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.

Safety and efficacy of IV theophylline for regadenoson-associated side effect reversal.

BACKGROUND: Aminophylline injection has been on an intermittent nation-wide shortage due to manufacturing delays leaving a need for an alternative reversal agent for regadenoson-associated side effects. Intravenous theophylline should be a logical acceptable pharmacological alternative; however, data regarding its safety and efficacy as a reversal agent are lacking. METHODS: Utilizing electronic medical records at the University of Colorado hospital, we identified patients ≥ 18 years of age who had a pharmacologic stress test using regadenoson during periods of aminophylline shortage (3/1/2013 to 5/31/2013 and 4/1/2018 to 8/30/2018) in which theophylline was used as an alternative antidote for side effect reversal. Intravenous theophylline was prepared by the inpatient pharmacy to a concentration of 0.8 mg/mL in a total volume of 100 mL D5W. Specific side effects and side effect resolution were evaluated. RESULTS: Of the 122 patients evaluated, theophylline was administered in doses ranging from 40 to 75 mg with the majority receiving 40 mg. Complete resolution of regadenoson side effects occurred in 98 patients with 12 experiencing partial resolution and 1 without resolution. No adverse effects or events were reported. CONCLUSION: Due to limited availability of aminophylline, theophylline may be a safe and effective alternative to reverse regadenoson-associated side effects.

Update in Paravalvular Leak Closure.

PURPOSE OF REVIEW: Given the low occurrence of clinically important paravalvular leak (PVL), there are no large registries or trials in this space to investigate management strategies. This review integrates newer evidence, particularly in imaging guidance for these complex procedures, novel techniques and approaches that our group has taken, as well as approaches to more complex PVL plugging reported in case reports. RECENT FINDINGS: Perhaps the largest area of growth in the management of PVL is the use of advanced imaging in both pre-procedure evaluation and intra-procedural guidance with gated cardiac CT, 3D TEE, and fluoroscopy fusion technologies. Outside the USA, a new device, the Occlutech PLD, has become available with early data indicating high success rates. There remains little randomized data to support the efficacy of percutaneous PVL closure. Gated cardiac CT has become key to the pre-procedure evaluation for transcatheter closure as it allows for increased procedural efficiency and more accurate pre-procedure planning, particularly when combined with 3D printing. Intra-procedural TEE-fluoro fusion allows for more rapid crossing of defects by providing a visual target for interventionalists. The advent of purpose-built devices for PVL closure may further increase the efficacy and efficiency of percutaneous closure, but significant barriers remain for approval of these devices in the USA.

Echocardiography-fluoroscopy fusion imaging: The essential features used in congenital and structural heart disease interventional guidance.

Increased catheter-based interventions in congenital and structural heart disease require imaging modalities to be oriented in the same visual perspective. The use of echocardiography-fluoroscopy fusion (EFF) imaging has been developed for better characterization of complex anatomy and to facilitate key steps in interventional procedures. This review will detail the technology behind EFF, the differences between the two ultrasound fusion systems, and essential features of EFF imaging in congenital and structural heart disease interventions.

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.

Preprocedural imaging in patients with transposition of the great arteries facilitates placement of cardiac resynchronization therapy leads.

OBJECTIVE: The purpose of this study is to review a series of patients with complex congenital heart disease in whom preprocedural imaging was used to assist placement of cardiac resynchronization therapy (CRT) leads. BACKGROUND: CRT may be beneficial in patients with a failing systemic ventricle and transposition of the great arteries (TGA). However, complex coronary venous anatomy can be challenging for placement of CRT leads. METHODS: Between October 2006 and June 2012, seven patients with either dextro-TGA (d-TGA) or levo-TGA (l-TGA) underwent preprocedural imaging prior to placement of CRT leads (three, d-TGA and four, l-TGA). Three patients underwent cardiac computed tomography (CT) and four underwent coronary angiography, which included levophase imaging of the coronary sinus (CS) or direct contrast injection of the CS. Where CS anatomy was appropriate with drainage into the systemic venous circulation, a transvenous approach was planned. In all other cases, the patient was referred for surgical placement of epicardial leads. RESULTS: Seven patients were identified with either d-TGA or l-TGA who had undergone preprocedural imaging prior to placement of CRT leads (three, d-TGA and four, l-TGA). Three patients underwent cardiac CT and four underwent coronary angiography, which included levophase imaging of the CS or direct contrast injection of the CS. All seven patients had successful CRT lead placement guided by preprocedure imaging. Three patients required surgical placement whereas four were able to undergo transvenous placement. There were no complications. The majority of patients (four of seven) had improvement in New York Heart Association class as well as subjective improvement in exercise tolerance and energy. The majority of patients also had subjective improvement in systemic right ventricular function by echocardiogram and objective improvement in fractional area change of the right ventricle. The follow-up period ranged from 13 months to 55 months with a mean follow-up of 39 months. CONCLUSIONS: Placement of biventricular leads for CRT in patients with l-TGA or d-TGA is feasible. Preprocedural imaging of the CS allows for better assessment of its anatomy and helps determine procedural approach for CRT placement, thereby limiting unnecessary procedures. In the majority of patients, there was subjective improvement in functional status and right ventricular function; in addition, there was objective improvement in echocardiographic parameters of right ventricular function after CRT placement.

Procedural guidance using advance imaging techniques for percutaneous edge-to-edge mitral valve repair.

The complexity of structural heart disease interventions such as edge-to edge mitral valve repair requires integration of multiple highly technical imaging modalities. Real time imaging with 3-dimensional (3D) echocardiography is a relatively new technique that first, allows clear volumetric imaging of target structures such as the mitral valve for both pre-procedural diagnosis and planning in patients with degenerative or functional mitral valve regurgitation. Secondly it provides intra-procedural, real-time panoramic volumetric 3D view of structural heart disease targets that facilitates eye-hand coordination while manipulating devices within the heart. X-ray fluoroscopy and RT 3D TEE images are used in combination to display specific targets and movement of catheter based technologies in 3D space. This integration requires at least two different image display monitors and mentally fusing the individual datasets by the operator. Combined display technology such as this, allow rotation and orientation of both dataset perspectives necessary to define targets and guidance of structural disease device procedures. The inherently easy concept of direct visual feedback and eye-hand coordination allows safe and efficient completion of MitraClip procedures. This technology is now merged into a single structural heart disease guidance mode called EchoNavigator(TM) (Philips Medical Imaging Andover, MA). These advanced imaging techniques have revolutionized the field of structural heart disease interventions and this experience is exemplified by a cooperative imaging approach used for guidance of edge-to-edge mitral valve repair procedures.

Magnetic Resonance Imaging Characterization and Clinical Outcomes of Dilated and Arrhythmogenic Left Ventricular Cardiomyopathies.

BACKGROUND: Nondilated left ventricular cardiomyopathy (NDLVC) has been recently differentiated from dilated cardiomyopathy (DCM). A comprehensive characterization of these 2 entities using cardiac magnetic resonance (CMR) and genetic testing has never been performed. OBJECTIVES: This study sought to provide a thorough characterization and assess clinical outcomes in a large multicenter cohort of patients with DCM and NDLVC. METHODS: A total of 462 patients with DCM (227) or NDLVC (235) with CMR data from 4 different referral centers were retrospectively analyzed. The study endpoint was a composite of sudden cardiac death or major ventricular arrhythmias. RESULTS: In comparison to DCM, NDLVC had a higher prevalence of pathogenic or likely pathogenic variants of arrhythmogenic genes (40% vs 23%; P < 0.001), higher left ventricular (LV) systolic function (LV ejection fraction: 51% ± 12% vs 36% ± 15%; P < 0.001) and higher prevalence of free-wall late gadolinium enhancement (LGE) (27% vs 14%; P < 0.001). Conversely, DCM showed higher prevalence of pathogenic or likely pathogenic variants of nonarrhythmogenic genes (23% vs 12%; P = 0.002) and septal LGE (45% vs 32%; P = 0.004). Over a median follow-up of 81 months (Q1-Q3: 40-132 months), the study outcome occurred in 98 (21%) patients. LGE with septal location (HR: 1.929; 95% CI: 1.033-3.601; P = 0.039) was independently associated with the risk of sudden cardiac death or major ventricular arrhythmias together with LV dilatation, older age, advanced NYHA functional class, frequent ventricular ectopic activity, and nonsustained ventricular tachycardia. CONCLUSIONS: In a multicenter cohort of patients with DCM and NDLVC, septal LGE together with LV dilatation, age, advanced disease, and frequent and repetitive ventricular arrhythmias were powerful predictors of major arrhythmic events.

Implementation of real-time three-dimensional transesophageal echocardiography for mitral balloon valvuloplasty.

BACKGROUND: Transthoracic (TTE) and intracardiac echocardiography (ICE) have both been established as modalities for imaging guidance in mitral balloon valvuloplasty (MBV). Real-time three-dimensional transesophageal echocardiography (RT3D-TEE) improves depth resolution, characterization of pathology and visualization of interventional catheters and devices. Three-dimensional imaging should enhance catheter navigation but improvements in procedural outcomes are not easily quantified. Using time from transseptal puncture to balloon inflation, procedure time and radiation exposure as surrogates for improvements linked to image guidance, we describe our early experience in implementing RT3D-TEE during MBV, a prototypical left-sided structural intervention. METHODS: Using a dedicated interventional procedures database, we reviewed the clinical and procedural variables of 70 consecutive cases of MBV utilizing either RT3D-TEE or TTE combined with ICE from 12/2004 to 4/2009. RESULTS: The clinical characteristics of both groups were well matched and there was no difference in mean gradient reduction or complication rates. Fluoroscopy times (TTE/ICE 26.7 ± 5.6 min. vs. RT3D-TEE 23.3 ± 6 min. P = 0.02) and radiation dose-area product (TTE/ICE 216.2 ± 96.6 vs. RT3D-TEE 171.5 ± 63.9) were lower with the RT3D-TEE cohort. Time from 1st transseptal puncture attempt to 1st balloon inflation was found to be lower in the RT-3DTEE cohort (TTE/ICE 36 ± 8 min vs. 28 ± 8 min P <0.01) CONCLUSION: RT3D-TEE is associated with expedited transseptal puncture and balloon catheter navigation as reflected in the decreased transseptal to balloon time. RT3D-TEE is associated with less reliance on fluoroscopic navigation as compared to using TTE/ICE. This series demonstrates the feasibility and advantages of implementing RT3D-TEE for MBV.

A sinus venosus atrial septal defect is diagnosed by echocardiography with an unusual bubble study.

A 68-year-old man underwent echocardiogram with agitated saline for a presumed diagnosis of primary pulmonary hypertension. Surprisingly, the bubbles from the agitated saline enter the left heart before filling the right side, leading to a diagnosis of Eisenmeger's syndrome from a sinus venosus atrial septal defect. Because of high right-sided pressure, the bubbles preferentially travel from the superior vena cava through the defect to the right superior pulmonary vein and left atrium, rather than the right side. This diagnosis was later confirmed on cardiac MRI.

Aortic valve chordae tendineae: A rare cause of aortic stenosis.

We describe a rare case of severe low-flow, low-gradient aortic stenosis due to a calcified aortic valve chordae tendineae. The chordae was captured on cardiac computed tomography (CT) using advanced 3-dimensional image reconstruction to reveal the fibrous strand tethering the non-coronary cusp to the left ventricular outflow tract, rendering it functionally immobile. This is one of the first reported cases of severe aortic stenosis from an aortic valve chordae tendineae which highlights the utility of advanced image processing techniques in cardiac CT.

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.

Right Ventricular Dysfunction During Endurance Exercise as Determined by Pressure-Volume Analysis.

A 37-year-old athlete completed invasive endurance (90 km) bicycle exercise testing for right ventricular pressure-volume analysis. Increased right ventricular afterload caused declines in ventricular-arterial coupling and cardiac output, causing increased arteriovenous oxygen difference to maintain oxygen uptake. These findings demonstrate effects of changes in right ventricular performance on exercise capacity. (Level of Difficulty: Intermediate.).

Transcatheter Closure of Left Ventricle to Coronary Sinus Fistula Post-MVR and Septal Myectomy.

This paper describes the case of a patient who developed refractory heart failure due to a fistula from the left ventricle to the coronary sinus that was unintentionally created after a surgical myectomy and mitral valve replacement. Advanced image guidance with a pre-procedure 3-dimensional physical model and intraprocedure echocardiography fusion facilitated transcatheter plugging of the shunt with symptom resolution. (Level of Difficulty: Advanced.).

Rapid prototyping: a new tool in understanding and treating structural heart disease.

As the appreciation of structural heart disease in children and adults has increased and as catheter-based closure procedures are now being performed in clinical practice, cardiovascular physicians have multiple compelling new reasons to better understand cardiac anatomic and spatial relationships. Current 2-dimensional imaging techniques remain limited both in their ability to represent the complex 3-dimensional relationships present in structural heart disease and in their capacity to adequately facilitate often complex corrective procedures. This review discusses the cardiovascular applications of rapid prototyping, a new technology that may not only play a significant role in the planning of catheter-based interventions but also may serve as a valuable educational tool to enhance the medical community's understanding of the many forms of structural heart disease.

Implementation of real time three-dimensional transesophageal echocardiography in percutaneous mitral balloon valvuloplasty and structural heart disease interventions.

Percutaneous interventions for structural heart disease are performed in a dynamic and complex environment that necessitates multiple imaging modalities to achieve procedural success. Structural interventions are routinely guided by two-dimensional (2D) modalities such as x-ray fluoroscopy, transesophageal echocardiography (TEE), and intracardiac echocardiography. Real time imaging with three-dimensional (3D) echocardiography is a novel method of guidance to facilitate complex structural interventions with the promise of greater safety and efficacy. Real time 3D TEE (RT3D-TEE) affords the capability of imaging catheters and devices, the interventional objective, and adjacent structures simultaneously. We present an overview of RT3D-TEE and explore its functionality in structural heart interventions by using percutaneous mitral balloon valvuloplasty as a model.

Congenital and Structural Heart Disease Interventions Using Echocardiography-Fluoroscopy Fusion Imaging.

With the increasing frequency of catheter-based interventions in congenital heart disease and structural heart disease, the use of fusion imaging has become a major enhancement for understanding complex anatomy and facilitating key steps in interventional procedures. Because transesophageal echocardiography and fluoroscopy are displayed in different visual perspectives, the interventional cardiologist must mentally reregister the images from the two modalities during the procedure. Echocardiography-fluoroscopy fusion (EFF) imaging displays the x-ray and ultrasound overlay images in the same visual perspective. This new technology allows for enhanced team communication, improved visual guidance, and more efficient navigation. The purpose of this review is to describe the EFF imaging technology, current uses of EFF imaging in congenital and structural heart disease, and future directions that will enhance this unique imaging technology to guide interventional procedures.

A comparison of echocardiographic modalities to guide structural heart disease interventions.

Percutaneous techniques to treat structural heart disease are rapidly evolving based on innovative interventions and the considerable advancement in image guidance technology. While two-dimensional transthoracic and transesophageal echocardiography have been integral to procedural planning and execution, intracardiac and three-dimensional echocardiography supply unique visualization of target structures with a potential improvement in patient safety and procedural efficacy. The choice of image guidance modality is based on specific differences between imaging systems, as well as other variables including cost, patient safety, operator expertise, and complexity of procedure. We will compare the adjunctive imaging tools for structural heart disease interventions, with a focus on intracardiac echocardiography and real-time three-dimensional transesophageal echocardiography.

Left ventricular outflow tract obstruction in the presence of asymmetric septal hypertrophy and accessory mitral valve tissue treated with alcohol septal ablation.

Redundant or accessory mitral valve tissue (AMVT) is a rare clinical condition. It is an even rarer cause of left ventricular outflow tract obstruction. We report a case of an adult male with medically unresponsive hypertrophic obstructive cardiomyopathy in whom real-time three-dimensional transesophageal echocardiography was used to both diagnose the presence of coexistent asymmetric septal hypertrophy and AMVT as well as confirm the safety and efficacy of treatment with alcohol septal ablation.

Myocardial gene expression in dilated cardiomyopathy treated with beta-blocking agents.

BACKGROUND: Beta-blocker therapy may improve cardiac function in patients with idiopathic dilated cardiomyopathy. We tested the hypothesis that beta-blocker therapy produces favorable functional effects in dilated cardiomyopathy by altering the expression of myocardial genes that regulate contractility and pathologic hypertrophy. METHODS: We randomly assigned 53 patients with idiopathic dilated cardiomyopathy to treatment with a beta-adrenergic-receptor blocking agent (metoprolol or carvedilol) or placebo. The amount of messenger RNA (mRNA) for contractility-regulating genes (those encoding beta1- and beta2-adrenergic receptors, calcium ATPase in the sarcoplasmic reticulum, and alpha- and beta-myosin heavy-chain isoforms) and of genes associated with pathologic hypertrophy (beta-myosin heavy chain and atrial natriuretic peptide) was measured with a quantitative reverse-transcription polymerase chain reaction in total RNA extracted from biopsy specimens of the right ventricular septal endomyocardium. Myocardial levels of beta-adrenergic receptors were also measured. Measurements were conducted at base line and after six months of treatment, and changes in gene expression were compared with changes in the left ventricular ejection fraction as measured by radionuclide ventriculography. RESULTS: Twenty-six of 32 beta-blocker-treated patients (those with complete mRNA measurements) had an improvement in left ventricular ejection fraction of at least 5 ejection-fraction (EF) units (mean [+/-SE] increase, 18.8+/-1.8). As compared with the six beta-blocker-treated patients who did not have a response (mean change, a decrease of 2.5+/-1.8 EF units), those who did have a response had an increase in sarcoplasmic-reticulum calcium ATPase mRNA and alpha-myosin heavy chain mRNA and a decrease in beta-myosin heavy chain mRNA. The change in sarcoplasmic-reticulum calcium ATPase was not present in the patients in the placebo group who had a spontaneous response. There were no differences between those who had a response and those who did not in terms of the change in mRNA or protein expression of beta-adrenergic receptors. CONCLUSIONS: In idiopathic dilated cardiomyopathy, functional improvement related to treatment with beta-blockers is associated with changes in myocardial gene expression.