Showing papers in "American Journal of Cardiology in 1991"

Accuracy of assessment of cardiac vagal tone by heart rate variability in normal subjects.

Abstract: The correlations of 11 indexes of heart rate variability were examined with pharmacologically determined cardiac vagal tone in 15 normal subjects at supine rest. After sympathetic influences by intravenous propranolol were eliminated, RR interval variability was measured for 10 minutes under controlled respiration (0.25 Hz), and cardiac vagal tone was determined as the decrease in mean RR interval following complete vagal blockade with atropine. Time domain indexes (standard deviation, coefficient of variance and mean successive difference) correlated strongly with vagal tone (r = 0.87, 0.81 and 0.92, respectively; p less than 0.001 for all). The same was true for frequency domain indexes for the high-frequency (0.25 Hz) component calculated both by autoregressive spectrum analysis (square root of power and coefficient of component variance) and by fast Fourier transform (mean amplitude) (r = 0.91, 0.85 and 0.86, respectively; p less than 0.0001 for all). However, frequency domain indexes for the low-frequency spectral component (0.03 to 0.15 Hz) correlated less strongly (r = 0.69, 0.55 and 0.70, respectively), and the fraction of power [power/(total power greater than 0.03 Hz)] of both components showed no correlation. Principal component analysis showed that the first 6 indexes with strong correlations contained solely the first principal component closely related to vagal tone, whereas the remaining 5 indexes also contained the second component unrelated to vagal tone. These results indicate that most of the time and frequency domain analyses in use provides an accurate and common measure of cardiac vagal tone at rest.

Intracellular compartmentation of cardiac troponin T and its release kinetics in patients with reperfused and nonreperfused myocardial infarction.

Abstract: In a previous study on the diagnostic efficiency of troponin T measurements in patients with suspected acute myocardial infarction (AMI), the authors found a high variability of troponin T serum concentration changes on day 1 in patients with AMI who underwent thrombolytic treatment. Therefore, the aims of the present study were to investigate the intracellular compartmentation of troponin T and to analyze the effects of AMI reperfusion on the appearance kinetics of cardiac troponin T in serum. Cardiac troponin T was measured with a newly developed bideterminant sandwich assay using cardiospecific, affinity-purified polyclonal antibodies and peroxidase-labeled monoclonal antibody. An unbound cytosolic troponin T pool was found in ultracentrifuged homogenates of myocardial tissue of different species ranging from 0.013 to 0.036 mg/g wet weight. The soluble troponin T molecule had electrophoretic properties identical to troponin T compartmented in the myofibrils. The clinical study group comprised 57 patients with AMI undergoing thrombolytic treatment. Blood flow to the infarct zone and point of time of reperfusion were tested by immediate and late angiography. The appearance of troponin T in serum on day 1 after the onset of AMI depended strongly on reperfusion and on duration of ischemia before reperfusion. Thus, in patients with early reperfused AMI, a marked peak in troponin T serum concentrations was found at 14 hours after the onset of pain. This early troponin T peak was absent in patients with AMI reperfusion occurring greater than 5.5 hours after the onset of pain and in patients with nonreperfused AMI. By contrast, the kinetics of troponin T release after the first day after AMI were unaffected by reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiographic evidence for the existence of a distinct diabetic cardiomyopathy (the framingham heart study)

Abstract: Although several reports have described early changes of cardiac structure and function in diabetic patients, controversy persists regarding the existence of a clinically distinct diabetic cardiomyopathy. To this end, sex-specific linear regression analyses were used to examine the contribution of diabetes mellitus and glucose intolerance to age-adjusted echocardiographic parameters in 1,986 men (mean age 48 years) and 2,529 women (mean age 50 years) from the original Framingham Study cohort and the Framingham Offspring Study. Subjects with evidence of cardiovascular disease at the time of echocardiogram were excluded. Diabetics had higher heart rates than nondiabetics (67.9 vs 64.0 beats/min (p = 0.002) in men, and 73.1 vs 68.3 beats/min (p = 0.004) in women). Diabetic women had increased left ventricular (LV) wall thickness (18.7 vs 17.1 mm, p less than 0.001), relative wall thickness (0.403 vs 0.377, p = 0.008), LV end-diastolic dimension (46.9 vs 45.7 mm, p = 0.03) and LV mass corrected for height (100.4 vs 82.2 g/m, p less than 0.001). Women with glucose intolerance showed similar, less significant trends (p = 0.007 for wall thickness, p less than 0.01 for LV mass). In diabetic men, fractional shortening was slightly reduced (0.355 vs 0.360, p less than 0.05). In a multivariate model that included potentially confounding factors, diabetes remained an independent contributor to LV mass (p = 0.004) and wall thickness (p = 0.008) in women. In a separate linear regression model, which assessed the association of age with LV mass, the age-coefficient for diabetic women was much higher than that for nondiabetics (13.6 vs 6.6 g/m per 10-year increment in age).(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction of uneventful cardioversion and maintenance of sinus rhythm from direct-current electrical cardioversion of chronic atrial fibrillation and flutter.

Abstract: The present study was undertaken to reassess prospectively the immediate and long-term results of direct-current electrical cardioversion in chronic atrial fibrillation or atrial flutter, and to determine factors predicting clinical outcome of the arrhythmia after direct-current cardioversion. Two-hundred forty-six patients underwent direct-current electrical cardioversion and were followed during a mean of 260 days. Multivariate analysis was used to identify factors predicting short- and long-term arrhythmia outcome. Cardioversion was achieved in 70% of patients with atrial fibrillation and in 96% of patients with atrial flutter. Stepwise logistic regression analysis revealed that arrhythmia duration (p less than 0.001), type of arrhythmia (fibrillation vs flutter, p less than 0.02) and age (p less than 0.05) independently influenced conversion rate. On an actuarial basis, 42 and 36% of patients remained in sinus rhythm during 1 and 2 years, respectively. Multivariate regression analysis revealed that the type of arrhythmia (p = 0.0008), low precardioversion functional class (p = 0.002) and the presence of nonrheumatic mitral valve disease (p = 0.03) independently increased the length of the arrhythmia-free episode. Rheumatic heart disease shortened this period (p = 0.03). In conclusion, patients having a high probability of conversion together with a prolonged post-shock arrhythmia-free episode can be identified. This may improve the cost-benefit ratio of cardioversion.

Sudden unexpected death in persons <40 years of age

Abstract: This study retrospectively assesses the underlying causes of sudden unexpected death and the occurrence of prodromal symptoms in 162 subjects (aged 9 to 39 years) over a 10-year period (1976 to 1985). Underlying cardiac diseases accounted for sudden death in 73% and noncardiac causes in 15% of subjects. In 12% of subjects, the causes were unidentifiable. Myocarditis (22%), hypertrophic cardiomyopathy (22%) and conduction system abnormalities (13%) were the major causes in 32 subjects aged less than 20 years. Major causes of 46 deaths in subjects 20 to 29 years were atherosclerotic coronary artery disease (24%), myocarditis (22%) and hypertrophic cardiomyopathy (13%). The largest number of deaths in 84 subjects aged greater than or equal to 30 years was attributed to coronary artery disease (58%), followed by myocarditis (11%). Among noncardiac causes of sudden death, intracranial hemorrhage was the most frequent (5%), followed by infectious disease (4%). Prodromal symptoms were reported by 54% of subjects; most frequent were chest pain (25%) in subjects aged greater than or equal to 20 years, and dizziness (16%) in those aged less than 20. Sudden death, which occurred during routine daily activity in 49% and during sleep in 23% of subjects, was related to physical exercise in 23% and emotional upset in 6%. Sudden unexpected death in the young is still an unresolved medical problem. The early recognition of prodromal symptoms could be crucial in the prevention of sudden death, specifically when exercise-related.

Comparison of the predictive characteristics of heart rate variability index and left ventricular ejection fraction for all-cause mortality, arrhythmic events and sudden death after acute myocardial infarction.

Abstract: Heart rate (HR) variability index and left ventricular ejection fraction (EF) were compared for the prediction of all-cause mortality, arrhythmic events and sudden death in 385 survivors of acute myocardial infarction. For arrhythmic events, where, for a sensitivity of 75%, HR variability index had a specificity of 76%, EF had a specificity of only 45%. An EF of ≤40% had a sensitivity of 42% and a specificity of 75% for arrhythmic events; for the same sensitivity an HR variability index of 20 U had a specificity of 92%. An EF ≤40% had a sensitivity of 40% and a specificity of 73% for sudden death; HR variability index had a specificity of 83% for the same sensitivity. For all cause mortality, where, for a sensitivity of 75%, HR variability index had a specificity of 52%, EF had a specificity of 40%. It is concluded that HR variability index appears a better predictor of important postinfarction arrhythmic complications than left ventricular EF, but both indexes perform equally well in predicting all-cause mortality.

Relative importance of activation sequence compared to atrioventricular synchrony in left ventricular function

Abstract: This study evaluated the relative hemodynamic importance of a normal left ventricular (LV) activation sequence compared to atrioventricular (AV) synchrony with respect to systolic and diastolic function. Twelve patients with intact AV conduction and AV sequential pacemakers underwent radionuclide studies at rest and Doppler echocardiographic studies at rest and during submaximal exercise, comparing atrial demand pacing (AAI) to sequential AV sensing pacing (DDD) and ventricular demand pacing (VVI). Studies at rest were performed at a constant heart rate between pacing modes, and the exercise study was performed at a constant heart rate and work load. Cardiac output was higher during AAI than during both DDD and VVI (6.2 +/- 1 vs 5.6 +/- 1 and 5.3 +/- 1 liters/min, p less than 0.05). LV ejection fraction was likewise higher during AAI (55 +/- 12 vs 49 +/- 11 vs 51 +/- 13, p less than 0.05). VVI with or without AV synchrony was associated with a paradoxical septal motion pattern, resulting in a 25% impairment of regional septal ejection fraction. In addition, LV contraction duration was more homogenous during AAI. Peak filling rate during AAI and VVI was higher than during DDD (2.86 +/- 1 and 2.95 +/- 1 vs 2.25 +/- 1 end-diastolic volume/s; p less than 0.05). During VVI, the time to peak filling was significantly shorter than during both AAI and DDD (165 +/- 34 vs 239 +/- 99 and 224 +/- 99 ms; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Stability over time of variables measuring heart rate variability in normal subjects

Abstract: Both time and frequency domain measures of heart rate (HR) variability have been used to assess autonomic tone in a variety of clinical conditions. Few studies in normal subjects have been performed to determine the stability of HR variability over time, or the correlation between and within time and frequency domain measures of HR variability. Fourteen normal subjects aged 20 to 55 years were studied with baseline and placebo 24-hour ambulatory electrocardiograms performed 3 to 65 days apart to assess the reproducibility of the following time domain measures of cycle length variability: the standard deviation of all normal cycle intervals; mean normal cycle interval; mean day normal cycle interval; night/day difference in mean normal cycle interval; root-mean-square successive cycle interval difference; percentage of differences between adjacent normal cycle length intervals that are >50 ms computed over the entire 24-hour electrocardiographic recording (proportion of adjacent intervals >50 ms); and the frequency domain measures of high (0.15 to 40 Hz), low (0.003 to 0.15) and total (0.003 to 0.40) power. The mean and standard deviations of these measures were virtually identical between placebo and baseline measurements and within the studied time range. Variables strongly dependent on vagal tone (high-frequency, low-frequency and total power, root-mean-square successive difference, and percentage of differences between adjacent normal cycle intervals >50 ms computed over the entire 24-hour electrocardiographic recording) were highly correlated (r > 0.8). It is concluded that measures of HR variability are stable over short periods of time. Certain time and frequency domain variables are highly correlated and may serve as surrogates for each other, and no placebo effect on these variables is evident.

Effects on quality of life with comprehensive rehabilitation after acute myocardial infarction.

Abstract: This investigation was designed to determine the impact of a brief period of cardiac rehabilitation, initiated within 6 weeks of acute myocardial infarction (AMI), on both disease-specific and generic health-related quality of life, exercise tolerance and return to work after AMI. With a stratified, parallel group design, 201 low-risk patients with evidence of depression or anxiety, or both, after AMI, were randomized to either an 8-week program of exercise conditioning and behavioral counseling or to conventional care. Although the differences were small, significantly greater improvement was seen in rehabilitation group patients at 8 weeks in the emotions dimension of a new disease-specific, health-related Quality of Life Questionnaire, in their state of anxiety and in exercise tolerance. All measures of health-related quality of life in both groups improved significantly over the 12-month follow-up period. However, the 95% confidence intervals around differences between groups at the 12-month follow-up effectively excluded sustained, clinically important benefits of rehabilitation in disease-specific (limitations, -2.70, 1.40; emotions, -4.86, 1.10, where negative values favor conventional care and positive values favor rehabilitation) and generic health-related quality of life (time trade-off, -0.062, 0.052; quality of well-being, -0.042, 0.035) or in exercise tolerance (-38.5, 52.1 kpm/min); also, return to work was similar in the 2 groups (relative risk, 0.93; confidence interval, 0.71, 1.64).(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms of platelet activation: Thromboxane A2 as an amplifying signal for other agonists

Abstract: Thromboxane (Tx) A2 is a product of cyclooxygenase catalyzed metabolism of arachidonic acid, It is formed via prostaglandin (PG) endoperoxide intermediates (PGG2 and PGH2) by a specific synthase. PGH2 appears to exert the same biologic effects as TxA2 The cDNA for a TxA2 receptor has been cloned from a human placental library. Although pharmacologic and biochemical studies suggest the presence of multiple isoforms, this remains to be confirmed at the molecular level. A hydropathy plot of the deduced amino acid sequence of the available clone suggests that it has 7 transmembrane spanning domains, typical of a G protein linked receptor. Pharmacologic studies imply that Tx receptors in platelets are linked to phospholipase C activation via pertussis toxin insensitive G proteins. Candidates include the 42 kD Gq and the 60 kD Ge. TxA2 acts as an amplifying signal for platelet agonists and the response to this eicosanoid is tightly regulated. Mechanisms include rapid hydrolysis of the agonist to the inactive TxB2, autoinactivation of Tx synthase, rapid homologous TxA2 receptor desensitization due to receptor-G protein uncoupling, coincidental sensttization to counterregulatory Gs linked receptor systems and stimulation of prostacyclin formation by TxA2. Due to its role as an amplification signal in platelet activation, inhibition of Tx synthesis and action is an effective mechanism for preventing platelet-dependent vascular occlusion. Aspirin is of proven efficacy in this regard. Tx synthase inhibitors and antagonists are under clinical investigation.

Use of a morphologic classification to predict clinical outcome after dissection from coronary angioplasty.

Abstract: To determine if morphology of procedure-associated dissections could help predict clinical outcome, angiograms of 691 coronary artery dissections resulting from percutaneous transluminal coronary angioplasty were categorized according to the National Heart, Lung, and Blood Institute classification system. Classes of dissection were then correlated with clinical outcome: 543 patients with type B dissections had no increase in morbidity and mortality when compared with patients without dissection, with a similar success rate of 93.7%. Complications in this group were tow and compared favorably with complication rates in procedures not associated with dissection. One hundred forty-eight procedures associated with dissections of types C to F had a significant increase in in-hospital complications, including acute closure (31%), need for emergency coronary bypass surgery (37%), myocardial infarction (13%) and repeat angioplasty (24%). The overall clinical success rate for those with types C to F dissection was 38%. The differences in clinical success and acute complications between type B and types C to F dissections were statistically significant at p

Serial antiarrhythmic drug treatment to maintain sinus rhythm after electrical cardioversion for chronic atrial fibrillation or atrial flutter.

Abstract: The sequential use of different types of antiarrhythmic drugs may improve arrhythmia prognosis in chronic atrial fibrillation or flutter after successful electrical cardioversion. The rationale for serial treatment is that the arrhythmogenic mechanism may vary between patients, leading to different responses to 1 specific drug. To investigate this issue prospectively, 127 patients having chronic fibrillation or flutter exclusively, underwent serial drug treatment with flecainide (stage I) followed by sotalol or, if contraindicated, quinidine (stage II) and eventually amiodarone (stage III). Stages II and III were entered after electrical recardioversion for a recurrence during stages I or II, respectively. Calculated on an actuarial basis, the 2-year cumulative percentage of patients free of the arrhythmia increased from 31% after stage I to 63% at the end of serial treatment. To reach this result, a mean of 1.8 +/- 0.8 cardioversions per patient were needed, with 53 patients progressing to stage II and 34 to stage III. Sixteen patients stopped serial treatment prematurely and 15 patients were considered to have intractable atrial fibrillation at the end of stage III. Incidence of proarrhythmia was low. Multivariate analysis disclosed that an older age, in combination with a large number of previous episodes of arrhythmia, a long previous duration of arrhythmia and presence of mitral valve disease, were predictive for medical refractoriness during serial treatment. It is concluded that serial treatment may improve arrhythmia prognosis in atrial fibrillation or flutter, with an acceptable incidence of proarrhythmic events.

Prevalence of risk factors in men with premature coronary artery disease.

Abstract: The prevalence of modifiable cardiovascular risk factors (systemic hypertension, diabetes mellitus, cigarette smoking, low-density lipoprotein [LDL] cholesterol ≥ 160 mg/dl and high-density lipoprotein [HDL] cholesterol

In-hospital symptoms of psychological stress as predictors of long-term outcome after acute myocardial infarction in men

Abstract: The impact of high levels of psychological stress symptoms in the hospital after an acute myocardial infarction (AMI) was examined over 5 years among 461 men who took part in a trial of psychological stress monitoring and intervention. Psychological stress was assessed using the 20-item General Health Questionnaire (GHQ) 1 to 2 days before hospital discharge. Once discharged, patients in the treatment group responded to the GHQ by telephone on a monthly basis and, when they reported high levels of stress symptoms (GHQ ≥ 5), received visits from nurses to help them deal with their life problems. Control patients received routine medical care after discharge. Post-hoc subgroup analyses based on life-table methods showed that, for patients receiving routine care after discharge, high stress (GHQ ≥ 5) was associated with a close to threefold increase in risk of cardiac mortality over 5 years (p = 0.0003) and an approximately 1.5fold increase in risk of reinfarction over the same period (p = 0.09). In contrast, highly stressed patients who took part in the 1-year program of stress monitoring and intervention did not experience any significant long-term increase in risk. Although program impact was significant in terms of reduction of both cardiac mortality (p = 0.006) and AMI recurrences (p = 0.004) among highly stressed patients, there was little evidence of impact among patients with low levels of stress in the hospital. These results add to the growing body of research implicating psychosocial factors in post-AMI outcomes, and suggest that the patients who can benefit most from interventions to alter these factors may be identified before hospital discharge.

Usefulness of systolic excursion of the mitral anulus as an index of left ventricular systolic function.

Abstract: Studies in both humans and nonhuman animals show that the mitral anulus changes its size, shape and position during the cardiac cycle. 1–3 Left ventricular (LV) contraction results in shortening along both the short and long axis of the left ventricle. With each systole, the mitral anulus moves toward the apex in a cephalocaudal direction. 1–3 It has also been observed that the displacement of the mitral anulus during the systole is reduced with dilated cardiomyopathy. 4 We examined the relation between the amount of systolic excursion of the mitral anulus and LV systolic function as measured by radionuclide ventriculography and a variety of echocardiographic techniques.

Duration of the QT interval and total and cardiovascular mortality in healthy persons (The Framingham heart study experience)

Abstract: The baseline electrocardiograms of 5,125 original subjects of the Framingham Heart Study were measured to examine the relation of the QT interval corrected for heart rate (QTc) to risk of total mortality, sudden cardiac death, and death due to coronary artery disease over a 30-year follow-up period. Quintiles of QTc (seconds) less than or equal to 0.36, 0.36 to 0.38, 0.39 to 0.40, 0.41 to 0.43 and greater than or equal to 0.44 were studied in relation to these outcomes. There were no significant differences in the risk of total mortality, sudden cardiac death or death due to coronary artery disease according to QTc. A similar lack of significant association between QTc and these 3 outcomes was observed among all persons studied and in the 2 sexes after using a multiple regression analysis to control for several potentially confounding characteristics including age, gender, cigarette smoking, serum total cholesterol, systolic systemic blood pressure and Framingham relative weight. The results of this study fail to demonstrate an association between baseline QTc and overall mortality, and deaths due to sudden cardiac events or coronary artery disease in a large population-based cohort of essentially healthy persons in whom pathologic forms of QTc prolongation are uncommon.

Comparison of rubidium-82 positron emission tomography and thallium-201 SPECT imaging for detection of coronary artery disease

Abstract: The diagnostic performance of rubidium-82 (Rb-82) positron emission tomography (PET) and thallium-201 (Tl-201) single-photon emission-computed tomography (SPECT) for detecting coronary artery disease was investigated in 81 patients (52 men, 29 women). PET studies using 60 mCi of Rb-82 were performed at baseline and after intravenous infusion of 0.56 mg/kg dipyridamole in conjunction with handgrip stress. Tl-201 SPECT was performed after dipyridamole-handgrip stress and, in a subset of patients, after treadmill exercise. Sensitivity, specificity and overall diagnostic accuracy were assessed using both visually and quantitatively interpreted coronary angiograms. The overall sensitivity, specificity and accuracy of PET for detection of coronary artery disease (greater than 50% diameter stenosis) were 84, 88 and 85%, respectively. In comparison, the performance of SPECT revealed a sensitivity of 84%, specificity of 53% (p less than 0.05 vs PET) and accuracy of 79%. Similar results were obtained using either visual or quantitative angiographic criteria for severity of coronary artery disease. In 43 patients without prior myocardial infarction, the sensitivity for detection of disease was 71 and 73%, respectively, similar for both PET and SPECT. There was no significant difference in diagnostic performance between imaging modalities when 2 different modes of stress (exercise treadmill vs intravenous dipyridamole plus handgrip) were used with SPECT imaging. Thus, Rb-82 PET provides improved specificity compared with Tl-201 SPECT for identifying coronary artery disease, most likely due to the higher photon energy of Rb-82 and attenuation correction provided by PET. However, post-test referral cannot be entirely excluded as a potential explanation for the lower specificity of Tl-201 SPECT.

Evidence of endothelial dysfunction in coronary resistance vessels in patients with angina pectoris and normal coronary angiograms

Abstract: This study determines whether an impaired endothelium-mediated vasodilation in coronary resistance vessels exists in patients with microvascular angina. In 23 patients with clinically suspected coronary artery disease and smooth coronary arteries in the angiogram, coronary flow in response to an endothelium-related (acetylcholine) and endothelium-unrelated (dipyridamole) vasodilation was measured. Coronary flow was determined by the gas-chromatographic argon method (1) before, (2) with intracoronary acetylcholine infusion, and (3) after dipyridamole administered intravenously. In 8 patients, acetylcholine did not significantly increase coronary flow (from 91 +/- 28 to 118 +/- 37 ml/min.100 g), whereas flow was greatly increased after administration of dipyridamole (258 +/- 97 ml/min.100 g), indicating an endothelium-related vasodilator defect. In 6 patients, neither acetylcholine nor dipyridamole caused a significant increase in coronary flow, indicating an impaired coronary vasodilation on the vascular site. In 6 patients, coronary flow increased markedly after both administration of both acetylcholine and dipyridamole (from 81 +/- 26 to 191 +/- 68 and 234 +/- 87 ml/min.100 g). In 3 patients given acetylcholine, coronary artery constriction occurred. No significant correlation was found between the response to acetylcholine and that to dipyridamole (r = 0.40, p = not significant). The results indicate that in a subgroup of patients with smooth coronary arteries angina can be caused by an abnormality of the endothelial function in the microcirculation.

Dobutamine digital echocardiography for detecting coronary artery disease.

Abstract: To assess the value of dobutamine echocardiography for detecting coronary artery disease (CAD), 70 men (mean age 62 ± 8 years) presenting for coronary angiography were prospectively studied. Dobutamine (2.5 to 40 μg/kg/min) was infused in 3-minute stages. Digital echocardiograms were recorded on-line at baseline, during low- and igh-dose dobutamine infusion, and at recovery. An echocardiogram positive for CAD was defined as one showing a new wall motion abnormality induced by dobutamine. Compared with coronary angiography, the overall sensitivity of dobutamine echocardiography for detecting CAD was 86%, specificity 95% and accuracy 89%. The sensitivity for detecting 3-vessel CAD was 100%, 89% for 2-vessel and 69% for 1-vessel CAD. The accuracy of predicting multivessel disease by 2 methods was 71 and 84%, respectively. Heart rate at the echocardiographic ischemic threshold was lower in patients with 3- and 2-vessel CAD versus 1-vessel CAD (89 ± 17, 95 ± 18 and 118 ± 18 beats/min, respectively, p < 0.01); rate-pressure product was also lower in patients with 3-and 2-vessel CAD versus 1-vessel CAD (12.7 ± 3.6, 13.7 ± 2.8 and 18.9 ± 44 × 103 beats/ min × mm Hg, respectively, p < 0.01). Heart rate was the most important physiologic determinant of ischemia induced by dobutamine. There were no major complications during the study. Thus, dobutamine digital echocardiography is an excellent test for identifying CAD and should be beneficial in patients unable to exercise.

Effect of heart rate on left ventricular diastolic transmitral flow velocity patterns assessed by Doppler echocardiography in normal subjects.

Abstract: Although a number of factors, including age and ventricular loading, are known to influence the pattern of left ventricular (LV) filling as depicted by Doppler echocardiographic transmitral flow velocities, few and conflicting data are available regarding the influence of heart rate (HR). Therefore, 20 volunteers (mean age 30 years) were evaluated with pulsed-wave Doppler echocardiography, performed with the sample volume placed at the mitral anulus level in the apical 4-chamber projection. Transmitral flow measurements comprised peak and integrated early passive (E) and late atrial (A) filling velocities and the slope of velocity decline from peak E filling. Measurements were recorded during baseline (sinus rhythm, mean 70 beats/min) and during transesophageal atrial pacing (mean 88 beats/min). LV end-diastolic dimension, mean arterial pressure and PR interval (corrected for pacing-induced delay in interatrial conduction time) were unchanged during pacing versus baseline measurements. Peak and integrated E filling velocities averaged 0.59 +/- 0.09 m/s and 6 +/- 1 cm, respectively, at baseline and were not significantly greater at the higher HR. In contrast, baseline peak and integrated A velocities averaged 0.37 +/- 0.06 m/s and 2.3 +/- 0.7 cm, respectively, but were significantly greater at the higher HR (0.5 +/- 0.07 m/s and 3.2 +/- 1.1 cm, respectively [p less than 0.003 vs baseline for each]). Further analysis of a subgroup of 9 subjects for whom Doppler measurements were available at 3 HRs (sinus 70; pacing 80 and 90) yielded strong evidence for a linear relation between HR and peak A velocity (A = 0.008 HR - 0.21, with p less than 0.0001 for significance of the linear trend).(ABSTRACT TRUNCATED AT 250 WORDS)

Mean and range of the ambulatory pressure in normotensive subjects from a meta-analysis of 23 studies

Abstract: To perform a meta-analysis of published reports in an attempt to determine the mean and range of normal ambulatory blood pressure (BP), 23 studies including a total of 3,476 normal subjects were reviewed. Most studies were compatible with a mean 24-hour BP in the range of 115 to 120/70 to 75 mm Hg, a mean daytime BP of 120 to 125/75 to 80 mm Hg, and a mean nighttime BP of 105 to 110/60 to 65 mm Hg. With weighting for the number of subjects included in the individual studies, the 24-hour BP averaged 118/72 mm Hg, the daytime BP 123/76 mm Hg, and the nighttime BP 106/64 mm Hg. The night/day pressure ratio averaged 0.87 for systolic and 0.83 for diastolic BP, with ranges across the individual studies from 0.79 to 0.92 and from 0.75 to 0.90, respectively. If the mean +/- 2 standard deviation interval in the various studies was considered normal, the range of normality was on average 97 to 139/57 to 87 mm Hg for the 24-hour BP, 101 to 146/61 to 91 mm Hg for the daytime BP, and 86 to 127/48 to 79 mm Hg for the nighttime BP. Until the results of prospective studies on the relation between the ambulatory BP and the incidence of cardiovascular morbidity and mortality become available, the aforementioned intervals, which summarize the experience of 23 investigators, could serve as a temporary reference for clinical practice.

Coronary thrombosis: Pathogenesis and clinical manifestations

Abstract: The majority (greater than 75%) of major coronary thrombi are precipitated by a sudden rupture of the surface of an atherosclerotic plaque (plaque fissuring) causing platelet aggregation where thrombogenic subendothelial tissue has been exposed. Whether the thrombus remains mural and limited, just sealing the rupture, or evolves into an occlusive thrombus seems to depend on: (1) the amount and character of exposed thrombogenic material; (2) the actual thrombotic-thrombolytic equilibrium; and (3) local flow disturbances due to preexisting atherosclerotic stenosis. Thrombus formation may take place within the stenosis, where blood velocity and shear forces are highest, or it may take place or extend poststenotically, where flow separation, recirculation, and turbulence prevail. Platelet aggregation within the stenosis is responsible for the primary flow obstruction, but fibrin subsequently enmeshes the platelets and thus stabilizes the thrombus. Most thrombi have a layered structure, indicating an episodic growth that may alternate with thrombus fragmentation and peripheral embolization: thrombosis and thrombolysis are dynamic processes occurring simultaneously. If the platelet-rich thrombus at the rupture site evolves into an occlusive thrombus, the blood proximal and distal to the occlusion may stagnate and coagulate, giving rise to a secondarily formed red stagnation thrombosis consisting predominantly of erythrocytes held together by fibrin membranes. A ruptured plaque with a dynamic thrombosis superimposed (with or without spasm) seems to underlie the great majority of acute ischemic syndromes: unstable angina, acute infarction, and sudden death. The clinical presentation and the outcome depend on the severity and duration of ischemia: whether the obstruction is occlusive or nonocclusive, transient or persistent--modified by the magnitude of collateral flow.

Reproducibility and relation to mean heart rate of heart rate variability in normal subjects and in patients with congestive heart failure secondary to coronary artery disease.

Abstract: Before heart rate (HR) variability can be used for predictive purposes in the clinical setting, day-to-day variation and reproducibility need to be defined as do relations to mean HR. HR variability and mean HR were therefore determined in 2 successive 24-hour ambulatory electrocardiograms obtained from 33 normal subjects (age 34 +/- 7 years, group I), and 22 patients with coronary disease and stable congestive heart failure (CHF) (age 59 +/- 7 years, group II). Three measures were used: (1) SDANN (standard deviation of all mean 5-minute normal sinus RR intervals in successive 5-minute recording periods over 24 hours); (2) SD (the mean of the standard deviation of all normal sinus RR intervals in successive 5-minute recording periods over 24 hours); and (3) CV (coefficient of variation of the SD measure), a new measure that compensates for HR effects. Group mean HR was higher and HR variability lower in group II than in group I (80 +/- 10 vs 74 +/- 9 beats/min, p less than 0.04). Mean group values for HR and HR variability showed good correlations between days 1 and 2 (mean RR, r = 0.89, 0.97; SDANN, r = 0.87, 0.87; SD, r = 0.93, 0.97; CV, r = 0.95, 0.97 in groups I and II, respectively). In contrast, considerable individual day-to-day variation occurred (group I, 0 to 46%; group II, 0 to 51%). Low HR variability values were more consistent than high values. SDANN and SD correlated moderately with HR in both groups (r = 0.50 to 0.64). The CV measure minimizes HR effects on HR variability.(ABSTRACT TRUNCATED AT 250 WORDS)

Detection of silent myocardial ischemia in diabetes mellitus

Abstract: The prevalence of silent myocardial ischemia and its relation to autonomic dysfunction and pain threshold was studied in 58 men with diabetes mellitus and without cardiac symptoms. All patients underwent 48-hour ambulatory electrocardiographic monitoring and exercise testing after assessment of their autonomic function and pain threshold. Silent myocardial ischemia, defined as ≥1 mm of ST-segment depression on either exercise testing or ambulatory electrocardiographic monitoring, was corroborated by exercise-induced reversible defect(s) on tomographic thallium scintigraphy. Autonomic function was assessed by heart rate response to: (1) Valsalva maneuver, (2) deep breathing, and (3) upright posture, as well as by diastolic blood pressure response to sustained handgrip and systolic blood pressure response to upright posture. Autonomic dysfunction was defined as ≥2 abnormal responses. Pain threshold measurements were performed using electrical cutaneous stimulation of both forearms. Of the 58 diabetic patients, 21 were found to have autonomic dysfunction (36%). Silent myocardial ischemia was detected in 10 patients (17%), and was signficantly more frequent in patients with than without autonomic dysfunction (38 vs 5%, p = 0.003). There was no difference in the electrical pain threshold or tolerance in subjects with and without silent myocardial ischemia. It is concluded that silent myocardial ischemia in asymptomatic diabetic men occurs frequently and in association with autonomic dysfunction, suggesting that diabetic neuropathy may be implicated in the mechanism of silent myocardial ischemia.

Exercise echocardiography as a screening test for coronary artery disease and correlation with coronary arteriography

Abstract: We evaluated exercise echocardiography as a screening test for coronary artery disease in 228 patients, all of whom underwent subsequent coronary angiography. After an echocardiogram at rest was obtained, each patient performed maximal, symptom-limited, upright treadmill exercise, immediately after which repeat imaging was performed. The exercise echocardiogram was abnormal if any segment failed to become hypercontractile with exercise, and these regional wall motion abnormalities were used to predict the extent and distribution of coronary disease. At subsequent angiography, coronary stenosis was defined as significant if luminal diameter was reduced greater than or equal to 50%. Compared with electrocardiography, exercise echocardiography was more sensitive (97 vs 51%) and specific (64 vs 62%), and had higher positive (90 vs 82%) and negative (87 vs 28%) predictive accuracies. Exercise echocardiography was also highly predictive of the extent (no, 1-, 2- or 3-vessel disease) and distribution (which vessel) of coronary stenoses. It is concluded that exercise echocardiography is an excellent screening test for the presence, extent and distribution of coronary artery disease.

Insensitivity of noninvasive tests to detect coronary artery vasculopathy after heart transplant.

Abstract: Obstructive coronary artery vasculopathy can be a major problem after cardiac transplant. The use of noninvasive tests to detect coronary artery vasculopathy was studied in 73 consecutive patients after heart transplant. Angiographically or autopsyproved coronary artery disease was noted in 19 consecutive patients (26%) followed prospectively for 2.5 ± 1.3 years (mean ± standard deviation). Patients underwent yearly surveillance echocardiographic, rest/exercise-gated wall motion, oral dipyridamole thallium, ambulatory etectrocardiographic monitor and angiographic studies. Positive test results were defined by decrease in ejection fraction, wall motion abnormality, failure to increase ejection fraction, lack of systolic blood pressure increase, and ischemic ST changes at maximal exercise (or on ambulatory monitor). Wall motion abnormalities and depressed ejection fraction on echocardiography were also abnormal studies as were fixed or reversible perfusion defects on thallium scan. Angiograms were considered positive when 50% luminal narrowing was observed and autopsy coronary artery vasculopathy was defined as cross-sectional coronary obstruction ≥70%. No procedure that was examined proved to be a sensitive noninvasive detector of heart transplant coronary artery vasculopathy. All except ambulatory electrocardiographic monitoring had positive predictive values

A prospective study of parental history off myocardial infarction and coronary artery disease in men

Abstract: The relation between parental history of myocardial infarction (MI) and risk of coronary artery disease (CAD) was prospectively examined among 45,317 U.S. male health professionals who were free of diagnosed CAD, 40 to 75 years of age in 1986 and followed for 2 years. These men provided details of parental history of MI, including their parents' age at the first event, their personal history of hypertension, hypercholesterolemia and diabetes mellitus, and a detailed dietary assessment completed at baseline. During 72,454 person-years of follow-up, 181 non-fatal MIs were documented, 49 men died from MI or sudden death, and 140 underwent coronary artery surgery or angioplasty. Compared with men without any history of parental MI, those whose mothers or fathers had had an MI at less than 70 years of age had a substantially elevated risk of MI (relative risk = 2.2, 95% confidence interval, 1.2 to 3.8 for maternal history; relative risk = 1.7, 95% confidence interval 1.2 to 2.3 for paternal history). Risk of MI increased with decreasing age at parental MI. Paternal but not maternal history of MI was related to increased risk of coronary artery surgery. These associations were not appreciably altered by controlling for diet or established risk factors, either individually or in multivariate models. These prospective data indicate that a history of MI in either parent is associated with an increased risk of CAD among men.

Short- and long-term results of catheter balloon percutaneous transvenous mitral commissurotomy.

Abstract: Percutaneous transvenous mitral commissurotomy (PTMC) was performed in 219 patients with symptomatic, severe rheumatic mitral stenosis. There were 59 men and 160 women, aged 19 to 76 years (mean 43). Pliable, noncalcified valves were present in 139 (group 1), and calcified valves or severe mitral subvalvular lesions, or both, in 80 patients (group 2). Atrial fibrillation was present in 133 patients (61%) and 1+ or 2+ mitral regurgitation in 59 (27%). Technical failure occurred with 3 patients in our early experience. There was no cardiac tamponade or emergency surgery. The only in-hospital death occurred 3 days after the procedure in a group 2 premoribund patient in whom last-resort PTMC created 3+ mitral regurgitation. Mitral regurgitation appeared or increased in 72 patients (33%); 3+ mitral regurgitation resulted in 12 patients (6%). There were 3 systemic embolisms. Atrial left-to-right shunts measured by oximetry developed in 33 patients (15%). Immediately after PTMC, there were significantly reduced (p = 0.0001) left atrial pressure (24.2 ± 5.6 to 15.1 ± 5.1 mm Hg), mean pulmonary artery pressure (39.7 ± 13.0 to 30.6 ± 10.9 mm Hg) and mitral valve gradient (13.0 ± 5.1 to 5.7 ± 2.6 mm Hg). Mitral valve area increased from 1.0 ± 0.3 to 2.0 ± 0.7 cm2 (p = 0.0001) and cardiac output from 4.4 ± 1.4 to 4.7 ±1.2 liters/min (p 8, and valvular calcification and severe subvalvular lesions as independent predictors for suboptimal hemodynamic results. The cardiovascular event-free survival rate for group 1 was 100% up to 42 months; that for group 2 was 91% at 12 months, and held at 76% from 24 to 31 months. PTMC is safe, achieves good immediate and long-term results and is the procedure of choice in selected patients with mitral stenosis.

Cutting balloon: A novel approach to percutaneous angioplasty☆

Abstract: Balloon angioplasty typically injures the vessel wall by inducing irregular intimai tears, splits and stretches.1 Proliferative response to this injury,2 and elastic recoil3 after balloon angioplasty are implicated as causes of restenosis and acute closure, respectively. We hypothesized that sharp and regular endovascular surgical incisions may enhance the success of angioplasty by limiting both injury and elastic recoil. We designed devices to make radially directed, longitudinal surgical cuts from the luminal surface deepening into the medial layer. In this study we used 1 of the possible designs (Figure 1). One to 4 cutting edges of 0.1 to 0.4 mm metal blades were mounted on the surface of balloon catheters parallel with the longitudinal axis of the balloon (cutting balloon). The aims of the study were to (1) determine the immediate morphology of incisions made with the cutting balloon; (2) determine the healing response to the endovascular incisions; and (3) compare angiographie results obtained with standard and cutting balloons.