Obstructive sleep apnea (OSA) is highly prevalent in patients with atrial fibrillation (AF). Prior studies suggest that excessive daytime sleepiness (EDS), a common symptom of OSA, is less pronounced in patients with AF. This study focused on a subtype of OSA, positional OSA (POSA), and examined its association with EDS overall and separately in patients with and without AF. This study included 222 OSA patients with and without AF history who underwent in-lab polysomnography. POSA was defined using three criteria: conventional POSA (cPOSA; supine/non-supine apnea-hypopnea index [AHI] ratio ≥ 2), intermediately conservative POSA (iPOSA; supine/non-supine AHI ratio ≥ 3), and exclusive POSA (ePOSA; supine/non-supine AHI ratio ≥ 2 and non-supine AHI < 5 events/h). EDS was determined by an Epworth Sleepiness Scale score ≥ 11. Logistic regression was performed to assess the associations. Overall, 55.4

Peripheral artery disease (PAD), defined by stenosis or occlusion of the extremities (particularly the lower extremities), affects 200 million individuals worldwide, including an estimated 7% of adults in the United States alone. It is the third leading cause of atherosclerotic morbidity after coronary artery disease and stroke. Regardless of symptoms, individuals with PAD are known to be at a significantly increased risk for development of a major adverse cardiovascular event and have a higher all‐cause mortality than those without disease. Despite PAD underdiagnosis, higher atherosclerotic cardiovascular disease burden, and evidence of decreased atherosclerotic cardiovascular disease risk with lipid modification, lipid undertreatment and nontreatment remain common among patients with PAD. This review addresses (1) the role of lipids in the pathophysiology of incident PAD and in adverse outcomes in those with PAD, (2) the role of lipid‐modifying therapies in primary and secondary prevention of PAD, and (3) insights regarding future directions of the study of lipids as it relates to PAD.

Background: The distal superficial femoral artery (SFA) is most commonly affected in peripheral artery disease (PAD). The effects of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab added to statin therapy on SFA atherosclerosis, downstream flow, and walking performance are unknown. Methods: Thirty-five patients with PAD on maximally tolerated statin therapy were recruited. Patients were randomized to alirocumab 150 mg subcutaneously ( n = 18) or matching placebo ( n = 17) therapy every 2 weeks for 1 year. The primary outcome was change in SFA plaque volume by black blood magnetic resonance imaging (MRI). Secondary outcomes were changes in calf muscle perfusion by cuff/occlusion hyperemia arterial spin labeling MRI, 6-minute walk distance (6MWD), low-density lipoprotein (LDL) cholesterol, and other biomarkers. Results: Age (mean ± SD) was 64 ± 8 years, 20 (57%) patients were women, 17 (49%) were Black individuals, LDL was 107 ± 36 mg/dL, and the ankle–brachial index 0.71 ± 0.20. The LDL fell more with alirocumab than placebo (mean [95% CI]) (−49.8 [−66.1 to −33.6] vs −7.7 [−19.7 to 4.3] mg/dL; p < 0.0001). Changes in SFA plaque volume and calf perfusion showed no difference between groups when adjusted for baseline (+0.25 [−0.29 to 0.79] vs −0.04 [−0.47 to 0.38] cm 3 ; p = 0.37 and 0.22 [−8.67 to 9.11] vs 3.81 [−1.45 to 9.08] mL/min/100 g; p = 0.46, respectively), nor did 6MWD. Conclusion: In this exploratory study, the addition of alirocumab therapy to statins did not alter SFA plaque volume, calf perfusion or 6MWD despite significant LDL lowering. Larger studies with longer follow up that include plaque characterization may improve understanding of the effects of intensive LDL-lowering therapy in PAD (ClinicalTrials.gov Identifier: NCT02959047).

Obstructive sleep apnea (OSA) is a common, potentially modifiable condition implicated in the pathogenesis of atrial fibrillation (AF). The presence and severity of OSA is largely sleep position–dependent, yet there is high variability in positional dependence among patients with OSA. We investigated the prevalence of positional OSA (POSA) and examined associated factors in patients with AF. We recruited an equal number of patients with and without AF who underwent diagnostic polysomnography. Patients included had ≥ 120 min of total sleep time with 30 min of sleep in both supine and lateral positions. POSA was defined as an overall apnea hypopnea index (AHI) ≥ 5/h, supine AHI (sAHI) ≥ 5/h, and sAHI greater than twice the non-supine AHI. POSA prevalence was compared in patients with and without AF adjusting for age, sex, OSA severity, and heart failure. A total of patients (male: 56

: Hypertension is one of the most well-established risk factors for atrial fibrillation. Long-standing untreated hypertension leads to structural remodeling and electrophysiologic alterations causing an atrial myopathy that forms a vulnerable substrate for the development and maintenance of atrial fibrillation. Hypertension-induced hemodynamic, inflammatory, hormonal, and autonomic changes all appear to be important contributing factors. Furthermore, hypertension is also associated with several atrial fibrillation-related comorbidities. As such, hypertension may represent an important target for therapy in atrial fibrillation. Clinicians should be aware of pitfalls of the blood pressure measurement in atrial fibrillation. While the auscultatory method is preferred, the use of automated devices appears to be an acceptable method in the ambulatory setting. There are pathophysiologic bases and emerging clinical evidence suggesting the benefit of renin-angiotensin system inhibition in risk reduction of atrial fibrillation development particularly in patients with left ventricular hypertrophy or left ventricular dysfunction. A better understanding of hypertension’s pathophysiologic link to atrial fibrillation may lead to the development of novel therapies for the primary prevention of atrial fibrillation. Finally, future studies are needed to address optimal blood pressure goal to minimize the risk of atrial fibrillation-related complications.

Structural remodeling in chronic systolic heart failure (HF) is associated with neurohormonal and hemodynamic perturbations among HF patients presenting with cardiogenic shock (CS) and HF. Our objective was to test the hypothesis was that atrial remodeling marked by an increased right atrial volume index (RAVI) to left atrial volume index (LAVI) ratio is associated with adverse clinical outcomes in CS. Patients in this cohort were admitted to the intensive care unit with evidence of congestion (pulmonary capillary wedge pressure > 15) and cardiogenic shock (cardiac index < 2.2, systolic blood pressure < 90 mmHg, and clinical evidence supporting CS) and had an echocardiogram at the time of admission. RAVI was measured using Simpson’s method in the apical four-chamber view, while LAVI was measured using the biplane disc summation method in the four and two-chamber views by two independent observers. Cox proportional hazards regression analysis was used to assess the association of RAVI-LAVI with the combined outcome of death or left ventricular assist device (LVAD). Among 113 patients (mean age 59 ± 14.9 years, 29.2% female), median RAVI/LAVI was 0.84. During a median follow-up of 12 months, 43 patients died, and 65 patients had the combined outcomes of death or LVAD. Patients with RAVI/LAVI ratio above the median had a greater incidence of death or LVAD (Log-rank p ≤ 0.001), and increasing RAVI/LAVI was significantly associated with the outcomes of death or LVAD (HR 1.71 95% CI 1.11–2.64, chi square 5.91, p = 0.010) even after adjustment for patient characteristics, echocardiographic and hemodynamic variables. RAVI/LAVI is an easily assessed novel echocardiographic parameter strongly associated with the survival and or the need for mechanical circulatory support in patients with CS.

Percutaneous coronary intervention (PCI) for stable ischemic heart disease (SIHD) has made tremendous strides over the past several decades. On the one hand, the diversity and complexity of lesions treatable with PCI has increased significantly. At the same time, our understanding of the appropriateness of PCI in SIHD has been refined with the results of trials, such as COURAGE (Optimal Medical Therapy with or without PCI for Stable Coronary Disease), ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina), FAME (Fractional Flow Reserve versus Angiography for Guiding Percutaneous Coronary Intervention), and ISCHEMIA (Initial Invasive or Conservative Strategy for Stable Coronary Disease). Overall, PCI along with optimal medical therapy (OMT) appears to result in significant improvements in anginal symptoms compared with OMT alone. At ≈5 years of followup, PCI for SIHD does not lower mortality. The effect on myocardial infarction (MI) appears to be neutral: a longterm reduction in nonprocedural MI is balanced by a higher risk of periprocedural MI, although the prognostic implications of the 2 are likely different.1 Patients with chronic total occlusion (CTO) of a coronary artery present a challenging and somewhat enigmatic subset of patients with SIHD. Although CTOs are highly prevalent among patients with SIHD, CTO PCI was typically excluded from these landmark trials. Furthermore, these patients typically have a higher burden of comorbidities and are at higher risk of future cardiac events compared with similar patients with nonCTO SIHD.2,3 In addition, there are significant technical complexities and lower success rates with CTO PCI compared with nonCTO PCI, with success rates only recently improving in the setting of technological advances and operator skill set (75%– 80% earlier, now ≈90%– 95%). In addition, procedural complication rates remain higher than for nonCTO PCI.3– 5

BACKGROUND AND OBJECTIVE:The association between obstructive sleep apnea (OSA) and atrial fibrillation (AF) has been closely studied. However, obesity is a powerful confounder in the causal relationship between OSA and cardiovascular disease. The contribution of obesity in the relationship between OSA and AF remains unclear. METHODS:We recruited 457 consecutive patients equally with and without AF who underwent clinically indicated diagnostic polysomnography at a single academic sleep center. Multivariable logistic regression adjusting for age, sex, hypertension, and heart failure was performed to study the independent association between OSA and AF stratified by obesity. RESULTS:A total of 457 patients (male: 56.2%, mean age 63.1 ± 13.3 years) was included. OSA prevalence was similar between those with and without AF (52.6% vs. 47.4%, respectively; p = 0.24). In multivariable analysis, no association was found between AF and OSA regardless of obesity status. When severe OSA (vs. non-severe OSA) was modeled as a dependent variable, AF was associated with a higher likelihood of severe OSA in non-obese patients [odds ratio (OR): 2.29, 95% confidence interval (CI): 1.23-4.35, p = 0.01], but not in obese patients (OR: 0.95, 95% CI: 0.48-1.90, p = 0.89). CONCLUSION:The association of OSA with AF was present only in the non-obese and was limited to severe OSA patients. In contrast, no association was found in obese patients. The association between OSA and AF is partly dependent on the body habitus.

Background. Obstructive sleep apnea (OSA) has been linked to sudden cardiac death (SCD). Prolonged QT is a recognized electrocardiographic (ECG) marker of abnormal ventricular repolarization linked to increased risk of SCD. We hypothesized that individuals with OSA have more pronounced abnormality in daytime QT interval. Methods. We reviewed consecutive patients who underwent clinically indicated polysomnography with 12-lead ECG within 1 year at a single center. Heart rate-corrected QT interval (QTc) was compared by OSA severity class (normal/mild: apnea‐hypopnea index AHI<15/hr (n=72); moderate: 15-30 (n=72); severe: >30 (n=105)) adjusting for body mass index, age, sex, hypertension, and heart failure. Further evaluation was performed by dividing patients into severe (AHI>30) and nonsevere (<30) OSA. Logistic analysis was used to determine association of OSA severity and abnormal QTc (>450/>470 ms for men/women, respectively). Results. A total of 249 patients were included. QTc was similar between the normal/mild and moderate groups, and the overall QTc trend increased across OSA (normal/mild: 435.6 ms; moderate: 431.36; severe: 444.4; p trend=0.03). Abnormal QTc was found amongst 34% of male and 31% of female patients. Patients with severe OSA had longer QTc compared with normal/mild OSA (mean difference (95% CI): 10.0 ms (0.5, 19.0), p=0.04). When stratified dichotomously (as opposed to three groups), patients with severe OSA again had longer QTc (vs. nonsevere OSA) (444.4 ms vs. 433.48 ms, p=0.004). Severe OSA was also associated with abnormal QTc (OR (95% CI): 2.68 (1.34, 5.48), p=0.006). Conclusions. In a sleep clinic cohort, severe OSA was associated with higher QTc and clinically defined abnormal QTc compared with nonsevere OSA.

The association between obstructive sleep apnea (OSA) and sudden cardiac death (SCD) has been described. A prolonged QT interval is a recognized marker of abnormal ventricular repolarization linked to increased risk of SCD. We hypothesized that patients with OSA would have more marked abnormalities in daytime QT interval. We identified consecutive patients who underwent clinically indicated diagnostic polysomnography with a 12-lead ECG at a single academic sleep center. Heart rate-corrected QT intervals (QTc) were compared by OSA severity class (normal/mild: apnea hypopnea index (AHI) <15/hr; moderate: 15-30; severe: >30) adjusting for age, sex, body mass index, hypertension, and heart failure (HF). Further evaluation was performed by dichotomizing patients into severe (AHI >30/hr) and non-severe (<30/hr) OSA. Logistic analysis was used to determine the association of OSA severity and abnormal QTc (>450msec / >470msec for men/women, respectively). A total of 249 patients (50.2% female, mean age 57.2 [12.5]) were included. This cohort had a high burden of cardiovascular disease (73% with hypertension, 20% with HF). Abnormal QTc was present in 34% of males and 31% of females. QTc increased across OSA groups (normal/mild: 435.6 msec; moderate: 431.36; severe: 444.4, p= 0.03). Patients with severe OSA had longer QTc compared with normal/mild OSA (mean difference 10.0msec [0.5,19.0], p=0.04). When stratified dichotomously, patients with severe OSA had longer QTc compared to non-severe (444.4 msec vs. 433.48 msec, p=0.004). Severe OSA was also associated with abnormal QTc (OR 2.68 [1.34,5.48], p=0.006). There was significant interaction by HF status as the difference in QTc by OSA status (non-severe vs. severe) was more prominent in patients with HF (456.1 msec [435.3-476.8] vs. 480.5 [458.9-502.1], p=0.028). In a single sleep center cohort at elevated cardiovascular risk, patients with severe OSA had a prolonged daytime QTc compared to those with normal to mild OSA. Further, the prevalence of clinically significant abnormal QTc was higher in the severe (vs. non-severe) OSA group . The presence of severe OSA may represent a novel risk of SCD particularly in patients with HF. None

The association of obstructive sleep apnea (OSA) with atrial fibrillation (AF) has been well-described. However, obesity is a powerful confounder in the causal relationship between OSA and cardiovascular disease. The role of obesity in the relationship of OSA and AF remains unclear. We identified an equal number of consecutive patients with and without AF who underwent clinically indicated diagnostic polysomnography at a single academic sleep center. OSA was defined by AHI >15/hr, with severe OSA being AHI >30/hr. Obesity was defined as BMI >30kg/m2. Multivariable logistic regression adjusting for age, sex, hypertension, and heart failure (HF) was performed to examine the independent association between OSA and AF stratified by obesity. A total of 457 patients (male: 56%, mean age 62.6± 14.0 years) were included. There was a high prevalence of HF in the AF cohort (67.7%; low vs. high BMI group; 56.3% vs. 80%, p=0.0001). OSA prevalence was similar between those with and without AF (57.2% vs. 51.8%, p=0.24). The prevalence of OSA was higher in patients with AF in the non-obese group (47.1% vs. 60.5%, p= 0.037), but not in obese patients (57.0% vs. 53.6%, p=0.62). However, this association in non-obese group was lost in multivariable logistic analysis (OR 1.11 [0.59-2.08], p=0.74). Sensitivity analysis showed that presence of AF was associated with severe OSA in the non-obese group (OR 2.19 [1.08-4.48], p=0.03). Analysis excluding patients with HF yielded similar results. Among patients without AF or HF, age (OR 2.01, [1.02-4.06]), obesity (OR 1.86, [1.01-3.48]), and gender (OR 2.09, [1.16-3.80]) were risk factors associated with OSA. In those with both AF and HF, only male sex (OR 3.03, [1.51-6.19]) was associated with OSA. In high risk AF patients, the association of AF with OSA was present only in the non-obese, and was limited to severe OSA patients. In contrast no association was found in obese patients. This suggests that the association between AF and OSA is partly dependent on the body habitus. None

Introduction: Sleep apnea is highly-prevalent in patients with atrial fibrillation (AF), and is considered an important risk factor for AF recurrence following cardioversion or catheter-based ablat...

Background Defects in human cognition commonly result in clinical reasoning failures that can lead to diagnostic errors. A metacognitive structured reflection on what clinical findings fit and/or do not fit with likely and "can't miss" diagnoses may reduce such errors. Case presentation A 57-year-old man was sent to the emergency department from clinic with chest pain, severe shortness of breath, weakness, and cold sweats. Further investigation revealed multiple risk factors for coronary artery disease, sudden onset of exertional dyspnea, and chest pain that incompletely resolved with rest, mild tachycardia and hypoxia, an abnormal electrocardiogram (ECG), elevated serum cardiac biomarkers, and elevated B-type natriuretic peptide (BNP) in the absence of left-sided heart failure. He was treated for acute coronary syndrome (ACS), discharged, and quickly returned with worsening symptoms that eventually led to a diagnosis of submassive pulmonary embolism (PE). Conclusions Through integrated commentary on the diagnostic reasoning process from clinical reasoning experts at two institutions, this case underscores the importance of frequent assessment of fit along with explicit explanation of dissonant features in order to avoid premature closure and diagnostic error. A fishbone diagram is provided to visually demonstrate the major factors that contributed to the diagnostic error. A case discussant describes the importance of diagnostic schema as an analytic reasoning strategy to assist in the creation of a differential diagnosis, problem representation to summarize updated findings, a Popperian analytic approach of attempting to falsify less-likely hypotheses, and matching pertinent positives and negatives to previously learned illness scripts. Finally, this case provides clinical teaching points in addition to a pitfall, myth, and pearl specific to premature closure.

Sleep plays an integral role in maintaining health and quality of life. Obstructive sleep apnea (OSA) is a prevalent sleep disorder recognized as a risk factor for cardiovascular disease (CVD) and arrhythmias. Sudden cardiac death (SCD) is a common and devastating event. Out-of-hospital SCD accounts for the majority of deaths from cardiac disease, which is the leading cause of death globally. A limited but emerging body of research have further elaborated on the link between OSA and SCD. In this article, we aim to provide a critical review of the existing evidence by addressing the following: What epidemiologic evidence exists linking OSA to SCD? What evidence exists for a pathophysiologic connection between OSA and SCD? Are there electrocardiographic markers of SCD found in patients with OSA? Does heart failure represent a major effect modifier regarding the relationship between OSA and SCD? What is the impact of sleep apnea treatment on SCD and cardiovascular outcomes? Finally, we elaborate on ongoing research to enhance our understanding of the OSA-SCD association.

Mycobacterium immunogenum is a member of the rapidly growing non-tuberculous mycobacteria and is a relatively new species identified within this group. An 81-year-old immune-competent male was diagnosed with M. immunogenum infection of his peritoneal dialysis catheter exit site and surrounding soft tissue. To our knowledge, this is the first reported case of M. immunogenum infection of a peritoneal catheter. Treatment included catheter removal, local surgical debridement, and combination antimicrobial therapy. Herein, we review literature describing antibiotic management of M. immunogenum, an organism for which optimal therapy is not defined.

Abstract Background Mycobacterium immunogenum is a somewhat recently identified species of rapidly growing nontuberculous mycobacteria, genetically related to M. abscessus and M. chelonae. Resistance patterns of rapidly growing nontuberculous mycobacterium species can make them difficult to treat. This is particularly true of M. immunogenum, in part due to the infrequency of reported cases of human infection and limited data to guide therapy. Methods We present here a case of M. immunogenum skin and soft-tissue infection at the site of insertion of a peritoneal dialysis catheter in a patient with end-stage renal disease. He initially presented with nodular subcutaneous lesions around his catheter site that progressed through oral antibiotics. This led to sampling which confirmed the diagnosis of M. immunogenum. We conducted a review of the literature to identify previously reported cases of M. immunogenum, including skin and soft-tissue infections, and used these data to guide management. Results We reviewed 11 reports (cases and case series) of Mycobacterium immunogenum in the literature. Susceptibilities often take weeks to return, and so empiric therapy is based on case series, and then later adjusted based on susceptibilities. Patients received combined antimicrobial regimens with durations of 2 weeks to 12 months, with variable outcomes. Several required surgical debridement, as was the case with our patient. His PD catheter was removed and he was treated empirically with amikacin, azithromycin, and tigecycline intravenous induction. His ultimate long-term regimen was later switched to azithromycin, clofazimine, and tedizolid due to side effects and the eventually available susceptibility profile. Conclusion The treatment of M. immunogenum remains a challenge due to the relative scarcity of data to guide treatment, and consequent lack of systemic approach to therapy. Most reported cases involve the use of a macrolide, often in combination with an aminoglycoside or a fluoroquinolone. Several started with intravenous induction, followed by transition to oral therapy on the order of weeks to months. Others also require surgical debridement. More data are required to develop a standardized approach to the treatment of M. immunogenum. Disclosures All authors: No reported disclosures.