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Tissue factor deficiency causes cardiac fibrosis and left ventricular dysfunction.

Exposure of blood to tissue factor (TF) activates the extrinsic (TF:FVIIa) and intrinsic (FVIIIa:FIXa) pathways of coagulation. In this study, we found that mice expressing low levels of human TF ( approximately 1% of wild-type levels) in an mTF(-/-) background had significantly shorter lifespans than wild-type mice, in part, because of spontaneous fatal hemorrhages. All low-TF mice exhibited a selective heart defect that consisted of hemosiderin deposition and fibrosis. Direct intracardiac measurement demonstrated a 30% reduction (P < 0.001) in left ventricular function in 8-month-old low-TF mice compared with age-matched wild-type mice. Mice expressing low levels of murine FVII ( approximately 1% of wild-type levels) exhibited a similar pattern of hemosiderin deposition and fibrosis in their hearts. In contrast, FIX(-/-) mice, a model of hemophilia B, had normal hearts. Cardiac fibrosis in low-TF and low-FVII mice appears to be caused by hemorrhage from cardiac vessels due to impaired hemostasis. We propose that TF expression by cardiac myocytes provides a secondary hemostatic barrier to protect the heart from hemorrhage.

Animals↗

Determinants of severity of left ventricular dysfunction in Australian men and women with coronary disease aged 65 years or less.

BACKGROUND: The degree of left ventricular (LV) impairment is an important determinant of long term outcome in patients with coronary artery disease (CAD). AIM: We aimed to determine variables predictive of the severity of LV dysfunction in men and women aged 65 years or less with CAD, and to quantitate their contributions. METHODS: We documented atherogenic variables and extent of LV impairment and CAD severity at angiography in 521 consecutively studied men and women aged 65 years or less (381 males and 140 females). We assessed severity from an LV impairment score (Green Lane) and the ejection fraction. We related severity to quantitative and categorical variables which included the severity of angina (no angina, stable and unstable angina). RESULTS: The LV impairment score correlated closely (negatively) with the ejection fraction (r = -0.783, p = 0.0001). There were eight variables independently predictive of the severity of LV impairment assessed by the LV score. The variables in descending order of relative importance in predicting the LV scores were past history of myocardial infarction (MI), number of significantly diseased vessels (> 50% luminal obstruction), life-time smoking dose, log-triglycerides, total cholesterol to HDL-C ratio, hypertension, age and Body Mass Index (BMI). They were all positive relationships. Together they correctly classified the LV scores of 52.6% of the patients. Gender was not an independent contributor to the LV score when other variables were controlled. When the contributions to the variance in LV scores of past history of MI (15.4%) and number of significantly diseased vessels (2.6%) were controlled, life-time smoking dose independently explained 2.1% (p < 0.01) of the variance. The LV impairment score was 55% higher in heavy smokers than in non-smokers (p = 0.01). When we compared patients with stable and unstable angina, LV scores are higher and ejection fraction lower in the unstable angina patients consistent with them having a greater degree of LV dysfunction. CONCLUSION: We conclude that variables other than a history of MI and CAD severity contribute significantly to the variance of the degree in LV impairment in CAD patients among which the life-time smoking dose, triglycerides, TC/HDL-C, hypertension and increased BMI are all relevant to prevention, and that patients with unstable vs stable angina usually have more impaired LV function.

Adult↗

Effects of exercise on plasma level of brain natriuretic peptide in congestive heart failure with and without left ventricular dysfunction.

This study was designed to determine whether plasma brain natriuretic peptide (BNP) increases in response to exercise in patients with congestive heart failure and to show what kind of hemodynamic abnormalities induce increased secretion of BNP during exercise. Plasma levels of atrial natriuretic peptide (ANP) and BNP and hemodynamic parameters were measured during upright bicycle exercise tests in seven patients with dilated cardiomyopathy and nine with mitral stenosis. At rest, there were no intergroup differences in cardiac output or pulmonary capillary wedge pressure; however, the group with dilated cardiomyopathy had higher left ventricular end-diastolic pressures and lower left ventricular ejection fractions than did the group with mitral stenosis. Plasma ANP levels were comparable between the dilated cardiomyopathy group (170 +/- 77 [SE] pg/ml) and the mitral stenosis group (106 +/- 33 pg/ml) (p, not significant), whereas BNP was significantly higher in the dilated cardiomyopathy group (221 +/- 80 pg/ml) than in the other group (37 +/- 10 pg/ml) (p < 0.05). The plasma concentration of BNP but not of ANP significantly correlated with left ventricular end-diastolic pressure and volume. Exercise increased plasma ANP and BNP in the two groups. The dilated cardiomyopathy group had a larger increment in BNP (+157 +/- 79 pg/ml) than did the mitral stenosis group (+17 +/- 5 pg/ml) (p < 0.05), although the increase in pulmonary capillary wedge pressure was greater in the mitral stenosis group. Thus exercise increases plasma levels of BNP, and impaired left ventricular function may be a main factor in the greater increment in BNP during exercise in patients with congestive heart failure.

Atrial Natriuretic Factor↗

Cardiac resynchronization therapy in patients with systolic left ventricular dysfunction and symptoms of mild heart failure secondary to ischemic or nonischemic cardiomyopathy.

Cardiac resynchronization therapy (CRT) is beneficial in selected patients with moderate to severe heart failure (New York Heart Association [NYHA] classes III to IV). Patients with mildly symptomatic heart failure (NYHA class II) are currently not eligible for CRT and the potential beneficial effects in these patients have not been well studied. Fifty consecutive patients in NYHA class II heart failure and 50 consecutive patients in NYHA classes III to IV (control group) were prospectively included. All patients had left ventricular (LV) ejection fraction 120 ms. The effects of CRT in NYHA class II patients were compared with the results obtained in both groups. The severity of baseline LV dyssynchrony (assessed with color-coded tissue Doppler imaging) was comparable between patients in NYHA class II versus those in NYHA classes III to IV (83+/-49 vs 96+/-51 ms, p=NS); resynchronization was achieved in all patients. NYHA class II patients showed a significant improvement in LV ejection fraction (from 25+/-7% to 33+/-10%, p<0.001) and reduction in LV end-systolic volume (from 168+/-55 to 132+/-51 ml, p<0.001) after CRT, similar to patients in NYHA classes III to IV. In addition, only 8% of NYHA class II patients had progression of heart failure symptoms. In conclusion, CRT had comparable effects in patients in NYHA class II and in NYHA classes III to IV heart failure in terms of LV resynchronization, improvement in LV ejection fraction, and LV reverse remodeling.

Aged↗

Early experience with Levosimendan in children with ventricular dysfunction.

OBJECTIVE: To describe our preliminary experience with Levosimendan, a new calcium-sensitizing agent in critically unwell infants and children with severe heart failure. DESIGN: Retrospective cohort analysis. SETTING: Pediatric intensive care unit. PATIENTS: Fifteen children aged 7 days to 18 yrs (median age 38 months) with severe myocardial dysfunction secondary to end-stage heart failure, or acute heart failure, who were inotrope-dependent (requiring at least one catecholamine). INTERVENTIONS: A single dose (bolus and intravenous infusion over 24-48 hrs) of Levosimendan was given under continuous hemodynamic monitoring in our intensive care unit. Eleven children received a single dose, three children received two doses, and one child received four doses. Echocardiographic assessments of ventricular function were made before and 3-5 days after Levosimendan infusion. MEASUREMENTS AND MAIN RESULTS: Heart rate, systolic pressure, diastolic pressure, mean blood pressure, and central venous pressure were unchanged during and after Levosimendan. Levosimendan allowed for discontinuation of catecholamines in ten patients and a dose reduction in three. The dose of dobutamine was reduced from 6.4 microg/kg/min pre-Levosimendan to 1.8 microg/kg/min on day 5 (p < .01). Ejection fraction for the group as a whole improved from 29.8% to 40.5% (p = .015); this did not increase significantly in patients with end-stage heart failure but increased by 63% in the children with acute heart failure. CONCLUSIONS: Levosimendan can be safely administered to infants and children with severe heart failure. Levosimendan allowed for substantial reduction in catecholamine infusions in children with end-stage or acute heart failure and also produced an objective improvement in myocardial performance in children with acute heart failure.

Adolescent↗

Troponin I concentrations following primary percutaneous coronary intervention predict large infarct size and left ventricular dysfunction in patients with ST-segment elevation acute myocardial infarction.

The aim of this study was to investigate the ability of troponin I (cTnI) levels to predict myocardial infarction size in patients with ST-segment elevation acute myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). In 87 patients with STEMI undergoing primary PCI, serial plasma concentrations of cTnI and alpha-hydroxybutyrate deshydrogenase (HBDH) were measured before PCI and over the following 72 h. Enzymatic infarct size was estimated by the cumulative release of HBDH during the 72 h following PCI (QHBDH72). Delayed radionuclide left ventricular ejection fraction (LVEF) was measured in 63 patients. While cTnI concentrations at admission did not correlate with QHBDH72 or with LVEF, from the 3rd to the 72nd h following PCI, they did correlated with QHBDH72 (P<0.001; R: 0.76-0.86) and with LVEF (P<0.001; R: -0.42 to -0.50). Receiver-operator characteristic (ROC) curve analysis showed that admission concentrations of cTnI could not predict either a large infarct size (i.e., QHBDH72>10 g-eq l(-1)) or a low LVEF (i.e., LVEF<40%). However, 6 h and up until 72 h after PTCA, cTnI concentrations were predictive of large enzymatic infarct size (sensitivity: 91 and 95%, specificity: 90 and 87%, respectively) and of LVEF under 40% (sensitivity: 75 and 77%, specificity: 90 and 78%, respectively). Thus, our study suggests that in contrast with admission cTnI concentration, cTnI levels following primary PCI represent a reliable tool for predicting large enzymatic infarct size and may help in selecting patients with a high risk of low LVEF at 1 month.

Aged↗

Tachycardia-related cardiomyopathy: a common cause of ventricular dysfunction in patients with atrial fibrillation referred for atrioventricular ablation.

OBJECTIVE: To determine the frequency of tachycardia-related cardiomyopathy in patients with atrial fibrillation and systolic dysfunction referred for atrioventricular node ablation. PATIENTS AND METHODS: This prospective multicenter cohort study was conducted at 16 tertiary care centers. The ejection fraction was measured before and 3 and 12 months after atrioventricular node ablation. Patients with reduced systolic function (ejection fraction < or = 45%) before atrioventricular ablation were included in this study. Patients whose ejection fraction increased by at least 15 percentage points and to higher than 45% were considered to have tachycardia-related cardiomyopathy. RESULTS: Of 63 patients with systolic dysfunction, 48 had at least 1 adequate follow-up echocardiographic study. Sixteen (25%) of the 63 had marked improvement in the ejection fraction (mean +/- SD change, 27 +/- 8 percentage points) to a value higher than 45% after ablation. CONCLUSIONS: Tachycardia-related cardiomyopathy is common in patients with atrial fibrillation and systolic dysfunction referred for atrioventricular node ablation. This diagnosis should be considered in all patients in whom systolic dysfunction occurs subsequent to or concomitant with onset of atrial fibrillation.

Atrial Fibrillation↗

Implantable cardioverter-defibrillator placement in patients with mild-to- moderate left ventricular dysfunction: hemodynamics and recovery profile with two different anesthetics used during deep sedation.

OBJECTIVE: To compare the effects of thiopental and propofol during defibrillation threshold testing (DFT) on hemodynamics and recovery profile in patients requiring automatic internal cardioverter-defibrilator placement. DESIGN: Prospective clinical investigation. SETTING: University hospital. PARTICIPANTS: Thirty-four adult patients. INTERVENTIONS: After administration of midazolam, 0.025 mg/kg, and fentanyl, 0.5 to 1 mug/kg, surgery was performed under topical infiltration with 1% lidocaine. In group I (GI) (n = 17), patients received thiopental by slow injection and patients in group II (GII) (n = 17) received propofol before induction of ventricular fibrillation (VF). MEASUREMENTS AND MAIN RESULTS: Patients received 4.1 +/- 1.4 mg of midazolam, 114 +/- 34 mug of fentanyl, and 280 +/- 78 mg of thiopental in GI; and 4.6 +/- 1.7 mg of midazolam, 119 +/- 62 mug of fentanyl, and 147 +/- 40 mg of propofol in GII (p > 0.05). Hemodynamics did not show significant differences between the groups at any recording time. Average time needed to regain the pretest sedation level was 16.4 +/- 8.8 minutes in GI and 10.9 +/- 5.5 minutes in GII (p = 0.03). Time required to achieve a score of 10 using a modified Aldrete score was 26.4 +/- 9.3 minutes in GI and 17.4 +/- 4.9 in GII (p = 0.001). Seven patients in GII (41%) and 1 patient in GI (6%) became hypotensive after DFT (p = 0.04). CONCLUSIONS: Deepening the sedation level by slow injection of thiopental or propofol before DFT provided satisfactory conditions during brief episodes of VF. Delay in recovery of arterial pressure after DFT with propofol and delay in arousal and discharge of patients with thiopental are major disadvantages of the regimens.

Adrenergic beta-Agonists↗

Fructose 1,6-diphosphate administration attenuates post-ischemic ventricular dysfunction.

BACKGROUND: Cardiomyocyte energy production during ischemia depends upon anaerobic glycolysis inefficiently yielding two ATP per glucose. Substrate augmentation with fructose 1,6-diphosphate (FDP) bypasses the ATP consuming steps of glucokinase and phosphofructokinase thus yielding four ATP per FDP. This study evaluated the impact of FDP administration on myocardial function after acute ischemia. METHODS: Male Wistar rats, 250-300 g, underwent 30 min occlusion of the left anterior descending coronary artery followed by 30 min reperfusion. Immediately prior to both ischemia and reperfusion, animals received an intravenous bolus of FDP or saline control. After 30 min reperfusion, myocardial function was evaluated with a left ventricular intracavitary pressure/volume conductance microcatheter. For bioenergetics studies, myocardium was isolated at 5 min of ischemia and assayed for ATP levels. RESULTS: Compared to controls (n=8), FDP animals (n=8) demonstrated significantly improved maximal left ventricular pressure (100.5+/-5.4 mmHg versus 69.1+/-1.9 mmHg; p<0.0005), dP/dt (5296+/-531 mmHg/s versus 2940+/-175 mmHg/s; p<0.0028), ejection fraction (29.1+/-1.7% versus 20.4+/-1.4%; p<0.0017), and preload adjusted maximal power (59.3+/-5.0 mW/microL(2) versus 44.4+/-4.6 mW/microL(2); p<0.0477). Additionally, significantly enhanced ATP levels were observed in FDP animals (n=5) compared to controls (n=5) (535+/-156 nmol/g ischemic tissue versus 160+/-9.0 nmol/g ischemic tissue; p<0.0369). CONCLUSIONS: The administration of the glycolytic intermediate, FDP, by intravenous injection, resulted in significantly improved myocardial function after ischemia and improved bioenergetics during ischemia.

Adenosine Triphosphate↗

Relationship between radionuclide right ventricular ejection fraction and clinical status in patients with left ventricular dysfunction after myocardial infarction.

OBJECTIVE: To evaluate the influence of right ventricular (RV) function, determined by RV ejection fraction, on the clinical status of patients with ischemic heart disease and left ventricular (LV) EF under 40%. BACKGROUND: The role of RV function as a marker of prognosis in heart failure has been debated. We hypothesized that the degree of RV dysfunction is a determinant of the clinical status and outcome of patients with LV dysfunction after myocardial infarction. PATIENTS AND METHODS: 30 patients, 25 male, with previous myocardial infarction, more than 6 months age, were studied by equilibrium radionuclide angiography. Functional capacity was evaluated by cardiopulmonary exercise test with Naughton protocol. Patients were followed during a 12 month period for major clinical events: death or hospitalisation for congestive heart failure. Two groups of patients were considered according the value of RVEF (< or = 30% and > 30%). RESULTS: The values of EF were: LV = 25 +/- 7% and RV = 35 +/- 9%. Maximum oxygen consumption correlated with RVEF (r = 0.78, p < 0.001) but not with LVEF (r = 0.12, NS). The group of patients with RVEF > 30% had a greater exercise time (712 +/- 229 versus 441 +/- 208 seconds, p = 0.003), higher oxygen consumption (19.8 +/- 5.3 versus 13.5 +/- 3.3 ml/kg/min, p = 0.001) and oxygen consumption in relation to the maximum predicted for age and sex (71 +/- 19 versus 50 +/- 13%, p = 0.002). Cumulative frequency of major clinical events was greater in the group with RVEF < or = 30% (58% vs 6%, relative risk 3.14, 95% CI 1.23 to 5.05). There was no correlation between the values of LVEF and outcome. CONCLUSIONS: In this setting of ischemic LV dysfunction, the RVEF correlates with functional capacity in cardio-pulmonary exercise test and the presence of RV dysfunction is associated to a higher incidence of clinical events.

Adult↗

Non-invasive measurement of cardiac output by whole-body bio-impedance during dobutamine stress echocardiography: clinical implications in patients with left ventricular dysfunction and ischaemia.

OBJECTIVES: To compare non-invasive determination of cardiac index (CI) by whole body electrical bioimpedance using the NICaS apparatus and Doppler echocardiography, and the role of cardiac power index (Cpi) and total peripheral resistance index (TPRi) calculation during dobutamine stress echocardiography (DSE). SUBJECTS AND METHODS: We enrolled 60 consecutive patients undergoing DSE. Patients were prospectively divided into 3 groups: Group 1 (n = 20): normal DSE (control). Group 2 (n = 20): EF<40% without significant ischaemia. Group 3 (n = 20): patients with significant ischaemia on DSE. Measurements of CI were performed at the end of each stage of DSE by both echocardiographic left ventricular outflow track flow and the NICaS apparatus, using whole-body bio-impedance. MAP was measured simultaneously and TPRi and Cpi were calculated. RESULTS: The correlation between non-invasive CI as determined by NICaS and echocardiography was 0.81, although Echocardiographic readings of CI were higher during administration of higher doses of dobutamine. Lower EF correlated with lower Cpi, especially stress induced Cpi. Hence, patients with reduced EF (group 2) had a blunted increase in Cpi during stress. Patients with ischaemia (group 3) had a blunted increase in Cpi as well as a decrease in Cpi and increase in TPRi during the last stages of DSE. CONCLUSION: Measurement of CI by NICaS correlated well with Doppler derived CI. The calculation of Cpi and TPRi changes during dobutamine stress may provide important clinical information.

Cardiac Output↗

Management of perioperative ventricular dysfunction.

With the recognition of the clinical importance of the right ventricle; the development of new techniques for the perioperative evaluation of RV function, particularly transesophageal echocardiography; and new treatment modalities (pharmacologic and mechanical), clinicians will be able to more accurately diagnose and precisely manage patients who have sustained RV injury.

Assisted Circulation↗

[Heart tomography with 99mTc sestamibi and echocardiography with dobutamine in the identification of reversible left ventricular dysfunction in patients with acute myocardial infarction].

INTRODUCTION: We investigated the role of technetium-99m (99mTc) sestamibi cardiac imaging and dobutamine echocardiography in detecting myocardial viability early after acute myocardial infarction. MATERIAL AND METHODS: Nineteen patients (mean age 52 +/- 10 years) underwent coronary angiography, low-dose dobutamine echocardiography and rest 99mTc sestamibi imaging within 10 days of myocardial infarction. All patients were revascularized. Resting echocardiogram was repeated 8 months later to evaluate segmental functional recovery. RESULTS: Sixty-one of 108 akinetic or dyskinetic segments at baseline showed functional recovery after revascularization. Sensitivity in predicting segmental functional recovery was 87% for sestamibi imaging and 66% for dobutamine echocardiography (p < 0.001), while specificity and accuracy were comparable. Sestamibi activity was the strongest predictor of segmental functional recovery (p < 0.001). CONCLUSIONS: Dobutamine echocardiography predicts functional recovery after myocardial infarction. However, sestamibi imaging is useful to identify patients with dysfunctional segments without contractile reserve which may benefit by revascularization.

Cardiotonic Agents↗

[The intracardiac laser irradiation of the blood in correcting left ventricular dysfunction in progressive stenocardia].

The authors studied the effect of intracardiac irradiation of blood with a low intensity Helium-Neon laser on the pumping function of left ventricle in 73 patients with progressive angina pectoris. 47 patients underwent a course of laser hemotherapy while being given medicamentous therapy, the remaining 26 received nitrates, calcium antagonists and analgesics. Employment of laser light irradiation was associated with more satisfactory clinical effect than that in patients who had not had the procedure. It has also been established that intracardiac laser light irradiation of blood makes for the improvement of the characteristics of the intracardiac haemodynamics by diminishing the volumes and augmenting the left ventricular (LV) ejection fraction. Beneficial effect of laser hemotherapy on the intracardiac haemodynamics characteristics results from the stabilizing influence the method exerts on LV regional contractility and appear to be associated with its anti-ischemic effect.

Angina Pectoris↗