Atrial fibrosis by cardiac MRI is a correlate for atrial stiffness in patients with atrial fibrillation.

A relationship between left atrial strain and pressure has been demonstrated in many studies, but not in an atrial fibrillation (AF) cohort. In this work, we hypothesized that elevated left atrial (LA) tissue fibrosis might mediate and confound the LA strain vs. pressure relationship, resulting instead in a relationship between LA fibrosis and stiffness index (mean LA pressure/LA reservoir strain). Sixty-seven patients with AF underwent a standard cardiac MR exam including long-axis cine views (2 and 4-ch) and a free-breathing high resolution three-dimensional late gadolinium enhancement (LGE) of the atrium (N = 41), within 30 days prior to AF ablation, at which procedure invasive mean left atrial pressure (LAP) was measured. LV and LA Volumes, EF, and comprehensive analysis of LA strains (strain and strain rates and strain timings during the atrial reservoir, conduit and active, i.e. active atrial contraction, phases) were measured and LA fibrosis content (LGE (ml)) was assessed from 3D LGE volumes. LA LGE was well correlated to atrial stiffness index overall (R = 0.59, p < 0.001), and among patient subgroups. Pressure was only correlated to maximal LA volume (R = 0.32) and the time to peak reservoir strain rate (R = 0.32) (both p < 0.01), among all functional measurements. LA reservoir strain was strongly correlated with LAEF (R = 0.95, p < 0.001) and LA minimum volume (r = 0.82, p < 0.001). In our AF cohort, pressure is correlated to maximum LA volume and time to peak reservoir strain. LA pressure/ LA reservoir strain, a metric of stiffness, correlates with LA fibrosis (LA LGE), reflecting Hook's Law.

Atrial Fibrosis by cardiac MRI is a correlate for atrial stiffness in patients with atrial fibrillation.

Aims: A relationship between left atrial strain and pressure has been demonstrated in many studies, but not in an atrial fibrillation (AF) cohort. In this work, we hypothesized that elevated left atrial (LA) tissue fibrosis might mediate and confound the LA strain vs. pressure relationship, resulting instead in a relationship between LA fibrosis and stiffness index (mean pressure/LA reservoir strain). Methods and Results: Sixty-seven patients with AF underwent a standard cardiac MR exam including long-axis cine views (2 and 4-ch) and a free-breathing high resolution three-dimensional late gadolinium enhancement (LGE) of the atrium (N=41), within 30 days prior to AF ablation, at which procedure invasive mean left atrial pressure (LAP) was measured. LV and LA Volumes, EF, and comprehensive analysis of LA strains (strain and strain rates and strain timings during the atrial reservoir, conduit and active phases) were measured and LA fibrosis content (LGE (ml)) was assessed from 3D LGE volumes. LA LGE was well correlated to atrial stiffness index (LA mean pressure/LA reservoir strain) overall (R=0.59, p<0.001), and among patient subgroups. Pressure was only correlated to maximal LA volume (R=0.32) and the time to peak reservoir strain rate (R=0.32), among all functional measurements. LA reservoir strain was strongly correlated with LAEF (R=0.95, p<0.001) and LA minimum volume (r=0.82, p<0.001). Conclusion: In our AF cohort, pressure is correlated to maximum LA volume and time to peak reservoir strain. LA LGE is a strong marker of stiffness.

Quantitative cardiovascular magnetic resonance findings and clinical risk factors predict cardiovascular outcomes in breast cancer patients.

BACKGROUND: Cardiac magnetic resonance (CMR) global longitudinal strain and circumferential strain abnormalities have been associated with left ventricular ejection fraction (LVEF) reduction and cardiotoxicity from oncologic therapy. However, few studies have evaluated the associations of strain and cardiovascular outcomes. OBJECTIVES: To assess CMR circumferential and global longitudinal strain (GLS) correlations with cardiovascular outcomes including myocardial infarction, systolic dysfunction, diastolic dysfunction, arrhythmias and valvular disease in breast cancer patients treated with and without anthracyclines and/or trastuzumab therapy. METHODS: Breast cancer patients with a CMR from 2013-2017 at Yale New Haven Hospital were included. Patient co-morbidities, medications, and cardiovascular outcomes were obtained from chart review. Biostatistical analyses, including Pearson correlations, competing risk regression model, and competing risk survival curves comparing the two groups were analyzed. RESULTS: 116 breast cancer with CMRs were included in our analysis to assess differences between Anthracycline/Trastuzumab (AT) (62) treated versus non anthracycline/trastuzumab (NAT) (54) treated patients in terms of imaging characteristics and outcomes. More AT patients 17 (27.4%) developed systolic heart failure compared to the NAT group 6 (10.9%), p = 0.025. Statin use was associated with a significant reduction in future arrhythmias (HR 0.416; 95% CI 0.229-0.755, p = 0.004). In a sub-group of 13 patients that underwent stress CMR, we did not find evidence of microvascular dysfunction by sub-endocardial/sub-epicardial myocardial perfusion index ratio after adjusting for ischemic heart disease. CONCLUSIONS: In our study, CMR detected signs of subclinical cardiotoxicity such as strain abnormalities despite normal LV function and abnormal circumferential strain was associated with adverse cardiovascular outcomes such as valvular disease and systolic heart failure. Thus, CMR is an important tool during and after cancer treatment to identity and prognosticate cancer treatment-related cardiotoxicity.

Implementation of supervised exercise therapy in a veteran population with symptomatic claudication.

BACKGROUND: Real-world implementation of supervised exercise therapy (SET) referral for symptomatic intermittent claudication has been limited by poor provider awareness around reimbursement and low patient adherence owing to factors including limited center availability and long travel distances to sites. METHODS: In this study, 76 of 77 consecutive male veteran patients with intermittent claudication managed at a single-center vascular specialty clinic were referred to SET prior to revascularization. Pre- and post-SET submaximal exercise treadmill testing was performed for assessment of exercise capacity in metabolic equivalents (METs). RESULTS: In the 48.7% of subjects who completed 36 sessions of SET (n = 37), the average improvement in METs was 60.3%, reflecting improvement from baseline average of 3.4 METs to 5.5 METs after SET. Another 14 patients pursued self-guided exercise therapy and 25 patients declined any participation in exercise therapy. Reasons for declining participation in SET included inadequate transportation, cost of copayment, and interference with full-time work schedules. There was a nonsignificant numeric trend toward improved change in ankle-brachial index in the combined SET and self-guided exercise groups compared to those that declined exercise therapy (0.011 ± 0.124 vs -0.040 ± 0.105, p = 0.156). CONCLUSION: High acceptance of referral to SET is possible, despite the limitations to implementation. Incorporation of novel pre- and post-SET submaximal exercise treadmill testing allows for assessment of change in exercise capacity and aids in risk stratification and management of intermittent claudication symptoms.

Post-9/11 veterans' heart disease knowledge, self-perceived risk, and prevention beliefs and behaviors.

OBJECTIVE: Veterans, including the growing number of women veterans, have a greater risk of heart disease than nonveterans, and the incidence of heart disease is increasing among the most recent veterans who participated in post-9/11 military conflicts. Investigating heart disease-related knowledge, self-perceived risk, and prevention beliefs and behavior among these veterans, and identifying potential differences in knowledge, risk, beliefs and behavior between men and women, may guide prevention strategies. METHOD: Cross-sectional data from a nationwide survey of 1,141 (53% women) post-9/11 veterans were used to examine heart disease awareness and information-seeking, perceived risk and importance of heart disease risk factors, beliefs about traditional (e.g., weight, blood pressure) and nontraditional (e.g., stress, sleep) factors, and engagement in prevention behaviors. Differences between men and women were also tested, using t-tests, chi-square, and Fisher's exact tests. RESULTS: Only one-third reported they felt very informed or sought information about heart disease, or that their providers had discussed heart disease with them. Although veterans generally believe that addressing traditional and nontraditional factors can reduce their risk of heart disease, far fewer endorsed the value of mental health treatment in prevention. Overall, women were slightly more knowledgeable about heart disease risk, and of behaviors that can lower this risk, but for both men and women, this knowledge did not translate to engaging in equivalent prevention behaviors. CONCLUSIONS: Post-9/11 veterans, and potentially their providers, may each benefit from improved education regarding their risk of heart disease. Veterans may also require better, more personalized approaches to prevention. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Relation of Cardiovascular Risk Factors to Mortality and Cardiovascular Events in Hospitalized Patients With Coronavirus Disease 2019 (from the Yale COVID-19 Cardiovascular Registry).

Individuals with established cardiovascular disease or a high burden of cardiovascular risk factors may be particularly vulnerable to develop complications from coronavirus disease 2019 (COVID-19). We conducted a prospective cohort study at a tertiary care center to identify risk factors for in-hospital mortality and major adverse cardiovascular events (MACE; a composite of myocardial infarction, stroke, new acute decompensated heart failure, venous thromboembolism, ventricular or atrial arrhythmia, pericardial effusion, or aborted cardiac arrest) among consecutively hospitalized adults with COVID-19, using multivariable binary logistic regression analysis. The study population comprised 586 COVID-19 positive patients. Median age was 67 (IQR: 55 to 80) years, 47.4% were female, and 36.7% had cardiovascular disease. Considering risk factors, 60.2% had hypertension, 39.8% diabetes, and 38.6% hyperlipidemia. Eighty-two individuals (14.0%) died in-hospital, and 135 (23.0%) experienced MACE. In a model adjusted for demographic characteristics, clinical presentation, and laboratory findings, age (odds ratio [OR], 1.28 per 5 years; 95% confidence interval [CI], 1.13 to 1.45), previous ventricular arrhythmia (OR, 18.97; 95% CI, 3.68 to 97.88), use of P2Y12-inhibitors (OR, 7.91; 95% CI, 1.64 to 38.17), higher C-reactive protein (OR, 1.81: 95% CI, 1.18 to 2.78), lower albumin (OR, 0.64: 95% CI, 0.47 to 0.86), and higher troponin T (OR, 1.84; 95% CI, 1.39 to 2.46) were associated with mortality (p <0.05). After adjustment for demographics, presentation, and laboratory findings, predictors of MACE were higher respiratory rates, altered mental status, and laboratory abnormalities, including higher troponin T (p <0.05). In conclusion, poor prognostic markers among hospitalized patients with COVID-19 included older age, pre-existing cardiovascular disease, respiratory failure, altered mental status, and higher troponin T concentrations.

MENTOR study: Matching expectations and needs to optimize relationships in cardiovascular fellowship training.

Study objective: Mentorship is a key component of successful cardiology training. This study sought to understand the alignment of mentorship priorities for fellow-in-training (FIT) mentees and faculty mentors. Design: Cross-sectional survey study. Setting: Online. Participants: Cardiology mentors and FIT mentees in the State of Connecticut. Interventions: None. Main outcome measures: Likert-scale graded valuations on the importance of and satisfaction with various categories of mentorship by both mentors and mentees. Results were analyzed using Mann-Whitney, Kruskal-Wallis and Wilcoxon signed-rank tests, where appropriate. Results: Forty-eight percent of FITs (n = 34) and 16% of faculty mentors (n = 34) responded to the survey. Of those, 74% of FITs identified a mentor within the first year of fellowship either by directly contacting the mentor or meeting them through a clinical rotation. Mentors significantly undervalued the importance to FITs of providing research opportunities (4.5 vs 3.6, p < 0.05), helping them make contacts (4.5 vs 3.7, p < 0.05) and providing job-search support (4.3 vs 3.3, p < 0.05). In contrast, mentors overestimated the value of work-life balance and clinical mentorship to FITs. Conclusions: FITs value support in research, job search support, and networking more than mentors realize, leading to an expectation-satisfaction gap in those areas of mentorship. Further studies to examine how mentors and mentees can best align their expectations may improve the efficacy of the mentorship process.

Effects of Psychological Stress on Vascular Physiology: Beyond the Current Imaging Signal.

PURPOSE OF REVIEW: This review describes the effects of psychological stress on the physiology of the entire vascular system, from individual cellular components to macrovascular and microvascular responses, and highlights the importance of the vascular system in the context of current limitations in cardiac imaging for evaluation of the cardiovascular response to mental stress. RECENT FINDINGS: The physiological responses that mediate vascular changes are based on evolutionary needs, but there is increasing evidence that the long-term consequences of psychological stress can precipitate the development and progression of cardiovascular disease (CVD). While there is an extensive body of literature describing localized physiological responses or overt cardiovascular manifestations, often framed within the organ-specific scope of cardiovascular imaging, there has not been a comprehensive description of the global vascular effects of psychological stress. Given the global nature of these processes, targeted cardiovascular imaging modalities may be insufficient. Here we approach the vascular response to mental stress systematically, describing the effects on the endothelium, vascular smooth muscle, and adventitia. We then address the mental stress effects on large vessels and the microvascular compartment, with a discussion of the role of microvascular resistance in the pathophysiology of mental stress-induced myocardial ischemia. Vascular responses to psychological stress involve complex physiological processes that are not fully characterized by routine cardiovascular imaging assessments. Future research incorporating standardized psychological assessments targeted toward vascular mechanisms of stress responses is required to guide the development of behavioral and therapeutic interventions.

The Foundational Role of Cardiovascular Imaging in the Characterization of Mental Stress-Induced Myocardial Ischemia in Patients with Coronary Artery Disease.

PURPOSE OF REVIEW: Mental stress-provoked myocardial ischemia (MSIMI) is an ischemic phenomenon provoked by the experience of psychologically stressful circumstances. While MSIMI was initially identified 50 years ago during activities of daily living through the use of wearable Holter monitor, subsequent research utilized the technologies of cardiac imaging-ventriculography and myocardial perfusion-under controlled conditions to pursue an understanding of pathophysiology and prognosis. This work revealed that MSIMI occurs in almost half of patients with stable coronary artery disease (CAD) and is associated with cardiac events and early mortality. We provide a focused review of the instrumental role that cardiac imaging has played in elucidating how stress affects cardiac physiology and how emerging diagnostic techniques will allow for further research on stress-mediated changes in the coronary macro- and microvasculature. RECENT FINDINGS: Observations about the cardiac response to mental stress diverge from underlying cornerstones of the traditional CAD paradigm which is based upon myocardial oxygen demand and the degree of epicardial coronary stenosis. Evidence from studies utilizing non-invasive and invasive studies of coronary perfusion indicates perturbations in the microvascular compartment in response to mental stress. Cardiovascular imaging enjoined with mental stress provocation may be a commanding tool to advance our understanding of non-obstructive CAD and the coronary microvasculature. This further understanding will facilitate incorporation of mental stress testing in the clinical care of patients with discrepant diagnostic work-up of CAD and in patients who experience anginal symptoms due to non-exertional and/or emotional triggers. Such algorithms will be crucial to identify treatment targets to modify the risk associated with mental stress-associated ischemia and adverse prognosis.

Cardiovascular Imaging of Biology and Emotion: Considerations Toward a New Paradigm.

Central activation in response to emotion and cognitive stress induces perturbations in the heart and the peripheral vasculature that differ in physiology and clinical manifestations when compared with exercise-induced changes. While our conventional framework of epicardial coronary artery disease is foundational in cardiology, an expanded paradigm is required to address the cardiovascular response to mental stress (MS) and its associated risks, thus addressing the intersection of the patient's ecological and psychosocial experience with cardiovascular biology. To advance the field of MS in cardiovascular health, certain core challenges must be addressed. These include differences in the trigger activation between exercise and emotion, identification and interpretation of imaging cues as measures of pathophysiologic changes, characterization of the vascular response, and identification of central and peripheral treatment targets. Sex and psychosocial determinants of health are important in understanding the emerging overlap of MS-induced myocardial ischemia with microvascular dysfunction and symptoms in the absence of obstructive disease. In overcoming these critical knowledge gaps, integration of the field of MS will require implementation studies to guide use of MS testing, to support diagnosis of MS induced cardiac and vascular pathophysiology, to assess prognosis, and understand the role of endotying to direct therapy.

Coronary Aneurysm: An Enigma Wrapped in a Mystery.

Coronary aneurysms are defined as localized dilatations of the coronary arteries. In this review, we will analyze the most important aspects of this rare condition while trying to provide answers to the following questions: What is a coronary aneurysm? What causes coronary aneurysm? Do coronary aneurysms cause symptoms? Can coronary aneurysms rupture? How do we treat coronary aneurysms?

Left atrial fibrosis correlates with extent of left ventricular myocardial delayed enhancement and left ventricular strain in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is associated with increased left ventricular (LV) mass, decreased myocardial strain, and the presence of LV fibrosis and scar. The relationship between LV scar and fibrosis with left atrial (LA) fibrosis in the setting of HCM has not been examined. The purpose of this study is to demonstrate a correlation between the degree of LA fibrosis and LV parameters in subjects with HCM. Twenty-eight subjects with HCM were imaged on a 1.5T MRI scanner with cine, LV and LA late gadolinium enhancement (LGE) sequences. LA LGE and LA measurements were correlated with LV measurements of volumes, mass, strain, and LGE. Other clinical conditions and medication usage were also examined and evaluated for correlation with LA and LV parameters. LV LGE was identified in 24 (86%) of the cases and LA LGE was identified in all of the cases. Extent of LA fibrosis significantly correlated with percent LV LGE (r = 0.64, p = 0.001), but not with indexed LV mass or maximum wall thickness. Extent of LA fibrosis also moderately correlated with decreased LV global strain (radial, r = - 0.50, p = 0.013; circumferential, r = 0.47, p = 0.02; longitudinal, r = 0.52, p = 0.013). Increased LA systolic volume correlated moderately with LV end diastolic volume (r = 0.50, p = 0.006). Patients on therapy with Renin-Angiotensin-Aldosterone System (RAAS) Inhibition had significantly less LA LGE compared to those without (18.6% vs 10.8%, p = 0.023). LA fibrosis, as measured by LGE, is prevalent in HCM and is correlated with LV LGE. The correlation between LA and LV LGE might suggest either that LA fibrosis is a consequence of LV remodeling, or that LA and LV fibrosis are both manifestations of the same cardiomyopathic process. Further study is warranted to determine the causality of LA scar in this population.

Multimodality Imaging Involving Magnetic Resonance Facilitates Giant Symptomatic Myxoma Resection.

Myxoma, the most common adult primary cardiac tumor, can manifest with profound symptoms. The preferred treatment of symptomatic myxoma is surgical resection, which can be curative. Preoperatively, multimodality imaging provides crucial information on the number, size, location, and proximity of myxoma or myxomas to adjacent structures, thereby facilitating an optimal operative approach. This report presents a case of symptomatic, giant left atrial myxoma and the utility of multimodality imaging to guide surgical planning.

Assessment of diastolic function and atrial remodeling by MRI - validation and correlation with echocardiography and filling pressure.

Atrial fibrosis can be estimated noninvasively by magnetic resonance imaging (MRI) using late gadolinium enhancement (LGE), but diastolic dysfunction is clinically assessed by transthoracic echocardiography (TTE), and rarely by MRI. This study aimed to evaluate well-established diastolic parameters using MRI, and validate them with TTE and left ventricular (LV) filling pressures, and to study the relationship between left atrial (LA) remodeling and parameters of diastolic function. The study retrospectively included 105 patients (53 ± 16 years, 39 females) who underwent 3D LGE MRI between 2012 and 2016. Medical charts were reviewed for the echocardiographic diastolic parameters E, A, and e' by TTE, and pressure catheterizations. E and A were measured from in-plane phase-contrast cardiac MRI images, and e' by feature-tracking, and validated with TTE. Interobserver and intraobserver variability was examined. Furthermore, LA volumes, function, and atrial LGE was correlated with diastolic parameters. Evaluation of e' in MRI had strong agreement with TTE (r = 0.75, P < 0.0001), and low interobserver and intraobserver variability. E and A by TTE showed strong agreement to MRI (r = 0.77, P = 0.001; r = 0.73, P = 0.003, for E and A, respectively). Agreement between E/e' by TTE and MRI was strong (r = 0.85, P = 0.0004), and E/e' by TTE correlated moderately to invasive pressures (r = 0.59, P = 0.03). There was a strong relationship between LA LGE and pulmonary capillary wedge pressure (r = 0.81, P = 0.01). In conclusion, diastolic parameters can be measured with good reproducibility by cardiovascular MRI. LA LGE exhibited a strong relationship with pulmonary capillary wedge pressure, an indicator of diastolic function.

Relative predictive value of lung cancer screening CT versus myocardial perfusion attenuation correction CT in the evaluation of coronary calcium.

Coronary artery calcium scores (CACS) from lung cancer screening computed tomography (LCSCT) or myocardial perfusion attenuation correction computed tomography (ACCT) are not routinely performed or reported. CACS from LCSCT and ACCT have not been directly compared in the same patient population. We identified 66 patients who underwent both LCSCT (non-gated) and ECG-gated cardiac CT (CCT) within a 2-year span. Of this population, 40 subjects had also undergone ACCT. Using the Agatston method, CACS for 264 individual vessels from the LCSCT population and for 160 vessels from ACCT population were calculated and evaluated for agreement with ECG-gated CCT as the gold standard. Secondary analysis included a comparison of individual vessel contribution to variations in agreement and a comparison of total CACS from CCT, LCSCT, and ACCT for respective MACE prediction. CACS from LCSCT demonstrated a strong Pearson correlation, r = 0.9017 (0.876-0.9223), with good agreement when compared to CACS from CCT. CACS from ACCT demonstrated a significantly (P < 0.00001) weaker correlation, r = 0.5593 (0.4401-0.6592). On an individual vessel basis, CACS from all major vessels (LM, LAD, LCX, and RCA) contributed to the weaker correlation. For total vessel CACS, LCSCT demonstrated comparable area under the curve (AUC) for the receiver operating characteristic (ROC) curve (LCSCT AUC = 0.8133 and CCT AUC = 0.8302, P = 0.691) for prediction of MACE. Although ACCT demonstrated a similar AUC (ACCT AUC = 0.7969, P = 0.662) for MACE prediction the cutoff value for elevated risk was extremely low. In conclusion, LCSCT outperformed ACCT at calcium scoring by providing better agreement and comparable risk assessment to CCT despite the absence of ECG-gating. It is therefore reasonable to use LCSCT images to derive and report Agatston-based CACS for cardiovascular risk assessment, whereas the use of ACCT images to report Agatston-based CACS is not currently practical.

Rac2 Modulates Atherosclerotic Calcification by Regulating Macrophage Interleukin-1ß Production.

OBJECTIVE: The calcium composition of atherosclerotic plaque is thought to be associated with increased risk for cardiovascular events, but whether plaque calcium itself is predictive of worsening clinical outcomes remains highly controversial. Inflammation is likely a key mediator of vascular calcification, but immune signaling mechanisms that promote this process are minimally understood. APPROACH AND RESULTS: Here, we identify Rac2 as a major inflammatory regulator of signaling that directs plaque osteogenesis. In experimental atherogenesis, Rac2 prevented progressive calcification through its suppression of Rac1-dependent macrophage interleukin-1ß (IL-1ß) expression, which in turn is a key driver of vascular smooth muscle cell calcium deposition by its ability to promote osteogenic transcriptional programs. Calcified coronary arteries from patients revealed decreased Rac2 expression but increased IL-1ß expression, and high coronary calcium burden in patients with coronary artery disease was associated with significantly increased serum IL-1ß levels. Moreover, we found that elevated IL-1ß was an independent predictor of cardiovascular death in those subjects with high coronary calcium burden. CONCLUSIONS: Overall, these studies identify a novel Rac2-mediated regulation of macrophage IL-1ß expression, which has the potential to serve as a powerful biomarker and therapeutic target for atherosclerosis.