Antonia Sambola

Contemporary Epidemiology and Prognosis of Health Care–Associated Infective Endocarditis

BACKGROUND The aim of this study was to describe the characteristics of health care-associated infective endocarditis (HAIE) and to establish the risk factors for mortality. METHODS We conducted a prospective, observational cohort study. HAIE was defined according to the following conditions: (1) symptom onset >48 h after hospitalization or within 6 months after hospital discharge; or (2) ambulatory manipulations causing endocarditis. RESULTS Eighty-three episodes of HAIE (accounting for 28.4% of all cases of endocarditis) were diagnosed. Compared with patients with community-acquired endocarditis, patients with HAIE were older (median age +/- standard deviation, 65.3 +/- 16.4 years vs. 57.8 +/- 17.0 years; P = .001), were in poorer health before disease onset (Charlson index, 2.5 +/- 2.3 vs. 1.7 +/- 2.1; P = .006), had more staphylococcal (55.4% vs. 28.3% of cases) and enterococcal infections (22.9% vs. 7.7% of cases; P < .005), underwent fewer surgeries (22.9% vs. 45.9% of cases; P < .005), and experienced a higher rate of in-hospital (45.8% vs. 22.0%) and 1-year mortality (59.5% vs. 29.6%; P < .005). In the HAIE cohort, independent predictors of in-hospital death were stroke (odds ratio [OR], 8.95; 95% confidence interval [CI], 2.04-39.31; P = .004), congestive heart failure (OR, 5.48; 95% CI, 1.77-17.03; P = .003), surgery indicated but not performed (OR, 3.74; 95% CI, 1.22-11.45; P = .021), and enterococcal infection (OR, 0.18; 95% CI, 0.04-0.78; P = .022). Independent predictors of 1-year mortality were surgery indicated but not performed (OR, 7.81; 95% CI, 2.06-29.67; P = .003), acute renal failure (OR, 7.18; 95% CI, 1.32-39.18; P = .023), and enterococcal infection (OR, 0.18; 95% CI, 0.04-0.81; P = .026). For the series overall (292 episodes), HAIE was an independent predictor of in-hospital (OR, 2.83; 95% CI, 1.34-5.98; P = .007) and 1-year mortality (OR, 2.59; 95% CI, 1.25-5.39; P = .011). CONCLUSIONS HAIE is an important health problem associated with considerable mortality. New strategies to prevent HAIE should be assessed.

Dual antiplatelet therapy versus oral anticoagulation plus dual antiplatelet therapy in patients with atrial fibrillation and low-to-moderate thromboembolic risk undergoing coronary stenting: design of the MUSICA-2 randomized trial.

BACKGROUND Oral anticoagulation (OAC) is the recommended therapy for patients with atrial fibrillation (AF) because it reduces the risk of stroke and other thromboembolic events. Dual antiplatelet therapy (DAPT) is required after percutaneous coronary intervention and stenting (PCI-S). In patients with AF requiring PCI-S, the association of DAPT and OAC carries an increased risk of bleeding, whereas OAC therapy or DAPT alone may not protect against the risk of developing new ischemic or thromboembolic events. OBJECTIVE The MUSICA-2 study will test the hypothesis that DAPT compared with triple therapy (TT) in patients with nonvalvular AF at low-to-moderate risk of stroke (CHADS2 score ≤2) after PCI-S reduces the risk of bleeding and is not inferior to TT for preventing thromboembolic complications. DESIGN The MUSICA-2 is a multicenter, open-label randomized trial that will compare TT with DAPT in patients with AF and CHADS2 score ≤2 undergoing PCI-S. The primary end point is the incidence of stroke or any systemic embolism or major adverse cardiac events: death, myocardial infarction, stent thrombosis, or target vessel revascularization at 1 year of PCI-S. The secondary end point is the combination of any cardiovascular event with major or minor bleeding at 1 year of PCI-S. The calculated sample size is 304 patients. CONCLUSIONS The MUSICA-2 will attempt to determine the most effective and safe treatment in patients with nonvalvular AF and CHADS2 score ≤2 after PCI-S. Restricting TT for AF patients at high risk for stroke may reduce the incidence of bleeding without increasing the risk of thromboembolic complications.

Increased von Willebrand factor, P-selectin and fibrin content in occlusive thrombus resistant to lytic therapy

Therapeutic fibrinolysis is ineffective in 40 % of ST-segment elevation acute myocardial infarction (STEMI) patients, but understanding of the mechanisms is incomplete. It was our aim to compare the composition of coronary thrombus in lysis-resistant STEMI patients with that of lysis-sensitive patients. Intracoronary thrombi (n=64) were obtained by aspiration in consecutive STEMI patients. Of them, 20 had received fibrinolysis and underwent rescue percutaneous coronary intervention (r-PCI, lysis-resistant patients) and 44 underwent primary PCI (p-PCI). Lysis-sensitivity was determined in vitro by clot permeability measurements and turbidimetric lysis in plasma of 44 patients undergoing p-PCI and 20 healthy donors. Clot-lysis sensitivity was defined as a clot-lysis time not greater than 1 SD over the mean of healthy donors. Coronary thrombus composition in 20 lysis-resistant and in 20 lysis-sensitive patients was analysed by immunofluorescence with confocal microscopy. Plasma biomarkers (P-selectin, VWF, PAI-1, t-PA, D-dimer, TF pathway markers, plasmin and CD34+) were measured simultaneously on peripheral blood. Lysis-resistant clots had higher levels of fibrin (p=0.02), P-selectin (p=0.03) and VWF (p=0.01) than lysis-sensitive clots. Among thrombi obtained ≤ 6 hours after onset of symptoms, those from lysis-resistant patients showed a higher content in fibrin than those from p-PCI patients (p=0.01). Plasma PAI-1 (p=0.02) and D-dimer levels were significantly higher (p=0.003) in lysis-resistant patients, whereas plasmin levels were lower (p=0.03). Multivariate analysis showed the content of fibrin and VWF within thrombus as predictors of thrombolysis resistance. In conclusion, coronary thrombi in STEMI patients resistant to fibrinolysis are characterised by higher fibrin, P-selectin and VWF content than lysis-sensitive thrombi.

Impact of Triple Therapy in Elderly Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention

Background and Purpose Selecting an ideal antithrombotic therapy for elderly patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) can be challenging since they have a higher thromboembolic and bleeding risk than younger patients. The current study aimed to assess the efficacy and safety of triple therapy (TT: oral anticoagulation plus dual antiplatelet therapy: aspirin plus clopidogrel) in patients ≥75 years of age with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). Methods A prospective multicenter study was conducted from 2003 to 2012 at 6 Spanish teaching hospitals. A cohort study of consecutive patients with AF undergoing PCI and treated with TT or dual antiplatelet therapy (DAPT) was analyzed. All outcomes were evaluated at 1-year of follow-up. Results Five hundred and eighty-five patients, 289 (49%) of whom were ≥75 years of age (79.6±3.4 years; 33% women) were identified. TT was prescribed in 55.9% of patients at discharge who had a higher thromboembolic risk (CHA2DS2VASc score: 4.23±1.51 vs 3.76±1.40, p = 0.007 and a higher bleeding risk (HAS-BLED ≥3: 88.6% vs 79.2%, p = 0.02) than those on DAPT. Therefore, patients on TT had a lower rate of thromboembolism than those on DAPT (0.6% vs 6.9%, p = 0.004; HR 0.08, 95% CI: 0.01–0.70, p = 0.004). Major bleeding events occurred more frequently in patients on TT than in those on DAPT (11.7% vs 2.4%, p = 0.002; HR 5.2, 95% CI: 1.53–17.57, p = 0.008). The overall mortality rate was similar in both treatment groups (11.9% vs 13.9%, p = 0.38); however, after adjustment for confounding variables, TT was associated with a reduced mortality rate (HR 0.33, 95% CI: 0.12–0.86, p = 0.02). Conclusions In elderly patients with AF undergoing PCI, the use of TT compared to DAPT was associated with reduced thromboembolism and mortality rates, although a higher rate of major bleeding.

Effects of Triple Therapy in Patients With Non-Valvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention Regarding Thromboembolic Risk Stratification

BACKGROUND The effects of dual antiplatelet therapy (DAPT) and triple therapy (TT: DAPT plus oral anticoagulation) in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) regarding to CHA2DS2-VASc score remain undefined.We compare the effect of TT vs. DAPT in this setting regarding the CHA2DS2-VASc score. METHODSANDRESULTS In a prospective multicenter registry, 585 patients (75.2% male, 73.2 ± 8.2 years) with AF undergoing PCI were followed up during 1 year. Of them, 157 (26.8%) had a CHA2DS2-VASc=1, and 428 (73.2%) had a CHA2DS2-VASc ≥2. TT was prescribed in 51.6% with CHA2DS2-VASc=1 and in 55.5% with CHA2DS2-VASc ≥ 2. Patients with CHA2DS2-VASc=1 receiving TT had a similar thromboembolism rate to those on DAPT (1.2% vs. 1.3%, P=0.73), but more total (19.5% vs. 6.9%, P=0.01) and a tendency to more major (4.9% vs. 0%, P=0.06) bleeding. However, patients with CHA2DS2-VASc ≥ 2 receiving TT had a lower thromboembolism rate (1.7% vs. 5.3%, P=0.03) and a trend towards more bleeds (21.8% vs. 15.6%, P=0.06), with an excess of major bleeding (8.4% vs. 3.1%, P=0.01). Rates of major adverse cardiac events (MACE) in both CHA2DS2-VASc subgroups were similar, irrespective of treatment. In a Cox multivariate analysis, TT was associated to major bleeding, but not with MACE. CONCLUSIONS In patients with AF and CHA2DS2-VASc=1 undergoing PCI, the use of TT involves a high risk of bleeding without a significant benefit in preventing thromboembolism.

Prognostic impact of tissue factor pathway on long-term ischemic events of ST-elevated myocardial infarction treated with a primary percutaneous coronary intervention.

pacing in Becker muscular dystrophy as assessed by tissue Doppler imaging. Heart Lung 2005;34:317–20. [10] Finsterer J, Bittner RE, Grimm M. Cardiac involvement in Beckers muscular dystrophy, necessitating heart transplantation, 6 years before apparent skeletal muscle involvement. Neuromuscul Disord 1999;9:598–600. [11] Wu RS, Gupta S, Brown RN, et al. Clinical outcomes after cardiac transplantation in muscular dystrophy patients. J Heart Lung Transplant 2010;29:432–8. [12] Finsterer J, Stollberger C, Meng G. Progressive respiratory insufficiency in the absence of cardiac disease in late-stage duchenne muscular dystrophy. Respir Care Mar 2013;58:e28–30.

Transient apical ballooning complicated with left ventricular thrombus and repeated embolic events with fatal outcome despite anticoagulant therapy

A 78 year-old woman without previous cardiac disease was trans-ferred to our center for suspected acute myocardial infarction. Shehad a historyof hypertension, dyslipidemia, bronchial hyperreactivityand depression and was receiving ACE inhibitors, beta-blockers,statins, bronchodilators and antidepressant drugs. She complainedof abdominal pain, constipation, and nausea that had started fourdays earlier and were associated to general discomfort and asthenia,without chest pain or dyspnea. A fecaloma was extracted at homeby her primary care nurse without relief. She was referred to theemergency room of her community hospital. Blood pressure was110/75 mm Hg, pulse was regular at 91/min, breathing rate 22/min,oxygen saturation 93% (on 26% oxygen), no abnormal cardiac orbreath sounds were heard, mild, diffuse abdominal tenderness wasnoted and the rectal ampule was empty. The ECG showed sinusrhythm, narrow QRS and ST elevation up to 2 mm in leads V1–V4without reciprocal changes and a chest radiograph was normal.Blood tests were remarkable for mild leukocytosis (10,500/μL), creat-inine 1.3 mg/dL and troponin T 0.39 ng/mL. Although she did notrefer ischemic symptoms, she was transferred to our hospital for ur-gent coronary angiography. This exam was normal and she was ad-mitted to the coronary unit. An echocardiogram immediately afteradmission showed a non-dilated left ventricle with apical dyskinesia,35% ejectionfraction and a mural thrombus (30×15 mm) attached toits septoapical wall (Fig. 1).Anticoagulationwithsubcutaneousenoxaparin(1 mg/kgbid),inad-dition to oral aspirin, enalapril and carvedilol was initiated. Forty-eighthours after admission, she acutely became stuporous and developedleft hemiparesis and dysarthria. A cranial CT-scan and supra-aorticdupplex ultrasound were normal and an embolic stroke was diag-nosed. A new echocardiogram showed improvement of apical con-tractile dysfunction, ejection fraction 43% and persisting ventricularthrombus, now protruding, lobulated and markedly mobile. Anti-Xafactor levels were monitored and were always within the therapeuticrange. The neurological status improved, although some residualmotor deficit persisted. The ECG evolved to normalization of theST-segmentanddevelopmentofnegativeT-wavesandanechocardio-gram on the 5th day showed mild apical hypokinesia, 55% ejectionfraction and persisting ventricular thrombus.Onthe 7thdayshecomplainedof abdominalpainaccompaniedbyprogressive abdominal distension and metabolic acidosis. An abdom-inal CT-scan exhibited a large thrombus at the trunk and branchesof the superior mesenteric artery (Fig. 2) with signs of severe and dif-fuse bowel ischemia. After discussing the management options withher family, comfort measures were adopted and the patient devel-oped progressive hypotension and died on the same day. The thoracic

Glycative and oxidative stress are associated with altered thrombus composition in diabetic patients with ST-elevation myocardial infarction

BACKGROUND The role of type 2 diabetes (T2DM) on composition of thrombus has not been fully characterized in patients with ST-elevation myocardial infarction (STEMI). AIMS To elucidate the differences between diabetic and non-diabetic patients with STEMI in relation to the composition of coronary thrombus, and the potential association of these differences with glycated haemoglobin levels and markers of oxidative stress. METHODS Intracoronary thrombi from consecutive thrombus aspiration procedures in STEMI patients, 25 diabetic and 28 non-diabetic, were analyzed by immunofluorescence with confocal microscopy. Plasma biomarkers (P-selectin, vWF, PAI-1, t-PA, D-dimer, TF pathway markers, plasmin and CD34+) were measured in peripheral blood, and the oxidative capacity of plasma as indirect measure of oxidative stress was measured in parallel. RESULTS Patients with T2DM had higher levels of fibrin (P=0.03), P-selectin (P=0.0001), PAI-1 (P=0.03) and vWF (P=0.006) in the thrombus and higher plasma TF activity (P=0.01) compared to non-diabetics. TF activity and plasmin correlated with HbA1C levels (R2=0.71, P=0.0001; R2=0.46, P=0.04, respectively) and TF was inversely correlated with TFPI (R2=-0.44, P=0.008) and tPA (R2=-0.48, P=0.003). Diabetic patients showed a higher oxidative response of plasma (26.47±6.88% vs 22.06±6.96% of oxidized lipids, P=0.04) (measured by H-NMR spectroscopy) that was associated to increased fibrin content into thrombus (R2=0.76, P=0.01). CONCLUSION Diabetic patients with STEMI display an increased thrombogenicity that results in a different thrombus composition respect to non-diabetic patients with STEMI. The increased thrombogenicity present in T2DM is related to higher glycoxidative stress, as quantified by HbA1C levels and oxidative response in plasma.

Giant Right Atrial Myxoma and Refractory Hypoxia: An Unexpected Combination

Myxoma is the most frequent cardiac tumor, representing 50% of cases, and is considered benign, although there have been some reports of associated cerebral or pulmonary emboli. We describe the case of a woman with right atrial myxoma with an unusual clinical presentation due to the location of the tumor, which posed a difficult diagnostic dilemma. This was a 57-year-old woman who was admitted from the emergency department with a 6-month history of progressive dyspnea with associated occasional episodes of palpitations, dizziness, and general malaise. The patient had hypertension, diabetes, and obesity, but no past cardiological history. On arrival, blood pressure was 115/73 mmHg, heart rate was 78 bpm, and oxygen saturation was 80% at rest on room air, which was recorded on various occasions. Arterial blood gases showed severe hypoxemia (pO2, 49 mmHg) with hypocapnia (pCO2, 24 mmHg). There were no signs of pulmonary edema, but there were signs of right heart failure in the form of jugular venous distension, hepatojugular reflux, hepatomegaly of 2 cm, and mild ankle edema. Auscultation revealed a systolic murmur and an early diastolic tumor ‘‘plop’’ at the left parasternal edge. Electrocardiography showed sinus rhythm and an S1Q3T3 pattern. Full blood count showed mild polycythemia (hemoglobin, 16.7 g/dL; hematocrit, 51.8%). On chest X-ray, there was a mild increase in right atrial volume with no pulmonary changes. The first suspected diagnosis was pulmonary thromboembolism. However, computed tomography with contrast showed no evidence of acute emboli but did show a large mass in the right atrium (Figures A-B). Transthoracic echocardiography confirmed the existence of a mass suggestive of myxoma, which was anchored to the interatrial septum and prolapsed through the tricuspid annulus, causing obstruction during diastole, with alternating severe tricuspid regurgitationstenosis (Figure C). Pulmonary artery pressures could not be assessed. The patient was admitted to the acute coronary care unit, where, in the first few hours, persistent dyspnea and severe desaturation were recorded, which worsened on sitting up despite administration of high-flow oxygen. Cardiac telemetry revealed atrial tachycardia alternating with periods of sinus bradycardia. The patient’s refractory hypoxemia, not fully explained by the obstruction from the right atrial myxoma or by pulmonary disease, led to suspicion of an intracardiac shunt. An echocardiogram was performed with administration of agitated saline, which held the key to the diagnosis. Bubbles were observed passing into the left atrium in the first 3 cardiac cycles through a patent foramen ovale with a significant right-toleft shunt (video in supplementary material). Rev Esp Cardiol. 2016;69(12):1219–1232