Perceived Anxiety, Coping, and Autonomic Function in Takotsubo Syndrome Long after the Acute Event.

BACKGROUND: Anxiety and depressive disorders represent predisposing factors for the autonomic dysfunctions that characterize the acute phase of Takotsubo syndrome (TS). However, there is insufficient data on this relationship after the acute event. The present study aimed at evaluating the psychological and autonomic status of patients with a history of TS. METHODS: Ten TS patients whose acute event occurred at least 1 year prior to the evaluation and nine healthy age- and sex-matched subjects were evaluated. The cardiovascular assessment included a clinical examination, beat-to-beat heart rate monitoring to assess heart rate variability, and a psychological examination using the 16 Personality Factors-C Form (16PF), the Acceptance and Action Questionnaire-II, the Coping Orientations to Problems Experienced (COPE), the Beck Depression Inventory-II, and the State-Trait Anxiety Inventory (STAI). RESULTS: TS patients scored significantly higher on the STAI (i.e., Anxiety Trait), 16PF (i.e., Tension), and COPE (i.e., Transcendental Orientation). TS patients also showed lower heart rate variability. Moreover, a significant inverse correlation was found between sympathetic tone (LF/HF ratio) and coping orientation. CONCLUSIONS: Long after the acute event, TS patients are characterized by elevated anxiety, high tension, and a specific religious coping strategy.

Red blood cell distribution width as a novel prognostic marker after myocardial revascularization or cardiac valve surgery.

The red blood cell distribution width (RDW) measures the variability in the size of circulating erythrocytes. Previous studies suggested a powerful correlation between RDW obtained from a standard complete blood count and cardiovascular diseases in both primary and secondary cardiovascular prevention. The current study aimed to evaluate the prognostic role of RDW in patients undergoing cardiac rehabilitation after myocardial revascularization and/or cardiac valve surgery. The study included 1.031 patients with available RDW levels, prospectively followed for a mean of 4.5 ± 3.5 years. The mean age was 68 ± 12 years, the mean RDW was 14.7 ± 1.8%; 492 patients (48%) underwent cardiac rehabilitation after myocardial revascularization, 371 (36%) after cardiac valve surgery, 102 (10%) after valve-plus-coronary artery by-pass graft surgery, 66 (6%) for other indications. Kaplan-Meier analysis and Cox hazard analysis were used to associate RDW with mortality. Kaplan-Meier analysis demonstrated worse survival curves free from overall (log-rank p < 0.0001) and cardiovascular (log-rank p < 0.0001) mortality in the highest RDW tertile. Cox analysis showed RDW levels correlated significantly with the probability of overall (HR 1.26; 95% CI 1.19-1.32; p < 0.001) and cardiovascular (HR 1.31; 95% CI 1.23-1.40; p < 0.001) mortality. After multiple adjustments for cardiovascular risk factors, hemoglobin, hematocrit, C-reactive protein, microalbuminuria, atrial fibrillation, glomerular filtration rate,left ventricular ejection fraction and number of exercise training sessions attended, the increased risk of overall (HR 1.10; 95% CI 1.01-1.27; p = 0.039) and cardiovascular (HR 1.13; 95% CI 1.01-1.34; p = 0.036)mortality with increasing RDW values remained significant. The RDW represents an independent predictor of overall and cardiovascular mortality in secondary cardiovascular prevention patients undergoing cardiac rehabilitation.

Sex Differences in Heart Rate Nonlinearity by Multifractal Multiscale Detrended Fluctuation Analysis.

Recent developments of detrended fluctuation analysis (DFA) provide multifractal/multiscale (MFMS) descriptions of the heart rate self-similarity, a promising approach to cardiovascular complexity. However, it is unclear whether the MFMS DFA may also describe the nonlinear components of heart rate variability. Our aim is to define MFMS DFA indices for quantifying the short-term and long-term degree of the heart-rate nonlinearity and to apply these indices to detect possible sex-related differences.We recorded the inter-beat-interval (IBI) series in 42 male and in 42 female healthy participants sitting at rest for about 2 hours. For each series j, we generated 100 phase-randomized surrogate series. We applied the MFMS DFA to estimate the self-similarity coefficients α over scales τ between 8 and 512 s and moment orders q between -5 and +5, obtaining coefficients for the original series, αO,j (q, τ), and for each surrogate, αi,j (q, τ) with 1≤i≤100. We first evaluated πj(q, τ), percentile of αi,j (q, τ) distribution in which was αO,j (q, τ). Then we calculated the percentages of scales where πj(q, τ) was <5% for 8≤τ≤16 s (short-term nonlinearity index NL1(q)) and for 16≤τ≤512 s (long-term nonlinearity index NL2(q)). We found that NL1(q) was generally greater than 50% at all q≥0 but q=2 (i.e., moment order of the monofractal DFA), while at q<0 it was high in males only, with significant sex differences at q=-1 and q=-2. Results indicate that the multifractal DFA may highlight nonlinear heart-rate components at the short scales that are not revealed by the traditional monofractal DFA and that appear related to gender differences.Clinical Relevance- This supports the use of MFMS DFA to integrate the linear information from traditional spectral methods of heart rate variability in clinical studies aimed at improving the stratification of the cardiovascular risk.

In-hospital day-by-day systolic blood pressure variability during rehabilitation: a marker of adverse outcome in secondary prevention after myocardial revascularization.

OBJECTIVE: Although it is known that increased visit-to-visit or home day-by-day variability of blood pressure (BP), independently of its average value, results in an increased risk of cardiovascular events, the prognostic value of in-hospital day-by-day BP variability in secondary cardiovascular prevention has not yet been established. METHODS: We studied 1440 consecutive cardiac patients during a cardiovascular rehabilitation program of about 12 days after coronary artery bypass graft (CABG) and/or valve surgery. We measured auscultatory BP at the patient bed in each rehabilitation day twice, in the morning and the afternoon. We correlated SBP variability assessed as standard deviation (SBP-SD) and coefficient of variation (SBP-CoV) of the daily measures with overall mortality, cardiovascular mortality and major adverse cardiocerebrovascular events (MACCEs) after a mean follow-up of 49 months by Cox hazard analysis. RESULTS: In our patients (age 68 ±â€Š11years, 61% hypertensive patients) the ranges of SBP-SD tertiles were: 4.1-9.1, 9.2-11.5 and 11.6-24.5 mmHg. Fifty-five percent of the patients underwent CABG, 33% underwent valve surgery, 12% both CABG and valve surgery. In CABG patients, the highest SBP-SD tertile showed the highest overall mortality, cardiovascular mortality and MACCEs (P < 0.01). Results remained significant after multivariate analysis adjusting for age, sex, mean SBP, BMI, hypertension, hyperlipidaemia, and diabetes. No association between SBP-SD and mortality or MACCEs was found in valve surgery patients. CONCLUSION: In-hospital day-by-day SBP variability predicts mortality and MACCEs in CABG patients, possibly representing a target during rehabilitation and treatment in secondary cardiovascular prevention.

Cardiopulmonary exercise testing for personalized job reintegration after acute cardiovascular attacks: a pilot cross-sectional study.

BACKGROUND: Cardiovascular diseases (CVD), particularly the ischemic heart disease, are a growing public health issue. In addition, the return to work after an acute cardiovascular attack represents a complex challenge. OBJECTIVES: To evaluate utility and safety of cardiopulmonary exercise testing (CPET), particularly performed "on site", to promote a return to work in line with the residual working capacity. METHODS: Fifty-nine workers affected by a major cardiovascular event, aged 18-63 years, have been enrolled between 2015 and 2018. All the patients underwent a cardiopulmonary exercise testing (CPET) in outpatient clinic. Eleven workers also underwent the "on site" CPET, recorded during their working activities. RESULTS: Outpatient clinic CPET outcomes (i.e. normal, mild impairment or moderate/severe impairment of cardiopulmonary function) were associated with the subjective perception of workers' health status after returning to work. The "on site" CPET was found to be safe and reliable to promote a personalized return to work of patients. In 7 out of 11 patients, the values of O2 consumption (VO2) during the working activity were higher than 40% of VO2 max as obtained from laboratory CPET. CONCLUSIONS: This study provides evidence for safety and usefulness of "on site" CPET for a personalized statement of fitness for work. This may facilitate the job retention of patients characterized by a high risk of unnecessary job loss. The use of CPET represents a first step of energy expenditure evaluation associated with specific working tasks.

Sodium Intake and Hypertension.

The close relationship between hypertension and dietary sodium intake is widely recognized and supported by several studies. A reduction in dietary sodium not only decreases the blood pressure and the incidence of hypertension, but is also associated with a reduction in morbidity and mortality from cardiovascular diseases. Prolonged modest reduction in salt intake induces a relevant fall in blood pressure in both hypertensive and normotensive individuals, irrespective of sex and ethnic group, with larger falls in systolic blood pressure for larger reductions in dietary salt. The high sodium intake and the increase in blood pressure levels are related to water retention, increase in systemic peripheral resistance, alterations in the endothelial function, changes in the structure and function of large elastic arteries, modification in sympathetic activity, and in the autonomic neuronal modulation of the cardiovascular system. In this review, we have focused on the effects of sodium intake on vascular hemodynamics and their implication in the pathogenesis of hypertension.

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 ±â€¯26 months 939 subjects with available QRS and T axis data; mean age was 68 ±â€¯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.

Risk stratification in secondary cardiovascular prevention.

Although a substantial reduction in post-myocardial infaction mortality has been obtained in recent decades, one-year mortality rates are still high and 20% of patients who survive after the acute phase suffer a second cardiovascular event in the first year. In the setting of secondary cardiovascular prevention, the long-term cardiovascular risk stratification represents one of the most interesting and charming challenge for physician. Lifestyle changes and long-term control of traditional cardiovascular risk factors remain the cornerstone of secondary cardiovascular prevention and continue to offer the most powerful prognostic implications in the field of preventive cardiology with strong evidence of reduction in mortality and morbidity. In this regard, clinical, ECG, echocardiographic, cardiopulmonary exercise test data as well as biochemical markers of adverse prognosis are useful tool to identify patients at risk of developing future cardiovascular events. An integrated approach based on the analysis of all cardiovascular risk factors (traditional and emerging) along with instrumental and laboratory data represents the better way to predict prognosis in secondary cardiovascular prevention.

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.

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.

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.

Multifractal multiscale dfa of cardiovascular time series: Differences in complex dynamics of systolic blood pressure, diastolic blood pressure and heart rate.

The heart-rate fractal dynamics can be assessed by Detrended Fluctuation Analysis (DFA), originally proposed for estimating a short-term coefficient, α1 (for scales n≤12 beats), and a long-term coefficient α2 (for longer scales). Successively, DFA was extended to provide a multiscale α, i.e. a continuous function of n, α(n); or a multifractal α, i.e. a function of the order q of the fluctuations moment, α(q). Very recently, a multifractal-multiscale DFA was proposed for evaluating multifractality at different scales separately. Aim of this work is to describe the multifractal multiscale dynamics of three cardiovascular signals often recorded beat by beat in physiological and clinical settings: systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse interval (PI, inverse of the heart rate). We recorded SBP, DBP and PI for at least 90' in 65 healthy volunteers at rest, and adapted the previously proposed multifractal multiscale DFA to estimate α as function of the temporal scale, τ, between 15 and 450 s, and of the order q, between -5 and 5. We report, for the first time: 1) substantial differences among α(q,τ) surfaces of PI, SBP and DBP; 2) a strong dependency of the degree of multifractality on the temporal scale.

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.

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 ß-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.

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.

Prognostic value of new left atrial volume index severity partition cutoffs after cardiac rehabilitation program in patients undergoing cardiac surgery.

BACKGROUND: Previous studies showed that left atrial enlargement is an independent marker of adverse outcomes in both primary and secondary cardiovascular prevention. However, no data are available on long-term outcomes in patients undergoing valve surgery and/or coronary artery by-pass graft (CABG) surgery. Aim of the study was to evaluate long-term prognostic role of left atrial volume index (LAVi) after cardiac surgery, using the cutoff values recently proposed by the European Association of Cardiovascular Imaging and American Society of Echocardiography. METHODS: We created a retrospective registry of 1703 consecutive patients who underwent cardiovascular rehabilitation program after cardiac surgery, including CABG, valve surgery and valve + CABG surgery. LAVi was calculated as ratio of left atrium volume to body surface area, in ml/m(2) at discharge; 563 patients with available LAVi data were included in the study. RESULTS: In the whole population LAVi was 36 ± 14 ml/m(2) (mean ± SD) and the follow-up time was 5 ± 1.5 years. Increased LAVi (>34 ml/m(2)) predicted major adverse cardiovascular and cerebrovascular events (MACCEs) (HR = 2.1; CI95 %: 1.4-3.1; p < 0.001) and cardiovascular mortality (HR = 2.2; CI95 %: 1.0-4.5; p = 0.032). An increased LAVi remained MACCEs predictor after adjustement for age, gender, diabetes, atrial fibrillation at discharge, echocardiographic E/A ratio and left ventricular ejection fraction (HR = 1.8; CI95 %: 1.0-3.0; p = 0.036). When the study population was split according to increasing LAVi values, left atrium enlargement resulted a predictor of progressively worse adverse outcome. CONCLUSIONS: LAVi is a predictor of long-term adverse cardiovascular outcome after cardiac surgery, even after correction for main clinical and echocardiographic variables. The recently recommended LAVi severity cutoffs appear adequate to effectively stratify outcome in patients undergoing rehabilitation after cardiac surgery.