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PubMed2004

Gene and cell-based therapies for heart disease.

Heart disease remains the prevalent cause of premature death and accounts for a significant proportion of all hospital admissions. Recent developments in understanding the molecular mechanisms of myocardial disease have led to the identification of new therapeutic targets, and the availability of vectors with enhanced myocardial tropism offers the opportunity for the design of gene therapies for both protection and rescue of the myocardium. Genetic therapies have been devised to treat complex diseases such as myocardial ischemia, heart failure, and inherited myopathies in various animal models. Some of these experimental therapies have made a successful transition to clinical trial and are being considered for use in human patients. The recent isolation of endothelial and cardiomyocyte precursor cells from adult bone marrow may permit the design of strategies for repair of the damaged heart. Cell-based therapies may have potential application in neovascularization and regeneration of ischemic and infarcted myocardium, in blood vessel reconstruction, and in bioengineering of artificial organs and prostheses. We expect that advances in the field will lead to the development of safer and more efficient vectors. The advent of genomic screening technology should allow the identification of novel therapeutic targets and facilitate the detection of disease-causing polymorphisms that may lead to the design of individualized gene and cell-based therapies.

Coronary Artery Disease↗
PubMed1993

Exercise, fibrinogen, and other risk factors for ischaemic heart disease. Caerphilly Prospective Heart Disease Study.

OBJECTIVE: To examine the associations between physical activity and a wide range of risk factors for ischaemic heart disease including fibrinogen concentration and viscosity. DESIGN: Cross sectional evidence from the 2398 men aged 50-64 years in the Caerphilly Prospective Heart Disease Study. METHODS: Validated questionnaires were used to quantify energy expenditure on leisure activities and to grade activities related to occupation. Risk factors for heart disease examined included blood pressure, lipids, fibrinogen, and plasma viscosity. Possible confounding variables included smoking, employment, and prevalent heart disease (angina, previous myocardial infarction, and electrocardiographic evidence of ischaemia). RESULTS: Fibrinogen concentration was lower by 0.24 g/l and viscosity by 0.026 cP in the third of men who were most active in leisure activities (about 0.25 x 1 SD). A weak positive relation was found with high density lipoprotein cholesterol, but none with total cholesterol or fasting glucose concentrations or blood pressure. Triglyceride concentrations seem to be substantially lower in the most active men, although the evidence for this is not consistent. Work related activity showed relation with the lipid concentration but not with the haemostatic tests. CONCLUSIONS: Leisure activities of all levels seem to affect haemostatic and lipid factors beneficially. These effects correspond to a difference in the risk of heart disease for an active man and a sedentary man of at least 7% or 8%. Fasting triglyceride concentrations have already been shown to be strongly predictive of heart disease in this cohort of men, and the effect of exercise on this factor is also likely to confer benefit.

Blood Viscosity↗
PubMedDate not supplied

Adherence to National Cholesterol Education Program Treatment goals in postmenopausal women with heart disease. The Heart and Estrogen/Progestin Replacement Study (HERS). The HERS Research Group.

OBJECTIVES: To determine the proportion of volunteer women with established heart disease who have low-density lipoprotein cholesterol (LDL-C) levels at or below the National Cholesterol Education Program Adult Treatment Panel goals and to determine what factors are associated with levels above goal or not receiving lipid-lowering medication when indicated. DESIGN: Cross-sectional measurement of lipids and lipoproteins, blood pressure, height, weight, and other demographic and cardiovascular risk factors in 2763 postmenopausal women with heart disease. SETTING: At 18 centers throughout the United States, participants were recruited by means of lists of women with coronary heart disease from coronary units and catheterization laboratories, direct mail to age-eligible women, and advertisements. PATIENTS: Mean age of the cohort was 66.7 years (range, 44-79 years) and the distribution by race/ethnicity was 88.7% white, 7.9% African American, 2.0% Hispanic/Latina, 0.8% Asian/Pacific Islander, and 0.7% other. INTERVENTION: We report cross-sectional analysis of the cohort at baseline. OUTCOME MEASURES: We measured the frequency of achieving 1988 and 1993 Adult Treatment Panel treatment goals, and of being on a regimen of lipid-lowering medication. RESULTS: Although 47% of participants were taking a lipid-lowering medication, 63% did not meet the 1988 treatment goal of LDL-C level less than 3.4 mmol/L (130 mg/dL) and 91% did not meet the 1993 goal of LDL-C level less than 2.6 mmol/L (100 mg/dL). Factors independently associated with achieving the earlier goal were use of lipid-lowering medication, marital status, education, body mass index, exercise, hypertension, diabetes, gallbladder disease, and first diagnosis of coronary heart disease after 1990. Failure to use lipid-lowering medication was associated with age, being African American, marital status, body mass index, lack of exercise, alcohol consumption, current smoking, and first diagnosis of coronary heart disease before 1985. CONCLUSION: The majority of women enrolled in the trial had LDL-C levels that significantly exceeded the treatment goals set by the 1988 and 1993 Adult Treatment Panel guidelines. Better implementation of these guidelines among women with coronary disease would be highly desirable.

Aged↗
PubMed2007

Electrophysiological interventions for treatment of congestive heart failure in pediatrics and congenital heart disease.

Heart failure therapy, while well tested in the adult population, therapeutic interventions are less well defined in the pediatric population. Several treatment strategies are available for the adult patient with heart failure, thought few of these therapies have been proven in children. Morbidity and mortality in the pediatric population with a failing heart is significant, and rhythm management as well as strategies to improve hemodynamics are important in the care of these children. This review will address issues of rhythm management and resynchronization therapy in pediatric and congenital heart disease patients with heart failure.

Adrenergic beta-Antagonists↗
PubMed1996

Endothelium-dependent vasodilatation is not selectively impaired in patients with chronic heart failure secondary to valvular heart disease and congenital heart disease.

This study examined possible selective impairment of endothelial dysfunction in the peripheral vascular bed in patients with chronic heart failure in the absence of confounding factors influencing endothelial function (i.e. hypertension, hypercholesterolaemia and diabetes mellitus). Several recent studies have suggested that endothelium-dependent peripheral vasodilation is impaired but endothelium-independent vasodilation is preserved in patients with chronic heart failure. However, a classical paper has demonstrated that sodium nitrite-mediated calf blood flow is clearly depressed in patients with valvular heart disease and cardiomyopathy. We examined forearm blood flow changes mediated by acetylcholine and nitroprusside in patients with valvular heart disease (n = 55) or congenital heart disease (n = 13), and a comparison was made with healthy volunteers (n = 21). The blood flow changes mediated by acetylcholine and nitroprusside were significantly impaired in both patient groups (P < 0.01). When blood flow responses were collected from all patients, two types of vasodilatory capacity were found to have decreased significantly with increasing clinical severity of heart failure (New York Heart Association functional class; P < 0.01). This suggests that the peripheral vasodilatory responses mediated by endothelium-dependent and endothelium-independent vasodilators are significantly impaired in patients with symptomatic chronic heart failure due to non-ischaemic heart disease.

Acetylcholine↗
PubMed2003

Risk factors and secondary prevention in women with heart disease: the Heart and Estrogen/progestin Replacement Study.

BACKGROUND: Risk factors for coronary heart disease events have most commonly been evaluated in healthy men. OBJECTIVE: To assess risk factors, event rates, and use of secondary prevention treatments in women with preexisting coronary disease. DESIGN: A prospective cohort of clinical trial participants. SETTING: 20 U.S. clinical centers. PARTICIPANTS: 2763 postmenopausal women with known coronary disease in the Heart and Estrogen/progestin Replacement Study (HERS). MEASUREMENTS: Myocardial infarction or death from coronary heart disease. RESULTS: On multivariable analysis, the researchers found 11 risk factors: 6 noted by history (nonwhite ethnicity, lack of exercise, treated diabetes, angina, congestive heart failure, and more than one previous myocardial infarction) and 5 that were measured (blood pressure, low-density lipoprotein cholesterol level, high-density lipoprotein cholesterol level, lipoprotein(a) level, and creatinine clearance). The annual rate of coronary events was 1.3% (95% CI, 0.7% to 2.5%) in women with no risk factors and 8.7% (CI, 7.1% to 10.8%) in women with five or more risk factors (a sixfold increase). At entry into HERS, 83% of participants were receiving aspirin or other antiplatelet agents, 33% were receiving beta-blockers, 18% were receiving angiotensin-converting enzyme inhibitors, and 53% were receiving lipid-lowering drugs. Women with more risk factors were less likely to be taking aspirin (P < 0.001) and lipid-lowering drugs (P = 0.006). CONCLUSIONS: Women with coronary disease are at high risk for myocardial infarction or death from coronary heart disease even in the absence of other risk factors, and their risk increases up to sixfold when many risk factors are present. Established drugs for secondary prevention, including aspirin, beta-blockers, and lipid-lowering agents, are underused in these women, especially those at highest risk.

Adrenergic beta-Antagonists↗
PubMed2002

Pregnancy and valvular heart disease.

Heart disease can affect anyone at any time, and pregnant women are not exceptions. Some type of cardiac pathologic disease can be seen in 1% to 2% of all pregnant women. Because of the high fetal mortality rate and the high relative rate of maternal mortality in surgery, medical management is the first line of treatment. Nevertheless, when medical treatment fails, cardiac surgery may be necessary. Here we present such a case of cardiac valvular disease complicated by pregnancy. Current decision-making, treatment, and trends are reviewed.

Adult↗
PubMed1998

Pregnancy and pre-existing heart disease.

Heart disease is encountered in nearly 1% of pregnancies, and the incidence is increasing. This is likely due to advances in cardiac management over the past 25 years, particularly advances in cardiac surgery and drugs, which have allowed more women with congenital and other abnormalities not only to survive to reach the age of child-bearing but also to carry a pregnancy to term successfully. Cardiac diseases of particular importance include stenotic valvular lesions, cyanotic disorders, and lesions accompanied by pulmonary hypertension. These abnormalities are associated with increased fetal and maternal morbidity and mortality, and therefore require very close monitoring during pregnancy. The physician also should be familiar with the more common cardiac disorders seen in pregnancy, be familiar with cardiovascular drugs and their potential effects on the pregnant patient and fetus, and be aware of cardiac disorders which are relative and absolute contraindications to pregnancy due to high rates of maternal mortality.

Female↗
PubMed2005

Analysis of left ventricular systolic function using midwall mechanics in patients >60 years of age with hypertensive heart disease and heart failure.

Normal ejection fraction (EFs) is often equated with normal systolic function. However, midwall mechanics reveal systolic dysfunction in hypertensive heart disease accompanied by hypertrophic remodeling. Midwall mechanics are unstudied in patients with acute diastolic heart failure (HF). This study analyzed left ventricular (LV) midwall stress-shortening relations in 61 patients aged >60 years with hypertensive heart disease, HF, and normal EF. Sixty-one hypertensive patients (mean age 78 +/- 10 years) who presented with HF, each with an EF >50%, underwent echocardiography. Midwall mechanics were compared with those of 79 controls (mean age 75 +/- 8 years) without structural heart disease. Relative wall thickness (0.63 +/- 0.11 vs 0.46 +/- 0.10 mm) and LV mass (237 +/- 67 vs 177 +/- 57 g) were significantly greater in patients with HF compared with controls. Mean EFs were similar in patients with HF and controls (64 +/- 9% vs 67 +/- 9%). Although mean endocardial fractional shortening (35 +/- 7% vs 37 +/- 7%) was not significantly different, midwall shortening in patients with HF was significantly less compared with controls (16 +/- 2% vs 19 +/- 3%, p <0.05). Eighteen of the 61 patients with HF (30%) had midwall shortening that was <95% confidence intervals of the normal midwall stress-shortening relations. By this criterion, these patients had systolic dysfunction despite normal EF; they had smaller LV chambers (in dimension and volume), greater relative wall thickness, and smaller stroke volumes. In conclusion, almost 1/3 of patients hospitalized with diastolic HF had systolic dysfunction, characterized by abnormal midwall stress-shortening relations.

Aged↗
PubMedDate not supplied

Prevalence of significant coronary heart disease in valvular heart disease in Indian patients.

Records of 326 patients were analysed to determine the prevalence of coronary heart disease (CHD) in patients with valvular heart disease (VHD) and to identify the group in whom coronary arteriography is essential. Significant CHD (60% or more luminal narrowing) was found in 7 per cent of cases, and its prevalence was 3 per cent in mitral, 10 per cent in aortic, and 6 per cent in combined mitral and aortic valve disease. Angina was present in 14 per cent of patients with mitral, 39 per cent with aortic, and 21 per cent with combined mitral and aortic valve disease. Seventy-three per cent of patients with CHD had angina whereas only 19 per cent with angina had CHD. The prevalence of CHD was higher in patients above 50 years (13%) and in males (98%) as compared to those below 50 years (3%) and females (none). We conclude that the prevalence of CHD is low in our patients with VHD. Routine coronary arteriography is recommended only in males over the age of 50 years.

Adult↗
PubMed1993

Balloon dilation of tricuspid and pulmonary valves in carcinoid heart disease.

Heart involvement is usually the cause of death in patients with carcinoid syndrome, who may survive a long time even after the disease has entered an advanced stage. For this reason, carcinoid heart disease patients have undergone surgical replacement of affected valves. Two of our patients were not good candidates for surgery, due to the extent of hepatic metastasis. Alternatively, we performed percutaneous balloon valvuloplasty on both the tricuspid and pulmonary valves in both patients. To our knowledge, there has been only 1 previous report of successful tricuspid valvuloplasty in a case of carcinoid heart disease, and this did not involve concomitant pulmonary valvuloplasty. Before the procedure, both of our patients had low cardiac output with restriction in the right ventricle, pulmonary and tricuspid stenosis, and moderate tricuspid regurgitation. In the 1st patient, valvuloplasty reduced tricuspid and pulmonary gradients without change in cardiac output. This patient experienced initial clinical improvement but died 8 months after the procedure, of portal hypertension and extensive hepatic metastasis. The 2nd patient showed notably diminished gradients and a very significant increase in cardiac output. She advanced from New York Heart Association functional class IV to class I, and is now maintained with diuretic therapy. In our judgment, balloon valvuloplasty is a sound alternative to surgery for patients with carcinoid heart disease, especially when stenosis is the dominant symptom. Valvuloplasty is contraindicated in cases of severe tricuspid regurgitation.

Adult↗
PubMed2006

Valvular heart disease and heart failure: dental management considerations.

Approximately 5 million people are diagnosed with valvular heart disease in the United States each year. Many of these will present to the general dentist for routine dental care. The dentist must then understand the implications of this disease process to treat these patients safely and effectively. Of course patients with pathologic valve disease are managed in close consultation with their physicians. Even so, a dentist with knowledge of the disease process, as well as its diagnosis and treatment, has greater confidence when treating these patients. This article summarizes issues related to valvular heart disease and heart failure and provides guidance to dentists treating patients with such conditions.

Antibiotic Prophylaxis↗
PubMed1986

A comparison of two radionuclide ejection-fraction techniques with contrast angiography in ischemic heart disease and valvular heart disease.

First-pass radionuclide angiography (FPRA) in the 30 degree right anterior oblique and equilibrium gated radionuclide angiography (EGNA) in the 45 degree left anterior oblique were used for quantitative measurements of left ventricular ejection fraction (LVEF). Equipment used was a 400T gamma-camera interfaced with a Simis III Informatek computer. The results were compared with contrast angiography (CA). The aim of this study was to determine the sensitivity of both radionuclide techniques. The present data are based on 65 patients in whom CA and EGNA were performed. In 47 patients both FPRA and EGNA were performed. Results suggested that in ischemic heart disease (IHD) and valvular heart disease (VHD) the EGNA technique is well correlated with CA (r = 0.9 and 0.73, respectively). FPRA correlated well only with CA in IHD (r = 0.86), but not in VHD (r = 0.18). This study indicates that both FPRA and EGNA are sensitive, noninvasive techniques for measuring ejection fraction in IHD, while in VHD, EGNA is more sensitive technique than FPRA.

Adolescent↗
PubMed1994

Relationship between various parameters derived from 123I-labelled beta-methyl-branched fatty acid whole-body scintigraphy and left ventricular ejection fraction in patients with ischaemic heart disease.

Heart uptake and clearance of 123I-15-(p-iodophenyl)-3(R,S)-methyl- pentadecanoic acid (BMIPP) by whole-body scintigraphy in relation to left ventricular ejection fraction (LVEF) was evaluated in 34 patients with ischaemic heart disease. At 45 and 210 min after injection, anterior whole-body images were obtained. In each patient, multigated blood pool scintigraphy was also performed, and LVEF was calculated. The percentage heart uptake of BMIPP did not have a significant correlation with LVEF (R = -0.299, NS). In contrast, there was a positive correlation between LVEF measured by multigated blood pool scintigraphy and BMIPP count density of the heart (R = 0.467, P = 0.005). Myocardial BMIPP washout rate also positively correlated with LVEF (R = 0.472, P = 0.005). In addition to these observations, there was a positive correlation between the BMIPP count density of the heart and myocardial BMIPP washout rate (R = 0.0543, P = 0.001). Thus, the BMIPP count density of the heart and myocardial BMIPP washout rate derived from BMIPP whole-body scintigraphy directly correlated with LVEF. However, the correlations between these parameters and LVEF were not strong enough to allow left ventricular dysfunction to be assessed precisely.

Adult↗
PubMed1993

Long-term echocardiographic follow-up of acromegalic heart disease.

Heart muscle disease in acromegaly manifests usually as cardiac hypertrophy. Based on a retrospective analysis, it was suggested that cardiac hypertrophy is slowly reversible after normalization of plasma growth hormone levels. The reversibility of acromegalic heart muscle disease during and after treatment of acromegaly was studied prospectively. A cohort of 78 patients was examined echocardiographically in 1981, and 38 survivors of this group were reexamined 10 years later. Patients were classified according to original hormonal activity in 1981, and change in hormonal activity during follow-up into the following 4 groups: group I--hormonally inactive for entire follow-up (n = 10); group II--hormonally active for entire follow-up (n = 11); group III--initially hormonally inactive with later resurgence (n = 6); and group IV--initially hormonally active with later normalization of growth hormone levels (n = 11). No significant echocardiographic changes occurred during follow-up in group I. Left ventricular posterior wall and septal diastolic thickness, and left ventricular mass increased significantly (all p < 0.05) in group II. Left ventricular posterior wall thickness, mass and diastolic volume increased significantly (p < 0.05, < 0.01 and < 0.001, respectively) in group III. On the contrary, there were significant decreases in left ventricular mass, and both diastolic and systolic left ventricular volumes (p < 0.01, < 0.05 and < 0.05, respectively) in group IV. It is concluded that both hypertrophy and dilatation of the left ventricle in acromegaly are slowly reversible after successful treatment. On the contrary, continuing or relapsed hyperproduction of growth hormone causes further deterioration of acromegalic heart disease.

Acromegaly↗