Biomedical subjects

Dalane W Kitzman

Publications and source records attributed to Dalane W Kitzman.

At least 55 records · Page 3Linked to original sources

PubMed2002

Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure.

CONTEXT: Many older patients with symptoms of congestive heart failure have a preserved left ventricular ejection fraction (LVEF). However, the pathophysiology of this disorder, presumptively termed diastolic heart failure (DHF), is not well characterized and it is unknown whether it represents true heart failure. OBJECTIVE: To assess the 4 key pathophysiological domains that characterize classic heart failure by systematically performing measurements in older patients with presumed DHF and comparing these results with those from age-matched healthy volunteers and patients with classic systolic heart failure (SHF). DESIGN AND SETTING: Observational clinical investigation conducted in 1998 in a general community and teaching hospital in Winston-Salem, NC. PARTICIPANTS: A total of 147 subjects aged at least 60 years. Fifty-nine had isolated DHF defined as clinically presumed heart failure, LVEF of at least 50%, and no evidence of significant coronary, valvular, or pulmonary disease. Sixty had typical SHF (LVEF < or =35%). Twenty-eight were age-matched healthy volunteer controls. MAIN OUTCOME MEASURES: Left ventricular structure and function, exercise capacity, neuroendocrine function, and quality of life. RESULTS: By echocardiography, mean (SE) LVEF was 60% (2%) in patients with DHF vs 31% (2%) in those with SHF and 54% (2%) in controls. Mean (SE) LV mass-volume ratio was markedly increased in patients with DHF (2.12 [0.14] g/mL) vs those with SHF (1.22 [0.14] g/mL) (P<.001) and vs controls (1.49 [0.17] g/mL) (P =.002). Peak oxygen consumption by expired gas analysis during cycle ergometry was similar in the DHF and SHF groups (14.2 [0.5] and 13.1 [0.5] mL/kg per minute, respectively; P =.40) and in both was markedly reduced compared with healthy controls (19.9 [0.7] mL/kg per minute) (P =.001 for both). Ventilatory anaerobic threshold was similar in the DHF and SHF groups (9.1 [0.3] and 8.7 [0.3] mL/kg per minute, respectively; P<.001) and in both was reduced compared with healthy controls (11.5 [0.4] mL/kg per minute) (P<.001). Norepinephrine levels were similar in the DHF (306 [64] pg/mL) and SHF (287 [62] pg/mL) groups (P =.56) and in both were markedly increased vs healthy controls (169 [80] pg/mL) (P =.007 and.03, respectively). Brain natriuretic peptide was substantially increased in both the DHF (56 [30] pg/mL) and the SHF (154 [28] pg/mL) groups compared with healthy controls (3 [38] pg/mL) (P =.02 and.001, respectively). Quality-of-life decrement score as assessed by the Minnesota Living with Heart Failure Questionnaire was substantially increased from the benchmark score of 10 in both groups (SHF: 43.8 [3.9]; DHF: 24.8 [4.4]). CONCLUSION: Patients with isolated DHF have similar though not as severe pathophysiologic characteristics compared with patients with typical SHF, including severely reduced exercise capacity, neuroendocrine activation, and impaired quality of life.

Aged↗

PubMed2002

Outcome of congestive heart failure in elderly persons: influence of left ventricular systolic function. The Cardiovascular Health Study.

BACKGROUND: Most persons with congestive heart failure are elderly, and many elderly persons with congestive heart failure have normal left ventricular systolic function. OBJECTIVE: To evaluate the relationship between left ventricular systolic function and outcome of congestive heart failure in elderly persons. DESIGN: Population-based longitudinal study of coronary heart disease and stroke. SETTING: Four U.S. sites: Forsyth County, North Carolina; Sacramento County, California; Allegheny County, Pennsylvania; and Washington County, Maryland. PARTICIPANTS: 5888 persons who were at least 65 years of age and were recruited from the community. MEASUREMENTS: Total mortality and cardiovascular morbidity and mortality. RESULTS: Of 5532 participants, 269 (4.9%) had congestive heart failure. Among these, left ventricular function was normal in 63%, borderline decreased in 15%, and overtly impaired in 22%. The mortality rate was 25 deaths per 1000 person-years in the reference group (no congestive heart failure and normal left ventricular function at baseline); 154 deaths per 1000 person-years in participants with congestive heart failure and impaired left ventricular systolic function; 87 and 115 deaths per 1000 person-years in participants with congestive heart failure and normal or borderline systolic function, respectively; and 89 deaths per 1000 person-years in persons with impaired left ventricular function but no congestive heart failure. Although the risk for death from congestive heart failure was lower in persons with normal systolic function than in those with impaired function, more deaths were associated with normal systolic function because more persons with heart failure fall into this category. CONCLUSIONS: Community-dwelling elderly persons, especially those with impaired left ventricular function, have a substantial risk for death from congestive heart failure. However, more deaths occur from heart failure in persons with normal systolic function because left ventricular function is more often normal than impaired in elderly persons with heart failure.

Aged↗

PubMed2002

Appetite suppressants and valvular heart disease in a population-based sample: the HyperGEN study.

PURPOSE: Previous studies of the association between the use of appetite suppressants and valvular heart disease have not accounted for the effects of valvular structure and aortic root diameter, which are associated with obesity. We assessed whether the use of the appetite suppressants fenfluramine/dexfenfluramine, either alone or with phentermine, was associated with aortic regurgitation while adjusting for these variables. SUBJECTS AND METHODS: The sample included 2524 adult participants in the population-based Hypertension Genetic Epidemiology Network study. Information regarding current drug use was assessed during a clinical examination. Medication use was continued at the time of echocardiographic study. Expert readers blinded to current therapy read echocardiograms centrally at Cornell Medical Center. Analyses of the associations between use of fenfluramine/dexfenfluramine (alone or with phentermine) and aortic regurgitation adjusted for potential confounders, including aortic root dilatation and valve fibrocalcification. RESULTS: Nineteen participants, all of whom had hypertension, were being treated with fenfluramine or dexfenfluramine (5 on these agents alone, 14 also with phentermine). Aortic regurgitation was present in 32% (n = 6) of those taking fenfluramine or dexfenfluramine versus 6% (162/2505) of remaining subjects (P = 0.001). In multivariate-adjusted analyses, treatment with fenfluramine or dexfenfluramine was associated with aortic regurgitation (odds ratio [OR] = 4.9; 95% confidence interval [CI]: 1.7 to 14) and aortic fibrocalcification (OR = 5.2; 95% CI: 1.9 to 15). CONCLUSION: In a population-based sample, use of fenfluramine or dexfenfluramine, alone or in combination with phentermine, was associated with aortic regurgitation independent of aortic dilatation or fibrocalcification.

Aortic Valve Insufficiency↗

PubMed2002

Gender difference in diastolic function in hypertension (the HyperGEN study).

Although several studies indicate that there are gender differences in left ventricular (LV) systolic function, it remains unclear whether similar differences exist with regard to diastolic function. Accordingly, Doppler echocardiograms were analyzed in 515 male and 839 female, mostly treated (95%) hypertensive participants enrolled in the Hypertension Genetic Epidemiology Network (HyperGEN) study with no evidence of abnormal wall motion or significant valvular heart disease. There was no difference in age between genders, but after adjusting for age and race, men had lower body mass indexes (29.8 +/- 5.2 vs 32.3 +/- 7.6 kg/m(2)) and heart rates (67 +/- 12 vs 69 +/- 11 beats/min) and higher systolic and diastolic blood pressures (BP) than women (134 +/- 20 vs 130 +/- 21 and 80 +/- 11 vs 72 +/- 11 mm Hg, all p <0.001). LV mass/height(2.7) was slightly greater in women than in men (43 +/- 10 vs 42 +/- 9 g/m(2.7), p <0.05). After adjusting for age, race, systolic BP, body mass index, heart rate, and LV hypertrophy, both mitral E-wave (70 +/- 18 vs 77 +/- 19) and A-wave (74 +/- 15 vs 79 +/- 17, both p <0.001) velocities were lower in men than in women, but the mitral E/A ratio and atrial filling fraction were nearly identical in both genders. Deceleration time (221 +/- 55 vs 214 +/- 46 cm/s, p = 0.018) and isovolumic relaxation time (IVRT) were longer in men than in women (85 +/- 18 vs 81 +/- 17 cm/s, p <0.001). Prolonged IVRT was present in more men than women (14% vs 7%, p <0.05). In analyses of covariance, adjusting for age, race, systolic BP, body mass index, heart rate, and medications, male gender remained related to prolonged deceleration time and IVRT. Thus, in this population-based sample of hypertensive adults, men had evidence of slower early diastolic LV filling than women. This gender difference in diastolic function may provide insight into gender differences in congestive heart failure and other specific cardiovascular diseases.

Age Distribution↗

PubMed2002

Blood pressure responses to acute stress and left ventricular mass (The Hypertension Genetic Epidemiology Network Study).

Left ventricular (LV) hypertrophy is a major risk factor for cardiovascular morbidity. This study examined the extent to which exaggerated blood pressure (BP) reactivity is associated with LV mass and relative wall thickness (RWT) in a large sample of middle-aged hypertensive men and women. Participants included 1,012 African-Americans and 655 Caucasians recruited for the Hypertension Genetics Epidemiology Network (HyperGEN) study. A laboratory stress protocol was implemented, consisting of BP measurement during rest, handgrip, and a mental arithmetic stressor. This was followed by a 2-dimensional guided M-mode echocardiographic evaluation to measure LV mass. LV mass was greater among African-Americans relative to Caucasians (p <0.01). Systolic BP at rest was positively associated with LV mass and RWT in African-Americans (p <0.001) and in Caucasian women (p <0.0001). LV mass and RWT were compared in participants and participants were classified as high or low reactors based on their systolic BP responses to the 2 laboratory stressors. RWT demonstrated positive associations with systolic BP responses to both tasks. Associations with LV mass were mostly nonsignificant with the exception of a negative association in African-Americans between systolic BP responses to the arithmetic task and LV mass. We conclude that in this cohort of hypertensive middle-aged men and women, BP reactivity did not predict LV mass. Positive associations of systolic BP responses with RWT suggest that exaggerated reactivity may particularly be related to LV changes influenced by vascular tonus.

Adult↗

PubMed2002

Eight-year results of aortic root replacement with the freestyle stentless porcine aortic root bioprosthesis.

BACKGROUND: Stentless porcine aortic valves offer several advantages over traditional valves. Among these are superior hemodynamics, laminar flow patterns, lack of need for anticoagulation, and perhaps improved durability. METHODS: One hundred four patients were operated on from September 17, 1992, to October 31, 1997, as part of a multicenter worldwide investigation of the Medtronic Freestyle stentless porcine bioprosthesis. All patients received a total aortic root replacement. The patients were evaluated postoperatively at discharge, at 3 to 6 months, and yearly by clinical examination and color flow Doppler echocardiography. RESULTS: Operative mortality was 3.9%. No patient experienced structural valve deterioration, nonstructural deterioration, perivalvular leak, or unacceptable hemodynamic performance. At 8 years, survival was 59.8%. Freedom from thromboembolic complications was 83.3%. Freedom from postoperative endocarditis was 96.9%. Freedom from reoperation was 100%. Mean systolic gradients did not change over the time period studied. They were 6.4 +/- 3.8 mm Hg at 1 year and 6.7 +/- 2.6 mm Hg at 8 years. Correspondingly, effective orifice area was 1.9 +/- 0.7 cm2 at 1 year and 1.8 +/- 0.8 cm2 at 8 years. The incidence of any aortic insufficiency also did not change over the length of follow-up. At 1 year, 98% of patients had no or trivial aortic insufficiency and 2% had mild aortic insufficiency. At 8 years, 100% of patients evaluated were free of any aortic insufficiency. CONCLUSIONS: The Medtronic Freestyle aortic root bioprosthesis can be used safely to replace the aortic root or aortic valve for aortic valve and aortic root pathology. Total root replacement allows optimal hemodynamic performance with no significant aortic regurgitation. Results up to 8 years show excellent survival and no signs of degeneration. Further follow-up is still needed to determine valve durability.

Aged↗

PubMed2002

Linkage of left ventricular early diastolic peak filling velocity to chromosome 5 in hypertensive African Americans: the HyperGEN echocardiography study.

BACKGROUND: Altered diastolic filling is an important contributor to several cardiovascular disorders. Multiple lines of evidence suggest a genetic contribution to left ventricular (LV) diastolic filling; however, chromosomal locations harboring genes involved in impaired LV diastolic filling have not been reported. The aim of this study was to identify chromosomal regions contributing to variation of LV transmitral early and late peak filling velocities (E and A velocities), Doppler echocardiographic measures of LV diastolic filling. METHODS: We adjusted E and A velocities for age, age squared, heart rate, body mass index, systolic blood pressure, field center, and antihypertensive medication in sex- and ethnicity-specific linear regression models. Standardized residuals were calculated and used in multipoint variance components linkage analysis (GENEHUNTER). Anonymous markers (Cooperative Human Linkage Center set 8) were available for 167 white hypertensive sibships (397 subjects, mean age 60 years) and 182 African American (393 subjects, mean age 52 years) hypertensive sibships. RESULTS: For E velocity, linkage was detected on chromosome 5 at 133.6 centimorgan (cM) in African Americans (logarithm of the odds [LOD] = 4.13), and suggestive linkage (LOD >1.9) was observed for regions on chromosome 10 (80.8 cM) and chromosome 20 (1.5 cM). For A velocity, suggestive linkage was found for chromosome 12 (GATA85A04) in whites and for chromosome 8 (122.9 cM) in African Americans. Genes contained in and around the linked region are important candidates for diastolic filling (calcium-modulating cyclophilin ligand [5q23], alpha-1B adrenergic receptor [5q23-32]). CONCLUSION: Significant linkage was detected for LV early diastolic peak filling velocity on chromosome 5 in African Americans, indicating that a genomic region may contribute to interindividual variation in LV diastolic filling.

Black People↗

PubMed2002

Relation of insulin to left ventricular geometry and function in African American and white hypertensive adults: the HyperGEN study.

BACKGROUND: It has been suggested that the trophic effects of insulin may contribute to left ventricular (LV) hypertrophy in hypertension, but few population-based data exist to assess the potential impact of insulin level on LV structure or systolic function. METHODS: Fasting plasma insulin levels (log-transformed) in 1,542 nondiabetic African American or white hypertensive participants in the Hypertension Genetic Epidemiology Network (HyperGEN) study were compared to indices of LV geometry and function, with adjustment for potential confounders (age, sex, ethnicity, blood pressure (BP), body mass index, height and antihypertensive drugs). RESULTS: In simple correlation analysis, a weak positive relation (r = 0.078, P =.002) was found between LV mass and insulin, principally due to positive correlations (r = 0.22 and 0.50) of both variables to body mass index. Multivariate analysis, adjusting for age, sex, ethnicity, body size, systolic BP, and antihypertensive drugs revealed a modest negative relation between insulin and LV mass (r = -0.08, P =.001) due to a negative relationship between insulin with LV chamber size (r = - 0.10, P <.001) and no significant relation to LV wall thicknesses. These results were confirmed in additional analysis controlling for a positive relation (r =.19, P <.0001) of insulin to heart rate, and the relation with insulin became slightly more negative when LV mass was indexed for height(2.7) (r = -0.13, P <.001). After adjustment for covariates, there were no significant relations of insulin to LV ejection fraction or stress-corrected midwall shortening; however, insulin was negatively related to stroke volume (r = -0.12, p < 0.001) and was weakly related positively to relative wall thickness (r =.053) (P =.04). CONCLUSIONS: After adjustment for body mass index and other covariates, insulin in nondiabetic hypertensive individuals has weak negative relations to LV chamber size, mass, and stroke volume, and also has weak positive relations to relative wall thickness but not to measures of LV systolic function. Thus, native plasma insulin level may not play a major independent role in the pathogenesis of hypertensive LV hypertrophy or dysfunction.

Adult↗

PubMed2002

Diastolic heart failure in the elderly.

It is now clear that diastolic heart failure (DHF) is an important, perhaps even dominant form of heart failure in older Americans. However, our knowledge base regarding the epidemiology, pathophysiology, natural history, and therapy of this relatively recently recognized disorder is limited. A number of normal age related changes in the heart and vascular system may predispose to or lower the threshold for expression of DHF. Recent reports from large population-based observational studies indicate that over 50% of persons 65 years and older who have heart failure have normal LV systolic function (presumed DHF). Among these, 45% have no other confounding variables (coronary, valvular, or pulmonary disease) and meet the criteria for isolated DHF. DHF is substantially more common in older women than men. A history of systemic hypertension and left ventricular hypertrophy are almost invariably present. Mortality rates are about 50% lower in DHF than in systolic heart failure (SHF) when stable outpatients are considered. However, in hospitalized and very elderly patients, the mortality rate appears similar in DHF and SHF. Furthermore, due to its higher prevalence, the total mortality in the older population attributable to DHF exceeds that of SHF. Morbidity in DHF is substantial and approaches that of SHF. In the chronic setting, DHF patients can have severe exercise intolerance related to failure of the Frank-Starling mechanism with reduced peak cardiac output, heart rate, and stroke volume and increased LV filling pressure. DHF patients also appear to have increased vascular stiffness, accelerated systolic blood pressure response to exercise, neuroendocrine activation, and reduced quality of life. Acute exacerbations (pulmonary edema) frequently occur and are associated with severe hypertension, sodium indiscretion, and medication non-compliance. Surprisingly, overt myocardial ischemia appears to infrequently play a role in these acute exacerbations. Therapy is currently empiric and multicenter, randomized, controlled trials are urgently needed. Anecdotally, control of blood pressure appears to improve symptoms and reduce the frequency of acute exacerbations. In addition, non-pharmacologic intervention, including multi-disciplinary case management is useful.

Aged↗

PubMed2002

Associations between angiotensinogen gene variants and left ventricular mass and function in the HyperGEN study.

BACKGROUND: The angiotensinogen M235T polymorphism is positively associated with plasma angiotensinogen, hypertension, and coronary heart disease. However, the association of M235T polymorphism with left ventricular (LV) mass and function is not well defined at the population level. We investigated whether 2 tightly linked polymorphisms of angiotensinogen gene, M235T and G-6A, are associated with LV mass and function in a large population-based sample, composed mostly of patients with hypertension. METHODS: Two-dimensional guided M-mode and pulsed Doppler scan echocardiograms were performed in 605 participants. The angiotensinogen M235T was analyzed with a standard polymerase chain reaction test, and the G-6A variant was measured with mass spectrophotometry. RESULTS: The association of angiotensinogen gene to LV mass and LV mass indexed to body surface area (LVMI) differed significantly between subjects with normotensive and hypertensive conditions with respect to the direction of association (P <.005). The methionine-threonine/threonine-threonine genotype was negatively associated with LV mass and LVMI in patients with hypertension after adjustment for blood pressure, antihypertensive medication use, weight, and other covariates (P <.001), and patients with normotensive conditions with the methionine-threonine/threonine-threonine genotype had higher LV mass and LVMI (P =.04, for LV mass; P =.14, for LVMI). The association in patients with normotensive conditions was not influenced by blood pressure but was partly confounded by weight. CONCLUSION: Variation in the angiotensinogen gene was modestly associated with LV mass independently of covariates in patients with hypertensive conditions. The direction of the association was opposite to that observed in patients with normotensive conditions, probably because of the influence of other risk factors or antihypertensive medication use or both.

Analysis of Variance↗

PubMed2002

Association of left ventricular hypertrophy with metabolic risk factors: the HyperGEN study.

OBJECTIVE: To determine whether combinations of metabolic risk factors (obesity, diabetes and hypercholesterolemia) influence the magnitude of left ventricular (LV) mass and prevalence of LV hypertrophy. DESIGN: Cross-sectional, relational. METHODS: A total of 1627 hypertensive (85.9% treated, 1036 women, 1041 African Americans) and 342 normotensive (180 women, 183 African Americans) participants in the Hypertension Genetic Epidemiology Network (HyperGEN) Study, without prevalent cardiovascular disease, were studied. Echocardiographic LV mass, normalized by height(2.7) or fat-free mass or body surface area (BSA) and the ratio of stroke volume to pulse pressure as a percentage of predicted (as a crude estimate of arterial compliance) were analyzed in relation to obesity [by body mass index (BMI)], central fat distribution (by waist circumference), diabetes (by ADA criteria) and hypercholesterolemia. RESULTS: Obesity, hypercholesterolemia, and diabetes were more frequent among hypertensives than normotensives (all P < 0.001). After controlling for age, sex, race and type and combination of antihypertensive medication, LV mass/height(2.7), but not LV mass/fat-free mass and LV mass/BSA, increased with the number of metabolic risk factors, both in normotensive and hypertensive participants, also after further adjustment for blood pressure (all P < 0.001). Stroke volume/pulse pressure also decreased in hypertensive, but much less in normotensive subjects, with increasing number of metabolic risk factors, independently of relevant confounders (P < 0.0001). Prevalence of LV hypertrophy was predicted by older age, hypertension, central fat distribution, black race and independently increased with the number of associated metabolic risk factors (P < 0.0001). CONCLUSIONS: The progressive addition of metabolic risk factors including central obesity, diabetes and hypercholesterolemia is associated with higher LV mass normalized by height(2.7), independently of hypertension and other important biological covariates. Obesity played a major role in this association. This finding indicates that LV mass is a potentially useful bioassay of strategies of global cardiovascular prevention.

Adipose Tissue↗

PubMed2002

Sibling resemblance for left ventricular structure, contractility, and diastolic filling.

Although there is evidence that left ventricular (LV) function is genetically controlled, the contribution of familial factors to variation and covariation of LV diastolic filling, contractility, and structure is unknown. Single- and cross-trait sibling correlations were estimated using bivariate familial correlation models in 200 white (400 pairs) and 374 black (539 pairs) hypertensive sibships. LV transmitral early and late peak filling velocities, isovolumic relaxation time, atrial filling fraction, stress-corrected midwall shortening, and LV mass and structure were measured and adjusted for important covariates in race-specific linear regression models. Single-trait sibling correlation was strongest for early peak filling velocity. Significant cross-trait sibling correlation was detected between early and late peak filling velocities. In whites, early peak filling velocity and atrial filling fraction, and isovolumic relaxation time and end-diastolic posterior wall thickness, were also significantly correlated. Familial factors common to early and late peak filling velocities contributed to 64% and 54% of sibling resemblance in early peak filling velocity and to 76% and 77% in late peak filling velocity in blacks and whites, respectively. In whites, 100% of sibling resemblance in isovolumic relaxation time was shared by posterior wall thickness, whereas 75% of sibling influence in posterior wall thickness was common to isovolumic relaxation time. In conclusion, significant cross-trait sibling resemblance was detected between (1) early and late filling parameters and (2) isovolumic relaxation time and posterior wall thickness, suggesting pleiotropy and/or common environment on these traits. These data have potential importance in understanding heritability of LV diastolic function in hypertension.

Diastole↗

PubMedDate not supplied

Exercise intolerance.

Patients with heart failure and normal EF have severe chronic exercise intolerance. The pathophysiology of exercise intolerance in this syndrome is incompletely understood, but as in systolic heart failure, it is likely multifactorial. Current data suggest that important contributors include decreased LV diastolic compliance, decreased aortic distensibility, exaggerated exercise systolic blood pressure, relative chronotropic incompetence, and possibly anemia and skeletal muscle remodeling. Because it is a primary determinant of quality of life, can be quantified objectively, is reproducible, and is modifiable, exercise intolerance is an attractive therapeutic target.

Exercise↗

PubMedDate not supplied