A longitudinal assessment of chronic care pathways in real-life: self-care and outcomes of chronic heart failure patients in Tuscany.

BACKGROUND: Worldwide healthcare systems face challenges in assessing and monitoring chronic care pathways and, even more, the value generated for patients. Patient-reported outcomes measures (PROMs) represent a valid Real-World Evidence (RWE) source to fully assess health systems' performance in managing chronic care pathways. METHODS: The originality of the study consists in the chance of adopting PROMs, as a longitudinal assessment tool for continuous monitoring of patients' adherence to therapies and self-care behavior recommendations in clinical practice and as a chance to provide policy makers insights to improve chronic pathways adopting a patient perspective. The focus was on PROMs of patients with chronic heart failure (CHF) collected in the Gabriele Monasterio Tuscan Foundation (FTGM), a tertiary referral CHF centre in Pisa, Italy. During the hospital stay, CHF patients were enrolled and received a link (via SMS or email) to access to the first questionnaire. Follow-up questionnaires were sent 1, 7 and 12 months after the index hospitalisation. Professionals invited 200 patients to participate to PROMs surveys. 174 answers were digitally collected at baseline from 2018 to 2020 and analysed. Quantitative and qualitative analyses were conducted, using Chi2, t-tests and regression models together with narrative evidence from free text responses. RESULTS: Both quantitative and qualitative results showed FTGM patients declared to strongly adhere to the pharmacological therapy across the entire pathway, while seemed less careful to adhere to self-care behavior recommendations (e.g., physical activity). CHF patients that performed adequate Self-Care Maintenance registered outcome improvements. Respondents declared to be supported by family members in managing their adherence. CONCLUSIONS: The features of such PROMs collection model are relevant for researchers, policymakers and for managers to implement interventions aimed at improving pathway adherence dimensions. Among those, behavioral economics interventions could be implemented to increase physical activity among CHF patients since proven successful in Tuscany. Strategies to increase territorial care and support patients' caregivers in their daily support to patients' adherence should be further explored. Systematic PROMs collection would allow to monitor changes in the whole pathway organization. This study brings opportunities for extending such monitoring systems to other organizations to allow for reliable benchmarking opportunities.

Tuscany Sangiovese grape juice imparts cardioprotection by regulating gene expression of cardioprotective C-type natriuretic peptide.

PURPOSE: A regular intake of red grape juice has cardioprotective properties, but its role on the modulation of natriuretic peptides (NPs), in particular of C-type NP (CNP), has not yet been proven. The aims were to evaluate: (1) in vivo the effects of long-term intake of Tuscany Sangiovese grape juice (SGJ) on the NPs system in a mouse model of myocardial infarction (MI); (2) in vitro the response to SGJ small RNAs of murine MCEC-1 under physiological and ischemic condition; (3) the activation of CNP/NPR-B/NPR-C in healthy human subjects after 7 days' SGJ regular intake. METHODS: (1) C57BL/6J male and female mice (n = 33) were randomly subdivided into: SHAM (n = 7), MI (n = 15) and MI fed for 4 weeks with a normal chow supplemented with Tuscany SGJ (25% vol/vol, 200 µl/per day) (MI + SGJ, n = 11). Echocardiography and histological analyses were performed. Myocardial NPs transcriptional profile was investigated by Real-Time PCR. (2) MCEC-1 were treated for 24 h with a pool of SGJ small RNAs and cell viability under 24 h exposure to H2O2 was evaluated by MTT assay. (3) Human blood samples were collected from seven subjects before and after the 7 days' intake of Tuscany SGJ. NPs and miRNA transcriptional profile were investigated by Real-Time PCR in MCEC-1 and human blood. RESULTS: Our experimental data, obtained in a multimodal pipeline, suggest that the long-term intake of SGJ promotes an adaptive response of the myocardium to the ischemic microenvironment through the modulation of the cardiac CNP/NPR-B/NPR-C system. CONCLUSIONS: Our results open new avenue in the development of functional foods aimed at enhancing cardioprotection of infarcted hearts through action on the myocardial epigenome.

Implications of atrial volumes in surgical corrected Tetralogy of Fallot on clinical adverse events.

BACKGROUND: While left atrial (LA) size has been shown as a strong predictor of cardiovascular diseases in various studies, the role of right atrial (RA) enlargement, especially in the growing population of patients with congenital heart diseases (CHD) is largely unknown. We sought to evaluate (1) RA and LA volumes in patients with repaired Tetralogy of Fallot (TOF) and assess correlations to (2) functional parameters and (3) clinical adverse events. METHODS: 169 patients with repaired TOF were enrolled following a targeted protocol for Cardiovascular magnetic resonance imaging (CMR), Cardiopulmonary exercise tests (CPET), Echocardiography and Measurement of NT-proBNP. Clinical history was assessed at enrollment and during a median Follow-up of 23 months (IQR 9-40). The primary clinical endpoint was a composite of all cause mortality, aborted sudden cardiac death and sustained VT. Prespecified secondary surrogate endpoint included worsening heart failure (NYHA III-IV), non-sustained VT and sustained supraventricular tachycardia. RESULTS: RA Systolic indexed volume (RASVi) correlated with LA Systolic indexed volume (LASVi) (r = 0.59, p < 0.001) and both correlated with the patient age (r = 0.52, p < 0.001; r = 0.59, p < 0.001 respectively). Patients in the upper tertil of RASVi (>58 ml/m2) had higher NT-proBNP levels, longer QRS duration, larger ventricle diameters, higher RV mass and lower peak oxygen uptake. RASVi was associated with the primary composite adverse event at univariate Cox-regression analysis (HR: 1.044, CI: 1.008-1.08, p = 0.01). Bayesian Multivariate model averaging revealed RASVi as predictor of secondary surrogate adverse outcome (HR: 1.06, CI: 1.053-1.068, Pb = 0,889). CONCLUSION: Among patients with repaired TOF, RA dilatation is an independent predictor for adverse clinical events. As such, routine assessment of RA volumes could be useful to further improve decision-making and management of these patients in the future.

Measurement of myocardial amyloid deposition in systemic amyloidosis: insights from cardiovascular magnetic resonance imaging.

BACKGROUND: Cardiac involvement in systemic amyloidosis is caused by the extracellular deposition of misfolded proteins, mainly immunoglobulin light chains (AL) or transthyretin (ATTR), and may be detected by cardiovascular magnetic resonance (CMR). The aim of this study was to measure myocardial extracellular volume (ECV) in amyloid patients with a novel T1 mapping CMR technique and to determine the correlation between ECV and disease severity. METHODS: Thirty-six patients with biopsy-proven systemic amyloidosis (mean age 70 ± 9 years, 31 men, 30 with AL and six with ATTR amyloidosis) and seven patients with possible amyloidosis (mean age 64 ± 10 years, six men) underwent comprehensive clinical and CMR assessment, with ECV estimation from pre- and postcontrast T1 mapping. Thirty healthy subjects (mean age 39 ± 17 years, 21 men) served as the control group. RESULTS: Amyloid patients presented with left ventricular (LV) concentric hypertrophy with impaired biventricular systolic function. Cardiac ECV was higher in amyloid patients (definite amyloidosis, 0.43 ± 0.12; possible amyloidosis, 0.34 ± 0.11) than in control subjects (0.26 ± 0.04, P < 0.05); even in amyloid patients without late gadolinium enhancement (0.35 ± 0.10), ECV was significantly higher than in the control group (P < 0.01). A cut-off value of myocardial ECV >0.316, corresponding to the 95th percentile in normal subjects, showed a sensitivity of 79% and specificity of 97% for discriminating amyloid patients from control subjects (area under the curve of 0.884). Myocardial ECV was significantly correlated with LV ejection fraction (R(2)  = 0.16), LV mean wall thickness (R(2)  = 0.41), LV diastolic function (R(2)  = 0.21), right ventricular ejection fraction (R(2)  = 0.13), N-terminal fragment of the pro-brain natriuretic peptides (R(2)  = 0.23) and cardiac troponin (R(2)  = 0.33). CONCLUSION: Myocardial ECV was increased in amyloid patients and correlated with disease severity. Thus, measurement of myocardial ECV represents a potential noninvasive index of amyloid burden for use in early diagnosis and disease monitoring.

Plasma leptin and vascular endothelial growth factor (VEGF) in normal subjects at high altitude (5050 m).

CONTEXT: High altitude (HA) is a model of severe hypoxia exposure in humans. We hypothesized that nocturnal hypoxemia or acute maximal exercise at HA might affect plasma leptin and VEGF levels. OBJECTIVES: Plasma leptin, VEGF and other metabolic variables were studied after nocturnal pulse oximetry and after maximal exercise in healthy lowlanders on the 3rd-4th day of stay in Lobuche (5050 m, HA) and after return to sea level (SL). RESULTS: Leptin was similar at SL or HA in both pre- and post-exercise conditions. Pre-exercise VEGF at HA was lower, and cortisol was higher, than at SL, suggesting that nocturnal intermittent hypoxia associated with periodic breathing at HA might affect these variables. CONCLUSIONS: Leptin levels appear unaffected at HA, whereas nocturnal hypoxic stress may affect plasma VEGF. Future HA studies should investigate the possible role of nocturnal intermittent hypoxemia on metabolism.

Individual patient meta-analysis of exercise training effects on systemic brain natriuretic peptide expression in heart failure.

BACKGROUND: Brain natriuretic peptide (BNP) predicts exercise performance and exercise training may modulate BNP and its N-terminal portion (NT-pro-BNP), we therefore conducted an individual patient analysis of exercise training effects on BNP and NT-pro-BNP. AIMS: To use an individual patient meta-analysis to relate changes in BNP, NT-pro-BNP, and peak VO(2); to link these changes to volume parameters of exercise training programmes (intensity etc.); and to identify patient characteristics likely to lead to greater improvements in BNP, NT-pro-BNP, and peak VO(2). DESIGN: Individual patient meta-analysis. METHODS: A systematic search was conducted of Medline (Ovid), Embase.com, Cochrane Central Register of Controlled Trials, and CINAHL (until July 2008) to identify randomized controlled trials of aerobic and/or resistance exercise training in systolic heart failure patients measuring BNP and/or NT-pro-BNP. Primary outcome measures were change in BNP, NT-pro-BNP, and peak VO2. Subanalyses were conducted to identify (1) patient groups that benefit most and (2) exercise programme parameters enhancing favourable changes in primary outcome measures. RESULTS: Ten randomized controlled studies measuring BNP or NT-pro-BNP met eligibility criteria, authors provided individual patient data for 565 patients (313 exercise and 252 controls). Exercise training had favourable effects on BNP (-28.3%, p < 0.0001), NT-pro-BNP (-37.4%, p = < 0.0001), and peak VO(2) (17.8%, p < 0.0001). The analysis showed a significant change in primary outcome measures; moreover, change in BNP (r = -0.31, p < 0.0001) and NT-pro-BNP (r = -0.22, p < 0.0001) were correlated with peak VO(2) change. CONCLUSION: Exercise training has favourable effects on BNP, NT-pro-BNP, and peak VO(2) in heart failure patients and BNP/NT-pro-BNP changes were correlated with peak VO(2) changes.

Exercise intolerance at high altitude (5050 m): critical power and W'.

The relationship between work rate (WR) and its tolerable duration (t(LIM)) has not been investigated at high altitude (HA). At HA (5050 m) and at sea level (SL), six subjects therefore performed symptom-limited cycle-ergometry: an incremental test (IET) and three constant-WR tests (% of IET WR(max), HA and SL respectively: WR(1) 70±8%, 74±7%; WR(2) 86±14%, 88±10%; WR(3) 105±13%, 104±9%). The power asymptote (CP) and curvature constant (W') of the hyperbolic WR-t(LIM) relationship were reduced at HA compared to SL (CP: 81±21 vs. 123±38 W; W': 7.2±2.9 vs. 13.1±4.3 kJ). HA breathing reserve (estimated maximum voluntary ventilation minus end-exercise ventilation) was also compromised (WR(1): 25±25 vs. 50±18 l min(-1); WR(2): 4±23 vs. 38±23 l min(-1); WR(3): -3±18 vs. 32±24 l min(-1)) with near-maximal dyspnea levels (Borg) (WR(1): 7.2±1.2 vs. 4.8±1.3; WR(2): 8.8±0.8 vs. 5.3±1.2; WR(3): 9.3±1.0 vs. 5.3±1.5). The CP reduction is consistent with a reduced O(2) availability; that of W' with reduced muscle-venous O(2) storage, exacerbated by ventilatory limitation and dyspnea.

Prevalent cardiac phenotype resulting in heart transplantation in a novel LMNA gene duplication.

Mutations in the lamin A/C gene (LMNA) are known to be involved in several diseases such as Emery-Dreifuss muscular dystrophy, limb-girdle muscular dystrophy type 1B and dilated cardiomyopathies with conduction disease, with considerable phenotype heterogeneity. Here we report on a novel autosomal dominant mutation in LMNA in two direct relatives presenting with different clinical phenotypes, characterized by severe life-threatening limb-girdle muscle involvement and cardiac dysfunction treated with heart transplantation in the proband, and by ventricular tachyarrhythmias with preserved cardiac and skeletal muscle function in her young son. To our knowledge, this is the first report of a duplication in the LMNA gene. The two phenotypes described could reflect different clinical stages of the same disease. We hypothesize that early recognition and initiation of therapeutic manoeuvres in the younger patient may retard the rate of progression of the cardiomyopathy.

Amino-terminal fragment of pro-brain natriuretic hormone identifies functional impairment and right ventricular overload in operated tetralogy of Fallot patients.

To evaluate the relationship between plasma concentration of amino-terminal fragment of pro-brain natriuretic peptide (NT-proBNP), functional capacity, and right ventricular overload in survivors of tetralogy of Fallot (TOF) repair, we prospectively studied 70 operated TOF patients (44 males, 21 +/- 1 years old; mean +/- SEM) who underwent, during the same day, echocardiography, cardiac magnetic resonance imaging, neurohormonal characterization (plasma NT-proBNP, catecholamines, plasma renin activity, and aldosterone assay), and cardiopulmonary exercise testing. Forty-eight age- and sex-matched healthy volunteers served as the control group. Compared to controls, maximal workload and peak oxygen consumption (VO2/kg) were lower in operated TOF patients (p < 0.001), whereas NT-proBNP concentration was elevated (p < 0.001). No difference was found among the other neurohormones. In operated TOF patients, NT-proBNP showed a significant positive correlation with right ventricular (RV) end systolic and end diastolic volumes and RV systolic pressure, and it showed a negative correlation with peak VO2/kg and RV ejection fraction. From multivariable analysis, NT-proBNP concentration was found to be an independent predictor of peak VO2/kg, RV end systolic volume, and RV systolic pressure. These results show an association among RV overload, decrease in functional capacity, and cardiac natriuretic peptide expression in operated TOF patients. NT-proBNP plasma assay may be a useful tool for diagnostic purposes and for decision making in this setting.

[Natriuretic peptides in heart failure]. / Peptidi natriuretici come guida alla prognosi e terapia nello scompenso cardiaco.

The recent discovery of cardiac endocrine function, together with the development of accurate and feasible assay methods for cardiac natriuretic hormone evaluation, i.e. for B-type natriuretic peptide (BNP) and inactive peptide NT-proBNP have confirmed their pathophysiological and clinical significance for cardiovascular disease assessment. Concerning heart failure, their value is for diagnostic screening in selected/unselected populations, for differential diagnosis of dyspnea and for prognostic stratification, and as a guide for follow-up and treatment of patients. Recent Italian recommendations pointed out that BNP/NT-proBNP has a role in ruling-out the diagnosis of heart failure in patients with dubious signs/symptoms: plasma BNP/NT-proBNP concentrations help in the clinical evaluation of chronic heart failure patients when risk stratification is needed, whereas the routine BNP/NT-proBNP assay is still not recommended to guide therapeutic decision-making.

Sympathetic and parasympathetic baroreflex dysfunction in familial dysautonomia.

OBJECTIVE: To assess the possible abnormalities in the baroreflex modulation of both the heart and the arterial vasculature, in order to better evaluate the role of baroreflex abnormalities in the generation of the cardiovascular symptoms and complications affecting the familial dysautonomia (FD) patient. METHODS: Twenty-one FD patients and 22 controls underwent 3 minutes of passive head-up tilt (HUT) and baroreceptor stimulation by means of sinusoidal neck suction (NS; 0 to -30 mm Hg; 0.1 Hz [LF] and 0.2 Hz [HF]). Respiration was maintained constant during NS at 15 breaths/minute. The authors monitored RR-intervals (RRI), blood pressure (BP) (Colin), and respiration. NS induced changes of RRI and BP were determined by spectral analysis. RESULTS: HUT showed orthostatic hypotension without compensatory tachycardia in FD patients but not in controls. LF-NS increased LF power of RRI and BP and HF-NS increased HF power of RRI in controls, but not in FD patients. CONCLUSIONS: Familial dysautonomia patients have a widespread baroreflex abnormality, involving both the efferent sympathetic arm on the resistance vessels, and the sympathetic and parasympathetic efferent arms on the heart. Therefore, the abnormalities in the control of blood pressure-i.e., supine hypertension, orthostatic hypotension, blood pressure lability-and heart rate-i.e., bradyarrhythmias-are likely due to baroreflex abnormalities.

Cerebral vasoreactivity in Andeans and headache at sea level.

Headache is common in Cerro de Pasco (CP), Peru (altitude 4338 m) and was present in all patients with chronic mountain sickness (CMS) in CP reported here. Forty-seven percent of inhabitants report headache. Twenty-four percent of men have migraine with aura, with an average of 65 attacks a year. We assessed vasoreactivity of the cerebral vessels to CO2 by rebreathing and to NO by the administration of isosorbite dinitrate (IDN), a nitric oxide (NO) donor, using transcranial Doppler ultrasound in the middle cerebral artery (MCA) in natives of CP, some of whom suffered from CMS. We repeated the measurements in Lima (altitude 150 m) in the same subjects within 24 h of arrival. Vasodilatation in the middle cerebral artery supply territory in response to CO2 and NO, both physiologic vasodilators, is defective in Andean natives at altitude and in the same subjects at sea level. Incapacitating migraine can occur with impaired cerebral vasoreactivity to physiologic vasodilators. We propose that susceptibility to migraine might depend in part on gene expression with consequent alterations of endothelial function.

Widespread cardiovascular autonomic dysfunction in primary amyloidosis: does spontaneous hyperventilation have a compensatory role against postural hypotension?

OBJECTIVE: To investigate the possible causes of abnormal blood pressure control in light chain related (primary, AL) amyloidosis. DESIGN: Cardiovascular, autonomic, and respiratory response to passive tilting were investigated in 51 patients with primary amyloidosis (mean (SEM) age 56 (2) years) and in 20 age matched controls. Spontaneous fluctuations in RR interval, respiration, end tidal carbon dioxide, blood pressure, and skin microcirculation were recorded during supine rest and with tilting. The values were subjected to spectral analysis to assess baroreflex sensitivity and the autonomic modulation of cardiac and vascular responses. SETTING: Tertiary referral centre. RESULTS: Autonomic modulation of the heart and blood pressure was nearly absent in the patients with amyloidosis: thus baroreflex sensitivity and the low frequency (0.1 Hz) fluctuations in all cardiovascular signals were severely reduced (p < 0.01 or more), as were respiratory fluctuations in the RR interval, and no change was observed upon tilting. Despite reduced autonomic modulation, blood pressure remained relatively stable in the amyloid group from supine to tilting. End tidal carbon dioxide was reduced in the amyloid patients (p < 0.001) indicating persistent hyperventilation; the breathing rate correlated inversely with the fall in blood pressure on tilting (p < 0.05). CONCLUSIONS: In primary amyloidosis, pronounced abnormalities in arterial baroreflexes and cardiovascular autonomic modulation to the heart and the vessels may be partly compensated for by hyperventilation at a slow breathing rate.

Prognostic value of serum gamma-glutamyl transferase activity after myocardial infarction.

AIMS: Serum gamma-glutamyl transferase activity (gamma-GT) is able to catalyse low-density lipoprotein oxidation and has been detected in coronary atherosclerotic plaques. gamma-GT has been documented as an independent risk factor for cardiac mortality in middle-aged men. The purpose of this study is to determine the prognostic value of gamma-GT in patients with coronary artery disease. METHODS AND RESULTS: In a prospective study, gamma-GT and other cardiac risk factors were evaluated in 469 consecutive subjects with angiographically documented coronary artery disease, using mortality and mortality plus non-fatal myocardial infarction as end-points. gamma-GT showed an independent prognostic value beyond known established risk factors in the subgroup of 262 patients with previous myocardial infarction. At a 6-year follow-up, cardiac mortality was 25.2% in patients with gamma-GT >40 U x l(-1)vs 13.9% in those with gamma-GT <40 U x l(-1)(P=0.038). When both cardiac mortality and non-fatal myocardial infarction were considered as end-points, these events were recorded in 32.7% of patients with gamma-GT >40 U x l(-1)and in 20.4% of those with levels <40 U x l(-1)(P=0.031). Excess mortality and non-fatal infarction in patients with high gamma-GT levels were concentrated in the first 2 years of follow-up (P=0.014). The association of gamma-GT values >40 U x l(-1), previous myocardial infarction, and multiple vessel disease identified a subgroup of 168 patients with the highest risk of cardiac events at 6 years (P=0.024). The relationship between gamma-GT levels and cardiac events remained significant after adjustment for cardiac risk factors, and possible confounders, including alcohol consumption. gamma-GT did not show significant prognostic value in the 207 patients without previous myocardial infarction. CONCLUSION: gamma-GT is an independent cardiac risk factor in ischaemic patients with established coronary atherosclerosis and previous myocardial infarction.

Hyperthyroidism is associated with lengthening of ventricular repolarization.

OBJECTIVE: Lengthened ventricular repolarization, as assessed by the QT interval on electrocardiogram (ECG), can predispose to an increased risk of cardiac dysrhythmias; no data are available on QT corrected for heart rate (QTc) in hyperthyroidism in vivo. DESIGN: QT and RR intervals from 24 h ambulatory ECG Holter recording were measured in patients with hyperthyroidism and again following pharmacological achievement of stable euthyroidism for at least 2 months. PATIENTS: We enrolled a total of 16 hyperthyroid patients with Graves' disease, six males and 10 females (mean age 47 +/- 4 years, mean +/- SEM); 13 healthy age- and sex-matched subjects were utilized as a control group. MEASUREMENTS: The QT analysis was carried out by a computerized algorithm (QTc was corrected by the heart rate by Bazett's formula). Serum total T4, total T3, free T4, free T3 and TSH concentrations were measured by a fully automated immunoenzymometric assay; plasma norepinephrine by automatized high-pressure liquid chromatography, potassium and chloride by a potentiometric method, magnesium and calcium by a colourimetric method. RESULTS: The 24-h average QTc in the hyperthyroid patients was significantly prolonged compared to controls (458 +/- 7 vs. 431 +/- 6 ms, P = 0.01) and it returned to normal after treatment of thyrotoxicosis (432 +/- 6 ms, P < 0.05 vs. time H, NS vs. controls). QTc positively correlated with FT3 (r = 0.63, P < 0.001) and with FT4 (r = 0.481, P < 0.02). Conversely, QTc did not correlate with plasma basal norepinephrine levels, nor with electrolytes. CONCLUSIONS: Hyperthyroidism is associated with prolonged QTc that normalizes once the patient becomes euthyroid. The strong positive correlation between FT3 and QTc supports the hypothesis of an important role of thyroid hormone on modulation of QTc lengthening.

Breathing patterns and cardiovascular autonomic modulation during hypoxia induced by simulated altitude.

OBJECTIVE: To assess the influence of different breathing patterns on autonomic cardiovascular modulation during acute exposure to altitude-induced hypoxia. DESIGN: We measured relative changes in minute ventilation (VE), oxygen saturation (%SaO2), spectral analysis of RR interval and blood pressure, and response to stimulation of carotid baroreceptors (neck suction) at baseline and after acute (1 h) hypobaric hypoxia (equivalent to 5,000 m, in a hypobaric chamber). METHODS: We studied 19 human subjects: nine controls and 10 Western yoga trainees of similar age, while breathing spontaneously, at 15 breaths/min (controlled breathing) and during 'complete yogic breathing' (slow diaphragmatic + thoracic breathing, approximately 5 breaths/min) in yoga trainees, or simple slow breathing in controls. RESULTS: At baseline %SaO2, VE and autonomic pattern were similar in both groups; simulated altitude increased VE in controls but not in yoga trainees; %SaO2 decreased in all subjects (P< 0.0001), but more in controls than in yoga trainees (17 versus 12%, 14 versus 9%, 14 versus 8%, all P< 0.05 or better, during spontaneous breathing, controlled breathing and yogic or slow breathing, respectively). Simulated altitude decreased RR interval (from 879 +/- 45 to 770 +/- 39, P < 0.01) and increased indices deducted from spectral analysis of heart rate variability (low frequency/high frequency (LF/HF) ratio from 1.6 +/- 0.5 to 3.2 +/- 1.1, P < 0.05) and systolic blood pressure (low-frequency fluctuations from 2.30 +/- 0.31 to 3.07 +/- 0.24 In-mmHg2, P< 0.05) in controls, indicating sympathetic activation; these changes were blunted in yoga trainees, and in both groups during slow or yogic breathing. No effect of altitude was seen on stimulation of carotid baroreceptors in both groups. CONCLUSIONS: Well-performed slow yogic breathing maintains better blood oxygenation without increasing VE (i.e. seems to be a more efficient breathing) and reduces sympathetic activation during altitude-induced hypoxia.