Longitudinal tracking of muscle sympathetic nerve activity and its relationship with blood pressure in subjects with prehypertension.

Prehypertension is associated with increased cardiovascular events. While the "tracking phenomenon" is an important longitudinal characteristic of blood pressure (BP), changes in muscle sympathetic nerve activity (MSNA) over time remain unclear. This study tested the hypothesis that MSNA tracking contributes to BP trends in prehypertension. BP and MSNA were assessed in 13 prehypertensive males at rest, during hand grip and mental stressors at baseline and after 8 years. Baseline office BP averaged 127 ± 2/81 ± 2 mmHg and MSNA 24 ± 4 bursts/min. BP increased by 7 ± 2/5 ± 2 mmHg (P < 0.01) and MSNA by 11 ± 2 bursts/min (P < 0.001) at follow-up. SBP and DBP were interrelated at baseline (r = 0.65, P = 0.02) and at follow-up (r = 0.78, P = 0.002). MSNA tracking (r = 0.82; P < 0.001) was similar to BP. MSNA was strongly related to DBP at baseline (r = 0.73; P < 0.01) and follow-up (r = 0.64; P = 0.01), more so than SBP. BMI increased (P < 0.001) at follow-up but was unrelated to BP or MSNA. Despite comparable pressor and cardiac increases to handgrip and mental stressors, sympathetic responses were blunted, more pronounced to isometric test (P < 0.006) at follow-up. In conclusion, the trend in MSNA corresponds with BP changes over time suggesting that tonic sympathetic activation may contribute to time-related increase in resting BP and the development of sustained hypertension in prehypertension.

New perspectives of nitric oxide donors in cardiac arrest and cardiopulmonary resuscitation treatment.

Nitric oxide (NO) is often used to treat heart failure accompanied with pulmonary edema. According to present knowledge, however, NO donors are contraindicated when systolic blood pressure is less than 90 mmHg. Based on recent findings and our own clinical experience, we formulated a hypothesis about the new breakthrough complex lifesaving effects of NO donors in patients with cardiac arrest and cardiopulmonary resuscitation therapy. It includes a direct hemodynamic effect of NO donors mediated through vasodilation of coronary arteries in cooperation with improvement of cardiac function and cardiac output through reversible inhibition of mitochondrial complex I and mitochondrial NO synthase, followed by reduction in reactive oxygen species and correction of myocardial stunning. Simultaneously, an increase in vascular sensitivity to sympathetic stimulation could lead to an increase in diastolic blood pressure. Confirmation of this hypothesis in clinical practice would mean a milestone in the treatment for cardiac arrest and cardiopulmonary resuscitation.

Interatrial pressure gradients during simulated obstructive sleep apnea: a catheter-based study.

OBJECTIVES: We set to measure the interatrial pressure gradient during simulated obstructive sleep apnea (OSA). BACKGROUND: OSA occurs when a sleeping patient attempts to inhale against an obstructed airway. How this event affects the interatrial pressure gradient has not been defined. We hypothesized that simulated OSA in a conscious subject (Mueller maneuver [MM], inspiration against obstruction) would promote increased right-to-left pressure gradient, and then the substrate for right-to-left atrial shunting. METHODS: Selected patients underwent simultaneous measurement of airway and atrial pressures (both left and right atrium [LA, RA]) using high-fidelity micromanometry at rest, during MM, and during VM, during right heart catheterization. RESULTS: Ten patients (age 55 ± 11 years, two women) were successfully studied. During the onset of MM, RA pressure transiently but consistently exceeded LA pressure in response to the steep decline in intrathoracic pressure (maximum RA-LA pressure gradient increased from 0.1 ± 1.4 mm Hg at baseline to 7.0 ± 4.3 mm Hg during MM, P < 0.001). The maximum right-to-left atrial pressure gradient during Mueller maneuver was higher than that achieved during the Valsalva maneuver release (P < 0.007). CONCLUSIONS: The onset of MM increased right-to-left pressure gradient across the atrial septum, likely as a result of greater blood return to the RA from extrathoracic veins. The RA-LA pressure gradient achieved during MM was greater than that observed during VM. These findings delineate the hemodynamic substrate for right to left shunting during OSA.

Chemoreflexes, sleep apnea, and sympathetic dysregulation.

Obstructive sleep apnea (OSA) and hypertension are closely linked conditions. Disordered breathing events in OSA are characterized by increasing efforts against an occluded airway while asleep, resulting in a marked sympathetic response. This is predominantly due to hypoxemia activating the chemoreflexes, resulting in reflex increases in sympathetic neural outflow. In addition, apnea - and the consequent lack of inhibition of the sympathetic system that occurs with lung inflation during normal breathing - potentiates central sympathetic outflow. Sympathetic activation persists into the daytime, and is thought to contribute to hypertension and other adverse cardiovascular outcomes. This review discusses chemoreflex physiology and sympathetic modulation during normal sleep, as well as the sympathetic dysregulation seen in OSA, its extension into wakefulness, and changes after treatment. Evidence supporting the role of the peripheral chemoreflex in the sympathetic dysregulation seen in OSA, including in the context of comorbid obesity, metabolic syndrome, and systemic hypertension, is reviewed. Finally, alterations in cardiovascular variability and other potential mechanisms that may play a role in the autonomic imbalance in OSA are also discussed.

Forced aggregation and defined factors allow highly uniform-sized embryoid bodies and functional cardiomyocytes from human embryonic and induced pluripotent stem cells.

In vitro human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) can differentiate into functional cardiomyocytes (CMs). Protocols for cardiac differentiation of hESCs and hiPSCs include formation of the three-dimensional cell aggregates called embryoid bodies (EBs). The traditional suspension method for EB formation from clumps of cells results in an EB population heterogeneous in size and shape. In this study we show that forced aggregation of a defined number of single cells on AggreWell plates gives a high number of homogeneous EBs that can be efficiently differentiated into functional CMs by application of defined growth factors in the media. For cardiac differentiation, we used three hESC lines and one hiPSC line. Our contracting EBs and the resulting CMs express cardiac markers, namely myosin heavy chain α and ß, cardiac ryanodine receptor/calcium release channel, and cardiac troponin T, shown by real-time polymerase chain reaction and immunocytochemistry. Using Ca(2+) imaging and atomic force microscopy, we demonstrate the functionality of RyR2 to release Ca(2+) from the sarcoplasmic reticulum as well as reliability in contractile and beating properties of hESC-EBs and hiPSC-EBs upon the stimulation or inhibition of the ß-adrenergic pathway.

MicroRNAs involved in the lipid metabolism and their possible implications for atherosclerosis development and treatment.

Hyperlipidemia is a well-accepted risk factor in the development of atherosclerosis. MicroRNAs (miRNAs), a novel class of posttranscriptional regulators of gene expression, are involved in a variety of biological and pathological processes, including the regulation of the lipid metabolism and atherosclerosis. As our knowledge of miRNAs expands, a new class of "circulating miRNAs" has recently been described. It includes miRNAs which may be found in various bodily fluids packaged in microvesicles/exosomes, or bound to specific transporting proteins. High-density lipoprotein (HDL) particles have been identified as one such carrier. As this class of miRNAs likely plays a role in intercellular communication, it may also contribute to the atherosclerosis development and progression. This review aims to provide a comprehensive explanation of the roles of distinct miRNAs involved in the regulation of the lipid metabolism. These microRNAs seem to be promising therapeutic agents, as documented in rodents and African green monkeys. The second part of the review focuses on circulating miRNAs and their involvement in the atherosclerosis, especially as their levels have been described as altered in patients with dyslipidemia/hyperlipidemia. Special emphasis is placed on miRNAs transported in a complex with HDL particles and on those which may be considered potential atherosclerosis biomarkers.

High-normal blood pressure is associated with increased resting sympathetic activity but normal responses to stress tests.

OBJECTIVE: High-normal blood pressure (BP) increases the risk of cardiovascular (CV) disease. The mechanisms underlying this increased risk are not clear. Sympathetic activation appears to be a potential mechanism linking high-normal BP to CV disease. This study examined whether high-normal BP compared with optimal BP is linked to sympathoexcitation at rest and/or during laboratory stressors. METHODS: Heart rate (HR), BP and muscle sympathetic nerve activity (MSNA) were obtained at rest and during stress tests (sustained handgrip and mental stress) in 18 subjects (15 males and three females) with high-normal BP (systolic BP of 130-139 mmHg, diastolic BP of 85-89 mmHg, or both) and in 12 subjects (10 males and two females) with optimal BP (< 120/80 mmHg) matched for age (34 ± 3 years in both groups) and body mass index (25 ± 2 kg/m(2) in both groups). RESULTS: Despite the higher resting BP levels, MSNA was higher in subjects with high-normal BP than in the optimal BP group (26 ± 3 vs 18 ± 2 bursts/min, p< 0.05). During sustained handgrip, MSNA increased by 37 ± 14% in high-normal BP group compared with an increase of 49 ± 15% in optimal BP group (p = 0.55). Changes during mental stress were 50 ± 28% and 37 ± 12%, respectively (p = 0.73). There were no significant differences in SBP responses to handgrip and mental stress between the high-normal and optimal BP groups. Baseline HR and chronotropic responses to stress tests were comparable between the two groups. CONCLUSION: In comparison with optimal BP, high-normal BP is associated with increased resting MSNA, but normal neural and circulatory responses to stress tests. These findings suggest that tonic activation of the sympathetic nervous system may precede overt arterial hypertension and contribute to an excess risk of CV disease in subjects with high-normal BP.

Increased heart rate with sleep disordered breathing in hypertrophic cardiomyopathy.

BACKGROUND: Current guidelines recommend medications with rate control properties for symptomatic patients with hypertrophic cardiomyopathy (HCM) based on the rationale that lowering heart rate (HR) improves their symptoms. Whether sleep disordered breathing (SDB) is associated with increased HR in HCM patients is not known. METHOD: We diagnosed uncontrolled SDB (oxygen desaturation index ≥5) in consecutive echocardiographically confirmed HCM patients seen at Mayo Clinic, Rochester, and analyzed their HR as recorded by a 24-h Holter monitor. We compared mean, minimum, maximum HR between those with vs without SDB. In a pilot subanalysis of HCM patients with SDB who also underwent subsequent diagnostic polysomnography (PSG), we analyzed RR interval changes coinciding with obstructive sleep apnea and hypopnea episodes. RESULTS: Of the 230 HCM patients included in this study (age 54 ± 16 years; 138 male; LVOT pressure gradient at rest 45 ± 39 mmHg), 115 (50%) patients had SDB. HCM patients with SDB were recorded to have higher mean HR (71 vs. 67 bpm; p = .002, adjusted p = .001), and this difference was most pronounced during night hours of 10 PM to 5 AM (61 vs. 67 bpm; p < .001). In the pilot analysis of the available PSG data, the release of obstructive sleep apneas and hypopneas coincided with fluctuation of HR. CONCLUSIONS: SDB is independently associated with higher mean HR in patients with HCM, and this difference is most significant during sleep. Treatment of SDB, which is readily available, should be tested as a complementary modality to the currently recommended pharmacotherapy aimed at lowering HR in patients with symptomatic HCM.

Smoking is associated with chronic sympathetic activation in hypertension.

OBJECTIVE: Previous studies have shown that smoking contributes importantly to short-term modulation of sympathetic nerve traffic. However, effect of smoking status on resting muscle sympathetic nerve activity (MSNA) in hypertension is unknown. Therefore, we tested the hypothesis that smoking is associated with chronic sympathetic activation in patients with essential hypertension. METHODS: We measured MSNA, heart rate (HR) and blood pressure during undisturbed supine rest and in 30 hypertensive smokers (22 males, age 38+/-4 years, body mass index, BMI 27+/-1 kg/m(2), mean+/-SEM). These measurements were compared with those obtained 38 non-smoking hypertensive patients matched for gender, age and BMI. All hypertensives underwent 24-h ambulatory blood pressure monitoring. Patients were newly diagnosed, never treated for hypertension and were free of any other known diseases. RESULTS: In comparison with non-smokers, smokers had smaller office-daytime systolic blood pressure difference (6+/-2 vs 15+/-3 mmHg, respectively; p<0.01). Despite similar resting values, HR in smokers was greater than in non-smokers during both daytime (86+/-3 vs 77+/-2 beats/min, respectively; p< 0.001) and night-time (73+/-3 vs 66+/-2 beats/min, respectively; p<0.01). MSNA was elevated in smokers (36+/-3 bursts/min) compared with non-smokers (28+/-3 bursts/min; p<0.01). Similar results were obtained when MSNA was expressed as bursts/100 heart beats. Multiple linear regression analysis revealed that only age and smoking status were linked independently to MSNA (R(2)=0.42, p< 0.001). CONCLUSIONS: In patients with essential hypertension, smoking is independently associated with chronic increase in MSNA. These findings may have implications for our understanding of the mechanisms linking smoking to cardiovascular events.

Association Between Hypoxemia and Mortality in Patients With COVID-19.

OBJECTIVE: To identify markers associated with in-hospital death in patients with coronavirus disease 2019 (COVID-19)-associated pneumonia. PATIENTS AND METHODS: A retrospective cohort study was conducted of 140 patients with moderate to critical COVID-19-associated pneumonia requiring oxygen supplementation admitted to the hospital from January 28, 2020, through February 28, 2020, and followed up through March 13, 2020, in Union Hospital, Wuhan, China. Oxygen saturation (SpO2) and other measures were tested as predictors of in-hospital mortality in survival analysis. RESULTS: Of 140 patients with COVID-19-associated pneumonia, 72 (51.4%) were men, with a median age of 60 years. Patients with SpO2 values of 90% or less were older and were more likely to be men, to have hypertension, and to present with dyspnea than those with SpO2 values greater than 90%. Overall, 36 patients (25.7%) died during hospitalization after median 14-day follow-up. Higher SpO2 levels after oxygen supplementation were associated with reduced mortality independently of age and sex (hazard ratio per 1-U SpO2, 0.93; 95% CI, 0.91 to 0.95; P<.001). The SpO2 cutoff value of 90.5% yielded 84.6% sensitivity and 97.2% specificity for prediction of survival. Dyspnea was also independently associated with death in multivariable analysis (hazard ratio, 2.60; 95% CI, 1.24 to 5.43; P=.01). CONCLUSION: In this cohort of patients with COVID-19, hypoxemia was independently associated with in-hospital mortality. These results may help guide the clinical management of patients with severe COVID-19, particularly in settings requiring strategic allocation of limited critical care resources. TRIAL REGISTRATION: Chictr.org.cn Identifier: ChiCTR2000030852.

Short-term effects of cardiac resynchronization therapy on sleep-disordered breathing in patients with systolic heart failure.

OBJECTIVES: We evaluated the short-term effect of cardiac resynchronization therapy (CRT) on sleep apnea in patients with systolic heart failure. BACKGROUND: Sleep-disordered breathing is common in patients with left ventricular systolic dysfunction. METHODS: Twelve patients (mean [+/-SE] age, 59.6+/-7.8 years; mean left ventricular ejection fraction, 28.0+/-2.8%) with an implanted atrial-synchronized biventricular pacemaker for the treatment of left ventricular systolic dysfunction were selected and studied. Each subject underwent polysomnography on 3 consecutive nights with CRT on the first night, CRT off the second night, and CRT on the third night. Echocardiography was performed prior to each polysomnogram. RESULTS: The central sleep event index (ie, the number of central sleep apneas [CSAs] and hypopneas per hour of sleep) score was lower with CRT compared to that without CRT (mean central sleep event index score with CRT on, 6.9+/-1.7 events per hour of sleep; mean central sleep event index score with CRT off, 14.3+/-2.9 events per hour of sleep; mean central sleep event index score with CRT on, 8.1+/-1.5 events per hour of sleep; p<0.001). Similarly, the cumulative duration of central sleep events (the number of minutes per hour of sleep during CRT) was one half that observed without CRT (CRT on, 2.8+/-0.7 min per hour of sleep; CRT OFF 6.2+/-1.2 min per hour of sleep; CRT ON 3.1+/-0.7 min per hour of sleep; p<0.001). There was a significant correlation between mitral regurgitant volume and central sleep event index on all three nights (r>or=0.77; p<0.01). CONCLUSIONS: CRT reduces CSA severity in the short term. This reduction correlated significantly with the CRT-mediated reduction of mitral regurgitation.

Feasibility of directional percutaneous epicardial ablation with a partially insulated catheter.

PURPOSE: To demonstrate the feasibility of directional percutaneous epicardial ablation using a partially insulated catheter. METHODS: Partially insulated catheter prototypes were tested in 12 (6 canine, 6 porcine) animal studies in two centers. Prototypes had interspersed windows to enable visualization of epicardial structures with ultrasound. Epicardial unipolar ablation and ablation between two electrodes was performed according to protocol (5-60 W power, 0-60 mls/min irrigation, 78 s mean duration). RESULTS: Of 96 epicardial ablation attempts, unipolar ablation was delivered in 53.1%. Electrogram evidence of ablation, when analyzable, occurred in 75 of 79 (94.9%) therapies. Paired pre/post-ablation pacing threshold (N = 74) showed significant increase in pacing threshold post-ablation (0.9 to 2.6 mA, P < .0001). Arrhythmias occurred in 18 (18.8%) therapies (11 ventricular fibrillation, 7 ventricular tachycardia), mainly in pigs (72.2%). Coronary artery visualization was variably successful. No phrenic nerve injury was noted during or after ablation. Furthermore, there were minimal pericardial changes with ablation. CONCLUSIONS: Epicardial ablation using a partially insulated catheter to confer epicardial directionality and protect the phrenic nerve seems feasible. Iterations with ultrasound windows may enable real-time epicardial surface visualization thus identifying coronary arteries at ablation sites. Further improvements, however, are necessary.

Sympathetic neural responses to coronary occlusion during balloon angioplasty.

OBJECTIVE: The sympathetic nervous system is a key modulator of prognosis and outcome in cardiac ischaemia and infarction. The effects of acute cardiac ischaemia on sympathetic neural traffic in humans are unknown. We tested the hypothesis that angioplasty, and associated transient myocardial ischaemia, elicits changes in neural circulatory control, including direct intraneural measures of sympathetic traffic. METHODS: We measured muscle sympathetic nerve activity (MSNA), blood pressure and heart rate in 12 patients (11 men, one woman) undergoing clinically indicated elective coronary angioplasty of the left anterior descending (n = 7) or circumflex (n = 5) coronary artery. Baseline data were obtained for 2 min before occlusion. Each balloon inflation was designed to last up to 120 s. RESULTS: Coronary occlusion had no significant effect on blood pressure or heart rate. In contrast, occlusion resulted in a significant increase in MSNA, in 10 of the 12 patients, and in all seven of those patients undergoing angioplasty of the left anterior descending artery. The group mean increase in MSNA during occlusion was 36 +/- 11% (P = 0.008 versus preocclusion). MSNA increased within 60 s of occlusion (129 +/- 12% of baseline; n = 12; P = 0.04), and increased further during the next 60 s to 141 +/- 12% of baseline levels (n = 10; P < 0.001). Increases in MSNA were similar in patients with and without significant chest pain (39 +/- 9% versus 34 +/- 13%, respectively; P = 0.84). CONCLUSION: Acute coronary occlusion during angioplasty increases central sympathetic outflow, but there is no systematic change in heart rate. The increase in sympathetic nerve traffic cannot be explained by blood pressure changes or occlusion-related chest pain.

Tonic chemoreflex activation contributes to the elevated muscle sympathetic nerve activity in patients with chronic renal failure.

OBJECTIVE: Sympathetic activation may contribute to both cardiovascular morbidity and the progression of chronic kidney disease. The role of the chemoreceptors in determining sympathetic nerve discharge in patients with chronic renal failure (CRF) is unknown. We tested the hypothesis that tonic activation of excitatory chemoreceptor afferents contributes to the elevated sympathetic activity in patients with CRF. METHODS: Utilizing a double-blind, randomized, vehicle-controlled design, we examined the effects of chemoreflex deactivation on muscle sympathetic nerve activity (MSNA). We compared effects of breathing 100% oxygen for 15 min with effects of breathing room air for 15 min in 12 stable patients with CRF and in 12 control individuals with similar age, gender, blood pressure and body mass index. RESULTS: The baseline MSNA was elevated significantly in the patients with CRF as compared with the control individuals (50 +/- 2 vs 42 +/- 2 bursts/min; P < 0.05). Reductions in systolic blood pressure and pulse pressure in response to the administration of 100% oxygen were significantly different from those observed during administration of room air in patients with CRF. In patients with CRF, MSNA decreased by 29 +/- 7% (P < 0.01) during hyperoxia but did not change during administration of room air (5 +/- 6%; P = NS). By contrast, neither 100% oxygen or room air changed any measures in control individuals. CONCLUSIONS: Tonic activation of excitatory chemoreflex afferents contributes to increased efferent sympathetic activity to muscle circulation and to blood pressure control in patients with CRF. These findings may have important implications for understanding mechanisms underlying the link between CRF and cardiovascular disease.

Electrocardiography cannot reliably differentiate transient left ventricular apical ballooning syndrome from anterior ST-segment elevation myocardial infarction.

OBJECTIVE: The presentation and electrocardiographic (ECG) characteristics of transient left ventricular apical ballooning syndrome (TLVABS) can be similar to that of anterior ST-segment elevation myocardial infarction (STEMI). We tested the hypothesis that the ECG on presentation could reliably differentiate these syndromes. SUBJECTS AND METHODS: Between January 1, 2002 and July 31, 2004, we identified 18 consecutive patients with TLVABS who were matched with 36 subjects presenting with acute anterior STEMI due to atherothrombotic left anterior descending coronary artery occlusion. RESULTS: All patients with TLVABS were women (mean age, 72.0 +/- 13.1 years). The heart rate, PR interval, QRS duration, and corrected QT interval were similar between groups. Distribution of ST elevation was similar, but patients with anterior STEMI exhibited greater ST elevation. Regressive partitioning analysis indicated that the combination of ST elevation in lead V2 of less than 1.75 mm and ST-segment elevation in lead V3 of less than 2.5 mm was a suggestive predictor of TLVABS (sensitivity, 67%; specificity, 94%). Conditional logistic regression indicated that the formula: (3 x ST-elevation lead V2) + (ST-elevation V3) + (2 x ST-elevation V5) allowed possible discrimination between TLVABS and anterior STEMI with an optimal cutoff level of less than 11.5 mm for TLVABS (sensitivity, 94%; specificity, 72%). Patients with TLVABS were less likely to have concurrent ST-segment depression (6% vs 44%; P = .003). CONCLUSIONS: Women presenting with TLVABS have similar ECG findings to patients with anterior infarct but with less-prominent ST-segment elevation in the anterior precordial ECG leads. These ECG findings are relatively subtle and do not have sufficient predictive value to allow reliable emergency differentiation of these syndromes.

Dynamic coupling between heart rate and ventricular repolarisation.

A novel model for the coupling between ventricular repolarisation and heart rate (QT/RR) is presented. It is based upon a transfer function (TRF) formalism that describes the static and dynamic properties of this coupling, i.e., the behaviour after a sudden change in heart rate. Different TRF models were analysed by comparing their capability to describe experimental data collected from 19 healthy volunteers using several RR stimulation protocols: (i) rest with deep breathing at 0.1 Hz; (ii) tilt with controlled breathing at 0.1 and 0.33 Hz; and (iii) cycling. A search for the best TRF led to unambiguous identification of a three-parameter model as the most suitable descriptor of QT/RR coupling. Compared with established static models (linear or power-law), our model predictions are substantially closer to the experimental results, with errors approximately 50% smaller. The shape of the frequency and step responses of the TRF presented is essentially the same for all subjects and protocols. Moreover, each TRF may be uniquely identified by three parameters obtained from the step response, which are believed to be of physiological relevance: (i) gain for slow RR variability; (ii) gain for fast RR variability; and (iii) time during which QT attains 90% of its steady-state value. The TRF successfully describes the behaviour of the RR control following an abrupt change in RR interval, and its parameters may offer a tool for detecting pharmacologically induced changes, particularly those leading to increased arrhythmogenic risk.

Differential likelihood of NSTEMI vs STEMI in patients with sleep apnea.

BACKGROUND: Sleep apnea (SA) is associated with intermittent hypoxemia that may lead to ischemic preconditioning in the myocardium. This potential cardioprotective effect of SA may play a role in the development of non-ST-elevation myocardial infarction (NSTEMI) versus ST-elevation myocardial infarction (STEMI) during acute ischemia. However, there is limited evidence about the relative prevalence of NSTEMI versus STEMI in SA patients. We therefore prospectively investigated the prevalence of these two types of MI in patients with SA. METHODS: We prospectively studied 782 consecutive patients admitted with the diagnosis of acute MI (both NSTEMI and STEMI). All subjects underwent sleep evaluations using a portable diagnostic device after at least 48h post-admission, provided they were in stable condition. Six hundred and seven out of 782 patients had technically adequate sleep studies, and therefore were included in the final analysis. RESULTS: SA was present in 65.7% (n=399) and NSTEMI in 30% (n=182) of patients. Increasing severity of SA was associated with increasing likelihood of NSTEMI, and with decreasing likelihood of STEMI (p<0.001). Relative frequency of NSTEMI in the moderate to severe SA group (AHI≥15events/h) was 40.6% versus 29.9% for STEMI (p=0.01). CONCLUSION: The prevalence of NSTEMI increases with increasing severity of SA. This finding may suggest a cardioprotective role of SA, which may attenuate the development of STEMI, perhaps through ischemic preconditioning.

Sleep, sleep deprivation, autonomic nervous system and cardiovascular diseases.

Sleep deprivation (SD) has become a relevant health problem in modern societies. We can be sleep deprived due to lifestyle habits or due to sleep disorders, such as insomnia, obstructive sleep apnea (OSA) and neurological disorders. One of the common element of sleep disorders is the condition of chronic SD, which has complex biological consequences. SD is capable of inducing different biological effects, such as neural autonomic control changes, increased oxidative stress, altered inflammatory and coagulatory responses and accelerated atherosclerosis. All these mechanisms links SD and cardiovascular and metabolic disorders. Epidemiological studies have shown that short sleep duration is associated with increased incidence of cardiovascular diseases, such as coronary artery disease, hypertension, arrhythmias, diabetes and obesity, after adjustment for socioeconomic and demographic risk factors and comorbidities. Thus, an early assessment of a condition of SD and its treatment is clinically relevant to prevent the harmful consequences of a very common condition in adult population.

A Novel Defibrillation Tool: Percutaneously Delivered, Partially Insulated Epicardial Defibrillation.

INTRODUCTION: Epicardial defibrillation systems currently require surgical access. We aimed to develop a percutaneous defibrillation system with partially-insulated epicardial coils to focus electrical energy on the myocardium and prevent or minimize extra-cardiac stimulation. METHODS: We tested 2 prototypes created for percutaneous introduction into the pericardial space via a steerable sheath. This included a partially-insulated defibrillation coil and a defibrillation mesh with a urethane balloon acting as an insulator to the face of the mesh not in contact with the epicardium. The average energy associated with a chance of successful defibrillation 75% of the time (ED75) was calculated for each experiment. RESULTS: Of 16 animal experiments, 3 pig experiments had malfunctioning mesh prototypes such that results were unreliable; these were excluded. Therefore, 13 animal experiments were analyzed - 6 canines (29.8±4.0kg); 7 pigs (41.1±4.4kg). The overall ED75 was 12.8±6.7J (10.9±9.1J for canines; 14.4±3.9J in pigs [P=0.37]). The lowest ED75 obtained in canines was 2.5J while in pigs it was 9.5J. The lowest energy resulting in successful defibrillation was 2J in canines and 5J in pigs. There was no evidence of coronary vessel injury or trauma to extra-pericardial structures. CONCLUSION: Percutaneous, epicardial defibrillation using a partially insulated coil is feasible and appears to be associated with low defibrillation thresholds. Focusing insulation may limit extra-cardiac stimulation and potentially lower energy requirements for efficient defibrillation.