Mortality and Morbidity in Adults With Rheumatic Heart Disease.

Importance: Rheumatic heart disease (RHD) remains a public health issue in low- and middle-income countries (LMICs). However, there are few large studies enrolling individuals from multiple endemic countries. Objective: To assess the risk and predictors of major patient-important clinical outcomes in patients with clinical RHD. Design, Setting, and Participants: Multicenter, hospital-based, prospective observational study including 138 sites in 24 RHD-endemic LMICs. Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary outcomes were cause-specific mortality, heart failure (HF) hospitalization, stroke, recurrent rheumatic fever, and infective endocarditis. This study analyzed event rates by World Bank country income groups and determined the predictors of mortality using multivariable Cox models. Results: Between August 2016 and May 2022, a total of 13 696 patients were enrolled. The mean age was 43.2 years and 72% were women. Data on vital status were available for 12 967 participants (94.7%) at the end of follow-up. Over a median duration of 3.2 years (41 478 patient-years), 1943 patients died (15% overall; 4.7% per patient-year). Most deaths were due to vascular causes (1312 [67.5%]), mainly HF or sudden cardiac death. The number of patients undergoing valve surgery (604 [4.4%]) and HF hospitalization (2% per year) was low. Strokes were infrequent (0.6% per year) and recurrent rheumatic fever was rare. Markers of severe valve disease, such as congestive HF (HR, 1.58 [95% CI, 1.50-1.87]; P < .001), pulmonary hypertension (HR, 1.52 [95% CI, 1.37-1.69]; P < .001), and atrial fibrillation (HR, 1.30 [95% CI, 1.15-1.46]; P < .001) were associated with increased mortality. Treatment with surgery (HR, 0.23 [95% CI, 0.12-0.44]; P < .001) or valvuloplasty (HR, 0.24 [95% CI, 0.06-0.95]; P = .042) were associated with lower mortality. Higher country income level was associated with lower mortality after adjustment for patient-level factors. Conclusions and Relevance: Mortality in RHD is high and is correlated with the severity of valve disease. Valve surgery and valvuloplasty were associated with substantially lower mortality. Study findings suggest a greater need to improve access to surgical and interventional care, in addition to the current approaches focused on antibiotic prophylaxis and anticoagulation.

Rivaroxaban in Rheumatic Heart Disease-Associated Atrial Fibrillation.

BACKGROUND: Testing of factor Xa inhibitors for the prevention of cardiovascular events in patients with rheumatic heart disease-associated atrial fibrillation has been limited. METHODS: We enrolled patients with atrial fibrillation and echocardiographically documented rheumatic heart disease who had any of the following: a CHA2DS2VASc score of at least 2 (on a scale from 0 to 9, with higher scores indicating a higher risk of stroke), a mitral-valve area of no more than 2 cm2, left atrial spontaneous echo contrast, or left atrial thrombus. Patients were randomly assigned to receive standard doses of rivaroxaban or dose-adjusted vitamin K antagonist. The primary efficacy outcome was a composite of stroke, systemic embolism, myocardial infarction, or death from vascular (cardiac or noncardiac) or unknown causes. We hypothesized that rivaroxaban therapy would be noninferior to vitamin K antagonist therapy. The primary safety outcome was major bleeding according to the International Society of Thrombosis and Hemostasis. RESULTS: Of 4565 enrolled patients, 4531 were included in the final analysis. The mean age of the patients was 50.5 years, and 72.3% were women. Permanent discontinuation of trial medication was more common with rivaroxaban than with vitamin K antagonist therapy at all visits. In the intention-to-treat analysis, 560 patients in the rivaroxaban group and 446 in the vitamin K antagonist group had a primary-outcome event. Survival curves were nonproportional. The restricted mean survival time was 1599 days in the rivaroxaban group and 1675 days in the vitamin K antagonist group (difference, -76 days; 95% confidence interval [CI], -121 to -31; P<0.001). A higher incidence of death occurred in the rivaroxaban group than in the vitamin K antagonist group (restricted mean survival time, 1608 days vs. 1680 days; difference, -72 days; 95% CI, -117 to -28). No significant between-group difference in the rate of major bleeding was noted. CONCLUSIONS: Among patients with rheumatic heart disease-associated atrial fibrillation, vitamin K antagonist therapy led to a lower rate of a composite of cardiovascular events or death than rivaroxaban therapy, without a higher rate of bleeding. (Funded by Bayer; INVICTUS ClinicalTrials.gov number, NCT02832544.).

Cardiovascular autonomic responses during head-up tilt test in newly diagnosed type 2 diabetes.

BACKGROUND: Autonomic dysfunction is commonly observed in patients with long-standing type 2 diabetes. Previous studies have confirmed the value of both subjectively assessed symptoms and objective measurements of autonomic nervous system function in diagnosing cardiovascular autonomic neuropathy. However, the head-up tilt test (HUTT) has been rarely used to investigate cardiovascular autonomic responses in subjects with high risk of newly diagnosed type 2 diabetes (nT2D). OBJECTIVE: To evaluate autonomic cardiovascular responses through passive orthostatic challenge along the diabetes continuum. METHODS: The study population was stratified as normoglycemic (n = 16), prediabetes (n = 20), and nT2D (n = 20). The prevalence of orthostatic intolerance and autonomic cardiovascular responses was evaluated with the Task Force Monitor during a 30-min passive HUTT. Spectral indices of heart rate and blood pressure variability and baroreceptor effectiveness index (BEI) were calculated through the HUTT. BEI was obtained by the sequence method. RESULTS: There were no differences in the prevalence of orthostatic intolerance or in the indices of heart rate and blood pressure variability among the three groups of study. The BEI was attenuated in the nT2D group in supine rest and throughout HUTT compared with normoglycemic and prediabetes groups. The multivariable linear regression analysis showed that BEI was associated with fasting glucose (ß = - 0.52, p < 0.001) and HbA1c (ß = - 0.57, p  < 0.001) independently of cardiovascular risk factors. CONCLUSION: Cardiovascular autonomic neuropathy, expressed as blunted BEI, is the only abnormal autonomic nervous test detected in nT2D, and it was independently associated with fasting glucose and HbA1c values.

Post-Acute COVID-19 Symptoms, a Potential Link with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A 6-Month Survey in a Mexican Cohort.

The aim of this study was to describe the clinical evolution during 6 months of follow-up of adults recovered from COVID-19. We tried to determine how many met the definition of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). A total of 130 patients (51.0 ± 14 years, 34.6% female) were enrolled. Symptoms were common, participants reported a median number of 9 (IQR 5-14) symptoms. Fatigue was the most common symptom (61/130; 46.9%). Patients with fatigue were older 53.9 ± 13.5 years compared with 48.5 ± 13.3 years in those without fatigue (p = 0.02) and had a longer length of hospital stay, 17 ± 14 days vs. 13 ± 10 days (p = 0.04). There was no difference in other comorbidities between patients with fatigue and those without it, and no association between COVID-19 severity and fatigue. After multivariate adjustment of all baseline clinical features, only age 40 to 50 years old was positively associated with fatigue, OR 2.5 (95% CI 1.05-6.05) p = 0.03. In our survey, only 17 (13%) patients met the Institute of Medicine's criteria for "systemic exertion intolerance disease," the new name of ME/CFS. In conclusion, in some patients, the features of post-acute COVID-19 syndrome overlap with the clinical features of ME/CFS.

Early Cerebral Hypoperfusion in Patients with Orthostatic Intolerance Without Tachycardia During Head-Up Tilt Test is Independent of Vasovagal Response.

BACKGROUND: Cerebral hypoperfusion before syncope has been shown in patients with chronic orthostatic intolerance (OI) without tachycardia, but it is unknown if an initial decrease of cerebral blood flow velocity (CBFv) could be related to the vasovagal response (VVR) to head-up tilt test (HUTT). OBJECTIVE: The objective of the study was to compare cardiovascular, cerebrovascular, and autonomic variables during HUTT in OI patients with or without a VVR. METHODS: We included 74 subjects (58% female, mean age 33 ± 12 years) who underwent a 30-min HUTT and were divided into three groups: OI with VVR positive (VVR+), OI without VVR negative (VVR-), and asymptomatic healthy subjects with negative HUTT (control group). Cardiovascular, cerebrovascular, and autonomic variables were assessed beat-to-beat during HUTT with a Task Force monitor and a trans-cranial Doppler. Mean values were evaluated at baseline and throughout the first 10 min of tilting. RESULTS: Cardiovascular variables were similar in the three groups. Systolic, diastolic, and mean CBFv were similar in VVR+ and VVR-, but both groups had lower CBFv than the control group. Systolic and diastolic CBFv decreased from baseline since min 1 in VVR+ and VVR- and since min 5 in the control group. The mean CBFv had a significant decrease since min 1 compared to baseline in all groups. Spectral indices of heart rate and blood pressure variability showed a similar autonomic response to HUTT in all groups. CONCLUSION: Patients with chronic OI without tachycardia have early postural cerebral hypoperfusion, regardless of the VVR during HUTT.

Transient Orthostatic Hypertension During Head-Up Tilt Test in Young Adults: A Phenotype of Blood Pressure Variability.

PURPOSE: The mechanisms underlying orthostatic hypertension (OHT) remain poorly understood. The authors evaluated the cardiovascular, cerebrovascular dynamics, and autonomic response to head-up tilt test (HUTT) in young adults with symptoms of orthostatic intolerance and transient OHT. METHODS: Forty-four female subjects were included (34 ± 13 years old) and categorized in three groups after a 30-minute 70° passive HUTT: symptomatic patients with OHT (surge of systolic blood pressure ≥20 mm Hg for at least 5 minutes at any given time during HUTT), orthostatic intolerance (symptomatic patients without orthostatic blood pressure changes), and healthy asymptomatic control subjects. RESULTS: At baseline, OHT patients had lower systolic blood pressure than orthostatic intolerance patients (103 ± 8 vs. 116 ± 10 mm Hg, p < 0.01) and lower baroreflex sensitivity than control subjects (15.8 ± 8.3 vs. 27.1 ± 11.7 ms/mm Hg, p = 0.01). On tilt, cardiac output decreased in OHT patients from 6.1 ± 1.4 L/minute during baseline to 5.2 ± 0.8 L/minute after 10 minutes of HUTT (p = 0.01). In OHT patients at 30 minutes of HUTT, sympathetic efferent heart activity was higher (77.4 ± 14.9 normalized units or nu) than orthostatic intolerant patients (63.5 ± 11.8 nu, p = 0.02) and control subjects (65.8 ± 11.2 nu, p = 0.05). Cerebrovascular resistance in OHT was higher than control subjects after 30 minutes (2.2 ± 0.8 vs. 1.6 ± 0.3 cm/second, respectively, p = 0.02). CONCLUSIONS: This study demonstrates that transient OHT can occur at any given time during HUTT. These patients exhibit a decrease in cardiac output and a hyperadrenergic response to tilt.

Anticoagulation Therapy by Age and Embolic Risk for Nonvalvular Atrial Fibrillation in Mexico, an Upper-Middle-Income Country: The CARMEN-AF Registry.

Background: Documenting the patterns of oral anticoagulation therapy (OAT) is essential to prevent thromboembolic complications of nonvalvular atrial fibrillation (NVAF). Objective: To report the patterns of OAT according to age and thromboembolic risk in patients included in CARMEN-AF, a nationwide registry of NVAF in Mexico, an upper middle-income country. Material and methods: There were 1,423 consecutive patients ≥18 years old and with at least one thromboembolic risk factor enrolled in the CARMEN-AF Registry at their regular clinical visit during a three-year period. They were analyzed according to 1) age, 2) AF type, and 3) CHA2DS2-VASc score. Results: Overall, 16.4% of patients did not receive antithrombotic treatment, 19.4% received antiplatelet drugs (APD), 29.2% vitamin K antagonists (VKA), and 34.6% direct oral anticoagulants (DOAC). With increasing age, the proportion of subjects treated with VKA decreased significantly from 36.2% in subjects <65 years to 22.5% in those ≥75 years old (P <0.0001). Concomitantly, an increase in both APD and no antithrombotic treatment was observed with increasing age. DOAC were prescribed equally among all age groups (34.2% in <65, 36.0% in 65-74, and 33.9% in ≥75). According to the type of AF, VKA use was more common in patients with permanent AF (32.7%). A lower use of DOAC was observed in high thromboembolic risk subjects (33.6% in CHA2DS2-VASc ≥2) compared with the moderate risk group (41% in CHA2DS2-VASc = 1). Conclusions: VKA use for NVAF in Mexico decreased in relation to increasing age. The proportion of DOAC therapy was the same in all age groups. Nevertheless, elderly patients with high thromboembolic risk received a suboptimal thromboprophylaxis. These data could help to improve gaps in the implementation of global guidelines. Clinical trial registration: http://www.clinicaltrials.gov. Unique identifier: NCT02334852. Highlights: CARMEN-AF is a nationwide multi-centric registry seeking to bridge the data gap on anticoagulation therapy for NVAF in Mexico.Elderly patients are more prone to receive suboptimal OAT for NVAF.DOAC were less frequently used in high thromboembolic risk patients (CHA2DS2-VASc ≥2).

Similar Cerebral Blood Flow and Autonomic Responses to Upright Tilt Test in Adult Patients With Different Hemodynamic Mechanisms Leading to Reflex Syncope.

PURPOSE: Although the underlying mechanisms of reflex syncope remain under debate, there is evidence that it results from decreased cardiac output related to splanchnic blood pooling or a fall in systemic vascular resistance. The aim was to evaluate the response of cerebrovascular and autonomic variables to passive orthostatic challenge in adult patients with different mechanisms leading to reflex syncope. METHODS: The study included 30 subjects (66% women, mean age 34 ± 14 years) who suffered a hemodynamic collapse during a drug-free head-up tilt test. They were categorized into three groups according to their hemodynamic cardiovascular response during the head-up tilt test: (1) reduced cardiac output (patients, n = 10), (2) reduced systemic vascular resistance (patients, n = 10), and (3) reduced cardiac output and systemic vascular resistance, (reduced cardiac output reduced systemic vascular resistance patients, n = 10). Cardiovascular and cerebrovascular dynamics, as well as autonomic variables, were noninvasively assessed during the head-up tilt test and median values were calculated at baseline and throughout the three phases of the tilt. RESULTS: At baseline, the reduced systemic vascular resistance group had lower cardiac output and higher total peripheral resistance index and a sustained increase of heart rate throughout the head-up tilt test in comparison to the other groups. Cerebrovascular dynamics and autonomic variables showed no difference among groups throughout the test. Compared with baseline, these variables had similar percentual change during the orthostatic challenge. CONCLUSIONS: Although different cardiovascular hemodynamic mechanisms of reflex syncope exist in adult patients, cerebrovascular hypoperfusion and autonomic modulation occur to a similar extent.

Gender differences and management of stroke risk of nonvalvular atrial fibrillation in an upper middle-income country: Insights from the CARMEN-AF registry.

BACKGROUND: Atrial Fibrillation (AF) is associated with an increased risk of stroke and systemic embolism. Several studies have suggested that female AF patients could have a greater risk for stroke. There is scarce information about clinical characteristics and use of antithrombotic therapies in Latin American patients with nonvalvular AF. OBJECTIVE: To describe the gender differences in clinical characteristics, thromboembolic risk, and antithrombotic therapy of patients with nonvalvular AF recruited in Mexico, an upper middle-income country, into the prospective national CARMEN-AF Registry. METHODS: A total of 1423 consecutive patients, with at least one thromboembolic risk factor were enrolled in CARMEN-AF Registry during a three-year period (2014-2017). They were categorized according to Gender. RESULTS: Overall, 48.6% were women, mean age 70 ±â€¯12 years. Diabetes, smoking, alcoholism, non-ischemic cardiomyopathy, coronary artery disease, and obstructive sleep apnea were higher in men. Most women were found with paroxysmal AF (40.6%), and most men with permanent AF (44.0%). No gender differences were found in the use of vitamin K antagonists (VKA) (30.5% in women vs. 28.0% in men). No gender differences were found in the use of direct oral anticoagulants (DOAC) (33.8% women vs 35.4% men). CONCLUSIONS: CARMEN-AF Registry demonstrates that in Mexico, regardless of gender, a large proportion of patients remain undertreated. No gender differences were found in the use of VKA or DOAC.

Temporal cardiovascular causality during orthostatic stress by extended partial directed coherence.

The aim of this study was to investigate the temporal dynamic behavior of cardiovascular interactions between heart period and systolic blood pressure during a 20-min head-up tilt test at 70° in young women with orthostatic intolerance compared to healthy women. Methods included the lagged and extended partial directed coherence applied to short-term windows shifted by 5 seconds, extracted from a multivariate set of cardiovascular and respiratory time series. Findings revealed significantly increased information flow (p <; 0.01) in patients from: a) heart period to blood pressure during supine position which subsequently decreased and b) blood pressure to heart period during the progression of orthostatic phase. Controls developed balanced cardiovascular interactions with smaller information flows than patients.

Cardiovascular variability in young male and female subjects in health and orthostatic intolerance.

The aim of this study was to investigate the effect of head-up tilt (HUT) test on male and female young patients, diagnosed with orthostatic intolerance (OI), in comparison to male and female healthy subjects. Twenty seven OI patients (21 women, 6 men) and 26 age-matched healthy subjects (13 women, 13 men) were enrolled in a 70° HUT test. In addition to hemodynamic variables, cardiovascular and respiratory parameters were determined using linear and nonlinear methods to analyze heart rate (HRV) and blood pressure variability (BPV). During the complete test, HRV was lower in healthy men than in female controls. Decreased HRV and increased BPV were observed in female patients compared to healthy women. Furthermore, systolic BPV was increased in male and female patients. However, linear (rmssd) and nonlinear (plvar2) parameters indicated that diastolic BPV decreased in male patients during orthostatic phase, but remained unchanged in female patients. Findings indicated gender dependent mechanisms for the regulation of diastolic blood pressure during orthostatic stress in patients.

Study of impaired cardiovascular and respiratory coupling during orthostatic stress based on joint symbolic dynamics.

The present study investigates the instantaneous coupling among the cardiac, vascular, and respiratory systems, using the heart rate, respiration, and systolic and diastolic blood pressure variability in 12 healthy and 16 vasovagal syncope female subjects during a head-up tilt (HUT) testing protocol at 70° This study contributes to the coupling analysis by using a nonlinear joint symbolic dynamics (JSD) in a high-temporal resolution scheme, based on 5 min segments of the time series that are shifted every minute. For each segment, a bivariate JSD matrix was constructed to obtain global and local coupling indices in accordance to Shannon's entropy and the probability of occurrence of various bivariate words, respectively. The novel approach revealed important findings in the coupling dynamics of the systems, thus allowing the detection of group differences during the early orthostatic phase, and during the HUT test, before the occurrence of any pre-syncopal symptoms. In patients, the global indices indicated a significant decrease of cardiovascular coupling, starting at 10 min after the tilt-up, manifested by reduced baroreflex sensitivity and cardiorespiratory coupling that was initiated 8 min after the onset of the orthostatic phase (OP). A decreased autonomic control on cardiovascular-respiratory couplings was further evidenced by increased alterations of the JSD indices during the OP compared to the supine position in patients compared to controls. Furthermore, findings based on local indices demonstrated that female patients showed reductions and disengagements in cardiovascular (p < 0.001) and cardiorespiratory (p < 0.01) couplings, as early as the first 5 min and during the complete OP.

Multivariate symbolic dynamics for analysis of respiratory-cardiovascular interactions.

In this work, a nonlinear method to study multivariate interactions, called multivariate symbolic dynamics (MSD), was introduced. The usefulness of this technique was studied on respiratory-cardiovascular data from young women with vasovagal syncope (VVS) and from healthy subjects. The study included 16 female patients diagnosed with VVS and 24 age-matched healthy subjects (12 women). All subjects were enrolled in a head-up tilt (HUT) test, breathing normally, including 5 min of supine position and 18 to 28 min of 70° orthostatic phase. The MSD parameters were dynamically obtained for 5-min windows shifted by 1 min during HUT test. In supine position there were no considerable differences. During orthostatic phase, parameters from MSD showed a highly significantly (p=0.00005) increased occurrence of impaired respiratory-cardiovascular interactions in female patients susceptible to vasovagal syncope. This study provided promising results for a new multivariate method to investigate respiratory-cardiovascular interactions.

The World Heart Federation Roadmap for Nonvalvular Atrial Fibrillation.

BACKGROUND: The World Heart Federation has undertaken an initiative to develop a series of Roadmaps to promote development of national policies and health systems approaches, and to identify potential roadblocks on the road to effective prevention, detection, and management of cardiovascular disease in low-and middle-income countries (LMICs) and develop strategies for overcoming these. This Roadmap focuses on atrial fibrillation (AF). AF is the most common, clinically significant arrhythmia and, among other clinical outcomes, is associated with increased risk of stroke. METHODS: Development of this Roadmap included a review of published guidelines and research papers, and consultation with an expert committee comprising experts in clinical management of AF and health systems research in LMICs. The Roadmap identifies 1) key interventions for detection, diagnosis, and management of AF; 2) gaps in implementation of these interventions (knowledge-practice gaps); 3) health system roadblocks to implementation of AF interventions in LMICs; and 4) potential strategies for overcoming these. RESULTS: More research is needed on determinants and primary prevention of AF. Knowledge-practice gaps for detection, diagnosis, and management of AF are present worldwide, but may be more prominent in LMICs. Potential barriers to implementation of AF interventions include long distances to health facilities, shortage of health care professionals with training in AF, including interpretation of ECG, unaffordability of oral anticoagulants for patient households, reluctance on the part of physicians to initiate oral anticoagulant (OAC) therapy, and lack of awareness of the importance of persistent adherence to OAC therapy. Potential solutions include training of nonphysician health workers and pharmacists in pulse-taking, use of telemedicine technologies to transmit electrocardiogram results, engagement of nonphysician health workers in OAC therapy adherence support, and country-specific support and education programs for noncardiologist health care professionals. CONCLUSIONS: AF affects millions of people worldwide and, left untreated, increases the risk and severity of stroke and heart failure. Although guidelines for the detection, diagnosis, and management of AF exist, there are gaps in implementation of these guidelines globally, and in particular in LMICs. This Roadmap identifies some potential solutions that may improve AF outcomes in LMICs but require further evaluation in these settings.

Men and women should be separately investigated in studies of orthostatic challenge due to different gender-related dynamics of autonomic response.

In studies of autonomic regulation during orthostatic challenges only a few nonlinear methods have been considered without investigating the effect of gender in young controls. Especially, the temporal development of the autonomic regulation has not yet been explicitly analyzed using short-term segments in supine position, transition and orthostatic phase (OP). In this study, nonlinear analysis of cardiovascular and respiratory time series was performed to investigate how nonlinear indices are dynamically changing with respect to gender during orthostatic challenges. The analysis was carried out using shifted short-term segments throughout a head-up tilt test in 24 healthy subjects, 12 men (26 ± 4 years) and 12 age-matched women (26 ± 5 years), at supine position and during OP at 70°. The nonlinear methods demonstrated statistical differences in the autonomic regulation between males and females. Orthostatic stress caused significantly decreased heart rate variability due to increased sympathetic activity mainly in men, already at the beginning and during the complete OP, revealed by (a) increased occurrence of specific word types with constant fluctuations as pW111 from symbolic dynamics, (b) augmented fractal correlation properties by the short-term index alpha1 from detrended fluctuation analysis, (c) increased slope indices (21ati and 31ati) from auto-transinformation and (d) augmented time irreversibility indices demonstrating more temporal asymmetries and nonlinear dynamics in men than in women. After tilt-up, both men and women increased their sympathetic activity but in a different way. Time-dependent gender differences during orthostatic challenge were shown directly between men and women or indirectly comparing baseline and different temporal stages of OP. The proposed dynamical study of autonomic regulation has the advantage of screening the fluctuations of the sympathetic and vagal activities that can be quantified by the temporal behavior of nonlinear indices. The findings in this paper strongly suggest the need for gender separation in studies of the dynamics of autonomic regulation during orthostatic challenge.

Orthostatic stress causes immediately increased blood pressure variability in women with vasovagal syncope.

The cardiovascular and respiratory autonomic nervous regulation has been studied mainly by hemodynamic responses during different physical stressors. In this study, dynamics of autonomic response to an orthostatic challenge was investigated by hemodynamic variables and by diverse linear and nonlinear indices calculated from time series of beat-to-beat intervals (BBI), respiratory cycle duration (RESP), systolic (SYS) and diastolic (DIA) blood pressure. This study included 16 young female patients (SYN) with vasovagal syncope and 12 age-matched female controls (CON). The subjects were enrolled in a head-up tilt (HUT) test, breathing normally, including 5min of baseline (BL, supine position) and 18min of 70° orthostatic phase (OP). To increase the time resolution of the analysis the time series were segmented in five-minute overlapping windows with a shift of 1min. Hemodynamic parameters did not show any statistical differences between SYN and CON. Time domain linear analysis revealed increased respiratory frequency and increased blood pressure variability (BPV) in patients during OP meaning increased sympathetic activity and vagal withdrawal. Frequency domain analysis confirmed a predominance of sympathetic tone by steadily increased values of low over high frequency power in BBI and of low frequency power in SYS and DIA in patients during OP. The nonlinear analysis by symbolic dynamics seemed to be highly suitable for differentiation of SYN and CON in the early beginning of OP, i.e., 5min after tilt-up. In particular the index SYS_plvar3 showed less patterns of low variability in patients reflecting a steadily increase in both BPV and sympathetic activity. The proposed dynamical analysis could lead to a better understanding of the temporal underlying mechanisms in healthy subjects and patients under orthostatic stress.

Delta space plot analysis of cardiovascular coupling in vasovagal syncope during orthostatic challenge.

In this work, a graphical method to study cardiovascular coupling, called delta space plot analysis (DSPA), was introduced. The graphical representation is susceptible to be parameterized in shape and orientation. The usefulness of this technique was studied on cardiovascular data from patients with vasovagal syncope (VVS) and from controls. The study included 15 female patients diagnosed with VVS and 11 age-matched healthy female subjects. All subjects were enrolled in a head-up tilt (HUT) test, breathing normally, including 5 minutes of supine position (baseline) and 18 minutes of 70° orthostatic phase. The DSPA parameters were obtained at different times during the HUT test, i.e., at baseline, early (first 5 min) and late (10-15 min) orthostatic phases. In baseline there were no considerable differences between female controls and female patients. During the late orthostatic phase, parameters from DSPA showed highly significantly (p=0.000003) reduced cardiovascular coupling in patients. Findings indicated a loss of control on cardiovascular coupling in female patients susceptible to vasovagal syncope during orthostatic challenge. In addition, this study provided promising results for a new graphical method to investigate cardiovascular coupling.

Temporal analysis of cardiac autonomic regulation during orthostatic challenge by short-term symbolic dynamics.

The gradual shift of cardiac autonomic regulation toward sympathetic predominance and vagal withdrawal during graded head-up tilt test in young controls has been demonstrated by parameters from symbolic dynamics obtained from short-term heart rate variability (HRV) analysis. In this study, the influence of gender and vasovagal syncope (VVS) on the autonomic response to an orthostatic challenge was investigated by HRV analysis using short-term symbolic dynamics (STSD). This study included 24 healthy young subjects (12 males; 12 age-matched females) and 16 female patients diagnosed with VVS. All subjects were enrolled in a head-up tilt (HUT) test, breathing normally, including 5 minutes of supine position (baseline) and 20-40 minutes of 70° orthostatic phase. The STSD parameters were obtained following their behavior at different times during the HUT test, i.e., at baseline, early and middle orthostatic phases. Gender differences including increased sympathetic activity in men were already present in baseline and in the middle tilt phase. In baseline there were no differences between female controls and female patients, but parameters from STSD showed highly significantly (p=0.0007) reduced heart rate variability due to increased sympathetic activity in female patients in the middle tilt phase. Furthermore a new nonlinear index for the estimation of sympatho-vagal balance was introduced.

Gender differences in cardiovascular and cardiorespiratory coupling in healthy subjects during head-up tilt test by Joint Symbolic Dynamics.

Gender related-differences in the autonomic regulation of the cardiovascular and cardiorespiratory systems have been studied mainly by hemodynamic responses during different physical stressors. In this study, the influence of gender on the autonomic response to an orthostatic challenge was investigated by obtaining the cardiovascular and cardiorespiratory coupling using the nonlinear technique known as joint symbolic dynamics (JSD) representation. This study includes 24 healthy young subjects. Males (N=12) and age-matched females (N=12) were enrolled in a head-up tilt (HUT) test, breathing normally, including 5 minutes of supine position (baseline) and 25-40 minutes of 70° orthostatic phase. The cardiovascular and cardiorespiratory couplings were obtained at baseline, early and middle orthostatic phases. Although in baseline there were some gender differences, parameters from JSD showed highly significant (p=0.0004) differences in specific cardiovascular coupling patterns in the early tilt phase. Furthermore, JSD analysis revealed that in males, due to increased sympathetic activity, exist a lower degree of cardiovascular coupling accompanied with an increased occurrence of tachycardic patterns. On the other hand, the cardiorespiratory coupling revealed only very few slightly significant differences in all three phases.

[Psychopathology and personality in patients with vasovagal syncope]. / Estudio descriptivo de la personalidad y psicopatología en pacientes con síncope vasovagal.

UNLABELLED: Syncope is characterized by a sudden and brief Loss of the normal state of consciousness (fainting), caused by multiple factors (biological, psychological and social), which consequences can be Lethal if it is not timely diagnosed and treated. These episodes affect the total sphere of the subject (on an individual, work, school, social, and family level). PURPOSE OF THE STUDY: Contribute to the study of vasovagal syncope (WS) patients, describing their personality and psychopathological characteristics. METHOD: Minnesota Multiphasic Personality Inventory (MMPI) was used to evaluate psychopathology in a sample of 30 subjects diagnosed with (WS), attended in the National Institute of Cardiology "lgnacio Chávez", making a descriptive analysis of the complete sample, regarding demographic variables and inventory scores. RESULTS: The scales with higher scores found within these subjects were hypochondriasis (= 67.43), depression (= 69.83), hysteria (= 67.83) among others. CONCLUSIONS: In general, patients with (WS) show significant levels of anxiety and depression, dissatisfaction, bad mood, pessimism, concern, somatic complaints, difficulty to solve problems adaptively, among others. This study remarks the importance of knowing these characteristics to implement treatments that manage this disease properly and may improve patients quality of life, as well as their physical and mental health.