A Systematic Review of Delayed High-Grade Atrioventricular Block After Transcatheter Aortic Valve Implantation.

Background: High-grade atrioventricular block (HGAVB) is common after transcatheter aortic valve implantation (TAVI), often necessitating permanent pacemaker (PPM) implantation. Delayed HGAVB has varying definitions but typically refers to onset 48 hours after TAVI or following discharge and may cause syncope and sudden cardiac death. This review estimates the incidence of delayed HGAVB and identifies limitations of current literature. Methods: A systematic review was performed of the following online databases: Medline, Cochrane, Web of Science, and Scopus. Studies that labelled the outcome of "delayed" or "late" atrioventricular block after TAVI were included; patients with previous PPM or aortic valve surgery were excluded. Initial search yielded 775 studies, which, after screening, was narrowed to 19 studies. Results: Nineteen studies with 14,898 patients were included. Mean age was 81.7 years, and 46.3% were male. Mean Society of Thoracic Surgeons (STS) score was 5.6%, and 31.3% of patients had known atrial fibrillation. The most common access site was transfemoral (84.8%), whereas balloon-expandable valves were used in 62.1%, self-expanding valves in 34.0%, and mechanically expanding valves in 3.9% of cases. The incidence of delayed HGAVB ranged from 1.7% to 14.6%, with significant methodologic heterogeneity noted among the included studies. Conclusions: Delayed HGAVB is a common and potentially serious complication of TAVI, with similar risk factors to acute HGAVB. With a move toward an early discharge strategy post-TAVI, further prospective study of delayed HGAVB is warranted to improve understanding of predisposing factors, incidence, timing, and implications.

Contexte: L'apparition d'un bloc atrioventriculaire de haut degré (BAVHD) est fréquente après l'implantation valvulaire aortique par cathéter (IVAC), ce qui nécessite souvent l'implantation d'un stimulateur cardiaque permanent. Les définitions d'un BAVHD tardif varient, mais elles font habituellement référence à l'apparition du bloc 48 heures après l'IVAC ou après le congé de l'hôpital. Le bloc peut alors provoquer une syncope et une mort subite d'origine cardiaque. Cette analyse vise à estimer l'incidence de la formation d'un BAVHD tardif et à définir les lacunes dans les publications actuelles. Méthodologie: Une analyse des études publiées dans les bases de données en ligne suivantes a été menée : Medline, Cochrane, Web of Science et Scopus. Les études dont le libellé comprenait l'issue du bloc atrioventriculaire tardif ou éloigné (« delayed ¼ ou « late ¼) ont été retenues. Les patients qui avaient antérieurement reçu un stimulateur cardiaque permanent ou subi une intervention chirurgicale de la valve aortique ont été exclus. La recherche initiale a permis de recenser 775 études, nombre qui a été réduit à 19 après l'application des critères de sélection. Résultats: Dix-neuf études totalisant 14 898 patients ont été retenues. L'âge moyen était 81,7 ans, et 46,3 % des patients étaient des hommes. Le score STS (Society of Thoracic Surgeons) moyen était de 5,6 %, et 31,3 % des patients avaient une fibrillation auriculaire. Le point d'accès le plus fréquent était par l'artère fémorale (84,8 %). Des valves expansibles par ballonnet ont été utilisées dans 62,1 % des cas, des valves auto-expansibles dans 34,0 % des cas et des valves expansibles mécaniquement dans 3,9 % des cas. L'incidence du BAVHD tardif variait de 1,7 % à 14,6 %, mais la méthodologie était très hétérogène d'une étude à l'autre. Conclusions: Le BAVHD tardif est une complication fréquente et potentiellement grave de l'IVAC, et ses facteurs de risque sont comparables à ceux du BAVHD aigu. Étant donné la volonté d'adopter une stratégie de congé précoce après une IVAC, une autre étude prospective sur le BAVHD tardif s'impose pour mieux comprendre les facteurs prédisposants, l'incidence, la chronologie et les implications.

Utility of cardiac magnetic resonance imaging in diagnosing eosinophilic myocarditis in a patient recently recovered from COVID-19: a grand round case report.

Background: Eosinophilic myocarditis (EM) secondary to eosinophilic granulomatosis with polyangiitis (EGPA) is a rare disease, for which cardiac magnetic resonance imaging (CMRI) is a useful non-invasive modality for diagnosis. We present a case of EM in a patient who recently recovered from COVID-19 and discuss the role of CMRI and endomyocardial biopsy (EMB) to differentiate between COVID-19-associated myocarditis and EM. Case summary: A 20-year-old Hispanic male with a history of sinusitis and asthma, and who recently recovered from COVID-19, presented to the emergency room with pleuritic chest pain, dyspnoea on exertion, and cough. His presentation labs were pertinent for leucocytosis, eosinophilia, elevated troponin, and elevated erythrocyte sedimentation rate and C-reactive protein. The electrocardiogram showed sinus tachycardia. Echocardiogram showed an ejection fraction of 40%. The patient was admitted, and on day 2 of admission, he underwent CMRI which showed findings of EM and mural thrombi. On hospital day 3, the patient underwent right heart catheterization and EMB which confirmed EM. The patient was treated with steroids and mepolizumab. He was discharged on hospital day 7 and continued outpatient heart failure treatment. Discussion: This is a unique case of EM and heart failure with reduced ejection fraction as a presentation of EGPA, in a patient who recently recovered from COVID-19. In this case, CMRI and EMB were critical to identify the cause of myocarditis and helped in the optimal management of this patient.

Prospective observational study on the accuracy of predictors of high-grade atrioventricular conduction block after transcatheter aortic valve implantation (CONDUCT-TAVI): study protocol, background and significance.

INTRODUCTION: Aortic stenosis is the most common cardiac valve pathology worldwide and has a mortality rate of over 50% at 5 years if left untreated. Transcatheter aortic valve implantation (TAVI) is a minimally invasive and highly effective alternative treatment option to open-heart surgery. High-grade atrioventricular conduction block (HGAVB) is one of the most common complications after TAVI and requires a permanent pacemaker. Due to this, patients are typically monitored for 48 hours post TAVI, however up to 40% of HGAVB may delayed, and occur after discharge. Delayed HGAVB can cause syncope or sudden unexplained cardiac death in a vulnerable population, and no accurate methods currently exist to identify patients at risk. METHODS AND ANALYSIS: The prospective observational study on the accuracy of predictors of high-grade atrioventricular conduction block after transcatheter aortic valve implantation (CONDUCT-TAVI) trial is an Australian-led, multicentre, prospective observational study, aiming to improve the prediction of HGAVB, after TAVI. The primary objective of the trial is to assess whether published and novel invasive electrophysiology predictors performed immediately before and after TAVI can help predict HGAVB after TAVI. The secondary objective aims to further evaluate the accuracy of previously published predictors of HGAVB after TAVI, including CT measurements, 12-lead ECG, valve characteristics, percentage oversizing and implantation depth. Follow-up will be for 2 years, and detailed continuous heart rhythm monitoring will be obtained by inserting an implantable loop recorder in all participants. ETHICS AND DISSEMINATION: Ethics approval has been obtained for the two participating centres. Results of the study will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ACTRN12621001700820.

Platypnea-Orthodeoxia Syndrome in the Setting of Patent Foramen Ovale Without Pulmonary Hypertension or Major Lung Disease.

Background Patent foramen ovale (PFO)-associated platypnea-orthodeoxia syndrome is characterized by dyspnea and hypoxemia when upright. The pathogenesis is thought to involve an increase in right atrial pressure or change in degree of right to left shunting with upright posture. Methods and Results We sought to characterize patients with platypnea-orthodeoxia syndrome related to PFO without pulmonary hypertension. We retrospectively reviewed databases at 3 tertiary referral hospitals in New South Wales, Australia from 2000 to 2019. Fourteen patients with a mean age of 69±14 years had a PFO with wide tunnel separation. Mean New York Heart Association Classification was II (±0.9) and 7 inpatients had been confined to bed (from postural symptoms). Baseline oxygen saturations supine were 93%±5% and 84%±6% upright. Two patients had a minor congenital heart defect and 4 had mild parenchymal lung disease with preserved lung function. The mean aortic root diameter was 37±6 mm and distance between aortic root and posterior atrial wall was 16±2 mm. Platypnea-orthodeoxia syndrome was preceded by surgery in 5 patients and 1 patient had mild pneumonia. Successful closure of the PFO using an Amplatzer device was performed in 11 of 14 patients. Post-closure, all patients had New York Heart Association Classification I (improvement 1.6±0.9, P<0.003) and semi-recumbent oxygen saturations increased by 13%±8% (P<0.001, n=10). Conclusions Platypnea-orthodeoxia syndrome is a debilitating condition, curable by PFO closure. Anatomical distortion of the atrial septum related to a dilated aortic root or shortening of the distance between the aortic root and posterior atrial wall may contribute to the syndrome.

Predicting Patients With Troponin Positive Chest Pain and Unobstructed Coronary Arteries With Electrocardiogram, Troponin Kinetics and GRACE Score.

BACKGROUND: Troponin positive chest-pain with unobstructed coronary arteries (TPCP-UCA), occurs in 6% of cases of patients presenting with acute coronary syndrome (ACS). Whilst TPCP-UCA patients are known to be younger with less cardiovascular risk factors when compared to obstructive coronary disease (MICAD), no validated methods exist to reliably delineate these two conditions prior to coronary angiography. METHODS: We analysed 142 patients with MICAD and 127 patients with TPCP-UCA from 2015 to 2019. Several key predetermined clinical, biochemical and electrocardiograph (ECG) parameters, as well as Global Registry of Acute Coronary Events (GRACE) score, were collected for all patients. All TPCP-UCA patients underwent cardiac magnetic resonance imaging (cMRI). RESULTS: Patients with TPCP-UCA were younger than MICAD (44 vs 68 yrs, p<0.01), and with less cardiac risk factors of hypertension (31% vs 68%, p<0.01), hypercholesterolaemia (23% vs 56%, p<0.01), diabetes (11% vs 45%, p<0.01), prior ischaemic heart disease (8% vs 42%, p<0.01) and smoking history (29% vs 50%, p<0.01). Peak troponin (MICAD 2,084.5 ng/L vs TPCP-UCA 847.0 ng/L, p=0.02), serial-to-initial troponin ratio (MICAD 13.5 vs TPCP-UCA 5.1, p<0.01), and peak-to-initial troponin ratio (MICAD 69.6 vs TPCP-UCA 14.0, p<0.01) were all higher in the MICAD group. GRACE scores were significantly different across the two cohorts (TPCP UCA 74 vs MICAD 106, p<0.01), with a receiver operator characteristic (ROC) curve statistic of 0.794 (95% CI 0.739-0.850). On ECG analysis, MICAD had greater prevalence and sum of ST depression (40% vs 19% p<0.01; 1.6 mm vs 0.44 mm, p<0.01) and T wave inversion (37% vs 17%, p<0.01), whilst TPCP-UCA had greater presence of PR depression (20% vs 3% p<0.01), and longer repolarisation (T wave peak to end 89 ms vs 83 ms, p=0.04; T wave peak to end/corrected QT 0.208 ms vs 0.193 ms, p=0.03). All TPCP-UCA patients underwent cMRI. Aetiology was found in 82% of cases, with the leading diagnosis being myocarditis (58%), followed by infarction (8%), whilst 18% had a normal cMRI. CONCLUSIONS: TPCP-UCA is an important differential for patients presenting with ACS, and has several key demographic, biochemical and electrocardiographic differences. The present findings are hypothesis generating, thus prospective studies are required to determine and validate potential clinical utility.

Segmental testicular infarct with an associated testicular artery aneurysm: Case report of a rare clinical entity.

Segmental testicular infarct is a rare clinical entity and can be a diagnostic challenge. Although cases are often idiopathic, underlying etiologies can include testicular torsion, epididymo-orchitis, trauma, vasculitis, and hypercoagulable states. Once suspected, an underlying testicular neoplasm should be excluded. We present a case of a 43-year-old male who developed acute onset left sided scrotal pain. A diagnostic scrotal ultrasound showed a focal, heterogeneous region in left testicle with absent focal Doppler signal, concerning for a segmental testicular infarction. There was no history of trauma, urinary symptoms, sexually transmitted diseases, or constitutional symptoms. Work up for associated underlying etiologies was negative. A computed tomography angiogram scan of the abdomen and pelvis revealed an incidental left testicular artery aneurysm. The patient's consulting multidisciplinary care teams included urology and vascular surgery. Urology deemed surgical intervention inappropriate for the segmental testicular infarct, and vascular surgery elected not to intervene on the testicular artery aneurysm due to risk of completing testicular infarct and damaging blood supply to the testis. The patient was discharged after achieving adequate pain control, and completion of inpatient work up. No underlying malignancy was diagnosed on follow up, and pain symptoms resolved. To the authors' knowledge, no literature exists describing the concurrent incidence of a segmental testicular infarct and an ipsilateral testicular artery aneurysm. In this report, we aim to further describe both diagnoses, and explore the association between the 2 entities.

Cystic fibrosis transmembrane conductance regulator modulates enteric cholinergic activities and is abnormally expressed in the enteric ganglia of patients with slow transit constipation.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) was recently found in the enteric nervous system, where its role is unclear. We aimed to identify which enteric neuronal structures express CFTR, whether CFTR modulates enteric neurotransmission and if altered CFTR expression is associated with slow transit constipation (STC). METHODS: Immunofluorescence double labeling was performed to localize CFTR with various neuronal and glial cell markers in the human colon. The immunoreactivity (IR) of CFTR and choline acetyltransferase (ChAT) on myenteric plexus of control and STC colon was quantitatively analyzed. In control colonic muscle strips, electrical field stimulation (EFS) evoked contractile responses and the release of acetylcholine (ACh) was measured in the presence of the CFTR channel inhibitor, CFTR(inh)-172. RESULTS: CFTR-IR was densely localized to myenteric ganglia, where it was co-localized with neuronal markers HuC/D and ß-tubulin, and glial marker S-100 but little with glial fibrillary acidic protein. Vesicular ACh transport was almost exclusively co-localized with CFTR, but neurons expressing nitric oxide synthase were CFTR negative. Significant reductions of CFTR-IR (P < 0.01) and ChAT-IR (P < 0.05) were observed on myenteric ganglia of STC compared to control. Pre-treatment of colonic muscle strips with CFTR(inh)-172 (10 µM) significantly inhibited EFS-evoked contractile responses (P < 0.01) and ACh release (P < 0.05). CONCLUSIONS: Co-localization of CFTR-IR with cholinergic markers, inhibition of EFS-induced colonic muscle contractility and ACh release by CFTR(inh)-172 suggest that CFTR modulates enteric cholinergic neurotransmission. The downregulation of CFTR and ChAT in myenteric ganglia of STC correlated with the impaired contractile responses to EFS.

The value of endomyocardial biopsy in diagnosis and guiding therapy.

Endomyocardial biopsy (EMB) is a highly-specialised procedure that is associated with some controversy as to its diagnostic role due to its inconsistency in diagnosing a wide variety of cardiac diseases. Given the advances and sophistication in echocardiography and cardiac magnetic resonance imaging (MRI), the vast majority of cardiac diseases can be diagnosed by these non-invasive procedures. Under-sampling and the fact that biopsy site is limited to the right side of the interventricular septum further limits its value. In spite of all these limitations, there still remains a group of pathological conditions that require biopsy for a conclusive diagnosis such as myocarditis, amyloidosis, sarcoidosis and giant cell myocarditis. Correct patient selection and the quantity of tissue samples impart a significant influence on the accuracy of the diagnosis, and thus the value of EMB is variable for each patient. The purpose of this study was to evaluate the role of EMB in patient care, through its ability to either change clinical diagnosis or alter patient management. Our study was based in a single teaching centre. An audit of cardiac biopsies performed over a 10 year period identified 250 patients. We assessed indications, histology, electron microscopic findings, final clinical diagnosis and how they influenced patient management. A definite diagnosis on histology was given in 44 of 250 patients (17.6%). Non-specific findings were observed in the remaining 206 patients (82.4%). Histology influenced patient management in 73 (29.2%) patients. Histological examination in the remaining 177 biopsies (70.8%) did not provide a definite diagnosis or influence patient management. It was additionally found that the number of tissue fragments sampled has significant impact on diagnostic accuracy. A more accurate diagnosis of 45% was obtained when ≥5 fragments were sampled, as compared to 1-3 fragments where accuracy dropped to 20%. Our study indicated that sampling for electron microscopy has very limited value. We found that of 245 biopsies sampled for electron microscopy, only three biopsies (1.2%) had diagnostically useful findings. In our institution procedure related complications were observed in 7 of 250 patients (2.8%). The diagnostic value of EMB is important but limited. Strict triaging of patients according to clinical suspicion and adequate sampling of tissue may increase useful diagnostic information.

A Vector Force Model of Upper Eyelid Position in the Setting of a Trabeculectomy Bleb.

PURPOSE: A vector force model for the determination of upper eyelid position in the setting of a trabeculectomy bleb is presented. The model is used to explain the clinical courses of 5 patients with bleb-induced upper eyelid malposition and the efficacy of modalities previously described for the treatment of bleb-induced upper eyelid retraction. The novel use of botulinum toxin in the treatment of bleb-induced eyelid retraction and unique surgical considerations in patients with trabeculectomy blebs undergoing upper eyelid surgery are discussed. METHODS: A vector force analysis was conducted and a force diagram constructed. The clinical and surgical courses of 5 patients with trabeculectomy blebs and upper eyelid malposition were reviewed. The vector force model was applied to these cases and the previously described treatment modalities for bleb-induced upper eyelid retraction. RESULTS: Vector force analysis demonstrates that in the case of trabeculectomy bleb-induced upper eyelid retraction, the net force vector, which represents the sum of all the individual forces acting on the eyelid, has a positive vertical component resulting in superior displacement of the eyelid. In contrast, bleb-induced ptosis results when the net force vector has a negative vertical component. In 3 patients, alterations in the bleb resulted in resolution of upper eyelid malposition. Botulinum toxin was used to achieve a normal upper eyelid position in 1 patient with lateral canthal tendon disinsertion and unilateral eyelid retraction and 1 patient with bilateral eyelid retraction. One patient developed unilateral ptosis in concert with the emergence of a large Tenon cyst that resolved with the treatment of the cyst via eyelid massage. One patient with unilateral ptosis and an ipsilateral bleb underwent external levator advancement but was unable to achieve the desired upper eyelid height as retraction over the bleb occurred with any attempt to elevate the eyelid above a marginal reflex distance of 1.5 mm. The efficacy of previously reported modalities for the treatment of trabeculectomy bleb-induced upper eyelid retraction can be explained by either a reduction in the positive vertical component of the net force vector or augmentation of the negative vertical component. CONCLUSIONS: A vector force model systematically accounts for the multiple determinants of upper eyelid position in the setting of a trabeculectomy bleb. This model provides a framework for the evaluation of bleb-induced upper eyelid malposition and offers a logical, mathematical explanation for the occurrence of bleb-induced upper eyelid retraction and the usefulness of previously reported treatment modalities for this clinical entity.