Dalane W. Kitzman

Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: Failure of the Frank-Starling mechanism☆

Invasive cardiopulmonary exercise testing was performed in 7 patients who presented with congestive heart failure, normal left ventricular ejection fraction and no significant coronary or valvular heart disease and in 10 age-matched normal subjects. Compared with the normal subjects, patients demonstrates severe exercise intolerance with a 48% reduction in peak oxygen consumption (11.6 +/- 4.0 versus 22.7 +/- 6.1 ml/kg per min; p less than 0.001), primarily due to a 41% reduction in peak cardiac index (4.2 +/- 1.4 versus 7.1 +/- 1.1 liters/min per m2; p less than 0.001). In patients compared with normal subjects, peak left ventricular stroke volume index (34 +/- 9 versus 46 +/- 7 ml/min per m2; p less than 0.01) and end-diastolic volume index (56 +/- 14 versus 68 +/- 12 ml/min per m2; p less than 0.08) were reduced, whereas peak ejection fraction and end-systolic volume index were not different. In patients, the change in end-diastolic volume index during exercise correlated strongly with the change in stroke volume index (r = 0.97; p less than 0.0001) and cardiac index (r = 0.80; p less than 0.03). Pulmonary wedge pressure was markedly increased at peak exercise in patients compared with normal subjects (25.7 +/- 9.1 versus 7.1 +/- 4.4 mm Hg; p less than 0.0001). Patients demonstrated a shift of the left ventricular end-diastolic pressure-volume relation upward and to the left at rest. Increases in left ventricular filling pressure during exercise were not accompanied by increases in end-diastolic volume, indicating a limitation to left ventricular filling.(ABSTRACT TRUNCATED AT 250 WORDS)

Age-Related Changes in Normal Human Hearts During the First 10 Decades of Life. Part II (Maturity): A Quantitative Anatomic Study of 765 Specimens From Subjects 20 to 99 Years Old

Heart weights, ventricular wall thicknesses, and valve circumferences were measured in 765 autopsy specimens from normal hearts from persons 20 to 99 years old. Body weight was a better predictor of normal heart weight than was body surface area or height, and mean heart weights were greater in men than in women at all ages. When heart weights were indexed (divided by body surface area), the mean values per decade increased significantly in women between the 3rd and 10th decades of life (P less than 0.01) but remained relatively constant with time in men. We found no significant differences in ventricular wall thicknesses between men and women. Although indexed mean values for left and right ventricular wall thicknesses remained relatively constant in all decades, ventricular septal thickness increased significantly between the 3rd and 10th decades of life (P less than 0.001). Beyond the seventh decade of life, the mean ratio of septal to left ventricular free wall thicknesses exceeded 1.20, and the upper 95% confidence limit exceeded 1.50--an important consideration in evaluation of hypertrophic cardiomyopathy in elderly patients. Mean valve circumferences were usually greater in men than in women, but the opposite pertained when values were indexed by body surface area. In both sexes, all indexed mean valve circumferences increased progressively throughout adult life, although this trend was greater for semilunar than for atrioventricular valves. The mean circumference of the aortic valve surpassed that of the pulmonary valve in the 4th decade and approached that of the mitral valve by the 10th decade of life. Thus, in evaluation of annuloaortic ectasia, investigators should take into account the normal age-related changes in aortic valve dimensions.

Age-related alterations of Doppler left ventricular filling indexes in normal subjects are independent of left ventricular mass, heart rate, contractility and loading conditions☆☆☆

The purpose of this study was to determine whether age-related alterations in Doppler diastolic filling indexes occur independent of cardiovascular disease and confounding physiologic variables. Ten old (62 to 73 years) and 10 young (21 to 32 years) healthy male volunteers were rigorously screened for cardiovascular disease and underwent comprehensive Doppler echocardiography, radionuclide ventriculography and invasive measurements of right heart and left atrial pressures. There were no differences between the two groups in the physiologic variables of left ventricular mass, volumes, ejection fraction, end-systolic wall stress, left atrial size, heart rate and right atrial, pulmonary artery, pulmonary capillary wedge and systemic arterial pressures. However, there were marked differences in Doppler left ventricular filling indexes. Compared with the young group, the old group had reduced peak early diastolic flow velocity (56 +/- 13 vs. 82 +/- 12 cm/s, p = 0.0002) and increased atrial diastolic flow velocity (59 +/- 14 vs. 43 +/- 10 cm/s, p = 0.009) and had a peak atrial/early flow velocity (A/E) ratio twice that of the young group (1.09 +/- 0.29 vs. 0.54 +/- 0.15, p less than 0.0001). Similar results were obtained for the time-velocity integrals of the peaks. Subjects in the old group also had a markedly reduced peak filling rate (274 +/- 62 vs. 448 +/- 152 ml/s, p = 0.004). In univariate and multivariate regression analyses, peak early and atrial flow velocities were not related to any of the physiologic variables measured once age was accounted for, although peak filling rate, a volumetric measure flow, was related to body surface area as well as age.(ABSTRACT TRUNCATED AT 250 WORDS)

Age-Related Changes in Normal Human Hearts During the First 10 Decades of Life. Part I (Growth): A Quantitative Anatomic Study of 200 Specimens From Subjects From Birth to 19 Years Old

Heart weight, ventricular wall thicknesses, and valve circumferences were measured in 200 autopsy specimens of normal hearts from persons who ranged from birth to 19 years old. During this period of body growth, all cardiac measurements increased progressively and correlated with both age and body size (height, weight, and surface area). For most measurements, the mean predicted values were greater in male than in female subjects. Heart weight correlated better with body weight and body surface area than with body height or age of patients. In contrast, ventricular wall thicknesses and valve circumferences correlated better with age of the patients than with measurements of body size. In both sexes at all ages, the thickness of the left ventricle was greater than that of the right ventricle and was generally less than that of the ventricular septum. The circumference of the tricuspid valve usually exceeded that of the mitral valve, but aortic and pulmonary valve circumferences were similar. On the basis of these data, equations were derived and reference tables were constructed to predict normal values for heart weight, ventricular wall thicknesses, and valve circumferences.

Evaluation of a Supervised Exercise Program in a Geriatric Population

Most studies that assess the effects of exercise in the elderly involve subjects who are in good health. The objective of this prospective longitudinal study was to examine the impact of exercise on cardiovascular fitness, flexibility, and strength in an elderly population that included chronically ill individuals. Patients were recruited initially from a population of veterans over 64 years of age who use a VA outpatient clinic as their regular source of care. The exercise intervention consisted of 90 minutes of exercise 3 days per week at 70% of the patients maximal capacity. Activities included stationary cycling, stretching, weight training, and walking. Of 69 patients who began the program, 49 (71%) reached 4‐month follow‐up. Most patients completing follow‐up (76%) had at least one chronic disease, such as arthritis, hypertension, or heart disease. Patients who dropped out were more likely to have multiple chronic illnesses than those who remained in the program. Average weekly attendance was 65% and was stable over time. Improvements in cardiovascular fitness at 4‐month follow‐up were significant: Metabolic equivalents increased from 7.1 ± 2.3 to 8.3 ± 1.6 (P < .001), treadmill time increased from 8.5 ± 3.8 to 11.2 ± 4.1 minutes (P < .001), submaximal heart rate decreased from 123.7 ± 18.8 to 118.8 ± 19.4 beats per minute (P < .001) and resting heart rate decreased from 68.1 ± 10.6 to 63.3 ± 11.6 beats per minute (P = .005). Hip flexibility also increased significantly from 58.5 ± 13.8 to 67.7 ± 9.9 degrees (P < .001), and abdominal strength increased significantly from 88.8 ± 32.4 to 104 ± 28.4 foot‐pounds (P < .001). No major complications resulted from exercise. This study demonstrates that elderly individuals, including those with chronic diseases, will participate in an exercise program and experience improvements in cardiovascular fitness, strength, and flexibility. Whether these improvements will enable elderly individuals to live independently for a longer period of time and avoid or postpone the need for long‐term care requires additional study and follow‐up.

Exercise Intolerance in Patients with Heart Failure: Role of Diastolic Dysfunction

Most patients with severe left ventricular dysfunction have exercise intolerance. Maximal oxygen consumption during a standardized exercise protocol is an objective measure of exercise tolerance. Since oxygen consumption is the product of cardiac output and arteriovenous oxygen difference, and cardiac output is the product of stroke volume and heart rate, exercise tolerance will be related to these or associated factors. We describe a series of studies that examined the determinants of exercise performance in normal humans, in a group of patients with heart failure and severely reduced resting LV systolic function, and in a group of patients with heart failure and normal resting LV systolic function. Cardiac output increased 3.2-fold during exercise in normal subjects. Increased stroke volume contributed significantly to the increase in cardiac output, and the increased stroke volume was due to the Frank— Starling mechanism and increased contractility.

Erratum regarding incorrect spelling of author name

Heart failure with preserved ejection (HFpEF) accounts for over 50 % of all HF cases, and the proportion is higher among women and older individuals. A hallmark feature of HFpEF is dyspnoea on exertion and reduced peak aerobic power (VO2peak) secondary to central and peripheral abnormalities that result in reduced oxygen delivery to and/or utilisation by exercising skeletal muscle. The purpose of this brief review is to discuss the role of exercise training to improve VO2peak and the central and peripheral adaptations that reduce symptoms following physical conditioning in patients with HFpEF.

STATINS AND EXERCISE TRAINING RESPONSE IN HEART FAILURE PATIENTS: INSIGHTS FROM THE HF-ACTION TRIAL

Recent data suggest that statins may attenuate exercise training (ET) response, but limited data exist in patients with heart failure (HF), many of whom use statins. HF-ACTION was a randomized, controlled (usual care vs ET) trial of 2,331 chronic ambulatory HF patients with ejection fraction ≤ 35

RELATIONSHIP BETWEEN EXERCISE TRAINING AND CHANGES IN BIOMARKERS OF MYOCARDIAL STRESS, INJURY AND INFLAMMATION IN PATIENTS WITH CHRONIC HEART FAILURE

Elevations in NTproBNP, hsCRP, and cTnT are associated with increased risk of adverse outcomes in patients with chronic HF. The effect of exercise training on these markers and the association of changes in biomarkers with outcomes has not been well studied. NTproBNP, hsCRP, and cTnT levels were