were examined by serial radionuclide studies in 46 patients with coronary artery disease. In 20 patients with ejection fractions (EFs) > 35% (group 1A), verapamil, 0.1 mg/kg given over 1-1'/2 minutes, had a biphasic effect: first, a transient decrease in EF accompanied by increased left ventricular (LV) volumes and cardiac output equivalents; then, an overshoot of EF to values above control, accompanied by a decrease in peripheral vascular resistance and a drastic decrease in LV volumes, while cardiac output equivalent remained slightly elevated. In eight patients with EFs < 35% (group 1B), only the first effect on EF was noted. In 10 patients with EFs > 35% (group 2), verapamil, 0.0640.075 mg/kg, exerted qualitatively similar but milder effects on hemodynamic function. Finally, verapamil, 0.1 mg/kg given more slowly, over 2-21/2 minutes, produced no significant changes in EF or LV volumes in another eight patients (group 3). The acute effects of verapamil are thus both time-related and dose-dependent. They are also related to the baseline functional reserve of the left ventricle. This study documents that verapamil exerts a depressant effect on LV function. However, the transient nature of this depression and the quick recovery to normal or above-normal values indicate that verapamil, in the doses used in this study, is safe to use intravenously in patients with coronary artery disease.

Background: Thrombophilia refers to series of acquired and inherited conditions that confer a tendency to thrombus formation. The exact relationship between thrombophilia and MI is not well established. Objectives: To determine the prevalence of thrombophilia, in young patients with their first MI and few conventional risk factors. Methods: We evaluated the baseline characteristics and the thrombophilia profile, including anti-cardiolipin antibodies, activated protein C resistance (APCR) with the factor V Leiden mutation, prothrombin G20210A mutation, protein C, protein S, and antithrombin-III levels, among 85 consecutive patients (< 50 year old) who were admitted to CCU with their first MI. Patients were divided into two groups: group A-patients with <= 1 risk factor and group B-patients with >= 2 risk factors. Results: 92% were male and 55% with anterior wall MI. Overall, the risk factor profile was: smoking in 60%, hyperlipidemia in 42%, positive family history in 29%, hypertension in 18%, diabetes mellitus in 13%, and obesity in 8%. Forty-seven percent of patients had <= 1 risk factor (n = 40, group A) and 53% had >= 2 risk factors (it = 45, group 13). The prevalence of the prothrombin mutation was 15% in group A compared to 7% in group B (p = 0.12). APCR secondary to a heterozygous genotype of factor V Leiden mutation was found in 20% in group A compared to 2% in group B (p < 0.01). Anti-cardiolipin antibodies were found in 16% in group A compared to 22% in group B (p = ns). Finally, we have found that the likelihood of identifying at least one thrombophilia marker was 50% in group A compared to 29% in group B (p = 0.046). Conclusions: The likelihood to detect at least one thrombophilia marker in young patients with MI and few conventional risk factors is significantly high. Thrombophilia may contribute to the development of MI in this specific group of young patients. (c) 2004 Elsevier Ireland Ltd. All rights reserved.

Leptin is secreted into the circulation and communicates the peripheral nutritional status to specific hypothalamic centers. Recent studies suggest that leptin may be involved in the acute response to stress, and that its interaction with the hypothalamo-pituitary-adrenal axis and the inflammatory cytokine system may be of clinical importance. Since these systems are activated during acute myocardial infarction (AMI), we studied leptin and cortisol levels during hospitalization in 30 consecutive patients admitted for AMI. The results show that leptin reached its peak on the second day of hospitalization, with a 2-fold increase from its baseline level on admission (p < 0.02). On day 3, leptin levels declined, and were 46%, 9%, and 6% above baseline on days 3, 4 and 5, respectively. The mean cortisol level was elevated on day 1 and decreased toward normal levels thereafter (p < 0.001). The cortisol level did not correlate with leptin concentration throughout the study. These findings suggest that leptin may have a role in the metabolic changes taking place during the first days after an AMI.

During routine fetal echocardiographic studies, we incidentally observed abrupt beat-to-beat changes in blood flow velocity and direction during bouts of hiccups in fetuses with a normal heart and regular and synchronized atrioventricular cardiac rhythm. The effect of hiccups on blood flow velocity and direction varied depending on the time of occurrence of hiccups during the cardiac cycle. In systole, a significant transient reduction of peak flow velocity occurred at the aortic and pulmonic valves, and brief tricuspid regurgitation appeared synchronously with each hiccup. In diastole, a transient reversal of flow direction was recorded simultaneously with the hiccup at the aorta and ductus arteriosus, and acceleration of peak flow velocity was observed across the tricuspid and mitral valves. Throughout the entire cardiac cycle, marked blood flow acceleration was observed in the superior vena cava, inferior vena cava, and ostium secundum simultaneously with the hiccup. A direct transmission of briefly augmented, negative intrathoracic pressure to a compliant aorta and systemic veins appears to be a reasonable explanation for most of our observations.

Infiltration by mononuclear cells, mostly monocytes: into necrotic myocardial tissue can be detected beyond the 3rd day after the onset of infarction. These monocytes, mobilized by an unknown mechanism, initiate phagocytosis of necrotic tissue. We observed in patients having sustained an acute myocardial infarction (AMI) a significant increase in monocyte count 2-3 days following presentation, possibly representing peripheral recruitment of monocytes to the injured myocardium. To establish this observation, we prospectively documented monocyte and neutrophil counts throughout hospitalization in 186 consecutive patients (118 patients having sustained an AMI, 34 patients with angina, and 34 patients admitted for nonischemic reasons). Average monocyte count, which rose on the 2nd day and reached a peak on day 3, was significantly elevated in these patients compared with control subjects (p < 0.001). Neutrophil count exhibited a similar phase-shifted response. Peak monocyte count exceeded 800/mm(3) (upper limit of normal range) in 69 (58%) of AMI patients but in only 3 of the 68 (4%) non-AMI patients, yielding a sensitivity and specificity of 58 and 95%, respectively, for the diagnosis of AMI by this criterion. A significant correlation between maximal creatine kinase (CK) representing the extent of myocardial necrosis and peak monocyte count was shown (r = 0.51, p < 0.0001). A correlation between CK and monocyte count sum of days 1-3 (r = 0.51, p < 0.001) was found in a substudy of 25 patients with AMI. Similarly, a correlation was shown with cardiac function score as evaluated by 2-dimensional echocardiography (p < 0.001 and p < 0.008 for difference between CK sum and monocyte count sum of high and low echo score groups, respectively). Hence, the peak monocyte count recorded during the immediate postinfarction period provides a bedside marker of the extent of myocardial damage that is the preponderant prognostic determinant, if validated in future studies this phenomenon may have diagnostic and prognostic implications.

Objectives, This study sought to evaluate expression of adhesion molecules on neutrophils and monocytes throughout the acute phase of myocardial infarction.Background. Neutrophil and monocyte counts increase within days from onset of acute myocardial infarction, Because leukocytes are recruited to the involved myocardial region, we postulated that these activated cells would display an increased expression of adhesion molecules necessary for effective endothelial transmigration.Methods. We measured the expression of neutrophil and monocyte lymphocyte function associated antigen-1 (LFA-1), Mac-1, very late after activation antigen-4 (VLA-4) and intercellular adhesion molecule-1 (ICAM-1) by flow cytometry throughout the acute phase of acute myocardial infarction in 25 patients and 10 age-matched control subjects.Results. Expression of Mac-1 on neutrophils increased significantly, whereas no expression of VLA-4 and ICAM-1 was detected. The expression of LFA-1, Mac-1, VLA-4 and ICAM-1 on the monocyte cell membrane in patients with an acute myocardial infarction was increased compared with that in control subjects by 228 (on day 7), 67%, 13% and 44% (all on day 4), respectively (all p < 0.001), Elevated density of monocyte-specific CD14 in the AMI versus the control group was also shown (30%, p < 0.001).Conclusions. Increased expression of neutrophil and monocyte adhesion molecules may contribute to their adhesion to endothelium in the ischemic territory, This adhesion could feasibly precipitate vasoconstriction or add a local thrombotic effect due to tissue factor expression secondary to Mac-1 engagement. In addition, the manifestation of increased density of LFA-1 and Mac-1 by activated leukocytes with monocytes also expressing ICAM-1 suggests that leukocytes may form microaggregates that could cause microvascular plugging, This mechanism may facilitate the occurrence of the "no-reflow" phenomenon or slow coronary filling after acute myocardial infarction. (C) 1998 by the American College of Cardiology.

Long QT syndrome (LQTS) is a potentially lethal, yet highly treatable, cardiac channelopathy. Cardiac transplantation has been reported anecdotally for patients with severe LQTS refractory to standard therapies.The purpose of this study was to evaluate the incidence of and risk factors for cardiac transplantation in children evaluated and treated in an LQTS specialty center.This was a retrospective review of 349 children with LQTS (mean age at diagnosis, 8.0 ± 5.7 years; mean corrected QT interval, 469 ± 51 ms; long QT syndrome type 1 [LQT1] in 46%, LQT2 in 31%, and LQT3 in 9%) evaluated from 2000 to 2013. A subset analysis was performed on patients referred for cardiac transplantation.Only 3 patients (0.9%; all LQT3; 2 female) underwent cardiac transplantation at ages 4, 11, and 17 years. Overall, 90 of 349 (26%) were symptomatic (exhibited LQTS-associated cardiac events) before LQTS diagnosis, including those who ultimately underwent transplant. Age at sentinel event was associated with transplantation (3 of 26 [12%] with an event at <1 year of life were transplanted vs 0 of 64 with an event after age 1; P = .02). Genotype was also a risk factor (3 of 32 patients with LQT3 were transplanted [9.4%] vs 0 of 270 patients with LQT1 or LQT2; P = .001). Before transplant, all patients had recurrent ventricular fibrillation–terminating shocks despite combination drug therapy and bilateral sympathetic denervation. All transplanted patients are alive at follow-up.Cardiac transplantation is seldom necessary for the management of LQTS. However, patients with LQT3 and in utero/neonatal expressivity are at higher risk of treatment failure and refractory ventricular arrhythmias with standard therapy, and cardiac transplantation should be considered for this malignant subset of LQTS.

Severe tricuspid regurgitation (TR) has occasionally been known to lead to marked pulsatility of varicose veins.1–3 We present an unusual case in which the presence of unilateral venous varicosities in only the right leg caused the appearance of unilateral pulsations.

Controlled clinical trials have demonstrated the efficacy of reducing the Mood levels of tow-density lipoprotein cholesterol in reducing the incidence of coronary artery disease in hypercholesterolemic middle-aged men. However, a similar reversibility of the risk of coronary artery disease has not been demonstrated for high-density lipoprotein cholesterol elevation and triglyceride reduction. Therefore, the effect of administering 400 mg of bezafibrate retard daily versus placebo (double Mind) to patients with myocardial infarction preceding randomization by 6 months to 5 years, or a clinically manifest anginal syndrome documented by objective evidence of dynamic myocardial ischemia, or both, is being investigated. Three thousand subjects (aged 45 to 74 years) are being enrolled from 19 cardiac departments in Israel, with total serum cholesterol between 180 and 250 mg/dl, high-density lipoprotein cholesterol ≤45 mg/dl and triglycerides ≤300 mg/dl. In addition, tow-density lipoprotein cholesterol concentrations are required to be ≤180 mg/dl (≤160 mg/dl for patients aged <50 years). Patients needing lipid-modifying therapy, exhibiting ≥1 prespecified exclusion criterion or not giving informed consent, or a combination, are not randomized. The primary end points for evaluating efficacy are the incidence of fatal and nonfatal myocardial infarction, and sudden death. The hypothesized effect of bezafibrate administration under the aforementioned protocol is to reduce an estimated cumulative end point event incidence of ≥15% by 20 to 25% over an average follow-up period of 6.25 years, through early 1998, when the last patient recruited will have completed 5 years. The sample size was determined on the basis of previous studies of the natural history of myocardial infarction in Israel, a plan for 2 interim analyses, an experiment-wise, 2-sided significance level of 0.05, and a power of 0.8 to detect an effect on end point incidence. Patient safety, and protocol and medication adherence are being monitored throughout.

A modified subcostal short-axis cross-sectional echocardiographic view for imaging the patent ductus arteriosus (PDA) was studied. A total of 22 newborns with PDA and various associated cardiac anomalies and 16 newborns without PDA were examined. The PDA was imaged in the subcostal view in 19 newborns. In the control group, the absence of the PDA was established in 13 newborns and considered probable in three. The PDA was optimally imaged in the subcostal view in patients with normal or enlarged pulmonary artery, mainly those with the hypoplastic left heart. Among the eight patients with small pulmonary artery (pulmonary atresia or severe tetralogy of Fallot), the PDA was imaged in the subcostal view in three and in the suprasternal view in eight. By combining the suprasternal and the subcostal views, the PDA was imaged in each instance.

Various mechanisms have been postulated for the supernormal phase of intraventricular conduction where relatively early impulses are conducted with normal intraventricular conduction and relatively late impulses with abnormal intraventricular conduction. The cases presented here illustrate how asynchronous recovery of conducting tissue may result in fortuitous momentary synchrony early on in the recovery phase with asynchronous conduction properties in the later phases of recovery. This will facilitate potential synchronous conduction early on in the cycle which would result in a normal QRS complex, and potential asynchronous conduction in the later phases which would manifest with a bundle branch block QRS complex.