Luciano Bernardi

Diabetic neuropathies: Update on definitions, diagnostic criteria, estimation of severity, and treatments

Preceding the joint meeting of the 19th annual Diabetic Neuropathy Study Group of the European Association for the Study of Diabetes (NEURODIAB) and the 8th International Symposium on Diabetic Neuropathy in Toronto, Canada, 13–18 October 2009, expert panels were convened to provide updates on classification, definitions, diagnostic criteria, and treatments of diabetic peripheral neuropathies (DPNs), autonomic neuropathy, painful DPNs, and structural alterations in DPNs.

Effects of controlled breathing, mental activity and mental stress with or without verbalization on heart rate variability

OBJECTIVES To assess whether talking or reading (silently or aloud) could affect heart rate variability (HRV) and to what extent these changes require a simultaneous recording of respiratory activity to be correctly interpreted. BACKGROUND Sympathetic predominance in the power spectrum obtained from short- and long-term HRV recordings predicts a poor prognosis in a number of cardiac diseases. Heart rate variability is often recorded without measuring respiration; slow breaths might artefactually increase low frequency power in RR interval (RR) and falsely mimic sympathetic activation. METHODS In 12 healthy volunteers we evaluated the effect of free talking and reading, silently and aloud, on respiration, RR and blood pressure (BP). We also compared spontaneous breathing to controlled breathing and mental arithmetic, silent or aloud. The power in the so called low- (LF) and high-frequency (HF) bands in RR and BP was obtained from autoregressive power spectrum analysis. RESULTS Compared with spontaneous breathing, reading silently increased the speed of breathing (p < 0.05), decreased mean RR and RR variability and increased BP. Reading aloud, free talking and mental arithmetic aloud shifted the respiratory frequency into the LF band, thus increasing LF% and decreasing HF% to a similar degree in both RR and respiration, with decrease in mean RR but with minor differences in crude RR variability. CONCLUSIONS Simple mental and verbal activities markedly affect HRV through changes in respiratory frequency. This possibility should be taken into account when analyzing HRV without simultaneous acquisition and analysis of respiration.

Effect of rosary prayer and yoga mantras on autonomic cardiovascular rhythms: comparative study

Abstract Objective: To test whether rhythmic formulas such as the rosary and yoga mantras can synchronise and reinforce inherent cardiovascular rhythms and modify baroreflex sensitivity. Design: Comparison of effects of recitation of the Ave Maria (in Latin) or of a mantra, during spontaneous and metronome controlled breathing, on breathing rate and on spontaneous oscillations in RR interval, and on blood pressure and cerebral circulation. Setting: Florence and Pavia, Italy. Participants: 23 healthy adults. Main outcome measures: Breathing rate, regularity of breathing, baroreflex sensitivity, frequency of cardiovascular oscillations. Results: Both prayer and mantra caused striking, powerful, and synchronous increases in existing cardiovascular rhythms when recited six times a minute. Baroreflex sensitivity also increased significantly, from 9.5 (SD 4.6) to 11.5 (4.9) ms/mm Hg, P<0.05. Conclusion: Rhythm formulas that involve breathing at six breaths per minute induce favourable psychological and possibly physiological effects. What is already known on this topic Reduced heart rate variability and baroreflex sensitivity are powerful and independent predictors of poor prognosis in heart disease Slow breathing enhances heart rate variability and baroreflex sensitivity by synchronising inherent cardiovascular rhythms What this study adds Recitation of the rosary, and also of yoga mantras, slowed respiration to almost exactly 6/min, and enhanced heart rate variability and baroreflex sensitivity The rosary might be viewed as a health practice as well as a religious practice

Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management

The Cardiovascular Autonomic Neuropathy (CAN) Subcommittee of the Toronto Consensus Panel on Diabetic Neuropathy worked to update CAN guidelines, with regard to epidemiology, clinical impact, diagnosis, usefulness of CAN testing, and management. CAN is the impairment of cardiovascular autonomic control in the setting of diabetes after exclusion of other causes. The prevalence of confirmed CAN is around 20%, and increases up to 65% with age and diabetes duration. Established risk factors for CAN are glycaemic control in type 1 and a combination of hypertension, dyslipidaemia, obesity, and glycaemic control in type 2 diabetes. CAN is a risk marker of mortality and cardiovascular morbidity, and possibly a progression promoter of diabetic nephropathy. Criteria for CAN diagnosis and staging are: (1) one abnormal cardiovagal test result identifies possible or early CAN; (2) at least two abnormal cardiovagal test results are required for definite or confirmed CAN; and (3) the presence of orthostatic hypotension in addition to abnormal heart rate test results identifies severe or advanced CAN. Progressive stages of CAN are associated with increasingly worse prognosis. CAN assessment is relevant in clinical practice for (1) diagnosis of CAN clinical forms, (2) detection and tailored treatment of CAN clinical correlates (e.g. tachycardia, orthostatic hypotension, non‐dipping, QT interval prolongation), (3) risk stratification for diabetic complications and cardiovascular morbidity and mortality, and (4) modulation of targets of diabetes therapy. Evidence on the cost‐effectiveness of CAN testing is lacking. Apart from the preventive role of intensive glycaemic control in type 1 diabetes, recommendations cannot be made for most therapeutic approaches to CAN. Copyright

Cardiovascular, cerebrovascular, and respiratory changes induced by different types of music in musicians and non-musicians: the importance of silence

Objective: To assess the potential clinical use, particularly in modulating stress, of changes in the cardiovascular and respiratory systems induced by music, specifically tempo, rhythm, melodic structure, pause, individual preference, habituation, order effect of presentation, and previous musical training. Design: Measurement of cardiovascular and respiratory variables while patients listened to music. Setting: University research laboratory for the study of cardiorespiratory autonomic function. Patients: 12 practising musicians and 12 age matched controls. Interventions: After a five minute baseline, presentation in random order of six different music styles (first for a two minute, then for a four minute track), with a randomly inserted two minute pause, in either sequence. Main outcome measures: Breathing rate, ventilation, carbon dioxide, RR interval, blood pressure, mid-cerebral artery flow velocity, and baroreflex. Results: Ventilation, blood pressure, and heart rate increased and mid-cerebral artery flow velocity and baroreflex decreased with faster tempi and simpler rhythmic structures compared with baseline. No habituation effect was seen. The pause reduced heart rate, blood pressure, and minute ventilation, even below baseline. An order effect independent of style was evident for mid-cerebral artery flow velocity, indicating a progressive reduction with exposure to music, independent of style. Musicians had greater respiratory sensitivity to the music tempo than did non-musicians. Conclusions: Music induces an arousal effect, predominantly related to the tempo. Slow or meditative music can induce a relaxing effect; relaxation is particularly evident during a pause. Music, especially in trained subjects, may first concentrate attention during faster rhythms, then induce relaxation during pauses or slower rhythms.

Slow Breathing Improves Arterial Baroreflex Sensitivity and Decreases Blood Pressure in Essential Hypertension

Sympathetic hyperactivity and parasympathetic withdrawal may cause and sustain hypertension. This autonomic imbalance is in turn related to a reduced or reset arterial baroreflex sensitivity and chemoreflex-induced hyperventilation. Slow breathing at 6 breaths/min increases baroreflex sensitivity and reduces sympathetic activity and chemoreflex activation, suggesting a potentially beneficial effect in hypertension. We tested whether slow breathing was capable of modifying blood pressure in hypertensive and control subjects and improving baroreflex sensitivity. Continuous noninvasive blood pressure, RR interval, respiration, and end-tidal CO2 (CO2-et) were monitored in 20 subjects with essential hypertension (56.4±1.9 years) and in 26 controls (52.3±1.4 years) in sitting position during spontaneous breathing and controlled breathing at slower (6/min) and faster (15/min) breathing rate. Baroreflex sensitivity was measured by autoregressive spectral analysis and “alpha angle” method. Slow breathing decreased systolic and diastolic pressures in hypertensive subjects (from 149.7±3.7 to 141.1±4 mm Hg, P<0.05; and from 82.7±3 to 77.8±3.7 mm Hg, P<0.01, respectively). Controlled breathing (15/min) decreased systolic (to 142.8±3.9 mm Hg; P<0.05) but not diastolic blood pressure and decreased RR interval (P<0.05) without altering the baroreflex. Similar findings were seen in controls for RR interval. Slow breathing increased baroreflex sensitivity in hypertensives (from 5.8±0.7 to 10.3±2.0 ms/mm Hg; P<0.01) and controls (from 10.9±1.0 to 16.0±1.5 ms/mm Hg; P<0.001) without inducing hyperventilation. During spontaneous breathing, hypertensive subjects showed lower CO2 and faster breathing rate, suggesting hyperventilation and reduced baroreflex sensitivity (P<0.001 versus controls). Slow breathing reduces blood pressure and enhances baroreflex sensitivity in hypertensive patients. These effects appear potentially beneficial in the management of hypertension.

Impaired circadian modulation of sympathovagal activity in diabetes. A possible explanation for altered temporal onset of cardiovascular disease.

BackgroundDiabetic subjects have a high incidence of cardiovascular accidents, with an altered circadian distribution. Abnormalities in the circadian rhythm of autonomic tone may be responsible for this altered temporal onset of cardiovascular disease. Methods and ResultsTo assess circadian changes of sympathovagal balance in diabetes, we performed 24-hour power spectral analysis of RR interval fluctuations in 54 diabetic subjects (age, 44±2 years) with either normal autonomic function or mild to severe autonomic neuropathy and in 54 age-matched control subjects. The power in the low-frequency (LF, 0.03–0.15 Hz) and high-frequency (HF, 0.18–0.40 Hz) bands was considered an index of relative sympathetic and vagal activity, respectively. Diabetic subjects with autonomic abnormalities showed a reduction in LF compared with control subjects (5.95±0.12 In-msece versus 6.73±0.11, p<0.001) and an even greater reduction in LF, particularly during the night and the first hours after awakening (5.11±0.18 In-msece versus 6.52±0.14, p<0.001). Day-night rhythm in sympathovagal balance was reduced or absent in diabetic subjects compared with control subjects. ConclusionsDiabetic subjects with or without signs of autonomic neuropathy have a decreased vagal activity (and hence a relatively higher sympathetic activity) during night hours and at the same time of the day, during which a higher frequency of cardiovascular accidents has been reported. These observations may provide insight into the increased cardiac risk of diabetic patients, particularly if autonomic neuropathy is present.

Physical activity influences heart rate variability and very-low-frequency components in Holter electrocardiograms

OBJECTIVE A major proportion of RR interval variability in long-term recordings is due to slow (< 0.03 Hz) fluctuations, which seem to be a good predictor of survival after myocardial infarction, whose origin remains unclear. METHODS To study the effect of physical activity we compared by spectral analysis of the RR interval in 10 healthy human subjects (aged 28[s.e. 2] years) during 1-h periods each of rest (no activity), alternating rest and mild exercise (rhythmic activity), and normal spontaneous (random) activity. RESULTS Compared to rest, during both random and rhythmic activities, the RR variance increased significantly (from 5802[1030] to 13388[1448] ms2, P < 0.05, and to 24959[2901], P < 0.001) due to an increase in power below 0.03 Hz (from 3017[467] to 9606[966] ms2, P < 0.01, and to 21 103[2298] ms2, P < 0.001) which explained 55.4, 73.2 and 86.1% of total RR variance, respectively. CONCLUSIONS The amount of RR variability and its slower fluctuations largely depend on physical activity, regardless of its regular or irregular occurrence. Attempts to predict cardiovascular prognosis on the basis of RR fluctuations should therefore take account of the confounding effect of physical activity since healthier subjects would probably be more active.

Effect of breathing rate on oxygen saturation and exercise performance in chronic heart failure

BACKGROUND In chronic heart failure (CHF), impaired pulmonary function can independently contribute to oxygen desaturation and reduced physical activity. We investigated the effect of breathing rate on oxygen saturation and other respiratory indices. METHODS Arterial oxygen saturation (SaO2) and respiratory indices were recorded during spontaneous breathing (baseline) and during controlled breathing at 15, six, and three breaths per min in 50 patients with CHF and in 11 healthy volunteers (controls). 15 patients with CHF were randomly allocated 1 month of respiratory training to decrease their respiratory rate to six breaths per min. Respiratory indices were recorded before training, at the end of training, and 1 month after training. FINDINGS During spontaneous breathing, mean SaO2 was lower in CHF patients than in controls (91-4% [SD 0.4] vs 95.4% [0.2], p<0.001). Controlled breathing increased SaO2 at all breathing rates in patients with CHF. Compared with baseline, minute ventilation increased at 15 breaths per min (+45.9% [9.8], p<0.01), did not change at six breaths per min, and decreased at three breaths per min (-40.3% [4.8], p<0.001). In the nine CHF patients who had 1 month of respiratory training, resting SaO2 increased from 92.5% (0.3) at baseline to 93.2% (0.4) (p<0.05), their breathing rate per min decreased from 13.4 (1.5) to 7.6 (1.9) (p<0.001), peak oxygen consumption increased from 1157 (83) to 1368 (110) L/min (p<0.05), exercise time increased from 583 (29) to 615 (23) min/s (p<0.05), and perception of dyspnoea reduced from a score of 19.0 (0.4) to 17.3 (0.9) on the Borg scale (p<0.05). There were no changes in the respiratory indices in the patients who did not have respiratory training. INTERPRETATION Slowing respiratory rate reduces dyspnoea and improves both resting pulmonary gas exchange and exercise performance in patients with CHF.

Modulatory effects of respiration

Respiration is a powerful modulator of heart rate variability, and of baro- and chemoreflex sensitivity. Abnormal respiratory modulation of heart rate is often an early sign of autonomic dysfunction in a number of diseases. In addition, increase in venous return due to respiration may help in maintaining blood pressure during standing in critical situations. This review examines the possibility that manipulation of breathing pattern may provide beneficial effects in terms not only of ventilatory efficiency, but also of cardiovascular and respiratory control in physiologic and pathologic conditions, such as chronic heart failure. This opens a new area of future research in the better management of patients with cardiovascular autonomic dysfunction.