Cardiac mechanics in response to proteasome inhibition: a prospective study.

AIM: Ubiquitin-Proteasome System (UPS) is of paramount importance regarding the function of the myocardial cell. Consistently, inhibition of this system has been found to affect myocardium in experimental models; yet, the clinical impact of UPS inhibition on cardiac function has not been comprehensively examined. Our aim was to gain insight into the effect of proteasome inhibition on myocardial mechanics in humans. METHODS AND RESULTS: We prospectively evaluated 48 patients with multiple myeloma and an indication to receive carfilzomib, an irreversible proteasome inhibitor. All patients were initially evaluated and underwent echocardiography with speckle tracking analysis. Carfilzomib was administered according to Kd treatment protocol. Follow-up echocardiography was performed at the 3rd and 6th month. Proteasome activity (PrA) was measured in peripheral blood mononuclear cells.At 3 months after treatment, we observed early left ventricular (LV) segmental dysfunction and deterioration of left atrial (LA) remodelling, which was sustained and more pronounced than that observed in a cardiotoxicity control group. At 6 months, LV and right ventricular functions were additionally attenuated (P < 0.05 for all). These changes were independent of blood pressure, endothelial function, inflammation, and cardiac injury levels. Changes in PrA were associated with changes in global longitudinal strain (GLS), segmental LV strain, and LA markers (P < 0.05 for all). Finally, baseline GLS < -18% or LA strain rate > 1.71 were associated with null hypertension events. CONCLUSION: Inhibition of the UPS induced global deterioration of cardiac function.

Epidemiology, reperfusion management, and outcomes of patients with myocardial infarction in Greece: The ILIAKTIS study.

OBJECTIVE: Acute myocardial infarction (AMI) is one of the leading causes of death; however, updated data regarding clinical presentation and current management are missing in Greece. This study aimed to prospectively record the demographic and clinical characteristics of a representative sample of patients suffering from AMI, their management, and short-term outcomes. METHODS: ILIAKTIS is a national, prospective, multicenter, noninterventional study conducted under the auspices of Hellenic Society of Cardiology (HCS) and the European Initiative Stent - Save a Life. From 1st April 2020 to 30th June 2020, consecutive adult patients with STEMI or NSTEMI were enrolled in the 50 participating hospitals, appropriately selected to match the geographical and population distribution in the Greek territory. RESULTS: In total, 1862 patients (mean age: 64.2 ± 13.2 yrs.; 77.2% males) with AMI were enrolled. More patients presented with NSTEMI (56.8%) than with STEMI (43.2%). Primary PCI (pPCI) was the preferable treatment option for STEMI patients in PCI-hospitals (76.9% vs. 39.9% for non-PCI, p < .001) and thrombolysis in non-PCI-hospitals (47.3% vs. 17.9% for PCI-hospitals, p < .001). The mean length of hospital stay was 5.6 days. In-hospital mortality was less likely in NSTEMI compared to that in STEMI patients (aOR = 0.30; 95% CI 0.18 to 0.49). Patients initially admitted in non-PCI-hospitals showed increased risk for in-hospital (aOR = 2.29; 95% CI 1.20 to 4.42) and 30-day mortality (aOR = 1.88; 95% CI 1.20 to 2.96). CONCLUSION: This study shows that the proportion of STEMI and NSTEMI patients managed interventionally has significantly increased, resulting in better clinical outcomes compared to previous Greek surveys.

Intestinal necrosis and sigmoid colon obstruction due to bilateral strangulated femoral hernia in a male: a rare surgical and anatomic case report.

Bilateral femoral hernia is a peculiar clinical condition, with female predominance, with only a few cases reported in the literature. There are only two cases of bilateral strangulated femoral hernias, and these occur solely in females. To our knowledge, in the present manuscript, a bilateral strangulated femoral hernia in a male patient is reported for the first time. A 68-year-old male proceeded to the emergency department of our institution with symptoms of bowel obstruction. Abdominal computed tomography, magnetic resonance imaging and subsequent emergency laparotomy revealed obstruction of the sigmoid colon and simultaneous necrosis of several loops of the small intestine due to bilateral strangulated femoral hernia. The operation was uneventful. Despite the scarcity of this clinical condition, surgeons' awareness is fundamental, in addition to deep knowledge of the pathology and the anatomy of femoral hernias, in order to diagnose and treat adequately strangulated and incarcerated femoral hernias.

Effect of late revascularization of a totally occluded coronary artery after myocardial infarction on mortality rates in patients with renal impairment.

Renal dysfunction is an independent predictor of cardiovascular events and a negative prognostic indicator after myocardial infarction (MI). Randomized data comparing percutaneous coronary intervention to medical therapy in patients with MI with renal insufficiency are needed. The Occluded Artery Trial (OAT) compared optimal medical therapy alone to percutaneous coronary intervention with optimal medical therapy in 2,201 high-risk patients with occluded infarct arteries >24 hours after MI with serum creatinine levels ≤2.5 mg/dl. The primary end point was a composite of death, MI, and class IV heart failure (HF). Analyses were carried out using estimated glomerular filtration rate (eGFR) as a continuous variable and by eGFR categories. Long-term follow-up data (maximum 9 years) were used for this analysis. Lower eGFR was associated with development of the primary outcome (6-year life-table rates of 16.9% for eGFR >90 ml/min/1.73 m(2), 19.2% for eGFR 60 to 89 ml/min/1.73 m(2), and 34.9% for eGFR <60 ml/min/1.73 m(2); p <0.0001), death, and class IV HF, with no difference in rates of reinfarction. On multivariate analysis, eGFR was an independent predictor of death and HF. There was no effect of treatment assignment on the primary end point regardless of eGFR, and there was no significant interaction between eGFR and treatment assignment on any outcome. In conclusion, lower eGFR at enrollment was independently associated with death and HF in OAT participants. Despite this increased risk, the lack of benefit from percutaneous coronary intervention in the overall trial was also seen in patients with renal dysfunction and persistent occlusion of the infarct artery in the subacute phase after MI.

Anomalous origin of the left main coronary artery from the main pulmonary artery in an elderly patient.

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) syndrome is an extremely rare diagnosis in elderly patients. We describe a 73-year-old female with ALCAPA who underwent successful repair of this coronary anomaly.

Superselective embolization of renal hemorrhage occurring after percutaneous coronary intervention.

A 69-year-old female was hospitalized for acute coronary syndrome and received full antiplatelet and anticoagulant therapy. The patient underwent angioplasty and stent implantation on right coronary and left circumflex arteries with good angiographic result. After the procedure, the patient developed hemorrhagic shock due to massive left renal hemorrhage. An emergent digital subtraction angiography showed bleeding from a left segmental renal artery. The hemorrhage was successfully managed with transcatheter superselective embolization. The patient was discharged after 22 days in good general condition with normal renal function. One-year follow-up was uneventful.

Primary myxofibrosarcoma of the left atrium: case report and review of the literature.

A 63-year-old woman with progressive dyspnea underwent transthoracic echocardiography and was found to have a large multilobed mass in the left atrium that was attached to lateral wall. On inspection during surgery, the tumor was found to infiltrate the posterior mitral annulus and leaflet. The patient underwent surgical resection of the tumor and mitral valve replacement. Histologic and cytochemical evaluation confirmed that the tumor was a myxofibrosarcoma. Despite chemotherapy, the tumor recurred and the patient died 3 months after surgery.

Enoxaparin versus tinzaparin in non-ST-segment elevation acute coronary syndromes: results of the enoxaparin versus tinzaparin (EVET) trial at 6 months.

BACKGROUND: We have previously reported significant benefits of using enoxaparin, compared to tinzaparin, in the 7- and 30-day incidence of the composite triple end point of death, myocardial infarction (MI), or recurrent angina in patients with non-ST-segment elevation acute coronary syndromes (NSTACS). In the present study, we aimed to determine whether the observed benefits of enoxaparin were maintained beyond the early phase and report the results of the 6-m follow-up of patients in the EVET study. METHODS: We recruited 438 patients with NSTACS. All patients received oral aspirin and were randomized to also receive enoxaparin, 100 IU/kg subcutaneously twice daily (equivalent to 1 mg/kg twice daily; n = 220), or tinzaparin, 175 IU/kg subcutaneously once daily (n = 218), for up to 7 days. RESULTS: At 6 m, the incidence of the composite triple end point of death, MI, or recurrent angina was lower among patients receiving enoxaparin compared to those receiving tinzaparin (25.5% vs 44.0%, P < .001). A lower incidence of the secondary composite end point of death or MI was also found in the enoxaparin group compared to tinzaparin group (2.7% vs 6.9%, P = .046). The need for revascularization procedures was also lower in the enoxaparin group compared to tinzaparin group (23.2% vs 37.2%, P = .002). CONCLUSIONS: In patients with NSTACS, enoxaparin significantly reduced the rates of recurrent ischemic events and therapeutic procedures in the short term, with sustained benefit at 6 m compared to tinzaparin.

One year effectiveness of BiodivYsio dexamethazone-eluting stent compared to BiodivYsio stent implantation in the treatment of single vessel coronary artery disease.

OBJECTIVE: To investigate the impact of BiodivYsio dexamethazone-eluting stent versus BiodivYsio stent on the 12-month outcomes after revascularisation of patients with single vessel coronary artery disease. METHODS: From March 2003 to February 2004, 102 patients with non-ST elevation acute coronary syndromes, angina or silent ischemia after recent ST elevation myocardial infarction (<1 month) or stable angina pectoris, and single-vessel coronary artery disease were treated solely with dexamethazone-eluting stent implantation in our institution. Patients were followed up prospectively for twelve months. We compared their outcomes to a control group with similar clinical and angiographic characteristics of 160 patients treated solely with BiodivYsio stents in the preceding study enrolment period (January 2002 to March 2003). RESULTS: Approximately 85% of the patients in both groups were treated after an acute coronary syndrome. At 12 months, the major adverse cardiac events rates (death or non-fatal myocardial infarction or target lesion revascularization) were similar in the 2 groups (10.8% in the dexamethazone-eluting and 11.3% in the BiodivYsio group, p=1.00). No difference was found in the individual rates of death, non-fatal myocardial infarction and target lesion revascularization between the 2 groups. CONCLUSIONS: We conclude that utilization of dexamethazone-eluting stents has no effect in reducing the incidence of major adverse cardiac events after 12 months, as compared with BiodivYsio stent implantation in the treatment of single vessel coronary artery disease.

Primary stenting produces earlier and more efficient myocardial reperfusion than primary PTCA alone in patients with acute ST segment elevation MI.

Restoration of blood flow in the infarct-related artery and subsequent myocardial reperfusion are major goals of both thrombolysis and primary percutaneous interventions. Whether percutaneous transluminal coronary angioplasty (PTCA) with immediate stenting (primary stenting) produces reperfusion more rapidly than primary PTCA alone is uncertain. This study determines whether primary stenting produces earlier myocardial reperfusion than primary PTCA alone in patients with acute ST segment elevation myocardial infarction using troponin T release kinetics. Primary stenting was performed on 60 patients and primary PTCA alone on 44 patients with typical ischemic chest pain and greater than 1.5 MV ST segment elevation in more than 2 contiguous electrocardiographic leads. Serum troponin T concentrations were measured before and after intervention; every 6 hours for 24 hours; then at 36, 48 and 72 hours. The mean time from onset of chest pain to peak serum troponin T concentration was 7.8 +/- 2.7 hours after primary stenting and 14.5 +/- 4.4 hours after primary PTCA (p < 0.0005). The mean peak serum troponin T concentration was 9.8 +/- 6.3 ng/dL after primary stenting and 13.6 +/-6.4 ng/dL after primary PTCA (p < 0.012). A significant univariate association with time to peak concentration of serum troponin T was identified for primary stenting (p < 0.0005), time from onset of chest pain to intervention (p < 0.04), and diabetes mellitus (p < 0.01). The only significant univariate marker associated with peak concentration of serum troponin T was primary stenting (p < 0.012). Multivariate analysis indicated that primary stenting (p < 0.0005), time from onset of chest pain to intervention (p < 0.048), and diabetes mellitus (p < 0.022) significantly influenced time to peak serum concentration or troponin T. Primary stenting produces earlier myocardial reperfusion than primary PTCA in patients with acute ST segment elevation myocardial infarction.

Relation of troponin T release kinetics to long-term clinical outcome in patients with acute ST segment elevation myocardial infarction treated with a percutaneous intervention.

The purpose of this study was to determine the relation of troponin T release kinetics to long-term clinical outcome in patients with an acute ST segment elevation myocardial infarction treated with a primary percutaneous intervention. One hundred and four patients with typical ischemic chest pain and > 1.5 mm ST segment elevation in > 2 contiguous leads underwent primary stenting (n = 60) or primary percutaneous transluminal coronary angioplasty (n = 44). Serum troponin T concentrations were obtained prior to and serially postintervention for 72 hr. Mean time to peak serum troponin T concentration was significantly longer in patients with cardiac death (P = 0.02), reinfarction (P = 0.007), target lesion reintervention (P = 0.03), and the composite of these events (13.2 +/- 5.3 vs. 9.3 +/- 4.0 hr; P < 0.0005). Multivariate analysis identified age, Killip class > 2, and time to peak serum troponin T concentration as independent predictors of long-term cardiac event-free survival. Thus, time to peak serum troponin T concentration independently predicts long-term cardiac event-free survival in patients with acute ST segment elevation myocardial infarction treated with a primary percutaneous intervention.

Anomalous left coronary artery arising from the right sinus of valsalva in a man with unstable angina pectoris and right coronary artery stenosis.

A 54-year-old man developed unstable angina pectoris and was found to have both an anomalous left coronary artery, which arose from the right sinus of Valsalva and followed an intramyocardial (septal) course, and severe atherosclerotic stenosis of the mid-right coronary artery. Stress perfusion imaging showed ischemia in the distribution of the right coronary artery, leading to successful percutaneous transluminal balloon angioplasty of the right coronary artery rather than surgical correction of the congenital anomaly.