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PubMed1998

AgNORs in the myocardium in ischaemic heart disease complicated by heart failure: a postmortem study.

AIM: To evaluate the interphase ribosomal RNA cistron activity of cardiomyocytes in case with ischaemic heart disease complicated by heart failure. METHODS: Nucleoli were investigated in postmortem myocardium samples from 31 cases with ischaemic heart disease (mean (SEM), 57.4 (6.5) years) with or without severe heart failure (18 and 13, respectively) and from eight healthy people who died in accidents (mean (SEM) 25.3 (4.0) years). Myocardium obtained within one hour after death was frozen in liquid nitrogen. Silver staining for nucleolar organiser regions (AgNOR) was performed with a standard procedure and the mean score obtained. On the basis of these data, the average number of AgNORs per nucleus was determined. The Student's t test was used to compare groups. RESULTS: Compared with controls, the mean numbers of AgNORs per nucleus in cardiomyocytes from ischaemic heart disease patients not complicated with severe heart failure were higher (8.0 v 9.9; p < 0.05), but cases with severe heart failure had a progressive decrease in cardiomyocyte AgNORs. A difference in AgNOR numbers between cases with different ischaemic heart disease courses was found when cases with the same New York Heart Association (NYHA) functional stage III of heart failure were studied. CONCLUSIONS: The significant decrease of AgNORs in cardiomyocytes from cases with severe ischaemic heart disease complicated by heart failure seems to be connected with cardiomyocyte adaptation (a variant of hibernation) to a diminished circulation that, hypothetically, may affect the level of ribosomal RNA synthesis.

Adult↗
PubMed2002

Metoprolol CR/XL in female patients with heart failure: analysis of the experience in Metoprolol Extended-Release Randomized Intervention Trial in Heart Failure (MERIT-HF).

BACKGROUND: Underrepresentation of women in heart failure clinical trials has limited conclusions regarding the effect of various management strategies on survival in women with heart failure and decreased left ventricular ejection fraction (LVEF). METHODS AND RESULTS: MERIT-HF (Metoprolol Extended-Release Randomized Intervention Trial in Heart Failure) was a randomized, placebo-controlled study, the purpose of which was to evaluate the effect of metoprolol controlled-release/extended-release (CR/XL) in 3991 patients with New York Heart Association class II to IV heart failure and LVEF < or =0.40. We performed a post hoc analysis to evaluate the effect of metoprolol CR/XL on outcome in women (n=898), including the outcome in 183 women with severe heart failure (New York Heart Association class III/IV and LVEF < 0.25). Treatment with metoprolol CR/XL in women resulted in a 21% reduction in the primary combined end point of all-cause mortality/all-cause hospitalizations (164 versus 137 patients; P=0.044). The number of cardiovascular hospitalizations was reduced by 29% (164 versus 120; P=0.013), and hospitalization for worsening heart failure was reduced by 42% (95 versus 56; P=0.021). Similar results were noted in the subgroup of women with severe heart failure, with a 57% reduction in cardiovascular hospitalizations (63 versus 30; P=0.005) and a 72% reduction in hospitalization due to worsening heart failure (46 versus 14; P=0.0004). A pooling of mortality results from MERIT-HF, the Cardiac Insufficiency Bisoprolol Study (CIBIS II), and the Carvedilol Prospective Randomized Cumulative Survival Study (COPERNICUS) showed very similar survival benefits in women and men. CONCLUSIONS: The beneficial effects of metoprolol CR/XL extend to women with heart failure, including women with clinically stable severe heart failure.

Adrenergic beta-Antagonists↗
PubMed2003

Prevention of Heart Failure in Patients in the Heart Outcomes Prevention Evaluation (HOPE) Study.

BACKGROUND: Previous trials in the prevention of heart failure have been restricted to patients with low ejection fraction or hypertension. We assessed an angiotensin-converting enzyme (ACE) inhibitor, ramipril, to prevent the development of heart failure in high-risk patients without known low ejection fraction or heart failure. METHODS AND RESULTS: We randomly assigned 9297 patients to receive double-blind ramipril (10 mg daily) or matching placebo for 4.5 years. Death attributable to heart failure, hospitalization for heart failure, initiation of open-label ACE inhibitor for heart failure, or development of typical signs or symptoms of heart failure developed in 951 patients and was associated with a 4.01-fold increase in the risk of death (P<0.0001). The rate of developing heart failure was significantly increased with coronary disease (risk ratio, 2.17), microalbuminuria (1.82), left ventricular hypertrophy (1.47), increasing age (by decade, 1.37), and diabetes (1.36). Ramipril reduced new-onset heart failure rate from 11.5% to 9.0% (relative risk, 0.77; 95% CI, 0.68 to 0.87; P<0.0001). Ramipril consistently reduced heart failure rate both in those with (relative risk, 0.87) and those without an interim myocardial infarction (relative risk, 0.78). Ramipril also reduced the heart failure rate more in patients with baseline systolic pressure above the median (139 mm Hg) (relative risk, 0.67) compared with those below the median (relative risk, 0.91; P=0.024 for interaction of group by treatment). CONCLUSION: Ramipril significantly reduces the rate of development of heart failure in patients at high risk of cardiovascular events.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1981

Identification of beta-adrenergic receptors using [3H]dihydroalprenolol in fetal sheep heart: direct evidence of qualitative similarity to the receptors in adult sheep heart.

The fetal sheep heart responds to beta-adrenergic stimuli; however, in vivo studies show the response of the fetal heart is less than that of the adult heart. We used [3H]dihydroalprenolol (DHA) to study directly beta-adrenergic receptors in heart particulates of fetal sheep at term and adult sheep. [3H]DHA binding to fetal heart particulates was rapid, reversible (t 1/2 = 2.9 +/- 0.3 min), stereoselective, saturable (101.2 +/- 7.4 fmoles/mg protein), and of high affinity (4.8 +/- 0.4 nM). The rank order of agonists competing for [3H]DHA binding was isoproterenol (0.32 +/- 0.10 microM) greater than epinephrine (1.19 +/- 0.23 muM) approximately equal to norepinephrine (2.67 +/- 0.69 muM), which is compatible with beta 1-adrenergic potencies. [3H]DHA also bound to the adult sheep heart in a manner expected for beta 1-receptors. No difference in the binding affinity of [3H]DHA or agonists' competition was demonstrated between the fetal and adult sheep heart. Comparison of the concentration of beta-adrenergic receptors in fetal and adult hearts was confounded by the choice of the denominator for unit expression. The concentration was higher in the adult when expressed as a function of protein content or 5'-nucleotidase activity (0.52 +/- 0.07 versus 1.12 +/- 0.06). However, there was no difference when tissue weight, Na+ - K+-ATPase, or NaF-stimulated adenylate cyclase was used. Furthermore, isoproterenol-stimulated adenylate cyclase and cardiac contractile response to a threshold dose of isoproterenol were identical in the fetal and adult sheep heart. We conclude that beta-receptors can be studied with [3H]DHA in the fetal sheep heart, this receptor is qualitatively similar to the beta-receptor in the adult sheep heart, and it is unlikely that there is a difference in the concentration of beta-adrenergic receptors in fetal and adult sheep heart.

Adenylyl Cyclases↗
PubMed2004

Another person's heart: magical and rational thinking in the psychological adaptation to heart transplantation.

BACKGROUND: The goal of this study was to examine heart transplant recipients' psychological adaptation to another person's heart, with particular emphasis on recipients' attitudes toward graft and donor. METHOD: Thirty-five male heart recipients were examined by: the Symptom Distress Checklist (revised) (SCL-90-R); the Depression Adjective Checklist (DACL); a Post-Traumatic Stress Disorder Questionnaire (PTSD-Q); a Heart Image Questionnaire (HIQ); and a Semi-Structured Interview (SSI), aimed at eliciting attitudes and fantasies regarding the transplanted heart. RESULTS: All instruments indicated high levels of stress even several years after the transplant, but, simultaneously, 73% of recipients felt that acquiring a new heart had had a dramatic influence on their lives with a new appreciation of the preciousness of life and a shift of priorities, toward altruism and spirituality. Sixty percent returned to work after the transplant but some had to adapt to a changed attitude from those around them who regarded them as anything from mystical creatures to vulnerable or still-sick individuals. While all recipients possessed a scientific knowledge of the anatomy and physiological significance of the heart (as revealed in the HIQ), many endorsed fantasies and displayed magical thinking: 46% of the recipients had fantasies about the donor's physical vigor and prowess, 40% expressed some guilt regarding the death of the donor, 34% entertained the possibility of acquiring qualities of the donor via the new heart. When asked to choose a most and least preferred imagined donor, 49% constructed their choices according to prejudices, desires, or fears related to ethnic, racial or sexual traits attributed to the donor. CONCLUSIONS: This study confirms the intuitive idea that heart transplant involves a stressful course of events that produces an amplified sense of the precariousness of existence. Simultaneously, it gives rise to rejoicing at having been granted a new lease on life and a clear sense of new priorities, especially with regard to relationships. Less expectedly, this study shows that, despite sophisticated knowledge of anatomy and physiology, almost half the heart recipients had an overt or covert notion of potentially acquiring some of the donor's personality characteristics along with the heart. The concomitance of the magical and the logical is not uncommon in many areas of human existence, and is probably enhanced by the symbolic nature of the heart, and maybe, also, by the persistent stress that requires an ongoing, emotionally intense, adaptation process.

Adaptation, Psychological↗
PubMedDate not supplied

Myocardial performance and metabolism in non-ketotic, diabetic rat hearts: myocardial function and metabolism in vivo and in the isolated perfused heart under the influence of insulin and octanoate.

The influence of a non-ketonic, chronically diabetic state (60 mg/kg streptozotocin) on cardiac function and metabolism was studied under in vivo conditions by inserting a Millar-tip catheter into the left ventricle and in the model of the isolated perfused heart. In vivo heart rate and maximal left ventricular systolic pressure were reduced after a diabetes duration of 4 and 12 weeks. The maximal rise and fall in left ventricular pressure progressively declined with the duration of diabetes. The reduced myocardial function was associated with a loss in ATP and adenine nucleotides. In the perfused heart of chronically diabetic rats, heart function was also impaired and could not be restored in vitro by perfusion with glucose and insulin. In the presence of octanoate--a substrate which can be metabolized independently from insulin--heart function of diabetic rats was improved, but remained lowered as compared to controls. Since the content of myocardial creatine phosphate was reduced in diabetic hearts perfused with octanoate, these findings indicate that the suppression of cardiac performance is not only a result of an impaired glucose metabolism, but of a more general defect in energy provision and utilization. In contrast to hearts of acutely diabetic, ketotic rats most often used, the rate of lipolysis of endogenous triglycerides and the contribution of fatty acids to energy production was low in the chronically diabetic state. Inhibition of fatty acid oxidation by an inhibitor of carnitine palmitoyltransferase (CPTI) did not restore the reduced responsiveness of diabetic hearts to insulin. Analysis of intracardiac metabolites revealed that in the perfused heart of chronically diabetic rats glucose-6-phosphate and citrate do not accumulate as in hearts of ketotic, diabetic rats. Therefore, the impaired glucose metabolism presumably reflects a reduced uptake of glucose rather than in inhibition of glycolysis as in hearts of ketotic, diabetic rats.

Animals↗
PubMed2001

Heart and heart-lung transplantation: standards and improvements.

Standards and new developments of thoracic organ transplantation are reviewed with particular focus on current treatment strategies, alternatives to transplantation, and xenotransplantation. The current indications for heart, single and bilateral sequential lung, and heart-lung transplantation as well as the technical aspects of each procedure are presented. Criteria for transplant recipients and absolute and relative contraindications are pointed out. Criteria for donor selection are also reviewed. The results of single, double-sequential, and heart-lung transplantation over the past 10 years as reported by the International Society for Heart and Lung Transplantation Database are stated. In addition, the experience of the lung and heart-lung transplantation program at the Hannover Medical School is reviewed, including the current immunosuppression regimens. This experience includes 1075 heart,heart-lung, and lung transplantations since 1983. The 1- and 5-year actuarial survival rates for heart transplant recipients are 81% and 70%, for heart-lung recipients 76% and 61%, and for single and double lung transplant recipients 77% and 59%, respectively. During the past decade there has been continuous improvement in the results of heart, lung, and heart-lung transplantation. Alternatives to thoracic organ transplantation, living-related lobar transplantation, new antirejection agents, and xenograft transplantation are areas for continuing and future investigation.

Heart Failure↗
PubMed1989

Subnormal heart period variability in heart failure: effect of cardiac transplantation.

Heart period variability and arterial baroreceptor-cardiac reflex function were studied in cardiac transplant patients to determine if correction of heart failure restores parasympathetic control mechanisms toward normal. Heart period variability (standard deviation [SD] of 120 consecutive RR or PP intervals) was measured at supine rest in 34 patients with congestive heart failure (23 patients receiving diuretics, digoxin or vasodilators and 11 patients weaned from all medications), 30 cardiac transplant patients (both innervated recipient and denervated donor atrial rates) and 16 age-matched healthy control subjects. Arterial baroreflex gain was evaluated with intravenous bolus injections of phenylephrine in 22 transplant patients. Mean heart period variability (+/- SEM) was significantly lower (p less than 0.05) in the heart failure groups (22 +/- 3 ms for medicated and 17 +/- 3 ms for nonmedicated) than in the transplant patients (41 +/- 5 ms) or control subjects (58 +/- 5 ms). Heart period variability of the transplant patients was less than that of the control patients (p less than 0.05). A stepwise regression model revealed that heart period variability was inversely related to systolic arterial pressure and directly related to time after transplantation (R2 = 0.39; p = 0.03) in the transplant patients. Baroreflex gain of normotensive transplant patients was normal (11.7 +/- 1.0 ms/mm Hg) and correlated directly with heart period variability (r = 0.62; p less than 0.001). These data suggest that subnormal levels of cardiac parasympathetic activity at rest associated with congestive heart failure can be restored progressively toward normal by correction of congestive heart failure after cardiac transplantation. Post-transplant hypertension opposes this correction of baseline parasympathetic activity.

Adult↗
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMed1976

Effect of heart work and insulin on the incorporation of [14C]glucose into hexose phosphates, uridine diphosphate glucose and glycogen in the normal and insulin-deficient perfused rat heart under working and non-working conditions.

1. The specific radioactivities of glucose 1-phosphate, glucose 6-phosphate, fructose 6-phosphate, UDP-glucose and glycogen, derived from [14C]gluocose, were determined in the normal and insulin-deficient (streptozotocin-diabetic and anti-insulin-serum-treated) perfused non-working and working rat heart. 2. The specific radioactivities of all glucose metabolities reached a plateau after about 10 min, except that for glycogen, which increased slightly but steadily over the whole observation period of 30min. 3. The specific radio-activities of fructose 6-phosphate, UDP-glucose and glycogen were slignificantly lower in the streptozotocin-diabetic heart than in the normal heart. 4. Mechanical work in the normal rat heart increased the specific radioactivities of glucose 1-phosphate, UDP-glucose and glycogen, but had little or no effect on those of gluose 6-phosphate and fructose 6-phosphate. 5. In the normal heart insulin strongly increased the specific radioactivities of all gluocse metabolites under all conditions tested. The maximum values achieved in the normal working heart in the presence of insulin were only about 15-20% above those in the normal non-working heart in the presence of insulin for the phosphorylated intermediates and about 40% above for glycogen. 6. In the streptozotocin-diabetic heart, work restored the specific radioactivities of all glucose metabolities to about normal values. 7. In the streptozotocin-diabetic heart insulin strongly increased the specific radioactivities of the direct glycogen precursors glucose 1-phosphate and UDP-glucose; the effect of insulin on glucose 6-phosphate and fructose 6-phosphate was less marked. These results confirm previous findings that the primary metabolic lesion in diabetic heart muscle is a defect of glycogen synthesis. The specific radioactivity of glycogen itself was increased sixfold. 8. Under all conditions tested the specific radioactivity of glucose 1-phosphate was always found to be higher than that of glucose 6-phosphate. This indicated either compartmentation of a small but metabolically very active pool of glucose 6-phosphate, or the existence of a hitherto unknown pathway of metabolism in which glucose 1-phosphate is the primary reaction product. For a number of reasons the authors prefer the first explanation, which could also account for the observation that in the perfused normal working and non-working heart the specific radioactivity of fructose 6-phosphate was always found to be higher than that of glucose 6-phosphate. This difference disappeared or was reversed in the rat hearts rendered insulin-insufficent by either streptozotocin or anti-insulin treatment.

Animals↗
PubMed1985

Risk factors for ischaemic heart disease: the prospective phase of the British Regional Heart Study.

Risk factors for major ischaemic heart disease (acute myocardial infarction or sudden death) have been investigated in a prospective study of 7735 men aged 40-59 years drawn from general practices in 24 British towns. After a mean follow-up of 4.2 years, there have been 202 cases of major ischaemic heart disease. Univariate estimates of the risk of ischaemic heart disease show that serum total cholesterol, HDL-cholesterol and triglyceride concentrations, systolic and diastolic blood pressures, cigarette smoking, and body mass index are all associated with increased risk of ischaemic heart disease. Evidence of ischaemic heart disease at initial examination is also strongly associated with increased risk of subsequent ischaemic heart disease. All these factors were then considered simultaneously using multiple logistic models. Definite myocardial infarction on electrocardiogram and recall of a doctor diagnosis of ischaemic heart disease remained predictive of subsequent major ischaemic heart disease, after allowance for all other risk factors. Serum total cholesterol, blood pressure, and cigarette smoking each remained as highly significant independent risk factors whereas overweight, above average levels of HDL-cholesterol and serum triglyceride were not predictive of risk after allowance for the above factors. Men with and without pre-existing ischaemic heart disease were examined separately in the same way (using multiple logistic models). The strength of association between the principal risk factors and subsequent major ischaemic heart disease was reduced in the men with pre-existing ischaemic heart disease, only age and serum total cholesterol remaining highly significant. Overall the levels of the major risk factors commonly encountered in British men have a marked effect on the risk of ischaemic heart disease. Modification of these risk factors in the general population constitutes an important national priority.

Adult↗
PubMed2001

The outflow tract of the heart is recruited from a novel heart-forming field.

As classically described, the precardiac mesoderm of the paired heart-forming fields migrate and fuse anteriomedially in the ventral midline to form the first segment of the straight heart tube. This segment ultimately forms the right trabeculated ventricle. Additional segments are added to the caudal end of the first in a sequential fashion from the posteriolateral heart-forming field mesoderm. In this study we report that the final major heart segment, which forms the cardiac outflow tract, does not follow this pattern of embryonic development. The cardiac outlet, consisting of the conus and truncus, does not derive from the paired heart-forming fields, but originates separately from a previously unrecognized source of mesoderm located anterior to the initial primitive heart tube segment. Fate-mapping results show that cells labeled in the mesoderm surrounding the aortic sac and anterior to the primitive right ventricle are incorporated into both the conus and the truncus. Conversely, if cells are labeled in the existing right ventricle no incorporation into the cardiac outlet is observed. Tissue explants microdissected from this anterior mesoderm region are capable of forming beating cardiac muscle in vitro when cocultured with explants of the primitive right ventricle. These findings establish the presence of another heart-forming field. This anterior heart-forming field (AHF) consists of mesoderm surrounding the aortic sac immediately anterior to the existing heart tube. This new concept of the heart outlet's embryonic origin provides a new basis for explaining a variety of gene-expression patterns and cardiac defects described in both transgenic animals and human congenital heart disease.

3T3 Cells↗
PubMed2005

Effect of posture on heart rate variability spectral measures in children and young adults with heart disease.

BACKGROUND: Reduction of heart rate variability as a consequence of heart disease and postural change has been well documented. However, the data on the effect of postural change in pediatric patients are incomplete and the effect is not fully understood. The aim of the study was to investigate effect of postural change on heart rate variability in relation to the extent of severity of heart disease. METHODS: The dependence of heart rate variability on posture in 41 children and young adults (8-20 years) with heart disease has been investigated and compared with control. Short-term electrocardiograms (ECGs) were assessed in supine rest and active standing, and spectral measures of heart rate variability were determined. RESULTS: Two types of response to the change of supine to standing posture were determined in both healthy and diseased subjects. In majority of subjects, the increased heart rate induced by standing was accompanied by a decrease in high-frequency power. However, in about 30% of all subjects, increased heart rate during standing was accompanied by an increased high-frequency power. Independently of posture and disease, high-frequency and low-frequency power were positively correlated. In subjects characterized by a reduction of heart rate variability in standing, the high-frequency power in both postures is reduced in diseased subjects compared to control. CONCLUSIONS: These results demonstrate that in this age range, the response to posture is not unique because of the difference in high-frequency power, which implies a variety of vagal modulations of heart rate.

Adolescent↗
PubMed2004

Applying standard therapies to new targets: the use of ACE inhibitors and B-blockers for heart failure in adults with congenital heart disease.

Increasingly, patients and clinicians are being confronted with congestive heart failure (CHF) as a late complication of congenital heart disease. However, medical management of heart failure in this patient group represents a challenge because of complex hemodynamics and a lack of evidence from large randomized controlled trials to guide therapy. This article will review the evidence of the use angiotensin converting enzyme inhibitors (ACEIs) and beta-blockers (BBs) in left heart failure, discuss the mechanisms of heart failure as they pertain to congenital heart disease and review the limited literature of the use of neurohormonal antagonists in congenital heart disease. Some recommendations for use of angiotensin converting enzyme inhibitors and beta-blockers in heart failure due various congenital heart lesions are offered. Well-designed clinical trials are urgently needed to extend the impressive reductions in morbidity and mortality achieved with neurohormonal blockade in left ventricular (LV) heart failure to adults with congenital heart disease.

Adrenergic beta-Antagonists↗
PubMed2006

Successful heterotopic heart transplant after cardiopulmonary bypass rescue of an arrested donor heart.

Global heart transplantation has declined due to the donor shortage. The use of marginal donors has therefore been reintroduced. According to the history of heart transplantation, heterotopic heart transplant has played an important role in the precyclosporine era. In those circumstances, native heart and donor heart worked together to support each other against rejection or progressive heart failure. However, heterotopic transplantation has complicated surgical techniques and requirements for postoperative surveillance. Most training fellows have limited experience with this approach. At present more than 1000 cardiac surgical centers perform heart transplantation, but only 50 centers have experience in performing-heterotopic procedures. Using mechanical circulatory support for the posttransplant period is well developed in most centers. However, using mechanical circulatory support for heart donor with the intention of rescuing the heart has not been reported. Herein, we report a successful heterotopic heart transplantation after rescue with cardiopulmonary bypass of an arrested donor heart.

Cardiopulmonary Bypass↗
PubMed1997

Right and left ventricular diastolic function in patients with and without heart failure: effect of age, sex, heart rate, and respiration on Doppler-derived measurements.

Doppler echocardiography is widely used to assess right and left ventricular diastolic function. Although the factors affecting Doppler-derived measurements have been described in unaffected patients, there is little information available for patients with heart failure. Therefore we performed two-dimensional Doppler echocardiography studies of right and left ventricular function in 140 subjects, 88 with congestive heart failure and 52 age-matched normal subjects. The separate effects of age, sex, heart rate, and respiration were assessed by correlation analysis and multiple linear regression. In normal subjects both left and right ventricular parameters significantly correlated with age and heart rate. No significant effect of respiration was apparent in left ventricular function, but in the right ventricle inspiration caused a significant increase in transtricuspid peak E-wave velocity, E/A ratio, and shortening of the E-wave deceleration time. There was a significant correlation between left and right ventricular diastolic parameters. In heart failure, age correlated weakly with mitral valve peak A wave (r = 0.23, p = 0.03) and with tricuspid valve peak E-wave velocity (r = 0.37, p < 0.001), although in those with a restrictive filling pattern age was associated with a significant increased shortening of the mitral E-wave deceleration time (r = -0.8; p = 0.0015). Heart rate and deceleration time of mitral and tricuspid E wave significantly correlated, but heart rate did not correlate with either mitral or tricuspid peak E-wave or A-wave velocities or E/A ratio. In heart failure the effect of respiration was similar to normal subjects. Sex was not associated with Doppler variables in either normals or heart failure subjects. Thus this study demonstrates that age, heart rate, and respiration have important and separate associations with Doppler echo diastolic parameters of the right and left ventricle in normal subjects and similar, although weaker relations in patients with heart failure.

Adult↗
PubMed1997

Echocardiography for hemodynamic assessment of patients with advanced heart failure and potential heart transplant recipients.

OBJECTIVES: This study sought to assess the accuracy of Doppler echocardiographic techniques for the determination of right heart catheterization hemodynamic variables in patients with advanced heart failure and in potential heart transplant recipients. BACKGROUND: Doppler echocardiographic techniques permit the noninvasive acquisition of hemodynamic variables traditionally used for the assessment of patients with advanced heart failure and potential heart transplant candidates. However, the accuracy of these techniques has not been sufficiently well documented for clinical application in individual patients. METHODS: Echocardiographic data required for estimation of mean right atrial, pulmonary artery and mean left atrial pressures and cardiac output were obtained. Right heart catheterization was performed immediately after Doppler echocardiographic data were acquired, before any intervention that might have altered the subject's hemodynamic status. RESULTS: A complete Doppler echocardiographic hemodynamic data set was acquired in 21 (84%) of 25 subjects. For all variables, invasive and noninvasive hemodynamic values were highly correlated (p < 0.001), with minimal bias and narrow 95% confidence limits. An algorithm constructed from the noninvasive hemodynamic variable values identified all patients with adverse pulmonary vascular hemodynamic variables (i.e., transpulmonary gradient > or = 12 mm Hg, pulmonary vascular resistance > or = 3 Wood units or pulmonary vascular resistance index > or = 6 Wood units x m2). This algorithm identified 12 (71%) of 19 patients for whom right heart catheterization was unnecessary. CONCLUSIONS: Doppler echocardiographic estimates of hemodynamic variables in patients with advanced heart failure are accurate and reproducible. This noninvasive methodology may assist with monitoring and optimization of medical therapy in patients with advanced heart failure and may obviate the need for routine right heart catheterization in potential heart transplant candidates.

Algorithms↗
PubMed2001

Expression of RGS3, RGS4 and Gi alpha 2 in acutely failing donor hearts and end-stage heart failure.

BACKGROUND: Regulators of G-protein Signalling (RGS) proteins have been shown to limit in vitro signalling of G proteins. In common with end-stage heart failure, we have recently shown that upregulation of the inhibitory G-protein, Gialpha, occurs in acutely failing donor hearts unused for transplantation due to severe myocardial dysfunction. In light of recent data on RGS proteins, we have evaluated mRNA and protein expression of RGS3, RGS4 and Gialpha2 in the myocardium from normal, end-stage failing and acutely failing unused donor hearts. METHODS AND RESULTS: Myocardial samples were obtained from end-stage failing hearts explanted prior to transplantation (n=19), unused donor hearts with ejection fractions < 30% (n=14) and used donor hearts with good function (ejection fraction > 60%) (n=4-7). mRNA levels were quantified using quantitative reverse transcriptase polymerase chain reaction. Levels of RGS3 and RGS4 mRNA were found to be significantly upregulated in unused donor and end-stage failing myocardium (P < 0.05 and 0.01, and P < 0.05 and 0.02, respectively) compared to non-failing hearts. Protein abundance of RGS3 and RGS4 was found to be higher in myocardium from end-stage failing hearts, and relative RGS4 expression higher in unused donor hearts. CONCLUSIONS: We show here that RGS3 and RGS4 mRNA and protein expression is upregulated in human heart failure. These observations suggest that RGS4 may be induced in the heart to regulate cell signalling pathways in response to hypertrophy, and support the existence of a negative feedback loop for the long-term regulation of hypertrophy.

Algorithms↗