Klarich, Kyle W.

Abstract Background Cardiac papillary fibroelastoma (PFE) is the most common benign primary cardiac tumor. Despite their benign pathology, PFEs pose a significant embolic risk, which can lead to severe neurological sequelae. However, subclinical or silent emboli often go undetected, presenting a diagnostic challenge. This study aims to assess the prevalence of silent emboli in patients with pathology-proven PFEs using brain magnetic resonance imaging (MRI). Methods We conducted a retrospective review of 385 cases of pathology-confirmed PFEs. Inclusion criteria was those with brain MRI performed within 5 years of surgical resection of the PFE and no clinical neurological events. Patients with a history of symptomatic cerebral infarction (stroke or TIA) were excluded. Patient demographics and PFE imaging features were analyzed by two cardiologists experienced in cardiac tumors. Clinical neurological data, and MRI findings were analyzed by two neurologists with expertise in cerebrovascular disease. Results Out of 385 patients, 132 underwent brain MRI. In the entire cohort, 105/385 patients (27%) experienced clinically overt embolic events. After excluding patients with symptomatic cerebral infarctions and MRI scans older than 5 years, 27 patients (mean age: 71±9.6, gender: 66% female) met the inclusion criteria. Of these, 8 patients (30%) showed signs of silent infarctions on MRI, with 4 (15%) displaying findings consistent with cerebral infarction highly suggestive for embolic source. Conclusion This study underscores the substantial risk of silent cerebral embolic events in patients with PFE. The limited availability of MRI data, largely attributable to the absence of standardized neuroimaging protocols, indicates that the true prevalence of silent embolization in this population is likely underestimated. Given the propensity of PFE to generate clinically silent emboli, systematic cerebral MRI should be strongly considered as part of the diagnostic assessment of patients with cardiac masses, irrespective of neurological symptoms. Early identification of subclinical cerebrovascular lesions may facilitate timely therapeutic decision-making and secondary prevention strategies, thereby reducing the risk of future symptomatic and potentially disabling ischemic strokes.

Background: Papillary fibroelastomas (PFE) arising between the left upper pulmonary vein and left atrial appendage, commonly referred to as the coumadin ridge or Q-tip, are extremely rare and best detected by transesophageal echocardiography (TEE). Although PFEs are benign, they have been associated with a range of serious embolic events. Objective: To analyze the characteristics, clinical findings, and diagnostic techniques of PFEs originating from the coumadin ridge. Methods: We describe 13 cases of pathology proven papillary fibroelastomas uniquely attached to the Q-tip. Patient data, including demographics, mass characteristics and diagnostic imaging were collected and analyzed. Results: Thirteen patients with pathology-proven PFEs attached to the coumadin ridge were included in the study. The median age of the cohort is 73 (IQR 67-77), and 54% of the patients were male. Tumor sizes ranged from 2mm to 20mm with a median of 5mm (IQR 3.5-8.5). Twelve (92%) of the PFEs were initially visualized on TEE, and one case was diagnosed postoperatively by pathologists after the excision of the left atrial appendage. The majority of cases were incidental diagnoses, with 46% of cases incidentally discovered intraoperatively by routine TEE, and 30% visualized on TEE done for diverse reasons including valvular assessment, exclusion of infective endocarditis, and coronary artery disease (CAD) assessment. One case was incidentally detected on CMR performed as part of a metastatic tumor workup. Four (30%) patients presented with symptoms of stroke/TIA, of which 2 had a previous history of stroke. One patient had symptoms of both TIA and angina pectoris. Cardiovascular disease risk factors were prevalent: 69% had hyperlipidemia, 46% had atrial fibrillation (Afib), 31% had CAD, 54% had hypertension, and 46% were former smokers. Conclusions: Masses on the Q-tip are rare but significant intracardiac sources of embolism. Accurate identification and categorization of these masses are challenging, yet critical, to guide appropriate surgical intervention and improve patient outcomes. Further studies are needed to establish standardized diagnostic and treatment protocols for this unique presentation of PFEs.

Abstract Background Non-bacterial thrombotic endocarditis (NBTE) is a non-infectious condition characterized by thrombotic and/or inflammatory depositions involving the cardiac valves. It is a challenging diagnosis of exclusion. Purpose This study aimed to better characterize patients with pathologically proven NBTE and assess its clinical, echocardiographic characteristics and prognostic implications. Methods We retrospectively identified patients with pathology-proven NBTE at a single center. Patients with positive preoperative blood cultures, a history of active or treated infective endocarditis, or identification of valvular organisms by special stains were excluded from the study. Patients with pathology reports of valve perforation or chordal rupture were also excluded because of the high likelihood of an infectious etiology for these lesions. Results A total of 53 patients with NBTE (median age 57 years; 61% females) were identified. In this cohort, 22% had a history of malignancy, 30% had connective tissue disease, 32% had coronary artery disease, and 11% prior history of NBTE. Neurological events accounted for 18 (34%) of the presenting symptoms (TIA n=17, CVA n=9), while new valvular dysfunction in 7 (13%) and fever in 8 (15%) of patients. Five patients (9%) had NBTE involving more than one valve. NBTE involved the mitral valve in 64%, aortic valve in 38% prosthetic/mechanical valve in 11%, and tricuspid valve in 5%. NBTE was identified at the time of autopsy in 34% of patients. NBTE recurred in 3 patients during follow-up. Excluding patients diagnosed at the time of autopsy, 9% of patients died within 1 year of NBTE diagnosis. Conclusion NBTE was diagnosed pathologically in the presence of hyper-inflammatory states due to critical illness or immunological diseases. It was predominantly on the left side of the heart and was associated with embolic phenomena, either clinically or on imaging. Patients diagnosed with antemortem with NBTE have a high mortality in the first year (9%).

Background Previous studies have shown that women with hypertrophic obstructive cardiomyopathy (HCM) have worse long‐term outcomes irrespective of intervention. However, the outcomes of patients undergoing alcohol septal ablation (ASA) based on sex have not been described. Hence, this study aimed to evaluate pressure changes and long‐term mortality in patients with HCM undergoing ASA based on sex. Methods and Results This is a single‐center retrospective study evaluating hemodynamic changes and long‐term mortality in patients with HCM treated with ASA according to sex. A total of 259 patients were included (aged 68.4±11.9 years, 62.2% women). Women had higher age and baseline pressures at the time of ASA, with a greater percent reduction in mean left atrial pressure (men versus women: 2.2% versus 15.9%, respectively; P =0.02). Women had better survival (median survival rate of men versus women: 8.6 versus 12.5 years, respectively; P =0.011). On Cox multivariable regression, predictors of mortality were age (per group change <60 years, 61–70 years, 71–80 years, and >80 years; hazard ratio [HR], 1.45 [95% CI, 1.10–1.91], P =0.008), female sex (HR, 0.59 [95% CI, 0.35–0.99], P =0.048), chronic kidney disease (HR, 1.88 [95% CI, 1.06–3.33], P =0.031), and left ventricular outflow tract gradient reduction ≤86% (HR, 1.91 [95% CI, 1.14–3.19], P =0.014). Conclusions Women with HCM undergoing ASA are older and have higher left‐sided baseline pressures compared with men yet have better survival. Further studies exploring the mechanisms of differential outcomes according to sex in patients with HCM undergoing ASA are needed.

Background Symptomatic limitations in apical hypertrophic cardiomyopathy may occur because of diastolic dysfunction with resultant elevated left ventricular filling pressures, cardiac output limitation to exercise, pulmonary hypertension (PH), valvular abnormalities, and/or arrhythmias. In this study, the authors aimed to describe invasive cardiac hemodynamics in a cohort of patients with apical hypertrophic cardiomyopathy. Methods and Results Patients presenting to a comprehensive hypertrophic cardiomyopathy center with apical hypertrophic cardiomyopathy were identified (n=542) and those who underwent invasive hemodynamic catheterization (n=47) were included in the study. Of these, 10 were excluded due to postmyectomy status or incomplete hemodynamic data. The mean age was 56±18 years, 16 (43%) were women, and ejection fraction was preserved (≥50%) in 32 (91%) patients. The most common indication for catheterization was dyspnea (48%) followed by suspected PH (13%), and preheart transplant evaluation (10%). Elevated left ventricular filling pressures at rest or exercise were present in 32 (86%) patients. PH was present in 30 (81%) patients, with 6 (20%) also having right‐sided heart failure. Cardiac index was available in 25 (86%) patients with elevated resting filling pressures. Of these, 19 (76%) had reduced cardiac index and all 6 with right‐sided heart failure had reduced cardiac index. Resting hemodynamics were normal in 8 of 37 (22%) patients, with 5 during exercise; 3 of 5 (60%) patients had exercise‐induced elevation in left ventricular filling pressures. Conclusions In patients with apical hypertrophic cardiomyopathy undergoing invasive hemodynamic cardiac catheterization, 86% had elevated left ventricular filling pressures at rest or with exercise, 81% had PH, and 20% of those with PH had concomitant right‐sided heart failure.

Abstract Aims Echocardiographic assessment of cancer-associated non-bacterial thrombotic endocarditis (Ca-NBTE) is limited to case reports and small clinical series. The study aimed to identify heart valve abnormalities and its relation to embolic complications and cancer types. Methods and results Manual review of echocardiographic images and medical records of Mayo Clinic patients (31 March 2002–30 June 2022) was performed. Ca-NBTE in 111 patients (mean age 63.2 ± 9.7 years, 66.7% female) predominantly affected mitral valves (MV) (69), 56 aortic (AV), 8 tricuspid (TV), and rarely pulmonic (PV) (1). In 18 patients, 2 valves were involved, 3 and 4 valve involvement in only a single patient each. Embolic complications were prevalent (n = 102, 91.9%). Ca-NBTE affected MV more frequently on the upstream (atrial) (90% vs. 49.3%) and TV downstream (ventricular) side (75% vs. 37.5%). NBTE size (cm) varied significantly among valves, with TV hosting the largest masses (0.63–2.40 × 0.39–1.77), compared with MV [(0.11–1.81 × 0.11–1.62), (length P = 0.001; width P = 0.03)] and AV [(0.20–2.70 × 0.11–1.51), (length P = 0.001; width P = 0.056)]; MV masses were borderline longer in systemic compared with cerebral emboli (P = 0.057). Majority of MV (79.6%) and AV (69.6%) had thickened leaflets. NBTE lesions commonly affected closing margins (73.9% MV, 85.7% AV, and 62.5% of TV) but rarely commissures of MV (8.7%), yet fairly frequently of AV (41.1%). Five patients had severe regurgitation of MV and 5 AV. Conclusion Ca-NBTE manifests mainly as thrombotic mobile masses attached to thickened MV and AV, with distinct variations in size based on valve type. Embolic destination but not cancer type is associated with NBTE mass size and location.

Abstract Premortem clinical presentation of cancer‐associated non‐bacterial thrombotic endocarditis (Ca‐NBTE), therapy, and the clinal course is limited to case reports and small clinical series. An electronic search of Mayo Clinic records (03/31/2002–06/30/2022) with a subsequent manual review was performed to identify adult patients with echocardiographically detected NBTE and active malignancy, excluding those with infectious endocarditis or lupus anticoagulant/antiphospholipid antibodies. In this retrospective cohort study, we analyzed 115 Ca‐NBTE patients (mean age 63.2 ± 9.7 years, 66.1% female) involving 71 (61.7%) mitral, 58 (50.4%) aortic, 8 (6.9%) tricuspid, and 1 (0.9%) pulmonary valve. The most common cancer was lung ( n = 45 cases (39.1%), followed by pancreatic ( n = 19, 16.5%), gynecological (17, 14.8%), gastrointestinal ( n = 10, 8.7%), and 10 (8.7%) with hematologic malignancy; 6 patients had two active cancers. Embolic complications at presentation were frequent: 94 (81.7%) brain, 11 splenic, 10 renal, 6 coronary, and 4 to the extremities. Of 104 anticoagulated patients, 60 received low molecular weight heparin, 17 unfractionated heparin, 16 apixaban, 8 warfarin, and 3 rivaroxaban. There were 18 arterial thromboembolisms; the Kaplan–Meier estimates of the incidence at 2 years were consistent with a rate of 15.9% [95% Confidence Interval (CI) 9.9–23.3], including 14 strokes (12.4%, 95%CI, 7.1–19.2), and 8 other arterial emboli (10.5%, 95%CI, 4.7–18.9); there were 10 venous thromboembolisms (8.9%, 95%CI, 4.5–15.0). Fourteen major bleedings occurred (12.8%, 95%CI, 7.3–19.9) and 94 patients died during follow‐up (77.9%, 95%CI, 71.1–85.8). Ca‐NBTE predominantly affected women with lung adenocarcinoma or digestive tract cancers and manifested by stroke with high mortality and frequent embolic and bleeding complications during anticoagulation therapy.

Background: Ca-NBTE primarily affects the mitral valve (MV) and aortic valve (AV), with rare involvement of the right heart valves. Premortem descriptions of this condition are limited to a few case reports. This study presents an initial clinical series focusing on patients with Ca-NBTE specifically affecting their right heart valves. We describe the underlying cancers, types of valve lesions, and associated embolic complications. Patients and Methods: A electronic search of medical records (March 31, 2002, to June 30, 2022) was followed by a manual review to identify adult patients with echocardiographically detected NBTE, active cancer, and no infectious endocarditis or lupus anticoagulant/antiphospholipid antibodies. Results: Out of 115 identified patients with Ca-NBTE (mean age 63.2±9.7 years, 66.1% female), there were 8 cases (7.0%) affecting right heart valves (mean age 64.5±12.1 years, 3 females) with underlying cancer: pancreatic (n=3), lung (n= 2), genitourinary (n=1), gastric (n=1) and neck sarcomatoid carcinoma (n=1). TV was affected in 8 patients and PV in one case; 4 patients had Ca-NBTE limited only to PV, 2 patients had MV and TV, 1 patient had mitral, aortic and TV, and 1 patient with pancreatic cancer had all four valves affected by NBTE. 5 patients had embolic complications to the brain with one patient in that group also experiencing emboli to the kidney and spleen. Out of 4 patients with NBTE limited to TV, two still had brain emboli, one had only pulmonary embolism, and one patient had no embolic complications. Conclusion: Around 7% of Ca-NBTE cases involve the right heart valves, with half of these cases limited to the TV. The cancer profile in these cases resembles that seen in left heart valve involvement.

Primary cardiac tumors (CTs) are exceptionally rare, and are predominantly benign masses. Myxomas make up more than 60% of these lesions and most frequently develop in the left atrium (LA), followed by the right atrium (RA). Carney complex (CNC) is a rare, typically autosomal dominant, multiple endocrine neoplasia characterized by cutaneous findings, myxomas, endocrine and/or nonendocrine neoplasms. We report a rare case of CNC involving biatrial and recurrent myxomas. A 36-year-old female presented to Cardiology Clinic at our center for management of CNC. Three years prior, she was evaluated at a local hospital for acute stroke where TTE showed a myxoma (2 x 2 x 2.5cm) attached to the left atrial septum, prompting resection. On followup TTE 2 years later, she had a mass in the LA, prolapsing through the mitral valve into the left ventricle. She underwent resection of the myxoma (2.9 x 3.9 cm) and left atrial appendage, which was complicated by recurrent stroke. She was found to have a PRKAR1A gene mutation (c.97 deletion) suggestive of CNC and was referred to our center. At Cardiology Clinic, she denied chest pain, dyspnea, presyncope, and syncope. Her father and children did not have the gene mutation. Exam revealed lentigines on her lower lip and pigmentation of an inner canthus. She was diagnosed with primary pigmented nodular adrenal disease by Endocrinology. On TEE, she was found to have a recurrent LA mass (1 x 1 x 0.8 cm) attached to the interatrial septum, but no right-to-left atrial shunt. This prompted surgery consultation. Numerous intracardiac myxomas were removed during surgery; one in the LA attached to the septum, 3-4 smaller ones, and one 2 cm myxoma located in the RA. The interatrial septum was also resected given recurrent myxoma in this region. She underwent cryoablation to prevent recurrence and did well post-surgery. CTs, which includes primary CTs and secondary metastatic disease, are uncommon where the former has an incidence of 0.001-0.3%. We presented a case of recurrent and biatrial cardiac myxomas in the setting of CNC, which is seldomly reported in the literature. Taken together, given the rarity of primary CTs, genetic predispositions or syndromes should be considered especially in the setting of recurrence and/or multiple masses.

Hepatocellular carcinoma (HCC), constituting the predominant manifestation of liver cancer, stands as a formidable medical challenge. The prognosis subsequent to surgical intervention, particularly for individuals presenting with a solitary tumor, relies heavily on the degree of invasiveness. The decision-making process surrounding therapeutic modalities in such cases assumes paramount importance. This case report illuminates a rather unusual clinical scenario. Here, we encounter a patient who, following a disease-free interval, manifested an atypical presentation of HCC, specifically, a solitary cardiac metastasis. The temporal interval of remission adds an additional layer of complexity to the case. Through a multidisciplinary planning process, the decision was made for surgical removal of the metastatic tumor.