus of GP IIb/IIIa inhibitor, followed by IV infusion. Compared with the echocardiographic findings within 3 days after PCI, LV ejection fraction was higher at 1 year, with no significant differences between the IV and IC groups (IV: 44% vs. 49%, p = 0.001; IC: 43% vs. 48%,p < 0.001). LV diastolic function (E/E') did not significantly change at 1 year by either approach. CONCLUSIONS: LV systolic function improved by a similar magnitude following primary PCI, with either IC or IV bolus administration of GP IIb/IIIa inhibitor therapy. However, no significant changes were observed in LV diastolic function.

Clopidogrel plus indobufen in acute coronary syndrome patients with hypersensitivity to aspirin undergoing percutaneous coronary intervention.

The prescription of aspirin (acetylsalicylic acid (ASA)) to patients with a history of hypersensitivity to this drug could prove harmful. The aim of the study was to assess the antiplatelet activity and safety of a combined antiplatelet treatment with indobufen and clopidogrel in acute coronary syndrome (ACS) patients with hypersensitivity to aspirin, undergoing coronary stenting. Forty-two consecutive ACS patients treated with stent implantation were randomly assigned to receive clopidogrel 75 mg daily (loading dose 300 mg) plus indobufen 100 mg twice a day (group A), or clopidogrel 75 mg daily, after 300 mg of loading dose (group B). Platelet activity and safety were monitored in both groups at 1, 3, 6, 12, and 18 months with laboratory and clinical evaluation. A lower value of max % platelet aggregation to arachidonic acid and collagen was found in group A compared to group B (31.79 ± 27.33 vs. 73.67 ± 19.92; p < 0.0001 and 28.53 ± 21.32 vs. 73.58 ± 17.71; p < 0.0001, respectively). There was no difference in max % of platelet inhibition to adenosine diphosphate between the two groups (14.23 ± 18.92 vs. 10.30 ± 18.97; p = 0.23). In the population that was under indobufen treatment, the serum thromboxane B2 (TXB2) production at 1 week and 1 month was very low (2.6 ± 1.6 ng/ml and 3.0 ± 2.7 ng/ml, respectively; p = 0.82). The combined treatment was well tolerated in group A patients. This study suggests that the combined antiplatelet treatment with clopidogrel and indobufen could be a good option in ACS patients with hypersensitivity to aspirin undergoing coronary stenting.

Acute Aortic Dissection Mimicking STEMI in the Catheterization Laboratory: Early Recognition Is Mandatory.

Coronary malperfusion due to type A aortic dissection is a life-threatening condition where timely recognition and treatment are mandatory. A 77-year-old woman underwent an acute evolving type A aortic dissection mimicking acute myocardial infarction. Two pathophysiologic mechanisms are discussed: either thrombosis migrating from a previously treated giant aneurism of proximal left anterior descending or a local arterial complication due to left main stenting. Recognition of these occurrences in the catheterization laboratory is important to look immediately for surgery.

Anoxia-reoxygenation enhances platelet thromboxane A2 production via reactive oxygen species-generated NOX2: effect in patients undergoing elective percutaneous coronary intervention.

OBJECTIVE: Platelets undergoing anoxia-reoxygenation (AR) simultaneously increase reactive oxygen species (ROS) and thromboxane (Tx) B(2). Our aim was to assess whether there is an interplay between activation of NOX2, the catalytic subunit of NADPH oxidase, and platelet TxB(2) in vitro and in vivo. METHODS AND RESULTS: Platelets that underwent AR had enhanced ROS. This was associated with NOX2 activation and was inhibited by incubation with NOX2-blocking peptide. AR was associated with TxB(2) and isoprostane production, which were inhibited by NOX2-blocking peptide, vitamin C, and the inhibitor of phospholipase A(2). Platelet incubation with 100 µmol/L aspirin fully prevented AR-induced TxA(2) but did not affect isoprostane production. We included 56 aspirin-treated patients undergoing elective percutaneous coronary intervention (PCI) who were randomly allocated to receive either placebo or intravenous infusion of 1 g of vitamin C. Blood TxB(2), isoprostanes, and soluble NOX2-derived peptide, a marker of systemic NADPH oxidase activation, significantly increased at 60 and 120 minutes after PCI in placebo-treated but not in vitamin C-treated patients. CONCLUSIONS: AR is associated with overproduction of platelet TxB(2) and isoprostanes, which is dependent on NOX2-dependent ROS generation. Low doses of aspirin are unable to prevent TxB(2) formation in patients who undergo PCI.

Ascorbic acid infusion blunts CD40L upregulation in patients undergoing coronary stent.

OBJECTIVES: To reduce the increase of oxidative stress and the upregulation of CD40L during stenting procedure using ascorbic acid infusion. BACKGROUND: CD40L upregulation occurring after coronary percutaneous coronary intervention predicts vascular events but the underlying mechanism is still unclear. METHODS: Fifty-six patients undergoing elective coronary stenting were randomly allocated to intravenous infusion of the antioxidant ascorbic acid or placebo. Platelet CD40L and plasma levels of soluble CD40L and of 8-hydroxy-2'-deoxyguanosine, a marker of oxidative stress, were measured before and after coronary stenting. In vitro study was also done to measure reactive oxidant species and CD40L expression in platelets exposed to anoxia-reoxygenation. RESULTS: Placebo-treated patients showed a significant increase of platelet CD40L, soluble CD40L and 8-hydroxy-2'-deoxyguanosine compared to baseline values. Patients given ascorbic acid showed no change of soluble CD40L and platelet CD40L but a significant decrease of 8-hydroxy-2'-deoxyguanosine. After 60 and 120 min, soluble CD40L, platelet CD40L and 8-hydroxy-2'-deoxyguanosine were significantly lower in the ascorbic acid-treated group compared to the placebo-treated one. A significant correlation between platelet CD40L and soluble CD40L and between soluble CD40L and 8-hydroxy-2'-deoxyguanosine was observed. Platelets, in vitro exposed to anoxia-reoxygenation, had a burst of ROS and an upregulation of CD40L that were inhibited by ascorbic acid or apocynin, an inhibitor of NADPH oxidase. CONCLUSIONS: This study shows that in patients undergoing coronary stenting CD40L is upregulated with a mechanism which is likely mediated by oxidative stress.

Angina in fabry disease reflects coronary small vessel disease.

BACKGROUND: Chest pain is frequently reported in Fabry disease (FD). However, its mechanism and clinical relevance are unclear. METHODS AND RESULTS: Basal troponin I level, exercise stress test, single-photon emission computed tomography imaging with (99m)Tc sestamibi, coronary angiography with thrombolysis in myocardial infarction (TIMI) frame count and left ventricular angiography and endomyocardial biopsy were obtained in 13 patients with FD with angina. Ratio of external to lumen diameter of intramural arteries (E/L ratio), myocyte diameter, and extent of fibrosis were morphometrically evaluated by using tissue sections. Controls for coronary angiography and histology were 25 patients with FD without angina and 20 mitral stenosis patients with normal left ventricular function. Troponin I level was elevated in 6 of the 13 patients. Exercise stress test showed evidence of myocardial ischemia, and single-photon emission computed tomography was positive for stress-induced perfusion defects in all patients with FD with angina. Epicardial coronaries were structurally normal but showed slow flow in all and were associated with aneurisms of posterior left ventricular wall in 3 cases. Histology showed remarkable lumen narrowing of most intramural arteries (mean E/L ratio=3.5+/-1.2; P<0.001 versus both control groups), because of hypertrophy and proliferation of smooth muscle and endothelial cells, both engulfed by glycosphingolipids. Replacement fibrosis exceeded that of both controls (P<0.001). Small vessel disease correlated with coronary slow flow and extent of fibrosis, but did not with patients' age, sex, and degree of left ventricular hypertrophy. CONCLUSIONS: patients with FD with angina have perfusion defects, slow coronary flow, and luminal narrowing of intramural arteries. Small vessel disease may contribute to symptomatic limitation and progressive myocardial dysfunction.