Evidence that human cardiac myocytes divide after myocardial infarction.
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Death, Sudden, Cardiac↗
Biomedical subjects
P F Binkley
Publications and source records attributed to P F Binkley.
Histologic compaison of allograft myocardium between short- and long-term survivors of human cardiac transplantation.
Myocardial histology of cardiac allografts differed between short-term (<5 years) and long-term (>5 years) survivors after transplantation. These differences may partially be attributable to a higher prevalence of systemic hypertension and allograft rejection in the short-term survivors, affecting hemodynamics and allograft function.
Adult↗
PlA2, a variant of GPIIIa implicated in coronary thromboembolic complications.
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Antigens, CD↗
Plasma atherogenic markers in congestive heart failure and posttransplant (heart) patients.
OBJECTIVES: We hypothesized that plasma factors important for the development of atherosclerosis play a major role in the occurrence of cardiac allograft vasculopathy (CAV). BACKGROUND: Cardiac allograft vasculopathy is a major cause of death among heart transplant recipients, has a poorly understood pathogenesis and has similarities to atherosclerotic coronary disease. METHODS: The study population consisted of 93 postcardiac transplant recipients. Thirty-one patients with congestive heart failure (CHF) and 18 healthy individuals served as control subjects. Posttransplant coronary anatomy was evaluated by angiography and intravascular ultrasound. Laboratory analyses of lipids, homocysteine, vitamin B12 and folate, fibrinogen, von Willebrand factor antigen (vWFAg) and renin were obtained on all participants. RESULTS: Posttransplant patients were found to have elevated serum triglycerides, total cholesterol/ high-density lipoprotein cholesterol ratio, lipoprotein (a), homocysteine, vWFAg, fibrinogen and renin and lower high-density lipoprotein cholesterol. Most of these laboratory atherogenic factors were also elevated to a similar degree in the CHF control population. Although most atherogenic markers were elevated, there was little correlation with CAV severity. Cardiac allograft vasculopathy severity varied with time after transplantation, 3-hydroxy-methyl-glutaryl-coenzyme A reductase inhibitor use and prior cytomegalovirus infection. Even within the normal range, lower RBC folate levels were associated with increased severity of CAV. CONCLUSIONS: The posttransplant course is associated with increased clinical and laboratory atherogenic factors, some of which likely contribute to the severity of coronary vasculopathy. Compared with normal control subjects, many of these markers are already increased in pretransplant CHF patients with or without occlusive coronary artery disease.
Adult↗
Dissociation between ACE activity and autonomic response to ACE inhibition in patients with heart failure.
BACKGROUND: Administration of angiotensin-converting enzyme (ACE) inhibitors to patients with congestive heart failure has been shown to increase parasympathetic tone as indicated by increases in high-frequency heart rate variability. The mechanism for this effect, including its relation to changes in baroreflex activity, blood pressure variability, and suppression of ACE activity, remains undefined. This study was designed to test the relation of these variables, which may govern changes in autonomic activity, to the previously described increase in parasympathetic tone. METHODS: Seven patients with heart failure received a 3-hour infusion of the ACE inhibitor enalaprilat. Hemodynamic variables and parameters of heart rate and blood pressure variability, baroreflex gain derived from the interaction of heart rate and blood pressure variability, and serum ACE activity were measured during and after the infusion. Measures of heart rate and blood pressure variability were also compared against a historic control group. RESULTS: Serum ACE activity was significantly suppressed throughout and after enalaprilat infusion. Hemodynamic measures did not change other than a small decline in right atrial and pulmonary capillary wedge pressures. Parasympathetic tone showed an initial significant increase with a peak at 2 hours but then declined below baseline 8 hours after initiation of enalaprilat infusion. Sympathetically influenced low-frequency heart rate variability was significantly increased above baseline in the enalaprilat treatment group 8 hours after initiation of the infusion. Baroreflex gain showed a significant trend to an increase with the maximum value coinciding with the peak in parasympathetic tone. There was no change in blood pressure variability in the enalaprilat group and no change in baroreflex gain, heart rate variability, or blood pressure variability in the control group. CONCLUSIONS: Parasympathetic tone and baroreflex gain increased with parenteral administration of an ACE inhibitor but subsequently decreased below baseline values despite continued suppression of serum ACE activity. The dissociation between ACE suppression and autonomic response to ACE inhibition indicates that enzyme systems not reflected by plasma ACE activity or independent from the classic pathways of angiotensin formation contribute to the regulation of the autonomic response to ACE inhibition in patients with heart failure. The absence of significant change in hemodynamic variables or in blood pressure variability indicates that these autonomic changes are not an indirect reflex response to ACE inhibitor-induced vasodilation or hemodynamic baroreceptor stimulation.
Adult↗
The problem of ventricular dysrhythmias and sudden death mortality in heart failure: the impact of current therapy.
Congestive heart failure (CHF), one of the few cardiovascular conditions increasing in incidence and prevalence, is characterized by high morbidity and mortality. Up to 50% of the mortality is attributable to dysrhythmic sudden death. Risk stratification to identify those most susceptible to sudden death remains imperfect. The advances in CHF therapeutics and management over the past 16 years have had a favorable impact on CHF mortality including sudden death. The role of amiodarone and implantable cardioverter-defibrillator intervention is evolving and discussed in the context of current CHF management and available trials.
Anti-Arrhythmia Agents↗
Quantitative investigation of cardiomyocyte hypertrophy and myocardial fibrosis over 6 years after cardiac transplantation.
OBJECTIVES: This study was performed to determine the degree and time course over 6 years of cardiomyocyte hypertrophy and myocardial fibrosis of the cardiac allograft in transplanted patients. BACKGROUND: Diastolic dysfunction and to a certain extent systolic dysfunction are common cardiac findings after heart transplantation. The development of posttransplant cardiomyocyte hypertrophy and myocardial fibrosis likely contributes to these derangements. METHODS: Cardiomyocyte diameter and percent fibrosis were determined in serial endomyocardial biopsy specimens obtained from 1 month up to 6 years following heart transplantation in 50 patients. Endomyocardial biopsy specimens from 40 patients with primary dilated cardiomyopathy and 11 normal subjects were similarly analyzed for control data. Analyses were performed in a blinded format using a validated computerized image analysis system (Optimas 5.2). RESULTS: Early (1 month) cardiomyocyte enlargement decreased to the smallest diameter 6 months posttransplant, but thereafter progressively increased by 10% to 20% over the subsequent 5- to 6-year period. Although not statistically established, principal stimuli may include a discrepancy in body size (recipient > donor), coronary allograft vasculopathy and posttransplant systemic hypertension. Percent myocardial fibrosis rose early (1 to 2 months) posttransplant and thereafter remained at the same modest level of severity. CONCLUSIONS: Cardiomyocyte diameter of the transplanted heart gradually increases over time, while percent myocardial fibrosis rises early and remains in a modestly elevated plateau after 2 months posttransplant. These histostructural changes likely contribute to the hemodynamic and cardiac functional alterations commonly observed posttransplant.
Adolescent↗
Removal from the "waiting list" for heart transplantation: a risk factor for sudden death?
METHODS AND RESULTS: Over an 18-month period, the patients on the heart transplantation waiting list at our institution were evaluated to determine if continued listing was appropriate. Ten patients were removed because of significant improvement in clinical status and exercise capacity (n = 9) or because of criteria violation (n = 1). Four of these patients died suddenly and unexpectedly within 4 months of delisting, resulting in a 6-month survival of 60% for the patients removed. During the same period, the 6-month survival for newly listed patients (n = 10) was 80% and that for newly transplanted patients (n = 13) was 92%. An elevated pulmonary capillary wedge pressure (> or = 18 mmHg) was the only clinical or laboratory feature that appeared to distinguish the four patients who died suddenly following delisting. CONCLUSION: The results of this preliminary study suggest that removal of a patient from a heart transplant waiting list may represent a risk for sudden death, particularly in patients with elevated ventricular filling pressures, irrespective of otherwise favorable clinical status and exercise performance.
Adult↗
Role of spectral measures of heart rate variability as markers of disease progression in patients with chronic congestive heart failure not treated with angiotensin-converting enzyme inhibitors.
Measures of heart rate variability in the frequency domain quantify autonomic activity. However, the relation of these measures to the severity of ventricular dysfunction in patients with congestive heart failure remains uncertain. We applied spectral analysis of heart rate variability to 24-hour Holter monitor recordings obtained from 20 patients with congestive heart failure who were not treated with angiotensin-converting enzyme inhibitors to determine whether significant changes in parameters of heart rate variability reflect the progression of symptoms in patients with ventricular failure. Both total and low-frequency heart rate spectral power were seen to decrease with worsening New Heart Associate (NYHA) functional class. A significant (p = 0.04) higher total power was noted in NYHA class II than in class III patients (3.0 x 10(-3) +/- 3.6 10(-4) and 2.5 x 10(-3) +/- 5.9 x 19(-4) [beats/min]2, respectively). Similarly, low-frequency heart rate spectral power was significantly (p = 0.008) higher in class II than in class III patients (1.7 x 10(-3) +/- 4.6 x 10(-4) and 1.1 x 10(-3) +/- 3.5 x 10(-4) [beats/min]2, respectively). Only the low-frequency component of the spectrum was directly correlated with left ventricular ejection fraction (LVEF) (r = 0.40) with a trend toward statistical significance (p = 0.07). Measures of heart rate variability and the changes in autonomic tone that they reflect may therefore serve as markers of the extent of disease progression in patients with congestive heart failure.
Adult↗
Vascular hypertrophy is an early finding in essential hypertension and is related to arterial pressure waveform contour.
The effects of hypertension on the arterial vasculature were examined in a study group of 20 patients with newly diagnosed essential hypertension, 18 patients with chronic essential hypertension, and 32 control subjects with normal blood pressure. Left ventricular mass was determined echocardiographically. Carotid artery intimal-medial thickness was measured by means of B-mode ultrasound imaging, and carotid arterial waveforms were obtained by applanation tonometry. Compared with that in control subjects, carotid intimal-medial thickness was increased in patients with chronic hypertension (0.74 +/- 0.17 mm vs 0.61 +/- 0.15 mm in control subjects; p < 0.01) and in patients with newly diagnosed hypertension (0.66 +/- 0.12 mm vs 0.61 +/- 0.15 mm in control subjects; p < 0.05). Left ventricular mass was also higher in patients with chronic hypertension than in control subjects but was very similar between control subjects and those with newly diagnosed hypertension. Both the group with early hypertension and the group with chronic hypertension had an increased incidence of early waveform reflection evident on carotid arterial waveform examination. By multiple regression analysis, independent predictors of increased carotid intimal-medial thickness were age, systolic arterial pressure, and Murgo class of arterial waveform. Conduit arterial wall thickening precedes left ventricular remodeling in essential hypertension and is significantly related to the degree of pressure elevation and the arterial waveform contour.
Age Factors↗
Heart rate variability: two eras of investigation.
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Cardiovascular Diseases↗
Increased ventricular contractility is not sufficient for effective positive inotropic intervention.
Positive inotropic intervention with dobutamine in patients with congestive heart failure is accompanied by complementary vascular changes, as measured by the aortic input impedance spectrum, that promote the efficient transfer of augmented myocardial contractile power. It is unknown whether this is a nonspecific response to increased ventricular contractility or is a function of the properties of the positive inotropic agent employed. Therefore, the influence of two different positive inotropic interventions, dobutamine and dopamine, on ventricular-vascular coupling was examined in 15 patients with congestive heart failure. Significant reductions in characteristic aortic impedance, wave reflection, and low-frequency impedance moduli were noted with dobutamine and were not seen with dopamine. Consequently, a significantly (P = 0.0008) greater increase in pulsatile, rather than steady-state, power output was noted with dopamine that was reflective of a significantly diminished efficiency of power transfer. Therefore, optimal transfer of increased ventricular contractile power in patients with congestive heart failure requires increases in large vessel compliance and complementary changes in ventriculoarterial coupling.
Aged↗
Prospective study of the circadian pattern of blood pressure after heart transplantation.
BACKGROUND: Previous reports indicate that heart transplant recipients lack a normal nocturnal decline in blood pressure. This prospective study was designed to determine the evolution of circadian blood pressure patterns after heart transplantation. METHODS: Twenty-four-hour ambulatory blood pressure and heart rate was measured in eight heart transplant recipients early (47 +/- 35 days) and late (740 +/- 10 days) after transplantation. RESULTS: Early transplant recordings and the normal control group recordings showed similar daytime systolic blood pressure but had different nighttime systolic blood pressure (138 +/- 15 mm Hg versus 112 +/- 9 mm Hg, p = 0.0002). The percent nocturnal change in systolic blood pressure showed a nocturnal increase in blood pressure in the early recordings versus a decrease in the healthy subjects (+4 +/- 2.7 versus -13 +/- 5.4, p < 0.0001). The late recordings showed a significant decrease in the nighttime systolic blood pressure (138 +/- 15 mm Hg versus 119 +/- 7 mm Hg, p = 0.011). The percent nocturnal change in systolic blood pressure was also significantly different between the early and late recordings (+4 +/- 2.7 versus -9 +/- 9, p = 0.0082) indicating a return of a nocturnal decline in systolic blood pressure. Similar patterns in diastolic blood pressure were observed. No significant change in the percent nocturnal change in heart rate occurred (-10 +/- 4.1 versus -7 +/- 5.5). CONCLUSIONS: Prospective follow-up of this heart transplant population showed that diurnal blood pressure variation is restored in some patients; diurnal variation is not related to corticosteroids, cyclosporine, or heart rate.
Antihypertensive Agents↗
Early left ventricular dysfunction elicits activation of sympathetic drive and attenuation of parasympathetic tone in the paced canine model of congestive heart failure.
BACKGROUND: Although autonomic imbalance is known to be characteristics of patients with clinically overt symptomatic congestive heart failure, it is currently unknown whether this autonomic response arises early in the course of left ventricular dysfunction or is restricted to the later stages of circulatory failure. METHODS AND RESULTS: This investigation utilized the technique of spectral analysis of heart rate variability in a paced canine model of congestive heart failure that permits an examination of autonomic activity at the earliest stages of ventricular dysfunction to determine whether early systolic dysfunction in congestive heart failure is characterized by autonomic imbalance, which may contribute to subsequent myocardial and vascular dysfunction. The results indicate that autonomic imbalance as reflected in an abnormal pattern of heart rate variability evolves early in the course of ventricular systolic dysfunction consisting of both a significant increase in sympathetically influenced low-frequency heart rate variability and a significant reduction of parasympathetically mediated high-frequency variability. This was quantified by a marked and significant increase in the area under the low-frequency region from 0.053 +/- 0.037 (beats per minute)2 at baseline to 0.182 +/- 0.143 (beats per minute)2 at 48 hours to 0.253 +/- 0.202 (beats per minute)2 after 7 days of pacing (ANOVA, P < .04). The area under the high-frequency region of the curve showed a decrease from a baseline value of 0.945 +/- 0.037 (beats per minute)2 to 0.811 +/- 0.152 (beats per minute)2 at 48 hours to 0.733 +/- 0.197 (beats per minute)2 after 7 days of pacing (ANOVA, P < .03). This resulted in a shift in autonomic balance away from parasympathetic tone and toward augmented sympathetic drive as reflected by the ratio of high- to low-frequency areas from a baseline value of 15.2 +/- 9.6 to 10.1 +/- 6.89 at 48 hours and 0.004 +/- 0.001 at 7 days (ANOVA, P < .01). CONCLUSIONS: The results indicate that autonomic imbalance as reflected in an abnormal pattern of heart rate variability evolves early in the course of ventricular systolic dysfunction consisting of both a significant increase in sympathetically influenced low-frequency heart rate variability and a significant reduction of parasympathetically mediated high-frequency variability. The early appearance of these autonomic abnormalities suggests that autonomic imbalance plays a significant role in promoting the progression of circulatory failure.
Animals↗
Effects of physiologic and pharmacologic adrenergic stimulation on heart rate variability.
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Exercise↗
Differing autonomic response to dobutamine in the presence and absence of ischemia: implications for the autonomic contribution to positive inotropic intervention.
Although it is well recognized that dobutamine is a powerful positive inotropic agent mediating increased myocardial contractility through direct beta-adrenergic stimulation, the mechanism of its overall circulatory effects appears more complex than that which may be ascribed solely to this direct action on the myocardium. Previous investigations have implied that reflex alterations in autonomic balance may contribute significantly to the response to this agent, but direct evidence describing such a response has not been reported. The objective of this investigation was to assess changes in autonomic tone induced by dobutamine in the presence and absence of ischemia through the measurement of heart rate variability in patients undergoing dobutamine stress echocardiography. Of 25 consecutive patients undergoing dobutamine stress echocardiography, 16 were found to have unequivocal evidence for or against the presence of ischemia during dobutamine infusion. Heart rate data from these 16 patients were submitted for spectral analysis of heart rate variability and quantification of parasympathetically governed high-frequency heart rate variability and sympathetically influenced low-frequency heart rate variability. Of the 16 patients nine were not found to have evidence for ischemia (group 1), and seven were found to have echocardiographic findings consistent with dobutamine-induced ischemia (group 2). The two groups significantly differed (p = 0.04) in the change in parasympathetic tone associated with dobutamine with a significant (p = 0.04) increase in parasympathetic tone in group 1 and a numeric decrease in group 2. A significant (p = 0.04) decrease in sympathetic tone was noted in group 1 as reflected by low-frequency heart rate variability with a numeric increase in this measure in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Assessment of autonomic tone over a 24-hour period in patients with congestive heart failure: relation between mean heart rate and measures of heart rate variability.
Patients with congestive heart failure (CHF) are characterized by an imbalance of the autonomic nervous system, which may contribute to the progression of circulatory failure and influence survival. However, it is still unclear whether CHF is characterized by a suppression of the diurnal variation in autonomic tone that is observed in normal subjects. To characterize the circadian variation in autonomic tone in patients with ventricular failure, ambulatory 24-hour Holter monitor recordings were obtained in 20 patients with CHF; 4-minute epochs of data from every hour of each 24-hour recording were selected. For each epoch we calculated the mean heart rate (HR) and, by applying spectral analysis of heart rate variability (HRV), we quantified the magnitude of the total (0.02 to 0.9 Hz), sympathetically governed low frequency variability (0.02 to 0.1 Hz), and parasympathetically mediated high-frequency variability (0.1 to 0.9 Hz). These areas were also expressed as a ratio to total variability and a ratio of high to low variability. A highly significant change in the mean HR over 24 hours was observed (p = 0.0001); no changes in the measures of HRV were obtained (p < 0.3). No significant correlation was found between mean HR and any frequency domain measures. We conclude that the sustained imbalance of autonomic tone over a 24-hour period, as shown by the spectral analysis of HRV, may promote the progression of circulatory failure and predispose patients with CHF to malignant ventricular arrhythmias and sudden cardiac death.(ABSTRACT TRUNCATED AT 250 WORDS)
Autonomic Nervous System↗