Objectives This study sought to evaluate respiratory disturbances as potential triggers for arrhythmia in those with sleep-disordered breathing (SDB). Background SDB is associated with increased risk of atrial fibrillation (AF) and non-sustained ventricular tachycardia (NSVT) as well as a predilection for sudden cardiac death during nocturnal sleeping hours. However, prior research has not established whether respiratory disturbances operate as triggers for nocturnal arrhythmias. Methods Overnight polysomnograms (PSGs) from the Sleep Heart Health Study (n = 2816) were screened for paroxysmal atrial fibrillation (PAF) and NSVT. We used the case-crossover design to determine whether apneas and/or hypopneas are temporally associated with episodes of PAF or NSVT. For each arrhythmia, 3 periods of sinus rhythm were identified as control intervals. PSGs were examined for the presence of respiratory disturbances, oxygen desaturations, and cortical arousals within a 90-second hazard period preceding each arrhythmia or control period. Results Fifty-seven participants with a wide range of SDB contributed 62 arrhythmias (76% NSVT). The odds of an arrhythmia following a respiratory disturbance were nearly 18-times (OR 17.5; 95% CI 5.3–58.4) the odds of an arrhythmia occurring following normal breathing. The absolute rate of arrhythmia associated with respiratory disturbances was low (1 excess arrhythmia/40000 respiratory disturbances). Neither hypoxia nor EEG-defined arousals alone increased arrhythmia risk. Conclusions Although the absolute arrhythmia rate is low, the relative risk of PAF and NSVT during sleep is markedly increased shortly after a respiratory disturbance. These results support a direct temporal link between SDB events and the development of these arrhythmias.

Atrial fibrillation (AF) is more common in those with obstructive sleep apnea (OSA) than in unaffected individuals and recurs more frequently in the presence of severe OSA after electrical cardioversion and AF ablation. However, it is unknown whether severity of OSA influences the efficacy of anti-arrhythmic drug (AAD) therapy in patients with OSA and AF. This study examined the impact of OSA severity on treatment of symptomatic AF with AADs. We studied 61 patients (62 ± 15 years; 21 women) treated with AADs for symptomatic AF who had overnight polysomnography. Rhythm control was prospectively defined as successful if a patient remained on the same AAD therapy for a minimum of 6 months with ≥75% reduction in symptomatic AF burden. Twenty-four patients (40%) had severe OSA. Thirty patients (49%) were rhythm controlled with AADs. Non-responders to AADs were more likely to have severe OSA than milder disease (52% vs 23%; p < 0.05); those with severe OSA were less likely to respond to AADs than participants with non-severe OSA (39% vs 70%; p = 0.02). Non-responders had higher apnea-hypopnea indices than responders (34 ± 25 vs 22 ± 18 events/hour; p = 0.05), but there were no differences between these groups in minimum oxygen saturation or % time spent in REM sleep. In conclusion, patients with severe OSA are less likely to respond to AAD therapy for AF than those with milder forms of OSA.

Purpose of review To provide an update on the connection between obstructive sleep apnea (OSA) and cardiovascular disease. Recent findings Large prospective studies have established that OSA is associated with an increased incidence of hypertension and, in men, of coronary disease, stroke, and heart failure. Advances in understanding the pathophysiologic basis for these associations include identification of a role for OSA in inducing abnormalities in hepatic lipid-metabolizing enzymes, endothelial dysfunction, and upregulation of pro-inflammatory and pro-thrombotic mediators. A large body of data implicates OSA as playing a significant role in the occurrence and resistance to treatment of atrial fibrillation. Clinical trials have shown small to modest improvements in blood pressure associated with continuous positive airway pressure (CPAP) use, with smaller or uncontrolled studies suggesting that CPAP may improve cardiovascular outcomes or intermediate markers. Summary OSA and cardiovascular disease commonly co-aggregate. Multiple studies indicate that OSA contributes to or exacerbates cardiovascular disease, and thus may be a novel target for cardiovascular risk reduction. While the evidence supports screening and treatment of OSA in patients at risk for cardiovascular disease, it also underscores a need for well powered clinical trials to examine the role of CPAP and other therapies in these populations.

Cocaine, in concentrations similar to those found clinically, induces activation of individual platelets studied in whole blood from some but not all donors, and platelet response to physiological agonists is enhanced by cocaine. Thus, cocaine-induced platelet activation may contribute to thrombosis following cocaine ingestion.

Pulmonary arterial hypertension (PAH) is increasingly recognized as a systemic disease driven by alteration in the normal functioning of multiple metabolic pathways affecting all of the major carbon substrates, including amino acids. We found that human pulmonary hypertension patients (WHO Group I, PAH) exhibit systemic and pulmonary-specific alterations in glutamine metabolism, with the diseased pulmonary vasculature taking up significantly more glutamine than that of controls. Using cell culture models and transgenic mice expressing PAH-causing BMPR2 mutations, we found that the pulmonary endothelium in PAH shunts significantly more glutamine carbon into the tricarboxylic acid (TCA) cycle than wild-type endothelium. Increased glutamine metabolism through the TCA cycle is required by the endothelium in PAH to survive, to sustain normal energetics, and to manifest the hyperproliferative phenotype characteristic of disease. The strict requirement for glutamine is driven by loss of sirtuin-3 (SIRT3) activity through covalent modification by reactive products of lipid peroxidation. Using 2-hydroxybenzylamine, a scavenger of reactive lipid peroxidation products, we were able to preserve SIRT3 function, to normalize glutamine metabolism, and to prevent the development of PAH in BMPR2 mutant mice. In PAH, targeting glutamine metabolism and the mechanisms that underlie glutamine-driven metabolic reprogramming represent a viable novel avenue for the development of potentially disease-modifying therapeutics that could be rapidly translated to human studies.

Aims Pulmonary transit time (PTT; the time for ultrasound contrast to travel from the right ventricle [RV] to the left atrium) may provide a single metric that reports on cardiopulmonary function while overcoming some of the challenges of standard echocardiographic measures. We conducted a pilot study to test the feasibility and reproducibility of echocardiographically derived PTT and to determine its association with established measures of cardiopulmonary function. Methods and Results Thirty-nine patients receiving clinically indicated ultrasound contrast were prospectively enrolled. PTT was measured in the apical four-chamber view using commercially available software. Reproducibility and inter-observer agreement were assessed in 9 patients. PTT was correlated with established measures of left ventricular systolic and diastolic function, RV function, and pulmonary vascular status. PTT could be measured in 89% (33/37) of patients without a contraindication to ultrasound contrast; all measurements from the last 20 patients were interpretable and obtained independently by a sonographer. Reproducibility and inter-observer agreement were excellent. PTT correlated well with standard echocardiographic indicators of cardiac status. A PTT > 4.5 seconds accurately identified all but 1 patient with cardiopulmonary dysfunction. Conclusions This pilot study demonstrates that measurement of PTT using ultrasound contrast is highly reproducible, accurately reflects global cardiopulmonary function across a range of cardiopulmonary disease, and can be readily obtained by an independent sonographer. Further studies are needed to determine whether PTT has incremental value in diagnosis and prognosis compared to conventional echocardiographic parameters.

There is substantial discordance in HEART scores between ED physicians and cardiologists. A triage cardiology system may help refine risk stratification of patients presenting to the ED with chest pain, even when the HEART Pathway tool is used.

We present two novel entropy-based measures that quantify sleep-stage transition dynamics (sleep structure) from polysomnogram derived hypnograms: Walsh spectral entropy (WSE) and Haar spectral entropy (HSE). These measures quantify patterns of temporal regularity of a categorical time series without requiring numerical encoding (scaling) of the (categorical) sleep stages. Additionally, we show that conditional entropy (CE) is well suited for quantifying predictability of the hypnogram. The relationship of those measures with traditional sleep fragmentation indices (arousal index, total sleep time, and sleep efficiency) is explored for a 394 participant sample of the Cleveland Family Study, an epidemiologic study in which standardized single-night polysomnogram data were collected. The new entropy-based sleep structure measures (WSE, HSE, and CE) are positively correlated (moderate to weak) with the traditional sleep fragmentation indices. Because the sleep structure measures developed in this paper provide direct information related to temporal patterns of sleep that is not contained in traditional sleep fragmentation measures, the correlation between these new alternative sleep structure measures and the traditional sleep fragmentation measures is less important. Our goal is not to develop alternative measures that correlate highly with traditional measures of sleep fragmentation, but rather to provide methods to quantify sleep structure by examining other (e.g., dynamic sleep-stage transition) properties of the hypnogram. Additionally, the relationship of the new entropy-based and traditional measures with daytime sleepiness as quantified by the Epworth sleepiness scale (ESS) is investigated. Multiple linear regression analysis shows that WSE has a stronger relationship with ESS than the traditional measures, even after both are adjusted for common confounders (age, race, gender, and body mass index). This further suggests that the entropy-based measures, especially WSE, are capturing additional temporal patterns of sleep not captured in the traditional sleep fragmentation measures, and have a relationship with daytime sleepiness.