Arrhythmogenic Left Ventricular Mass as the Initial Presentation of Cardiac Sarcoidosis.

Cardiac tumors of the left ventricle are rare, and cardiac magnetic resonance is the preferred imaging tool for evaluation given superior tissue characterization. We present a case of a patient with arrhythmia and left ventricular mass that was ultimately diagnosed with cardiac sarcoidosis, reminding us that tissue is the issue.

Consensus statement on the processing, interpretation and reporting of temporal artery biopsy for arteritis.

Giant cell arteritis (GCA) is the most common systemic vasculitis in adults in Europe and North America, typically involving the extra-cranial branches of the carotid arteries and the thoracic aorta. Despite advances in noninvasive imaging, temporal artery biopsy (TAB) remains the gold standard for establishing a GCA diagnosis. The processing of TAB depends largely on individual institutional protocol, and the interpretation and reporting practices vary among pathologists. To address this lack of uniformity, the Society for Cardiovascular Pathology formed a committee tasked with establishing consensus guidelines for the processing, interpretation, and reporting of TAB specimens, based on the existing literature. This consensus statement includes a discussion of the differential diagnoses including other forms of arteritis and noninflammatory changes of the temporal artery.

Differences in Aortic Histopathology in Patients Undergoing Valve Reimplantation Surgery for Various Clinical Syndromes.

OBJECTIVES: The study aims to investigate aortic histopathologic differences among patients undergoing aortic valve reimplantation, suggest different mechanisms of aortic root aneurysm pathogenesis, and identify factors associated with long-term success of reimplantation. METHODS: From 2006 to 2017, 568 adults who underwent reimplantation for repair of aortic root aneurysm, including patients with tricuspid aortic valves with no connective tissue disease (TAV/NoCTD, n = 314/568; 55.3%), bicuspid aortic valves (BAVs, n = 86/568; 15.1%), or connective tissue disease (CTD, n = 177/568; 31.2%), were compiled into three comparison groups. Patients with both BAV and CTD (n = 9/568; 1.6%) were omitted to increase study power. Patient records were analyzed retrospectively, focusing on pathology reports, which were available for 98.42% of patients, and were classified based on their descriptions of aortic tissue samples, primarily from the noncoronary sinus. Mean follow-up time available for patients was 2.97 years. RESULTS: Aortitis, medial fibrosis, and smooth muscle loss were more common histopathologic findings in patients with TAV/NoCTD than in patients with BAV and CTD (p < 0.05). Cystic medial degeneration was most often found in patients with CTD, then TAV/NoCTD, and least in BAV (p < 0.01). Increases in mucopolysaccharides were found more often in the BAV group than in the TAV/NoCTD and CTD groups (p < 0.01). There were no differences in the frequency of elastic laminae fragmentation/loss across these three groups. Among all patients, 1.97% (n = 11/559) had an unplanned reintervention on the aortic valve after reimplantation, but no significant demographic or histopathologic differences were identified. CONCLUSION: Despite some common histopathologic features among patients undergoing aortic valve reimplantation, there were enough distinguishing features among aortic tissue samples of TAV/NoCTD, BAV, and CTD patients to suggest that these groups develop root aneurysms by different mechanisms. No histopathologic features were able to predict the need for late reintervention on the aortic valve.

Association Between Atrial Uptake on Cardiac Scintigraphy With Technetium-99m-Pyrophosphate Labeled Bone-Seeking Tracers and Atrial Fibrillation.

BACKGROUND: Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized disease, in which atrial fibrillation (AF) has been shown to be prevalent. Cardiac scintigraphy with technetium-99m-pyrophosphate (99mTc-PyP) labeled bone-seeking tracers is used to noninvasively make the diagnosis of ATTR-CA, based on ventricular myocardial uptake. Assessment of atrial wall uptake (AU) on 99mTc-PyP is currently not used in the clinical setting Methods: We analyzed a cohort of patients referred for 99mTc-PyP scan at a tertiary center to explore AU and associations between any and incident AF, ATTR-CA, and all-cause mortality. RESULTS: Among 580 patients included, 296 patients (51%) had a diagnosis of AF; 164 patients (28%) had scans consistent with ATTR-CA while 117 patients (20%) had AU. Of 117 patients with AU, 107 (91%) had any AF. In contrast, of 463 patients without AU 191(41%) had any AF. Of those with AU, 59/117(50%) patients had a 99mTc-PyP diagnosis of ATTR-CA while 58/117(50%) patients did not have such a diagnosis (P=1.00). Patients with AU had significantly more any AF (hazard ratio [HR], 1.03 [95% CI, 1.02-1.04]; P<0.001), independent of ATTR-CA diagnosis and sex. On multivariable Cox proportional hazards analyses adjusting for age, AU, ATTR-CA diagnosis, sex, smoking, hypertension, diabetes, left ventricular ejection fraction, and coronary artery disease, both age (HR, 1.03 [95% CI, 1.02-1.04]; P<0.0001) and AU (HR, 2.68 [95% CI, 2.11-3.41]; P<0.0001) were independently associated with the development of any AF. Freedom from incident AF at 1-year was significantly lower in patients with AU, both in patients with and without ATTR-CA respectively (HR, 2.27 [95% CI, 1.37-3.78]; P<0.0001 versus HR, 2.21 [95% CI, 1.46-3.34]; P<0.0001). CONCLUSIONS: In a consecutive cohort of patients undergoing 99mTc-PyP scans, 20% had AU, which was statistically associated with any AF, independently of ATTR-CA diagnosis and sex. AU was associated with significantly lower freedom from incident AF at 1-year. Overlooking AU on 99mTc-PyP scans could potentially miss an earlier disease manifestation, or an additional risk factor for any/incident AF.

Invasive Aortic Valve Endocarditis: Clinical and Tissue Findings From a Prospective Investigation.

BACKGROUND: Advanced aortic valve infective endocarditis (IE) with progression and destruction beyond the valve cusps-invasive IE-is incompletely characterized. This study aimed to characterize further the invasive disease extent, location, and stage and correlate macroscopic operative findings with microscopic disease patterns and progression. METHODS: A total of 43 patients with invasive aortic valve IE were prospectively enrolled from August 2017 to July 2018. Of these patients, 23 (53%) had prosthetic valve IE, 2 (5%) had allograft IE, and 18 (42%) had native aortic valve IE. Surgical findings and intraoperative photography were analyzed for invasion location, extent, and stage. Surgical samples were formalin fixed and analyzed histologically. The time course of disease and management were evaluated. RESULTS: Pathogens included Staphylococcus aureus in 17 patients (40%). Invasion predominantly affected the non-left coronary commissure (76%) and was circumferential in 15 patients (35%) (14 had prosthetic valves). Extraaortic cellulitis was present in 29 patients (67%), abscess in 13 (30%), abscess cavity in 29 (67%), and pseudoaneurysm in 8 (19%); 7 (16%) had fistulas. Histopathologic examination revealed acute inflammation, abscess formation, and lysis of connective tissue but not of myocardium or elastic tissue. Median time from onset of symptoms to antibiotics was 5 days, invasion confirmation 15 days, and surgery 37 days. Patients with S aureus had a 21-day shorter time course than patients non-S aureus. New or worsening heart block developed in 8 patients. CONCLUSIONS: Advanced invasive aortic valve IE demonstrates consistent gross patterns and stages correlating with histopathologic findings. Invasion results from a confluence of factors, including pathogen, time, and host immune response, and primarily affects the fibrous skeleton of the heart and expands to low-pressure regions.

Mitral annular calcification and valvular dysfunction: multimodality imaging evaluation, grading, and management.

Mitral annular calcification (MAC) refers to calcium deposition in the fibrous skeleton of the mitral valve. It has many cardiovascular associations, including mitral valve dysfunction, elevated cardiovascular risk, arrhythmias, and endocarditis. Echocardiography conventionally is the first-line imaging modality for anatomic assessment, and evaluation of mitral valve function. Cardiac computed tomography (CT) has demonstrated importance as an imaging modality for the evaluation and planning of related procedures. It also holds promise in quantitative grading of MAC. Currently, there is no universally accepted definition or classification system of MAC severity. We review the multimodality imaging evaluation of MAC and associated valvular dysfunction and propose a novel classification system based on qualitative and quantitative measurements derived from echocardiography and cardiac CT.

A Clinico-Pathologic Approach to the Differential Diagnosis of Pericardial Tumors.

PURPOSE OF REVIEW: Tumors of the pericardium are rare, but a wide variety of congenital, infectious, inflammatory, and neoplastic processes have been reported. Pericardial tumors can be categorized as non-neoplastic or neoplastic. Neoplastic lesions can be further divided into benign or malignant, with malignancies being either primary or secondary (metastatic). Clinical, radiographic, and pathologic features of the most common entities are discussed. RECENT FINDINGS: Metastatic neoplasms involving the heart and pericardium are far more common than primary pericardial neoplasms. Of primary pericardial malignancies, mesothelioma is the most common; notably, cytology of effusion fluid is relatively insensitive to the diagnosis. The prognosis for most malignancies of the pericardium, primary or secondary, is poor. Increasingly, clinically recognized diseases that involve the pericardium include Erdheim-Chester and IgG4-related disease. This article provides a comprehensive review of the most recent literature to develop a structured framework to the differential diagnosis of pericardial tumors.

Case report of isolated cardiac sarcoidosis presenting as hypertrophic obstructive cardiomyopathy-a clinical picture printed on lenticular paper.

BACKGROUND: Cardiac sarcoidosis (CS) is an inflammatory granulomatous process of the myocardium that can be asymptomatic or have several different clinical phenotypes. One of its rarely described presentations consists of hypertrophy of the septal myocardium, similar to hypertrophic cardiomyopathy (HCM). Isolated cardiac sarcoidosis that haemodynamically mimics hypertrophic obstructive cardiomyopathy (HOCM) has been rarely described in the literature. CASE SUMMARY: A 64-year-old Caucasian female previously diagnosed with non-critical aortic stenosis presented with pre-syncope, and echocardiography showed significant obstruction based on left ventricular outflow tract gradients, confirmed by cardiac magnetic resonance (CMR), concerning for a phenocopy of HCM. Septal myectomy was performed and pathology specimen revealed non-caseating granulomata consistent with cardiac sarcoidosis. She was started on oral corticosteroids and initial cardiac fluorodeoxyglucose positron emission tomography (FDG-PET) done after 1 month of treatment was negative. Repeat FDG-PET 15 months later, in the setting of haemodynamic decompensation, demonstrated diffuse FDG uptake in the myocardium without extra-cardiac involvement. DISCUSSION: Our case brings together two entities: isolated cardiac sarcoidosis and its presentation mimicking HOCM, which has been very rarely described in the literature. And it also shows the scenario of surgical pathology diagnosis of sarcoidosis that was not suspected by initial CMR or FDG-PET, despite adequate preparation, only appearing on repeat FDG-PET done 15 months later. Isolated cardiac sarcoidosis should remain a differential diagnosis for any non-ischaemic cardiomyopathy without a clear cause, despite imaging evidence of HCM.

Development of sacral/buttock retiform purpura as an ominous presenting sign of COVID-19 and clinical and histopathologic evolution during severe disease course.

Retiform purpura has been described as a relatively frequent cutaneous finding in patients with coronavirus disease 2019 (COVID-19). The etiology is hypothesized to be related to thrombotic vasculopathy based on lesional biopsy specimen findings, but the pathogenesis of the vasculopathy is not completely understood. Here, we present a case of a retiform purpuric patch on the sacrum/buttocks in a hospitalized patient prior to subsequent diagnosis of COVID-19 and an eventual fatal disease course. Two lesional biopsy specimens at different time points in the disease course revealed thrombotic vasculopathy, despite therapeutic anticoagulation. Detailed histopathologic evaluation using immunohistochemical markers suggest the etiology of the vasculopathy involves both persistent complement activation and platelet aggregation, which possibly promote ongoing thrombus formation. This case highlights that sacral/buttock retiform purpuric patches may be a presenting sign of infection with SARS-CoV-2 virus and may represent an ominous sign supporting a future severe disease course. In addition, biopsy specimen findings at separate time points demonstrate that cutaneous vasculopathy may persist despite adequate systemic anticoagulation, possibly due to the combination of persistent complement and platelet activation. Finally, occlusive thrombi in sacral/buttock retiform purpuric patches may contribute to future ulceration and significant cutaneous morbidity in patients who survive COVID-19.

Clostridium septicum-infected aortic aneurysm or graft is a deadly diagnosis.

BACKGROUND: Clostridium septicum is an anaerobic, motile, spore-forming, toxin-producing gram-positive bacillus that can lead to rapidly progressive gas gangrene due to the release of alpha toxin. Aortic aneurysm secondary to C. septicum infection is a rare condition with 60 cases reported in the literature; however, we have recently treated several patients with the condition in our large tertiary care and aortic center. METHODS: Blood and tissue culture results collected between January 2005 and January 2018 and maintained in the microbiology laboratory database at the Cleveland Clinic were reviewed to identify those with C. septicum reported. Each was reviewed to determine radiographic or histopathologic correlation with aortic disease. RESULTS: Seven cases of C. septicum aortitis were reviewed. Underlying malignant disease was found in four cases and a history of remote malignant disease in one case. The most common location for infection was the infrarenal abdominal aorta. Vascular surgery had previously been performed in three of the cases. Five of the seven patients underwent operative repair. All patients were treated with ß-lactam antibiotics. The two patients who did not undergo an operation died, which is consistent with the 100% mortality described in the literature. Of the five patients who underwent an operation, there was only one documented survivor and one was lost to follow-up. CONCLUSIONS: In the largest reported case series, only a small percentage of patients with C. septicum-infected aortic aneurysms survived >1 year. In the patients described, those who did not receive an operation had 100% mortality. Earlier recognition and prompt operation with appropriate antimicrobial therapy are needed to improve the outcome of patients diagnosed with this rare infection.

Unrecognized Cardiac Amyloidosis at the Time of Mitral Valve Surgery: Incidence and Outcomes.

OBJECTIVE: It is increasingly recognized that cardiac amyloidosis can occur in patients with severe aortic stenosis undergoing both surgical and transcatheter valve replacements. We aimed to investigate whether unrecognized cardiac amyloidosis may also occur in patients with severe mitral valve disease undergoing surgery. METHODS: The pathology department database at our center was retrospectively analyzed over a 10-year period for cases in which the mitral valve or another type of cardiac tissue removed at the time of mitral surgery demonstrated incidental amyloidosis. Clinical and echocardiographic variables were collected from the electronic medical record and the echocardiographic database. RESULTS: Between 2007 and 2016, a total of 7,733 mitral valve surgical specimens were received. Of these, there were 15 cases in which the mitral valve, or another type of cardiac tissue removed at surgery, demonstrated incidentally detected amyloidosis. The most frequent comorbidities were hypertension (87%) and atrial fibrillation (80%); 13 patients (87%) underwent bioprosthetic mitral valve replacement, and 2 patients (13%) underwent mitral valve repair. Sites of amyloid deposition were the mitral valve (80%), left atrial appendage (33%), and subaortic tissue (7%); 14 patients (93%) had wild-type transthyretin amyloid. The mean duration of follow-up was 1,023 days (range: 29-2,811 days). There were no surgical complications in the follow-up period. CONCLUSIONS: Over a 10-year period, incidentally detected cardiac amyloidosis occurred in 0.2% of the mitral valve surgical cases. The outcomes for these patients undergoing mitral valve surgery were excellent, with no complications or deaths attributable to surgery at a mean follow-up of 1,023 days.

Outcomes Among 196 Patients With Noninfectious Proximal Aortitis.

OBJECTIVE: Noninfectious aortitis may occur in the context of a recognized systemic disease or as a topographically limited lesion without systemic features, which is called clinically isolated aortitis (CIA). This study was undertaken to better define and stress the limitations of this diagnostic category in a large population of patients in a single center dedicated to aortic diseases and to suggest recommendations for care. METHODS: Records of patients undergoing thoracic aortic surgery (1996-2012) at the Cleveland Clinic were reviewed to identify 196 patients with histopathologically proven aortitis. Clinical diagnoses (giant cell arteritis [GCA], Takayasu arteritis [TAK], CIA, or Other) were determined at the time of surgery. Clinical features, laboratory findings, and imaging results were recorded throughout the follow-up period. At least 6 months of follow-up data were available for 73 CIA patients. RESULTS: The mean age of the patients at time of surgery was 65.6 years (range 15-88 years); 67% of patients were female, and 90.3% were white. At the time of surgery, 129 patients (65.8%) met criteria for CIA, 42 (21.4%) for GCA, 14 (7.1%) for TAK, and 11 (5.6%) met criteria for other systemic inflammatory diseases. During a mean follow-up period of 56.2 months, 19% of CIA patients developed new symptoms, 45% developed new radiographic vascular lesions, 40% underwent additional vascular surgery, and 12% died (n = 9). Eleven of 73 patients (15%) initially classified as having CIA developed features of a systemic disease, most often GCA. CONCLUSION: The majority of patients (66%) with histopathologically proven aortitis have CIA at the time of surgery. CIA patients infrequently report new symptoms over time, but new vascular lesions requiring surgery commonly occur. Serial follow-up including large vessel imaging is strongly advised for all aortitis patients.

Progress in diagnosing and managing cardiac amyloidosis.

The last decade has seen major advances in diagnosing and treating cardiac amyloidosis. Early diagnosis can often now be made using noninvasive laboratory testing and imaging. New treatments are effective and well tolerated.

Tenosynovial and Cardiac Amyloidosis in Patients Undergoing Carpal Tunnel Release.

BACKGROUND: Patients with cardiac amyloidosis often have carpal tunnel syndrome that precedes cardiac manifestations by several years. However, the prevalence of cardiac involvement at the time of carpal tunnel surgery has not been established. OBJECTIVES: The authors sought to identify the prevalence and type of amyloid deposits in patients undergoing carpal tunnel surgery and evaluate for cardiac involvement. The authors also sought to determine if patients with soft tissue transthyretin (TTR) amyloid had abnormal TTR tetramer kinetic stability. METHODS: This was a prospective, cross-sectional, multidisciplinary study of consecutive men age ≥50 years and women ≥60 years undergoing carpal tunnel release surgery. Biopsy specimens of tenosynovial tissue were obtained and stained with Congo red; those with confirmed amyloid deposits were typed with mass spectrometry and further evaluated for cardiac involvement with biomarkers, electrocardiography, echocardiography with longitudinal strain, and technetium pyrophosphate scintigraphy. Additionally, serum TTR concentration and tetramer kinetic stability were examined. RESULTS: Of 98 patients enrolled (median age 68 years, 51% male), 10 (10.2%) had a positive biopsy for amyloid (7 ATTR, 2 light chain [AL], 1 untyped). Two patients were diagnosed with hereditary ATTR (Leu58His and Ala81Thr), 2 were found to have cardiac involvement (1 AL, 1 ATTR wild-type), and 3 were initiated on therapy. In those patients who had biopsy-diagnosed ATTR, there was no difference in plasma TTR concentration or tetramer kinetic stability. CONCLUSIONS: In a cohort of patients undergoing carpal tunnel release surgery, Congo red staining of tenosynovial tissue detected amyloid deposits in 10.2% of patients. Concomitant cardiac evaluation identified patients with involvement of the myocardium, allowing for implementation of disease-modifying therapy. (Carpal Tunnel Syndrome and Amyloid Cardiomyopathy; NCT02792790).