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Background The effectiveness trial “Stress echo (SE) 2020” evaluates novel applications of SE in and beyond coronary artery disease. The core protocol also includes 4-site simplified scan of B-lines by lung ultrasound, useful to assess pulmonary congestion. Purpose To provide web-based upstream quality control and harmonization of B-lines reading criteria. Methods 60 readers (all previously accredited for regional wall motion, 53 B-lines naive) from 52 centers of 16 countries of SE 2020 network read a set of 20 lung ultrasound video-clips selected by the Pisa lab serving as reference standard, after taking an obligatory web-based learning 2-h module ( http://se2020.altervista.org ). Each test clip was scored for B-lines from 0 (black lung, A-lines, no B-lines) to 10 (white lung, coalescing B-lines). The diagnostic gold standard was the concordant assessment of two experienced readers of the Pisa lab. The answer of the reader was considered correct if concordant with reference standard reading ±1 (for instance, reference standard reading of 5 B-lines; correct answer 4, 5, or 6). The a priori determined pass threshold was 18/20 (≥ 90%) with R value (intra-class correlation coefficient) between reference standard and recruiting center) > 0.90. Inter-observer agreement was assessed with intra-class correlation coefficient statistics. Results All 60 readers were successfully accredited: 26 (43%) on first, 24 (40%) on second, and 10 (17%) on third attempt. The average diagnostic accuracy of the 60 accredited readers was 95%, with R value of 0.95 compared to reference standard reading. The 53 B-lines naive scored similarly to the 7 B-lines expert on first attempt (90 versus 95%, p = NS). Compared to the step-1 of quality control for regional wall motion abnormalities, the mean reading time per attempt was shorter (17 ± 3 vs 29 ± 12 min, p

Twenty-two patients with coronary artery disease were studied first by radionuclide angiography (RNA) and then by contrast ventriculography. Cardiac medications were discontinued at least 72 hr before study. The patients were studied during atrial pacing at heart rates close to their spontaneous sinus rhythm. Contrast ventriculography was performed at 50 frames/sec in the 30 degrees right anterior oblique projection using 40 ml of a nonionic contrast medium (iopamidol) at a flow rate of 10-12 ml/sec. The contours of the left ventricular silhouette at contrast ventriculography were traced, frame by frame, on a graphic table with a digitizing penlight. Equilibrium 99mTc RNA was performed in the best septal 45 degrees left anterior oblique projection, acquiring 150,000 cts/frame, at 50 frames/sec and with a 5% gate tolerance. Time-activity curves from both end-diastolic and end-systolic ROIs were built and interpolated. Both RNA and contrast ventriculography volume curves were filtered with Fourier five harmonics. A close relationship was found between RNA and contrast ventriculography measurements of peak filling rate normalized to end-diastolic cps (r = 0.87, p less than 0.001) and stroke count (r = 0.87, p less than 0.001), ejection fraction (r = 0.94, p less than 0.001). Thus, in patients with coronary artery disease, LV filling can be accurately assessed using RNA.

The effectiveness and tolerability of nitrendipine (Bay e 5009) and atenolol in the treatment of mild or moderate arterial hypertension in monotherapy and in association were evaluated in a randomized double-blind study. The drugs were administered once daily at the dose of 20 mg for nitrendipine and 100 mg for atenolol. The trial consisted in two phases of monotherapy and of a combined regimen phase, whose sequence was randomly established; tablets were administered according to a double-dummy design. The results were evaluated according to the criteria of the Hypertension Detection and Follow-up Program Cooperative Group. 5/20 patients were considered "responders" after atenolol treatment, 4/20 after nitrendipine alone, and 14/20 after combined therapy. Side effects resulted mild in severity, and their incidence was lower during the association phase. The combination of atenolol and nitrendipine appears to improve the effectiveness and acceptability of both drugs.

We report a case of moderate thrombocytopenia associated with purpura-like phenomenon (four ecchymoses) that occurred within 72 hours of clopidogrel initiation and resolved promptly with drug withdrawal. This 61-year-old patient previously experienced an adverse skin reaction to ticlopidine without changes in the platelet count and without any other laboratory abnormalities. Since the introduction of clopidogrel instead of ticlopidine for the prevention or treatment of several cardiovascular diseases, only 11 cases of thrombotic thrombocytopenic purpura among more than 3 million individuals treated with clopidogrel have been reported. Recently, a case of severe thrombocytopenia, without concomitant purpura-like lesions, during therapy with clopidogrel has been described. To our knowledge, this is the first case of thrombocytopenia associated with purpura-like lesions with no evidence of thrombotic thrombocytopenic purpura during clopidogrel treatment.

The article describes the main legal challenges for regulating the sharing (or collaborative) economy in Europe and explains how the existing body of EU law applies to these new business models. In the last part, it makes a few brief comments on the need for future regulation.

BACKGROUND: The factors that influence infarct expansion early after myocardial infarction have been identified; however, there is less information about late-phase left ventricular enlargement. This study was designed to identify the clinical, haemodynamic, echocardiographic, and radionuclide angiographic criteria that predict the progress of left ventricular dilation after discharge for a first-anterior myocardial infarction. METHODS: Sixty-seven patients with first Q-wave acute anterior myocardial infarction not treated with thrombolytic agents underwent baseline echocardiographic, haemodynamic, and radionuclide angiographic evaluation 4-7 days after the onset of symptoms. The echocardiographic and radionuclide evaluations were repeated after 1 year in the 55 patients who completed the follow-up. By multivariate stepwise linear regression analysis, left ventricular end-diastolic volume after 1 year and change from baseline were modelled as a function of baseline left ventricular end-diastolic volume and other potential predictors. RESULTS: A model including left ventricular end-diastolic pressure, global wall motion score, baseline left ventricular end-diastolic volume, and a Thrombolysis in Myocardial Infarction (TIMI) score of 0-1 was able to predict 84% of the left ventricular end-diastolic volume at the follow-up; a TIMI score of 0-1, the transverse end-diastolic diameter, global wall motion score, and the number of coronary vessels with 70% stenosis accounted for 81% of the variation in left ventricular end-diastolic volume from baseline, while the transverse end-diastolic diameter was inversely related to this parameter. CONCLUSIONS: The results of this study demonstrate that after an anterior myocardial infarction, the patency of the infarct-related artery is the major determinant of late left ventricular dilation, while left ventricular end-diastolic pressure influences early left ventricular dilation and baseline end-diastolic volume. Therefore, to improve left ventricular remodelling, it appears necessary to increase the patency of the infarct-related artery and improve the diastolic loading of the left ventricle at an early stage in the infarction. The inverse relationship between baseline left ventricular transverse diameter and the change in left ventricular volume after discharge indicates that the higher the baseline left ventricular volume, the less it changed during the follow-up. The global wall motion score appears to be a non-invasive parameter that is useful for identifying patients with a high risk of progressive left ventricular dilation.

Objectives. This study was designed to increase asynchrony with sequential atrioventricular (AV) pacing and to study its effects on left ventricular isovolumetric relaxation, rapid filling and stiffness. Background. Left ventricular nonuniformity is a major determinant of diastolic function. Methods. Thirteen patients with coronary artery disease were studied by simultaneous equilibrium radionuclide angiography and cardiac catheterization during atrial and AV pacing. Ejection fraction and peak filling rate were measured by radionuclide angiography. Regional analysis was obtained by analyzing time-activity curves of four left ventricular sectors; systolic and diastolic asynchrony were evaluated as the coefficient of variation of time to end-systole and, respectively, time to peak filling rate in the four sectors. Cardiac index and left ventricular pressure were measured with high fidelity catheters at cardiac catheterization. The time constant of isovolumetric relaxation was derived from left ventricular pressure. Pressure-volume loops were assembled and constants of chamber stiffness were computed. Results. Atrioventricular pacing led to a decrease in cardiac index (3.7 ± 0.9 to 3.3 ± 0.8 liters/min per m2, p = 0.01) and peak filling rate (352 ± 125 to 287 ± 141 ml/s, p = 0.03; 2.4 ± 0.8 to 2.0 ± 0.8 end-diastolic counts/s, p = 0.02; 4 ± 1.3 to 3.2 ± 1.0 stroke counts/s, p = 0.008). The time constant of isovolumetric relaxation increased (57 ± 10 to 64 ± 12 ms, p = 0.04) and the global diastolic pressure-volume relation shifted upward. Conclusions. Atrioventricular pacing induces left ventricular asynchrony, which is associated with a slower rate of isovolumetric relaxation. The isovolumetric relaxation lasts after the filling phase has begun, thereby reducing the rate of rapid filling.

This study assesses whether administration of recombinant tissue-type plasminogen activator (rt-PA) up to 8 hours after onset of symptoms of acute myocardial infarction (AMI) may result in a significant improvement in left ventricular function. Sixty patients were classified into 3 groups: group A (n = 21) received rt-PA within 4 hours from symptom onset; the remaining 39 patients, admitted between 4 and 8 hours, were randomized into 2 groups--group B (n = 19) received rt-PA, and group C (n = 21) was treated with conventional therapy. Coronary and left ventricular angiograms were recorded 8 to 10 days after rt-PA administration. The patency rate of the infarct-related artery was 76% in group A, and 63 and 35% in group B and C, respectively. The Thrombolysis in Myocardial Infarction trial perfusion grade was higher in group A and B than in group C (A vs C: p less than 0.005; B vs C: p less than 0.01). Left ventricular ejection fraction was significantly higher in group A (60.2 +/- 10%) and B (54.7 +/- 12%) compared with group C (44.2 +/- 12%) (A vs C: p less than 0.01; B vs C: p less than 0.05). Regional wall motion of the entire ischemic zone was better in group A and B than in group C (A vs C: p less than 0.001; B vs C: p less than 0.01). In contrast, the kinesis of the central ischemic zone was significantly better in group A than in both group B and C (A vs B: p less than 0.05; A vs C: p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate the effects of late thrombolysis on left ventricular volume and function in acute myocardial infarction, two-dimensional echocardiography and radionuclide angiography were performed before discharge and after 1 year of follow-up study in 34 patients with acute anterior myocardial infarction. Of these, 10 admitted to the coronary care unit within 4 h from the onset of symptoms were treated with recombinant tissue-type plasminogen activator (rt-PA) (Group A) and 24 admitted between 4 and 8 h after onset were randomly assigned to receive either rt-PA (Group B, n = 12) or conventional therapy (Group C, n = 12). Seven to 10 days after admission, all patients underwent cardiac catheterization and coronary angiography. Patency of the infarct-related vessel was 70% in Group A, 66% in Group B and 33% in Group C and the average Thrombolysis in Myocardial Infarction (TIMI) coronary perfusion grade was 1.9 +/- 0.8 for Group A, 1.6 +/- 1.0 for Group B and 0.84 +/- 0.95 for Group C (Group A versus Group C p less than 0.01; Group B versus Group C p less than 0.05). At predischarge evaluation, mean left ventricular end-systolic and end-diastolic volumes were higher in Group C than in Group B (p less than 0.001 and 0.05, respectively) and Group A (p less than 0.005 for both); mean left ventricular ejection fraction at rest was lower in Group C than in Group B and Group A (p less than 0.05 for both). At 1 year follow-up study, end-systolic and end-diastolic volumes remained higher in Group C than in Group B (p less than 0.05 for both) and Group A (p less than 0.005 for end-systolic volume and p less than 0.001 for end-diastolic volume); ejection fraction at rest was lower in Group C than in Groups A and B (p less than 0.05 for both); during exercise, it increased more in Group A than in Group C (p less than 0.01). Comparison of data obtained before discharge and at the 1 year follow-up study revealed a significant differences in end-systolic volume (p less than 0.05) in Group C patients and in end-diastolic volume in patients in Groups B (p less than 0.05) and C (p less than 0.001). The beneficial effect of late thrombolysis with rt-PA may be related to a reduction in myocardial expansion and thus to a favorable influence on postinfarction left ventricular remodeling.

Background. Abnormal blood-pressure response during exercise occurs in about one third of patients with hypertrophic cardiomyopathy (HCM), and it has been associated with a high risk of sudden cardiac death. We assessed the hemodynamics of exercise in HCM patients with abnormal blood-pressure response by using ambulatory radionuclide monitoring (VEST) of left-ventricular (LV) function, and exercise tolerance by oxygen consumption. Methods. Twenty-two HCM patients uderwent treadmill exercise during VEST monitoring. A cardiopulmonary exercise test was performed a few days after. The VEST data were averaged for I minute. Stroke volume, cardiac output, and systemic vascular resistance were expressed as percent of baseline. Exercise tolerance was assessed as maximal oxygen consumption. Results. In eight HCM patients (36%) with an abnormal blood-pressure response, end-systolic volume increased more (52% +/- 21% vs 31% +/- 28%, P = .012), and the ejection fraction (-31% +/- 17% vs -14% +/- 22%, P = .029) and stroke volume (-21% +/- 21% vs 3% +/- 28%, P = .026) fell more, than in patients with normal response. Cardiac output increased less in the former patients (49% +/- 44% vs 94% +/- 44%, P = .012). Systemic vascular resistance decreased similarly, irrespective of blood-pressure response (-28% +/- 26% vs -34% +/- 26%, P = N.S.). Percent of maximal predicted oxygen consumption was lower in HCM patients with an abnormal blood-pressure response (63% +/- 11% vs 78% +/- 15%, P = .025). Conclusions. In HCM patients, abnormal blood-pressure response was associated with exercise-induced LV systolic dysfunction and impairment in oxygen consumption. This may cause hemodynamic instability, associated with a high risk of sudden cardiac death.

1 ABSTRACT: Background. Hypertrophic cardiomyopathy (HCM) is characterized by asymmetric LV hypertrophy (LVH) and impairment in diastolic function. We assess the relationship between LVH and invasive indexes of diastolic function. Methods. 21 HCM patients underwent cardiac catheterization to assess pulmonary capillary wedge pressure, LV end-diastolic pressure (measured by microtip catheters), and LV volumes (calculated by simultaneous radionuclide angiography). We calculated from LV pressure the time constant of isovolumetric relaxation (τ, variable asymptote method, ms), and from LV pressure and volume the constant of chamber stiffness (k, ml -1 ). LVH was assessed by different indexes: maximal wall thickness, number of hypertrophied LV segments, LVH index, and Wigle's score. Results. Wigle's score was directly related to pulmonary capillary Wedge pressure (r=0.436, p=0.048), peak V wave of pulmonary capillary wedge pressure (r=0.503, p=0.024), LV end-dias- tolic pressure (r=0.643, p=0.002) and k (r=0.564, p=0.015). HCM patients were divided into 2 groups according to Wigle's score: 10 with mild or moderate LVH (< 8), and 11 with severe LVH (≥ 8). HCM patients with severe LVH showed a higher pulmonary capillary Wedge pressure (15.1±7.2 vs 9.5±2.4, p=0.033), peak V wave of pulmonary capillary wedge pressure (20.7±4.6 vs 14.6±4.9, p=0.011), LV end-diastolic pressure (23.9±10.9 vs 10.6±2.5, p=0.002), k (0.0465±0.032 vs 0.015±0.007, p=0.022) and LV outflow tract gradient (72±36 mmHg vs 29±30 mmHg, p=0.01). τ was similar in the two groups. Other indexes of LVH were not related to dias- tolic function. Conclusions. Wigle's score is the only index of LVH that relates to invasive indices of diastolic function. (Heart International 2006; 2: 106-14)

Objectives. The aim of this study was to assess whether prostaglandin endoperoxides, which continue to be formed in the setting of thromboxane A2 synthase inhibition, might influence the fate of ischemic myocardium in a model of coronary occlusion and reperfusion. Background. It was recently demonstrated that thromboxane A2 synthase inhibitors reduce ischemic myocardial injury through a redirection of prostaglandin (PG) endoperoxides toward the synthesis of ''cardioprotective'' prostaglandins, such as PGI2, PGE2 and PGD2. However, part of these prostaglandin endoperoxides may also stimulate a receptor, shared with thromboxane A2, mediating platelet aggregation and vasoconstriction. Methods. New Zealand White rabbits were subjected to 30 min of coronary occlusion, followed by 5.5 h of reperfusion. Fifteen minutes before reperfusion, the animals were randomized to receive 1) saline solution (control animals, n = 8); 2) SQ 29548, a potent and selective thromboxane A2/PGH2 receptor antagonist (n = 8); 3) dazoxiben, a selective thromboxane A2 synthase inhibitor (n = 8); 4) R 68070 (Ridogrel), a drug with dual thromboxane A2 synthase-inhibiting and thromboxane A2/PGH2 receptor-blocking properties (n = 8); or 5) aspirin + R 68070 (n = 8). Results. Dazoxiben and R 68070, but not SQ 29548, significantly reduced thromboxane B2 formation and increased plasma levels of 6-keto-PGF1alpha, PGE2 and PGF2alpha. Ex vivo platelet aggregation induced by U46619 (a thromboxane A2 mimetic) Was inhibited by SQ 29548 and R 68070 but not by dazoxiben. In control animals, infarct size determined at the end of the experiment by triphenyltetrazolium chloride staining averaged 57.7 +/-3.2% of the area at risk of infarction. The administration of SQ 29548 did not significantly reduce infarct size compared with that in control animals, whereas dazoxiben and R 68070 significantly reduced infarct size to 36.7 +/- 2.8% and 16.6 +/- 3.6% of area at risk of infarction, respectively (p < 0.001 vs. control values). In rabbits treated with R 68070, infarct size was also significantly smaller than that of dazoxiben-treated rabbits (p < 0.01). This protective effect of R 68070 was completely abolished when the drug was administered with aspirin, infarct size in this group averaging 59.7 +/- 1.6% (p = NS vs. control values). No differences in regional myocardial blood flow, systemic blood pressure, heart rate or extent of area at risk were observed among groups. Conclusions. Thus, prostaglandin endoperoxides play an important role in modulating the cardioprotective effects of thromboxane A2 synthase inhibitors. The simultaneous inhibition of thromboxane A2 Synthase and blockade of thromboxane A2/PGH2 receptors by R 68070 identify a pharmacologic interaction of potential therapeutic importance.

BACKGROUND Experimental studies on the effects of alpha 2-adrenoceptors on regional coronary blood flow in normal and ischemic myocardium are highly controversial. A beneficial effect on regional ischemic myocardium has been demonstrated in different animal preparations with either alpha 2-adrenoceptor blockade or stimulation. Animal studies also demonstrated that postsynaptic alpha 2-adrenoceptors mediate vasoconstriction in coronary and femoral vascular beds. The aims of the study were 1) to investigate the effects of regional alpha 2-adrenoceptor stimulation on regional coronary blood flow in subjects with angiographically normal coronary arteries, 2) to assess the effect of alpha 2-adrenoceptor blockade on coronary circulation in control subjects, and 3) to examine the influence of atherosclerosis on coronary blood flow response to alpha 2-adrenoceptor blockade. METHODS AND RESULTS The effect of regional administration of BHT 933 (a selective alpha 2-adrenoceptor agonist) was studied in eight subjects with angiographically normal coronary arteries. The coronary blood flow velocity was measured using a subselective intracoronary 3F Doppler catheter and coronary diameter by quantitative coronary angiography. BHT 933 induced a reduction in coronary artery diameter from 2.5 +/- 0.6 mm to 1.8 +/- 0.4 mm (p less than 0.05) as well as in coronary blood flow velocity (from 6.4 +/- 0.9 cm/sec to 4.6 +/- 1.9 cm/sec, p less than 0.01). In some subjects, ST segment abnormalities occurred. In patients with angiographically normal coronary arteries (n = 6), the regional infusion of a selective alpha 2-adrenoceptor blocking agent after beta-blockade did not change coronary diameter or coronary blood flow velocity. In contrast, in patients with significant coronary stenoses (n = 6), regional infusion of an alpha 2-adrenoceptor blocking agent reduced regional coronary artery diameter (from 2.3 +/- 0.5 mm to 2.1 +/- 0.6 mm, p less than 0.01) as well as coronary blood flow velocity (from 5.8 +/- 0.8 cm/sec to 3.7 +/- 0.6 cm/sec, p less than 0.05); in addition, alpha 2-adrenoceptor blockade significantly increased coronary sinus plasma norepinephrine levels (from 300 +/- 144 pg/ml to 429 +/- 207 pg/ml, p less than 0.01). CONCLUSIONS The selective in vivo stimulation of alpha 2-adrenoceptors produces a reduction in coronary blood flow and diameter in humans with angiographically normal coronary arteries. alpha 2-Adrenergic blockade does not change coronary blood flow in subjects with angiographically normal coronary arteries (suggesting no resting alpha 2-adrenergic vasoconstrictor tone), whereas in patients with coronary artery stenosis, regional coronary blood flow decreases after alpha 2-receptor blockade. Finally, our data also suggest that alpha 2-adrenoceptors participate in the modulation of sympathetic neuronal norepinephrine release in the human heart.

This study evaluated the effect of bolus infusion of digoxin (0.014 mg/kg in 10 minutes, intravenously) on large coronary arteries measured by quantitative digital angiography. Twenty-two patients (mean age +/- standard deviation 47 +/- 12 years) divided into 3 groups were studied. The effects of digoxin infusion (after 10 and 20 minutes) and sublingual administration of isosorbide dinitrate were investigated in group I (patients with angiographically normal coronary arteries, n = 9) and in group II (patients with atherosclerotic coronary arteries, n = 8). To determine whether the effects of digoxin were mediated by activation of alpha-adrenergic receptors, coronary angiography was performed in group III after alpha-adrenoceptor blockade (phentolamine 0.11 mg/kg, intravenously) (n = 5). Ten minutes after the end of digoxin infusion, the cross-sectional area decreased from 7.7 +/- 4.1 to 6.0 +/- 2.2 mm2, and after 20 minutes to 5.6 +/- 2.6 mm2 (p < 0.05) in group I. Isosorbide dinitrate reverted digoxin-induced vasoconstriction as cross-sectional area increased to 8.5 +/- 3.4 mm2 (p = not significant versus baseline). Twenty minutes after digoxin infusion, heart rate significantly decreased from 79 +/- 16 to 74 +/- 13 beats/min (p < 0.01). Ten minutes after digoxin infusion, peripheral vascular resistance increased significantly from 1,396 +/- 693 to 1,693 +/- 984 dynes . s . cm-5 (p < 0.05), whereas cardiac output did not change. Twenty minutes after digoxin infusion, minimal stenosis diameter decreased significantly from 1.6 +/- 0.5 to 1.4 +/- 0.5 mm (p < 0.05) in group II. Again, isosorbide dinitrate reverted digoxin-induced vasoconstriction as minimal stenosis diameter increased (p = not significant versus control values). In group III, alpha-adrenoceptor blockade with phentolamine did not prevent the decrease in coroary artery diameter in patients with angiographically normal coronary arteries, from 2.3 +/- 0.7 to 1.9 +/- 0.7 mm (p < 0.001). Thus, bolus infusion of digoxin induced vasoconstriction of normal epicardial coronary arteries and reduced minimal stenosis diameter in patients with coronary artery disease. Digoxin-induced vasoconstriction was not mediated by an alpha-adrenergic mechanism and was revertedby sublingual administration of isosorbide dinitrate.

Background. Studies in animals have shown that serotonin constricts coronary arteries if the endothelium is damaged, but in vitro studies have revealed a vasodilating effect on isolated coronary segments with an intact endothelium. To investigate the effect of serotonin in humans, we studied coronary-artery cross-sectional area and blood flow before and after the infusion of serotonin in seven patients with angiographically normal coronary arteries and in seven with coronary artery disease. Methods. We measured the cross-sectional area of the coronary artery by quantitative angiography and coronary blood flow with an intracoronary Doppler catheter. Measurements were obtained at base line and during intracoronary infusions of serotonin (0.1, 1, and 10-mu-g per kilogram of body weight per minute, for two minutes). We repeated the measurements after an infusion of ketanserin, an antagonist of serotonin receptors that is thought to block the effect of serotonin on receptors in the arterial wall but not in the endothelium. Results. In patients with normal coronary arteries, the highest dose of serotonin increased cross-sectional area by 52 percent (P < 0.001) and blood flow by 58 percent (P < 0.01). The effect was significantly potentiated by administration of ketanserin. In patients with coronary-artery atherosclerosis, serotonin reduced cross-sectional area by 64 percent (P < 0.001) and blood flow by 59 percent (P < 0.001). Ketanserin prevented this effect. Conclusions. Serotonin has a vasodilating effect on normal human coronary arteries; when the endothelium is damaged, as in coronary artery disease, serotonin has a direct, unopposed vasoconstricting effect. When considered with other evidence, these data suggest that platelet-derived factors such as serotonin may have a role in certain acute coronary ischemic syndromes.