Heart Rate Variability Measured Early in Patients with Evolving Acute Coronary Syndrome and 1-year Outcomes of Rehospitalization and Mortality

Objective: This study sought to examine the prognostic value of heart rate variability (HRV) measurement initiated immediately after emergency department presentation for patients with acute coronary syndrome (ACS). Background: Altered HRV has been associated with adverse outcomes in heart disease, but the value of HRV measured during the earliest phases of ACS related to risk of 1-year rehospitalization and death has not been established. Methods: Twenty-four-hour Holter recordings of 279 patients with ACS were initiated within 45 minutes of emergency department arrival; recordings with �18 hours of sinus rhythm were selected for HRV analysis (number [N] �193). Time domain, frequency domain, and nonlinear HRV were examined. Survival analysis was performed. Results: During the 1-year follow-up, 94 patients were event-free, 82 were readmitted, and 17 died. HRV was altered in relation to outcomes. Predictors of rehospitalization included increased normalized high frequency power, decreased normalized low frequency power, and decreased low/high frequency ratio. Normalized high frequency �42 ms2 predicted rehospitalization while controlling for clinical variables (hazard ratio [HR] �2.3; 95% confidence interval [CI] �1.4–3.8, P�0.001). Variables significantly associated with death included natural logs of total power and ultra low frequency power. A model with ultra low frequency power �8 ms2 ( HR �3.8; 95% CI �1.5–10.1; P�0.007) and troponin �0.3 ng/mL (HR �4.0; 95% CI �1.3–12.1; P�0.016) revealed that each contributed independently in predicting mortality. Nonlinear HRV variables were significant predictors of both outcomes. Conclusion: HRV measured close to the ACS onset may assist in risk stratification. HRV cut-points may provide additional, incremental prognostic information to established assessment guidelines, and may be worthy of additional study

Associations Between Heart Rate Variability and Metabolic Syndrome Risk Factors

Metabolic syndrome (MetS) is a clustering of risk factors for cardiovascular disease (CVD) and type 2 diabetes (T2D) – two major causes of morbidity and mortality worldwide. Heart rate variability (HRV) is a non-invasive measure of cardiac autonomic regulation that predicts mortality and morbidity. Additionally, HRV is reduced in CVD, T2D and MetS. As such, HRV has potential to be a novel cardiometabolic risk factor to be included in clinical risk assessment. Therefore, the purpose of this thesis was to examine the relationships between MetS and HRV. A systematic review of cross-sectional studies examining relationships between HRV and MetS was completed to consolidate existing evidence and to guide future studies. This was followed by a cross-sectional investigation of time and frequency domain and nonlinear HRV in a population with MetS risk factors to determine which MetS risk factors were associated with HRV parameters. A pilot study was then conducted to study the feasibility of conducting a mobile health (mHealth) and exercise intervention in a rural population, which was followed by a 24-week randomized clinical trial to examine the effects of the interactive mHealth exercise intervention compared to standard of care exercise in participants with MetS risk factors. Overall, HRV was reduced in women with MetS compared to those without, though there were no differences in men. Waist circumference and lipid profiles were most commonly related to HRV parameters when studied cross-sectionally. The changes in waist circumference and fasting plasma glucose were associated with the change in HRV parameters when studied longitudinally. Following the intervention period, waist circumference and blood pressure were improved with no other changes in MetS risk factors. HRV parameters indicative of vagal activity were reduced over the intervention period, but there were no changes in other HRV parameters. There were no differences in changes between the intervention and control groups. In conclusion, MetS and HRV are associated in women but not men. However, there were no clear associations between MetS and HRV to suggest that HRV would be a valuable clinical risk factor

Baroreflex sensitivity and heart rate variability are predictors of mortality in patients with aneurysmal subarachnoid haemorrhage.

OBJECT: We aimed to investigate the link between the autonomic nervous system (ANS) impairment, assessed using baroreflex sensitivity (BRS) and heart rate variability (HRV) indices, and mortality after aneurysmal subarachnoid haemorrhage (aSAH). METHODS: A total of 57 patients (56 ± 18 years) diagnosed with aSAH were retrospectively enrolled in the study, where 25% of patients died in the hospital. BRS was calculated using a modified cross-correlation method. Time- and frequency-domain HRV indices were calculated from a time-series of systolic peak intervals of arterial blood pressure signals. Additionally, cerebral autoregulation (CA) was assessed using the mean velocity index (Mxa), where Mxa > 0 indicates impaired CA. RESULTS: Both BRS and HRV indices were lower in non-survivors than in survivors. The patients with disturbed BRS and HRV had more extensive haemorrhage in the H-H scale (p = .040) and were more likely to die (p = .013) when compared to patients with the intact ANS. The logistic regression model for mortality included: the APACHE II score (p = .002; OR 0.794) and the normalised high frequency power of the HRV (p < <.001; OR 0.636). A positive relationship was found between the Mxa and BRS (R = 0.48, p = .003), which suggests that increasing BRS is moderately strongly associated with worsening CA. CONCLUSION: Our results indicated that lower values of HRV indices and BRS correlate with mortality and that there is a link between cerebral dysautoregulation and the analysed estimates of the ANS in aSAH patients

A Survey of Telecardiology Projects in Italy.

It is estimated that in Italy there are about three million people affected by chronic heart failure. Cardiology is the health care field currently getting the largest benefits from telemedicine. Transmission, using wireless devices, makes possible to achieve virtual hospitalization: it is possible to anticipate the time of discharging and the patient can be remotely controlled by the central station in the ICU of the department of Medicine. Teleconsulting (i.e. a distance consulting between physicians) is applied in telecardiology, it allows the realization of a consulting between cardiology departments and remote services in the same hospital or among far-away hospitals. In this paper some of the most significant cardiac telemonitoring projects in Italy are described. Also reported, the projects involving the applications of implantable cardiac devices which can be controlled remotely. In conclusion, we sketch out the future prospects of telecardiology research and its applications in Italy

Cardiovascular and Autonomic Nervous System Function: Impact of Glucose Ingestion, Hydration Status and Exercise in Heated Environments

Cardiovascular function is under the influence of autonomic nervous system, both of which can be assessed non-invasively. The purpose of this dissertation was to examine these non-invasive markers of cardiovascular and autonomic function and their relationships with exercise training, glucose ingestion and hydration status. A series of three studies were conducted to gain insight to various influences on cardiovascular and autonomic function. The first study examined the influence of exercise training of brachial artery flow-mediated dilation (BAFMD) using meta-analytic techniques. Sixty-six studies included in the analysis demonstrated exercise training improves BAFMD compared to controls. Results indicated exercise training significantly alters BAFMD, a well-known factor associated with prevention of cardiovascular diseases. Exercise training interventions including greater intensity and duration may optimize increases in BAFMD. The second study observed glucose ingestion alters autonomic nervous system function, shifting the sympathetic/parasympathetic balance to higher sympathetic activity. Higher exercise intensity decreased fasting heart rate variability 24-hrs after cessation of exercise whereas lower exercise intensity did not alter heart rate variability. Acute exercise increased heart rate variability after an oral glucose tolerance test, but was not affected by exercise intensity. The last study determined the effect of chronic dehydration on cardiovascular and sweat responses during exercise in a heated environment. Dehydration altered blood and urine markers of hydration status, but did not change cardiovascular and sweat response to exercise in the heat. . In addition, BAFMD was related to the change in weighted skin temperature and body temperature during exercise in the heat, and increased LF/HF at rest was associated with increased peak heat storage. Together these data suggest resting cardiovascular health may influence the ability to thermoregulate during exercise in the heat

The acute and chronic effects of isometric exercise on haemodynamic, autonomic and cardiac function in a pre-hypertensive population

Raised blood pressure (BP) remains the leading modifiable risk factor for cardiovascular disease morbidity and mortality globally. As such, primary prevention strategies are required to improve risk factors to prevent the development of hypertension (HTN). Isometric exercise training (IET) is becoming an established intervention for reducing resting BP. However, few studies have investigated the effects of IET in a population at increased risk of developing HTN. Therefore, this thesis examined the effects of IET, using a novel home-based wall squat intervention, in a pre-hypertensive male population. Specifically, the thesis aimed to explore the potential mechanism/s responsible for improved BP control using an acute isometric exercise (IE) stimuli and a four-week IET intervention. Firstly, acute IE was shown to elicit a step-wise increase in BP, heart rate and cardiac output and associated increase in sympathetic activity. In the immediate recovery period, there was a hypotensiveresponse, which was associated with parasympathetic activation, increased baroreceptor reflex control and reduced peripheral vascular resistance. The hypotensive response was also associated with improved indices of cardiac function, including a reduced estimated filling pressure. Four weeks of IET was shown to significantly reduce resting and ambulatory BP. Improved autonomic cardiovascular control, with increased parasympathetic over sympathetic activity, greater baroreceptor reflex sensitivity and reduced peripheral vascular resistance potentially mediated the decreased BP. A reduction in plasma interleukin-6 and asymmetric dimethylarginine suggests an anti-inflammatory response and improved vascular function, respectively, following IET. Finally, improved myocardial diastolic function suggests positive cardiac adaptations in response to BP reductions. Collectively, the findings of this thesis highlight potential mechanistic pathways for improved BP control in a prehypertensive population and demonstrates wider cardiovascular benefits of IET beyond BP reductions, which are important observations for risk reduction in this population

Sleep-time predictors of cardiovascular complications in surgical peripheral arterial disease

ABSTRACT Patients with peripheral arterial disease (PAD) undergoing surgical revascularisation are in high risk of postoperative cardiovascular complications and death, due to advancing age and multiple comorbidities in the population. In addition, PAD needing surgery represents a severe form of systemic atherosclerosis but the exact underlying pathophysiology of acute myocardial infarction (AMI) in these patients is unclear and predicting outcome especially in the long-term is challenging. Obstructive sleep apnoea (OSA) is increasingly common in the general population and independently associated with various manifestations of cardiovascular disease or their risk factors; OSA is highly prevalent in patients with coronary artery disease (CAD), stroke, hypertension and diabetes. To expand this knowledge, we determined the prevalence and severity (in terms of the apnoeahypopnoea index, AHI) of OSA in surgical PAD as well as its impact on the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) in this patient group. Heart rate variability (HRV) reflects fluctuations in sympathetic and parasympathetic activation responsible for neurocirculatory control in various physiological and pathophysiological situations. Depressed HRV is associated with increased cardiovascular morbidity and mortality following AMI and major surgery. In this study, the alterations of nocturnal HRV and their association with the severity of OSA and incidence of MACCE in patients with PAD was assessed, including the fractal correlation properties of HRV. HRV in a control group of 15 healthy subjects was also examined. Patients scheduled for sub-inguinal vascular surgery (n=84, age 67±9 years) underwent polysomnography and HRV analyses. OSA was detected in 86% of patients and in 56% it was moderate or severe. Age, male gender, depressed left ventricular function and decreasing high density lipoprotein/cholesterol ratio (HDL/Chol) predicted the presence and severity of OSA. The latter two remained significant after adjusting for age and gender. OSA with AHI ≥20/hour, used as a cut-off in the outcome analyses, predicted a higher risk of MACCE (p=0.001) along with pre-existing CAD (p=0.001), decreasing HDL/Chol (p=0.048) and <4 years history of PAD (p=0.018). HRV was altered in patients with PAD when compared to controls but the time domain measures were mostly unchanged. In the frequency domain, low frequency power was generally lower, high frequency power was mostly higher and fractal correlation was consistently lower. Very low frequency power was increased the most in patients with AHI 10-20/hour when compared to <10/hour while those with AHI ≥20/hour had lower fractal correlation in the morning. Patients suffering a MACCE had lower high frequency power during S3-4 and rapid eye movement sleep. In conclusion, OSA is associated with worsening atherosclerosis and predicts MACCE after vascular surgery. HRV alterations, although associated with PAD, have limited predictive value. Keywords: atherosclerosis, peripheral arterial disease, sleep apnoea, heart rate variabilityTIIVISTELMÄ Unenaikaiset sydänkomplikaatioiden ennustetekijät kirurgista hoitoa vaativassa perifeerisessä valtimotaudissa Perifeeristä valtimotautia sairastavilla potilailla on suuri leikkauksenjälkeisten sydänkomplikaatioiden riski johtuen yhä iäkkäämmästä väestöstä sekä lukuisista rinnakkaissairauksista. Lisäksi perifeerinen valtimotauti merkitsee vaikea-asteista yleistynyttä ateroskleroosia, mutta sydäninfarktin tarkka syntymekanismi näillä potilailla on epäselvä ja erityisesti pitkän aikavälin ennusteen arviointi on haastavaa. Obstruktiivinen uniapnea yleistyy väestössä ja sillä on itsenäinen yhteys useisiin sydän- ja verisuonisairauksiin ja niiden riskitekijöihin; uniapnea on erittäin yleinen sepelvaltimotauti-, aivohalvaus-, verenpainetauti- ja diabetespotilailla. Tämän tietopohjan laajentamiseksi tässä tutkimuksessa määritettiin uniapnean esiintyvyys ja vaikeusaste (määrittäjänä apnea-hypopneaindeksi, AHI) vaikea-asteista yleistynyttä ateroskleroosia sairastavilla potilailla sekä sen vaikutus vakavien sydän- ja aivotapahtumien ilmaantuvuuteen. Sydämen sykevaihtelu kuvastaa autonomisen hermoston toiminnan muutoksia, jotka puolestaan vastaavat verenkierron säätelystä erilaisissa fysiologisissa ja patofysiologisissa tilanteissa. Alentunut sykevaihtelu on yhteydessä lisääntyneeseen kardiovaskulaariseen sairastuvuuteen ja kuolleisuuteen sairastetun sydäninfarktin tai suuren leikkauksen jälkeen. Tässä tutkimuksessa arvioitiin yöllisen sydämen sykevaihtelun muutosten yhteyttä uniapnean vaikeusasteeseen sekä vakavien sydän- ja aivotapahtumien ilmaantuvuuteen, mukaan lukien sykevaihtelun fraktaalikorrelaatio-ominaisuudet. Tutkimuksessa analysoitiin sykevaihtelu myös 15 terveen henkilön vertailuryhmältä. Nivustason alapuoliseen verisuonileikkaukseen meneville potilaille (n=84, ikä 67±9 vuotta) tehtiin unipolygrafia ja sykevaihteluanalyysi. Uniapnea todettiin 86 %:lla potilaista ja 56 %:lla se oli kohtalainen tai vaikea. Ikä, miessukupuoli, heikentynyt vasemman kammion toiminta ja alentunut HDL-kolesterolin suhde kokonaiskolesteroliin ennustivat uniapneaa ja sen vaikeutumista; 2 viimeksi mainittua säilyivät merkitsevinä ikä- ja sukupuolivakioinnin jälkeen. AHI ≥20/tunti, joka valittiin kynnysarvoksi päätetapahtumaanalyyseihin, ennusti merkitsevästi vakavia sydän- ja aivotapahtumia (p=0.001). Muita merkitseviä tekijöitä olivat sepelvaltimotauti (p=0.001), alentunut HDL-suhde (p=0.048) ja lyhyt (alle 4 vuotta) perifeerisen valtimotaudin kesto ennen leikkaushoidon tarvetta (p=0.018). Sykevaihtelu oli muuttunut valtimotautipotilailla verrattuna kontrolleihin, mutta aikakenttäparametrit säilyivät lähes ennallaan. Pienitaajuuksinen sykevaihtelu oli yleisesti vähäisempää, suuritaajuuksinen enimmäkseen voimakkaampaa ja fraktaalikorrelaatio johdonmukaisesti heikompaa. Hyvin pienitaajuuksinen vaihtelu oli eniten lisääntynyt AHI 10-20/tunti -alaryhmässä verrattuna AHI <10/tunti -ryhmään, mutta AHI ≥20/tunti -potilailla aamun fraktaalikorrelaatio oli heikompaa. Potilaiden, jotka saivat vakavia sydän- ja aivotapahtumia, suuritaajuusvaihtelu oli heikompaa syvän unen ja vilkeunen aikana. Johtopäätöksinä todetaan, että uniapnea on yhteydessä vaikeutuvaan valtimotautiin sekä ennustaa vakavia sydän- ja aivotapahtumia verisuonileikkauksen jälkeen sykevaihtelun muutosten ennustearvon ollessa tässä aineistossa hyvin rajallinen. Avainsanat: ateroskleroosi, perifeerinen valtimotauti, uniapnea, sykevaihtel

The effects of an ultra-endurance event on heart rate variability and cognitive performance during induced stress in Ironman triathletes

Includes abstract.Includes bibliographical references (leaves 55-79).The effects of long-term participation in ultra-endurance exercise on the cardiovascular system have recently been the subject of much interest. It is well known that HRV, a marker of autonomic activity, is enhanced with long-term aerobic exercise training. However, after acute exercise, HRV is reduced, but recovers over time depending on the intensity of the prior bout of exercise. A limitation of previous research is that exercise bouts of only up to 120 minutes have been studied. A modified Stroop Task is a laboratory stressor to assess executive cognitive function by means of reaction time and accuracy. The resting HRV is directly related to these prefrontal neural functions, but the effect of an altered HRV on cognitive function has never been investigated. We determined the effects of an ultra duration (10 – 15 hours) exercise event on parameters of HRV and cognitive function during a Modified Stroop Task, 60 – 200 minutes after the 2007 South African Ironman Triathlon event (3,6km swim; 180 Km cycle; 42,2 Km run). 1 Female and 13 male competing triathletes (IRON; ages 33.7±7.9) and 7 control subjects (CON; 2 female and 5 males aged 42 ±4.5) completed a Modified Stroop Task before and after the event. The individual HRV parameters, heart rate (HR), respiratory frequency (RF), reaction time (RT) and % of mistakes made were recorded via the Biopac MP150WSW System (Goletta, California, USA). Data was transformed by auto regressive analyses (Biomedical signal analysis group, University of Kuopio, Finland) into LF (0.04 - 0.15 Hz) and HF (0.15 - 0.5 Hz) components. Additional calculations included %LF and %HF as well as the central or peak frequencies in both the LF and HF bands

Clinical studies of the renin-angiotensin-aldosterone system and cardiac autonomic regulation in man

The work embodied in this thesis was designed to explore the interaction between the renin -angiotensin -aldosterone system (RAAS) and the autonomic nervous system. It was stimulated by the observations that the neurohormonal suppression of the RAAS by ACE inhibitors in chronic heart failure (CHF) is inadequate, and that high residual levels of circulating aldosterone have been shown to have detrimental autonomic modulating effects independent of angiotensin II in experimental models.The effects of aldosterone blockade with spironolactone therapy were examined in CHF patients already established on ACE inhibitors. It was observed that spironolactone has beneficial parasympathomimetic properties, improving heart rate variability and reducing heart rate, particularly during the early morning hours of the day when ACTH -induced aldosterone secretion is maximal. The interaction between the RAAS and the parasympathetic tone was explored further in a series of normal volunteer studies. Although the effects of ACE inhibitors are well recognised, not much is known about the parasympathomimetic properties of direct angiotensin II or aldosterone receptor antagonism. In this thesis, it was demonstrated that losartan, an angiotensin II receptor antagonist, and enalapril, an ACE inhibitor, were equally effective in improving the vagally-mediated baroreflex response in salt depleted normotensive subjects. It was also demonstrated that direct intravenous aldosterone administration impaired the baroreflex response to vasopressor agents in healthy subjects.The observed vagomimetic effects of aldosterone blockade may have important therapeutic implications, suggesting the possibility that spironolactone may have anti -ischaemic or anti -arrhythmic properties. However, aldosterone blockade did not appear to have any significant impact on either autonomic tone or ischaemic events when administered to patients with ischaemic heart disease but preserved LV function. The reasons for the latter remain unclear but may reflect differences in disease -state (less neurohormonal activation, and a larger proportion of these patients was established on beta -blockers -which may influence autonomic tone - and only a minority was taking concomitant ACE inhibitors, compared to the CHF cohort). In CHF however, spironolactone was shown to improve QT dispersion, a surrogate marker of arrhythmic activity and sudden cardiac death. Mechanisms in which aldosterone may contribute towards dispersion of the QT intervals on the electrocardiogram are probably multifactorial. Aldosterone increases cardiac afterload (by increasing vascular tone and potentiating vascular smooth muscle hypertrophy) and it is demonstrated that cardiac afterload would increase QT dispersion through mechano- electrical feedback. Vagal tone modulation itself however did not contribute towards QT dispersion.These studies demonstrate how inextricably linked the RAAS and the autonomic nervous system is. In particular, the detrimental autonomic effects of aldosterone in CHF have been highlighted. The findings of these studies highlight possible mechanisms and provide valuable insights as to why further therapeutic mileage is gained by the addition of an aldosterone antagonist in CHF patients who have already been established on ACE inhibitors