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.

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.

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.

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.

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.

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.

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.

Spotlight from the American Society for Preventive Cardiology on Key Features of the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guidelines on the Management of Blood Cholesterol.

The 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol retains focus on recommendations for statin treatment in the original four statin-eligible groups [those with atherosclerotic cardiovascular disease (ASCVD), diabetes, low-density lipoprotein cholesterol (LDL-C) ≥ 190 mg/dL, and higher risk primary prevention] without the use of treatment initiation or target LDL-C levels from the earlier 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline, but has several new features. First, patients with primary prevention are divided into those who are at low (< 5%), borderline (5% to < 7.5%), intermediate (7.5% to < 20%), and high (≥ 20%) risk based on the ASCVD risk estimator. Moreover, the new guideline goes further to consider a wider range of factors [now called "risk enhancers"-premature family history of ASCVD, persistently high LDL-C, chronic kidney disease (CKD), metabolic syndrome, conditions specific to women, inflammatory diseases, and high-risk ethnicities] that can be used to better inform the treatment decision. Moreover, more detailed recommendations on how the results of coronary calcium scanning can be used to inform the treatment decision are provided, including how it may be used to "de-risk" certain patients for delaying or avoiding the use of statin therapy. There are also specific sections for cholesterol management in other patient subgroups including women, children, certain ethnic groups, those with CKD, chronic inflammatory disorders and HIV, as well as discussion on the management of hypertriglyceridemia. Importantly, for persons with known ASCVD, a distinction is made for those who are at "very high risk" based on having had two major ASCVD events or one major event and two or more other high risk conditions, such as diabetes or other major risk factors, or bypass surgery or percutaneous intervention. Finally, the concept of a threshold LDL-C for initiating a non-statin therapy (after considering highest tolerated statin dosage) is provided, with ezetimibe recommended as the key non-statin to be added if the LDL-C still remains ≥ 70 mg/dL for all ASCVD patients, and in those who are at "very high risk", further consideration for using a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. While the new guideline does have greater detail (and arguably, complexity), the refinements provide a strategy for guiding the clinician to target both statin and non-statin therapy to those most likely to derive benefit.

Frequency and Influence of Exercise-Induced Artifact in Electrocardiograms During Exercise Treadmill Testing for Detection of Myocardial Ischemia.

BACKGROUND: Exercise treadmill testing (ETT) is frequently utilized for noninvasive detection of myocardial ischemia and coronary artery disease. The frequency of electrocardiogram (ECG) artifacts (ECGA) during ETT and their influence on the identification of exercise-induced ischemia are not known. METHODS: We reviewed all ETTs with ST segment depression in the University of California, Davis, Medical Center treadmill database during each of the years 2012 and 2016 to identify tests with exercise-induced ST segment depression in the inferior and inferolateral leads. We identified cases with ECGA during progressive phases of the test, and we assessed the influence of comorbidities and the impact of ECGA on the diagnosis of coronary artery disease. Tests were considered false or true positive based on the result of confirmatory tests. RESULTS: Of 2,100 tests, we identified 123 patients with exercise-induced ST segment depression in inferior or inferolateral leads (men, 43%; mean age, 59 ± 10 years; white, 59%). Tests were symptom-limited: maximum heart rate, 153 ± 18; peak METs (metabolic equivalents of resting total oxygen consumption), 9.4 ± 2.7; ECGA occurred in 91% of tests at peak exercise with earlier occurrence among females. Tests were less likely to be true positive with peak ECGA than those without ECGA (13% vs. 50%, p = 0.05). CONCLUSIONS: ECGA at peak exercise are frequent and related to peak heart rate and peak metabolic equivalents of resting total oxygen consumption, suggesting a motion effect. ECGA affected the diagnostic accuracy of ETT examinations, indicating that algorithms to reduce artifact for improved diagnosis of ETT require further investigation.

Identification and Management of Intermediate Risk Patients in the Chest Pain Unit.

OBJECTIVE: We examined low risk (LR) patients admitted to our chest pain unit (CPU) with negative cardiac injury markers, normal electrocardiogram, and clinical stability. We hypothesized that there is a sub-group of intermediate risk (IR) patients within the larger LR population. METHODS: Criteria for IR were the aforementioned 3 indicators of LR and ≥1 of the following: (1) known coronary artery disease (CAD), (2) men ≥45 yo, women ≥55 yo, and (3) ≥3 cardiac risk factors. We compared patient characteristics, use of pre-discharge testing (PDT), and major adverse cardiac events (MACE). RESULTS: IR patients numbered 371, whereas LR patients totaled 70. IR patients were older (61 vs 46 years), more had known CAD (28 vs. 0%), had a higher median number of risk factors (2 vs. 1) and were less likely to be women (49 vs. 81%), all P < 0.0001. IR patients received a greater median number of tests compared with LR patients (1 vs. 0, P < 0.0001). CONCLUSIONS: Among the IR group, 16 patients (4%) had a cardiac event at the index CPU visit, 2 (0.5%) experienced MACE at 30-day follow-up, and 2 (0.5%) had MACE at 6 months follow-up. No LR patients had MACE at any point in the study. Thus, the majority of CPU patients are IR, have more risk factors than LR group, and are more likely to receive PDT. IR patients were managed safely in a CPU, while maintaining low rates of MACE post-discharge.

Pre-diabetes, diabetes and predictors of incident angina among older women and men in the Cardiovascular Health Study.

Diabetes mellitus and angina pectoris are important conditions in older persons. The utility of pre-diabetes mellitus, diabetes mellitus and other risk factors as predictors of incident angina pectoris among older adults has not been characterized. We examined incident angina pectoris rates by sex and diabetes mellitus status in 4511 adults aged ⩾65 years without coronary heart disease at baseline from the Cardiovascular Health Study. Cox regression examined predictors of incident angina pectoris, including pre-diabetes mellitus or diabetes mellitus adjusted for sociodemographic characteristics and other risk factors, over 12.2 ± 6.9 years of follow-up. Overall, 39.1% of participants had pre-diabetes mellitus, 14.0% had diabetes mellitus and 532 (11.8%) had incident angina pectoris. Incident angina pectoris rates per 1000 person-years in those with neither condition, pre-diabetes mellitus, and diabetes mellitus were 7.9, 9.0 and 12.3 in women and 10.3, 11.2 and 14.5 in men, respectively. Pre-diabetes mellitus and diabetes mellitus were not independently associated with incident AP; however, key predictors of AP were male sex, low-density lipoprotein-cholesterol, triglycerides, systolic blood pressure, antihypertensive medication and difficulty performing at least one instrumental activity of daily living (all p < 0.05 to p < 0.01). In our cohort of older adult participants, while the incidence of AP is greater in those with diabetes mellitus, neither diabetes mellitus nor pre-diabetes mellitus independently predicted incident angina pectoris.

Intermittent Nonhabitual Coffee Consumption and Risk of Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Though it is a widely held belief that caffeinated beverages predispose individuals to arrhythmias, it is not clear whether regular coffee consumption is associated with development of atrial fibrillation (AF). OBJECTIVE: We examined the association between long-term coffee consumption and development of AF in both habitual (≥0.5 cups of daily coffee) and nonhabitual (<0.5 cups/day) drinkers. METHODS: A total of 5,972 men and women, aged 45-84 years and without a history of cardiovascular disease at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA) were followed from 2000 to 2014 for incident AF with baseline coffee consumption assessed in 2000-2002 via a Food Frequency Questionnaire and divided into quartiles of 0 cups/day, >0 to <0.5 cups/day, ≥0.5 to 1.5 cups/day, and ≥1.5 cups/day. RESULTS: Out of the 828 incident cases of AF, intermittent coffee consumption (>0 to 0.5 cups of daily coffee) was associated with a greater risk of incident AF (HR 1.22, 95% CI 1.01-1.48) relative to 0 cups/day in multivariable Cox proportional hazards models after adjustment for numerous AF risk factors. This relation was particularly pronounced in men (adjusted HR=1.36, 95% CI 1.04-1.77). Higher coffee consumption was not associated with AF risk (HR 1.03, 95%CI 0.93-1.14 for ≥0.5 to 1.5 cups/day and 1.05, 95%CI 0.97-1.13 for ≥1.5 cups/day). CONCLUSIONS: While there appears to be no dose-response association between habitual coffee intake and AF risk, we found evidence that intermittent, but not habitual, coffee consumption is associated with a modestly increased risk of incident AF that deserves further study.

Usefulness of Excellent Functional Capacity in Men and Women With Ischemic Exercise Electrocardiography to Predict a Negative Stress Imaging Test and Very Low Late Mortality.

Exercise electrocardiography (ExECG) is widely employed to assess patients for coronary artery disease but it has limited diagnostic accuracy. Many patients with positive (ischemic) tests based on exercise-induced ST depression undergo secondary evaluation by noninvasive stress imaging. We hypothesized that high functional capacity in patients with positive ExECG could predict: (1) negative results in secondary evaluation by exercise echocardiography (ESE) or myocardial perfusion scintigraphy (MPS) and (2) low mortality on late follow-up. We evaluated 511 consecutive patients (312 men, 199 women; age 51 ± 9 years) referred for ESE or MPS after an ischemic ExECG at a treadmill workload of ≥10 metabolic equivalents. All-cause mortality was also obtained. Of 511 patients, 401 underwent ESE and 110 had MPS for secondary study. ESE was negative in 94% (376 of 401) and positive in 6% (25 of 401). MPS was also negative in 94% (103 of 110) and positive in 6% (7 of 110). Total stress imaging results were negative in 92% (286 of 312) of men and 97% (193 of 199) of women. During follow-up of approximately 6 years, there were 3 deaths with total all-cause mortality of 0.6% and average annual mortality of 0.1%. In conclusion, high functional capacity in patients with an ischemic ExECG predicts a negative ESE or MPS in a large majority of patients and very favorable late survival in both men and women. These results suggest that patients with ischemic ExECGs and a workload of ≥10 metabolic equivalents during ExECG may not require additional noninvasive or invasive evaluation.

Usefulness of Predischarge Cardiac Testing in Low Risk Women and Men for Safe, Rapid Discharge from a Chest Pain Unit.

Predischarge cardiac testing (PDT) in low-risk patients evaluated for acute coronary syndrome in a chest pain unit (CPU) remains a challenge. It is unclear whether PDT varies by gender. We analyzed consecutive low-risk women and men evaluated in our CPU over a 2-year period and compared the utilization of PDT (exercise treadmill test, myocardial stress perfusion scintigraphy, exercise stress echocardiography, invasive coronary angiography, or no test), and incidence of major adverse cardiac events (MACE) at 30 days and 6 months. The study group comprised 619 patients (54% women). A large proportion of both genders did not undergo PDT, although this finding was more frequent in women (50% women vs 40% men, p = 0.01). At 30 days, there were no MACE in either gender. After 6 months of follow-up, MACE remained very low in both women and men (2 [1%] vs 2 [1%]), and in patients who did and did not receive PDT (2 [1%] vs 2 [1%]). Mean length of stay in the CPU was 5.4 hours in patients without PDT and 9.8 hours in those with PDT (p <0.0001) without altering postdischarge MACE. When referred for PDT, women more often underwent myocardial stress perfusion scintigraphy than men (22% vs 14%, p = 0.005) and less often received exercise treadmill test (20% vs 39%, p <0.0001). Yield of abnormal PDT was low in both women and men although it was lower in women (1% vs 5%, p = 0.02). In conclusion, many low-risk women and men evaluated in a CPU for acute coronary syndrome can be safely and rapidly discharged without PDT and with low risk for MACE at 30 days and at 6 months. Exclusion of PDT was associated with significantly reduced length of stay while maintaining safety in terms of postdischarge MACE.