Efficacy of balloon-expandable extreme-low-temperature ventricular epicardial cryoablation: A preclinical proof of concept evaluation.

BACKGROUND: Current epicardial ablation technologies are limited by the inability to create adequate depth lesions and risk of collateral injury to extracardiac structures. OBJECTIVE: The purpose of this study was to evaluate the feasibility and efficacy of ventricular epicardial ablation with a novel balloon-expandable extreme-low-temperature (XLT) cryoablation catheter with an embedded insulation pontoon for protection of extracardiac structures, which has been specifically designed for epicardial ablation. METHODS: Ten healthy swine underwent surgical (n = 6) and subxiphoid percutaneous (n = 4) epicardial access. A total of 3-6 sites were targeted in the right and left ventricular wall for different exposure durations. Ablation was performed with a large footprint (surgical) and smaller footprint (percutaneous) version of the HeartPad (Corfigo Inc., Montclair, NJ) XLT system. The system consists of the balloon-expandable cryoablation catheter and a console. The console vaporizes liquid helium (-269°C) and controls continuous delivery of extremely cold helium gas at high flow rates through a high-efficiency ablation element mounted on an expandable insulation pontoon to protect extracardiac structures. Ablation lesions were assessed by gross pathology and histologic examination. RESULTS: A total of 42 epicardial lesions were created. Mean lesion depth increased progressively with ablation time (surgical catheter: 11 ± 2 mm at ≤30 seconds, 13 ± 4 mm at 60 seconds, 15 ± 3 mm at ≥120 seconds, P = .001; percutaneous catheter: 10 ± 2 mm at 30 seconds, 14 ± 2 mm at 60 seconds, 16 ± 2 mm at 120 seconds, P = .001). Lesion geometry seemed unaffected by presence and thickness of epicardial fat. One episode of ventricular fibrillation occurred after ablation over the atrioventricular groove and 2 adjacent obtuse marginal arteries. CONCLUSION: Surgical or percutaneous epicardial ablation using the HeartPad XLT cryoablation system is feasible and can efficiently produce deep ventricular lesions in different epicardial locations.

Comparative Efficacy and Safety of Pulsed Field Ablation Versus Radiofrequency Ablation of Idiopathic LV Arrhythmias.

BACKGROUND: Comparative efficacy and safety data on radiofrequency ablation (RFA) versus pulsed field ablation (PFA) for common idiopathic left ventricular arrhythmia (LV-VAs) locations are lacking. OBJECTIVES: This study sough to compare RFA with PFA of common idiopathic LV-VAs locations. METHODS: Ten swine were randomized to PFA or RFA of LV interventricular septum, papillary muscle, LV summit via distal coronary sinus, and LV epicardium via subxiphoid approach. Ablations were delivered using an investigational dual-energy (RFA/PFA) contact force (CF) and local impedance-sensing catheter. After 1-week survival, animals were euthanized for lesion assessment. RESULTS: A total of 55 PFA (4 applications/site of 2.0 KV, target CF ≥10 g) and 36 RFA (CF ≥10 g, 25-50 W targeting ≥50 Ω local impedance drop, 60-second duration) were performed. LV interventricular septum: average PFA depth 7.8 mm vs RFA 7.9 mm (P = 0.78) and no adverse events. Papillary muscle: average PFA depth 8.1 mm vs RFA 4.5 mm (P < 0.01). Left ventricular summit: average PFA depth 5.6 mm vs RFA 2.7 mm (P < 0.01). Steam-pop and/or ventricular fibrillation in 4 of 12 RFA vs 0 of 12 PFA (P < 0.01), no ST-segment changes observed. Epicardium: average PFA depth 6.4 mm vs RFA 3.3 mm (P < 0.01). Transient ST-segment elevations/depressions occurred in 4 of 5 swine in the PFA arm vs 0 of 5 in the RFA arm (P < 0.01). Angiography acutely and at 7 days showed normal coronaries in all cases. CONCLUSIONS: In this swine study, compared with RFA, PFA of common idiopathic LV-VAs locations produced deeper lesions with fewer steam pops. However, PFA was associated with higher rates of transient ST-segment elevations and depressions with direct epicardium ablation.

Gender Identity in Forensic Death Investigation: A Narrative Review and Suggested Guidelines for Documenting and Reporting.

ABSTRACT: In the current body of forensic literature, there is little guidance available regarding death investigations of transgender, intersex, and gender diverse individuals. An increase in the prevalence of gender diverse identifying people and the frequency in which these individuals experience a premature death makes it more likely these deaths will fall under the jurisdiction of the medical examiner's office. The inability to navigate these diverse cases due to a lack of training, education, and support may leave forensic professionals without the tools needed to accurately represent these deaths.This narrative review is intended to provide the foundational knowledge needed by forensic death investigators when investigating gender identity in death, including suggested guidelines for a more effective and empathetic death investigation. A better understanding of the implications and applications of this information when included in reports will bolster the quality and quantity of the data reported and collected. This will lead to more accurate monitoring and reporting of violent, suicidal, and homicidal deaths of transgender, intersex, and other gender diverse individuals, and a higher identification rate of unidentified remains with gender diverse markers.

The Forensic Perspective of Infectious Endocarditis: A Retrospective Study With Recommendations for the Future.

Increasing rates of infectious endocarditis (IE) are well-described in the United States and worldwide, yet forensic literature regarding IE is sparse. Autopsy databases may help identify subsets of patients at increased risk of mortality. We reviewed all deaths due to IE in our office between 2010 and 2022 (with full autopsy performed) and found 29. The average age was 44 years. Manners of death included natural (69%), accident (28%), and homicide (3%). For all accidental deaths, acute intoxication was included in either part I or II. The aortic valve was most affected (62%), followed by tricuspid (28%) and mitral (24%). Seventy-six percent of affected valves were native, and 24% were prosthetic. Common risk factors included intravenous drug use (48%) and chronic ethanolism (21%). No sustained increase in deaths due to IE was identified. These data show marked differences from clinical literature, including a lower average age and higher incidence of substance use disorders, and it is unlikely selection bias is the sole reason. There was inconsistency in death certification, most notably by not including pertinent IE risk factors. Improving consistency and quality of IE death certification will aid in detecting regional trends and assist multi-institutional collaboration efforts.

Myocardial Calcification: An Unusual Complication of Remote Trauma With Coidentified Amyloidosis.

We present the heart of a 38-year-old man with paraplegia due to a remote traumatic spinal cord injury. In the 20 years following his injury, he experienced chronic decubitus ulcers, osteomyelitis, neurogenic bladder, malnutrition, and urinary tract infections. He was admitted to the hospital with septic shock secondary to multiple decubitus ulcers and osteomyelitis and expired after a two-month hospitalization. At autopsy, there was marked replacement of left ventricle and interventricular septal myocardium by gritty, firm, yellow-white tissue. Microscopic examination demonstrated a remote infarct with marked dystrophic calcification and unexpected amyloid deposition. This example demonstrates the extraordinary extent to which dystrophic calcifications can replace myocardium and highlights multiple potential etiologies of myocardial calcifications. Of note, this is the first report documenting myocardial calcification as a complication of remote, non-iatrogenic trauma. The role of the amyloidosis in the development of calcification is unclear, but a contributory effect cannot be excluded.

Thoracic Aortic Aneurysm and Dissection: Review and Recommendations for Evaluation.

ABSTRACT: Aortic dissection and rupture (collectively termed "sudden aortic death") are commonly encountered by forensic pathologists, with an estimated incidence at autopsy between 0.6% and 7.7%. Despite this, there is no standard of practice for the evaluation of sudden aortic death at autopsy.Recent studies have shown 20% of patients with thoracic aortic aneurysm or dissection (TAAD) have an identifiable genetic syndrome, and 19% will have an affected first-degree relative. The past 2 decades have seen identification of new culprit genes and syndromes, which can have subtle or nonexistent external phenotypes. A high index of suspicion is warranted to identify possible hereditary TAAD (H-TAAD), allowing family members to obtain screening to avoid catastrophic vascular events. Forensic pathologists need broad knowledge of the spectrum of H-TAAD and awareness of the relative significance of hypertension, pregnancy, substance use, and microscopic changes of aortic architecture.This article reviews the common subtypes of H-TAAD, including Marfan syndrome, vascular Ehlers-Danlos, Loeys-Dietz, and familial thoracic aortic aneurysm and dissection. Recommendations for the evaluation of sudden aortic death at autopsy are presented, including (1) performance of a complete autopsy, (2) documentation of aortic circumference and valve morphology, (3) notifying family of the need for screening, and (4) preservation of a sample for potential genetic testing.

Histologic and Immunohistochemical Features of Antemortem Thrombus Compared to Postmortem Clot: Updating the Definition of Lines of Zahn.

CONTEXT.­: Distinguishing true antemortem thrombus (AMT) from artifactual postmortem clot (PMC) can occasionally be challenging at autopsy. Lines of Zahn are cited as pathognomonic of AMT, but review of literature reveals heterogeneous definitions of the term. Neutrophil karyorrhexis and CD61 immunohistochemistry can also be used to define AMT, but there has been no systematic study determining the specificity of these features. OBJECTIVE.­: To identify features that distinguish AMT from PMC, and to clarify the definition of lines of Zahn. DESIGN.­: PMC from the heart was collected in 50 hospital autopsies. Fifty arterial and 50 venous surgical thrombectomy specimens were reviewed for comparison. The microscopic features with hematoxylin-eosin staining, phosphotungstic acid-hematoxylin (PTAH) staining, and CD61 immunohistochemistry were documented. RESULTS.­: Thin curvilinear strands of fibrin and clumps of fibrin were frequently observed in both AMT and PMC. Thick bands of nested platelets wrapped in fibrin were nearly exclusive to AMT. Neutrophil karyorrhexis was readily apparent on low power in AMT but was seen in 40 of 50 PMCs (80%) only sparsely on high-power examination. Bone marrow elements were identified in 38 of 50 PMCs (76%). CD61 staining showed a geographic pattern in AMT and a speckled pattern in PMC. PTAH staining confirmed features seen with hematoxylin-eosin. CONCLUSIONS.­: Thin curvilinear strands of fibrin are found in both AMT and PMC and can be misinterpreted as lines of Zahn. We define lines of Zahn as thick bands formed by nested platelets wrapped in fibrin. Diffuse neutrophil karyorrhexis is common in AMT; in contrast, bone marrow elements are often seen in PMC.

Atrial Endocardial Unipolar Voltage Mapping for Detection of Viable Intramural Myocardium: A Proof-of-Concept Study.

BACKGROUND: Endocardial bipolar voltage amplitude is largely derived from endocardial and subendocardial wall layers. This may result in situations of low bipolar voltage amplitude despite the presence of mid-myocardial including epicardial (ie, intramural-epicardial) viable myocardium. This study examined the utility of endocardial unipolar voltage mapping for detection of viable intramural-epicardial atrial myocardium. METHODS: In 15 swine, an atrial intercaval ablation line with an intentional gap was created. Animals survived for 6 to 8 weeks before electroanatomical mapping followed by sacrifice. Gaps were determined by the presence of electrical conduction and classified based on the histopathologiclly layer(s) of viable myocardium into the following: (1) transmural, (2) endocardial, and (3) intramural-epicardial. Voltage data from healthy, scar, and gap points were exported into excel. The sensitivity and specificity of bipolar and unipolar voltage amplitude to detect intramural-epicardial gaps were compared using receiver operating characteristic analysis. RESULTS: In 9 of 15 (60%) swine, a focal ablation gap was detected in the intercaval line, while in the remainder 6 of 15 (40%), the line was complete without gaps. Gaps were classified into transmural (n=3), endocardial (n=3), or intramural-epicardial (n=3). Intramural-epicardial gaps were characterized by very low bipolar voltage amplitude that was similar to areas with transmural scar (P=0.91). In comparison, unipolar voltage amplitude in intramural-epicardial gaps was significantly higher compared to transmural scar (P<0.001). Unipolar voltage amplitude had higher sensitivity (93% versus 14%, respectively) and similar specificity (95% versus 98%, respectively) to bipolar voltage for detection of intramural-epicardial gaps. CONCLUSIONS: Atrial unipolar voltage mapping may be a useful technique for identifying viable intramural-epicardial myocardium in patients with endocardial scar.

Effect of Pulsed-Field and Radiofrequency Ablation on Heterogeneous Ventricular Scar in a Swine Model of Healed Myocardial Infarction.

BACKGROUND: Pulsed-field ablation (PFA) is a nonthermal energy with higher selectivity to myocardial tissue in comparison to radiofrequency ablation (RFA). We compared the effects of PFA and RFA on heterogeneous ventricular scar in a swine model of healed infarction. METHODS: In 9 swine, myocardial infarction was created by balloon occlusion of the left anterior descending artery. After a survival period of 8 to 10 weeks, ablation with PFA or RFA was performed at infarct border zones identified by abnormal electrograms. In the PFA group (4 swine), ablation was performed with a lattice catheter (Sphere-9, Affera, Inc). In the RFA group (5 swine), ablation was performed using a 3.5-mm tip catheter (Thermocool ST-SF; Biosense Webster). To further investigate the effect of RFA on temperature development in scar tissue, intramyocardial temperature was measured in healthy and infarcted myocardium using an ex vivo bath model. RESULTS: A total of 11 PFA and 15 RFA lesions were created at infarct border zones with heterogeneous scar. PFA produced uniform and well-demarcated lesions exhibiting irreversible injury characterized by cardiomyocyte death, contraction bands, and lymphocytic infiltration. This effect of PFA extended from the subendocardium through collagen and fat to the epicardial layers. In contrast, the effect of RFA is less uniform and largely limited to the subendocardium with minimal effect on viable myocardium deeper to separating layers of collagen and fat. PFA produced deeper and more transmural lesions (6.4 [interquartile range, 5.5-7.5) versus 5.4 [interquartile range, 4.8-5.9]), 72% versus 30%, respectively; P≤0.02 for each comparison). The limited effect of RFA on viable myocardium at deeper infarct layers was related to a lower intramyocardial maximal temperature compared with healthy myocardium (P=0.01). CONCLUSIONS: PFA may be advantageous for ablation in ventricular scar, producing lesions that unlike RFA are not limited to the subendocardium, but also eliminate viable myocardium separated from the catheter by collagen and fat.

Incremental Utility of 3D Printing to Guide the Surgical Management of Apical Aneurysm.

A 24-year-old man presented with a nonischemic cardiomyopathy of unknown etiology, apical aneurysm, and a secondary mitral regurgitation. Computer tomography-derived 3-dimensional model of the patient's heart was an essential step in guiding the surgical management for an optimal outcome. (Level of Difficulty: Advanced.).

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.

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.

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.

Homicide by Unspecified Means: Cleveland 2008 to 2019.

ABSTRACT: The diagnosis homicide by unspecified means (HUM) is used to categorize deaths occurring under suspicious or criminal circumstances, but a specific cause of death cannot be identified. In 2010, Matshes and Lew (Am J Forensic Med Pathol. 2010;31(2):174-177) presented a HUM cases series, from which they derived 5 diagnostic criteria; however, the accuracy of these criteria has not been assessed.To identify a validation cohort, Cuyahoga County Medical Examiner's Office records were searched from 2008 to 2019 for cases certified as HUM. Thirteen cases were identified; on review, all cases fulfilled criteria 1, 4, and 5. Only 1 case had a potential anatomic cause of death identified (criterion 2).However, in 3 cases, toxicologic analyses could not be conducted because of skeletonization; in 2 cases, the decedents tested positive for cocaine/benzoylecgonine but were found in proximity to other victims for whom a specific violent cause of death was determined. By strict reading of criterion 3, these cases would have been excluded from the diagnosis of HUM. Perpetrators confessed to homicide in 7 cases, including the 5 cases that failed the toxicologic criterion. The 2010 diagnostic criteria are a reasonable foundation for the determination of HUM; modification of criterion 3 would provide improved flexibility based on clinical judgment.

Autopsy Service Death Certificate Review.

CONTEXT.­: Despite the importance of accurate death statistics for epidemiologic studies and public health initiatives, there remains a high frequency of errors in death certification. This deficiency can be addressed by the hospital autopsy service. OBJECTIVES.­: To improve the quality and accuracy of death certificates issued in the hospital and improve resident and clinician education by initiating a death certificate review process, performed by pathology residents while on their hospital autopsy rotation. DESIGN.­: A resident reviewed all death certificates issued in the hospital daily through the state electronic death certificate filing system and correlated with the decedent's medical record. When errors were found, the resident filed an amended death certificate with the state. If applicable, the Office of the Medical Examiner was contacted to investigate. The original certifying physician was then contacted via email with an explanation for the amendment. RESULTS.­: In 12 months, 590 death certificates were issued by the hospital. Eighty-eight of 590 (15%) were amended. Of those 88 amended, 41 (47%) were missing an underlying cause of death, 7 (8%) had an inaccurate cause of death, 41 (47%) failed to include relevant contributory causes of death, and 17 (19%) had major typographic errors. Of 88, 24 (27%) fell under the Office of the Medical Examiner's jurisdiction and were reported with a subsequent change in the manner of death in 23 of 88 cases (26%). CONCLUSIONS.­: Death certificate review by the autopsy service improves the accuracy of death certification, impacts resident and clinician education, and serves as quality assurance for both the hospital and the state.

Aspergillosis myocarditis in the immunocompromised host.

Invasive cardiac aspergillosis has been rarely described in immunocompromised patients. This disease is difficult to diagnose by conventional laboratory, microbiologic, and imaging techniques, and is often recognized only post-mortem. The authors present the case of a 60-year-old woman admitted with an exacerbation of eosinophilic granulomatosis with polyangitiis (EGPA) who subsequently died from Aspergillus myocarditis, and compare the patient's case to prior literature. This serves as an up-to-date literature review on the topic of invasive cardiac aspergillosis.