Left atrial strain, embolic stroke of undetermined source, and atrial fibrillation detection.

BACKGROUND: Atrial cardiopathy is a proposed mechanism of embolic stroke of undetermined source (ESUS). Left atrial (LA) strain may identify early atrial cardiopathy prior to structural changes. We aim to study the associations between LA strain, ESUS, and atrial fibrillation (AF) detection in ESUS. METHODS: The study population included patients with ESUS and noncardioembolic (NCE) stroke presenting to the Rhode Island Hospital Stroke Center between January 2016 and June 2017 who underwent transthoracic echocardiography. Speckle tracking echocardiography (STE) was used to measure the three phases of LA strain (reservoir, conduit, and contractile). Binary logistic regression analysis was performed to determine the associations between LA strain and stroke subtype (ESUS vs. NCE) as well as follow-up detection of AF in ESUS patients. RESULTS: We identified 656 patients, 307 with ESUS and 349 with NCE. In binary logistic regression, the lowest tertiles of LA reservoir (adjusted OR 1.944, 95% CI 1.266-2.986, p = .002), contractile (aOR 1.568, 95% CI 1.035-2.374, p = .034), and conduit strain (aOR 2.288, 95% CI 1.448-3.613, p = .001) were more likely to be significantly associated with ESUS compared to NCE stroke. Among all ESUS patients, the lowest tertiles of LA reservoir strain (OR 2.534, 95% CI 1.029-6.236, p = .043), contractile strain (OR 2.828, 95% CI 1.158-6.903, p = .022), and conduit strain (OR 2.614, 95% CI 1.003-6.815, p = .049) were significantly associated with subsequent detection of AF. CONCLUSION: Reduced LA strain is associated with ESUS occurrence and AF detection in ESUS patients. Therefore, quantification of LA strain in ESUS patients may improve risk stratification and guide secondary prevention strategies.

Association Between COVID-19 Diagnosis and In-Hospital Mortality in Patients Hospitalized With ST-Segment Elevation Myocardial Infarction.

IMPORTANCE: There has been limited research on patients with ST-segment elevation myocardial infarction (STEMI) and COVID-19. OBJECTIVE: To compare characteristics, treatment, and outcomes of patients with STEMI with vs without COVID-19 infection. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of consecutive adult patients admitted between January 2019 and December 2020 (end of follow-up in January 2021) with out-of-hospital or in-hospital STEMI at 509 US centers in the Vizient Clinical Database (N = 80 449). EXPOSURES: Active COVID-19 infection present during the same encounter. MAIN OUTCOMES AND MEASURES: The primary outcome was in-hospital mortality. Patients were propensity matched on the likelihood of COVID-19 diagnosis. In the main analysis, patients with COVID-19 were compared with those without COVID-19 during the previous calendar year. RESULTS: The out-of-hospital STEMI group included 76 434 patients (551 with COVID-19 vs 2755 without COVID-19 after matching) from 370 centers (64.1% aged 51-74 years; 70.3% men). The in-hospital STEMI group included 4015 patients (252 with COVID-19 vs 756 without COVID-19 after matching) from 353 centers (58.3% aged 51-74 years; 60.7% men). In patients with out-of-hospital STEMI, there was no significant difference in the likelihood of undergoing primary percutaneous coronary intervention by COVID-19 status; patients with in-hospital STEMI and COVID-19 were significantly less likely to undergo invasive diagnostic or therapeutic coronary procedures than those without COVID-19. Among patients with out-of-hospital STEMI and COVID-19 vs out-of-hospital STEMI without COVID-19, the rates of in-hospital mortality were 15.2% vs 11.2% (absolute difference, 4.1% [95% CI, 1.1%-7.0%]; P = .007). Among patients with in-hospital STEMI and COVID-19 vs in-hospital STEMI without COVID-19, the rates of in-hospital mortality were 78.5% vs 46.1% (absolute difference, 32.4% [95% CI, 29.0%-35.9%]; P < .001). CONCLUSIONS AND RELEVANCE: Among patients with out-of-hospital or in-hospital STEMI, a concomitant diagnosis of COVID-19 was significantly associated with higher rates of in-hospital mortality compared with patients without a diagnosis of COVID-19 from the past year. Further research is required to understand the potential mechanisms underlying this association.

Increased Left Atrial Appendage Density on Computerized Tomography is Associated with Cardioembolic Stroke.

BACKGROUND AND PURPOSE: While studies have stratified cardioembolic (CE) stroke risk by qualitative left atrial appendage (LAA) morphology and biomarkers of atrial dysfunction, the quantitative properties that underlie these observations are not well established. Accordingly, we hypothesized that LAA volume and contrast density (attenuation) on computerized tomography (CT) may capture the structural and hemodynamic processes that underlie CE stroke risk. METHODS: Data were collected from a single center prospective ischemic stroke database over 18 months and included all patients with ischemic stroke who previously underwent routine, nongated, contrast enhanced thin-slice (≤2.5 mm) chest CT. Stroke subtype was determined based on the inpatient diagnostic evaluation. LAA volume and attenuation were determined from CT studies performed for various clinically appropriate indications. Univariate and multivariable analyses were performed to determine factors associated with ischemic stroke subtype, including known risk factors and biomarkers, as well as LAA density and morphologic measures. RESULTS: We identified 311 patients with a qualifying chest CT (119 CE subtype, 109 Embolic Stroke of Undetermined Source (ESUS), and 83 non-CE). In unadjusted models, there was an association between CE (versus non-CE) stroke subtype and LAA volume (OR per mL increase 1.15, 95% CI 1.07-1.24, P < .001) and LAA density (4th quartile versus 1st quartile; OR 2.95, 95% CI 1.28-6.80, P = .011), but not with ESUS (versus non-CE) subtype. In adjusted models, only the association between LAA density and CE stroke subtype persisted (adjusted OR 3.71, 95% CI 1.37-10.08, P = .010). CONCLUSION: The LAA volume and density values on chest CT are associated with CE stroke subtype but not ESUS subtype. Patients with ESUS and increased LAA volume or attenuation may be a subgroup where the mechanism is CE and anticoagulation can be tested for secondary stroke prevention.

Left Atrial Volume Index Is Associated With Cardioembolic Stroke and Atrial Fibrillation Detection After Embolic Stroke of Undetermined Source.

Background and Purpose- Left atrial enlargement has been shown to be associated with ischemic stroke, but the association with embolic stroke mechanisms remains unknown. We aim to study the associations between left atrial volume index (LAVI) and embolic stroke subtypes and atrial fibrillation (AF) detection on cardiac event monitoring in patients with embolic stroke of unknown source. Methods- Data were collected from a prospective cohort of consecutive patients with ischemic stroke admitted to a comprehensive stroke center over 18 months. Stroke subtype was classified into cardioembolic stroke, noncardioembolic stroke of determined mechanism (NCE), or embolic stroke of undetermined source (ESUS). Univariate and prespecified multivariable analyses were performed to assess associations between LAVI and stroke subtype and AF detection in patients with ESUS. Results- Of 1224 consecutive patients identified during the study period, 1020 (82.6%) underwent transthoracic echocardiography and had LAVI measurements. LAVI was greater in patients with cardioembolic stroke than NCE (41.4 mL/m2±18.0 versus 28.6 mL/m2±12.2; P<0.001) but not in ESUS versus NCE (28.9 mL/m2±12.6 versus 28.6 mL/m2±12.2; P=0.61). In multivariable logistic regression models, LAVI was greater in cardioembolic stroke versus NCE (adjusted odds ratio per mL/m2, 1.07; 95% CI, 1.05-1.09; P<0.001) but not in ESUS versus NCE (adjusted odds ratio per mL/m2, 1.00; 95% CI, 0.99-1.02; P=0.720). Among 99 patients with ESUS who underwent cardiac monitoring, 18.2% had AF detected; LAVI was independently associated with AF detection in ESUS (adjusted odds ratio per mL/m2, 1.09; 95% CI, 1.02-1.15; P=0.007). Conclusions- LAVI is associated with cardioembolic stroke as well as AF detection in patients with ESUS, 2 subsets of ischemic stroke that benefit from anticoagulation therapy. Patients with increased LAVI may be a subgroup where anticoagulation may be tested for stroke prevention.

Echocardiographic Predictors of Tricuspid Ring Annuloplasty Repair Failure for Functional Tricuspid Regurgitation.

OBJECTIVE: Significant tricuspid regurgitation (TR) recurs after tricuspid valve repair of functional TR in 15% to 20% within the first year, and 30% to 70% within 5 years. Prior investigations report leaflet tethering, and not tricuspid valve annular diameter (TVAD), as predictive of recurrent TR. The authors hypothesize that pre-repair TVAD is predictive of repair failure for functional TR. PARTICIPANTS: Fifty-four patients with functional TR scheduled for left heart surgery and tricuspid valve repair with ring annuloplasty. DESIGN: Retrospective study design. Pre- and post-repair transthoracic and intraoperative transesophageal echocardiographic data included left and right ventricular functions, tricuspid leaflet tethering height, TVAD, and TR severity. Successful repair was defined as ≤2+ TR. SETTING: Tertiary care medical center. INTERVENTIONS: None. MEASUREMENTS: Forty-five patients had a successful repair and 9 did not. Preoperative and intraoperative TVAD in diastole (TVADdiast) ≥4.2 cm, and preoperative systole (TVADsyst) ≥3.7 cm, but not leaflet tethering, were predictive of repair failure. Right ventricular (RV) width >4.88 cm was associated with repair failure. Neither pre- nor post-repair pulmonary artery systolic pressures (PASP) were predictors of repair failure. However, PASP did not change nor did RV function improve in the nonsuccessful repair group. CONCLUSION: For patients with functional TR undergoing primary left heart surgery, preoperative TVAD (systole and diastole), RV width, and postoperative RV function were predictors of repair outcome. Earlier TV repair and optimizing right heart function may improve repair outcome.

The synergistic effects of anxiety and cerebral hypoperfusion on cognitive dysfunction in older adults with cardiovascular disease.

OBJECTIVES: Anxiety is a risk factor for cardiovascular disease (CVD) and is associated with neurocognitive outcomes. The effect of anxiety on brain perfusion in a CVD population has yet to be examined, and no study has investigated the interactive effects of anxiety and cerebral perfusion on cognition. METHODS: A total of 55 older adults with CVD completed the Beck Anxiety Inventory (BAI) and underwent arterial spin labeling to quantify cortical perfusion and thickness. Participants were administered the Mini-Mental State Examination (MMSE) and the Repeatable Battery for the Assessment of Neuropsychological Status. RESULTS: Reduced perfusion predicted poorer cognition and decreased cortical thickness. Higher anxiety score predicted worse memory performance and decreased frontal perfusion. Frontal lobe hypoperfusion combined with increased BAI scores exacerbated poorer MMSE performance. CONCLUSIONS: Higher anxiety may exacerbate the effects of cerebral hypoperfusion on cognitive impairment. Longitudinal studies are needed to confirm our findings and determine whether anxiety treatment improves neurocognitive outcomes in CVD.

Quantitative Assessment of Right Ventricular Volumes and Ejection Fraction in Patients with Left Ventricular Systolic Dysfunction by Real Time Three-Dimensional Echocardiography versus Cardiac Magnetic Resonance Imaging.

AIMS: The aim of this study was to assess the accuracy and reproducibility of real time three-dimensional echocardiographic (RT3DE) for the determination of right ventricular (RV) volumes and function in patients with left ventricular (LV) systolic dysfunction. METHODS AND RESULTS: Dedicated RT3DE was prospectively performed to assess RV volumes and EF in patients with LV systolic function identified on routine clinical cardiac magnetic resonance (CMR) imaging. RV end-diastolic volume (RV EDV), RV end-systolic volume (RV ESV), and RV EF were obtained using an offline analysis software (TomTec) by two observers blinded to CMR results. In this population of 27 patients with LV systolic dysfunction with a mean LV EF of 36 ± 12%, RV RT3DE dataset could be assessed in 27 of 30 patients (90%). High correlation was noted between RT3DE and CMR for RV EDV, ESV, and EF (r = 0.90, 0.89, and 0.77, respectively). RV EDV was lower by RT3DE as compared to CMR (129 ± 52 vs. 142 ± 53 mL, P = 0.005) while there was no significant difference in RV ESV and RV EF (71 ± 37 vs. 77 ± 45 mL, P = 0.146; 45 ± 11 vs. 48 ± 13%, P = 0.134, respectively). The intraclass correlation coefficient ranged from 0.94 to 0.94 between measurements and from 0.84 to 0.96 between observers. CONCLUSION: Overall, RV volumes and EF assessed by RT3DE correlate well with CMR measurements in patients with LV dysfunction. RT3DE may be used as a more widely available and versatile alternative to CMR for the quantitative assessment of RV size and function in patients with LV dysfunction.

Three-dimensional echocardiographic assessment of the repaired mitral valve.

OBJECTIVE: This study examined the geometric changes of the mitral valve (MV) after repair using conventional and three-dimensional echocardiography. DESIGN: Prospective evaluation of consecutive patients undergoing mitral valve repair. TYPE OF HOSPITAL: Tertiary care university hospital. PARTICIPANTS: Fifty consecutive patients scheduled for elective repair of the mitral valve for regurgitant disease. INTERVENTIONS: Intraoperative transesophageal echocardiography. MEASUREMENTS: Assessments of valve area (MVA) were performed using two-dimensional planimetry (2D-Plan), pressure half-time (PHT), and three-dimensional planimetry (3D-Plan). In addition, the direction of ventricular inflow was assessed from the three-dimensional imaging. MAIN RESULTS: Good correlations (r = 0.83) and agreement (-0.08 +/- 0.43 cm(2)) were seen between the MVA measured with 3D-Plan and PHT, and were better than either compared to 2D-Plan. MVAs were smaller after repair of functional disease repaired with an annuloplasty ring. After repair, ventricular inflow was directed toward the lateral ventricular wall. Subgroup analysis showed that the change in inflow angle was not different after repair of functional disease (168 to 171 degrees) as compared to those presenting with degenerative disease (168 to 148 degrees; p<0.0001). CONCLUSIONS: Three-dimensional imaging provides caregivers with a unique ability to assess changes in valve function after mitral valve repair.

Clinical predictors of right ventricular dysfunction and association with adverse outcomes in peripartum cardiomyopathy.

AIMS: We sought to identify factors associated with right ventricular (RV) dysfunction and elevated pulmonary artery systolic pressure (PASP) and association with adverse outcomes in peripartum cardiomyopathy (PPCM). METHODS AND RESULTS: We conducted a multi-centre cohort study to identify subjects with PPCM with the following criteria: left ventricular ejection fraction (LVEF) < 40%, development of heart failure within the last month of pregnancy or 5 months of delivery, and no other identifiable cause of heart failure with reduced ejection fraction. Outcomes included a composite of (i) major adverse events (need for extracorporeal membrane oxygenation, ventricular assist device, orthotopic heart transplantation, or death) or (ii) recurrent heart failure hospitalization. RV function was obtained from echocardiogram reports. In total, 229 women (1993-2017) met criteria for PPCM. Mean age was 32.4 ± 6.8 years, 28% were of African descent, 50 (22%) had RV dysfunction, and 38 (17%) had PASP ≥ 30 mmHg. After a median follow-up of 3.4 years (interquartile range 1.0-8.8), 58 (25%) experienced the composite outcome of adverse events. African descent, family history of cardiomyopathy, LVEF, and PASP were significant predictors of RV dysfunction. Using Cox proportional hazards models, we found that women with RV dysfunction were three times more likely to experience the adverse composite outcome: hazard ratio 3.21 (95% confidence interval: 1.11-9.28), P = 0.03, in a multivariable model adjusting for age, race, body mass index, preeclampsia, hypertension, diabetes, kidney disease, and LVEF. Women with PASP ≥ 30 mmHg had a lower probability of survival free from adverse events (log-rank P = 0.04). CONCLUSIONS: African descent and family history of cardiomyopathy were significant predictors of RV dysfunction. RV dysfunction and elevated PASP were significantly associated with a composite of major adverse cardiac events. This at-risk group may prompt closer monitoring or early referral for advanced therapies.

Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) After Infection During Pregnancy.

OBJECTIVE: To estimate the prevalence of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) after infection with SARS-CoV-2 during pregnancy and to characterize associated risk factors. METHODS: In a multicenter cohort study (NIH RECOVER [Researching COVID to Enhance Recovery]-Pregnancy Cohort), individuals who were pregnant during their first SARS-CoV-2 infection were enrolled across the United States from December 2021 to September 2023, either within 30 days of their infection or at differential time points thereafter. The primary outcome was PASC, defined as score of 12 or higher based on symptoms and severity as previously published by the NIH RECOVER-Adult Cohort, at the first study visit at least 6 months after the participant's first SARS-CoV-2 infection. Risk factors for PASC were evaluated, including sociodemographic characteristics, clinical characteristics before SARS-CoV-2 infection (baseline comorbidities, trimester of infection, vaccination status), and acute infection severity (classified by need for oxygen therapy). Multivariable logistic regression models were fitted to estimate associations between these characteristics and presence of PASC. RESULTS: Of the 1,502 participants, 61.1% had their first SARS-CoV-2 infection on or after December 1, 2021 (ie, during Omicron variant dominance); 51.4% were fully vaccinated before infection; and 182 (12.1%) were enrolled within 30 days of their acute infection. The prevalence of PASC was 9.3% (95% CI, 7.9-10.9%) measured at a median of 10.3 months (interquartile range 6.1-21.5) after first infection. The most common symptoms among individuals with PASC were postexertional malaise (77.7%), fatigue (76.3%), and gastrointestinal symptoms (61.2%). In a multivariable model, the proportion PASC positive with vs without history of obesity (14.9% vs 7.5%, adjusted odds ratio [aOR] 1.65, 95% CI, 1.12-2.43), depression or anxiety disorder (14.4% vs 6.1%, aOR 2.64, 95% CI, 1.79-3.88) before first infection, economic hardship (self-reported difficulty covering expenses) (12.5% vs 6.9%, aOR 1.57, 95% CI, 1.05-2.34), and treatment with oxygen during acute SARS-CoV-2 infection (18.1% vs 8.7%, aOR 1.86, 95% CI, 1.00-3.44) were associated with increased prevalence of PASC. CONCLUSION: The prevalence of PASC at a median time of 10.3 months after SARS-CoV-2 infection during pregnancy was 9.3% in the NIH RECOVER-Pregnancy Cohort. The predominant symptoms were postexertional malaise, fatigue, and gastrointestinal symptoms. Several socioeconomic and clinical characteristics were associated with PASC after infection during pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT05172024.

Left atrial size is independently associated with cognitive function.

Left atrial (LA) diameter is easily attainable from echocardiograph and sensitive to underlying cardiovascular disease severity, although its association with neurocognitive outcomes is not well understood. Fifty older adults (64.50 ± 9.41 years), recruited from outpatient cardiology clinics and local papers who underwent magnetic resonance imaging, were administered the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and completed psychosocial self-report measures. LA diameter was quantified using echocardiogram. Hierarchical regression analyses revealed that greater LA size was independently associated with reduced performance on the following RBANS composites: language, delayed memory, and total index (p < 0.05 for all). Hierarchical regression analysis demonstrated no significant association between LA diameter and whole brain volume (p > 0.05). The current study suggests that greater LA size is associated with cognitive dysfunction in older adults and prospective studies are needed to validate these findings and elucidate underlying mechanisms.

Brain-derived neurotrophic factor Val66Met polymorphism and cognitive function in persons with cardiovascular disease.

AIM: Cognitive impairment is common among persons with cardiovascular disease (CVD), and several potential aetiological mechanisms have been described, including contributions of genetic markers such as variations in the brain-derived neurotrophic (BDNF) gene. This current study examined the associations of BDNF genotype with cognitive function among individuals with CVD. METHODS: This study included 110 participants with CVD who completed a comprehensive neuropsychological battery that assessed global cognitive function, attention/executive function, memory, language, and visuospatial abilities. All participants also underwent blood draw to provide a DNA sample that was used to determine BDNF genotype. Carriers of either one or two copies of the methionine allele of BDNF were categorized into one group (n = 33); non-carriers were categorized into a second group (n = 77). RESULTS: After adjustment for demographic and medical characteristics, hierarchical regression analyses revealed persons with one or more methionine alleles displayed better performance than valine/valine individuals for attention/executive function (ß = 0.22, P = 0.047) and memory (ß = 0.25, P = 0.03), as well as a trend for language (ß = 0.19, P = 0.08) and visuospatial abilities (ß = 0.21, P = 0.06). CONCLUSIONS: BDNF Val66Met had little impact on cognitive functioning in a sample of older adults with CVD, and significant findings contradicted that predicted by past work. Future work is much needed to clarify the mechanisms of these findings, particularly studies examining both circulating BDNF levels and genetic variation in the BDNF gene and cognitive function over time.

Reduced memory in fat mass and obesity-associated allele carriers among older adults with cardiovascular disease.

BACKGROUND: Much attention has been paid to the prevalence and predisposition of the fat mass and obesity-associated (FTO) gene to obesity, although only a few studies have characterized the extent to which this affects cognitive function. This study examined differences between risk allele carriers (i.e. FTO-AC/AA) and non-carriers (i.e. FTO-CC) on indices of attention/executive function/psychomotor speed, memory, language, and visual-spatial ability in a sample of older patients with cardiovascular disease. METHODS: We recruited 120 older adults from an outpatient cardiology clinic who underwent blood draw and completed neuropsychological testing. Participants were classified into two groups: one for those who were homozygous for the non-risk-conferring allele (i.e. FTO-CC) (n= 49) and the other for those who had at least one copy of the obesity risk-conferring A allele (i.e. FTO-AC/AA) (n= 71). RESULTS: Mancova analyses adjusting for age and years of education revealed the FTO-AC/AA group performed significantly worse on indices of memory (λ= 0.94, F(2, 115) = 3.58, P= 0.03, partial η(2) = 0.06). Follow-up tests revealed a significant effect for the FTO-AC/AA group, relative to the non-carrier group, on encoding (i.e. California Verbal Learning Test Total Learning) and California Verbal Learning Test long-delay free recall (P < 0.05). No such differences between FTO carriers and non-carriers emerged on tests of attention/executive function/psychomotor speed, language, or visual-spatial ability (P > 0.05 for all). CONCLUSIONS: These findings suggest that the FTO risk allele is associated with reduced memory performance, particularly on aspects of memory encoding and delayed recall. To elucidate underlying mechanisms, these findings will need to be replicated in larger samples that utilize neuroimaging.