Alirocumab and plaque volume, calf muscle blood flow, and walking performance in peripheral artery disease: A randomized clinical trial.

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] cm3; 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).

Positional obstructive sleep apnea in patients with atrial fibrillation.

PURPOSE: 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. METHODS: 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. RESULTS: A total of patients (male: 56%, mean age 62 years) were included. POSA prevalence was similar between the two groups (46% vs. 39%; p = 0.33). Obesity and severe OSA (AHI ≥ 30/h) were associated with low likelihood of POSA (OR [CI] of 0.17 [0.09-0.32] and 0.28 [0.12-0.62]). In patients with AF, male sex was associated with a higher likelihood of POSA (OR [CI] of 3.16 [1.06-10.4]). CONCLUSION: POSA is common, affecting more than half of patients with AF, but the prevalence was similar in those without AF. Obesity and more severe OSA are associated with lower odds of POSA. Positional therapy should be considered in patients with mild OSA and POSA.

Atrial Fibrillation and Hypertension: "Quo Vadis".

Hypertension is one of the most well-established risk factors for atrial fibrillation. Longstanding 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 the pitfalls of 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 basis 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 the strategies of optimal blood pressure to minimize the risk of atrial fibrillation-related complications.

Right atrial volume index to left atrial volume index ratio is associated with adverse clinical outcomes in cardiogenic shock.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

The Influence of Obesity on the Association of Obstructive Sleep Apnea and Atrial Fibrillation.

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.

Daytime QT by Routine 12-Lead ECG Is Prolonged in Patients with Severe Obstructive Sleep Apnea.

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); moderate: 15-30 (n = 72); moderate: 15-30 (. 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 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 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 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). CONCLUSIONS: In a sleep clinic cohort, severe OSA was associated with higher QTc and clinically defined abnormal QTc compared with nonsevere OSA.

Lessons in clinical reasoning - pitfalls, myths, and pearls: a case of chest pain and shortness of breath.

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.

Withdrawal Notice: Atrial Fibrillation and Hypertension: "Quo Vadis"

The article has been withdrawn at the request of the editor of the journal Current Hypertension Reviews: Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php . BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Sleep Apnea and Sudden Cardiac Death.

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.

Management of a Mycobacterium immunogenum infection of a peritoneal dialysis catheter site.

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.

Feasibility, utility and symptom impact of modified mindfulness training in sarcoidosis.

A modified mindfulness-based exercise intervention has beneficial impact on people living with sarcoidosis http://ow.ly/XYTO30jtmms.

Cigarette smoking and male sex are independent and age concomitant risk factors for the development of ocular sarcoidosis in a New Orleans sarcoidosis population.

INTRODUCTION: Sarcoidosis is a multi-organ system granulomatous disease of unknown origin with an incidence of 1-40/100,000. Though pulmonary manifestations are predominant, ocular sarcoidosis (OS) affects 25-50% of patients with sarcoidosis and can lead to blindness. METHODS: A retrospective, single-center chart review of sarcoidosis cases investigated variables associated with the development of OS. Inclusion criteria were biopsy-proven sarcoidosis, disease duration greater than 1 year, documented smoking status on chart review and documentation of sarcoid-related eye disease. Multivariate analysis identified independent risk factors for OS. RESULTS: Of 269 charts reviewed, 109 patients met inclusion criteria. The OS group had a significantly higher proportion of smokers (71.4%) than without OS (42.0%, p=0.027) with no difference (p=0.61) in median number of pack years. Male sex was significantly higher in the OS group (57.1% versus 26.1%, p=0.009). Median duration of sarcoidosis was higher in the OS group (10 versus 4 years, p=0.031). Multivariate regression identified tobacco exposure (OR=5.25, p=0.007, 95% CI 1.58-17.41), male sex (OR=7.48, p=0.002, 95% CI 2.15-26.01), and age (OR=1.114, p=0.002, 95% CI 1.04-1.19) as concomitant risk factors for the development of OS. CONCLUSION: To date, there are few dedicated investigations of risk factors for OS, especially smoking. This investigation identified male sex, age, and tobacco exposure as independent risk factors for OS. Though disease duration did not withstand regression analysis in this moderately sized group, age at chart review suggests screening for OS should not remit but rather intensify in aging patients with sarcoidosis.