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Biomedical subjects

A Keren

Publications and source records attributed to A Keren.

At least 55 records · Page 3Linked to original sources

Circadian variations in ischemic threshold and their relation to the occurrence of ischemic episodes.

BACKGROUND: The occurrence of ischemic episodes during daily activity has been reported to exhibit a bimodal circadian distribution, yet its relation to the ischemic threshold (heart rate at 1-mm ST segment depression) has not been explored. METHODS AND RESULTS: To determine whether the ischemic threshold during daily activity exhibits a circadian pattern that might relate to the frequency of occurrence of ischemic episodes, we studied the time of occurrence and the heart rate at onset of ischemia in 1,371 ischemic episodes recorded in 41 patients with stable coronary disease, positive exercise testing, and repeated ischemic episodes during ambulatory ECG monitoring (AEM). All patients had 7 days of AEM; 23 were off any anti-ischemic therapy, while 18 were on low dose of beta-blockers. The occurrence of ischemic episodes exhibited the typical bimodal circadian distribution with a prominent peak between 7:00 and 11:00 AM and a second less prominent peak between 6:00 and 9:00 PM. The threshold of myocardial ischemia exhibited a different single-peaked circadian distribution; it was lowest between 1:00 and 3:00 AM and highest between 10 AM and 1 PM. Time series analyses indicated a strong hour-by-hour trend of each of the two circadian distributions, whereas the two series cross-correlated maximally at a lag of zero hours (p < 0.01), indicating a complex interplay between myocardial oxygen demand and supply in determining the occurrence of ischemic episodes during daily activity. The morning increase in the frequency of ischemic episodes could not be attributed to a reduced threshold but rather to an increase in demand. The low threshold at night-time might probably indicate that the mechanism of ischemia during these hours is reduced coronary flow due to increased coronary tone. Secondary analyses for several predefined patients' subsets gave similar results. Patients who received low-dose beta-blockers maintained the bimodal circadian distribution of the occurrence of ischemic episodes, whereas the ischemic threshold exhibited a constant pattern with no circadian changes. CONCLUSIONS: Our results demonstrate that myocardial oxygen demand is a major determinant of daily ischemia, yet changes in the ischemic threshold that probably reflect dynamic changes in coronary tone play also an important role. The relative contribution of increased demand and decreased threshold to the genesis of ischemic episodes during daily activity can be assessed by AEM and may help to optimize medical therapy.

Adrenergic beta-Antagonists↗

Doppler echocardiographic patterns of left ventricular filling in patients early after acute myocardial infarction.

Diastolic function is routinely assessed using Doppler-derived left ventricular (LV) filling patterns. Ratios between peak flow velocities during early filling and atrial contraction (E/A) of less than 1 are considered pathologic and diagnostic of impaired relaxation. Myocardial stiffness can normalize the E/A ratio, and thus, in some clinical settings, a normal E/A ratio may identify patients with high filling pressures. LV filling patterns were studied with Doppler echocardiography in 15 healthy subjects and 38 patients with recent acute myocardial infarction. The results were correlated with clinical and hemodynamic variables. E/A ratio less than 1 was found in 14 patients (37%) and in only 1 control subject; E/A ratio greater than 2 found in 5 patients (13%) and in only 1 control subject; 19 patients (50%) had an apparently normal E/A ratio. No correlation was found between LV filling pattern and ejection fraction or presence of diabetes or arterial hypertension. LV end-diastolic pressures were low to normal in patients with an E/A ratio less than 1 and were usually greater than 15 mm Hg in those with normal or abnormally increased (greater than 2) E/A ratios. Thus, an apparently normal E/A ratio in patients after myocardial infarction may identify those with more severe LV diastolic dysfunction and increased LV filling pressure.

Cardiac Catheterization↗

The prevalence of valvular regurgitation in children with structurally normal hearts: a color Doppler echocardiographic study.

To determine the prevalence of valvular regurgitation in children (from birth to 14 years old) with structurally normal hearts, the records of 1360 consecutive patients referred for echocardiographic and Doppler examination were analyzed. A total of 461 (33.9%) patients were found to have structurally normal hearts. Flow patterns across the four valves were examined by pulsed, continuous-wave, and color Doppler imaging techniques. Regurgitation was detected in 124 (26.9%). Pulmonic regurgitation was most commonly found and was detected in 101 (21.9%) patients, tricuspid regurgitation in 29 (6.3%), and mitral regurgitation in 11 (2.4%). Aortic regurgitation was not found. Regurgitation of one valve occurred in 106 (23.0%) patients and of two valves in 18 (3.9%) patients. No patient had regurgitation of more than two valves. The prevalence of pulmonic regurgitation increased significantly with age (p less than 0.0001), whereas the prevalence of mitral, tricuspid, and bivalvular regurgitation did not change with age. Valvular regurgitation was trivial or mild in 87% of patients. Thus mild valvular regurgitation is commonly found in children with structurally normal hearts.

Adolescent↗

Assignment of patients into the classification of cardiomyopathies.

The original classifications of the cardiomyopathies based on anatomic criteria from radiographic and necropsy studies, as well as hemodynamic criteria from clinical and catheterization data, have been supplemented in recent years by information from noninvasive techniques. Echocardiography, radionuclide methods, and ambulatory ECG, in particular, have facilitated the ethical screening of family members and those less symptomatic than patients on whom the original classification was based. These powerful methods show a broad spectrum of anatomy and ventricular physiology along the natural history of and within the traditional categories of the cardiomyopathies. They also provide data on the effect of ventricular loading conditions affecting a range of diastolic filling patterns. This review has attempted to point out the areas of overlap among and/or controversy about the categories that have led us to a feeling of frustration when trying to neatly classify individual patients. The addition of filling patterns from Doppler echocardiography and nuclear angiography to the standard methods has been reviewed and hopefully will lend more perspective to the range of physiology seen in these conditions. The categories of cardiomyopathy should not be seen as excluding patients with the newly recognized variations in anatomy and ventricular filling patterns. Rather, the classification provides a framework on which to build and expand our understanding of these important conditions.

Aging↗

Terminology of torsades de pointes.

Marked prolongation of the QT interval may be associated with life-threatening ventricular tachycardia. The ventricular tachycardia has a polymorphous appearance and is usually induced by antiarrhythmic drugs. This peculiar type of ventricular tachycardia was termed by Desserstenne torsades de pointes because of its twisting ORS axis. The main reason to give this entity a special name that differentiates it from other types of ventricular tachycardia is the unique therapeutic approach to its treatment. Torsades de pointes can be suppressed by interventions that shorten the QT interval by increasing the heart rate, such as ventricular or atrial pacing, isoproterenol infusion, or atropine. Recently intravenous magnesium was also shown to be extremely effective. If torsades de pointes is treated as a conventional ventricular tachycardia by drugs that may further prolong the QT interval, it may lead to fatal results. To draw the attention of physicians to this unusual form of ventricular tachycardia, we suggest that the term torsades de pointes be kept. This specific diagnosis will hopefully guide the treating physician in selecting the appropriate mode of therapy.

Animals↗

Torsades de pointes: prevention and therapy.

Torsades de pointes (TdP) is a life-threatening ventricular tachycardia that occurs in the setting of a prolonged QT interval and is most frequently related to administration of antiarrhythmic drugs. Patients with organic heart disease, with low serum electrolyte levels, with a previous episode of TdP and with bradycardia or baseline QT prolongation may be at increased risk of developing TdP. After initiation of a QT prolonging therapy, the dosage should be modified if the QT interval reaches 560-600 ms. Cessation of medication and immediate hospitalization are indicated in the presence of lightheadedness, syncope, or increased frequency and complexity of ventricular premature beats. The conventional therapy of TdP with isoproterenol or cardiac pacing, although usually effective, has certain disadvantages. Isoproterenol is contraindicated in patients with hypertension or ischemic heart disease, whereas institution of cardiac pacing requires skilled personnel and fluoroscopy. Recently, infusion of magnesium sulfate has been shown to abolish TdP both in the clinical and experimental setting. Compared with conventional therapy, magnesium sulfate has the advantage of safety and simplicity of its administration. In doubtful cases, if does not aggravate a ventricular tachycardia that is not TdP, as may occur with isoproterenol. This advantage and the prompt effectiveness of the drug in four clinical series, including 31 patients, support the use of magnesium sulfate as the first line of therapy for TdP.

Animals↗

Natural history of left ventricular thrombi: their appearance and resolution in the posthospitalization period of acute myocardial infarction.

A series of 198 consecutive patients with acute myocardial infarction were prospectively studied before hospital discharge and during 24.0 +/- 8.6 months of follow-up. A predischarge thrombus was found in 38 (31%) of 124 patients with anterior infarction but in none of 74 patients with inferior infarction (p less than 0.001). Early thrombolytic therapy in 34 patients did not decrease the rate of thrombus occurrence. Acute anterior infarction, ejection fraction less than or equal to 35% and apical dyskinesia or aneurysm (but not akinesia) were significantly related to the appearance of thrombus during hospitalization by stepwise logistic regression analysis. Echocardiographic follow-up of 159 patients for at least 6 months (mean 26.6 +/- 8.4) revealed that thrombus disappeared in 14 (48%) of 29. Disappearance of thrombus was related to predischarge apical akinesia (but not dyskinesia) and to warfarin therapy during the follow-up period. A new thrombus first appeared after hospital discharge in 13 of 130 patients, and in 7 of the 13 it resolved during further follow-up. Thus, 30% (13 of 42) of thrombi in these patients appeared after discharge from the hospital. Three factors were related to occurrence of new thrombi during the follow-up period: deterioration in left ventricular ejection fraction, predischarge ejection fraction less than or equal to 35% and ventricular aneurysm or dyskinesia. Systemic embolism occurred in six patients, all with a predischarge thrombus (p less than 0.001). Mobility of the thrombus was the only variable significantly related to subsequent embolic events (p = 0.001) by logistic regression analysis. Thus, the predischarge echocardiogram identifies patients with thrombus and those at highest risk of embolic events. It can indicate patients who are likely to have thrombus resolution and those at risk of developing a new thrombus after hospital discharge. Follow-up echocardiograms may help in guiding the length of long-term anticoagulant therapy. Four additional patients with a predischarge apical mobile thrombus (not part of the consecutive series) received thrombolytic therapy. In two of the four, lysis of thrombus was achieved without complications, but systemic embolism occurred in the other two, and proved fatal in one.

Echocardiography↗

Ventricular ectopic activity during myocardial ischemic episodes in ambulatory patients.

The association between ventricular ectopic activity (VEA) and ischemic episodes during everyday activities was investigated in ambulatory patients with stable angina pectoris. Seventy-five consecutive patients with proven coronary artery disease, ischemic episodes on Holter monitoring and positive treadmill tests, but without known ventricular arrhythmias, were prospectively studied. In these 75 patients, a total of 719 ischemic episodes were recorded during 127 twenty-four-hour monitoring periods. Forty-three patients had either no or only very low baseline VEA (less than 14 ventricular premature complexes [VPCs]/24 hours); none of these patients had increased VEA during any ischemic episode. However, among 32 patients who had greater than or equal to 14 VPCs/24 hours (average 243 VPCs/24 hours), increased VEA during ischemic episodes was observed in 11 (31%). These 11 patients had a total of 174 ischemic episodes and the increased VEA appeared in 47 (27%) of the episodes. During 40 of the ischemic episodes the number of single VPCs increased significantly compared to the baseline background VEA: during 4 episodes trigeminy appeared and during another 3 bigeminy was observed. More complex VEA was not observed. Among the 11 patients with increased VEA, only 4 developed VPCs during treadmill testing. No correlation was found between the severity of the ischemic episodes (degree of ST depression and duration of ischemia) and the increased VEA. In 83% of these episodes the increased VEA appeared during the last (possibly reperfusion) phase. No correlation was found between the appearance of ventricular arrhythmias during ischemic episodes and the presence or absence of chest pain at the same time.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗

The effect of disopyramide on uterine contractions during pregnancy.

To evaluate the effect of disopyramide on uterine contractions during pregnancy, the drug was given for 48 hours to 10 women with indications for labor induction. Placebo was given to 10 other women with the same indications for induction. During the study period, regular uterine contractions occurred in 10 women in the study group, as compared with none in the control group (p less than 0.0001). Eight women in the study group were delivered of infants within 48 hours, as compared with none in the control group (p less than 0.0001). The mean time until the appearance of regular uterine contractions in the study group (4.15 +/- 1.76 hours) was significantly shorter (p less than 0.001) than that in the control group (56.13 +/- 5.28 hours). Patients who were not delivered of infants within 48 hours received other medications (prostaglandin E2, oxytocin). The mean maternal blood level of disopyramide at the time of appearance of uterine contractions was 1.52 +/- 0.9 mg/ml. The mean maternal level at delivery was 0.93 +/- 0.43 mg/ml and the cord blood level at the time of delivery was 0.33 mg/ml (cord blood/maternal level ratio = 0.36, r = 0.73, p less than 0.05). These results indicate that disopyramide should not be used in pregnancy for antiarrhythmic purposes because it may induce uterine contractions and delivery.

Adult↗

Magnesium therapy in ventricular arrhythmias.

Magnesium (Mg) is the known activator of 300 enzymes which govern energy utilization, cell permeability, and ionic membrane currents in the cardiac conducting cells. This may explain the antiarrhythmic efficacy of Mg in specific clinical settings, despite its only modest electrophysiological effects. This review summarizes the effect of Mg administration in four clinical conditions: in digitalis toxicity; in drug-induced torsade de pointes; in patients with chronic diuretic therapy; and in acute myocardial infarction. Mg effectively abolished ventricular tachyarrhythmias associated with digitalis intoxication. This effect of Mg is related to the activation of sodium-potassium ATP-ase, which is inhibited by digitalis. Drug-induced torsade de pointes was promptly abolished by Mg sulfate in the clinical setting. Experimental studies showed that Mg suppresses the early afterdepolarizations and the triggered activity responsible for occurrence of the arrhythmia. In diuretic-treated hypertensives, potassium depletion has been associated with increased ventricular ectopy and sudden death. Mg has been found to be an important adjuvant for intracellular repletion of potassium in these patients. Several randomized, double-blind studies in patients with acute infarction showed that Mg administered on admission improved survival or reduced the incidence of complex ventricular arrhythmias. Thus, Mg should be employed as first-line therapy in digitalis intoxication and drug-related torsade de pointes, and should be considered an important adjuvant therapy in hypertensives treated with diuretics and patients with acute myocardial infarction.

Arrhythmias, Cardiac↗

Mildly dilated congestive cardiomyopathy. Use of prospective diagnostic criteria and description of the clinical course without heart transplantation.

Prognosis in classically described dilated congestive cardiomyopathy has been reported to be related to ventricular size. Mildly dilated congestive cardiomyopathy (MDCM) has been defined as end-stage heart failure of unknown etiology (New York Heart Association class IV, left ventricular ejection fraction less than 30%), occurring with neither typical hemodynamic signs of restrictive myopathy nor significant ventricular dilatation (less than 15% above normal range). The present study includes follow-up in 12 nontransplant patients. In the first 4 months after diagnosis, two patients improved and are living, and two showed cardiac dilation and clinical deterioration and died. Six of the remaining eight with persistent MDCM died (four with intractable heart failure and two, sudden deaths) without change in ventricular size before death, despite medical therapy over 20 +/- 8 months. Eight comparable transplanted patients with persistent MDCM demonstrated improved total survival by life table analysis (p less than 0.05). A family history of congestive cardiomyopathy was found in nine of 16 patients (56%) with persistent MDCM. Nontransplant patients were older (p less than 0.02), but other findings were similar in the two groups. Endomyocardial biopsies available in 14 of 16 cases showed little or no myofibrillar loss in spite of severe hemodynamic impairment. The degree of myofibrillar loss did not correlate with hemodynamic parameters but showed good correlation with left ventricular size, that is, five of six patients with no myofibrillar loss had normal ventricular size, whereas all eight patients with mild myofibrillar loss had mild cardiomegaly (p less than 0.002). Our current experience suggests a somewhat variable but negative prognosis after prospective diagnosis of MDCM, with poor survival in patients with persistence of the original diagnostic features during follow-up. Preservation of heart size in MDCM is probably related to lack of significant myofibrillar loss. Thus, irrespective of heart size or myofibrillar preservation on biopsy, heart transplantation should be strongly considered in MDCM if signs of severe cardiac dysfunction persist despite therapy.

Adult↗

Natural course of atrial septal aneurysm in children and the potential for spontaneous closure of associated septal defect.

Atrial septum aneurysm (ASA), usually involving the region of the fossa ovalis, has rarely been described in children. In this study, the incidence and natural course of this anomaly were prospectively evaluated in 3,500 children referred for echocardiographic examination. ASA was found in 35 patients, 19 female and 16 male (1.0%). Patients were 6 years of age or younger at the time of diagnosis and 18 were neonates. None of the 750 children with normal echocardiograms had ASA. The most common associated lesion was atrial septal defect (ASD), which occurred in 24 of the 35 patients (69%). Other associated cardiac lesions were ventricular septal defect in 10, pulmonary stenosis in 5, patient ductus arteriosus in 4 and coarctation or interruption of the aorta with subaortic membrane in 2. No clinical complications were associated with ASA. Six patients with complex heart disease died. When associated with ASD, the direction of the ASA motion and that of the shunt found by Doppler echocardiography were similar. Fourteen patients with ASD were followed for 0.5 to 4 years. In 8 the ASD closed and in 6 the ASA disappeared. In 6 patients the ASD and ASA persisted until the end of the follow-up (p less than 0.01). Thus, the incidence of ASA in children in this series was higher than previously presumed and usually was associated with other cardiac anomalies, mainly ASD. In children, ASA tends to disappear with age and may have a role in spontaneous closure of associated ASD.

Abnormalities, Multiple↗

Comparison of mortality and myocardial infarction rates in stable angina pectoris with and without ischemic episodes during daily activities.

The prognostic significance of ischemic changes during daily activities was assessed in 56 patients with stable angina pectoris. All patients had positive results on the treadmill stress test and angiographic evidence of significant coronary artery disease. Forty-three (77%) had ischemic episodes on Holter monitoring during everyday activities. During the follow-up period (mean 2 years), there were 6 deaths and 6 myocardial infarctions among the 43 patients with ischemic episodes, compared with none among the 13 patients without such changes (p less than 0.03). All 14 patients referred for coronary bypass surgery belonged to the group with ischemic episodes (p less than 0.02). The extent of coronary disease, the treadmill test parameters, and the duration and frequency of ischemia during daily activities were identical in the patients with and without subsequent cardiac events. Patients with only symptomatic ischemic episodes or those with both silent and symptomatic episodes had a frequency of cardiac events similar to that of patients with only silent episodes. Thus, it seems that patients with stable angina pectoris and ischemic episodes during daily activities have a worse prognosis than patients free from such episodes.

Activities of Daily Living↗