Vaccination-Associated Myocarditis and Myocardial Injury.

SARS-CoV-2 vaccine-associated myocarditis/myocardial injury should be evaluated in the contexts of COVID-19 infection, other types of viral myocarditis, and other vaccine-associated cardiac disorders. COVID-19 vaccine-associated myocardial injury can be caused by an inflammatory immune cell infiltrate, but other etiologies such as microvascular thrombosis are also possible. The clinical diagnosis is typically based on symptoms and cardiac magnetic resonance imaging. Endomyocardial biopsy is confirmatory for myocarditis, but may not show an inflammatory infiltrate because of rapid resolution or a non-inflammatory etiology. Myocarditis associated with SARS-COVID-19 vaccines occurs primarily with mRNA platform vaccines, which are also the most effective. In persons aged >16 or >12 years the myocarditis estimated crude incidences after the first 2 doses of BNT162b2 and mRNA-1273 are approximately 1.9 and 3.5 per 100 000 individuals, respectively. These rates equate to excess incidences above control populations of approximately 1.2 (BNT162b2) and 1.9 (mRNA-1273) per 100 000 persons, which are lower than the myocarditis rate for smallpox but higher than that for influenza vaccines. In the studies that have included mRNA vaccine and SARS-COVID-19 myocarditis measured by the same methodology, the incidence rate was increased by 3.5-fold over control in COVID-19 compared with 1.5-fold for BNT162b2 and 6.2-fold for mRNA-1273. However, mortality and major morbidity are less and recovery is faster with mRNA vaccine-associated myocarditis compared to COVID-19 infection. The reasons for this include vaccine-associated myocarditis having a higher incidence in young adults and adolescents, typically no involvement of other organs in vaccine-associated myocarditis, and based on comparisons to non-COVID viral myocarditis an inherently more benign clinical course.

Reliability and reproducibility of the venous excess ultrasound (VExUS) score, a multi-site prospective study: validating a novel ultrasound technique for comprehensive assessment of venous congestion.

Though the novel venous excess ultrasound (VExUS) score is increasingly used as a noninvasive means of venous congestion measurement, the inter-rater reliability (IRR), inter-user reproducibility (IUR), and utility of concurrent ECG have not been evaluated. We conducted a multicenter study of the IRR, IUR, and utility of ECG for VExUS interpretation between four attending physicians of diverse specialties, reporting the Kappa statistic (KS) and Intraclass Correlation Coefficient (ICC) for IRR and IUR for scans with and without ECG. Eighty-four paired VExUS exams from 42 patients, 60 of which had a concurrent ECG tracing, were interpreted. They showed substantial IRR, with a KS of 0.71 and ICC of 0.83 for the overall VExUS grade (p < 0.001), and IUR, with a KS 0.63 and ICC of 0.8. There was greater agreement among images with an ECG tracing. These results suggest that ECG-augmented VExUS may be a reliable and reproducible measure interpretable by clinicians with diverse backgrounds.

Pulmonary valve assessment by three-dimensional echocardiography.

The pulmonary valve (PV) has historically been ignored by imaging studies. Disorders of the PV encountered in adult cardiac patients are increasingly encountered due to advanced care of patients with congenital heart disease and associated PV diseases. Despite advances in PV imaging, multiple challenges remain when it comes to obtaining high quality PV images. While 2D TTE is the usual initial imaging tool for PV, excellent views of the PV annulus and its one or two leaflets are obtained in less than half of patients. The 3D echocardiography en face view allows all three leaflets to be evaluated concurrently, as well as assessments of the RV outflow tract and main pulmonary artery, which has improved quantitative assessment of PV diseases. Increasing image quality and experience with live/real time 3D TEE amplifies its utility in accurate evaluation and helps guide and monitor successful percutaneous PV interventions. 2D TTE remains the first line diagnostic tool; however, 3D TTE and 3D TEE provide better image quality which increases diagnostic accuracy and guidance to therapy. In this review article, we stress improvement in 3D echocardiography and its role in diagnostic and therapeutic options for PV diseases.

Transesophageal echocardiography simulation: A review of current technology.

Transesophageal echocardiography (TEE) has experienced tremendous increase in interest and demand alongside the rapid growth of transcatheter structural cardiac interventions. TEE instruction prolongs the procedure, increasing the risk of probe malfunction from overheating and patient complications from prolonged sedation. Echocardiographic simulation programs have been developed to hone the procedural skills of novice operators in a time-unrestricted, low-pressure environment before they perform TEEs on real patients. Simulators likely benefit training in interventional TEE for the same reasons. We searched PubMed, basic Google, and Google Scholar for currently marketed TEE simulators, including foreign as well as US companies. We queried the vendors regarding features of the simulators that pertain to effective instructional design for diagnostic TEE. We also queried regarding the simulators' applicability to training in interventional TEE. The vendors' responses are reported here. In addition, we discuss the specific training needs for structural heart interventions, for which echocardiographic simulation could be a powerful educational tool. Lastly, we discuss the role of simulation for formative and summative assessment, and the advances required to improve training in complex procedures within the field of interventional echocardiography.

Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts.

Pluripotent stem cells provide a potential solution to current epidemic rates of heart failure by providing human cardiomyocytes to support heart regeneration. Studies of human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) in small-animal models have shown favourable effects of this treatment. However, it remains unknown whether clinical-scale hESC-CM transplantation is feasible, safe or can provide sufficient myocardial regeneration. Here we show that hESC-CMs can be produced at a clinical scale (more than one billion cells per batch) and cryopreserved with good viability. Using a non-human primate model of myocardial ischaemia followed by reperfusion, we show that cryopreservation and intra-myocardial delivery of one billion hESC-CMs generates extensive remuscularization of the infarcted heart. The hESC-CMs showed progressive but incomplete maturation over a 3-month period. Grafts were perfused by host vasculature, and electromechanical junctions between graft and host myocytes were present within 2 weeks of engraftment. Importantly, grafts showed regular calcium transients that were synchronized to the host electrocardiogram, indicating electromechanical coupling. In contrast to small-animal models, non-fatal ventricular arrhythmias were observed in hESC-CM-engrafted primates. Thus, hESC-CMs can remuscularize substantial amounts of the infarcted monkey heart. Comparable remuscularization of a human heart should be possible, but potential arrhythmic complications need to be overcome.

Feasibility of pulmonary valve imaging using transesophageal echocardiography upper esophageal view.

BACKGROUND: The present study designed to evaluate feasibility of transesophageal echocardiographic (TEE) imaging of the pulmonary valve (PV) at the transaortic upper esophageal (TAUE) window. We hypothesized that patients with larger aorta would be more likely to have visualization of the PV from this TAUE window. METHODS: 2D TEE images of the PV were prospectively acquired by one operator at the TAUE window looking through the aortic arch. Patients were divided into four groups based on image quality of PV (group 1, not visualized; group 2, barely visualized; group 3, sufficient visualization; group 4, excellent visualization). Clinical, echocardiographic, and radiologic parameters were collected. RESULTS: A total of 212 consecutive patients (54 ± 14 years, 63.7% male) were enrolled. Group distribution was as follows: group 1, n = 60 (28.3%); group 2 n = 39 (18.4%); group 3, n = 27 (12.7%); group 4, n = 86 (40.6%). There were no differences between groups' baseline clinical characteristics. There was a weak although statistically negative correlation between PV image quality and aortic arch dimension (r = -0.17 P = 0.01). There was a stronger positive correlation between PV thickness (r = 0.38 P < 0.001) and PV image quality. Retrospective subgroup analysis of 76 patients with recent chest CT showed similar, but not significant trends as by TEE. CONCLUSION: The use of 2D TEE TAUE results in diagnostic image quality of the PV in the majority of patients and outstanding image quality in a subset of patients. PV image quality is negatively affected by increasing aorta diameter and positively affected by PV thickness.

The acute effects of edge-to-edge percutaneous mitral valve repair on the shape and size of the mitral annulus and its relation to mitral regurgitation.

BACKGROUND: The effects of edge-to-edge percutaneous mitral valve repair on the shape and size of the mitral annulus and its relation to mitral regurgitation (MR) have not been well characterized. We evaluated acute changes in mitral annular shape and dimensions, and their effect on MR severity, in patients with functional and degenerative MR following MitraClip® . METHODS: Patients that underwent MitraClip® between January 2013 and May 2016 at our institution were retrospectively reviewed. EXCLUSIONS: inadequate images, prior mitral valve repair, and rapid atrial fibrillation. Intra-procedure TEE 3D images acquired prior to and after implantation of MitraClip® were analyzed using software to model the mitral valve apparatus. RESULTS: Of seventy-eight patients that underwent MitraClip® procedure, 60 were eligible. Mean age was 78.3 ± 11 years. Severe MR (4+) was present in 37 patients, moderately/severe MR (3+) in 23. All patients achieved MR reduction to ≤2. 3D annular circumference, bicommissural diameter, and anteroposterior diameter had a significant size reduction after MitraClip® . None of the mitral annular measures had significantly different mean change between the large and small MR change groups at the 0.05 significance level. CONCLUSIONS: In patients with functional or degenerative MR, the MitraClip® significantly affect mitral annular dimensions; however, these changes do not correlate with the immediate MR reduction.

Incidence and Risk Factors for Postcontrast Acute Kidney Injury in Survivors of Sudden Cardiac Arrest.

STUDY OBJECTIVE: Survivors of sudden cardiac arrest may be exposed to iodinated contrast from invasive coronary angiography or contrast-enhanced computed tomography, although the effects on incident acute kidney injury are unknown. The study objective was to determine whether contrast administration within the first 24 hours was associated with acute kidney injury in survivors of sudden cardiac arrest. METHODS: This cohort study, derived from a prospective clinical trial, included patients with sudden cardiac arrest who survived for 48 hours, had no history of end-stage renal disease, and had at least 2 serum creatinine measurements during hospitalization. The contrast group included patients with exposure to iodinated contrast within 24 hours of sudden cardiac arrest. Incident acute kidney injury and first-time dialysis were compared between contrast and no contrast groups and then controlled for known acute kidney injury risk factors. RESULTS: Of the 199 survivors of sudden cardiac arrest, 94 received iodinated contrast. Mean baseline serum creatinine level was 1.3 mg/dL (95% confidence interval [CI] 1.4 to 1.5 mg/dL) for the contrast group and 1.6 mg/dL (95% CI 1.4 to 1.7 mg/dL) for the no contrast group. Incident acute kidney injury was lower in the contrast group (12.8%) than the no contrast group (17.1%; difference 4.4%; 95% CI -9.2% to 17.5%). Contrast administration was not associated with significant increases in incident acute kidney injury within quartiles of baseline serum creatinine level or after controlling for age, sex, race, congestive heart failure, diabetes, and admission serum creatinine level by regression analysis. Older age was independently associated with acute kidney injury. CONCLUSION: Despite elevated baseline serum creatinine level in most survivors of sudden cardiac arrest, iodinated contrast administration was not associated with incident acute kidney injury even when other acute kidney injury risk factors were controlled for. Thus, although acute kidney injury is not uncommon among survivors of sudden cardiac arrest, early (<24 hours) contrast administration from imaging procedures did not confer an increased risk for acute kidney injury.

A focused update to the 2019 NLA scientific statement on use of lipoprotein(a) in clinical practice.

Since the 2019 National Lipid Association (NLA) Scientific Statement on Use of Lipoprotein(a) in Clinical Practice was issued, accumulating epidemiological data have clarified the relationship between lipoprotein(a) [Lp(a)] level and cardiovascular disease risk and risk reduction. Therefore, the NLA developed this focused update to guide clinicians in applying this emerging evidence in clinical practice. We now have sufficient evidence to support the recommendation to measure Lp(a) levels at least once in every adult for risk stratification. Individuals with Lp(a) levels <75 nmol/L (30 mg/dL) are considered low risk, individuals with Lp(a) levels ≥125 nmol/L (50 mg/dL) are considered high risk, and individuals with Lp(a) levels between 75 and 125 nmol/L (30-50 mg/dL) are at intermediate risk. Cascade screening of first-degree relatives of patients with elevated Lp(a) can identify additional individuals at risk who require intervention. Patients with elevated Lp(a) should receive early, more-intensive risk factor management, including lifestyle modification and lipid-lowering drug therapy in high-risk individuals, primarily to reduce low-density lipoprotein cholesterol (LDL-C) levels. The U.S. Food and Drug Administration approved an indication for lipoprotein apheresis (which reduces both Lp(a) and LDL-C) in high-risk patients with familial hypercholesterolemia and documented coronary or peripheral artery disease whose Lp(a) level remains ≥60 mg/dL [∼150 nmol/L)] and LDL-C ≥ 100 mg/dL on maximally tolerated lipid-lowering therapy. Although Lp(a) is an established independent causal risk factor for cardiovascular disease, and despite the high prevalence of Lp(a) elevation (∼1 of 5 individuals), measurement rates are low, warranting improved screening strategies for cardiovascular disease prevention.

Mortality Associated With Proportionality of Secondary Mitral Regurgitation After Transcatheter Mitral Valve Repair: North American Mitraclip for Functional Mitral Regurgitation Registry.

The association, if any, between the effective regurgitant orifice area (EROA) to left ventricular end-diastolic volume (LVEDV) ratio and 1-year mortality is controversial in patients who undergo mitral transcatheter edge-to-edge repair (m-TEER) with the MitraClip system (Abbott Vascular, Santa Clara, CA). This study's objective was to determine the association between EROA/LVEDV and 1-year mortality in patients who undergo m-TEER with MitraClip. In patients with severe secondary (functional) mitral regurgitation (MR), we analyzed registry data from 11 centers using generalized linear models with the generalized estimating equations approach. We studied 525 patients with secondary MR who underwent m-TEER. Most patients were male (63%) and were New York Heart Association class III (61%) or IV (21%). Mitral regurgitation was caused by ischemic cardiomyopathy in 51% of patients. EROA/LVEDV values varied widely, with median = 0.19 mm2/ml, interquartile range [0.12,0.28] mm2/ml, and 187 patients (36%) had values <0.15 mm2/ml. Postprocedural mitral regurgitation severity was substantially alleviated, being 1+ or less in 74%, 2+ in 20%, 3+ in 4%, and 4+ in 2%; 1-year mortality was 22%. After adjustment for confounders, the logarithmic transformation (Ln) of EROA/LVEDV was associated with 1-year mortality (odds ratio 0.600, 95% confidence interval 0.386 to 0.933, p = 0.023). A higher Society of Thoracic Surgeons risk score was also associated with increased mortality. In conclusion, lower values of Ln(EROA/LVEDV) were associated with increased 1-year mortality in this multicenter registry. The slope of the association is steep at low values but gradually flattens as Ln(EROA/LVEDV) increases.

Myocardial Injury and Altered Gene Expression Associated With SARS-CoV-2 Infection or mRNA Vaccination.

SARS CoV-2 enters host cells via its Spike protein moiety binding to the essential cardiac enzyme angiotensin-converting enzyme (ACE) 2, followed by internalization. COVID-19 mRNA vaccines are RNA sequences that are translated into Spike protein, which follows the same ACE2-binding route as the intact virion. In model systems, isolated Spike protein can produce cell damage and altered gene expression, and myocardial injury or myocarditis can occur during COVID-19 or after mRNA vaccination. We investigated 7 COVID-19 and 6 post-mRNA vaccination patients with myocardial injury and found nearly identical alterations in gene expression that would predispose to inflammation, coagulopathy, and myocardial dysfunction.

Real time three-dimensional echocardiography evaluation of intracardiac masses.

The evaluation of cardiac masses is often a challenge for cardiac imaging techniques. The traditional standby has been two-dimensional echocardiography (2DE). Real time three-dimensional echocardiography (RT3DE) offers incremental value for the evaluation of intracardiac masses by providing more accurate assessment of the size and shape of the mass as well as in some cases, composition of the mass. RT3DE aids with the relationship between the mass and adjacent structures. Therefore, here we discuss the subject of RT3DE evaluation of cardiac masses is reviewed and discussed in detail.

Esophago-Pericardial Fistula as a Rare and Life-Threatening Complication of Epicardial Ventricular Tachycardia Ablation.

We describe a rare complication of esophago-pericardial fistula after epicardial ventricular tachycardia ablation. Echocardiogram revealed evidence of pneumopericardium and additional imaging studies confirmed esophageal leak with evidence of fistula formation requiring prompt surgical repair. (Level of Difficulty: Intermediate.).

Cor triatriatum evaluated by real time 3D TEE.

We present two cases of cor triatriatum, a rare congenital anomaly that consists of a membrane that divides the left atrium into two chambers. The first case involves an older adult man admitted for evaluation of left-sided weakness attributed to stroke. The second is a case of a middle-aged woman with dyspnea. Both patients had transthoracic echocardiograms as a part of their initial evaluation, which revealed abnormal structures in the left atrium, and both subsequently underwent transesophageal echocardiography. During these exams, real-time 3D imaging was utilized to more completely define the pathology.

The National Lipid Association scientific statement on coronary artery calcium scoring to guide preventive strategies for ASCVD risk reduction.

An Expert Panel of the National Lipid Association reviewed the evidence related to the use of coronary artery calcium (CAC) scoring in clinical practice for adults seen for primary prevention of atherosclerotic cardiovascular disease. Recommendations for optimal use of this test in adults of various races/ethnicities, ages and multiple domains of primary prevention, including those with a 10-year ASCVD risk <20%, those with diabetes or the metabolic syndrome, and those with severe hypercholesterolemia were provided. Recommendations were also made on optimal timing for repeat calcium scoring after an initial test, use of CAC scoring in those taking statins, and its role in informing the clinician patient discussion on the benefit of aspirin and anti-hypertensive drug therapy. Finally, a vision is provided for the future of coronary calcium scoring.

Does statin therapy affect the progression of atherosclerosis measured by a coronary calcium score?

Coronary atherosclerosis is a leading cause of death in the United States and worldwide, accounting for close to 1 million deaths annually in the United States alone. The evaluation of coronary disease by CT-derived calcium scores is a rapidly evolving field of medical imaging. Furthermore, until recently, whether or not regression or progression of coronary disease could accurately be assessed by coronary calcium scores had been a question of considerable debate among experts in this field. If the medical treatment of coronary artery disease by statin pharmacotherapy could be accurately assessed by coronary calcium scoring, this would take much of the current guess work out of statin pharmacotherapy. Initial retrospective studies and observational data suggested that statin treatment resulted in reduction of coronary calcium. More recently, five randomized controlled trials have demonstrated that not only does statin treatment not reduce coronary calcium, but in fact, the progression of coronary calcium by CT scanning is indistinguishable from placebo treatment.

Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts.

Cardiomyocytes derived from human embryonic stem (hES) cells potentially offer large numbers of cells to facilitate repair of the infarcted heart. However, this approach has been limited by inefficient differentiation of hES cells into cardiomyocytes, insufficient purity of cardiomyocyte preparations and poor survival of hES cell-derived myocytes after transplantation. Seeking to overcome these challenges, we generated highly purified human cardiomyocytes using a readily scalable system for directed differentiation that relies on activin A and BMP4. We then identified a cocktail of pro-survival factors that limits cardiomyocyte death after transplantation. These techniques enabled consistent formation of myocardial grafts in the infarcted rat heart. The engrafted human myocardium attenuated ventricular dilation and preserved regional and global contractile function after myocardial infarction compared with controls receiving noncardiac hES cell derivatives or vehicle. The ability of hES cell-derived cardiomyocytes to partially remuscularize myocardial infarcts and attenuate heart failure encourages their study under conditions that closely match human disease.

Exposure to traffic and left ventricular mass and function: the Multi-Ethnic Study of Atherosclerosis.

RATIONALE: Ambient air pollution has been associated with heart failure morbidity and mortality. The mechanisms responsible for these associations are unknown but may include the effects of traffic-related pollutants on vascular or autonomic function. OBJECTIVES: We assessed the cross-sectional relation between long-term air pollution, traffic exposures, and important end-organ measures of alterations in cardiac function-left ventricular mass index (LVMI) and ejection fraction-in the Multi-Ethnic Study of Atherosclerosis, a multicenter study of adults without previous clinical cardiovascular disease. METHODS: A total of 3,827 eligible participants (aged 45-84 yr) underwent cardiac magnetic resonance imaging between 2000 and 2002. We estimated air pollution exposures using residential proximity to major roadways and interpolated concentrations of fine particulate matter (less than 2.5 microns in diameter). We examined adjusted associations between these exposures and left ventricular mass and function. MEASUREMENTS AND MAIN RESULTS: Relative to participants living more than 150 m from a major roadway, participants living within 50 m of a major roadway showed an adjusted 1.4 g/m(2) (95% CI, 0.3-2.5) higher LVMI, a difference in mass corresponding to a 5.6 mm Hg greater systolic blood pressure. Ejection fraction was not associated with proximity to major roadways. Limited variability in estimates of fine particulate matter was observed within cities, and no associations with particulate matter were found for either outcome after adjustment for center. CONCLUSIONS: Living in close proximity to major roadways is associated with higher LVMI, suggesting chronic vascular end-organ damage from a traffic-related environmental exposure. Air pollutants or another component of roadway proximity, such as noise, could be responsible.