Severe Hypertriglyceridemia in a Patient With Metabolic Syndrome and Psoriasis on Risankizumab-Rzaa.

We report a case of severe hypertriglyceridemia (HTG) complicated by hyperviscosity syndrome as a possible adverse reaction to risankizumab-rzaa in a 49-year-old male with a history of longstanding uncontrolled type 2 diabetes, obesity, and coronary artery disease with prior ST-elevation myocardial infarction. On admission, the patient presented with xanthomatous plaques, chest and epigastric discomfort, and headache. Subsequent blood testing revealed severely elevated triglyceride (TG) levels at 7670 mg/dL (86.59 mmol/L) [reference range: <150 mg/dL; 1.69 mmol/L] and total cholesterol at 934 mg/dL (24.14 mmol/L) [reference range: <200 mg/dL; 5.17 mmol/L]. Triglyceride levels decreased and symptoms resolved with dietary restrictions and plasmapheresis. At follow-up, his TG remained elevated but improved, and he was advised to continue lipid-lowering medications as well as cessation of risankizumab. While the patient presented with high risk factors, we posit that the subacute presentation of severe HTG is a possible result of his recent course of risankizumab-rzaa therapy for management of psoriasis. This is noteworthy as pharmaceutical surveys and clinical trials do not list severe HTG as an adverse effect. Postmarketing surveillance studies are essential to confirm this potential association and monitor drug safety. In summary, this case highlights a possible link between risankizumab and severe HTG, emphasizing the importance of ongoing pharmacovigilance to identify and manage unexpected adverse effects associated with new medications.

Imaging of Cardiac Sarcoidosis: An Update and Future Aspects.

Cardiac sarcoidosis (CS), an increasingly recognized disease of unknown etiology, is associated with significant morbidity and mortality. Given the limited diagnostic yield of traditional endomyocardial biopsy (EMB), there is increasing reliance on multimodality cardiovascular imaging in the diagnosis and management of CS, with EMB being largely supplanted by the use of 18F-fluorodeoxyglucose (FDG-PET) and cardiac magnetic resonance imaging (CMR). This article aims to provide a comprehensive review of imaging modalities currently utilized in the screening, diagnosis, and monitoring of CS, while highlighting the latest developments in each area.

The Mechanism and Natural History of Mitral Regurgitation in Cardiac Sarcoidosis.

Cardiac sarcoidosis (CS) is an infl/ammatory cardiomyopathy that can present with mitral regurgitation (MR), but few studies describe the mechanisms and natural history of MR in CS. We queried an institutional registry of 512 patients with CS for moderate or greater MR at diagnosis. Baseline demographic and echocardiography (TTE) data were collected. MR was classified by Carpentier type. Positron emission tomography was analyzed for 2-deoxy-2-[fluorine-18] fluoro-d-glucose (FDG) avidity of anterolateral and posteromedial papillary muscles. Follow-up TTE and positron emission tomography imaging of patients treated with immunosuppression was analyzed for MR severity and FDG avidity changes. Fifty-four patients were identified. Mean left ventricular ejection fraction was 39.3%, effective regurgitant orifice 0.34 cm2, and MR regurgitant volume 46.3 ml. Carpentier type I was the most common MR mechanism (46.3%). Forty-one patients had follow-up TTE (median follow-up 1.7 years, interquartile range 2.6 years). Evaluating preprocedural follow-up TTE only, MR severity was significantly reduced, with 37% of patients showing reduction by at least 1 severity grade (p = 0.04). With postprocedural TTE included, 61% of patients showed alleviation of MR severity with mean decrease in grade - 0.98 (p <0.001). Sixty-eight percent of patients had anterolateral/posteromedial FDG avidity. Papillary muscle FDG avidity resolved in 80% of patients (n = 20, median follow-up 1.6 years, interquartile range 2.5 years). In conclusion, Carpentier type I functional MR is the most common MR mechanism in CS. MR severity and papillary muscle FDG avidity decrease after treatment, and MR resolution is further strengthened by procedural intervention in a minority of patients, suggesting an overall favorable natural history of MR in CS.

18F-FDG/13N-ammonia cardiac PET findings in ATTR cardiac amyloidosis.

18F-flurodeoxyglycose (FDG)/13N-ammonia positron emission tomography/computed tomography (PET/CT) is frequently utilized to evaluate cardiac sarcoidosis (CS) but findings can reflect other forms of myocardial inflammation or altered myocardial metabolic activity. Herein, we present five cases where cardiac PET findings suggested CS, but right ventricular endomyocardial biopsy samples revealed ATTR-type cardiac amyloidosis.

Cardiac resynchronization therapy response in cardiac sarcoidosis.

INTRODUCTION: Cardiac sarcoidosis (CS) is a nonischemic cardiomyopathy (NICM) characterized by infiltration of noncaseating granulomas involving the heart with highly variable clinical manifestations that can include conduction abnormalities and systolic heart failure. Cardiac resynchronization therapy (CRT) has shown significant promise in NICM, though little is known about its efficacy in patients with CS. OBJECTIVE: To determine if CRT improved cardiac remodeling in patients with CS. METHODS: We retrospectively reviewed all patients with a clinical or histological diagnosis of CS who underwent CRT implantation at the Mayo Clinic enterprise from 2000 to 2021. Baseline characteristics, imaging parameters, heart failure hospitalizations and need for advanced therapies, and major adverse cardiac events (MACE) were assessed. RESULTS: Our cohort was comprised of 55 patients with 61.8% male and a mean age of 58.7 ± 10.9 years. Eighteen (32.7%) patients had definite CS, 21 (38.2%) had probable CS, while 16 (29.1%) had presumed CS, and 26 (47.3%) with extracardiac sarcoidosis. The majority underwent CRT-D implantation (n = 52, 94.5%) and 3 (5.5%) underwent CRT-P implantation with 67.3% of implanted devices being upgrades from prior pacemakers or implantable cardioverter defibrillators. At 6 months postimplantation there was no significant improvement in ejection fraction (34.8 ± 10.9% vs. 37.7 ± 14.2%, p = .331) or left ventricular end-diastolic diameter (58.5 ± 10.2 vs. 57.5 ± 8.1 mm, p = .236), though mild improvement in left ventricular end systolic diameter (49.1 ± 9.9 vs. 45.7± 9.9 mm, p < .0001). Within the first 6 months postimplantation, 5 (9.1%) patients sustained a heart failure hospitalization. At a mean follow-up of 4.1± 3.7 years, 14 (25.5%) patients experienced a heart failure hospitalization, 11 (20.0%) underwent cardiac transplantation, 1 (1.8%) underwent left ventricular assist device implantation and 7 (12.7%) patients died. CONCLUSIONS: Our findings suggest variable response to CRT in patients with CS with no overall improvement in ventricular function within 6 months and a substantial proportion of patients progressing to advanced heart failure therapies.

Utilization of cardiac imaging in sarcoidosis.

INTRODUCTION: Cardiac sarcoidosis (CS) is the cardiac, and occasionally the only manifestation, of a systemic disease of unknown etiology inherently challenging to definitively diagnose due to the lack of a reliable gold standard, the current being endomyocardial biopsy, the yield of which is low owing to the patchy nature of involvement. Societal guidelines employ specific criteria to make a probabilistic diagnosis, integrating clinical assessment with conventional and advanced cardiac imaging. AREAS COVERED: This review begins with an introduction to CS, followed by a discussion of diagnostic guidelines commonly used, then delves into an in-depth review of the imaging modalities currently available to assess for CS. Particular attention is made to discussing findings, strengths, limitations, and future directions for each modality. EXPERT OPINION: The burden of CS may be significantly larger than previously thought. With the low yield of endomyocardial biopsy, advanced cardiac imaging is increasingly employed to determine CS likelihood. Cardiac magnetic resonance is adept at detecting myocardial scar and able to differentiate between CS and other cardiomyopathies. F-18 Fluorodeoxyglucose positron emission tomography is superior at detecting active disease (myocardial inflammation) which may be amenable to immunosuppressive treatment, as well as detecting extracardiac involvement and identifying potential biopsy sites.

Rituximab for the Treatment of Refractory Cardiac Sarcoidosis: A Single-Center Experience.

BACKGROUND: We sought to examine the effect of anti-B-cell therapy (rituximab) on cardiac inflammation and function in corticosteroid-refractory cardiac sarcoidosis. Cardiac sarcoidosis (CS) is a rare cause of cardiomyopathy characterized by granulomatous inflammation involving the myocardium. Although typically responsive to corticosteroid treatment, there is a critical need for identifying effective steroid-sparing agents for disease control. Despite increasing evidence on the role of B cells in the pathogenesis of sarcoidosis, there is limited data on the efficacy of anti-B-cell therapy, specifically rituximab, for controlling CS. METHODS AND RESULTS: We reviewed the clinical experience at a tertiary care referral center of all patients with CS who received rituximab after failing to improve with initial immunosuppression therapy, which included corticosteroids. Fluorodeoxyglucose positron emission tomography (FDG PET/CT) images before and after rituximab treatment were evaluated. All images were interpreted by 2 experienced nuclear medicine trained physicians. We identified 7 patients (5 men, 2 women; mean age at diagnosis, 49.0 ± 7.9 years) with active CS who were treated with rituximab. The median length of follow-up was 5.1 years. All individuals, but 1, had received prior steroid-sparing agents in addition to corticosteroids. Rituximab was administered either as 1000 mg intravenously ×1 or ×2 doses, separated by 2 weeks. Repeat dosing, if appropriate, was considered after 6 months. All tolerated the infusions well. Inflammation as assessed by maximum standardized uptake value on cardiac FDG PET/CT uptake significantly decreased in 6 of 7 patients (median 6.0-4.5, Wilcoxon signed rank z -1.8593, W 3), whereas the left ventricular ejection fraction improved or stabilized in 4 patients but decreased in 3. The mean left ventricular ejection fraction was 40.1% and 43.3% before and after treatment, respectively (P = .28). Three patients reported improved physical capacity, and 5 patients showed improved arrhythmic burden on Holter monitoring or implantable cardioverter-defibrillator interrogation. One patient subsequently developed a fungal catheter-associated infection and sepsis requiring discontinuation. CONCLUSIONS: Rituximab was well-tolerated and seemed to decrease inflammation, as assessed by cardiac FDG PET/CT in all but 1 patient with active CS. These data suggest that rituximab may be a promising therapeutic option for CS, which deserves merits further study.

Electrogram-guided endomyocardial biopsy yield in patients with suspected cardiac sarcoidosis and relation to outcomes.

OBJECTIVE: Endomyocardial biopsy (EMB) is a useful diagnostic tool though the yield may be limited in many myocardial diseases. Data on the diagnostic yield and prognostic significance of EMB guided by abnormal electrograms (EGM-Bx) in suspected cardiac sarcoidosis (CS) are scarce. METHODS: Seventy-nine patients (mean age: 56 ± 12 years; 61% men) with suspected CS based on clinical and imaging features underwent right or left ventricular EGM-Bx guided by electroanatomic mapping. Tissue samples were obtained from sites with abnormal EGMs and/or abnormal cardiac imaging. The diagnostic yield of EGM-Bx was evaluated in reference to histopathologic analysis. Left ventricular assist device (LVAD) and transplantation-free survival were compared between patients with positive and negative EGM-Bx for CS. RESULTS: A total of 254 samples were obtained from abnormal EGM sites, and 126 samples from normal EGM sites guided by pre-procedure imaging findings. Abnormal histopathology was noted in 65 (26%) and 10 (8%) samples from abnormal and normal EGM sites, respectively. Histopathology confirmed CS in 16 (20%) patients, while an alternative tissue diagnosis emerged in 10 (13%) patients. Abnormal EGMs at the biopsy site had sensitivity 89% and specificity 33% for a histopathologic diagnosis of CS. LVAD and transplantation-free survival were not significantly associated with the EGM-Bx result (log-rank p = .91). CONCLUSION: In patients with suspected CS, abnormal EGM-Bx has high sensitivity and low specificity for establishing a definite CS diagnosis. Consideration of substrate abnormalities apparent on preprocedural imaging as an adjunct for selection of biopsy sites may further improve EGM-Bx yield.

Identification of a novel presumed cardiac sarcoidosis category for patients at high risk of disease.

BACKGROUND: Histologic evidence is required for a definitive diagnosis of cardiac sarcoidosis (CS) by published guidelines; however, the sporadic nature of the disease may produce false negative biopsy results, causing CS to be underdiagnosed. We sought to establish a clinical category of CS absent histologic findings. METHODS: Patients evaluated for CS were stratified into 3 groups: probable CS and definite CS based on Heart Rhythm Society (HRS) criteria and presumed CS, ie, patients without any histologic evidence of sarcoidosis, but with unexplained high-grade atrioventricular block or ventricular arrhythmia and findings suggestive of CS on either cardiac magnetic resonance imaging or positron emission tomography. The primary end point was hospitalization-free and overall survival at 10 years. RESULTS: A total of 383 patients were included in the study: 59, definite CS; 223, probable CS; and 101, presumed CS (62, isolated CS and 39, systemic CS). Compared with patients meeting HRS criteria for CS, patients with presumed CS had lower odds of New York Heart Association class III or IV symptoms (odds ratio [OR], 0.44 [95% CI, 0.23-0.83]; P = .01) but greater odds of previous ventricular tachycardia (OR, 2.4 [95% CI, 1.4-4.0]; P = .001) or history of resuscitated sudden cardiac arrest (OR, 2.9 [95% CI, 1.0-8.6]; P = .05). Hospitalization-free and overall survival were similar among groups (P = .51 and P = .71, respectively). CONCLUSIONS: Clinical categorization of patients with presumed CS identified a high-risk cohort comparable to patients with histologic evidence of disease, although caution should be exercised in reaching this diagnosis without paying due diligence to the differential diagnosis.

State of the Art: Imaging for Myocardial Viability: A Scientific Statement From the American Heart Association.

A substantial proportion of patients with acute myocardial infarction develop clinical heart failure, which remains a common and major healthcare burden. It has been shown that in patients with chronic coronary artery disease, ischemic episodes lead to a global pattern of cardiomyocyte remodeling and dedifferentiation, hallmarked by myolysis, glycogen accumulation, and alteration of structural proteins. These changes, in conjunction with an impaired global coronary reserve, may eventually become irreversible and result in ischemic cardiomyopathy. Moreover, noninvasive imaging of myocardial scar and hibernation can inform the risk of sudden cardiac death. Therefore, it would be intuitive that imaging of myocardial viability is an essential tool for the proper use of invasive treatment strategies and patient prognostication. However, this notion has been challenged by large-scale clinical trials demonstrating that, in the modern era of improved guideline-directed medical therapies, imaging of myocardial viability failed to deliver effective guidance of coronary bypass surgery to a reduction of adverse cardiac outcomes. In addition, current available imaging technologies in this regard are numerous, and they target diverse surrogates of structural or tissue substrates of myocardial viability. In this document, we examine these issues in the current clinical context, collect current evidence of imaging technology by modality, and inform future directions.

Imaging and Quantification of Cardiac Sarcoidosis.

Cardiac sarcoidosis (CS) refers to the increasingly recognized cardiac involvement of an incompletely understood systemic disease entity-sarcoidosis. Endomyocardial biopsy can provide definitive diagnosis but is limited by its invasiveness and poor sensitivity. In the absence of a reliable gold standard, a combination of clinical, electrocardiographic, imaging, and histologic criteria are relied upon to provide probabilistic diagnosis. Within the last few years, societal documents have included advanced cardiovascular imaging modalities, 18F-FDG-PET/CT and cardiac magnetic resonance in their diagnostic algorithms. The current article provides a review of the imaging modalities used for screening and detection of CS, highlighting the principal findings of each with a specific focus on quantification, whenever applicable, and concluding with a proposed approach to the imaging of patients with suspected CS.

Imaging cardiac sarcoidosis and infiltrative diseases: diagnosis and therapeutic response.

Infiltrative heart disease is an encompassing term referring to different pathological entities that involve infiltration of the myocardium by either abnormal substances or inflammatory cells. These infiltrates can impair cellular function, induce necrosis and fibrosis, or otherwise disrupt myocardial architecture resulting in a wide spectrum of structural and functional impairment. Depending on the specific disorder and stage of disease, patients may present with minimal cardiac abnormalities, or may have findings of advanced restrictive and/or dilated cardiomyopathy. Furthermore, patients may often be misdiagnosed with more common conditions such as hypertensive, hypertrophic or ischemic cardiomyopathies. Correlation of cardiac findings with clinical, serologic or pathologic data is critical in many of these conditions. While cardiac involvement may be detected by echocardiography, other imaging modalities such as cardiac magnetic resonance, single-photon emission computed tomography, or positron emission tomography provide additional critical diagnostic, prognostic and therapeutic information. Advanced imaging modalities also provide quantitative data that can further risk stratify patients, monitor disease progression, and guide management. In this review we provide an overview of infiltrative heart disease from an imaging perspective, with a particular focus on cardiac sarcoidosis and cardiac amyloidosis.

Neoplasia and the Heart: Pathological Review of Effects With Clinical and Radiological Correlation.

The intersection of oncological and cardiovascular diseases is an increasingly recognized phenomenon. This recognition has led to the emergence of cardio-oncology as a true subspecialty. This field is not simply limited to primary cardiac tumors or complications of chemotherapeutic medications. Rather, it also encompasses metastatic cardiovascular complications and secondary cardiovascular effects of the underlying neoplasia. This review will broadly cover primary and metastatic cardiac neoplasms, as well as secondary cardiovascular effects of extracardiac neoplasia (e.g., amyloidosis, carcinoid valvulopathy, and chemotherapeutic cardiotoxicities).

Multimodality imaging of foreign bodies in and around the heart.

Foreign objects are occasionally seen on computed tomography and could pose a diagnostic challenge to the radiologist and clinicians. It is important to recognize, characterize and localize these objects and determine their clinical significance. Most foreign objects in and around the heart are the result of direct penetrating injury or represent venous embolization to the heart. Foreign objects may cause symptoms and require prompt medical attention or maybe asymptomatic. Clinicians should be familiar with foreign objects that are encountered and understand treatment options. This paper looks at some of foreign objects that can be found and correlates with pathology where possible.

Radionuclide Imaging in Congestive Heart Failure: Assessment of Viability, Sarcoidosis, and Amyloidosis.

Radionuclide imaging provides both established and emerging diagnostic and prognostic tools to assist clinicians in the management of patients with ischemic cardiomyopathy, cardiac sarcoidosis, and cardiac amyloidosis. This review highlights the underlying pathophysiology of each entity and associated diagnostic and clinical challenges, and describes the available radionuclide imaging techniques. Specific protocols, advantages and disadvantages, comparison with other noninvasive imaging modalities, and discussion of the evolving role of hybrid imaging are also included.

Benign lipomatous masses of the heart: a comprehensive series of 47 cases with cytogenetic evaluation.

Benign lipomatous lesions of the heart encompass an apparently etiologically diverse group of entities including neoplastic, congenital, and reparative phenomena. Among these, lipomas and lipomatous hypertrophy of the atrial septum (LHAS) represent 2 commonly encountered mass lesions. To date, no study has systematically and comparatively evaluated the morphologic and genetic characteristics of these lesions. Tissue registry archives of Mayo Clinic were queried for cases of cardiac lipoma and LHAS (1994-2011). Clinical, imaging, and pathologic findings were reviewed. Representative cases in each cohort were evaluated by fluorescence in situ hybridization (FISH) for HMGA1 and HMGA2 loci rearrangement and for MDM2/CPM locus amplification. Five cases of cardiac lipoma were identified (mean age, 67 years; range, 48-101; 3 men): 4 right atrial and 1 left ventricular. Forty-two cases of LHAS were identified (mean age, 75.6 years; range 45-95; 20 men), 39 of which were autopsy derived. The median size was 3.4 cm for lipomas and 2.8 cm for LHAS (n = 14). A single case each of cardiac lipoma and LHAS were found to harbor HMGA2 rearrangement, whereas no case showed cytogenetic abnormality of HMGA1 or CPM. This represents the largest series of histopathologically confirmed cardiac lipomas from a single institution. In addition, it is the first to evaluate cardiac lipomas and LHAS for genetic alterations associated with extracardiac lipomatous lesions. The genetic and morphologic similarities found provide evidence in support of the neoplastic classification of cardiac lipomas. A single case of LHAS contained an HMGA2 rearrangement, challenging the currently accepted hypothesis of pathogenesis for this lesion.