Effects of Multidisciplinary Rehabilitation Enhanced with Neuropsychological Treatment on Post-Acute SARS-CoV-2 Cognitive Impairment (Brain Fog): An Observational Study.

Concentration and memory impairment (named "brain fog") represents a frequent and disabling neuropsychological sequela in post-acute COVID-19 syndrome (PACS) patients. The aim of this study was to assess whether neurocognitive function could improve after a multidisciplinary rehabilitation program enhanced with individualized neuropsychological treatment. A prospective monocentric registry of PACS patients consecutively admitted to our Rehabilitation Unit was created. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive impairment at admission and discharge. A total of sixty-four (64) PACS patients, fifty-six (56) of them with brain fog, were treated with a day-by-day individualized psychological intervention of cognitive stimulation (45 min) on top of a standard in-hospital rehabilitation program. The mean duration of the acute-phase hospitalization was 55.8 ± 25.8 days and the mean in-hospital rehabilitation duration was 30 ± 10 days. The mean age of the patients was 67.3 ± 10.4 years, 66% of them were male, none had a previous diagnosis of dementia, and 66% of the entire sample had experienced severe COVID-19. At admission, only 12% of the patients had normal cognitive function, while 57% showed mild, 28% moderate, and 3% severe cognitive impairment. After psychological treatment, a significant improvement in the MoCA score was found (20.4 ± 5 vs. 24.7 ± 3.7; p < 0.0001) as a result of significant amelioration in the following domains: attention task (p = 0.014), abstract reasoning (p = 0.003), language repetition (p = 0.002), memory recall (p < 0.0001), orientation (p < 0.0001), and visuospatial abilities (p < 0.0001). Moreover, the improvement remained significant after multivariate analysis adjusted for several confounding factors. Finally, at discharge, 43% of the patients with cognitive impairment normalized their cognitive function, while 4.7% were discharged with residual moderate cognitive impairment. In conclusion, our study provides evidence of the effects of multidisciplinary rehabilitation enhanced with neuropsychological treatment on improvement in the cognitive function of post-acute COVID-19 patients.

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.

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.

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.

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.

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.

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.

Road Running After Gastric Bypass for Morbid Obesity: Rationale and Results of a New Protocol.

BACKGROUND: In recent years, the pandemic explosion of obesity has led to the definition of a pre-eminent therapeutic role for bariatric surgery, confining physical activity to a success parameter of surgery rather than a primary prevention measure. The aim of this study is to evaluate the role for aerobic physical activity (road running) in strengthening the metabolic and psychosocial effects of bariatric surgery. METHODS: Ten patients who underwent gastric bypass for morbid obesity were submitted to an intensive program of road running training, aimed at completing a 10.5-km competition in September 2013. Inclusion criteria included age (<50), BMI (<35), suitability for sport activity, and good compliance. A cohort of 10 patients excluded for logistical issues were enrolled as a control group. During the training period, patients were submitted to biometrical, sport performance, cardiopulmonary, metabolic, and psychiatric evaluations. RESULTS: Protocol adherence was 70 %; no physical injury was registered among participants. More than weight loss (BMI 29.3 to 27.1), the runners experienced a redistribution of body mass with significant differences in fat percentage and waist/hip ratio. Participants had a significant running performance improvement and, differently from the controls, a significant amelioration of echocardiographic and cardiopulmonary parameters, predicting a reduction in cardiovascular risk. Psychiatric evaluation underlined a tendency to a reduction in anxiety, depression, and general psychopathology symptoms. CONCLUSIONS: Road running seems to have an important supporting role in boosting bariatric surgery results. The utilization of monitored and regulated training programs represents a fundamental prerequisite to achieving satisfactory results and patient compliance.

The fractal structure of cardiovascular beat-to-beat series described over a broad range of scales: Differences between blood pressure and heart rate, and the effect of gender.

The fractal characteristics of heart rate variability are usually assessed by estimating short- and long-term scale coefficients, α1 and α2, by detrended fluctuation analysis. Recently we extended this approach introducing a temporal spectrum of scale coefficients, α(τ), that describes the deviations of self-similarity from the bi-fractal model at each scale τ. Until now relatively short recordings were considered and α(τ) was characterized only for scales τ<;100 s. Aim of this work is to describe α(τ) of cardiovascular signals extending the range τ by an order of magnitude with respect to previous studies. We considered 2-hour recordings of systolic and diastolic blood pressure (SBP and DBP) and of pulse interval (PI) in 68 volunteers (26 males, 42 females) sitting at rest. The α(τ) spectra were estimated for 5s ≤τ ≤1000s and compared. We found important differences between α(τ) of SBP, DBP and PI. In particular, α(τ) of PI was lower than α(τ) of SBP at all the scales τ, with a relative maximum at τ =26 s and a minimum at τ =300 s that were completely missing in α(τ) of DBP. Significant differences were also found between α(τ) of males and females, probably linked to gender differences in the cardiovascular autonomic tone.

[Groups with volunteers cardiac surgery patients: experience in a cardiovascular rehabilitation department]. / Incontro di gruppo con volontari già cardioperati: esperienza in un reparto di riabilitazione cardiovascolare.

OBJECTIVES: This article aimed to describe a new experience activated inside of a more general psychological approach for patients who underwent cardiac surgery intervention. MATERIAL AND METHODS: The first 100 patients taking part to the groups were subjected to a questionnaire in order to evaluate the satisfaction degree of the meeting. RESULTS: The questionnaire results, showed on the whole a good rating of the meeting. In addition to quantitative results, we express and discuss in this paper some considerations concerning the obtained results. CONCLUSIONS: Preliminary data analysis show that volunteers previously submitted to cardiac surgery seem to offer an important contribution to the psychological support of patients recently undergone cardiac surgery.