Cardiovascular Adaptations of Space Travel: A Systematic Review.

INTRODUCTION: Space travel imposes significant gravitational and radiation stress on both cellular and systemic physiology, resulting in myriad cardiovascular changes that have not been fully characterized. METHODS: We conducted a systematic review of the cellular and clinical adaptations of the cardiovascular system after exposure to real or simulated space travel in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed and Cochrane databases were searched in June 2021 for all peer-reviewed articles published since 1950 related to the following search terms entered in separate pairs: "cardiology and space" and "cardiology and astronaut." Only cellular and clinical studies in English concerning the investigation of cardiology and space were included. RESULTS: Eighteen studies were identified, comprising 14 clinical and 4 cellular investigations. On the genetic level, pluripotent stem cells in humans and cardiomyocytes in mice displayed increased beat irregularity, with clinical studies revealing a persistent increase in heart rate after space travel. Further cardiovascular adaptations included a higher frequency of orthostatic tachycardia but no evidence of orthostatic hypotension, after return to sea level. Hemoglobin concentration was also consistently decreased after return to Earth. No consistent change in systolic or diastolic blood pressure or any clinically significant arrhythmias were observed during or after space travel. CONCLUSION: Changes in oxygen carrying capacity, blood pressure, and post-flight orthostatic tachycardia may serve as reasons to further screen for pre-existing anemic and hypotensive conditions among astronauts.

An elderly woman with worrisome weakness: Take a pause to think of blocked PACs.

We present the case of a 93-year-old woman with dementia, with no pertinent cardiac history except for hyperlipidemia, who presented to the emergency department with six months of progressive dysphagia, weakness, and falls. While she had no seemingly cardiac symptoms and or remarkable cardiovascular examination features, the patient's initial electrocardiogram (ECG) showed occasional brief pauses with no atrial or ventricular activity. Computer interpretation of the rhythm was "sinus pause," but upon closer investigation, the true diagnosis was different, but with potential to be equally ominous if not accurately recognized and appropriately managed.

Carcinoid Heart Disease: Pathophysiology, Pathology, Clinical Manifestations, and Management.

Carcinoid heart disease (CHD) is a rare and potentially lethal manifestation of an advanced carcinoid (neuroendocrine) tumor. The pathophysiology of CHD is related to vasoactive substances secreted by the tumor, of which serotonin is most prominent in the pathophysiology of CHD. Serotonin stimulates fibroblast growth and fibrogenesis, which can lead to cardiac valvular fibrosis. CHD primarily affects right heart valves, causing tricuspid and pulmonic regurgitation and less frequently stenosis of these valves. Left heart valves are usually spared because vasoactive substances such as serotonin are enzymatically inactivated in the lung vasculature. The pathology of CHD is characterized by plaque-like deposition of fibrous tissue on valvular cusps, leaflets, papillary muscles, chordae, and ventricular walls. Symptomatic CHD usually presents between 50 and 70 years of age, initially as dyspnea and fatigue. Echocardiography is the mainstay of imaging and demonstrates thickened right heart valves with limited mobility and regurgitation. Treatment focuses on control of the underlying carcinoid syndrome, targeting subsequent valvular heart disease and managing consequent heart failure. Surgical valve replacement and catheter-directed valve procedures may be effective for selected patients with CHD.

Diagnostic Reclassification by a High-Sensitivity Cardiac Troponin Assay.

STUDY OBJECTIVE: Our objective is to describe the rates of diagnostic reclassification between conventional cardiac troponin I (cTnI) and high-sensitivity cardiac troponin T (hs-cTnT) and between combined and sex-specific hs-cTnT thresholds in adult emergency department (ED) patients in the United States. METHODS: We conducted a prospective, single-center, before-and-after, observational study of ED patients aged 18 years or older undergoing single or serial cardiac troponin testing in the ED for any reason before and after hs-cTnT implementation. Conventional cTnI and hs-cTnT results were obtained from a laboratory quality assurance database. Combined and sex-specific thresholds were the published 99th percentile upper reference limits for each assay. Cases underwent physician adjudication using the Fourth Universal Definition of Myocardial Infarction. Diagnostic reclassification occurred when a patient received a diagnosis of myocardial infarction or myocardial injury with one assay but not the other assay. Our primary outcome was diagnostic reclassification between the conventional cTnI and hs-cTnT assays. Diagnostic reclassification probabilities were assessed with sample proportions and 95% confidence intervals for binomial data. RESULTS: We studied 1,016 patients (506 men [50%]; median age 60 years [25th, 75th percentiles 49, 71]). Between the conventional cTnI and hs-cTnT assays, 6 patients (0.6%; 95% confidence interval 0.2% to 1.3%) underwent diagnostic reclassification regarding myocardial infarction (5/6 reclassified as no myocardial infarction) and 166 patients (16%; 95% confidence interval 14% to 19%) underwent diagnostic reclassification regarding myocardial injury (154/166 reclassified as having myocardial injury) by hs-cTnT. CONCLUSION: Compared with conventional cTnI, the hs-cTnT assay resulted in no clinically relevant change in myocardial infarction diagnoses but substantially more myocardial injury diagnoses.

Aspirin and clopidogrel high on-treatment platelet reactivity and genetic predictors in peripheral arterial disease.

OBJECTIVES: Our aims were to examine the prevalence and genetic predictors of aspirin and clopidogrel high on-treatment platelet reactivity (HoTPR), and associated adverse cardiovascular outcomes in patients with peripheral arterial disease (PAD). BACKGROUND: The association of aspirin and clopidogrel HoTPR with outcomes in PAD remains unclear. METHODS: This is a prospective cohort study of patients with angiographically documented PAD involving carotid and lower extremity arteries. Aspirin and clopidogrel HoTPR (using the VerifyNow Assay) and associated genetic predictors were compared to clinical outcomes. The primary end-point was a composite of major adverse cardiovascular events: all-cause mortality, myocardial infarction, stroke, target vessel revascularization (TVR) and limb-loss in patients who underwent extremity intervention. RESULTS: The study was stopped prematurely due to slow patient enrolment. Of 195 patients enrolled, the primary analysis was performed in 154 patients taking both drugs. Aspirin HoTPR was present in 31 (20%) and clopidogrel HoTPR in 76 (49%) patients. There was a trend toward more primary composite outcome events with PRU ≥ 235 (52% freedom-from-event rate vs. 70% for PRU < 235; P = 0.09). TVR was higher in those with PRU ≥ 235 (20 vs. 6%, unadjusted P = 0.02). There was no association between aspirin HoTPR and combined outcomes. Single nucleotide polymorphisms in serum paraoxonase/arylesterase 1 (PON1) gene was associated with aspirin HoTPR (P = 0.005) while SNP in phospholipase A2, group III (PLA2G3) gene was associated with clopidogrel HoTPR (P = 0.002). CONCLUSION: Clopidogrel HoTPR was significantly associated with TVR, while aspirin HoTPR was not associated with adverse clinical outcomes in patients with PAD.

Non-compressible ABIs are associated with an increased risk of major amputation and major adverse cardiovascular events in patients with critical limb ischemia.

Ankle-brachial indices (ABIs) are important for the assessment of disease burden among patients with peripheral artery disease. Although low values have been associated with adverse clinical outcomes, the association between non-compressible ABI (ncABI) and clinical outcome has not been evaluated among patients with critical limb ischemia (CLI). The present study sought to compare the clinical characteristics, angiographic findings and clinical outcomes of those with compressible (cABI) and ncABI among patients with CLI. Consecutive patients undergoing endovascular evaluation for CLI between 2006 and 2013 were included in a single center cohort. Major adverse cardiovascular events (MACE) were then compared between the two groups. Among 284 patients with CLI, 68 (24%) had ncABIs. These patients were more likely to have coronary artery disease ( p=0.003), diabetes ( p<0.001), end-stage renal disease ( p<0.001) and tissue loss ( p=0.01) when compared to patients with cABI. Rates of infrapopliteal disease were similar between the two groups ( p=0.10), though patients with ncABI had lower rates of iliac ( p=0.004) or femoropopliteal stenosis ( p=0.003). Infrapopliteal vessels had smaller diameters ( p=0.01) with longer lesions ( p=0.05) among patients with ncABIs. After 3 years of follow-up, ncABIs were associated with increased rates of mortality (HR 1.75, 95% CI: 1.12-2.78), MACE (HR 2.04, 95% CI: 1.35-3.03) and major amputation (HR 1.96, 95% CI: 1.11-3.45) when compared to patients with cABIs. In conclusion, ncABIs are associated with higher rates of mortality and adverse events among those undergoing endovascular therapy for CLI.

Long-term outcomes in patients with critical limb ischemia and heart failure with preserved or reduced ejection fraction.

The impact of heart failure (HF) on long-term survival in patients with critical limb ischemia (CLI) has not been well described. Outcomes stratified by left ventricular ejection fraction (EF) are also unknown. A single center retrospective chart review was performed for patients who underwent treatment for CLI from 2006 to 2013. Baseline demographics, procedural data and outcomes were analyzed. HF diagnosis was based on appropriate signs and symptoms as well as results of non-invasive testing. Among 381 CLI patients, 120 (31%) had a history of HF and 261 (69%) had no history of heart failure (no-HF). Within the HF group, 74 (62%) had HF with preserved ejection fraction (HFpEF) and 46 (38%) had HF with reduced ejection fraction (HFrEF). The average EF for those with no-HF, HFpEF and HFrEF were 59±13% vs 56±9% vs 30±9%, respectively. The likelihood of having concomitant coronary artery disease (CAD) was lowest in the no-HF group (43%), higher in the HFpEF group (70%) and highest in the HFrEF group (83%) ( p=0.001). Five-year survival was on average twofold higher in the no-HF group (43%) compared to both the HFpEF (19%, p=0.001) and HFrEF groups (24%, p=0.001). Long-term survival rates did not differ between the two HF groups ( p=0.50). There was no difference in 5-year freedom from major amputation or freedom from major adverse limb events between the no-HF, HFpEF and HFrEF groups, respectively. Overall, the combination of CLI and HF is associated with poor 5-year survival, independent of the degree of left ventricular systolic dysfunction.

Association of dual-antiplatelet therapy with reduced major adverse cardiovascular events in patients with symptomatic peripheral arterial disease.

OBJECTIVE: This study was conducted to determine whether there is additive benefit of dual-antiplatelet therapy (DAPT) with aspirin (acetylsalicylic acid [ASA]) and clopidogrel compared with ASA monotherapy among patients with symptomatic peripheral arterial disease. METHODS: This was an observational cohort analysis that included 629 patients with claudication or critical limb ischemia. The prevalence of patients taking ASA monotherapy vs DAPT was assessed monthly for up to 3 years. A propensity model was constructed to adjust for baseline demographic characteristics and to assess the effect of DAPT on major adverse cardiovascular events (MACEs) and major adverse limb events. RESULTS: At baseline, 348 patients were taking DAPT and 281 were taking ASA monotherapy. During 3 years of follow-up, 50 events (20%) occurred in the DAPT group vs 59 (29%) in the ASA monotherapy group. After propensity weighting, DAPT use was associated with a decreased risk of MACEs (adjusted hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.44-0.96) and overall mortality (adjusted HR, 0.55; 95% CI, 0.35-0.89). No association was found between DAPT use and the risk of major amputation (adjusted HR, 0.69; 95% CI, 0.37-1.29). In a subgroup of 94 patients who underwent point-of-care platelet function testing, 21% had decreased response to ASA and 55% had a decreased response to clopidogrel. No association was found between a reduced response to ASA or clopidogrel and adverse events at 1 year. CONCLUSIONS: DAPT may be associated with reduced rates of MACEs and death among patients with symptomatic peripheral arterial disease.

Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use is associated with reduced major adverse cardiovascular events among patients with critical limb ischemia.

Angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are recommended for secondary prevention in peripheral artery disease, but their effectiveness in patients with critical limb ischemia (CLI) is uncertain. We reviewed 464 patients with CLI who underwent diagnostic angiography or endovascular intervention from 2006-2013 at a multidisciplinary vascular center. ACEI or ARB use was assessed at the time of angiography. Major adverse cardiovascular events (MACE), mortality, and major adverse limb events (MALE) were assessed during three-year follow-up. Propensity weighting was used to adjust for baseline differences between patients taking and not taking ACEIs or ARBs. ACEIs or ARBs were prescribed to 269 (58%) patients. Patients prescribed ACEIs or ARBs had more baseline comorbidities including diabetes and hypertension (p<0.05). Patients prescribed ACEIs or ARBs had lower three-year unadjusted rates of MACE (40% versus 47%) and mortality (33% versus 43%). After propensity weighting, ACEI or ARB use was associated with significantly lower rates of MACE (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.58-0.99, p=0.04) and overall mortality (HR 0.71, 95% CI 0.53-0.95, p=0.02). There was no significant association between ACEI or ARB use and MALE (HR 0.97, 95% CI 0.69-1.35, p=0.2) or major amputation (HR 0.74, 95% CI 0.47-1.18, p=0.1). ACEI/ARB use is associated with lower MACE and mortality in patients with CLI, but there was no effect on limb-related outcomes.

Hospital patterns of medical management strategy use for patients with non-ST-elevation myocardial infarction and 3-vessel or left main coronary artery disease.

BACKGROUND: Patients with non-ST-elevation myocardial infarction (NSTEMI) and three-vessel or left main coronary disease (3VD/LMD) have a high risk of long-term mortality when treated with a medical management strategy (MMS) compared with revascularization. METHODS: We evaluated patterns of use and patient features across United States hospitals designated by MMS for NSTEMI patients with 3VD/LMD included in the ACTION Registry-GWTG from 2007-2012. RESULTS: A total of 42,535 patients without prior bypass surgery were found to have 3VD (≥50% stenosis in all major coronary vessels) or LMD (≥50% lesion) during in-hospital angiography at 423 hospitals with percutaneous and surgical revascularization capabilities. Hospitals (n = 316) with an adequate volume (≥25 NSTEMI patients treated) were stratified into tertiles defined by use of MMS; differences in patient characteristics and outcomes were analyzed. The proportion of NSTEMI patients treated with MMS at all hospitals varied from 16% to 19% each quarter and did not change significantly from 2007 to 2012 (P trend = .11). Among hospitals with adequate volume, the proportion of patients treated with MMS also varied widely (median 17.1%, range: 0.0-44.8%, P < .0001). Patient baseline characteristics, predicted mortality risk, actual in-hospital mortality rates, and discharge treatments were similar across hospital tertiles. CONCLUSIONS: Close to 20% of patients with NSTEMI and 3VD/LMD identified during in-hospital angiography are treated with MMS without revascularization in contemporary practice. Since the use of MMS varies widely across hospitals despite a relatively similar hospital-level case mix, these findings suggest that there is no standard threshold for the use of revascularization in NSTEMI patients with 3VD/LMD.

Smoking cessation is associated with decreased mortality and improved amputation-free survival among patients with symptomatic peripheral artery disease.

OBJECTIVE: Although smoking cessation is recommended for all patients with peripheral artery disease, there are little data regarding the prevalence of smoking among patients at the time of angiography or the effect of smoking cessation on clinical outcomes. METHODS: Consecutive patients with claudication or critical limb ischemia who underwent peripheral angiography from 2006 to 2013 were included in an observational cohort analysis. Smoking status was assessed at the time of angiography and during follow-up clinic visits. Kaplan-Meier analysis was used to assess the relationship between smoking cessation, mortality, and amputation-free survival. RESULTS: Among 739 patients (423 men and 316 women; mean age, 60 ± 12 years), 204 (28%) remained active smokers at the time of lower extremity angiography. At the time of angiography, the mean number of cigarettes smoked per day was 16 ± 10, and the mean pack-years was 40 ± 25. During the course of the subsequent year, 61 patients (30%) successfully quit smoking and maintained continued abstinence. Baseline medication use between groups did not differ significantly. The mean ankle-brachial index was also similar for quitters vs nonquitters (0.53 ± 24 vs 0.49 ± 0.22; P = .3). During follow-up to 5 years, patients who quit smoking had significantly lower all-cause mortality (14% vs 31%; hazard ratio, 0.40; 95% confidence interval, 0.18-0.90) and improved amputation-free survival (81% vs 60%; hazard ratio, 0.43, 95% confidence interval, 0.22-0.86) compared with patients who continued smoking, with most of the difference driven by reduced mortality among patients who quit smoking. The findings remained significant on multivariable analysis. CONCLUSIONS: Approximately one-third of active smokers with peripheral artery disease successfully quit smoking ≤ 1 year after lower extremity angiography. Patients who quit smoking have lower mortality and improved amputation-free survival compared with patients who continue smoking.

Association of elevated fasting glucose with lower patency and increased major adverse limb events among patients with diabetes undergoing infrapopliteal balloon angioplasty.

Diabetes mellitus (DM) is a significant risk factor for loss of patency after endovascular intervention, but the contribution of glycemic control to infrapopliteal artery patency among patients with DM is unknown. All percutaneous infrapopliteal interventions among patients with DM from 2006 to 2013 were reviewed and pre-procedure fasting blood glucose (FBG) was recorded. The primary endpoint was primary patency at 1 year as determined by duplex ultrasound. A total of 309 infrapopliteal lesions in 149 patients with DM were treated with balloon angioplasty during the study period. The median FBG was 144 mg/dL. At 1 year, the rate of primary patency was 16% for patients with FBG above the median, compared to 46% for patients with FBG below the median (hazard ratio (HR) 1.82 for FBG ≥144, p=0.005). Amputation rates at 1 year trended higher among patients with high versus low FBG (24% vs 15%, p=0.1). One year major adverse limb event rates were also higher for patients with high versus low FBG (35% vs 23%, p=0.05). Although patients with high FBG were more likely to have insulin-requiring DM (73% vs 50%, p=0.003) the association of high FBG with loss of primary patency remained significant even after adjusting for insulin use as well as other lesion-specific characteristics (adjusted HR 1.8, 95% CI 1.2-2.8). In conclusion, high fasting blood glucose at the time of infrapopliteal balloon angioplasty is associated with significantly decreased primary patency and may also be a risk factor for major adverse limb events among patients with a threatened limb.

Gender-related variation in the clinical presentation and outcomes of critical limb ischemia.

Critical limb ischemia (CLI) is a major cause of limb loss and mortality among patients with advanced peripheral artery disease. Our objective was to evaluate the gender-specific differences in patient characteristics and clinical outcomes among patients with CLI. We performed a retrospective analysis of 97 women and 122 men presenting with CLI who underwent angiography from 2006 to 2010. Baseline demographics, procedural details, and lesion characteristics were assessed for each patient. Kaplan-Meier analysis was used to assess long-term patient and lesion-level outcomes. Cox proportional hazard modeling was used to evaluate the relationship between gender and major adverse cardiovascular events (MACE). Compared to men, women were less likely to have a history of coronary artery disease (39% vs 54%, p = 0.02) or diabetes (57% vs 70%, p = 0.05) but had similar baseline medical therapy. At angiography, women were more likely to have significant femoropopliteal (77% vs 67%, p = 0.02) and multi-level infrainguinal disease (63% vs 51%, p = 0.02). Women were also more likely to undergo multi-vessel percutaneous intervention (69% vs 55%, p = 0.05), but had similar rates of limb salvage after percutaneous intervention or surgical bypass (HR 0.94 [95% CI 0.45-1.94], p = 0.9). During follow-up, women had higher rates of subsequent major adverse cardiovascular events (HR 1.63 [95% CI 1.01-2.63], p = 0.04). In conclusion, women with CLI are more likely to present with femoropopliteal and multi-level infrainguinal disease. Despite similar rates of limb salvage, women with CLI have an increased rate of subsequent major adverse cardiovascular events.

A 49-Year-Old Woman With Exertional Dyspnea and Dizziness.

CASE PRESENTATION: A 49-year-old woman with a history of right breast cancer status post radiation therapy presented to our ED with increasing chest pain, exertional dyspnea, fatigue, and dizziness for several weeks. She denied syncope or near-syncope, and she had no personal or family history of cardiac disease. Her outpatient medications included tamoxifen and venlafaxine.

Exercise and heart failure in the elderly.

In this review, we will examine the physiological responses to exercise in elderly populations (age > 65 years) with and without evidence of heart failure. Aging per se in both men and women is associated with a ~40% lower maximum oxygen consumption in sedentary subjects. In trained individuals, this value is 25-32% lower. A smaller SV accounts for nearly 50% of these age-related differences, and the remainder is explained by a lower maximal HR and reduced oxygen extraction. Exercise training is also associated with an increase in the arteriovenous O(2) difference in previously sedentary elderly men and women, which probably contributes to the overall beneficial effect of training in the elderly. However, during vigorous exercise (125 W), the cardiac output in the elderly is dependent upon an age-related increase in end-diastolic volume and stroke volume, which "compensates" partially for the age-related decrease in heart rate. Hence, in elderly individuals, the stroke volume during exercise depends upon diastolic filling. The changes that occur in the heart are also associated with an overall reduction in efferent sympathetic nerve activity. Despite this decline, the metaboreflex initiated by receptors in exercising muscles remains the main determinant of sympathetic activation (to maintain blood pressure) during exercise in the elderly. It is recognized that aging is associated with the development of heart failure, particularly in women in whom its prevalence increases >twofold from age 65-69 (6.6%) to age 85 years (14%). Almost half the people presenting with heart failure appear to have normal left ventricular systolic function, a phenomenon that is more common in women. Exercise training in elderly people with and without heart failure appears to have a beneficial effect in terms of enhancing the quality of life and functional capacity. Mortality benefit in the latter has not been established with certainty.

Effects of Supervised Exercise Training on Atrial Fibrillation: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS.

PURPOSE: Atrial fibrillation (AF) is associated with the comorbidities of a sedentary lifestyle. Endurance athletes also show an increased incidence of AF. The role of exercise in the treatment of AF is unknown so this study aimed to examine the effects of supervised exercise on AF. METHODS: A meta-analysis of randomized controlled trials (RCTs) examining supervised exercise training in participants with AF was performed. The primary outcome was AF recurrence and burden. Secondary outcomes included AF symptoms, quality of life, and cardiorespiratory fitness (CRF). RESULTS: Thirteen RCTs, involving 1155 participants, were included. Paroxysmal AF was present in 34% and persistent AF in 64%. The types of exercise were diverse and included cardiac rehabilitation (64%), aerobic training (7%), Qi Gong (4%), interval training (11%), and yoga (15%). Exercise training reduced AF recurrence (relative risk = 0.77: 95% CI, 0.60-0.99), improved quality of life in 5 of the 10 components of the Short Form 36 survey, and improved CRF (standardized mean difference [SMD] = 0.56: 95% CI, 0.27-0.85). The AF burden was reduced only in studies that included continuous ambulatory monitoring (SMD =-0.49: 95% CI, -0.96 to -0.01) but not when all studies were included (SMD =-0.12: 95% CI, -0.61 to 0.38). There was no difference in adverse events between exercise and control. CONCLUSIONS: Supervised exercise training is safe, reduces AF recurrence, and improves quality of life and CRF in participants with AF. Further large RCTs with ambulatory monitoring and robust exercise regimens are needed to assess the effects of exercise training on AF burden and AF symptoms.

Contrast-enhanced transesophageal echocardiography predicts neo-intimal coverage of device post-left atrial appendage closure.

BACKGROUND: Left atrial appendage (LAA) closure (LAAC) is a viable alternative to anticoagulation for stroke prevention in non-valvular atrial fibrillation. However, device-associated thrombosis (DAT) is known as a complication of LAAC as observed within the first few weeks after implantation. A noninvasive method is needed to predict the progress for endothelialization surveillance. The aim of the study was to develop a noninvasive visual contrast-enhanced transesophageal echocardiography (cTEE) method for monitoring the communication between left atrium (LA) and LAA post-LAAC by cTEE-score evaluating the contrast enhancement in LAA. METHODS: A total of 29 healthy dogs were studied by LAAC at < 24 h and 1, 2, 3 and 6-months. The LAAC procedure was assessed by TEE with color Doppler flow imaging (CDFI) and contrast imaging. The cTEE score was calculated based on the differential contrast opacification of LA and LAA cavities, the CDFI on the width of peri-device color flow, and that of histology on the level of occluder surface endothelialization in postmortem histological examination. Spearman's correlation analysis was used to correlate these scores. RESULTS: The correlation between cTEE and histology scores was superior to that between CDFI and histology scores. The trend of average cTEE score was tracked with that of histology, while that of CDFI was far from that of histology. The correlation coefficient of CDFI and histology scores was not significant (p > 0.05). CONCLUSIONS: The noninvasive visual cTEE is feasible and reliable to monitor communication between the LA and LAA post-LAAC. cTEE is superior to CDFI as a tool in predicting the progress for endothelialization surveillance.

Testing of low-risk patients presenting to the emergency department with chest pain: a scientific statement from the American Heart Association.

The management of low-risk patients presenting to emergency departments is a common and challenging clinical problem entailing 8 million emergency department visits annually. Although a majority of these patients do not have a life-threatening condition, the clinician must distinguish between those who require urgent treatment of a serious problem and those with more benign entities who do not require admission. Inadvertent discharge of patients with acute coronary syndrome from the emergency department is associated with increased mortality and liability, whereas inappropriate admission of patients without serious disease is neither indicated nor cost-effective. Clinical judgment and basic clinical tools (history, physical examination, and electrocardiogram) remain primary in meeting this challenge and affording early identification of low-risk patients with chest pain. Additionally, established and newer diagnostic methods have extended clinicians' diagnostic capacity in this setting. Low-risk patients presenting with chest pain are increasingly managed in chest pain units in which accelerated diagnostic protocols are performed, comprising serial electrocardiograms and cardiac injury markers to exclude acute coronary syndrome. Patients with negative findings usually complete the accelerated diagnostic protocol with a confirmatory test to exclude ischemia. This is typically an exercise treadmill test or a cardiac imaging study if the exercise treadmill test is not applicable. Rest myocardial perfusion imaging has assumed an important role in this setting. Computed tomography coronary angiography has also shown promise in this setting. A negative accelerated diagnostic protocol evaluation allows discharge, whereas patients with positive findings are admitted. This approach has been found to be safe, accurate, and cost-effective in low-risk patients presenting with chest pain.

Most important advances in preventive cardiology during this past decade: Viewpoint from the American Society for Preventive Cardiology.

The rapidly expanding field of preventive cardiology has brought with it several major advances in the past decade. Changes in guidelines for cholesterol mangement focusing on the identification of "statin eligible groups" and removal of actual low-density lipoprotein cholesterol (LDL-C) targets, in particular, as well as lower targets for blood pressure in updated hypertension guidelines, have made a major impact on healthcare. The availability of the sodium glucose transport protein-2 (SGLT2) inhibitors and glucagon-like peptide -1 receptor antagonists (GLP1-RA) for managing diabetes have shifted our focus in diabetes care beyond glucose lowering to addressing cardiovascular risk reduction. While many prior trials of fish oil therapy have failed to show benefit, the recent Reduction of Cardiovascular Events With EPA - Intervention Trial (REDUCE-IT) testing the efficacy of icosapent ethyl has shown dramatic benefit in further addressing residual atherosclerotic cardiovascular disease (ASCVD) risk beyond statin therapy not only in those with known ASCVD, but also in diabetic patients with multiple risk factors. The past decade also ushered in confirmation of the inflammation hypothesis of atherosclerosis with the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) using canakinumab, despite the fact the therapy was not approved by the Food and Drug Administration (FDA) for cardiovascular risk reduction. Also, to improve our understanding of heart disease in women, the emergence of novel concepts of ischemia or myocardial infarction in those with normal or nonobstructive atherosclerotic disease has been a major advance. Moreover, the past decade brought the emergence of proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody therapy and the cardiovascular risk reduction benefits seen in the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) and Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab (ODYSSEY OUTCOMES) trials, providing further evidence-based therapy for additional reduction of ASCVD risk beyond statin therapy. The PCSK9 monoclonal antibodies have facilitated the attainment of LDL-C levels never previously thought possible. Finally with the mRNA interference therapy inclisiran in development, we may soon have a "vaccine-like" approach for addressing dyslipidemia and atherosclerosis.