Increased metaboreceptor stimulation explains the exaggerated exercise pressor reflex seen in heart failure.
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Animals↗
Biomedical subjects
Massimo F Piepoli
Publications and source records attributed to Massimo F Piepoli.
Reduced peripheral skeletal muscle mass and abnormal reflex physiology in chronic heart failure.
BACKGROUND: The muscle hypothesis implicates abnormalities in peripheral muscle as a source for the stimulus to the symptoms and reflex abnormalities seen in chronic heart failure (CHF). We investigated the relationship between skeletal muscle mass (with dual-energy x-ray absorptiometry) and activation of the ergoreflex (a peripheral reflex originating in skeletal muscle sensitive to products of muscle work) in CHF patients and whether this rapport is affected by the progression of the syndrome. METHODS AND RESULTS: We assessed 107 consecutive CHF patients (mean age, 61.9+/-10.9 years; 95% male; 25 cachectics) and 24 age-matched normal subjects (mean age, 59.0+/-11.1 years; 91% male). Compared with normal subjects, patients had a higher ergoreflex (in ventilation, 6.2+/-.6.1 versus 0.6+/-0.6 L/min; P<0.0001) and a reduction in muscle mass (51.9+/-10.0 versus 60.3+/-8.8 kg; P<0.001). The ergoreflex was particularly overactive in cachectics (P<0.05), accompanied by marked muscle mass depletion (P<0.0005). In CHF, ergoreceptor hyperresponsiveness in both the arm and leg correlated with reduced muscle mass, abnormal indexes of exercise tolerance (peak V(O2), V(E)/V(CO2) slope), ejection fraction, and NYHA functional class (P<0.0001). In the cachectic population, the ventilatory response from ergoreflex to arm exercise was strongly inversely correlated with arm (r=-0.65), leg (r=-0.64), and total (r=-0.61) lean tissues (P<0.001 for all). Multivariate analysis showed that these relationships were independent of NYHA class, peak V(O2), and V(E)/V(CO2) slope. CONCLUSIONS: Depleted peripheral muscle mass is associated with ergoreflex overactivity and exercise limitation in CHF, particularly in cachectic patients. The systemic activation of the muscle reflex system in CHF may reflect progression and deterioration of the clinical syndrome.
Aged↗
Abnormal ventilatory response to exercise in adults with congenital heart disease relates to cyanosis and predicts survival.
BACKGROUND: Limited data exist with which to stratify risk in adult congenital heart disease (ACHD). An increased ventilatory response to exercise, expressed as ventilation per unit of carbon dioxide production (V(E)/V(CO2) slope), is an established predictor of impaired survival in acquired heart disease. We sought to establish the distribution, relation to cyanosis, and prognostic value of the V(E)/V(CO2) slope across a wide spectrum of ACHD patients. METHODS AND RESULTS: Five hundred sixty ACHD patients of varying diagnoses and 50 healthy controls underwent cardiopulmonary exercise testing at a single laboratory between 2001 and 2004. Patient age was 33.2 +/- 12.9 years (mean +/- SD). Peak oxygen consumption was 23.5 +/- 9.0 mL.kg(-1).min(-1).V(E)/V(CO2) slope for all patients was 36.3 +/-15.3. The slope was raised in all ACHD groups compared with controls and was 73% higher in cyanotic patients. Cyanosis, with or without pulmonary arterial hypertension, was the strongest predictor of abnormal V(E)/V(CO2) slope. The V(E)/V(CO2) slope was the most powerful univariate predictor of mortality in the noncyanotic group and the only independent predictor of mortality among exercise parameters on multivariate analysis. In cyanotic patients, no parameter was predictive of death. CONCLUSIONS: Ventilatory response to exercise is abnormal across the spectrum of ACHD. Cyanosis is a powerful stimulus for such exaggerated ventilatory patterns irrespective of the presence of pulmonary arterial hypertension. Increased V(E)/V(CO2) slope is the strongest exercise predictor of death in noncyanotic ACHD patients.
Adult↗
Aerobic training decreases B-type natriuretic peptide expression and adrenergic activation in patients with heart failure.
OBJECTIVES: We sought to evaluate the effect of physical training on neurohormonal activation in patients with heart failure (HF). BACKGROUND: Patients with HF benefit from physical training. Chronic neurohormonal activation has detrimental effects on ventricular remodeling and prognosis of patients with HF. METHODS: A total of 95 patients with HF were assigned randomly into two groups: 47 patients (group T) underwent a nine-month training program at 60% of the maximal oxygen uptake (VO2), whereas 48 patients did not (group C). The exercise load was adjusted during follow-up to achieve a progressive training effect. Plasma assay of B-type natriuretic peptide (BNP), amino-terminal pro-brain natriuretic peptide (NT-proBNP), norepinephrine, plasma renin activity, and aldosterone; quality-of-life questionnaire; echocardiogram; and cardiopulmonary stress test were performed upon enrollment and at the third and ninth month. RESULTS: A total of 85 patients completed the protocol (44 in group T, left ventricular ejection fraction [EF] 35 +/- 2%, mean +/- SEM; and 41 in group C, EF 32 +/- 2%, p = NS). At the ninth month, patients who underwent training showed an improvement in workload (+14%, p < 0.001), peak VO2 (+13%, p < 0.001), systolic function (EF +9%, p < 0.01), and quality of life. We noted that BNP, NT-proBNP, and norepinephrine values decreased after training (-34%, p < 0.01; -32%, p < 0.05; -26%, p < 0.01, respectively). Increase in peak VO2 with training correlated significantly with the decrease in both BNP/NT-proBNP level (p < 0.001 and p < 0.01, respectively). Patients who did not undergo training showed no changes. CONCLUSIONS: Clinical benefits after physical training in patients with HF are associated with blunting of adrenergic overactivity and of natriuretic peptide overexpression.
Aldosterone↗
Autonomic imbalance and immune activation in chronic heart failure - pathophysiological links.
Activation of the immune system and derangement of cardiorespiratory neural control are established elements of the complex pathophysiology of chronic heart failure (CHF). The magnitude of these abnormalities relates to disease progression and mortality. Less clear is the origin of these derangements and the sequence of triggering mechanisms in the course of the natural history of CHF. To date, immune activation and autonomic imbalance have been considered independently; we hypothesise they are closely related. Damaged heart muscle through autonomic afferents triggers functional and structural changes in the central nervous system, in part related to inflammatory processes. The altered function of the autonomic centres is expressed as a reduction of central parasympathetic tone. Diminished cholinergic signalling (mainly nicotinergic) activates inflammation and stimulates immune response. These two phenomena predict prognosis and represent therapeutic targets in the syndrome of CHF.
Autonomic Nervous System↗
Exercise training in heart failure.
The reduction of exercise capacity with early occurrence of fatigue and dyspnea is a hallmark of heart failure syndrome. There are objective similarities between heart failure and muscular deconditioning. Deficiencies in peripheral blood flow and skeletal muscle function, morphology, metabolism, and function are present. The protective effects of physical activity have been elucidated in many recent studies: training improves ventilatory control, skeletal muscle metabolism, autonomic nervous system, central and peripheral circulation, and heart function. These provide the physiologic basis to explain the benefits in terms of survival and freedom from hospitalization demonstrated by physical training also in heart failure.
Journal Article↗
Exercise intolerance in adults with congenital heart disease.
This article describes the ways to assess exercise capacity in adults with congenital heart disease (ACHD) and the impact of exercise intolerance in the population. It also discusses the likely pathogenesis of exercise intolerance in ACHD, the similarities between ACHD and acquired heart failure, and potential therapeutic options.
Adult↗
Statement on cardiopulmonary exercise testing in chronic heart failure due to left ventricular dysfunction. Recommendations for performance and interpretation.
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Exercise Test↗
Statement on cardiopulmonary exercise testing in chronic heart failure due to left ventricular dysfunction: recommendations for performance and interpretation Part II: How to perform cardiopulmonary exercise testing in chronic heart failure.
Basic and practical information related to equipment, methodology, exercise protocols, conduct of the test and quality control issues for cardiopulmonary exercise testing (CPET) will be addressed in this II part of the statement. CPET users have the responsibility for assuring that measurements remain accurate. CPT, especially when it features breath-by-breath gas exchange analysis, requires meticulous attention to calibration procedures to assure accurate and reproducible measurements. Skills and knowledge of personnel for supervision and test interpretation, as well as patient preparation and information are key features for a correct CPET conduction: all these issues will be faced. Finally, after the test, the investigator needs to format the results in a manner that optimises the ability to discriminate essential response features; that is, to establish 'interpretive clusters' of the variables of interest. An example of a cardiopulmonary summary exercise test data report will be provided, defining the most important information that should be incorporated in a final report.
Cardiology↗
Statement on cardiopulmonary exercise testing in chronic heart failure due to left ventricular dysfunction: recommendations for performance and interpretation. Part I: definition of cardiopulmonary exercise testing parameters for appropriate use in chronic heart failure.
Cardiopulmonary exercise testing (CPET) provides a global assessment of the integrated response to exercise involving the pulmonary, cardiovascular, haematopoietic, neuropsychological, and skeletal muscle systems. This information cannot be obtained through investigation of the individual organ systems in isolation. The non-invasive, dynamic physiological overview permits the evaluation of both submaximal and peak exercise responses, providing the physician with relevant information for clinical decision making. The use of CPET in management of the chronic heart failure patient is increasing with the understanding that resting pulmonary and cardiac function testing cannot reliably predict exercise performance and functional capacity and that, furthermore, overall health status and prognosis are predicted better by indices of exercise tolerance than by resting measurements. Our aim is to produce a statement which provides recommendations on the interpretation and clinical application of CPET in heart failure, based on contemporary scientific knowledge and technical advances: the focus is on clinical indications, issues of standardization, and interpretative strategies for CPET.
Cardiac Output↗
Cardiovascular variability is/is not an index of autonomic control of circulation.
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Animals↗
Attenuated autonomic function in multiple organ dysfunction syndrome across three age groups.
Multiple organ dysfunction syndrome (MODS) is the failure of several organs after a trigger event. The mortality is high, at up to 70%. We hypothesize that autonomic dysfunction may substantially contribute to the development of MODS and speculate that there is an age dependence of autonomic dysfunction in MODS. A total of 90 consecutively admitted MODS patients were assigned to this study. Three variables of autonomic function were analyzed: heart rate variability (HRV), baroreflex sensitivity (BRS) and chemoreflex sensitivity (CRS). The patient cohort was divided into three age groups. The main finding was that BRS, CRS and almost all indices of HRV were attenuated in comparison to normal range data and there was no age dependence for HRV indices or CRS, but there was for BRS. In conclusion, autonomic function in MODS is attenuated. The influence of MODS on autonomic function overwhelms the age dependence of autonomic function observed in healthy subjects.
Aging↗
Enhanced prognostic value from cardiopulmonary exercise testing in chronic heart failure by non-linear analysis: oxygen uptake efficiency slope.
AIMS: Predicting survival from peak exercise oxygen uptake (peak VO2) in chronic heart failure (CHF) is hindered by its reduction if exercise duration is submaximal. The oxygen uptake efficiency slope (OUES) is a non-linear description of the ventilatory response to exercise, which has the potential to describe abnormalities even early in exercise. We evaluated the physiology of OUES and assessed its potential for prognostic information in patients with CHF. METHODS AND RESULTS: Two hundred and forty-three patients with CHF (mean age 59+/-12 years) underwent cardiopulmonary exercise testing between May 1992 and July 1996. Mean peak VO2 was 16.2+/-6.7 mL/kg/min, VE/VCO2 slope 38+/-12.5, ventilatory anaerobic threshold 10.9+/-3.5 mL/kg/min, and OUES 1.6+/-0.7 L/min. The value for each variable fell across the New York Heart Association classes (P<0.0001 by analysis of variance for each). When only the first 50% of each exercise test was used to calculate the variables, the value obtained for OUES changed the least (peak VO2 25% difference and OUES 1% difference). After a median of 9 years of follow-up, 139 patients (57%) had died. Each of the exercise variables was a significant univariate predictor of prognosis but in a multivariable model, only OUES was identified as the sole significant independent prognostic variable. CONCLUSION: OUES provides an effective, independent measure of pathological exercise physiology. Its numerical value is relatively insensitive to the duration of exercise data from which it is calculated. Its prognostic value seems to be stronger than the best available existing measures of exercise physiology.
Aged↗
Chemo- and ergoreflexes in health, disease and ageing.
The chemo- and ergoreflexes (muscle receptors) are among the major reflex arches, which adapt the respiratory and the cardiovascular system to the needs of the body and contribute to its homeostasis. The present paper reviews the interplay of these reflexes with other major cardiovascular reflex arches; the methods used for their calculation and their normal range data. The clinical implications of chemoreflex sensitivities and ergoreflexes in chronic heart failure (CHF) as well as the application of chemoreflexes in coronary artery disease, sudden cardiac death and multiple organ dysfunction syndrome are discussed.
Aging↗
Exercise training in heart failure.
The reduction of exercise capacity with early occurrence of fatigue and dyspnea is a hallmark of heart failure syndrome. There are objective similarities between heart failure and muscular deconditioning. Deficiencies in peripheral blood flow and skeletal muscle function, morphology, metabolism, and function are present. The protective effects of physical activity have been elucidated in many recent studies: training improves ventilatory control, skeletal muscle metabolism, autonomic nervous system, central and peripheral circulation, and heart function. These provide the physiologic basis to explain the benefits in terms of survival and freedom from hospitalization demonstrated by physical training also in heart failure.
Cardiovascular Physiological Phenomena↗
Exercise hyperventilation in chronic heart failure is not caused by systemic lactic acidosis.
BACKGROUND: Patients with heart failure have an abnormally high ventilatory response to exercise associated with gas exchange defects and reduced arterial pCO(2). AIMS: We examined the possibility of lactic acidosis as the stimulus to this increased ventilation that abnormally depresses pCO(2) during exercise in heart failure. METHOD AND RESULTS: We studied 18 patients with chronic heart failure. We measured VE/VCO(2) slope during exercise, arterial blood gases and lactate concentrations during cardiopulmonary exercise testing (rest, peak exercise and one minute after the end of exercise). Neither VE/VCO(2) slope nor arterial pCO(2) were related to arterial lactate concentrations at peak exercise (r = -0.16, p = 0.65 and r = -0.15, p = 0.6). During early recovery, patients with a high VE/VCO(2) slope had a particularly pronounced rise in arterial lactate and hydrogen ion concentrations (r = 0.57, p < 0.05 and r = 0.84, p < 0.0001) and yet their arterial pCO(2) rose rather than fell (r = 0.79, p < 0.001). The rise in arterial pCO(2) correlated with the increase in arterial hydrogen concentration (r = 0.78, p < 0.001) and with arterial pCO(2) at peak exercise (r = -0.76, p < 0.001). CONCLUSIONS: In heart failure VE/VCO(2) slope and low arterial pCO(2) at peak exercise are not related to the degree of systemic lactic acidosis. Lactic acidosis is therefore not a plausible mechanism of exercise induced hyperventilation.
Acidosis, Lactic↗
Autonomic dysfunction predicts mortality in patients with multiple organ dysfunction syndrome of different age groups.
OBJECTIVE: Multiple organ dysfunction syndrome (MODS) is the sequential failure of several organ systems after a trigger event, like sepsis or cardiogenic shock. Mortality rate is high, up to 70%. Autonomic dysfunction may substantially contribute to the development of MODS. Our study aimed to characterize a) the spectrum of autonomic dysfunction of critically ill MODS patients; b) whether autonomic dysfunction is different in patients receiving sedation, mechanical ventilation, or catecholamines; c) the age dependency of autonomic dysfunction in MODS; and d) whether autonomic dysfunction predicts mortality in MODS. DESIGN: Prospective cohort study. SETTING: Twelve-bed medical intensive care unit in a university center. PATIENTS: Ninety consecutively admitted score-defined MODS patients. INTERVENTIONS: Assessment of heart rate variability, baroreflex sensitivity, and chemoreflex sensitivity as markers of autonomic dysfunction. The patients were followed for 28-day mortality. MEASUREMENTS AND MAIN RESULTS: Baroreflex sensitivity, chemoreflex sensitivity, and almost all indexes of heart rate variability were attenuated in comparison to normal range data. There was no association between the assessed heart rate variability variables, baroreflex sensitivity or chemoreflex sensitivity, and the presence of sedation or catecholamine therapy. Except for frequency-domain variables, pNN50 (percentage of differences of successive RR intervals differing >50 msecs) and rMSSD (root mean square of successive difference of N-N intervals), none of the measured variables were related to the presence of mechanical ventilation. Age dependency was detected for baroreflex sensitivity but not for heart rate variability indexes or chemoreflex sensitivity (across ages 24-96 yrs). lnVLF predicted 28-day mortality best in the entire cohort of patients and in a subgroup of patients with cardiogenic-triggered MODS. CONCLUSIONS: Autonomic function of MODS patients is blunted, and this attenuation has prognostic implications. The extensive influence of MODS on autonomic function overwhelms and masks the well-known age dependency of autonomic function seen in healthy persons.
Adult↗
Exercise rehabilitation in heart disease: the real "polypill" for primary and secondary prevention.
Our society is currently at war against the ominous enemy of chronic disease. Chronic disease presents a heavy burden to society, in terms of both medical costs and human suffering. It is our perception that: 1) much of the medical community underpractises primary prevention as regards appropriate levels of physical activity for health, and 2) much of the research community undervalues the importance of understanding the physiological, genetic and clinical bases of diseases caused by physical inactivity. For many, exercise is viewed solely as a research or diagnostic tool and not as a true weapon against chronic disease. In reality, however, exercise attacks the roots of chronic disease, i.e. physical inactivity. The first step in a common "battle plan" is to convince the medical community that chronic disease is rooted in physical inactivity. In this review, we focus on the biological evidence to date showing how physical inactivity leads to chronic disease. One purpose of this review is to demonstrate that exercise, such as treadmill testing of humans for cardiac dysfunctions, is more than a diagnostic tool but part of disease management itself.
Aspirin↗