Cardiac Dysautonomia Research Articles

Assessment of Heart Rate Variability in Children with Cancer after Elevated Cumulative Anthracycline Dose: A Prospective Study

Objective: Anthracyclines which are the main drug of chemotherapy protocols had cardiotoxicity as the most frequent and well-known side effect. We aimed to evaluate prospectively the heart rate variability with 24-hour Holter electrocardiography (ECG) in children with cancer who treated with anthracycline drugs. Material and Methods: The 24-hour Holter ECG monitoring was performed at the baseline, at time of 120 mg/m 2 and ≥240 mg/m 2 of cumulative anthracycline dose in patients with cancer who treated with anthracycline. The time-domain and frequency-domain measurements of heart rate variability (HRV) were obtained. The patients were classified into three groups as Group1:at baseline (n=54), Group 2:≥120mg/m 2 (n=54), Group 3:≥240mg/m 2 (n=54). Results: The median age was 48 months (range 9-192 months). All types of cancer were 38 patients (70.4%) of acute leukemia, two patients (3.8%) of T lymphoblastic lymphoma, and 14patients (25.8%) of other childhood cancer who treated with anthracycline. However, all heart rate variability parameters were decreased after each increased cumulative anthracycline dose, especially time-domain parameters such as nSDNN index, rMSSD, pNN50, frequency parameters such as LF, HF, and Total power were significantly altered among Group1 and Group 3. LF/HF ratio was also statistically significantly increased in Group 3. According the heart rate parameters, the mean average heart rate, mean minimum heart rate and mean RR were statistically significantly prolonged from Group1 to Group 3. Conclusion: Heart rate variability parameters are a noninvasive technique to demonstrate cardiac autonomic neural dysfunction and early myocardial injury. The 24-hour Holter ECG may be used for detecting early cardiac dysautonomia effect during anthracycline treatment with each elevated 120mg/m 2 anthracycline of cumulative dose.

Association of blood pressure and BMI to corrected QT interval in young adults.

Hypertension is often associated with obesity. Uncontrolled hypertension can lead to uncorrected cardiac dysautonomia that makes cardiac repolarization abnormally prolonged. Modern dietary habits, stress, and bad lifestyle habits make young adults vulnerable to hazards of health. We planned to study the association of body mass index (BMI) and blood pressure (BP) with corrected QT (QTc) intervals in young adults. After obtaining the written informed consent, 171 subjects were randomly selected in the age group of 18-35 years. A general history and physical examination were done before recording the BMI and BP. A 12-lead electrocardiogram was recorded and QTc calculated using Bazett's formula. The values obtained were compared and statistical analysis done. Of the 171 subjects 14.03% were hypertensive. The QTc interval was found to be prolonged in females and it is prolonged with age, BMI, and BP. QTc was significantly increased among the prehypertensive and hypertensive group and with the overweight and (or) obese BMI group compared with the normotensives and normal BMI group suggesting an altered autonomic homeostasis. This warrants lifestyle modification at a younger age to reduce the cardiovascular risk.

Abstract 17124: Severe Bradycardia in Critically Ill Patients With COVID-19

Cardiac manifestations of severe Covid19 infection are still poorly understood. From January to May 2020, 113 consecutive patients were admitted in intensive care units for severe Covid19 and 10 out of them presented an episode of bradycardia. Patients had a median age of 63 years, 6/10 were men, 7/10 were under mechanical ventilation for severe acute respiratory distress syndrome and 4/10 received a veno-venous extracorporeal membrane oxygenation. All bradycardias were due to sinus node bradycardia with a median heart rate of 36 bpm (range 10 - 45 bpm). For 6 patients, bradycardia was persistent and 3 required continuous isoprenaline infusion (Figure, patient A). Bradycardia was sudden for 4 patients and required brief resuscitation maneuvers for one (Figure, patient B) . Patients had normal baseline ECG and echocardiography, except for two patients who were under beta-blockers. For those two patients beta blockers were interrupted several days before bradycardia. A comprehensive review of patient’s files ruled out bradycardia due to drug-drug interactions, myocarditis, hyperkalemia, hypoxia or vagal physical stimulation. Holter ECG was performed for 7 patients: 3 recordings evoked vagal hyperactivity (low mean heart rate and elevated pNN50 / RMSSD, Figure Patient A), 3 others cardiac dysautonomia (SDNN<100ms, Figure Patient B). Amongst these 10 patients, 5 were discharged from ICU among which 2 returned home and five died from covid-19 associated multiple-organ failure. None of them required temporary or permanent cardiac pacing. To conclude, sinus bradycardia occurred commonly in severe Covid19 infection. This highlights the need to monitor cardiac rhythm. Even if the pathophysiology remains unclear, cardiac dysautonomia and vagal hyperactivity could be hypothesized rather than an intrinsic sinus node disease.

Manifestaciones cardiovasculares en el síndrome de Ehlers-Danlos tipo hipermóvil

Introducción.
 En el síndrome de Ehlers-Danlos hipermóvil (SEDHT) hay importante frecuencia de síntomas cardiovasculares, los estudios se han realizado en pacientes diagnosticados con criterios de Brighton. El objetivo de esta investigación fue determinar la frecuencia de síntomas y anomalías ecocardiográficas en población adulta no seleccionada, diagnosticada de SEDHT, en un consultorio de cardiología, con los criterios de la Clasificación Internacional de los síndromes de Ehlers-Danlos (CI), publicada el 2017.
 Métodos. 
 Estudio descriptivo en pacientes diagnosticados de SEDHT, mayores de 12 años, atendidos en consultorio externo de cardiología de San Salvador, El Salvador, entre 2012 y 2019. Se valoraron historia clínica, examen físico, antropometría, score de Beighton, test postural de 10 minutos y ecocardiografía (ECO).
 Resultados.
 Se diagnosticó SEDHT en 57 pacientes, relación de 9:1 entre géneros, predominio femenino; edad promedio 32,3+12,8 años. Se hizo ECO en 93% de sujetos. El síntoma más reportado fue palpitaciones (75,4%), pero había algún síntoma cardiovascular (dolor torácico, disnea, palpitaciones, presíncope o síncope) en 91,2% de casos. Disautonomía (POTS y/o hipotensión/intolerancia ortostática) estaba presentes en 53,6% de pacientes. El prolapso mitral tuvo frecuencia de 13,2%, cambios mixomatosos valvulares en 17% de casos. Un Z score aórtico anormal fue poco frecuente (4 de 53 pacientes, 7,5%). El ecocardiograma mostró al menos una anormalidad en el 26,4% de sujetos.
 Conclusión. 
 En el SEDHT se registra alta frecuencia de síntomas cardíacos, disautonomía y ECO anormal. Se justifica buscar anomalías cardiovasculares cuando se haga diagnóstico de SEDHT; recíprocamente, en pacientes jóvenes con manifestaciones cardiovasculares es conveniente pensar en SEDHT.

Defining Cardiac Dysautonomia - Different Types, Overlap Syndromes; Case-based Presentations.

The cardiovascular branch of autonomic nervous system (ANS) is responsible for the regulation of heart rate, blood pressure, and maintaining homeostasis during physiological stress such as exercise and standing upright. ANS constantly controls the rate and force of heart contractions and the vascular tone with the aim to maintain the sufficient tissue perfusion with oxygenated blood and secure venous return to the heart. Dysautonomias, result of ANS malfunction, are often found in patients with cardiovascular symptoms. Apart from the most prevalent one, arterial hypertension, the cardiovascular dysautonomic continuum encompasses other important although less known conditions: postural orthostatic tachycardia syndrome, inappropriate sinus tachycardia, orthostatic hypotension and reflex syncope. Moreover, heart diseases may evoke autonomic imbalance by themselves; cardiac pump failure is usually associated with sympathetic hyperactivity, neuroendocrine vasopressor activation, higher heart rate, reduced heart rate variability and baroreflex hyposensitivity, all of which are predictors of adverse outcomes. Cardiologists and electrophysiologist frequently see patients for the evaluation and management of unexplained syncope, orthostatic intolerance, heart rhythm abnormalities and symptoms of palpitations. Recognizing the presence of cardiac dysautonomia is an important skill which is necessary for the appropriate evaluation and treatment of these patients. Clinical presentations may overlap, and the importance of a thorough history cannot be over-emphasized. In this review we will present a cases of a patients with cardiac dysautonomia which is illustrative of a typical patient experience, followed by a review of the autonomic nervous system and discussion of prevalence, clinical presentation, and pathophysiology of common cardiac dysautonomias.

Post mortem evaluation of inflammation, oxidative stress, and PPARγ activation in a nonhuman primate model of cardiac sympathetic neurodegeneration.

Cardiac dysautonomia is a common nonmotor symptom of Parkinson's disease (PD) associated with loss of sympathetic innervation to the heart and decreased plasma catecholamines. Disease-modifying strategies for PD cardiac neurodegeneration are not available, and biomarkers of target engagement are lacking. Systemic administration of the catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA) recapitulates PD cardiac dysautonomia pathology. We recently used positron emission tomography (PET) to visualize and quantify cardiac sympathetic innervation, oxidative stress, and inflammation in adult male rhesus macaques (Macaca mulatta; n = 10) challenged with 6-OHDA (50mg/kg; i.v.). Twenty-four hours post-intoxication, the animals were blindly and randomly assigned to receive daily doses of the peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone (n = 5; 5mg/kg p.o.) or placebo (n = 5). Quantification of PET radioligand uptake showed increased oxidative stress and inflammation one week after 6-OHDA which resolved to baseline levels by twelve weeks, at which time pioglitazone-treated animals showed regionally preserved sympathetic innervation. Here we report post mortem characterization of heart and adrenal tissue in these animals compared to age and sex matched normal controls (n = 5). In the heart, 6-OHDA-treated animals showed a significant loss of sympathetic nerve fibers density (tyrosine hydroxylase (TH)-positive fibers). The anatomical distribution of markers of sympathetic innervation (TH) and inflammation (HLA-DR) significantly correlated with respective in vivo PET findings across left ventricle levels and regions. No changes were found in alpha-synuclein immunoreactivity. Additionally, CD36 protein expression was increased at the cardiomyocyte intercalated discs following PPARγ-activation compared to placebo and control groups. Systemic 6-OHDA decreased adrenal medulla expression of catecholamine producing enzymes (TH and aromatic L-amino acid decarboxylase) and circulating levels of norepinephrine, which were attenuated by PPARγ-activation. Overall, these results validate in vivo PET findings of cardiac sympathetic innervation, oxidative stress, and inflammation and illustrate cardiomyocyte CD36 upregulation as a marker of PPARγ target engagement.

Assessment of Conventional Autonomic Function Tests in Patients with Acute Intermittent Porphyria

Background and Aim: To assess the autonomic nerve functions in latent and manifest patients of acute intermittent porphyria. The aim of the present study was to study cardiovascular responses to autonomic nerve functions in patients of acute intermittent porphyria, we also tried to find out the relative sensitivity of the various tests employed to study cardiac dysautonomia in these cases. Methods: The study was carried out on thirty cases of acute intermittent porphyria to assess the cardiovascular reflexes. Twenty five healthy subjects closely matched for age and sex served as control. The cases were diagnosed by modified Watson Schwartz test, the cases of acute intermittent porphyria were divided into three groups. Results: The values of different autonomic nerve function tests were compared with control group and among the different groups of patients. The results were complied, compared and a conclusion was drawn. Immediate heart rate response to standing is more sensitive test than the Valsalva maneuver. Immediate heart rate response to standing is more sensitive and quite reliable which can easily be performed at bed side or even in outpatient departments, the test is simple and non–invasive. In our opinion, the test, beat to beat variation of heart rate to single deep breath is though easy to perform and more understandable, but lacks the sensitivity of other two tests. Conclusion: Significant cardiac dysautonomia is present in asymptomatic group, it is more marked in acute attack group. Immediate heart rate response to standing could be a more sensitive and reliable test in this dysfunction.

Vitamin D, vitamin D binding protein, vitamin D receptor levels and cardiac dysautonomia in patients with multiple sclerosis: a cross-sectional study.

Vitamin D is a pleiotropic steroid hormone that modulates the autonomic balance. Its deficiency has been described as an environmental risk factor for multiple sclerosis (MS). The aim of this study was to investigate the serum levels of vitamin D, vitamin D binding protein (VDBP) and vitamin D receptors (VDR) and to evaluate cardiac dysautonomia in MS patients due to bidirectional interaction between vitamin D and the autonomic nervous system. The current cross-sectional study was conducted on 26 patients with relapsing-remitting MS and on 24 healthy controls. Twenty-four-hour ambulatory blood pressure variability (BPV) was calculated and the participants were evaluated for orthostatic hypotension and supine hypertension. Serum levels of vitamin D, VDBP and VDR were measured. The mean serum vitamin D level was significantly lower in MS patients than in controls (p = 0.044); however there was no significant difference in terms of VDR and VDBP levels between the groups. Supine hypertension and orthostatic hypotension were significant and the 24-hour systolic BPV was significantly decreased in patients with MS (p < 0.05) compared to controls. No correlation was found between vitamin D, VDBP and VDR with supine hypertension, orthostatic hypotension and systolic BPV values (p > 0.05). Also, there was a negative correlation between VDBP and the EDSS (p = 0.039, r = -0.406). There was no correlation between orthostatic hypotension, supine hypertension and systolic BPV values and serum vitamin D, VDBP and VDR in MS patients. Future prospective studies with large number of patients may help us to better understand the relationship between vitamin D and the autonomic nervous system.

Rostral ventrolateral medullary catecholaminergic neurones mediate irregular breathing pattern in volume overload heart failure rats.

A strong association between disordered breathing patterns, elevated sympathetic activity, and enhanced central chemoreflex drive has been shown in experimental and human heart failure (HF). The aim of this study was to determine the contribution of catecholaminergic rostral ventrolateral medulla catecholaminergic neurones (RVLM-C1) to both haemodynamic and respiratory alterations in HF. Apnoea/hypopnoea incidence (AHI), breathing variability, respiratory-cardiovascular coupling, cardiac autonomic control and cardiac function were analysed in HF rats with or without selective ablation of RVLM-C1 neurones. Partial lesion (∼65%) of RVLM-C1 neurones reduces AHI, respiratory variability, and respiratory-cardiovascular coupling in HF rats. In addition, the deleterious effects of central chemoreflex activation on cardiac autonomic balance and cardiac function in HF rats was abolished by ablation of RVLM-C1 neurones. Our findings suggest that RVLM-C1 neurones play a pivotal role in breathing irregularities in volume overload HF, and mediate the sympathetic responses induced by acute central chemoreflex activation. Rostral ventrolateral medulla catecholaminergic neurones (RVLM-C1) modulate sympathetic outflow and breathing under normal conditions. Heart failure (HF) is characterized by chronic RVLM-C1 activation, increased sympathetic activity and irregular breathing patterns. Despite studies showing a relationship between RVLM-C1 and sympathetic activity in HF, no studies have addressed a potential contribution of RVLM-C1 neurones to irregular breathing in this context. Thus, the aim of this study was to determine the contribution of RVLM-C1 neurones to irregular breathing patterns in HF. Sprague-Dawley rats underwent surgery to induce volume overload HF. Anti-dopamine β-hydroxylase-saporin toxin (DβH-SAP) was used to selectively lesion RVLM-C1 neurones. At 8weeks post-HF induction, breathing pattern, blood pressures (BP), respiratory-cardiovascular coupling (RCC), central chemoreflex function, cardiac autonomic control and cardiac function were studied. Reduction (∼65%) of RVLM-C1 neurones resulted in attenuation of irregular breathing, decreased apnoea-hypopnoea incidence (11.1±2.9vs. 6.5±2.5 eventsh-1 ; HF+Veh vs. HF+DβH-SAP; P<0.05) and improved cardiac autonomic control in HF rats. Pathological RCC was observed in HF rats (peak coherence >0.5 between breathing and cardiovascular signals) and was attenuated by DβH-SAP treatment (coherence: 0.74±0.12vs. 0.54±0.10, HF+Veh vs. HF+DβH-SAP rats; P<0.05). Central chemoreflex activation had deleterious effects on cardiac function and cardiac autonomic control in HF rats that were abolished by lesion of RVLM-C1 neurones. Our findings reveal that RVLM-C1 neurones play a major role in irregular breathing patterns observed in volume overload HF and highlight their contribution to cardiac dysautonomia and deterioration of cardiac function during chemoreflex activation.

P2733Prognostic value of cardiac dysautonomia in AL amyloidosis

Abstract Introduction Cardiac involvement is the major prognostic factor in patients with light chain amyloidosis (AL). Cardiac dysautonomia can occur early in amyloidosis and can be assess by Iodine-123-metaiodobenzylguanidine (123I-MIBG) scintigraphy. Its prognostic value has been shown in TTR amyloidosis but is unknown in AL amyloidosis. We aimed to evaluate the prognosis impact of cardiac dysautonomia in patients with AL amyloidosis. Methods We carried out a prospective study in consecutive patients with biopsy-proven AL amyloidosis. All patients underwent clinical examination, EKG, echocardiography, cardiac MRI and biological tests. The 2012 Mayo clinic prognostic classification was calculated by using blood levels of NT-proBNP, cardiac T troponin and the differential of free light chains as recommended. The sympathetic cardiac innervation was assessed by using 123I-MIBGscintigraphy and measurement of the heart-to-mediastinum uptake ratio (late H/M) in the anterior view of the chest. A cardiac denervation was defined by late H/M &lt;1.8 4h after injection of 3 MBq/kg of 123I-MIBG. The primary end-point was all-cause mortality during follow-up. Results Fifty consecutive patients with AL amyloidosis were included. The median age was 68 years old [58–73]. By using both echocardiography and MRI, cardiac involvement was diagnosed in 33 patients (66%) and thirteen of these patients were NYHA class III or IV. By using Mayo clinic classification, patients were I, II, III and IV classes in 9 (18%), 14 (28%), 16 (32%) and 11 (22%) cases respectively. According to echocardiographic data, the median wall thickness of left ventricle was 13 mm [12–15]. The late H/M was 1.51 [1.33–1.67]. Cardiac denervation was found in 44 patients (88%). The 6 patients (12%) with a normal late H/M had no cardiac amyloidosis involvement. During a median follow-up of 24 months, 9 patients (18%) died. The area under the ROC curve of late H/M for predicting death was 0.74 (CI 95% 0.58–0.86). According to this curve, the best threshold was 1.44 and 7 of the 9 patients who died had late H/M ≤1.44. The figure shows the 2 year-survival according to late H/M. Late H/M ≤1.44 predicted all-cause death irrespective of the Mayo clinic classification: HR 8.0 (CI 95% 2.1–63) after adjustment on the Mayo clinic score (p=0.005). In addition, unplanned hospitalization for heart failure occurred in 8 patients with late H/M ≤1.44 versus 3 patients with late H/M &gt;1.44 (p=0.03). Survival according to late H/M Conclusion Late H/M ≤1.44 is predictive of adverse outcomes in patients with AL amyloidosis, independently of the Mayo Clinic prognostic classification.

Cardiac dysautonomia in depression - heart rate variability biofeedback as a potential add-on therapy.

Depressive disorders are among the most important health problems and are predicted to constitute the leading cause of disease burden by the year 2030. Aside significant impact on quality of life, psychosocial well-being and socioeconomic status of affected patients, depression is associated with impaired cardiovascular health and increased mortality. The link between affective and cardiovascular disease has largely been attributed to dysregulation of the autonomic nervous system resulting in a chronic shift toward increased sympathetic and decreased parasympathetic activity and, consecutively, cardiac dysautonomia. Among proposed surrogate parameters to capture and quantitatively analyze this shift, heart rate variability (HRV) and baroreflex sensitivity have emerged as reliable tools. Attenuation of these parameters is frequently seen in patients suffering from depression and is closely linked to cardiovascular morbidity and mortality. Therefore, diagnostic and therapeutic strategies were designed to assess and counteract cardiac dysautonomia. While psychopharmacological treatment can effectively improve affective symptoms of depression, its effect on cardiac dysautonomia is limited. HRV biofeedback is a non-invasive technique which is based on a metronomic breathing technique to increase parasympathetic tone. While some small studies observed beneficial effects of HRV biofeedback on dysautonomia in patients with depressive disorders, larger confirmatory trials are lacking. We reviewed the current literature on cardiac dysautonomia in patients suffering from depression with a focus on the underlying pathophysiology as well as diagnostic workup and treatment.

Cardio-circulatory exercise response in AL amyloidosis and comparison with hypertrophic cardiomyopathy

Cardiopulmonary exercise test (CPET) can help the physician in understanding mechanisms that underlie patients exercise limitation. We aimed to characterize exercise response in AL amyloidosis through CPET and to compare it with hypertrophic sarcomeric cardiomyopathy (HCM). We prospectively included 49 patients: 24 with cardiac amyloidosis (group A), 10 with amyloidosis without cardiac involvement (group B) and 15 HCM (group C). All were clinically stable and underwent clinical examination, ECG, echocardiography, cardiac MRI and CPET. CPET assessed systolic blood pressure (SBP) as well as heart rate (HR) responses, O 2 pulse response, peak VO 2 , circulatory power (SBPxVO 2 ) and VE/VCO 2 slope. The SBP response was 25 mmHg in group A from rest to peak exercise, 19 mmHg in group B and 49 mmHg in group C ( P < 0.05). Circulatory power was 2073 mmHg.mL −1 min _1 in group A, 2620 mmHg.mL −1 min _1 in group B and 4040 mmHg.mL −1 min _1 in group C ( P < 0.05). A chronotropic incompetence was observed in 46% of group A and 44% in group B versus 7% in group C ( P < 0.05). Peak VO 2 was 14 mL.min.Kg −1 in group A, 19 mL.min.Kg −1 in group B and 20 mL.min.Kg −1 in group C ( P < 0.05). The increase of O 2 pulse during exercise was 2 in group A versus 3 in group B and group C ( P < 0.05). The VE/VCO 2 slope was increased in group A compared to group B and C (respectively 40 vs. 31 and 30, P < 0.05). CPET quantifies and specifies determinants of the poor cardio-circulatory response during exercise in AL amyloidosis patients, including decrease of peak VO2 and low circulatory power suggestive of poor exercise inotropic reserve; a chronotropic incompetence that can be related to cardiac dysautonomia and an increase of VE/VCO2 slope suggestive of exercise pulmonary hypertension.

Anabolic androgenic steroid users: a tilt test study with young adult men

IntroductionAnabolic androgenic steroids (AASs) can induce cardiac dysautonomia, which is related to arrhythmias, vasovagal syncope (VVS) and sudden death. The aim of this study was to determine whether the use of AASs increases the susceptibility for VVS or autonomic dysfunction in AAS users by the head-up tilt test (HUTT).Material and methodsCross-sectional observational study conducted with physically active young men, users (AAS group; n = 10) and non-users (Control group, n = 13) of AAS. The history of physical activity and age of each participant were recorded and the following examinations were performed: physical, biochemical, hormonal, electrocardiogram (ECG), 24-hour Holter recorder equipment. The 24-hour Holter and HUTT were conducted to detect the presence of arrhythmias/heart rate variability, and VVS/dysautonomia, respectively. Of the 28 participants recruited, 5 were excluded for not having completed the examinations.ResultsCompared with non-users, users of AAS showed an increase in aspartate aminotransferase (Control: 29.7 ±1.8; AAS: 49.9 ±9.0 UI/l; p &lt; 0.05), in ventricular extrasystoles (Control: 2.5 ±2.3; AAS: 14.9 ±11.2, p &lt; 0.05), and reduction in the pNN50 index of Holter (Control: 24.3 ±4.0%; AAS: 14.8 ±4.0%, p &lt; 0.05). The HUTT showed that the maximum value of diastolic blood pressure was increased in the AAS user group (Control: 78.3 ±2.1; AAS: 90.0 ±5.4 mm Hg, p &lt; 0.05).ConclusionsThe study showed that the use of AAS is able to promote an autonomic dysfunction, with a ventricular arrhythmia. In addition it was found that among AAS users there was a positive result for the HUTT.

Cardiovascular Autonomic Neuropathy and its Association with Cardiovascular and All-cause Mortality in Patients with End-stage Renal Disease.

BackgroundEnd-stage renal disease frequently leads to increased cardiovascular mortality. Cardiovascular autonomic neuropathy (CAN) may be predictive of cardiac arrhythmias and sudden cardiac death in patients with end-stage renal disease.MethodsA total of 70 patients with end-stage renal disease were included in the study. The assessment of cardiac dysautonomia was based on the four standardized tests performed at the baseline and, again, at the end of the study. The criteria for CAN included at least two abnormal test results.ResultsFifty of 70 patients completed the study and were followed-up after one year. Out of the 50 patients, 44 (88%) had CAN at baseline. Twelve (24%) patients died at the one-year follow-up. Sudden cardiac death was reported in seven out of 12 (58%) patients. All seven patients who died had high dysautonomia scores (three abnormal tests) at the baseline. There was a significantly higher percentage of patients with all four abnormal tests amongst patients who died of any cause (56% vs. 17%; RR 6.07, 95% CI 1.29-28.49; p-value 0.02) or due to sudden cardiac death (43% vs. 10.5%; RR 6.37, 95% CI 1.03-39.36; p-value 0.04). All five patients who did not have CAN at the baseline developed this abnormality on repeat testing after one year.ConclusionThe prevalence of CAN in patients with end-stage renal disease on maintenance hemodialysis was significantly higher. CAN was an independent predictor of all-cause and cardiovascular mortality, which highlights it as a risk stratification tool in patients with end-stage renal disease.

Early Screening of Hypertension and Cardiac Dysautonomia in Each Hypertensive is Needed-inference from a Study of QTc Interval in Gujarat, India.

Background:Hypertension (HTN) is linked to cardiac dysautonomia that can end up as life-threatening arrhythmias. The same can be screened by simple electrocardiogram (ECG)-based QTc (QT corrected for heart rate) interval which indicates repolarization abnormality. We quantified QTc interval among treated hypertensives in comparison to controls, testing effect of age, gender, and blood pressure.Methods:We conducted a cross-sectional study was done at a tertiary care teaching hospital of Gujarat, India, on 142 hypertensives on monotherapy (60 males, 82 females) and 72 age-, sex-, and time-matched normotensives. ECG was recorded with minimum 10 complexes of Lead II. QTc was derived from average of 10 values, using Bazett's formula. QTc > 0.43 s in male and > 0.45 s in female was considered abnormal.Results:Hypertensives (mean age 40 and duration 5 years) had significantly higher QTc value than normotensives among males (0.42 vs. 0.40, P < 0.001), females (0.44 vs. 0.41, P < 0.001), and in total (0.43 vs. 0.41, P < 0.001) with 24% prevalence of ECG-based left ventricular hypertrophy. Hypertensives had odds ratio 1.63 in males (P = 0.15), 23.71 in females (P = 0.003), and 3.83 in total (P < 0.001) for prolonged QTc. QTc values were significantly affected by increasing age amongst hypertensives but not by duration of HTN or current blood pressure.Conclusions:Our study showed a high prevalence of prolonged QTc, both qualitatively and quantitatively, in hypertensives on monotherapy with poor pressure control, associated with female gender and age but not duration or blood pressure. This underscores high risk of repolarization abnormality induced future event, suggesting QTc screening as primary prevention.

Cardiac autonomic denervation and expression of neurotrophins (NGF and BDNF) and their receptors during experimental Chagas disease

Although cardiac dysautonomia is a distinctive feature of Chagas disease, its clinical and functional significance is still being speculated. Neurotrophic factors are potentially involved; however, studies of their effect in this infection are rare. Ultrastructural abnormalities in autonomic varicosities, levels of both nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF), as well as the expression of their receptors, were analysed in the heart of a rat model of Trypanosoma infection. Predominantly, at the early stage of the infection, cardiac autonomic varicosities displayed several signs of degeneration parallel to the elevation of cardiac levels of NGF, as well as expression of the receptors TrkA and p75NTR. For BDNF and TrkB, the changes were less conspicuous. Data obtained here can contribute to further clarify the factors related to the autonomic nervous system’s adaptive changes that could determine the evolution of different clinical forms of Chagas disease; mainly, the cardiac form.

To study the impact of glycemic control over cardiac autonomic neuropathy in type 1 and type 2 diabetics patients using bedside tests at a tertiary care hospital

Background: Cardiac autonomic neuropathy a serious complication of diabetes and is often overlooked. It is associated with higher cardiovascular mortality and poor quality of life in diabetic individuals. The Glycemic control has been well established as the risk factor for all the diabetes related microvascular and macrovascular complications. This stresses importance of role of glycemic control over CAN in Type 1 and Type 2 Diabetics in order to stop further progression to advanced and irreversible stages. The objective was to study the impact of various demographic and other clinical factors over prevalence of CAN in type 1 and type 2 diabetic patients who are asymptomatic for CAN using bedside testsMethods: A case control comparative clinical study was undertaken comprising of 100 diabetic patients, both type 1 and type 2 with duration from 5-10 years and &gt;10 years. The tests which were performed are deep breathing test, heart rate response to standing, hand grip test, cold pressor test, BP response to standing. Depending on these tests, patients were categorised as patients with cardiac autonomic neuropathy and without cardiac autonomic neuropathy.Results: The prevalence of cardiac dysautonomia was 68%. Type 2 diabetics had higher prevalence of cardiac dysautonomia than type 1 diabetics (p=0.025). Significant correlation was observed between cardiac autonomic neuropathy and poor glycemic status (type 1 p&lt;0.001; type 2 p&lt;0.001). The mean HbA1c in patients with and without CAN in type 1DM was 9.16+0.81 and 7.21+0.56 and in type 2 DM was 9.15+1.72 and 7.15+0.53 respectively. Similarly, presence of other microvascular complications increased the prevalence of CAN in both types of diabetes mellitus.Conclusions: Cardiac autonomic neuropathy is a common complication in long standing diabetes. Present results suggest that glycemic status of the diabetics is undoubtedly an important factor for the onset of cardiac dysautonomia which in turn account for high prevalence of cardiac mortality in diabetic patients. All asymptomatic diabetic patients should be evaluated for the presence of autonomic neuropathy and glycemic status should be controlled to prevent the further progression of CAN.

Depression and cardiac dysautonomia in eating disorders.

Individuals with eating disorder (ED) are at an increased risk of cardiac arrhythmias due to cardiac dysautonomia, which may be exacerbated if depression is also present. The aim of the study was to use heart rate analysis as a marker for cardiac dysautonomia in patients with eating disorders and depression as a comorbidity. Clinical data, including presence of depression, was obtained from all participants. A three-lead ECG was used to determine interbeat intervals, and these were analyzed using time domain, frequency domain, and nonlinear heart rate variability measures. Thirty ED patients and 44 healthy controls participated in the research. The presence of depression was associated with additional decreased time domain (RMSSD 36.8 ± 26 vs. 22.9 ± 12.3; p < 0.05), frequency domain (HF power 788 ± 1075 vs. 279 ± 261; p < 0.05), and nonlinear domain (DFAα2 0.82 ± 0.1 vs. 0.97 ± 0.1; p < 0.01) which results in the ED group compared to patients with no depression. The presence of depression in ED patients decreased HRV even further compared to the non-depressed patient group and controls, suggesting that higher vigilance and a holistic treatment approach may be required for these patients to avoid cardiac arrhythmia complications.

QT corrected for heart rate and qtc dispersion in Gujarati type 2 diabetics predominantly using preventive pharmacotherapy and with very low electrocardiogram left ventricular hypertrophy

Background: There is a rising trend in the incidence of type 2 diabetes mellitus, and hyperglycaemia is known to cause cardiac dysautonomia, which may lead to life-threatening arrhythmias. It can be screened by simple electrocardiogram (ECG)-based QTc (QT corrected for heart rate) and QTd (QTc dispersion) indicating cardiac repolarisation abnormality. We studied QTc and QTd intervals in treated type 2 diabetics (T2D), testing the effect of age, gender, duration and control of disease. Materials and Methods: We conducted a cross-sectional study in a tertiary care teaching hospital of Gujarat, India, on 199 T2D (67 males and 132 females). Standard 12-lead ECG was recorded to derive QTc by Bazett's formula, QTd and ECG left ventricular hypertrophy (LVH). QTc >0.43 s in male and >0.45 s in female, QTd >80 msec were considered abnormal. Results: T2D (mean age 56 years, duration 6 years, coexisting hypertension 69%, glycaemic control 32% and use of β-blockers 56%) had QTc and QTd abnormality prevalence 15% and 20% respectively with ECG LVH prevailing in 3%. Male gender, poor glycaemic control and increased duration had negative impact on QT parameters with statistical significance only for first two and not for all results. Conclusion: Our study showed low-to-moderate prevalence of prolonged QTc and QTd, qualitatively more than quantitatively, in T2D with very low LVH and high prevalence of preventive pharmacotherapy, associated with male gender and glycaemic control. It underscores high risk of repolarisation abnormality, though moderate, that can be further primarily prevented by early screening and strict disease control.

Heart rate variability regression and risk of sudden unexpected death in epilepsy

The exact mechanisms of sudden unexpected death in epilepsy remain elusive, despite there is consensus that SUDEP is associated with severe derangements in the autonomic control to vital functions as breathing and heart rate regulation. Heart rate variability (HRV) has been advocated as biomarker of autonomic control to the heart. Cardiac dysautonomia has been found in diseases where other branches of the autonomous nervous system are damaged, as Parkinson disease and multiple system atrophy. In this perspective, an impaired HRV not only is a risk factor for sudden cardiac death mediated by arrhythmias, but also a potential biomarker for monitoring a progressive decline of the autonomous nervous system. This slope may lead to an acute imbalance of the regulatory pathways of vital functions after seizure and then to SUDEP.