Matteo Bini

Hemodynamic and Autonomic Response to Different Salt Intakes in Normotensive Individuals

Background Even if sodium sensitivity represents a risk factor at any blood pressure (BP) level, limited evidence is available that it may influence cardiovascular control in normotensives, particularly in white individuals. Therefore, the aim of the study was to investigate whether sodium sensitivity alters hemodynamic or autonomic responses to salt in normotensives. Methods and Results We evaluated the Sodium‐Sensitivity Index (SS‐Index) in 71 white normotensives after 5 days of high‐ and low‐sodium diets. We measured BP continuously at the end of each period, estimating hemodynamic indices from BP waveform analysis, and autonomic indices from heart rate (HR) and BP variability. According to the SS‐Index distribution, we defined 1 sodium‐sensitive group (SS, with SS‐Index >15 mm Hg/[mmol·day]), 1 sodium‐resistant group, (unresponsive to sodium load with −15≤ SS‐Index ≤+15), and 1 inverse sodium‐sensitive group, responsive to sodium by decreasing BP, with SS‐Index <−15). We compared the effects of the diets among groups, and correlated autonomic/hemodynamic indices with the SS‐Index. After sodium loading, a significant decrease in systemic peripheral resistances, HR, spectral indices of BP modulation, and a significant increase of indices of HR vagal modulation were found in the inverse sodium‐sensitive group but not in SS normotensives. Moreover, the highest SS‐Indices were associated with the lesser vagal HR decelerations. Conclusions Our data suggest that salt sensitivity in white normotensive individuals is associated with impaired vasodilation and altered autonomic response to dietary salt. Such dysfunction may critically contribute to induce a BP response to dietary salt.

Improvement in aerobic capacity during cardiac rehabilitation in coronary artery disease patients: Is there a role for autonomic adaptations?

Background It has been previously shown in patients with heart failure that exercise-based rehabilitation programmes may improve functional capacity and autonomic response. The aim of this study was to investigate this issue further by evaluating whether an association exists between autonomic adaptations and improvements of aerobic capacity in a general population of coronary artery disease patients undergoing cardiac rehabilitation. Methods Ninety consecutive patients (age 60 ± 11 years) attended a rehabilitation programme of moderate continuous training (25 ± 8 sessions, 2–3 sessions/week). Functional capacity expressed as oxygen uptake (peak VO2) and autonomic function expressed as chronotropic response and heart rate recovery were evaluated by cardiopulmonary exercise tests before and after the rehabilitation programme. According to the expected mean increase in functional capacity, coronary artery disease patients were divided into two groups: those who improved peak VO2 by more than 2.6 ml/kg/min (R group) and those who did not (NR group). Effects of the rehabilitation programme were compared in R and NR groups. Results The number and intensity of exercise sessions did not differ between R (N = 39) and NR (N = 51) groups. However, only R patients improved chronotropic response (R: from 45.1 ± 16.9% to 72.7 ± 34.1%, P < 0.01; NR: from 49.3 ± 18.6% to 48.2 ± 36.5%, P = NS) and heart rate recovery (R: from 16.9 ± 7.0 bpm to 21.0 ± 8.7 bpm, P < 0.01; NR: from 15.2 ± 9.9 bpm to 15.8 ± 8.5 bpm, P = NS). After training both chronotropic response and heart rate recovery were significantly higher in R than NR patients. Conclusions The improvement in aerobic capacity of coronary artery disease patients following exercise-based cardiac rehabilitation programmes is associated with positive adaptations of autonomic function.

Multiscale Sample Entropy of Cardiovascular Signals: Does the Choice between Fixed- or Varying-Tolerance among Scales Influence Its Evaluation and Interpretation?

Multiscale entropy (MSE) quantifies the cardiovascular complexity evaluating Sample Entropy (SampEn) on coarse-grained series at increasing scales τ. Two approaches exist, one using a fixed tolerance r at all scales (MSEFT), the other a varying tolerance r(τ) adjusted following the standard-deviation changes after coarse graining (MSEVT). The aim of this study is to clarify how the choice between MSEFT and MSEVT influences quantification and interpretation of cardiovascular MSE, and whether it affects some signals more than others. To achieve this aim, we considered 2-h long beat-by-beat recordings of inter-beat intervals and of systolic and diastolic blood pressures in male (N = 42) and female (N = 42) healthy volunteers. We compared MSE estimated with fixed and varying tolerances, and evaluated whether the choice between MSEFT and MSEVT estimators influence quantification and interpretation of sex-related differences. We found substantial discrepancies between MSEFT and MSEVT results, related to the degree of correlation among samples and more important for heart rate than for blood pressure; moreover the choice between MSEFT and MSEVT may influence the interpretation of gender differences for MSE of heart rate. We conclude that studies on cardiovascular complexity should carefully choose between fixed- or varying-tolerance estimators, particularly when evaluating MSE of heart rate.

Autonomic function in Takotsubo syndrome long after the acute phase

OBJECTIVES Although it is well documented that an exaggerated sympathetic stimulation plays a role in the development of Takotsubo Syndrome (TS) during the acute phase, only few studies have focused on autonomic adaptations in stress-induced cardiomyopathy long after the acute phase. Aim of the study was to investigate whether an impairment of the autonomic function is still present long after a TS event. This was done by comparing the response to a maximal exercise test in TS patients after apparent recovery (>1-year after the acute event) with that obtained in healthy subjects and in post-myocardial infarction (post-MI) patients. METHODS To assess heart rate recovery (HRR) and chronotropic response (CR), 24 TS patients, 25 healthy subjects and 22 post-MI patients underwent maximal exercise test, after at least 3 days of β-blockers wash-out. RESULTS HRR in TS patients (19.2±9.7bpm) was lower than in healthy subjects (27.7±8.3, p=0.003), and similar to post-MI patients (19.3±8.4; p=0.99). A decreasing CR trend (p=0.06), higher in healthy subjects (72±13%) than in TS (65±22%) and post-MI (57±21%) patients, was also found. CONCLUSION Compared to healthy subjects, TS patients showed a blunted parasympathetic reactivation after exercise, similar to that observed in post-MI patients, thereby suggesting that vagal control of heart rate after exercise is abnormal long after the acute presentation of TS.

Predictive role of P-wave axis abnormalities in secondary cardiovascular prevention

Background Abnormal P-wave axis has been correlated with an increased risk of all-cause and cardiovascular mortality in a general population. We aimed to evaluate the prognostic role of abnormal P-wave axis in patients undergoing myocardial revascularisation or cardiac valve surgery. Methods We considered data of 810 patients with available P-wave axis measure from a prospective monocentric registry of patients undergoing cardiovascular rehabilitation. A total of 436 patients (54%) underwent myocardial revascularisation, 253 (31%) valve surgery, 71 (9%) combined valve and coronary artery bypass graft surgery and 50 (6%) cardiac surgery for other cardiovascular disease. Mean follow-up was 47 ± 27 months. Results Over the whole group, P-wave axis was 43.8° ± 27.5° and an abnormal P-wave axis was found in 94 patients (12%). The risk of overall (hazard ratio (HR) 2.5, 95% confidence interval (CI) 1.6–4.0, P < 0.001) and cardiovascular mortality (HR 2.9, 95% CI 1.5–5.8, P = 0.002) was significantly higher in patients with abnormal P-wave axis even after adjustment for age, other electrocardiographic variables (PR, QRS, QTc intervals), left ventricular ejection fraction and left atrial volume index. After dividing the population according to the type of disease, patients with abnormal P-wave axis and ischaemic heart disease had 3.9-fold higher risk of cardiovascular mortality (HR 3.9, 95% CI 1.3–12.1, P = 0.017), while a 2.2-fold higher risk of cardiovascular mortality (HR 3.6, 95% CI 1.3–10.1, P = 0.015) was found in those with cardiac valve disease. Conclusion An abnormal P-wave axis represents an independent predictor of both overall and cardiovascular mortality in patients undergoing myocardial revascularisation or cardiac valve surgery.

Anxiety disorders and stressful events in Takotsubo syndrome

BACKGROUND Anxiety disorders are more common in Takotsubo syndrome (TS) than in acute coronary syndrome patients. The aim of this study was to investigate whether pre-existing anxiety disorders predispose to TS triggered by exclusively emotional stressful events. METHODS Triggering events were compared in 58 TS patients with and without pre-existing anxiety disorders; clinical, electrocardiographic and echocardiographic data were also collected. RESULTS Thirty-one (53%) patients had a previous history of anxiety disorders. The exclusively emotional stressful event-rate was higher in TS patients with pre-existing anxiety disorder (74% vs. 30%, p = 0.001), while TS caused by an undetermined trigger were significantly higher in patients without anxiety disorders (33% vs. 10%, p = 0.027). Moreover, in TS patients without a previous history of anxiety disorders, a trend of higher prevalence of physical events was found (16% vs. 37%, p = 0.07). CONCLUSIONS In patients with pre-existing anxiety disorders, TS was predominantly triggered by exclusively emotional stressful events, thereby suggesting a possible relationship between anxiety and emotional cardiac frailty in TS patients.

Prognostic value of frontal QRS-T angle in patients undergoing myocardial revascularization or cardiac valve surgery

BACKGROUND An abnormal frontal QRS-T angle (fQRSTa) is associated with increased risk of death in primary and secondary cardiovascular prevention. The aim of this study was to evaluate the fQRSTa prognostic role in patients undergoing myocardial revascularization and/or cardiac valve surgery. METHODS We enrolled and prospectively followed for 48 ± 26 months 939 subjects with available QRS and T axis data; mean age was 68 ± 12 years, 449 patients (48%) underwent myocardial revascularization, 333 (35%) cardiac valve surgery, 94 (10%) valve plus bypass graft surgery and 63 (7%) cardiac surgery for other cardiovascular (CV) diseases. The ECG variables were collected at the end of the cardiac rehabilitation program and fQRSTa was considered normal if <60°, abnormal if >120°, borderline otherwise. Endpoints were overall and CV mortality. RESULTS The fQRSTa was normal in 333 patients (36%), borderline in 285 (30%) and abnormal in 321 (34%). Overall (p = 0.012) and cardiovascular (p = 0.007) mortality were significantly higher in patients with abnormal fQRSTa even after adjusting separately for gender, PR-, QTc- intervals, presence of right or left bundle branch block and left atrial volume index. The predictive value was confirmed in patients with stable coronary artery disease (SCAD), not in patients with acute coronary syndrome or valve disease. SCAD patients with abnormal both fQRSTa and QRS axis had higher risk of overall (hazard ratio = 2.9, p < 0.0001) and CV (hazard ratio = 4.4, p < 0.0001) mortality compared with SCAD patients with normal fQRSTa, even after multivariate adjustment for age, gender, ECG intervals, left-ventricle ejection fraction and mass index. CONCLUSIONS In SCAD patients undergoing myocardial revascularization, abnormal fQRSTa is independent predictor of overall and CV mortality.

Serum uric acid level predicts adverse outcomes after myocardial revascularization or cardiac valve surgery

Background High levels of serum uric acid have been associated with adverse outcomes in cardiovascular diseases such as myocardial infarction and heart failure. The aim of the current study was to evaluate the prognostic role of serum uric acid levels in patients undergoing cardiac rehabilitation after myocardial revascularization and/or cardiac valve surgery. Design We performed an observational prospective cohort study. Methods The study included 1440 patients with available serum uric acid levels, prospectively followed for 50 ± 17 months. Mean age was 67 ± 11 years; 781 patients (54%) underwent myocardial revascularization, 474 (33%) cardiac valve surgery and 185 (13%) valve-plus-coronary artery by-pass graft surgery. The primary endpoints were overall and cardiovascular mortality while secondary end-points were combined major adverse cardiac and cerebrovascular events. Results Serum uric acid level mean values were 286 ± 95 µmol/l and elevated serum uric acid levels (≥360 µmol/l or 6 mg/dl) were found in 275 patients (19%). Overall mortality (hazard ratio = 2.1; 95% confidence interval: 1.5–3.0; p < 0.001), cardiovascular mortality (hazard ratio = 2.0; 95% confidence interval: 1.2–3.2; p = 0.004) and major adverse cardiac and cerebrovascular events rate (hazard ratio = 1.5; 95% confidence interval: 1.0–2.0; p = 0.019) were significantly higher in patients with elevated serum uric acid levels, even after adjustment for age, gender, arterial hypertension, diabetes, glomerular filtration rate, atrial fibrillation and medical therapy. Moreover, strong positive correlations between serum uric acid level and probability of overall mortality (p < 0.001), cardiovascular mortality (p < 0.001) and major adverse cardiac and cerebrovascular events (p = 0.003) were found. Conclusions Serum uric acid levels predict mortality and adverse cardiovascular outcome in patients undergoing myocardial revascularization and/or cardiac valve surgery even after the adjustment for age, gender, arterial hypertension, diabetes, glomerular filtration rate and medical therapy.

Multiscale sample entropy of heart rate and blood pressure: Methodological aspects

The entropy of heart rate variability is one of the main features characterizing the complexity of the cardiovascular system. In order to take into account the multiscale nature of cardiovascular regulation, it was proposed to evaluate entropy with a multiscale approach, based on the estimation of Sample Entropy on progressively coarse-grained series (Multiscale Sample Entropy, MSE). Aim of this work is to investigate two methodological aspects related to MSE of cardiovascular signals. The first aspect regards the tolerance below which a couple of points are considered similar in a given embedding dimension, in particular how the way the tolerance is set at each level of coarse graining influences the MSE estimates. The second aspect regards whether heart rate and blood pressure (BP) signals are characterized by different MSE structures.To investigate these aspects, we analyzed 65 continuous BP recordings of more than 90-minute duration in healthy volunteers sitting at rest, and applied MSE estimators to beat-by-beat series of systolic BP, diastolic BP and pulse interval (inverse of heart rate). Results indicate that the way the tolerance is set during coarse graining influences substantially the MSE profile of cardiovascular signals, modifying the relative level of their unpredictability.