Antipsychotic use and risk of life-threatening medical events: umbrella review of observational studies.

OBJECTIVE: To quantify the risk of hip fracture, thromboembolism, stroke, myocardial infarction, pneumonia and sudden cardiac death associated with exposure to antipsychotics. METHODS: Systematic searches were conducted in Medline, Embase and PsycINFO from inception until 30/07/2018 for systematic reviews of observational studies. AMSTAR-2 was used for the quality assessment of systematic reviews, while the strength of associations was measured using GRADE and quantitative umbrella review criteria (URC). RESULTS: Sixty-eight observational studies from six systematic reviews were included. The association between antipsychotic exposure and pneumonia was the strongest [URC = class I; GRADE = low quality; odds ratio (OR) = 1.84, 95% confidence interval (CI) = 1.62-2.09; participants = 28 726; age = 76.2 ± 12.3 years], followed by the association with hip fracture (URC = class II; GRADE = low quality; OR = 1.57, 95% CI = 1.42-1.74; participants = 5 288 118; age = 55.4 ± 12.5 years), and thromboembolism (URC = class II; GRADE = very low quality; OR = 1.55, 95% CI = 1.31-1.83; participants = 31 417 175; age = 55.5 ± 3.2 years). The association was weak for stroke (URC = class III; GRADE = very low quality; OR = 1.45, 95% CI = 1.24-1.70; participants = 65 700; age = 68.7 ± 13.8 years), sudden cardiac death (URC = class III; GRADE = very low quality; OR = 2.24, 95% CI = 1.45-3.46; participants = 77 488; age = 52.2 ± 6.2 years) and myocardial infarction (URC = class III; GRADE = very low quality; OR = 2.21, 95% CI = 1.41-3.46; participants = 399 868; age = 74.1 ± 9.3 years). CONCLUSION: The most robust results were found for the risk of pneumonia, followed by the risk of hip fracture and thromboembolism. For stroke, sudden cardiac death and myocardial infarction, the strength of association was weak. The observational nature of the primary studies may represent a source of bias.

Vitamin D supplementation in primary allergy prevention: Systematic review of randomized and non-randomized studies.

BACKGROUND: To date, a systematic review of the evidence regarding the association between vitamin D and allergic diseases development has not yet been undertaken. OBJECTIVE: To review the efficacy and safety of vitamin D supplementation when compared to no supplementation in pregnant women, breastfeeding women, infants, and children for the prevention of allergies. METHODS: Three databases were searched through January 30, 2016, including randomized (RCT) and nonrandomized studies (NRS). Two reviewers independently extracted data and assessed the certainty in the body of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Among the 1932 articles identified, one RCT and four NRS were eligible. Very low certainty in the body of evidence across examined studies suggests that vitamin D supplementation for pregnant women, breastfeeding women, and infants may not decrease the risk of developing allergic diseases such as atopic dermatitis (in pregnant women), allergic rhinitis (in pregnant women and infants), asthma and/or wheezing (in pregnant women, breastfeeding women, and infants), or food allergies (in pregnant women). We found no studies of primary prevention of allergic diseases in children. CONCLUSION: Limited information is available addressing primary prevention of allergic diseases after vitamin D supplementation, and its potential impact remains uncertain.

Prebiotics for the prevention of allergies: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Prevalence of allergic diseases in infants is approximately 10% reaching 20 to 30% in those with an allergic first-degree relative. Prebiotics are selectively fermented food ingredients that allow specific changes in composition/activity of the gastrointestinal microflora. They modulate immune responses, and their supplementation has been proposed as an intervention to prevent allergies. OBJECTIVE: To assess in pregnant women, breastfeeding mothers, and infants (populations) the effect of supplementing prebiotics (intervention) versus no prebiotics (comparison) on the development of allergic diseases and to inform the World Allergy Organization guidelines. METHODS: We performed a systematic review of studies assessing the effects of prebiotic supplementation with an intention to prevent the development of allergies. RESULTS: Of 446 unique records published until November 2016 in Cochrane, MEDLINE, and EMBASE, 22 studies fulfilled a priori specified criteria. We did not find any studies of prebiotics given to pregnant women or breastfeeding mothers. Prebiotic supplementation in infants, compared to placebo, had the following effects: risk of developing eczema (RR: 0.68, 95% CI: 0.40 to 1.15), wheezing/asthma (RR, 0.37; 95% CI: 0.17 to 0.80), and food allergy (RR: 0.28, 95% CI: 0.08 to 1.00). There was no evidence of an increased risk of any adverse effects (RR: 1.01, 95% CI: 0.92 to 1.10). Prebiotic supplementation had little influence growth rate (MD: 0.92 g per day faster with prebiotics, 95% CI: 0 to 1.84) and the final infant weight (MD: 0.10 kg higher with prebiotics, 95% CI: -0.09 to 0.29). The certainty of these estimates is very low due to risk of bias and imprecision of the results. CONCLUSIONS: Currently available evidence on prebiotic supplementation to reduce the risk of developing allergies is very uncertain.

World Allergy Organization-McMaster University Guidelines for allergic disease prevention (GLAD-P): vitamin D

BACKGROUND: The prevalence of allergic diseases is approximately 10 % in infants whose parents and siblings do not have allergic diseases and 20-30 % in those with an allergic first-degree relative. Vitamin D is involved in the regulation of the immune system and it may play a role in the development, severity and course of asthma and other allergic diseases. OBJECTIVE: The World Allergy Organization (WAO) convened a guideline panel to develop evidence-based recommendations addressing the use of vitamin D in primary prevention of allergic diseases. METHODS: Our WAO guideline panel identified the most relevant clinical questions and performed a systematic review of randomized controlled trials and non-randomized studies (NRS), specifically cohort and case-control studies, of vitamin D supplementation for the prevention of allergic diseases. We also reviewed the evidence about values and preferences, and resource requirements (up to January 2015, with an update on January 30, 2016). We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. RESULTS: Having reviewed the currently available evidence, the WAO guideline panel found no support for the hypothesis that vitamin D supplementation reduces the risk of developing allergic diseases in children. The WAO guideline panel suggest not using vitamin D in pregnant women, breastfeeding mothers, or healthy term infants as a means of preventing the development of allergic diseases. This recommendation does not apply to those mothers and infants who have other indications for prophylactic or therapeutic use of vitamin D. The panel's recommendations are conditional and supported by very low certainty evidence. CONCLUSIONS: WAO recommendations about vitamin D supplementation for the prevention of allergic diseases support parents, clinicians and other health care professionals in their decisions whether or not to use vitamin D in preventing allergic diseases in healthy, term infants.(AU)

Detecting deep venous thrombosis with technetium-99m-labeled synthetic peptide P280.

UNLABELLED: Scintigraphy, using small, thrombus-avid, synthetic peptides labeled with gamma-emitting nuclides is an innovative approach to the noninvasive detection of acute deep venous thrombosis (DVT). The goal of this study was to evaluate clinically 99mTc-P280 for imaging DVT. The peptide P280 is a 26 amino acid dimer that binds with high affinity to the GPIIb/IIIa receptor expressed on activated platelets and can be labeled with 99mTc. METHODS: Scintigraphy with 99mTc-P280 (10-22 mCi) was performed in nine patients with clinical suspicion and diagnostic evidence of DVT. Planar and tomographic images of the legs, abdomen/pelvis, chest and head were obtained immediately, 1, 2, 4 and 24 hr after injection. RESULTS: No adverse effects were noted after 99mTc-P280 administration in any patient. Positive visualization of thrombi occurred in eight of nine cases with confirmed DVT within 1 hr of tracer injection. The majority of the patients had recent onset of DVT symptoms (less than 3 wk), while the only negative case was diagnosed 42 days earlier and was likely related to an accident 7 mo earlier. Thrombi-to-background ratios were essentially constant over the study. Technetium-99m-P280 accumulation was also discernible in two patients with pulmonary embolism, while in a third patient the radiotracer concentrated in a cerebellar hemangioblastoma. CONCLUSION: These human studies indicate that 99mTc-P280 is a potentially safe and sensitive procedure for diagnosing DVT and pulmonary embolism. It also may have substantial utility in monitoring active venous thrombosis.

Effects of converting enzyme inhibition on heart period variability in patients with acute myocardial infarction.

BACKGROUND: Heart period variability provides useful prognostic information on autonomic cardiac control, and a strong association has been demonstrated after myocardial infarction (MI) between cardiac mortality, sudden death, and reduced total power, ultralow-frequency (ULF) power, and very-low-frequency (VLF) power. Converting enzyme inhibitors are widely used in MI patients, but their influence on heart period variability remains to be defined. METHODS AND RESULTS: Time- and frequency-domain measures of heart period variability were calculated from 24-hour Holter monitoring in 40 patients with a first uncomplicated MI. After baseline examination between 48 and 72 hours after symptom onset, patients were randomly assigned to placebo or captopril administration, and on the third day, 24-hour Holter monitoring was repeated. No changes in time and frequency domain were detectable after placebo. After captopril, the SD of all normal RR (NN) intervals (SDNN) increased from 90 +/- 29 to 105 +/- 30 milliseconds (P < .01); the SD of the average NN intervals for all 5-minute segments (SDANN index) and the mean of the SDs of all NN intervals for all 5-minute segments (SDNN index) also increased from 74 +/- 24 to 90 +/- 26 milliseconds (P < .01) and from 45 +/- 17 to 49 +/- 15 milliseconds (P < .05), respectively. The root mean square successive difference (r-MSSD) and the percent of differences between adjacent NN intervals > 50 milliseconds (pNN50) remained unchanged. In regard to frequency-domain measures, after captopril, total power (ln unit) increased from 8.28 +/- 0.42 to 8.47 +/- 0.30 (P < .01); considering the frequency bands, a significant increase was observed in ULF (P < .01), VLF (P < .05), and low-frequency (LF) power (P < .05), whereas high-frequency (HF) power remained unchanged. CONCLUSIONS: This study supports the hypothesis that the renin-angiotensin system modulates the amplitude of ULF and VLF power. Furthermore, it demonstrates that in MI patients, converting enzyme inhibition favorably modifies measures of heart period variability strongly associated with a poor prognosis.

Left ventricular remodelling in the year after myocardial infarction: an echocardiographic, haemodynamic, and radionuclide angiographic study.

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.

Effects of acetylstrophanthidin on baroreflex sensitivity in patients with acute myocardial infarction.

We evaluated the effects of acetylstrophanthidin on baroreflex sensitivity in patients soon after an acute myocardial infarction. Baroreflex control of heart rate is frequently depressed after acute myocardial infarction and few data are available as to the effects of pharmacological intervention on this parameter. The reflex chronotropic response to arterial baroreceptor stimulation was assessed in 29 patients with uncomplicated acute myocardial infarction in control conditions (72-96 h after symptom onset) and 30 min after acetylstrophanthidin administration. To check for spontaneous baroreflex sensitivity variations, 24 patients with the same characteristics were evaluated at the same time intervals before and after a 10-cc bolus of saline placebo. Baroreflex sensitivity was assessed by calculating the regression line relating phenylephrine-induced increases in systolic blood pressure to the attendant changes in RR intervals. Mean baseline baroreflex sensitivity value for the whole study population was 7.4 +/- 4.5 ms/mmHg and was unchanged, 7.0 +/- 4.5 ms/mmHg, after acetylstrophanthidin (P = NS). Mean baroreflex sensitivity values were also comparable dividing patients according to the site of infarction both before and after acetylstrophanthidin. Despite the lack of difference in mean baroreflex sensitivity values between the two studies, at a post hoc analysis an inverse relation was found in the total study population between baseline baroreflex sensitivity values and their changes after acetylstrophanthidin (r = -0.62; P < 0.005). The inverse relation was also evident separately in anterior (r = -0.57; P < 0.05) and in inferior (r = -0.70; P < 0.005) myocardial infarction patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Incremental prognostic value of thallium imaging and coronary angiography in patients with a symptom-limited ECG stress test.

BACKGROUND: This study evaluates the incremental prognostic value of qualitative thallium-201 imaging and coronary angiography in patients with suspected or known coronary artery disease. METHODS: Within 1 month, 150 patients underwent diagnostic symptom-limited ECG stress test, thallium imaging, and coronary angiography. The incremental power of sequentially performed tests was evaluated by the overall likelihood ratio statistic. RESULTS: At 3-year follow-up, 16 patients had died from a cardiac cause, 12 had suffered a nonfatal myocardial infarction, and 34 had undergone revascularization procedures more than 60 days after testing. Considering hard events, thallium imaging did not improve the prognostic information provided by clinical exercise stress test data, while coronary angiography increased the predictive power of the combined, exercise stress test, and scintigraphic data (P < 0.001). Moreover, when thallium results were added to clinical, exercise, and coronary angiographic data, the predictive power was unchanged. When the analysis was repeated including the occurrence of late revascularization procedures, each test showed additional prognostic information to that obtained by the other combined tests (P < 0.001). CONCLUSIONS: This study demonstrates that in patients with a symptom-limited ECG stress test, coronary angiography adds prognostic information to combined clinical, exercise ECG, and thallium imaging data. The incremental prognostic value of qualitative thallium imaging is demonstrable only when late revascularization procedures are included as events.

Effects of sustained training on left ventricular structure and function in top level rowers.

The effects of vigorous training on left ventricular structure and function were evaluated in 15 top level rowers using electrocardiography, Doppler echocardiography and radionuclide angiography. All subjects were studied after 1 month of deconditioning and again after 5 months of vigorous training. After training there was an increase in the ventricular hypertrophy voltage criteria proposed by Sokolow-Lyon and by Friedman but not in that proposed by Casale; T wave amplitude in leads V5 and V6 increased in nine subjects, was unchanged in one and decreased in five; the mean values were also unchanged. Training induced a significant increase in left ventricular end-diastolic and end-systolic diameter and in left ventricular mass index, while peak systolic stress and mean wall stress index decreased. No change was detected after training in the mean values of Doppler echocardiographic and radionuclide angiographic data; nevertheless a significant relationship was found between changes in T wave height in V5 or V6 and in peak filling rate, and between changes in T wave height and ejection fraction. Our study confirms that the effect of vigorous training on left ventricular mass and dimensions does not include changes in mean values of systolic and diastolic function. The relationship between change in T wave amplitude and in peak filling rate values suggests that some metabolic or neurohumoral derangement occurs in the subset of athletes with T wave flattening, that is responsible for the slight reduction in peak filling rate and ejection fraction.

Effects of converting enzyme inhibition on baroreflex sensitivity in patients with myocardial infarction.

BACKGROUND: Baroreflex sensitivity provides useful prognostic information in patients after acute myocardial infarction. However, no data are available about the effects of converting enzyme inhibition on this variable. OBJECTIVES: The aim of the study was to evaluate the effects of angiotensin-converting enzyme inhibition on baroreflex sensitivity in patients after uncomplicated myocardial infarction. METHODS: Twenty-five patients after uncomplicated myocardial infarction underwent baroreflex sensitivity evaluation 72 to 96 h after symptom onset and after 4 days of captopril therapy. Twenty additional patients with the same characteristics were evaluated at the same time intervals before and after placebo administration to identify spontaneous baroreflex sensitivity variations. Baroreflex sensitivity was assessed by calculating the regression line relating phenylephrine-induced increases in systolic blood pressure to the attendant changes in the RR interval. RESULTS: The mean baroreflex sensitivity value increased after captopril administration from 6.5 +/- 4.2 to 11.8 +/- 6.1 ms/mm Hg (p less than 0.01) and in individual analyses increased by greater than 2 ms/mm Hg in 68% of patients. Mean plasma renin activity increased after captopril from 3.7 +/- 2.4 to 8.5 +/- 4.9 ng/ml per h (p less than 0.005). No difference was detectable in baroreflex sensitivity and plasma renin activity values according to the site of necrosis. In the control group, baroreflex sensitivity and plasma renin activity remained unchanged between the two studies. CONCLUSIONS: This study demonstrates that in patients with uncomplicated myocardial infarction, captopril significantly improves the chronotropic response to baroreceptor stimulation.

Characterization and prognostic significance of silent myocardial ischemia on predischarge electrocardiographic monitoring in unselected patients with myocardial infarction.

Characteristics and prognostic significance of ischemic ST changes at predischarge Holter monitoring were evaluated in 270 consecutive postinfarction patients. The 64 patients with ST changes had a greater incidence of non-Q-wave myocardial infarction (p less than 0.01) and ventricular premature contractions (p less than 0.01); they were more frequently in Moss class greater than 2 (p less than 0.01) and they had a lower wall motion score (p less than 0.05). At 2-year follow-up, patients with ST changes had a higher incidence of cardiac death and reinfarction. At multivariate analysis, Killip class (p less than 0.01) and ST changes (p less than 0.05) were the most predictive variables; when multivariate analysis was repeated including an additional variable--the inability to perform a stress test--Killip class was the most significant variable (p less than 0.01), and the presence of ST changes showed only borderline statistical significance (p less than 0.1). In the subset of patients who did not perform the stress test, ST change was the most important variable (p less than 0.01), followed by Killip class (p less than 0.05). Thus, after myocardial infarction, ST changes during Holter monitoring are associated with a poor prognosis and appear useful for stratifying patients who do not perform exercise stress tests.

Effects of captopril treatment on left ventricular remodeling and function after anterior myocardial infarction: comparison with digitalis.

The effects of captopril and digoxin treatment on left ventricular remodeling and function after anterior myocardial infarction were evaluated in a randomized unblinded trial. Fifty-two patients with a first transmural anterior myocardial infarction and a radionuclide left ventricular ejection fraction less than 40% were randomly assigned to treatment with captopril (Group A) or digoxin (Group B). The two groups had similar baseline hemodynamic, coronary angiographic, echocardiographic and radionuclide angiographic variables. Among the 40 patients (20 in each group) who were followed up for 1 year, echocardiographic end-diastolic and end-systolic volumes were unmodified in Group A and global wall motion index was improved (p less than 0.01); in Group B, end-diastolic and end-systolic volumes increased (p less than 0.001 for both) and global wall motion index was unchanged. Rest radionuclide ejection fraction increased significantly in both groups (p less than 0.001, Group A; p less than 0.005, Group B). A comparison of the changes in the considered variables between the two groups after 1 year of treatment showed a difference in end-diastolic (p less than 0.005) end-systolic volumes (p less than 0.001) and global wall motion index (p less than 0.005) without differences in radionuclide ejection fraction, which improved to a similar degree in both groups. The results of this study suggest that captopril therapy, started 7 to 10 days after symptom onset in patients with anterior myocardial infarction and an ejection fraction less than 40%, improves both left ventricular remodeling and function and prevents left ventricular enlargement and in these patients performs better than digitalis.

[Cardiac changes induced by deconditioning in athletes: an echocardiographic and electrocardiographic study]. / Modificazioni cardiache indotte dal decondizionamento nell'atleta: studio ecocardiografico ed elettrocardiografico.

The relationships between echocardiographic and electrocardiographic variations and the sensibility of three different electrocardiographic criteria of left ventricular (LV) hypertrophy were assessed during deconditioning in 18 top-level oarsmen (mean age 23 +/- 4 years). After seven months of training and on the 7th and 21st deconditioning days the oarsmen underwent clinical examination, electrocardiogram (ECG) and echocardiogram with Doppler evaluation. The following ECG measurements were obtained: heart rate (HR), QTc, QRS and T waves axes, QRS and T wave angular gradients, R, S and T wave amplitude and T wave area. Moreover, the sums of S wave in lead V1 plus R wave in lead V5 or V6, of S wave in lead V1 or V2 plus R wave in lead V5 or V6, and of R wave in lead aVL plus S wave in lead V3 were calculated as indices of left ventricular hypertrophy. The following echocardiographic parameters were also analyzed: intraventricular septal (IVST) and posterior wall thickness (PWT), LV internal diameter (LVID), left ventricular mass (LVM) and volumes, LV endocardial/epicardial diastolic surface area ratio, peak systolic meridional wall stress (PSS), end-systolic stress (ESS) and mean systolic wall stress (MWSI), LV ejection fraction (EF) and total peripheral resistances (TPR); early (E) and late (A) transmitral peak flow velocity, E/A ratio. Systolic blood pressure was reduced after 3 deconditioning weeks, while diastolic blood pressure and HR were unchanged. Left ventricular mass and end-systolic volume were reduced after 1 week, while LV end-diastolic volume only after 3 weeks; therefore, EF improved at the end of the first week when TPR were lower. End-systolic stress always remained unchanged; PSS increased at 1 week and then returned to previous values. In addition, the endocardial-epicardial area ratio increased after 1 week and then returned to starting values after 3 weeks. Doppler parameters were in the normal range and remained unchanged during the study. Amplitudes of R wave in aVL, V5, V6 and of S wave in V2 did not change, while S wave amplitude in V1 and V3 decreased after three weeks and one week, respectively. The most sensible criterion for LV hypertrophy was the sum of S wave in V1 or V2 plus R wave in V5 or V6 (range from 33.3% to 22.2%); the sum of S in V1 plus R in V5 or V6 performed better than the sum of R in aVL plus S in V3.(ABSTRACT TRUNCATED AT 400 WORDS)

[Influence of age on the short- and medium-term prognosis in patients with acute myocardial infarct]. / Influenza dell'età sulla prognosi a breve e medio termine nei pazienti con infarto acuto del miocardio.

Elderly patients with acute myocardial infarction (AMI) have a higher subsequent mortality than younger ones, yet the reasons for this adverse prognosis are poorly understood. We compared the clinical course and the prognosis of 163 patients aged 40 to 69 years with 112 patients older than 70 years. During hospitalization period 15.9% of younger and 37.5% of older patients died; at 1 year follow-up the cardiac mortality rate was 8.7% in younger and 12.9% in older patients. In elderly patients a greater prevalence of female gender, diabetes mellitus, anterior myocardial infarction, atrial fibrillation and a greater incidence of heart failure and shock were observed. Multivariate stepwise analysis identified shock and heart rate greater than or equal to 90 bpm at the time of admission as the most important prognostic variables for in-hospital mortality in both groups; heart failure (Killip class II and III) was significant in younger patients, while non Q wave myocardial infarction correlated with a better prognosis in elderly. In elderly patients who survived AMI, predischarge Holter monitoring showed higher frequency and complexity of ventricular arrhythmias, and radionuclide angiography lower left ventricular ejection fraction (E.F.) values. In these patients no difference was found in E.F. values despite myocardial infarction sites. At 1 year follow-up E.F. less than 40% and ventricular arrhythmias (3-4 Moss grading system) were significantly related to prognosis in younger patients, while E.F. less than 40% and clinical signs of heart failure in elderly. Therefore, low E.F. and heart failure account for a worse prognosis in elderly patients, while ventricular arrhythmias in younger ones. The results of this study support aggressive management even in elderly patients following AMI to preserve left ventricular function. In elderly patients a large use of antiarrhythmic drugs is not recommended because of low prognostic value of ventricular arrhythmias.

Prevalence and prognostic significance of silent myocardial ischaemia detected by exercise test and continuous ECG monitoring after acute myocardial infarction.

The incidence and prognostic significance of silent myocardial ischaemia in 165 patients who survived a first acute myocardial infarction were assessed by means of maximal exercise stress test and 24 h continuous ECG monitoring performed before discharge. During the 1 year follow-up period 10 cardiac deaths occurred; moreover seven patients suffered a fatal myocardial re-infarction and 14 developed unstable angina. Cardiac death occurred in five of 40 patients (12.5%) with ST segment depression on stress test by in only three of 117 (2.6%) without ST segment changes (P less than 0.01). One-hundred-and-three of 117 patients (88.0%) without angina or ST segment depression on stress testing survived 1 year without cardiac events, compared with 24 of 40 patients (60.0%) with ST segment depression whether or not associated with angina (P less than 0.001). Cardiac death occurred in five of 25 patients (20.0%) with ST segment depression on continuous ECG monitoring, compared with five of 140 (3.6%) without (P less than 0.01). One-hundred-and-seventeen out of 140 patients (83.6%) without angina or ST segment depression survived 1 year follow-up without cardiac events, compared with 13 of 25 (52.0%) with ST segment depression with or without angina (P less than 0.01). Classifying patients in a 2 x 5 contingency table according to the occurrence of ST segment depression on exercise testing and/or ECG ambulatory monitoring, the Yates corrected chi-square test showed a significant pattern when cardiac deaths and cardiac events were considered together (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of late administration of tissue-type plasminogen activator on left ventricular remodeling and function after myocardial infarction.

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.

[The clinical characterization and prognostic significance of episodes of transient myocardial ischemia in patients with a recent myocardial infarct]. / Caratterizzazione clinica e significato prognostico degli episodi di ischemia miocardica transitoria in pazienti con recente infarto del miocardio.

The incidence and prognostic significance of silent myocardial ischemia were assessed in 175 patients who survived a first acute myocardial infarction (AMI). This was done by means of a 24-hour continuous ECG monitoring which was performed before discharge. Twenty-six out of 175 patients (14.8%) showed one episode or more of S-T segment depression; 19 of these reported no pain at all while the other 7 reported both painful and painless episodes. A total of 65 ischemic episodes were registered; of these 53 (81.5%) were painless and 12 (18.5%) were painful. No difference in the duration of ischemic episodes or in heart rate at the onset of S-T segment depression was detected for painless or painful episodes. The S-T segment depression episodes showed a peak in the morning but were higher in the afternoon and this circadian pattern was statistically significant both with regard to duration (p less than 0.05) and to the number of episodes (p less than 0.05). Cardiac death occurred in 5 of the 26 patients (19.2%) with S-T segment depression during continuous ECG monitoring, and in 5 of the 149 (3.4%) without S-T segment depression (p less than 0.01). In patients with ischemia duration greater than 60 min/24 hours, the mortality rate was higher (p less than 0.05). No cardiac events (unstable angina, non-fatal re-infarction, balloon angioplasty and/or coronary by-pass) occurred in 117 out of 149 patients (78.5%) without ST-segment depression, while these events were observed in 13 out of the 26 patients (50%) with ischemic episodes during Holter monitoring (p less than 0.01). Sensitivity and specificity of S-T segment depression was respectively 29.3 and 89.5% for cardiac death and cardiac events considered together.(ABSTRACT TRUNCATED AT 250 WORDS)

[Nisoldipine in the therapy of stable exercise angina: evaluation of its efficacy in ergometric tests compared with propranolol]. / La nisoldipina nella terapia dell'angina stabile da sforzo: valutazione dell'efficacia mediante prove ergometriche e confronto con il propranololo.

The safety and efficacy of a new dihydropyridine calcium antagonist, nisoldipine, were studied in comparison with propranolol, in patients with stable angina. Following 2 weeks of wash-out of the current therapy and 1 week of placebo, 26 patients underwent two cycloergometer tests, before and 2 hours after placebo administration. Subsequently, 10 mg of nisoldipine twice daily or 40 mg of propranolol three times daily were administered over a 4 week period, in a randomized single-blind fashion. Cycloergometer tests were performed after 2 and 4 weeks, before and two hours after drug administration. Two patients, one out of the nisoldipine group and one out of the propranolol, were considered drop outs. Statistical analysis of the results was performed using two-way variance analysis. With both drugs, time to 1 mm exercise induced ST-segment depression (p less than 0.01), time to angina (p less than 0.01), and exercise tolerance (p less than 0.01) improved furthermore, ST-segment and heart rate recovery time decreased (p less than 0.01). Rate-pressure product values at ischemic threshold and at peak exercise remained unchanged with nisoldipine, while significant reductions were observed with propranolol (p less than 0.01). Maximum ST-segment depression was reduced (p less than 0.01) with both drugs and a further improvement was observed two hours after drug administration (p less than 0.05). At submaximum work-load, rate pressure product values and ST-segment depression were improved with both drugs (p less than 0.01); this improvement was more evident two hours after drug administration. No significant side effects were observed with either drug.(ABSTRACT TRUNCATED AT 250 WORDS)

[A Doppler echocardiographic study of normal and dysfunctioning Carpentier-Edwards bioprostheses]. / Studio eco-Doppler delle bioprotesi di Carpentier-Edwards normo e malfunzionanti.

The aim of this study was to delineate the Doppler echocardiographic characteristics of normal and dysfunctioning Carpentier-Edwards bioprostheses. Echocardiographic and Doppler studies were performed on 61 mitral and 41 aortic valves; by means of on clinical evaluation, 15 mitral and 12 aortic valves were considered to be abnormally functioning. The maximum velocity (Vmax) of diastolic left ventricular inflow, pressure half-time and valve orifice area were assessed for prostheses in mitral position, while the maximum velocity (Vmax) of transaortic flow was calculated for prostheses in aortic position. Moreover, the quantitative assessment of mitral and/or aortic regurgitation was performed using the mapping technique with pulsed Doppler wave mode. Normally functioning mitral prostheses were characterized by Vmax less than 2.20 m/s and pressure half-time less than 164 ms; furthermore, mean values of Vmax and pressure half-time were significantly lower in normal than in dysfunctioning prostheses (1.70 +/- 0.33 vs 2.09 +/- 0.52 m/s; p less than 0.01 and 96.14 +/- 29.76 vs 147.87 +/- 57.41 ms; p less than 0.01 respectively). All dysfunctioning mitral valves were characterized by regurgitation graded as severe in 8 cases and moderate in 7 but only 40 and 20% of these presented respectively Vmax and pressure half-time values which were higher than those of normally functioning valves (2.20 m/s and 164 ms respectively); no pure stenosis was found. In the aortic position, normally functioning prostheses were characterized by Vmax less than 3.10 m/s. Furthermore, mean Vmax values were lower in normal than in dysfunctioning prostheses (2.55 +/- 0.53 vs 3.18 +/- 0.80; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)