The Combined Treatment of Glutathione Sodium Salt and Ascorbic Acid for Preventing Contrast-Associated Acute Kidney Injury in ST-Elevation Myocardial Infarction Patients Undergoing Primary PCI: A Hypothesis to Be Validated.

The occurrence of Contrast-Associated Acute Kidney Injury (CA-AKI) in patients with ST-Elevation Myocardial Infarction (STEMI) has a negative impact on the length of hospital stay and mortality. Reactive Oxygen Species (ROS) release, along with vasoconstriction and hypoperfusion, play a key role in its development. To date, there is still no validated prophylactic therapy for this disease. The use of antioxidants, based on experimental and clinical studies, looks promising. Taking into consideration previous literature, we speculate that an early, combined and prolonged intravenous administration of both Glutathione (GSH) and ascorbic acid in STEMI patients undergoing primary Percutaneous Coronary Intervention (pPCI) may be of value in counteracting the occurrence of CA-AKI. We aimed at evaluating this hypothesis by applying a multicenter research protocol, using a double-blind randomized, placebo-controlled trial design. The primary endpoint will be to test the efficacy of this combined antioxidant therapy in reducing the occurrence of renal damage, in patients with acute myocardial infarction treated with pPCI. Furthermore, we will investigate the effect of the study compounds on changes in oxidative stress markers and platelet activation levels through bio-humoral analyses.

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.

Early metabolic response to acute myocardial ischaemia in patients undergoing elective coronary angioplasty.

Objective: Balloon-induced transient coronary ischaemia represents a model of myocardial ischaemia and reperfusion. We are interested in the very early systemic metabolic response to this event. Methods: Blood samples of patients with stable angina (SA) were collected before and after coronary angioplasty. Serum metabolic profiles were obtained using nuclear magnetic resonance spectroscopy. Univariate and multivariate analyses were used to investigate changes in metabolite concentrations. Results: Thirty-four consecutive patients with SA, undergoing elective coronary angioplasty at Policlinico Umberto I of Rome, were included in this study. Changes in metabolites concentration induced by balloon occlusion in venous and arterial sera were detected. In both serum types, a significant increase in ketone bodies, 2-hydroxybutyrate, glutamine and O-acetylcarnitine concentration is observed, while alanine, lactate, phenylalanine and tyrosine decreased after intervention. Most significant metabolic changes were detected in arterial serum. Conclusions: Our study points out two main global metabolic changes in peripheral blood after balloon-induced coronary ischaemia: ketone bodies increase and lactate decrease. Both could be related to compensation mechanisms finalised to fulfil heart's needs after short period of myocardial ischaemia and probably after reperfusion.

Moderate-to-high cardiovascular risk is associated with increased lower urinary tract storage symptoms in patients with benign prostatic enlargement.

BACKGROUND: To assess the association between cardiovascular risk (CVR) and lower urinary tract symptoms (LUTS) in men with benign prostatic enlargement (BPE). METHODS: We enrolled a consecutive series of men with LUTS/BPE. International Prostate Symptom Score (IPSS), voiding (vIPSS) and storage (sIPSS) subscore and prostate volume were evaluated. We defined CVR according to the European Association of Cardiologist Guidelines, and metabolic syndrome (MetS) according to the Adult Treatment Panel III (ATP III). RESULTS: A total of 509 patients were enrolled. Median age was 66 years (IQR: 60-72), IPSS 9 (IQR: 5-15), vIPSS 5 (IQR: 2-9), sIPSS 4 (IQR: 2-7), Prostate volume was 54 cc (IQR: 40-73). Overall 309/509 (60.7%) patients had a moderate/high CVR and 128/509 presented MetS (25.1%). 297/509 (58.3%) men had an IPSS>7 and 282/509 (55.4%) a sIPSS>3. Men with moderate-to-severe CVR had higher IPSS (9; IQR: 4-14 vs. 10; IQR: 5-16; P=0.01), higher vIPSS (6; IQR: 2-9 vs. 4; IQR: 2-8; P=0.06) and higher sIPSS (4; IQR: 2-8 vs. 3; IQR: 1-6; P=0.005) when compared with no/low CVR patients. On multivariate analysis CVR was associated with an increased risk of IPSS>7 (OR=1.794; 95% CI: 1.111-2.888; P=0.01) and sIPSS>3 (OR=1.593; 95% CI: 1.101-2.555; P=0.04). CONCLUSIONS: A moderate/high CVR is associated with an increased risk of LUTS, particularly storage LUTS. Although the pathophysiology is yet to be understood, it can be assumed that an increased CVR may be associated with LUTS/BPE presence.

Three-dimensional echocardiography and 2D-3D speckle-tracking imaging in chronic pulmonary hypertension: diagnostic accuracy in detecting hemodynamic signs of right ventricular (RV) failure.

BACKGROUND: Our aim was to compare three-dimensional (3D) and 2D and 3D speckle-tracking (2D-STE, 3D-STE) echocardiographic parameters with conventional right ventricular (RV) indexes in patients with chronic pulmonary hypertension (PH), and investigate whether these techniques could result in better correlation with hemodynamic variables indicative of heart failure. METHODS AND RESULTS: Seventy-three adult patients (mean age, 53±13 years; 44% male) with chronic PH of different etiologies were studied by echocardiography and cardiac catheterization (25 precapillary PH from pulmonary arterial hypertension, 23 obstructive pulmonary heart disease, and 23 postcapillary PH from mitral regurgitation). Thirty healthy subjects (mean age, 54±15 years; 43% male) served as controls. Standard 2D measurements (RV-fractional area change-tricuspid annular plane systolic excursion) and mitral and tricuspid tissue Doppler annular velocities were obtained. RV 3D volumes and global and regional ejection fraction (3D-RVEF) were determined. RV strains were calculated by 2D-STE and 3D-STE. RV 3D global-free-wall longitudinal strain (3DGFW-RVLS), 2D global-free-wall longitudinal strain (GFW-RVLS), apical-free-wall longitudinal strain, basal-free-wall longitudinal strain, and 3D-RVEF were lower in patients with precapillary PH (P<0.0001) and postcapillary PH (P<0.01) compared to controls. 3DGFW-RVLS (hazard ratio 4.6, 95% CI 2.79 to 8.38, P=0.004) and 3D-RVEF (hazard ratio 5.3, 95% CI 2.85 to 9.89, P=0.002) were independent predictors of mortality. Receiver operating characteristic curves showed that the thresholds offering an adequate compromise between sensitivity and specificity for detecting hemodynamic signs of RV failure were 39% for 3D-RVEF (AUC 0.89), -17% for 3DGFW-RVLS (AUC 0.88), -18% for GFW-RVLS (AUC 0.88), -16% for apical-free-wall longitudinal strain (AUC 0.85), 16 mm for tricuspid annular plane systolic excursion (AUC 0.67), and 38% for RV-FAC (AUC 0.62). CONCLUSIONS: In chronic PH, 3D, 2D-STE and 3D-STE parameters indicate global and regional RV dysfunction that is associated with RV failure hemodynamics better than conventional echo indices.

Bidirectional tachycardia after an acute intravenous administration of digitalis for a suicidal gesture.

Acute digoxin intoxication is a life-threating condition associated with severe cardiotoxicity. Female gender, age, low lean body mass, hypertension, and renal insufficiency may worsen the prognosis. Arrhythmias caused by digitalis glycosides are characterized by an increased automaticity coupled with concomitant conduction delay. Bidirectional tachycardia is pathognomonic of digoxin intoxication, but it is rarely observed. An 83-year-old woman was admitted to the Emergency Department after self-administration of 5 mg of digoxin i.v. for suicidal purpose. Her digoxin serum concentration was 17.4 ng/mL. The patient developed a bidirectional tachycardia and the Poison Control Center of the hospital provided digoxin immune fab. Bidirectional tachycardia quickly reversed and the patient remained stable throughout the hospital stay. This case shows that a multiple disciplinary approach, involving cardiologists and toxicologists, is essential for the management of digoxin intoxication. The optimal treatment of this rare event depends on the clinical conditions and on the serum drug concentration of the patient. Digoxin immune fab represents a safe, effective, and specific method for rapidly reversing digitalis cardiotoxicity and should be started as soon as the diagnosis is defined.

Right ventricular function in acute pulmonary embolism: a combined assessment by three-dimensional and speckle-tracking echocardiography.

BACKGROUND: The aim of this study was to assess changes in right ventricular (RV) parameters determined by three-dimensional (3D) echocardiography and speckle-tracking echocardiography in patients with acute pulmonary embolism and RV dysfunction without systemic hypotension (submassive pulmonary embolism). METHODS: Sixty-six patients were prospectively studied at the onset of the acute episode and after median follow-up periods of 30 days and 6 months. Sixty-six controls were selected. RV fractional area change, tricuspid annular plane systolic excursion, and myocardial performance index were determined. RV systolic pressure was assessed using continuous-wave Doppler echocardiography. Three-dimensional RV ejection fraction (RVEF) was calculated. Two-dimensional peak systolic RV longitudinal strain (RVLS) was measured in the basal free wall, mid free wall (MFW), and apical free wall and the septum. RESULTS: Tricuspid annular plane systolic excursion and fractional area change were smaller and myocardial performance index was larger compared with controls (P < .05). Global RVLS (P < .05), MFW RVLS (P < .001), and 3D RVEF (P < .001) were lower in patients with pulmonary embolism than in controls. There was earlier reversal of MFW RVLS values on 30-day follow-up and longer reversal of 3D RVEF and RV systolic pressure values at 6-month follow-up. Receiver operating characteristic curve analysis showed that changes in 3D RVEF and MFW RVLS were the most sensitive predictors of adverse events. By multivariate analysis, RV systolic pressure (P = .007), MFW RVLS (P = .002), and 3D RVEF (P = .001) were independently associated with adverse outcomes. CONCLUSIONS: Acute submassive pulmonary embolism has a significant impact on RV function as assessed by 3D echocardiography and speckle-tracking echocardiography. Decreases in MFW RVLS and 3D RVEF may persist during short-term and long-term follow-up and correlate with unfavorable outcomes.

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.

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.

Feasibility and clinical utility of transesophageal echocardiography in the acute phase of cerebral ischemia.

We evaluated the feasibility and clinical utility of transesophageal echocardiography (TEE) in the early management of ischemic stroke. TEE was performed in consecutive patients with acute cerebral ischemia within 48 hours of symptoms onset. The data were analyzed by age (<55 vs ≥55 years), and the baseline stroke etiology was classified (determined vs undetermined). TEE was feasible in 660 (61%) of 1,080 patients. Left atrial abnormalities and complicated aortic plaques prevailed in older patients (p <0.05), irrespective of the stroke etiology. A patent foramen ovale prevailed in younger patients (p <0.05) but even in older patients was present in 13% of the determined and 31% of the undetermined stroke subgroups. Overall, high-risk and potentially high-risk cardioembolic sources were detected in 47% of the patients, and stroke etiology was consequently reviewed: 40% of the baseline undetermined strokes were reclassified as cardioembolic, and 29% of lacunar, 42% of large artery, and 30% of other determined-cause strokes were reclassified as concurrent etiology. Subsequently, according to the current guidelines, 12% of patients were reassigned from antiplatelet to anticoagulant therapy and 17% of patients were treated with high-dose statins; overall, secondary prevention treatment was modified in 26% of patients. In conclusion, TEE was feasible in about 2/3 of the patients investigated within 48 hours of the index event, contributed to stroke classification in 1/3 of cases, and guided secondary prevention therapy in 1/4 of patients. Therefore, TEE is useful for defining patients' risk profile for stroke recurrence.

The role of intraoperative transoesophageal echocardiography in the diagnosis and management of a rare multiple fibroelastoma of aortic valve: a case report and review of literature.

Papillary fibroelastoma is the third most common primary tumour of the heart that usually involves the cardiac valves. Multiple papillary fibroelastomas are extremely rare. We report a case with multiple valve papillary fibroelastoma which was identified only by intraoperative transoesophageal echocardiography. The patient complained of atypical chest pains. She was affected by coronary artery disease and had previously had a myocardial infarct. This finding dictated a change in the operative approach. The aortic valve resection was performed in addition to coronary revascularization. If the intraoperative transoesophageal echocardiography was not performed, our patient would have had just coronary artery bypass graft surgery, probably without solving the symptoms. Furthermore, in future she would have undergone another cardiac operation for resection of aortic masses and valve replacement. The intraoperative use of Transoesophageal Echocardiography improves the diagnosis and the management of all cardiac surgical patients.