Partial Heart Transplant in a Neonate With Irreparable Truncal Valve Dysfunction.

Importance: The treatment of neonates with irreparable heart valve dysfunction remains an unsolved problem because there are no heart valve implants that grow. Therefore, neonates with heart valve implants are committed to recurrent implant exchanges until an adult-sized valve can fit. Objective: To deliver the first heart valve implant that grows. Design, Setting, and Participants: Case report from a pediatric referral center, with follow-up for more than 1 year. Participants were a recipient neonate with persistent truncus arteriosus and irreparable truncal valve dysfunction and a donor neonate with hypoxic-ischemic brain injury. Intervention: First-in-human transplant of the part of the heart containing the aortic and pulmonary valves. Main Outcomes and Measures: Transplanted valve growth and hemodynamic function. Results: Echocardiography demonstrated adaptive growth and excellent hemodynamic function of the partial heart transplant valves. Conclusions and Relevance: In this child, partial heart transplant delivered growing heart valve implants with a good outcome at age 1 year. Partial heart transplants may improve the treatment of neonates with irreparable heart valve dysfunction.

Functional mechanical behavior of the murine pulmonary heart valve.

Genetically modified mouse models provide a versatile and efficient platform to extend our understanding of the underlying disease processes and evaluate potential treatments for congenital heart valve diseases. However, applications have been limited to the gene and molecular levels due to the small size of murine heart valves, which prohibits the use of standard mechanical evaluation and in vivo imaging methods. We have developed an integrated imaging/computational mechanics approach to evaluate, for the first time, the functional mechanical behavior of the murine pulmonary heart valve (mPV). We utilized extant mPV high resolution µCT images of 1-year-old healthy C57BL/6J mice, with mPVs loaded to 0, 10, 20 or 30 mmHg then chemically fixed to preserve their shape. Individual mPV leaflets and annular boundaries were segmented and key geometric quantities of interest defined and quantified. The resulting observed inter-valve variations were small and consistent at each TVP level. This allowed us to develop a high fidelity NURBS-based geometric model. From the resultant individual mPV geometries, we developed a mPV shape-evolving geometric model (SEGM) that accurately represented mPV shape changes as a continuous function of transvalvular pressure. The SEGM was then integrated into an isogeometric finite element based inverse model that estimated the individual leaflet and regional mPV mechanical behaviors. We demonstrated that the mPV leaflet mechanical behaviors were highly anisotropic and nonlinear, with substantial leaflet and regional variations. We also observed the presence of strong axial mechanical coupling, suggesting the important role of the underlying collagen fiber architecture in the mPV. When compared to larger mammalian species, the mPV exhibited substantially different mechanical behaviors. Thus, while qualitatively similar, the mPV exhibited important functional differences that will need to accounted for in murine heart valve studies. The results of this novel study will allow detailed murine tissue and organ level investigations of semi-lunar heart valve diseases.

Comparison of Immersed Boundary Simulations of Heart Valve Hemodynamics Against In Vitro 4D Flow MRI Data.

The immersed boundary (IB) method is a mathematical framework for fluid-structure interaction problems (FSI) that was originally developed to simulate flows around heart valves. Direct comparison of FSI simulations around heart valves against experimental data is challenging, however, due to the difficulty of performing robust and effective simulations, the complications of modeling a specific physical experiment, and the need to acquire experimental data that is directly comparable to simulation data. Such comparators are a necessary precursor for further formal validation studies of FSI simulations involving heart valves. In this work, we performed physical experiments of flow through a pulmonary valve in an in vitro pulse duplicator, and measured the corresponding velocity field using 4D flow MRI (4-dimensional flow magnetic resonance imaging). We constructed a computer model of this pulmonary artery setup, including modeling valve geometry and material properties via a technique called design-based elasticity, and simulated flow through it with the IB method. The simulated flow fields showed excellent qualitative agreement with experiments, excellent agreement on integral metrics, and reasonable relative error in the entire flow domain and on slices of interest. These results illustrate how to construct a computational model of a physical experiment for use as a comparator.

Usefulness of cardiac computed tomography in prosthetic heart valve dysfunction.

BACKGROUND: Prosthetic heart valve (PHV) dysfunction is a serious complication. Echocardiography remains the first-line imaging investigation to assess PHV dysfunction. However, the role of Computed Tomography (CT) scanning in this type of case has not been thoroughly studied yet. The objective of our study was to determine if cardiac Computed Tomography (CT) had a potentially complementary role to play alongside echocardiography in diagnosing the mechanism of prosthetic valve dysfunction. METHODS AND RESULTS: This prospective cohort study was conducted on 54 patients with suspected PHV dysfunction. All patients underwent routine diagnosis work-up (transthoracic and transesophageal echocardiography) and additional cardiac CT. Cardiac CT showed findings that were not detected by echocardiography in seven patients (12%) namely aortic pannus (5) and pseudoaneurysm (2). An underlying thrombus was detected by echocardiography and missed by cardiac CT in 15 patients (27%). However, in these thrombotic cases, cardiac CT contributed to the functional evaluation of leaflets. CONCLUSION: This study demonstrates that an integrated approach including transthoracic, transesophageal echocardiography and computed tomography is useful in patients with suspected PHV dysfunction. While computed tomography is more accurate in the diagnosis of pannus formation and periannular complications, echocardiography is superior at detecting thrombus.

Three-Dimensional Printing of Patient-Specific Heart Valves: Separating Facts From Fiction and Myth From Reality.

The development of prosthetic heart valves by Dr. Charles Hufnagel in 1952 was a major clinical innovation; however, it was not an ideal solution. Mechanical prosthetic heart valves are rigid, immunogenic, require anticoagulation, do not grow with the patient, and have a finite life.1 An ideal prosthetic valve should overcome all these limitations. Considering the prevalence of valvular heart disorders, there is considerable interest in the creation of patient-specific heart valves. Following the introduction of three-dimensional (3D) printing in 1986 by Chuck Hill, rapid advances in multimodality 3D imaging and modeling have led to a generation of tangible replicas of patient-specific anatomy. The science of organogenesis has gained importance for a multitude of valid reasons: as an alternate source of organs, for realistic drug testing, as an alternative to animal testing, and for transplants that grow with the patient. What scientists imagined to be seemingly impossible in the past now seems just a step away from becoming a reality. However, due to the disruptive nature of this technology, often there are commercially-motivated claims of originality and overstatement of the scope and applicability of 3D printing. It often is difficult to separate fact from fiction and myth from reality. In this manuscript, the authors have reviewed the historic perspective, status of the basic techniques of organogenesis with specific reference to heart valves, and their potential.

Heart Valve Abnormalities in Systemic Sclerosis Patients: A Multicenter Cohort Study and Review of the Literature.

BACKGROUND: Systemic sclerosis (SSc) is a chronic autoimmune disease that is characterized by vasculopathy and fibrosis of the skin and visceral organs. Heart valve diseases are poorly described and generally not considered typical of SSc. We aimed to describe valvular abnormalities in a multicenter cohort of SSc patients and to investigate their correlation with SSc features. METHODS: We recruited 118 consecutive SSc patients (male/female, 14/104; mean age, 55.2 ± 12.1 years) in 3 rheumatology centers in Sicily, Italy, from January to October 2019. RESULTS: Mitral and tricuspid valve insufficiency was found in 85% and 91% of patients, respectively; regurgitations were generally mild and never severe. Mitral stenosis was rare (2%), and tricuspid stenosis was not observed. Sclerosis and calcification were present in 30% of mitral valves and in only 4% of tricuspid valves. The aortic valve was affected in 25% of cases, and it generally presented as regurgitation or sclerosis, whereas stenosis was rare (3%). Finally, 11% of SSc patients showed regurgitation of the pulmonary valve. No specific associations between SSc features and valve alterations were found. CONCLUSIONS: Valvular diseases are frequently observed in SSc patients, with a predominant pattern of valvular regurgitations. Therefore, echocardiography should be routinely performed during SSc patient follow-up, considering the potential influence of additional cardiac involvement in the prognosis of these patients.

Del Nido versus HTK cardioplegia for myocardial protection during adult complex valve surgery: a retrospective study.

BACKGROUND: Histidine-tryptophan-ketoglutarate (HTK) and del Nido (DN) cardioplegia are intracellular-type and extracellular-type solution respectively, both can provide a long period of myocardial protection with single-dose infusion, but studies comparing the two are rare for adult cardiac surgery. This study aims to evaluate whether DN is suitable for cardioplegia in complex and high-risk valve surgery with long-term cardiac ischemia when compared with HTK. METHODS: The perioperative records of adult patients infused with DN/HTK as a cardioplegic solution who underwent complex valve surgery with an expected myocardial ischaemic duration longer than 90 min between Oct 2018 and Oct 2019 were analysed retrospectively. RESULTS: Of the 160 patients who received DN/HTK and underwent complex valve surgery, we propensity matched 73 pairs. Both groups achieved satisfactory cardiac arrest effects, and no significant difference was found in their cTnI and CK-MB levels within 12 to 72 h postoperatively. The DN group had a higher rate of return to spontaneous rhythm (0.88 v 0.52, P < 0.001), a lower frequency of postoperative severe arrythmias (12% v 26%, P = 0.036), a higher postoperative stroke volume (65 v 59 ml, P = 0.011) and a higher cardiac output (6.0 v 4.9 L/min, P = 0.007) as evaluated by echocardiography, fewer transfusions and shorter ICU stays (both P < 0.05). The two groups had similar inotrope usage and similar incidences of low cardiac output, morbidities and mortality. Subgroup analysis showed that when the aortic clamping time was greater than 120 min, the advantages of DN were weakened. CONCLUSIONS: DN can be safely applied to complex valve surgery, and it has a similar myocardial protection effect as HTK. Further prospective studies are required to verify these retrospective findings. Trial registration retrospectively registered.

Comparison of outcomes of direct-acting oral anticoagulants vs. vitamin K antagonists in patients with bioprosthetic heart valves or valve repair: a systematic review and meta-analysis.

OBJECTIVE: To compare the outcomes between direct-acting oral anticoagulants and vitamin K antagonists, particularly for risk of stroke and bleeding, among patients with atrial fibrillation (AF) and bioprosthetic heart valve replacement or repair. MATERIALS AND METHODS: A systematic search was conducted in the PubMed, Scopus, Cochrane Database of Systematic Reviews and Google scholar databases. Studies that were done in patients with AF who underwent bioprosthetic heart valve replacement or repair and that compared the outcomes between the use of direct-acting oral anticoagulants (DOACs) and vitamin K antagonists were eligible for inclusion. Studies that were preferably randomized controlled trials or adopted a cohort approach or retrospective data-based studies were considered for inclusion. The strength of association was presented in the form of pooled hazards risk (HR). Statistical analysis was done using STATA version 16.0. RESULTS: A total of 8 articles were included in the meta-analysis. There were no significant differences in the risk of "all-cause stroke" [HR 0.72, 95% CI: 0.39, 1.34] and ischemic stroke [HR 0.79, 95% CI: 0.49, 1.29] between the two groups. The risk of "any bleeding" [HR 0.74, 95% CI: 0.64, 0.87], major bleeding [HR 0.60, 95% CI: 0.42, 0.86] and intra-cranial bleeding [HR 0.54, 95% CI: 0.36, 0.81] was much lower in those that received DOAC compared to warfarin. Compared to those receiving warfarin, those on DOACs had substantially reduced risk of any clinical thromboembolic events [HR 0.52, 95% CI: 0.39, 0.70]. No significant differences were noted for all-cause mortality [HR 0.88, 95% CI: 0.74, 1.05], cardiovascular events/myocardial infarction (MI) [HR 0.58, 95% CI: 0.33, 1.04] and and readmission rates [HR 0.85, 95% CI: 0.62, 1.18]. CONCLUSIONS: Findings suggest that the use DOACs in patients with AF with bioprosthetic valve replacement or repair is comparatively better than vitamin K antagonists in reducing the risk of bleeding and thrombo-embolic events. Future studies with a randomized design and larger sample sizes are needed to further substantiate these findings.

Quantification of peak blood flow velocity at the cardiac valve and great thoracic vessels by four-dimensional flow and two-dimensional phase-contrast MRI compared with echocardiography: a systematic review and meta-analysis.

AIM: To objectively examine the agreement and correlation between four-dimensional (4D) flow magnetic resonance imaging (MRI) and traditional two-dimensional (2D) phase-contrast (PC) MRI with the reference standard of Doppler echocardiography for measuring peak blood velocity at the cardiac valve and great arteries, and to assess if 4D flow MRI offers an advantage over the traditional 2D method. MATERIALS AND METHODS: The literature was searched systematically for studies that evaluate the degree of correlation and agreement between 4D flow MRI or 2D PC MRI and Doppler retrieved from PubMed, EMBASE, and the Cochrane Library. A meta-analysis was conducted to determine the peak velocity pooled bias with 95% limits of agreement (LoA) and correlation coefficient (r) for 4D flow MRI and 2D PC MRI compared with Doppler. RESULTS: Ten studies that compared 4D flow MRI with Doppler and 12 studies that compared 2D PC MRI with Doppler were included. 4D flow MRI showed an underestimation with bias and 95% LoA of -0.09 (-0.41, 0.24) m/s (p=0.079) while 2D PC MRI showed a poorer agreement with a bias and 95% LoA of -0.25 (-0.53, 0.03), p=0.596. 4D flow MRI and 2D PC MRI showed a strong correlation with R=0.80 (95% CI 0.75, 0.84; p<0.001) and R=0.83 (95% CI 0.79, 0.87; p<0.001), respectively. CONCLUSION: In this meta-analysis, 4D flow MRI provides improved assessment of peak velocity when compared with traditional 2D PC MRI. 4D flow MRI can be considered an important complement or substitute to Doppler echocardiography for peak velocity assessment.

Prosthetic heart valve thrombosis in pregnancy: a case series on acute management.

Rheumatic heart disease is one of the leading causes of valve dysfunction, resulting in prosthetic valve implantation. Changes in physiology and the haemodynamics of pregnancy increase the susceptibility of thrombosis to the prosthetic valve in the pregnant woman. Valve redo surgery carries a considerable risk of maternal and perinatal morbidity and mortality. Women of reproductive age should be well counselled regarding compliance with anticoagulation, contraception and pre-pregnancy planning.

Validation of Claims Data for the Identification of Intraoperative Transesophageal Echocardiography During Cardiac Surgery.

OBJECTIVE: The goal of this study was to assess the validity of Current Procedural Terminology (CPT) claims data for the identification of intraoperative transesophageal echocardiography (TEE) during cardiac surgery. DESIGN: This study was a retrospective, cohort analysis. SETTING: This study used data from electronic medical records (EMRs), in combination with CPT billing claims data, from two hospitals within the Penn Medicine Health System-Penn Presbyterian Medical Center and the Hospital of the University of Pennsylvania. PARTICIPANTS: The cohort consisted of adult patients, aged ≥18 years, undergoing open cardiac valve surgery (repair or replacement), coronary artery bypass graft surgery, or aortic surgery between April 1 and October 31, 2019. INTERVENTIONS: Agreement between TEE identified using CPT billing code(s) (93312-8 with or without 93320-1 or 93325) and TEE identified by manual EMR review. MEASUREMENTS AND MAIN RESULTS: As identified by a reference standard (ie, EMR review) of the 873 cases that met inclusion criteria, 867 (99.31%) cases were performed with TEE and six cases were performed without TEE (<1%). Of the 867 cases performed with TEE, CPT code(s) correctly identified 866 cases, as indicated by having at least one of the CPT codes (93312-8 with or without 93320-1 or 93325). These CPT codes identified intraoperative TEE with a 99.88% sensitivity, 100.00% specificity, 100.00% positive predictive value, and 85.71% negative predictive value. When billing claims for TEE were restricted to the CPT code 93312 alone, the results were identical. CONCLUSIONS: Billing claims using CPT code(s) identified true intraoperative TEE with a high sensitivity, specificity, excellent positive predictive value, and moderate negative predictive value. These results demonstrated that claims data are a valuable data source from which to study the effect of TEE in cardiac surgical patients.

Systemic thrombolysis in a patient with massive acute valvular thrombosis.

Prosthetic valve thrombosis (PVT) is considered an exceptionally rare condition, often associated with pro-thrombotic factors or suboptimal anticoagulant therapy. Guidelines recommend emergent surgery for patients with left heart valve prosthetic thrombosis who present in cardiogenic shock, and systemic thrombolysis is reserved in scenarios where surgery is not immediately available. However, several factors may affect surgical prognosis and are overlooked by current recommendations. We describe the case of a 34-year-old female who presented in the emergency department with cardiogenic shock and acute pulmonary edema due to acute valve thrombosis.

A Review of Ex Vivo X-ray Microfocus Computed Tomography-Based Characterization of the Cardiovascular System.

Cardiovascular malformations and diseases are common but complex and often not yet fully understood. To better understand the effects of structural and microstructural changes of the heart and the vasculature on their proper functioning, a detailed characterization of the microstructure is crucial. In vivo imaging approaches are noninvasive and allow visualizing the heart and the vasculature in 3D. However, their spatial image resolution is often too limited for microstructural analyses, and hence, ex vivo imaging is preferred for this purpose. Ex vivo X-ray microfocus computed tomography (microCT) is a rapidly emerging high-resolution 3D structural imaging technique often used for the assessment of calcified tissues. Contrast-enhanced microCT (CE-CT) or phase-contrast microCT (PC-CT) improve this technique by additionally allowing the distinction of different low X-ray-absorbing soft tissues. In this review, we present the strengths of ex vivo microCT, CE-CT and PC-CT for quantitative 3D imaging of the structure and/or microstructure of the heart, the vasculature and their substructures in healthy and diseased state. We also discuss their current limitations, mainly with regard to the contrasting methods and the tissue preparation.

Features of carcinoid heart disease identified by cardiac computed tomography.

BACKGROUND: Carcinoid heart disease (HD) is a rare form of valvular heart disease, the features of which have not been fully described by cardiac computed tomography (CT). METHODS: All patients with carcinoid HD that underwent cardiac CT, either preoperatively or for assessment of coronary arteries, between Apr-2006 and Dec-2019 at the Royal Free Hospital, UK, were reviewed. RESULTS: Of 32 patients with carcinoid HD, 29 (91%) had heart valve involvement. Abnormalities of the tricuspid and pulmonary valves were present in all patients, affecting all three leaflets in 23/26 (89%) unoperated patients for both valves. The aortic valve was affected in 4/29 (14%) patients and the mitral valve in 5/29 (17%). Left heart valves were affected in 6/29 (21%) patients. One patient (1/29; 3%) had all four valves affected. Severe changes with significant valvular regurgitation were seen in ≥75% of patients with tricuspid, pulmonary, and aortic valve abnormalities. Three patients had carcinoid myocardial metastases (3/32; 9%) and one patient had constrictive pericarditis (1/32; 3%). Ten patients had surgery of whom four (40%) had invasive coronary angiography preoperatively. Ten patients had a patent foramen ovale. Cardiac CT allowed an accurate assessment of damage to different leaflets/cusps, particularly of the pulmonary valve, where visualization with echocardiography was often (3/8; 38%) incomplete. CONCLUSION: Cardiac CT is a powerful tool for assessment of cardiac valve abnormalities, coronary arteries and the spatial relationship of coronary arteries with myocardial metastasis in patients with carcinoid HD, and should form part of multimodal imaging of this complex pathology.

Adipocytes and membranous fat necrosis within native cardiac valves: Clinicopathologic characterization of histologic constituents.

The constituents of normal cardiac valves as well as those involved by active and/or chronic processes have been detailed previously, however minor attention has been provided toward mature adipocytes within valves and correlation with other histologic, clinical, and echocardiographic data. The literature also contains a paucity of investigations examining the presence of a particular form of degenerative change of mature adipocytes termed membranous fat necrosis. We retrospectively reviewed the histologic findings of 1042 native cardiac valves which included identification of the presence of adipocytes and membranous fat necrosis within them, as well as correlation with other histopathologic features, and clinical and echocardiographic findings. Notable observations included that membranous fat necrosis was only present in valves with adipocytes, adipocytes and membranous fat necrosis were seen in older patients, and that Caucasians made up a greater proportion of patients while African Americans made up a lower proportion of patients when valves were found with adipocytes and membranous fat necrosis. Aortic valves contained adipocytes and membranous fat necrosis at a greater rate than compared to other valves, and aortic valves with adipocytes and membranous fat necrosis were more commonly tricuspid (as opposed to bicuspid) and with larger aortic valve area and lower peak and mean gradients. Further investigation is required to determine potential physiologic and/or pathologic consequence of their presence.