Estimating the probability that the Taser directly causes human ventricular fibrillation.

This paper describes the first methodology and results for estimating the order of probability for Tasers directly causing human ventricular fibrillation (VF). The probability of an X26 Taser causing human VF was estimated using: (1) current density near the human heart estimated by using 3D finite-element (FE) models; (2) prior data of the maximum dart-to-heart distances that caused VF in pigs; (3) minimum skin-to-heart distances measured in erect humans by echocardiography; and (4) dart landing distribution estimated from police reports. The estimated mean probability of human VF was 0.001 for data from a pig having a chest wall resected to the ribs and 0.000006 for data from a pig with no resection when inserting a blunt probe. The VF probability for a given dart location decreased with the dart-to-heart horizontal distance (radius) on the skin surface.

Comparison of combinations of drugs for treatment of obesity: body weight and echocardiographic status.

BACKGROUND: Obesity treatment with single drugs produces weight losses of about 8-10% of initial body weight. Few studies of combinations of drugs for treating obesity have been published. The combination of phentermine, an adrenergic agent, and fenfluramine, a serotonergic agent, (phen-fen) produced weight losses of about 15% of initial body weight. Fenfluramine is no longer available because it was associated with cardiac valve lesions. Phentermine-fluoxetine (phen-flu) has been proposed as an alternative for phen-fen. OBJECTIVE: To compare the efficacy of treatment and prevalence of cardiac valve abnormalities on phen-flu vs phen-fen. DESIGN: Retrospective chart review of all patients treated for at least 3 months with phen-flu (N=97) to a random sample of patients treated with phen-fen (N=98) in the Clinical Nutrition Clinic at the University of Wisconsin. Comparison of echocardiograms in all patients treated solely with phen-flu (N=21) to a random sample of patients treated with phen-fen (N=47), and to a group of subjects never treated with obesity drugs (N=26). RESULTS: With last observation carried forward analysis (LOCF), at 6 months of treatment the phen-fen patients lost 12.6+/-0.6% of baseline weight and phen-flu patients lost 9.0+/-0.6% (P<0.001). With completers analysis, there were no significant differences in weight loss as a percent of baseline weight at 6 months (14.4+/-0.6 vs 13.3+/-0.9%). LOCF decreases in body mass index (BMI) at 6 months were -5.3 and -3.6 kg/m(2) for phen-fen and phen-flu, respectively (P<0.001), and 6.2+/-0.3 vs 5.4+/-0.4 kg/m(2), respectively, for the completers analysis (P - NS). Dropout rate at 6 months was higher in phen-flu subjects (44 vs 28%). In subjects without atherosclerosis of valves (presumably pre-existing), cardiac valve lesions occurred in eight of 38 phen-fen subjects and in none of 15 phen-flu subjects or 25 control subjects who had not been treated with drugs. CONCLUSIONS: The combination of phentermine and fluoxetine was not as effective as phen-fen, but was not associated with cardiac valve lesions. Longer term, larger scale studies of phen-flu are warranted.

Assessing prosthetic mitral valve regurgitation by transoesophageal echo/Doppler.

Transoesophageal echocardiography has greatly improved our ability to detect structural and regurgitant abnormalities associated with prosthetic mitral valves.

Low-dose enoximone improves exercise capacity in chronic heart failure. Enoximone Study Group.

OBJECTIVES: This study was designed to evaluate the effects of low-dose enoximone on exercise capacity. BACKGROUND: At higher doses the phosphodiesterase inhibitor, enoximone, has been shown to increase exercise capacity and decrease symptoms in heart failure patients but also to increase mortality. The effects of lower doses of enoximone on exercise capacity and adverse events have not been evaluated. METHODS: This is a prospective, double-blind, placebo-controlled, multicenter trial (nine U.S. centers) conducted in 105 patients with New York Heart Association class II to III, ischemic or nonischemic chronic heart failure (CHF). Patients were randomized to placebo or enoximone at 25 or 50 mg orally three times a day. Treadmill maximal exercise testing was done at baseline and after 4, 8 and 12 weeks of treatment, using a modified Naughton protocol. Patients were also evaluated for changes in quality of life and for increased arrhythmias by Holter monitoring. RESULTS: By the protocol-specified method of statistical analysis (the last observation carried-forward method), enoximone at 50 mg three times a day improved exercise capacity by 117 s at 12 weeks (p = 0.003). Enoximone at 25 mg three times a day also improved exercise capacity at 12 weeks by 115 s (p = 0.013). No increases in ventricular arrhythmias were noted. There were four deaths in the placebo group and 2 and 0 deaths in the enoximone 25 mg three times a day and enoximone 50 mg three times a day groups, respectively. Effects on degree of dyspnea and patient and physician assessments of clinical status favored the enoximone groups. CONCLUSIONS: Twelve weeks of treatment with low-dose enoximone improves exercise capacity in patients with CHF, without increasing adverse events.

Transesophageal echocardiography for the evaluation and management of patients with cerebral ischemia.

To prevent recurrent strokes and transient ischemic attacks, considerable attention is devoted to investigating the etiology of acute cerebral ischemia in the large subpopulation of patients without an easily identifiable cause. In general, transthoracic echocardiography is an insensitive tool for the evaluation of patients with cerebral ischemia, unless clinical signs and/or symptoms of cardiac disease are present. Transesophageal echocardiography (TEE), because of its increased sensitivity for aortic arch atheromata, atrial septal pathology, left atrial thrombi, and valvular abnormalities, is the preferred cardiac imaging modality, especially in young patients, older patients with hypertension or systemic atherosclerosis, and patients with prosthetic heart valves. This paper reviews the prognostic and therapeutic impact of TEE in patients with cerebral ischemia, specifically focusing on the ability of information obtained by this technique to alter patient management and improve risk stratification.

Adenosine myocardial protection: preliminary results of a phase II clinical trial.

OBJECTIVE: To evaluate the safety, tolerance, and efficacy of adenosine in patients undergoing coronary artery bypass surgery. SUMMARY BACKGROUND DATA: Inadequate myocardial protection in patients undergoing coronary artery bypass surgery contributes to overall hospital morbidity and mortality. For this reason, new pharmacologic agents are under investigation to protect the regionally and globally ischemic heart. METHODS: In a double-blind, placebo-controlled trial, 253 patients were randomized to one of three cohorts. The treatment arms consisted of the intraoperative administration of cold blood cardioplegia, blood cardioplegia containing 500 microM adenosine, and blood cardioplegia containing 2 mM adenosine. Patients receiving adenosine cardioplegia were also given an infusion of adenosine (200 microg/kg/min) 10 minutes before and 15 minutes after removal of the aortic crossclamp. Invasive and noninvasive measurements of ventricular performance were obtained before, during, and after surgery. RESULTS: The high-dose adenosine cohort was associated with a trend toward a decrease in high-dose dopamine support and a lower incidence of myocardial infarction. A composite outcome analysis demonstrated that patients who received high-dose adenosine were less likely to experience one of five adverse events: high-dose dopamine use, epinephrine use, insertion of intraaortic balloon pump, myocardial infarction, or death. The operative mortality rate for all patients studied was 3.6% (9/253). CONCLUSIONS: Adenosine treatment is safe and well tolerated and may be associated with fewer postoperative complications.

High-voltage injury resulting in permanent right heart dysfunction.

This report describes the case of a 27-year-old man who survived a high-voltage chest injury that resulted in acute biventricular dysfunction. Although the prognosis is generally poor, complete recovery of cardiac function over days to weeks has been documented. This case is unique because the patient regained complete recovery of left ventricular function over 3 months, but had persistent right heart dysfunction on serial echocardiographic evaluations.

Ischemic stroke associated with activated protein C resistance and aortic valvular papillary fibroelastoma.

We report an unusual case of a pontine ischemic stroke associated with activated protein C resistance as well as an embolic source in the form of a cardiac valvular lesion. A 31-year-old man had a sudden onset of right hemiparesis and a severe dysarthria. Cranial magnetic resonance imaging (MRI) showed a nonhemorrhagic pontine lesion with essentially negative craniocervical MR angiography. His transesophageal echocardiogram showed a papillary fibroelastoma on the aortic valve. His laboratory studies showed significant activated protein C resistance at 1.7 (normal, >2.1). Other laboratory parameters, including sedimentation rate, were unremarkable. This case suggests that activated protein C resistance may serve as a cofactor in some cases of ischemic stroke, particularly stroke associated with emboligenic cardiac lesions.

Safety, tolerance, and efficacy of adenosine as an additive to blood cardioplegia in humans during coronary artery bypass surgery.

Myocardial stunning after heart surgery is associated with increased morbidity and mortality in patients with severe multivessel disease and reduced myocardial function. The purpose of this study was to evaluate the safety, tolerance, and efficacy of adenosine as a cardioprotective agent when added to blood cardioplegia in patients undergoing coronary artery bypass surgery. Sixty-one patients were randomized to standard cold-blood cardioplegia, or cold-blood cardioplegia containing 1 of 5 adenosine doses (100 microM, 500 microM, 1 mM, 2 mM, and 2 mM with a preischemic infusion of 140 microg/kg/min of adenosine). Invasive and noninvasive measurements of ventricular performance and rhythm were obtained preoperatively, prebypass, and then at 1, 2, 4, 8, 16, and 24 hours postbypass. Use of inotropic agents and vasoactive drugs pastoperatively was recorded; blood samples were collected for measurement of nucleoside levels. High-dose adenosine treatment was associated with a 249-fold increase in the plasma adenosine concentration and a 69-fold increase in the combined levels of adenosine, inosine, and hypoxanthine (p <0.05). Increasing doses of the adenosine additive were also associated with lower requirements of dopamine (p = 0.003) and nitroglycerine (p = 0.001). The 24-hour average doses for dopamine and nitroglycerine in the placebo group were 28-fold and 2.6-fold greater than their respective high-dose adenosine treatment cohorts. Finally, the placebo- and 100 microM-adenosine group was associated with a lower ejection fraction when compared to patients receiving the intermediate dose or high-dose treatment. These findings are consistent with the hypothesis that adenosine is effective in attenuating myocardial stunning in humans.

Adenosine reduces postbypass transfusion requirements in humans after heart surgery.

OBJECTIVE: The objective of this study was to determine the effect, if any, of adenosine blood cardioplegia on blood component usage after heart surgery. SUMMARY BACKGROUND DATA: The most common cause of nonsurgical postcardiopulmonary bypass bleeding is platelet dysfunction. For this reason, pharmacologic agents are under investigation in an effort to reduce the need for transfusion in this setting. METHODS: A posthoc analysis of blood product usage was performed in data obtained from a Phase I, single center, open label, randomized study performed in 63 patients. The trial was designed to test the safety and tolerance of adenosine when added to blood cardioplegia in increasing doses to enhance myocardial protection. The database provided information regarding the effect of adenosine cardioplegia on venous plasma adenosine concentrations, the amount of platelets, fresh frozen plasma and packed erythrocytes used, and the association between the adenosine dose and postoperative thoracic drainage. RESULTS: The postoperative thoracic drainage at 6 hours, 24 hours, and at the time of chest tube removal in the high-dose adenosine cardioplegia group was 68%, 76%, and 75% of the placebo and low-dose adenosine cardioplegia group (p < 0.05). The highest dose of adenosine studied increased baseline adenosine venous plasma levels 360-fold, from 0.17 +/- 0.09 mumol/L to 42.30 +/- 11.20 mumol/L (p < 0.05). This marked increase was associated with a 68%, 56%, and 58% reduction in platelet, fresh frozen plasma, and packed erythrocyte usage, respectively (p < 0.05). CONCLUSIONS: In addition to enhancing the heart's tolerance to ischemia, adenosine-supplemented cardioplegic solution also may reduce bleeding after cardiopulmonary bypass.

Transthoracic and transesophageal echocardiographic evaluation of the aortic root and subvalvular structures in ankylosing spondylitis.

OBJECTIVE: During the preclinical phase of cardiac involvement in ankylosing spondylitis (AS), examination, electrocardiography, and transthoracic echocardiography (TTE) may lack the sensitivity to detect cardiac abnormalities. Since transesophageal echocardiography (TEE) allows a closer view of the aortic root and subvalvular structures we investigated whether preclinical abnormalities of the aortic root and subvalvular structures could be detected. METHODS: Clinical and echocardiographic (TTE and TEE) evaluation of 29 male patients with AS and 13 age matched controls. RESULTS: No patient with AS had a high degree heart block. Aortic root dimensions were comparable between the study groups, but the anterior aortic wall was thinner in patients with AS than controls, 0.25 and 0.41 cm, respectively (p = 0.016). The posterior aortic wall was thicker and subjectively more echogenic than the anterior wall in 17/29 patients with AS compared to 4/13 controls. Aortic valve insufficiency was detected with TEE in 10/29 patients with AS. In 8/9 patients with AS studied with TEE, the subaortic structures were thickened and/or of increased echogenicity. This abnormal echo extended into the membranous septum. CONCLUSION: Abnormal subvalvular echoes consistent with fibrosis of the aortic root and membranous interventricular septum were detected with TEE but not TTE. The use of TEE may allow earlier diagnosis of cardiac involvement in AS.

Doppler echocardiographic characteristics of sinus of valsalva aneurysms.

This study evaluated the efficacy of a comprehensive transthoracic Doppler echocardiographic examination for correct detection of SVA and its associated lesions of VSD and aortic insufficiency. A consecutive series of 36 patients was obtained; all had surgical confirmation of the anatomic defects. The location of the SVA was correctly determined in 97% of patients, and the associated presence of a VSD was correctly determined in 79% of the studies. In the cases in which Doppler was available, all 11 patients with associated aortic insufficiency were detected. In this series 32 patients had right SVA, 3 had noncoronary sinus SVA, and 1 had a left SVA. Relative frequency of the rupture site location corresponded closely to that in previous necropsy studies. It is concluded that transthoracic Doppler echocardiography can correctly localize SVAs and most associated lesions.

The clinical utility of automatic boundary detection for the determination of left ventricular volume: a comparison with conventional off-line echocardiographic quantification.

The aim of this study was to compare measurements of echocardiographic volume with an on-line automatic boundary detection imaging system with those of a conventional off-line method for routine clinical studies. Automatic boundary detection imaging shows promise as a rapid, on-line method for quantitating left ventricular volumes by echocardiography. However, there is little information about the role of automatic boundary detection for routine clinical studies. Ninety-seven patients with a variety of clinical diseases who were referred for clinical transthoracic echocardiographic evaluation were studied in apical four-chamber and two-chamber imaging planes. End-diastolic volume, end-systolic volume, and ejection fraction obtained with automatic boundary detection images were compared with those of conventional off-line analysis. Segmental endocardial definition and border tracking were evaluated on all automatic boundary detection images. Left ventricular end-diastolic volumes obtained by automatic boundary detection correlated well but were systematically under-estimated compared with off-line analysis for the apical two-chamber (r = 0.83; underestimation = 42 +/- 33 ml; p < 0.05) and four-chamber views (r = 0.83; underestimation = 43 +/- 31 ml; p < 0.05). Left ventricular end-systolic volumes also correlated well but were underestimated by automatic boundary detection for the apical two-chamber (r = 0.83; underestimation = 14 +/- 26 ml; p < 0.05) and four-chamber views (r = 0.83; underestimation = 18 +/- 24 ml; p < 0.05). Ejection fraction was not predicted accurately for the entire study population (n = 97). However, for patients with complete endocardial definition (n = 32), automatic boundary detection accurately predicted ejection fraction with no systematic error compared with manually traced images for both the apical two-chamber (r = 0.86; p < 0.05) and four-chamber (r = 0.82; p < 0.05) views. Segmental analysis of endocardial tracking revealed significantly better tracking of the septal and lateral walls compared with other regions (p < 0.05). End-diastolic and end-systolic volumes determined by automatic boundary detection correlate well but underestimate volume compared with conventional off-line analysis. However, ejection fraction compares favorably for the two methods when there is complete endocardial definition.

Hemodynamic and volumetric response of the normal left ventricle to upright tilt testing.

The purpose of this study were to determine the specificity of the head-up tilt test in normal subjects when a graded isoproterenol infusion is used, and to evaluate the role of dynamic ventricular volume change during head-up tilt as a mechanism of syncope. We prospectively studied 12 normal volunteers, each of whom underwent an upright tilt test for 10 minutes at 80 degrees with and without an infusion of isoproterenol. A subgroup of five subjects had a third tilt test during administration of a combination of esmolol and isoproterenol. Blood pressure, heart rate, and left ventricular volumes and flow (obtained with Doppler echocardiography) were recorded in the following sequence: while supine, during upright tilt, while supine with isoproterenol, and during upright tilt with isoproterenol. During the initial head-up tilt, one subject had syncope. An additional eight subjects had presyncope or syncope during head-up tilt with isoproterenol. The remaining three subjects were asymptomatic. In subjects with syncope or near-syncope ("responders"), heart rate increased with isoproterenol but decreased markedly, to 76 +/- 5 beats/min, by the end of the protocol. Systolic blood pressure rose slightly above baseline during isoproterenol but fell from 118 +/- 4 to 85 +/- 5 mm Hg during head-up tilt with isoproterenol. The three asymptomatic subjects had only one significant change, an increase in heart rate with isoproterenol. In the five responders undergoing three tilt tests, left ventricular volume decreased significantly at end diastole (94 +/- 25 vs 58 +/- 22 ml) and end systole (34 +/- 13 vs 18 +/- 6 ml) when supine baseline is compared with initial upright tilt.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative efficacy of three indexes of left ventricular performance derived from pressure-volume loops in heart failure induced by tachypacing.

OBJECTIVES: The purpose of this study was to serially evaluate the response and variability of the end-systolic pressure-volume relation, the left ventricular end-diastolic volume-peak positive first derivative of left ventricular pressure (dP/dt) relation and the left ventricular end-diastolic volume-stroke work relation in the development of progressive left ventricular dysfunction. BACKGROUND: Evaluation of systolic performance of the failing left ventricle may be enhanced by using relatively load-insensitive measures of left ventricular performance. The end-systolic pressure-volume, left ventricular end-diastolic volume-peak positive dP/dt and left ventricular end-diastolic volume-stroke work relations adequately define left ventricular performance under multiple loading conditions, but efficacy has not been fully assessed in the failing heart, particularly in the intact circulation. METHODS: Fourteen dogs underwent instrumentation and rapid pacing to heart failure. Variably loaded pressure-volume beats were produced by inferior vena cava occlusion. The dogs were evaluated at baseline and at three progressively more severe levels of left ventricular dysfunction. RESULTS: There was a progressive increase in left ventricular volumes at end-diastole ([mean value +/- SE] 60 +/- 28 to 73 +/- 29 ml, p < 0.001) and end-systole (39 +/- 19 to 61 +/- 27 ml, p < 0.001) during the 3 weeks of rapid pacing and a progressive decline in peak positive dP/dt (1,631 +/- 410 to 993 +/- 222 mm Hg/s, p < 0.001) and ejection fraction (37 +/- 8% to 16 +/- 11%, p < 0.001). There was a corresponding decline in the slope of each of the three relations: for end-systolic pressure-volume, 6.3 +/- 2.2 to 2.8 +/- 0.7 (p < 0.05); for left ventricular end-diastolic volume-stroke work, 61.9 +/- 9.1 to 26.5 +/- 2.4 (p < 0.05); and for left ventricular end-diastolic volume-peak positive dP/dt, 47.1 +/- 13.6 to 20.31 +/- 6.8 (p < 0.05). There was also a corresponding increase in position volumes: for end-systolic pressure-volume, 33.6 +/- 3.9 to 61.2 +/- 6.6 ml (p < 0.05); for left ventricular end-diastolic volume-stroke work, 46.2 +/- 3.6 to 89.3 +/- 7.6 ml (p < 0.05); and for left ventricular end-diastolic volume-peak positive dP/dt, 29.1 +/- 19.1 to 68.6 +/- 25.9 ml (p < 0.05). The relative degree of change in each of the three relations was similar as more severe heart failure developed. The coefficients of variation for position were significantly less than the variation for slopes. The response of volume intercepts was heterogeneous. For left ventricular end-diastolic volume-stroke work, the intercept increased as ventricular performance decreased. The intercept of the end-systolic pressure-volume relation was significantly more variable than the left ventricular end-diastolic volume-stroke work relation and did not change with progressive heart failure. The intercept for left ventricular end-diastolic volume-peak positive dP/dt was highly variable and showed no consistent changes as left ventricular function declined. CONCLUSIONS: All three relations consistently describe changes in left ventricular performance brought about by tachypacing. Evolution of left ventricular dysfunction causes a decline in slope and a rightward shift of these relations. The position of the relation is the most sensitive and least variable indicator of left ventricular systolic performance.

Improved echocardiographic detection and characterization of left ventricular apical thrombi with a 5.0 MHz short-focus transducer.

Transthoracic echocardiography is a frequently used technique for detecting ventricular thrombi. This study compares the usefulness of a 5.0 MHz short focal length transducer (5-short) with standard frequency (2.5 or 3.5 MHz) transducers for the detection of left ventricular thrombi. In addition, the effect of body habitus on study quality was evaluated. A consecutive series of 101 patients sent for echocardiographic imaging with the diagnosis of myocardial infarction, dilated cardiomyopathy, or recent suspected embolic event were imaged in the apical four-chamber, apical long-axis, and apical two-chamber views with a standard transducer and also with the 5-short. Out of this group, 16 apical thrombi were identified, six with the 5-short only, three with standard transducers only, and seven by both techniques. The areas of the seven thrombi detected by both transducers were consistently larger when measured on 5-short images compared with standard transducer images (4.6 +/- 2.3 vs 3.7 +/- 2.3 cm2, p = 0.02). In the three studies positive only with the standard transducers, the 5-short demonstrated only prominent trabeculae but no thrombus. The studies positive only with the 5-short had significantly smaller calculated thrombi areas than those visualized by the standard transducers (1.6 +/- 1.2 vs 4.2 +/- 2.1 cm2, p = 0.02). No thrombus was detected by either technique in a normally contracting left ventricular apex. There were significantly fewer studies having near-field artifact when performed by the 5-short compared with those performed with standard transducers (14/101 vs 40/101, p = 0.00004).(ABSTRACT TRUNCATED AT 250 WORDS)

Doppler echocardiographic evaluation of ventricular septal defects in adults.

Ventricular septal defects account for 10% to 15% of all congenital heart defects observed in adults. The type of defects observed tend to fall at the extreme ends of the spectrum: small restrictive defects with minimal shunts, and large nonrestrictive defects associated with severe occlusive pulmonary vascular disease. Doppler echocardiography has evolved into a powerful diagnostic modality that comprehensively evaluates the anatomical and pathophysiological consequences of a ventricular septal defect. The spectrum of findings caused by ventricular septal defects is the subject of this review.

Relative contributions of cardiopulmonary and sinoaortic baroreflexes in causing sympathetic activation in the human skeletal muscle circulation during orthostatic stress.

The aim of this study was to reexamine the hypothesis that cardiopulmonary baroreflexes are more important than sinoaortic baroreflexes in causing vasoconstriction in the skeletal muscle circulation during orthostatic stress. We recorded muscle sympathetic nerve activity (MSNA) with microelectrodes in the peroneal nerve (and forearm blood flow with venous occlusion plethysmography) in normal subjects (innervated ventricles) and in heart transplant recipients (denervated ventricles) during graded lower body negative pressure (LBNP) performed alone and in combination with intravenous infusion of phenylephrine, which was titrated to eliminate the orthostatically induced fall in blood pressure and thus the unloading of both carotid and aortic baroreceptors. The principal new findings are as follows: (1) The increases in both MSNA and forearm vascular resistance during multiple levels of LBNP were not attenuated by heart transplantation, which causes ventricular but not sinoaortic deafferentation. (2) In heart transplant recipients, a small increase in MSNA during mild LBNP was dependent on a decrease in arterial pressure, but in normal subjects, a similar increase in MSNA occurred in the absence of any detectable decrease in the aortic pressure stimulus to the sinoaortic baroreceptors. (3) In normal subjects, the large increase in MSNA during a high level of LBNP was dependent on a decrease in arterial pressure and could be dissociated from the decrease in central venous pressure. Taken together, the findings strongly suggest that sinoaortic baroreflexes are much more important and ventricular baroreflexes are much less important than previously thought in causing reflex sympathetic activation and vasoconstriction in the human skeletal muscle circulation during orthostatic stress.