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This review focuses on the role of the myocardial force-frequency relation (FFR) in human ventricular performance and how changes in the FFR can reduce cardiac output and, ultimately, can contribute to altering the stability of the in-vivo cardiovascular system in a way that contributes to the progression of heart failure. Changes in the amplitude, shape, and position of the myocardial FFR occurring in various forms of heart failure are characterized in terms of maximal isometric twitch tension, slope of the ascending limb (myocardial reserve), and position of the peak of the FFR on the frequency axis (optimum stimulation frequency). All three of these parameters decline according to severity of myocardial disease in the following order: non-failing atrial septal defect, non-failing coronary artery disease, non-failing coronary artery disease with diabetes mellitus, failing mitral regurgitation, failing viral myocarditis, failing idiopathic dilated cardiomyopathy. Evidence is presented supporting a sarcoplasmic reticulum Ca-pump based mechanism for this progressive depression of the FFR. Intracellular calcium cycling and concentration and Ca-pump content all diminish in proportion to degree of depression of the FFR. Additional evidence from myocyte culture studies suggests a cause of diminished Ca-pump content is sustained, elevated levels of plasma norepinephrine. A hypothesis is presented to explain the mechanism of myocardial failure and its progression in terms of changes in the cardiovascular feedback control system that are triggered by reduced myocardial reserve. Sustained elevation of plasma norepinephrine levels depresses expression of sarcoplasmic reticulum Ca-pump protein causing depression of the FFR and this causes a compensatory further increase in norepinephrine levels and a further depression of Ca-pump protein.
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PMID:A mechanistic analysis of the force-frequency relation in non-failing and progressively failing human myocardium. 983 27

In this study, regional diastolic patterns and their relations with transmitral Doppler inflow were investigated in hypertrophic cardiomyopathy (HC) by pulsed Doppler tissue imaging (DTI). Doppler echocardiography and DTI of basal septum and lateral wall (apical 4-chamber view) were performed in 20 patients (15 men and 5 women) with HC and in 10 healthy subjects (7 men and 3 women). Diabetes, hypertension, coronary artery and valvular disease, mitral regurgitation, New York Heart Association functional classes III to IV, sinus tachycardia, atrial fibrillation, and inadequate echocardiograms were exclusion criteria. Peak velocity and time-velocity integral of early and late waves and their ratios, and deceleration and isovolumic relaxation times were determined by standard Doppler and by DTI at the septal and lateral wall levels. The 2 groups were comparable for age, heart rate, blood pressure, and ejection fraction. Transmitral peak velocity and time-velocity integral E/A ratios were reduced (both p <0.05) and deceleration and isovolumic relaxation times prolonged (both p <0.00001) in HC. Septal DTI showed lower peak velocity and time-velocity integral e/a ratios (p <0.00001 and p <0.001, respectively) and lengthened regional deceleration (p <0.01) and isovolumic (p <0.001) relaxation times. DTI of the lateral wall showed a prolongation of deceleration and isovolumic relaxation times (both p <0.01). By dividing HC according to transmitral E/A, 8 patients with E/A <1 had lower DTI septal e/a ratio (p <0.01) and prolonged septal deceleration and isovolumic relaxation times (both p <0.01) but no changes in DTI pattern of lateral wall than 12 patients with E/A > 1. In conclusion, DTI is useful and complementary to standard Doppler imaging to characterize diastolic properties in HC, reflecting a typical pattern of intramyocardial impaired relaxation at the level of hypertrophied septum and also providing information about the degree of this regional impairment. The lateral wall presents minor changes in diastolic times, which indicate how diastolic asynchrony is not confined to the hypertrophied segment in HC.
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PMID:Use of pulsed Doppler tissue imaging to assess regional left ventricular diastolic dysfunction in hypertrophic cardiomyopathy. 1172 73

The prevalence of coronary artery disease (CAD) and the incidence of new coronary events are similar in older men and women. Independent risk factors for new coronary events in older women include age, prior CAD, cigarette smoking, hypertension, diabetes mellitus, high serum total cholesterol and triglycerides, and low serum high-density lipoprotein cholesterol. Older women have a higher prevalence of hypertension than older men. In older women with hypertension, echocardiographic left ventricular hypertrophy is a powerful independent predictor of new coronary events, atherothrombotic brain infarction, and congestive heart failure (CHF). Older women have a higher prevalence of rheumatic mitral stenosis and of mitral annular calcium than older men. Older women and men have a similar prevalence of valvular aortic stenosis, aortic regurgitation, mitral regurgitation, hypertrophic cardiomyopathy, and idiopathic dilated cardiomyopathy. The prevalence and incidence of CHF increase with age. The prevalence of normal left ventricular ejection fraction associated with CHF increases with age and is higher in older women than in older men. The prevalence of chronic atrial fibrillation increases with age and is similar in older men and women. Atrial fibrillation is an independent predictor of new coronary events and thromboembolic stroke in older women. Older women with unexplained syncope should have 24-hour ambulatory electrocardiograms to determine whether pauses > 3 seconds are present, requiring permanent pacemaker implantation.
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PMID:Prevalence of heart disease in older women in a nursing home. 986 88

Phentermine and fenfluramine are widely used in the treatment of obesity. Despite the fact that primary pulmonary hypertension and mitral valve insufficiency have been associated with fenfluramine use, many of these patients need medication to achieve weight loss. Small degrees of weight loss have been shown to significantly improve obesity-related medical conditions such as hypertension, hypercholesterolemia, and noninsulin-dependent diabetes mellitus. Current practice is to give phentermine and fenfluramine in the morning and afternoon. Doses for phentermine have ranged from 15 to 37.5 mg and for fenfluramine from 20 to 120 mg per day. We report five cases of severely obese women with medical complications who were treated with phentermine 8 mg twice per day (at 1:00 p.m. and 4:00 p.m.) and fenfluramine 20 mg per day (at 4:00 p.m.). Because many obese patients skip breakfast and eat more in the afternoon and evening, medication was dosed in order to cover these high-risk eating periods. Overall, these patients lost a mean of 22.4% of their initial weight (range 18.6% to 32.8%) over an average of 8.4 months (range 3.5 to 16 months). These cases suggest that short-term weight loss can be achieved with a low dose of fenfluramine when both medications are given in the afternoon to better target the eating patterns of obese subjects.
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PMID:Lower dosages of phentermine-fenfluramine given in the afternoon: five cases with significant weight loss. 1020 59

Echocardiographic examination and 24-h electrocardiographic Holter monitoring were carried out on 35 patients with nodular rheumatoid arthritis (RA) and 35 with non-nodular RA, who were matched with the nodular RA group regarding age, sex and BSA. A further 35 patients with osteoarthrosis and spondyloarthrosis matched, with both RA groups, constituted a control group. Patients with a history of myocardial infarction, hypertension, rheumatic fever and diabetes were excluded from the study. Cardiac involvement, evaluated using echo-Doppler cardiography, 24-h electrocardiographic Holter monitoring and ECG at rest, occurred in 25 (71.9%) patients with nodular RA and in 15 (42.9%) with non-nodular RA in comparison to 8 (22.9%) control group patients (P < 0.0002). Holter electrocardiographic monitoring over 24 h did not present any essential differences in frequency of rhythm disorders between the examined groups and the control group. However, it revealed more patients with 1-mm ST depression in the nodular RA group than in the non-nodular and control groups. Echocardiographic examination revealed more cases of valvular heart abnormalities, especially those of mitral insufficiency, in nodular RA patients than in non-nodular and control patients. Both a mitral valve prolapse and a pericardial effusion were noted in 8.6% of nodular RA patients. Patients with nodular RA were noted to have a bigger aortic root diameter, but smaller ejection fraction, mean velocity of circumferential fibre shortening and fractional shortening in comparison to non-nodular and to control group patients.
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PMID:Echocardiographic findings and 24-h electrocardiographic Holter monitoring in patients with nodular and non-nodular rheumatoid arthritis. 1039 90

CAD is the most common cause of death in older men and was present in 44% of 664 men, mean age 80 years. Independent risk factors for new coronary events in older men include increasing age, prior CAD, cigarette smoking, hypertension, diabetes mellitus, high serum total cholesterol, and low serum HDL cholesterol. In older men with hypertension, echocardiographic LVH is a powerful independent predictor of new coronary events, atherothrombotic brain infarction, and CHF. In 554 older men with a mean age of 80 years, two-dimensional and Doppler echocardiography demonstrated that the prevalence of aortic stenosis was 14%, 1 + aortic regurgitation or greater was 31%, rheumatic mitral stenosis was 0.4, 1 mitral regurgitation or greater was 32%, mitral annular calcium was 35%, hypertrophic cardiomyopathy was 3%, idiopathic dilated cardiomyopathy was 1%, left atrial enlargement was 29%, LVH was 41%, and abnormal LVEF was 29%. The prevalence and incidence of CHF increase with age in older persons. The prevalence of a normal LVEF associated with CHF as a result of prior myocardial infarction or hypertension was 22% in men aged 60 to 69 years, 33% in men aged 70 to 79 years, 41% in men aged 80 to 89 years, and 47% in men aged 90 years or older.
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PMID:The older man's heart and heart disease. 1050 66

Although several studies demonstrated that the presence of significant mitral regurgitation was associated with reduced occurrence of thromboembolism, little data is available concerning the effect of mild mitral regurgitation on the occurrence of thromboembolic events. To evaluate the association between mild mitral regurgitation and thromboembolic events, we reviewed 232 patients' records between January 1996 and September 1997 who had nonrheumatic atrial fibrillation. There were 59 patients (25%) with mitral regurgitation > or = grade 2, 69 patients (30%) with grade 1 mitral regurgitation, and 104 patients (45%) with no mitral regurgitation. Patients with grade 1 mitral regurgitation had significantly higher prevalence of thromboembolic events (28%) than those with mitral regurgitation > or = grade 2 (8%, P=0.006) or those with no mitral regurgitation (11%, P=0.007). A history of previous thromboembolic events were compared between 173 patients with grade 1 mitral regurgitation and those with no mitral regurgitation using the logistic regression analysis adjusted for age, sex, administration of warfarin, and presence of hypertension, diabetes mellitus, structural heart disease, enlarged left atrium (> or = 40 mm), chronic atrial fibrillation, and grade 1 mitral regurgitation. Grade 1 mitral regurgitation (odds ratio=2.689, 95% confidence interval=1.039-7.189, P=0.0434) and no warfarin administration (odds ratio=0.045, 95% confidence interval=0.002-0.242, P=0.0036) were significantly associated with the history of thromboembolic events. The presence of mild mitral regurgitation in nonrheumatic atrial fibrillation was associated with higher prevalence of thromboembolic events.
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PMID:Mild mitral regurgitation was associated with increased prevalence of thromboembolic events in patients with nonrheumatic atrial fibrillation. 1071 32

Mitral regurgitation (MR) complicating acute myocardial infarction (AMI) is associated with increased mortality. The prognostic significance of only mild MR detected by echocardiography in patients with AMI is unknown. This study assessed the long-term risk associated with mild MR detected by color Doppler echocardiography within the first 48 hours of admission in 417 consecutive patients with AMI. No MR was detected in 271 patients (65%), mild MR was seen in 121 patients (29%), and moderate or severe MR was noted in 25 patients (6%). One-year mortality rates were 4.8%, 12.4%, and 24%, respectively (p<0.001). Multivariate analysis revealed that mild MR was independently associated with increased 1-year mortality (p<0.05) after adjustment for age, gender, previous myocardial infarction, diabetes mellitus, systemic hypertension, Killip grade > or =2 on admission, and left ventricular ejection fraction < or =40%. The hazard ratio for 1-year mortality was 2.31 (95% confidence interval 1.03 to 5.20) for mild MR and 2.85 (95% confidence interval 0.95 to 8.51) for moderate or severe MR. Thus, mild MR detected by color Doppler echocardiography within the first 2 days of admission in patients with AMI is a significant independent risk predictor for 1-year all-cause mortality.
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PMID:Prognostic significance of mild mitral regurgitation by color Doppler echocardiography in acute myocardial infarction. 1105 96

Previous studies have described the use of transesophageal echocardiography (TEE) with acoustic quantification (AQ) in assessing aortic elastic properties. We hypothesized that patients with a prior history of stroke (ST) may have a higher risk of atherosclerotic change in great vessels compared to nonstroke subjects (NST) and thus have decreased elastic properties. We assessed the elastic properties of the descending thoracic aorta (DTA) by TEE in ST patients and compared them with data in NST patients. Subjects included 31 with ST without any evidence of emboli originating from the heart (age 51 +/- 10 years, M:F = 20:11) and 25 age-matched NST (M:F = 8:17). Patients with significant valvular heart disease including aortic and mitral regurgitation, left ventricular dysfunction (ejection fraction < 55%), and congenital heart disease were excluded. Compliance (C), distensibility (D), and stiffness index (SI) were measured using AQ and M-mode measurement at a level of the left atrium. We scored atherosclerotic risk factors (ARF) such as a history of diabetes, hypertension, smoking, hypercholesterolemia, and the presence of atheroma of DTA. There was no evidence of atheroma of DTA in NST. There were no significant differences in heart rate and systolic and diastolic blood pressure between ST and NST patients. Fractional area change (FAC) of DTA was significantly lower in ST than in NST patients (3.2 +/- 1.6 vs 5.4 +/- 2.5%, P = 0.000). ST patients had significantly lower C (1.2 +/- 0.4 vs 1.5 +/- 0.7 x 10(-3) cm2 mmHg(-1), P = 0.039), lower D (0.8 +/- 0.3 vs 1.5 +/- 0.8 x 10(-3) mmHg(-1), P = 0.000), and higher SI (10.3 +/- 8.8 vs 5.3 +/- 2.9, P = 0.006) than NST patients. ST patients without atheroma of DTA (n = 21) also had significantly lower C (1.1 +/- 0.4 vs 1.5 +/- 0.7 x 10(-3) cm2 mmHg(-1), P = 0.038) and lower D (3.5 +/- 1.4 vs 4.8 +/- 2.4 x 10(-3) mmHg(-1), P = 0.021) than NST patients. There was a significant positive correlation between SI and the score of ARF (r = 0.51, P = 0.000). The regional elastic properties of DTA measured by TEE with AQ and M-mode method were abnormal in ST. Therefore, TEE with AQ technique may have a possible clinical application for the detection of early atherosclerotic changes such as alteration of elastic properties in morphological normal DTA.
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PMID:Assessment of elastic properties of the descending thoracic aorta by transesophageal echocardiography with acoustic quantification in patients with a stroke. 1115 17

Left ventricular hypertrophy LVH is supposed to be a useful marker of cardiovascular complications during the course of hypertension. Occurrence of other risk factors of atherosclerosis in these hypertensive patients such as hyperlipidemia and smoking deteriorate the prognosis too. The authors compared clinical findings in hypertensive patients with and without left ventricular hypertrophy defined by echocardiography. Hospital records of 185 hypertensive patients treated at our medical department during years 1996-1999 were analysed. Left ventricular hypertrophy was defined by echocardiography (Penn convention) as left ventricular mass index > 134 g/m2 in men and > 110 g/m2 in women. Presence of LVH was found in 109 patients (mean age 66.7 years), absence of LVH in 76 patients (mean age 64.7 years). Both groups of hypertensive patients were matched by demographic parameters by the presence of hyperlipidemia and by smoking habits. Hypertensive patients with diabetes mellitus and obesity were excluded. They were statistically significant in the incidence of heart failure, myocardial infarction, renal failure and mitral regurgitation, and non-significant in the incidence of left ventricular diastolic dysfunction. There were more cardiovascular complications in LVH-positive patients than in those with LVH-negative findings. The incidence of stroke was slightly higher in LVH-negative patients. Left ventricular hypertrophy in patients with hypertension brings usually a complicated course of the disease. The authors recommend to examine the patients with arterial hypertension for the presence of left ventricular hypertrophy as it complicates the course of the disease significantly. (Tab. 3, Fig. 2, Ref. 26.)
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PMID:[Left ventricular hypertrophy in hypertension]. 1115 71


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