Mortality in ST-Segment Elevation Myocardial Infarction With Nonobstructive Coronary Arteries and Mimickers.

Importance: The clinical characteristics and prognosis of patients with ST-segment elevation myocardial infarction (STEMI) with nonobstructive coronaries (MINOCA) are largely unknown. Objective: To assess differences in 5-year mortality in patients presenting with STEMI due to MINOCA and MINOCA mimickers as compared with obstructive disease. Design, Setting, and Participants: A retrospective analysis of a prospective registry-based cohort study of consecutive STEMI activations at 3 regional Midwest STEMI programs. STEMI without a culprit artery and elevated troponin levels were categorized as MINOCA (absence of coronary artery stenosis >50% and confirmed or suspected coronary artery plaque disruption, epicardial coronary spasm, or coronary embolism/thrombosis) or MINOCA mimickers (takotsubo cardiomyopathy, myocarditis, or nonischemic cardiomyopathy). Data were analyzed from March 2003 to December 2020. Main Outcomes and Measures: Adjusted Cox regression analysis was used to assess 5-year mortality risk in STEMI presenting with MINOCA and MINOCA mimickers in comparison with obstructive disease. Results: Among 8560 consecutive patients with STEMI, mean (SD) age was 62 (14) years, 30% were female (2609 participants), and 94% were non-Hispanic White (4358 participants). The cohort included 8151 patients with STEMI due to obstructive disease (95.2%), 120 patients with MINOCA (1.4%), and 289 patients with MINOCA mimickers (3.8%). Patients were followed up for a median (IQR) of 7.1 (3.6-10.7) years. Patients with MINOCA and MINOCA mimickers were less likely to be discharged with cardiac medications compared with obstructive disease. At 5-year follow-up, mortality in STEMI presenting with obstructive disease (1228 participants [16%]) was similar to MINOCA (20 participants [18%]; χ21 = 1.1; log-rank P = .29) and MINOCA mimickers (52 participants [18%]; χ21 = 2.3; log-rank P = .13). In adjusted Cox regression analysis compared with obstructive disease, the 5-year mortality hazard risk was 1.93 times higher in MINOCA (95% CI, 1.06-3.53) and similar in MINOCA mimickers (HR, 1.08; 95% CI, 0.79-1.49). Conclusions and Relevance: In this large multicenter cohort study of consecutive clinical patients with STEMI, presenting with MINOCA was associated with a higher risk of mortality than obstructive disease; the risk of mortality was similar in patients with MINOCA mimickers and obstructive disease. Further investigation is necessary to understand the pathophysiologic mechanisms involved in this high-risk STEMI population.

Prevalence of Diastolic Dysfunction in Adult Survivors of Childhood Cancer: A Report From SJLIFE Cohort.

Background: The prevalence of diastolic dysfunction has not been systematically evaluated in a large population of survivors of childhood cancer using established guidelines and standards. Objectives: This study sought to assess the prevalence and progression of diastolic dysfunction in adult survivors of childhood cancer exposed to cardiotoxic therapy. Methods: Comprehensive, longitudinal echocardiographic examinations of adult survivors of childhood cancer ≥18 years of age and ≥10 years from diagnosis in SJLIFE (St. Jude Lifetime Cohort Study) were performed. Diastolic dysfunction was defined based on 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. Results: Among 3,342 survivors, the median (25th-75th percentiles [quartile (Q)1-Q3]) age at diagnosis was 8.1 years (Q1-Q3: 3.6-13.7 years), 30.1 years (Q1-Q3: 24.4-37.0 years) at the baseline echocardiography evaluation (Echo 1), and 36.6 years (Q1-Q3: 30.8-43.6 years) at the last follow-up echocardiography evaluation (1,435 survivors) (Echo 2). The proportion of diastolic dysfunction was 15.2% (95% CI: 14.0%-16.4%) at Echo 1 and 15.7% (95% CI: 13.9%-17.7%) at Echo 2, largely attributable to concurrent systolic dysfunction. Less than 5% of survivors with preserved ejection fraction had diastolic dysfunction (2.2% at Echo 1, 3.7% at Echo 2). Using global longitudinal strain assessment in adult survivors with preserved ejection fraction (defined with a cutpoint worse than -15.9%), the proportion of diastolic dysfunction increased to 9.2% at baseline and 9.0% at follow-up. Conclusions: The prevalence of isolated diastolic dysfunction is low among adults who received cardiotoxic therapies for childhood cancer. The inclusion of left ventricular global longitudinal strain significantly increased the identification of diastolic dysfunction.

Characteristics and Long-term Mortality in Patients with ST-Segment Elevation Myocardial Infarction with Non-Obstructive Coronary Arteries (STE-MINOCA): A High Risk Cohort.

Background: The prognosis of ST-segment elevation myocardial infarction with non-obstructive coronaries (STE-MINOCA) is largely unknown. Methods: The objective of this study is to evaluate the prevalence, characteristics, and 5-year mortality of patients with STE-MINOCA compared to STEMI with coronary artery obstruction (STEMI-Obstruction) using a multicenter cohort of consecutive STEMI patients at 3 regional Midwest STEMI programs from 2003 to 2020. STE-MINOCA was defined based on (1) coronary stenosis < 60% by visual estimation, (2) ischemia with elevated troponin, and (3) no alternative diagnosis. STE-MINOCA was further classified based on American Heart Association (AHA) definition as AHA STE-MINOCA and AHA STE-MINOCA Mimicker. Results: 8,566 STEMI patients, including 420 (4.9%) STE-MINOCA (26.9% AHA STE-MINOCA and 73.1% AHA STE-MINOCA Mimicker) were followed for a median of 7.1 years. Compared to STEMI-Obstruction, STE-MINOCA were younger, more often female, had fewer cardiovascular risk factors, and were less likely to be discharged on cardiac medications. At five years, mortality was higher in STE-MINOCA compared with STEMI-Obstruction (18% vs. 15%, p=0.033). In propensity score-matched analysis, STE-MINOCA had a 1.4-fold (95% CI: 1.04-1.89, p=0.028) higher risk of 5-year all-cause mortality compared with STEMI-Obstruction. Furthermore, 5-year mortality risk was significantly higher in AHA STE-MINOCA Mimicker (19% vs. 15%, p=0.043) but similar in AHA STE-MINOCA (17% vs. 15%, p=0.42) compared with STEMI-Obstruction. Conclusions: In this large multicenter STEMI cohort, nearly 5% of patients presented with STE-MINOCA. At five years, mortality approached 20% among patients with STE-MINOCA. Despite the lower risk profile, STE-MINOCA patients were at 40% higher risk of 5-year all-cause mortality compared with STEMI-Obstruction. Additionally, 5-year all-cause mortality risk was higher in AHA STE-MINOCA Mimicker but similar in AHA STE-MINOCA compared to STEMI-Obstruction.

Moderate Aortic Stenosis in Patients With Heart Failure.

BACKGROUND AND OBJECTIVES: Moderate aortic stenosis (AS) confers a surprisingly adverse prognosis, approaching that of severe AS. The objective of this study was to describe the clinical course of patients with moderate AS with evidence of concomitant heart failure manifesting as elevated brain natriuretic peptide (BNP) levels. METHODS: This is a single-center, retrospective cohort study of 332 patients with elevated BNP. 165 patients with moderate AS were compared with 167 controls with none-mild AS. The Median follow-up duration was 3.85 years. The primary outcome was a composite endpoint of all-cause hospitalizations and all-cause mortality. RESULTS: BNP levels were 530 and 515 pg/mL in the study and the control groups, respectively. Moderate AS had significantly higher rates of primary composite endpoint in both univariate analysis (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.14-1.97; p=0.004) and adjusted analysis (HR, 1.45; 95% CI, 1.05-2.01; p=0.02). Moderate AS had 1.41 (95% CI, 1.18-1.69; p<0.001) times more all-cause hospitalization per patient-year of follow-up compared to controls in the univariate model. After adjustment for significant covariates, moderate AS remained an independent predictor of all-cause hospitalizations (incidence rate ratio [IRR], 1.45; 95% CI, 1.18-1.79; p=0.005). Furthermore, moderate AS was significantly associated with higher all-cause hospitalization rates in both heart failure with reduced ejection fraction (IRR, 1.33; 95% CI, 1.02-1.75; p=0.038) and heart failure with preserved ejection fraction [IRR], 1.31; 95% CI, 1.03-1.67; p=0.026). CONCLUSIONS: Moderate AS in conjunction with elevated BNP portends a significantly worse prognosis than those without moderate AS and should be followed closely.

Application of machine learning in screening for congenital heart diseases using fetal echocardiography.

There is a growing body of literature supporting the utilization of machine learning (ML) to improve diagnosis and prognosis tools of cardiovascular disease. The current study was to investigate the impact that the ML framework may have on the sensitivity of predicting the presence or absence of congenital heart disease (CHD) using fetal echocardiography. A comprehensive fetal echocardiogram including 2D cardiac chamber quantification, valvar assessments, assessment of great vessel morphology, and Doppler-derived blood flow interrogation was recorded. The postnatal echocardiogram was used to ascertain the diagnosis of CHD. A random forest (RF) algorithm with a nested tenfold cross-validation was used to train models for assessing the presence of CHD. The study population was derived from a database of 3910 singleton fetuses with maternal age of 28.8 ± 5.2 years and gestational age at the time of fetal echocardiography of 22.0 weeks (IQR 21-24). The proportion of CHD was 14.1% for the studied cohort confirmed by post-natal echocardiograms. Our proposed RF-based framework provided a sensitivity of 0.85, a specificity of 0.88, a positive predictive value of 0.55 and a negative predictive value of 0.97 to detect the CHD with the mean of mean ROC curves of 0.94 and the mean of mean PR curves of 0.84. Additionally, six first features, including cardiac axis, peak velocity of blood flow across the pulmonic valve, cardiothoracic ratio, pulmonary valvar annulus diameter, right ventricular end-diastolic diameter, and aortic valvar annulus diameter, are essential features that play crucial roles in adding more predictive values to the model in detecting patients with CHD. ML using RF can provide increased sensitivity in prenatal CHD screening with very good performance. The incorporation of ML algorithms into fetal echocardiography may further standardize the assessment for CHD.

Atrial function and geometry differences in transthyretin versus immunoglobulin light chain amyloidosis: a cardiac magnetic resonance study.

To determine the differences in left atrial (LA) function and geometry assessed by cardiac magnetic resonance (CMR) between transthyretin (ATTR) and immunoglobulin light chain (AL) cardiac amyloidosis (CA). We performed a retrospective analysis of 54 consecutive patients (68.5% male, mean age 67 ± 11 years) with confirmed CA (24 ATTR, 30 AL) who underwent comprehensive CMR examinations. LA structural and functional assessment including LA volume, LA sphericity index, and LA strain parameters were compared between both subtypes. In addition, 15 age-matched controls were compared to all groups. Patients with ATTR-CA were older (73 ± 9 vs. 62 ± 10 years, p < 0.001) and more likely to be male (83.3% vs. 56.7%, p = 0.036) when compared to AL-CA. No significant difference existed in LA maximum volume and LA sphericity index between ATTR-CA and AL-CA. LA minimum volumes were larger in ATTR-CA when compared with AL-CA. There was a significant difference in LA function with worse strain values in ATTR vs AL: left atrial reservoir [7.4 (6.3-12.8) in ATTR vs. 13.8 (6.90-24.8) in AL, p = 0.017] and booster strains [3.6 (2.6-5.5) in ATTR vs. 5.2 (3.6-12.1) in AL, p = 0.039]. After adjusting for age, LA reservoir remained significantly lower in ATTR-CA compared to AL-CA (p = 0.03), but not LA booster (p = 0.16). We demonstrate novel differences in LA function between ATTR-CA and AL-CA despite similar LA geometry. Our findings of more impaired LA function in ATTR may offer insight into higher AF burden in these patients.

Echocardiographic Reference Ranges of Non-invasive Myocardial Work Indices in Children.

Global myocardial work (GMW) is an emerging method to characterize left ventricle (LV) function with potential advantages over both ejection fraction and global longitudinal strain (GLS). We aimed to determine the feasibility and reproducibility for echocardiographic-derived GMW in a healthy pediatric population; establish normal reference values; and investigate the influence of age, gender, and other clinical factor on normal reference ranges. We prospectively enrolled 212 individuals (median age of 9 years; interquartile range, 6 to 12 years, 112 female). Global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were measured from LV pressure-strain loops. Quantification of GMW was performed using a GE Vivid E95 system and available software package (Echopac V.203, GE). The mean LV EF was 64 ± 3% with GLS of -21.3 ± 1.5%. GWI was 1688 ± 219 mmHg% with mean GWE of 96.5 ± 1.4%. The GCW was 1959 ± 207 mmHg%, and the mean GWW of 61.1 ± 30.9 mmHg%. No significant difference was found in MW indices across age group and gender (p > 0.05 for all). There were significant correlations between both GWI and GCW with GLS and systolic blood pressure (p < 0.001), but not with GWE and GWW. Linear regression model revealed that GWI and GCW were more closely correlated with systolic blood pressure than GLS. LV MW indices had good intra-observer and inter-observer reproducibility. This study establishes both the feasibility and reference ranges for non-invasive echocardiographic indices of GMW in healthy children. Myocardial work appears to be a complementary modality to assess LV performance in children.

Left Ventricular End-Diastolic Dimension and Clinical Outcomes After Centrifugal Flow Left Ventricular Assist Device Implantation.

The impact of preoperative end-diastolic left ventricular dimension (preLVEDD) on long-term outcomes with centrifugal continuous-flow left ventricular assist device (CF-LVAD) is not well established. Accordingly, we performed an analysis of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) registry to study this relationship. All patients with centrifugal CF-LVAD in the INTERMACS registry from June 2006 to December 2017 were screened. The final study group consisted of 3,304 patients. After a median follow-up of 9.0 months (interquartile range [IQR], 4.2-18.8 months), 2,596 (79%) patients were alive. After adjusting for significant covariates, increased preLVEDD was associated with lower mortality (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.84-0.98; p = 0.01), stroke (HR, 0.85; 95% CI, 0.77-0.93; p < 0.001), and gastrointestinal bleeding (HR, 0.88; 95% CI, 0.80-0.97; p = 0.01), although there were more arrhythmias (HR, 1.14; 95% CI, 1.05-1.24; p = 0.003). Our study suggests that preLVEDD is an independent predictor of mortality and adverse events in patients treated with centrifugal CF-LVAD. preLVEDD should be considered an important preimplant variable for risk stratification when considering a CF-LVAD.

Normal Ranges of Global Left Ventricular Myocardial Work Indices in Adults: A Meta-Analysis.

BACKGROUND: Recent studies have demonstrated that left ventricular myocardial work (MW) is incremental in diagnosis and prognostication compared with left ventricular ejection fraction and myocardial strain. The authors performed a meta-analysis of normal ranges of noninvasive MW indices including global work index, global constructive work, global wasted work, and global work efficiency and determined confounders that may contribute to variance in reported values. METHODS: Four databases (PubMed, Scopus, Embase, and the Cochrane Library) were searched through January 2021 using the key terms "myocardial work," "global constructive work," "global wasted work," "global work index," and "global work efficiency." Studies were included if the articles reported LV MW using two-dimensional transthoracic echocardiography in healthy normal subjects, either in a control group or comprising the entire study cohort. The weighted mean was estimated by using the random-effect model with a 95% CI. Heterogeneity across included studies was assessed using the I2 test. Funnel plots and the Egger regression test were used to assess potential publication bias. RESULTS: The search yielded 476 articles. After abstract and full-text screening, we included 13 data sets with 1,665 patients for the meta-analysis. The reported normal mean values of global work index and global constructive work among the studies were 2,010 mm Hg% (95% CI, 1,907-2,113 mm Hg%) and 2,278 mm Hg% (95% CI, 2,186-2,369 mm Hg%), respectively. Mean global wasted work was 80 mm Hg% (95% CI, 73-87 mm Hg%), and mean global work efficiency was 96.0% (95% CI, 96%-96%). Furthermore, gender significantly contributed to variations in normal values of global work index, global wasted work, and global work efficiency. No evidence of significant publication bias was observed. CONCLUSIONS: In this meta-analysis, the authors provide echocardiographic reference ranges for noninvasive indices of MW. These normal values could serve as a reference for clinical and research use.

Long-term outcomes of primary cardiac malignant tumors: Difference between African American and Caucasian population.

BACKGROUND: The survival outcome for primary cardiac malignant tumors (PMCTs) based on race has yet to be fully elucidated in previously published literature. This study aimed to address the general long-term outcome and survival rate differences in PMCTs among African Americans and Caucasian populations. METHODS: The 18 cancer registries database from the Surveillance, Epidemiology, and End Results (SEER) Program from 1975 to 2016 were utilized. Ninety-four African American (AA) and 647 Caucasian (CAU) patients from the SEER registry were available for survival analysis. The log-rank test was used to compare the difference in mortality between two populations and presented by the Kaplan-Meier curves. A multivariate Cox proportional hazards regression was used to determine the independent predictors of all-cause mortality. RESULTS: The overall 30-day, 1-year, and 5-year survival rates were 74%, 44.3%, and 16.6%, respectively, with a median survival of 10 months. There was no significant difference in survival rate between the two races (p-value = 0.55). The 1-year survival rate improved significantly during the study timeline in the AA population (13.3% during 1975-1998, 40.9% during 1999-2004, 50% during 2005-2010, and 59.7% during 2011-2016, p-value = 0.0064). Age of diagnosis, type of tumor, disease stage, and chemotherapy administration are the main factors that predict survival outcomes of PMCT patients. Interactive nomogram was developed based on significant predictors. CONCLUSIONS: PMCTs have remained one of the most lethal diseases with poor survival outcome. Survival rate improved during the timeline in AA patients, but in general, racial differences in survival outcome were not observed.

Right ventricular dysfunction and tricuspid regurgitation in functional mitral regurgitation.

AIM: The objective of this study was to investigate the prognostic importance of right ventricular dysfunction (RVD) and tricuspid regurgitation (TR) in patients with moderate-severe functional mitral regurgitation (FMR) receiving MitraClip procedure. RVD and TR grade are associated with cardiovascular mortality in the general population and other cardiovascular diseases. However, there are limited data from observational studies on the prognostic significance of RVD and TR in FMR receiving MitraClip procedure. METHODS AND RESULTS: A systemic review and meta-analysis were performed using MEDLINE, Scopus, and Embase to assess the prognostic value of RVD and TR grade for mortality in patients with functional mitral regurgitation (FMR) receiving MitraClip procedure. Hazard ratios were extracted from multivariate models reporting on the association of RVD and TR with mortality and described as pooled estimates with 95% confidence intervals. A total of eight non-randomized studies met the inclusion criteria with seven studies having at least 12 months follow-up with a mean follow-up of 20.9 months. Among the aforementioned studies, a total of 1112 patients (71.5% being male) were eligible for being included in our meta-analysis with an overall mortality rate of 28.4% (n = 316). Of the enrolled patients, RVD was present in 46.1% and moderate-severe TR in 29.2%. RVD was significantly associated with mortality compared to normal RV function (HR, 1.79, 95% CI, 1.39-2.31, P < 0.001, I2  = 0). Patients with moderate-severe TR showed increased risk of mortality compared with those in the none-mild TR group (HR, 1.61. 95% CI, 1.11-2.33, P = 0.01, I2  = 14). CONCLUSIONS: This meta-analysis demonstrates the prognostic importance of RVD and TR grade in predicting all-cause mortality in patients with significant FMR. RV function and TR parameters may therefore be useful in the risk stratification of patients with significant FMR undergoing MitraClip procedure.

Contractile Differences Detected by Speckle Tracking Echocardiography in Pediatric Patients with Mitral Valve Prolapse.

Mitral valve prolapse (MVP) is the most common valvar dysfunction in children. There is emerging evidence that MVP is not always a benign entity, hence identification of underlying mechanisms is pertinent to clinical management. Our group previously identified a ventricular contraction abnormality named end-systolic basal eversion (ESBE) in adults that contributed to MVP. The aim of this study was to evaluate regional circumferential strain in pediatric patients with MVP and ESBE compared to normal controls. Left ventricular circumferential strain was assessed in 16 pediatric patients referred for clinical echocardiographic examination with MVP and ESBE (MVP group) and compared to age-gender-matched healthy subjects. ESBE has been previously described as late systolic bileaflet mitral valve prolapse, papillary traction, and concomitant late systolic outward movement of the basal inferior myocardium. The mean age of the MVP group was 13.8 ± 4.6 year and 75% were female. All patients with MVP and controls had qualitatively normal systolic cardiac function. The MVP group had significantly lower regional strain values for 11/16 of the segments including all 6 basal segments. Importantly, the basal inferior (- 17.02 ± 8.32% vs. - 26.10 ± 3.18, p = 0.001) and basal inferolateral (- 19.53 ± 9.76 vs. - 26.10 ± 3.18, p = 0.03) had the lowest strain values compared to the average of all other segments suggesting weaker contraction in the basal inferior segments. Pediatric patients with MVP and ESBE are subject to a similar left ventricular mechanical dysfunction previously described in adults. ESBE was evident by decreased basal circumferential strain values. These findings denoted weaker contraction which is believed to propagate the late systolic outward movement of the basal ventricular myocardium.

Machine learning method for predicting pacemaker implantation following transcatheter aortic valve replacement.

BACKGROUND: An accurate assessment of permanent pacemaker implantation (PPI) risk following transcatheter aortic valve replacement (TAVR) is important for clinical decision making. The aims of this study were to investigate the significance and utility of pre- and post-TAVR ECG data and compare machine learning approaches with traditional logistic regression in predicting pacemaker risk following TAVR. METHODS: Five hundred fifity seven patients in sinus rhythm undergoing TAVR for severe aortic stenosis (AS) were included in the analysis. Baseline demographics, clinical, pre-TAVR ECG, post-TAVR data, post-TAVR ECGs (24 h following TAVR and before PPI), and echocardiographic data were recorded. A Random Forest (RF) algorithm and logistic regression were used to train models for assessing the likelihood of PPI following TAVR. RESULTS: Average age was 80 ± 9 years, with 52% male. PPI after TAVR occurred in 95 patients (17.1%). The optimal cutoff of delta PR (difference between post and pre TAVR PR intervals) to predict PPI was 20 ms with a sensitivity of 0.82, a specificity of 0.66. With regard to delta QRS, the optimal cutoff was 13 ms with a sensitivity of 0.68 and a specificity of 0.59. The RF model that incorporated post-TAVR ECG data (AUC 0.81) more accurately predicted PPI risk compared to the RF model without post-TAVR ECG data (AUC 0.72). Moreover, the RF model performed better than logistic regression model in predicting PPI risk (AUC: 0.81 vs. 0.69). CONCLUSIONS: Machine learning using RF methodology is significantly more powerful than traditional logistic regression in predicting PPI risk following TAVR.

Abnormal ventricular contractile pattern associated with late systolic mitral prolapse: a two-dimensional speckle tracking study.

We sought to study the mechanics of ventricular contraction in patients with and outward basal movement. Using echocardiographic parasternal long-axis views we retrospectively screened 760 echocardiograms to enroll 50 individuals with late systolic bileaflet prolapse, papillary muscle traction, and outward movement of the sub-annular base and posterior mitral annulus in late systole. Two-dimensional speckle tracking echocardiography was used to analyze the mechanics of contraction. Global and regional longitudinal strain values between the study group and 45 healthy control subjects were compared. The study group's global strain was lower compared to the control group. We identified a pattern of weak contraction of the inferior and lateral walls in the late systolic bileaflet prolapse group. The weakest segment in the study group was the basal-inferolateral segment (- 15.8% vs. - 21.5%, p < 0.001). There was no relationship between the mitral annular size, degree of leaflet prolapse, or degree of basal weakness. Late systolic bileaflet mitral prolapse and papillary muscle traction are accompanied by an outward movement of the sub-annular base and posterior mitral annulus in late systole. We demonstrated an abnormal contractile pattern in these ventricles characterized by a weaker contraction of the base, most significant at the inferolateral segment. This weakness of contraction may contribute to the outward movement of the base and posterior annulus.