Cardiology Commons^™

Novel Smad3 Variant Identified In A Patient With Familial Aortopathy Modeled Using A Zebrafish Embryo Assay, Mary Burchett Sheppard, Jeffrey D. Smith, Lisa L. Bergmann, Jakub Konrad Famulski

Saha Cardiovascular Research Center Faculty Publications

In human, pathogenic variants in smad3 are one cause of familial aortopathy. We describe a novel SMAD3 variant of unknown significance (VUS), V244F, in a patient who presented with aortic root dilation, right coronary artery ectasia, abdominal aortic aneurysm, right vertebral artery atresia, and cavernoma. Determination of variant pathogenicity impacted multiple aspects of the patient’s care, including the most appropriate surgical threshold for which to recommend a valve-sparing aortic root replacement. To determine whether the newly identified SMAD3 variant, and whether SMAD3 induced aortopathy in general, can be assayed in a zebrafish embryo model, we injected smad3a mRNA into Tg[kdrl:mCherry] …

Aortic Stress Activates An Adaptive Program In Thoracic Aortic Smooth Muscle Cells That Maintains Aortic Strength And Protects Against Aneurysm And Dissection In Mice, Chen Zhang, Yanming Li, Abhijit Chakraborty, Yang Li, Kimberly R. Rebello, Pingping Ren, Wei Luo, Lin Zhang, Hong S. Lu, Lisa A. Cassis, Joseph S. Coselli, Alan Daugherty, Scott A. Lemaire, Ying H. Shen

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: When aortic cells are under stress, such as increased hemodynamic pressure, they adapt to the environment by modifying their functions, allowing the aorta to maintain its strength. To understand the regulation of this adaptive response, we examined transcriptomic and epigenomic programs in aortic smooth muscle cells (SMCs) during the adaptive response to AngII (angiotensin II) infusion and determined its importance in protecting against aortic aneurysm and dissection (AAD).

METHODS: We performed single-cell RNA sequencing and single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) analyses in a mouse model of sporadic AAD induced by AngII infusion. We also examined the direct …

Early Feasibility Of Endovascular Repair Of Distal Aortic Arch Aneurysms Using Patient-Specific Single Retrograde Left Subclavian Artery Branch Stent Graft, Joshua Wong, Emanuel R Tenorio, Guilherme Lima, Marina Dias-Neto, Aidin Baghbani-Oskouei, Bernardo Mendes, Jarin Kratzberg, Laura Ocasio, Thanila A Macedo, Gustavo S Oderich

Faculty, Staff and Student Publications

OBJECTIVE: To describe the feasibility and outcomes of endovascular repair of distal aortic arch aneurysms using a patient-specific stent graft with a pre-loaded single retrograde left subclavian artery (LSA) branch stent graft.

METHODS: We reviewed the clinical data and outcomes of consecutive patients enrolled in an ongoing prospective, non-randomized physician-sponsored investigational device exemption study to evaluate the outcomes of endovascular aortic arch repair using patient-specific arch branch stent grafts (William Cook Europe, Bjaeverskov, Denmark) between 2019 and 2022. All patients received a design with triple-wide scallop and a single retrograde LSA branch with a pre-loaded catheter.

RESULTS: There were five …

Reducing The Risk Of Mortality In Chronic Obstructive Pulmonary Disease With Pharmacotherapy: A Narrative Review, Matthew Mintz, Igor Barjaktarevic, Donald A. Mahler, Barry Make, Neil Skolnik, Barbara Yawn, Bree Zeyzus-Johns, Nicola A. Hanania

Abington Jefferson Health Papers

In 2020, chronic obstructive pulmonary disease (COPD) was the fifth leading cause of death in the United States excluding COVID-19, and its mortality burden has been rising since the 1980s. Smoking cessation, long-term oxygen therapy, noninvasive ventilation, and lung volume reduction surgery have had a beneficial effect on mortality; however, until recently, the effects of pharmacologic therapies on all-cause mortality have been unclear. Inhaled pharmacologic treatments for patients with COPD include combinations of long-acting muscarinic receptor antagonists (LAMAs), long-acting-β2-agonists (LABAs), and inhaled corticosteroids (ICS). The recent IMPACT and ETHOS clinical trials reported mortality benefits with ICS/LAMA/LABA triple therapy compared with …

Gasdermin D Deficiency In Vascular Smooth Muscle Cells Ameliorates Abdominal Aortic Aneurysm Through Reducing Putrescine Synthesis, Jianing Gao, Yanghui Chen, Huiqing Wang, Xin Li, Ke Li, Yangkai Xu, Xianwei Xie, Yansong Guo, Nana Yang, Xinhua Zhang, Dong Ma, Hong S. Lu, Ying H. Shen, Yong Liu, Jifeng Zhang, Y. Eugene Chen, Alan Daugherty, Dao Wen Wang, Lemin Zheng

Saha Cardiovascular Research Center Faculty Publications

Abdominal aortic aneurysm (AAA) is a common vascular disease associated with significant phenotypic alterations in vascular smooth muscle cells (VSMCs). Gasdermin D (GSDMD) is a pore-forming effector of pyroptosis. In this study, the role of VSMC-specific GSDMD in the phenotypic alteration of VSMCs and AAA formation is determined. Single-cell transcriptome analyses reveal Gsdmd upregulation in aortic VSMCs in angiotensin (Ang) II-induced AAA. VSMC-specific Gsdmd deletion ameliorates Ang II-induced AAA in apolipoprotein E (ApoE)−/− mice. Using untargeted metabolomic analysis, it is found that putrescine is significantly reduced in the plasma and aortic tissues of VSMC-specific GSDMD deficient mice. High putrescine levels …

The Mechanism And Therapy Of Aortic Aneurysms, Jianing Gao, Huanhuan Cao, Gaofei Hu, Yufei Wu, Yangkai Xu, Hongtu Cui, Hong S. Lu, Lemin Zheng

Saha Cardiovascular Research Center Faculty Publications

Aortic aneurysm is a chronic aortic disease affected by many factors. Although it is generally asymptomatic, it poses a significant threat to human life due to a high risk of rupture. Because of its strong concealment, it is difficult to diagnose the disease in the early stage. At present, there are no effective drugs for the treatment of aneurysms. Surgical intervention and endovascular treatment are the only therapies. Although current studies have discovered that inflammatory responses as well as the production and activation of various proteases promote aortic aneurysm, the specific mechanisms remain unclear. Researchers are further exploring the pathogenesis …

Genetic Effect On Body Mass Index And Cardiovascular Disease Across Generations, Chloé Sarnowski, Matthew P Conomos, Ramachandran S Vasan, James B Meigs, Josée Dupuis, Ching-Ti Liu, Aaron Leong

Faculty, Staff and Student Publications

BACKGROUND: Whether genetics contribute to the rising prevalence of obesity or its cardiovascular consequences in today's obesogenic environment remains unclear. We sought to determine whether the effects of a higher aggregate genetic burden of obesity risk on body mass index (BMI) or cardiovascular disease (CVD) differed by birth year.

METHODS: We split the FHS (Framingham Heart Study) into 4 equally sized birth cohorts (birth year before 1932, 1932 to 1946, 1947 to 1959, and after 1960). We modeled a genetic predisposition to obesity using an additive genetic risk score (GRS) of 941 BMI-associated variants and tested for GRS-birth year interaction …

Association Of Metformin With The Development Of Age-Related Macular Degeneration, Amitha Domalpally, Samuel A Whittier, Qing Pan, Dana M Dabelea, Christine H Darwin, William C Knowler, Christine G Lee, Jose A Luchsinger, Neil H White, Emily Y Chew

Faculty, Staff and Student Publications

IMPORTANCE: Age-related macular degeneration (AMD) is a leading cause of blindness with no treatment available for early stages. Retrospective studies have shown an association between metformin and reduced risk of AMD.

OBJECTIVE: To investigate the association between metformin use and age-related macular degeneration (AMD).

DESIGN, SETTING, AND PARTICIPANTS: The Diabetes Prevention Program Outcomes Study is a cross-sectional follow-up phase of a large multicenter randomized clinical trial, Diabetes Prevention Program (1996-2001), to investigate the association of treatment with metformin or an intensive lifestyle modification vs placebo with preventing the onset of type 2 diabetes in a population at high risk for …

Inter-Observer Variability Of Expert-Derived Morphologic Risk Predictors In Aortic Dissection, Martin J Willemink, Domenico Mastrodicasa, Mohammad H Madani, Marina Codari, Leonid L Chepelev, Gabriel Mistelbauer, Kate Hanneman, Maral Ouzounian, Daniel Ocazionez, Rana O Afifi, Joan M Lacomis, Luigi Lovato, Davide Pacini, Gianluca Folesani, Ricarda Hinzpeter, Hatem Alkadhi, Arthur E Stillman, Anna M Sailer, Valery L Turner, Virginia Hinostroza, Kathrin Bäumler, Anne S Chin, Nicholas S Burris, D Craig Miller, Michael P Fischbein, Dominik Fleischmann

Faculty, Staff and Student Publications

OBJECTIVES: Establishing the reproducibility of expert-derived measurements on CTA exams of aortic dissection is clinically important and paramount for ground-truth determination for machine learning.

METHODS: Four independent observers retrospectively evaluated CTA exams of 72 patients with uncomplicated Stanford type B aortic dissection and assessed the reproducibility of a recently proposed combination of four morphologic risk predictors (maximum aortic diameter, false lumen circumferential angle, false lumen outflow, and intercostal arteries). For the first inter-observer variability assessment, 47 CTA scans from one aortic center were evaluated by expert-observer 1 in an unconstrained clinical assessment without a standardized workflow and compared to a …

Hybrid Epicardial-Endocardial Ablation For Long-Standing Persistent Atrial Fibrillation: A Subanalysis Of The Converge Trial., David B Delurgio, Christopher Blauth, Michael E Halkos, Karl J Crossen, David Talton, Saumil R Oza, Anthony R Magnano, Mark A Mostovych, Sreedhar Billakanty, Steven Duff, Christopher Stees, Jason Sperling, Syed Ahsan, John Yap, Christian Shults, David Pederson, James Garrison, Paul Tabereaux, David M Gilligan, Graham Bundy, Otto Costantini, Eric Espinal, Angelo La Pietra, Felix Yang, Yisachar Greenberg, Israel Jacobowitz, Jaswinder Gill

Heart and Vascular Articles

BACKGROUND: Favorable clinical outcomes are difficult to achieve in long-standing persistent atrial fibrillation (LSPAF) with catheter ablation (CA). The CONVERGE (Convergence of Epicardial and Endocardial Ablation for the Treatment of Symptomatic Persistent Atrial FIbrillation) trial evaluated the effectiveness of hybrid convergent (HC) ablation vs endocardial CA.

OBJECTIVE: The study sought to evaluate the safety and effectiveness of HC vs CA in the LSPAF subgroup from the CONVERGE trial.

METHODS: The CONVERGE trial was a prospective, multicenter, randomized trial that enrolled 153 patients at 27 sites. A post hoc analysis was performed on LSPAF patients. The primary effectiveness was freedom from …

Acoustic Voice And Speech Biomarkers Of Treatment Status During Hospitalization For Acute Decompensated Heart Failure, Olivia M Murton, G William Dec, Robert E Hillman, Maulik D Majmudar, Johannes Steiner, John V Guttag, Daryush D Mehta

Faculty, Staff and Student Publications

This study investigates acoustic voice and speech features as biomarkers for acute decompensated heart failure (ADHF), a serious escalation of heart failure symptoms including breathlessness and fatigue. ADHF-related systemic fluid accumulation in the lungs and laryngeal tissues is hypothesized to affect phonation and respiration for speech. A set of daily spoken recordings from 52 patients undergoing inpatient ADHF treatment was analyzed to identify voice and speech biomarkers for ADHF and to examine the trajectory of biomarkers during treatment. Results indicated that speakers produce more stable phonation, a more creaky voice, faster speech rates, and longer phrases after ADHF treatment compared …

Potential And Pitfalls Of Pharmacovigilance Databases In Oncology, Ilana Schlam, Michael S Ewer, Sandra M Swain

Faculty, Staff and Student Publications

No abstract provided.

Comparison Of Premature, Extremely Premature, And Older Adults With Coronary Artery Disease In Pakistan, Waqas Ullah, Rehan Malik, Faiza Bashir, Mustafa Khan, Saud Khan, Mahboob Alam, Zainab Samad, Miguel C. Achirica, Salim S. Virani, Bashir Hanif

Section of Cardiology

No abstract provided.

The Potential Of Brain Stimulation Techniques For Substance Use Disorder Treatment, Antonio F Corno, Taylor S Koerner, Jorge D Salazar

Faculty, Staff and Student Publications

No abstract provided.

What Did We Learn About Vads In 2022?, Maya Guglin

The VAD Journal

This is our 9^th annual literature review on mechanical circulatory support devices. Our previous reports were well received by the readers.

In this paper, we summarized the most interesting and important, from our standpoint, publications from 2022. There may be some slight overlap with the end of 2021 because some papers were published online first, and the year of the publication changed when they became available in print.

For the sixth time, we wrote a section on extracorporeal membrane oxygenation (ECMO) which primarily addresses new developments in veno-arterial ECMO.

Readers who wish to supplement this review, argue with the …

Monoclonal Antibodies, Gene Silencing And Gene Editing (Crispr) Therapies For The Treatment Of Hyperlipidemia-The Future Is Here, Melody Hermel, Madison Lieberman, Leandro Slipczuk, Jamal S. Rana, Salim S. Virani

Office of the Provost

Hyperlipidemia is a significant risk factor for atherosclerotic cardiovascular disease. Undertreatment of elevated lipids persists despite existing therapies. Here, we provide an update on monoclonal antibodies, gene silencing therapies, and gene editing techniques for the management of hyperlipidemia. The current era of cutting-edge pharmaceuticals targeting low density lipoprotein cholesterol, PCSK9, lipoprotein (a), angiopoietin-like 3, and apolipoprotein C3 are reviewed. We outline what is known, studies in progress, and futuristic goals. This review of available and upcoming biotechnological lipid therapies is presented for clinicians managing patients with familial hyperlipidemia, statin intolerance, hypertriglyceridemia, or elevated lipoprotein (a) levels.

Old But Not Vain : Two Cases Of Refractory Polymorphic Ventricular Tachycardia Associated With Coronary Artery Disease Successfully Treated With Quinidine, Tit-Kei Ng, Tommy King-Him Ma, Chi-Chun Au, Janice Woon-Yan Wong, Jenny Nga-Lai Chow, Andrew Vincent Li, Adrian Yin-Cheung Luk, Sze-Wah Lai, Candy Ming-Yan Cheuk, Jaclyn Chi-Lin Chan, Li-Wah Tam

Journal of the Hong Kong College of Cardiology

Post myocardial infarct polymorphic Ventricular Tachycardia (VT) triggered by injured Purkinje fibres can cause VT storms that are refractory to various treatment even after successful reperfusion or revascularization. We reported such recurrent polymorphic VT in two post myocardial infarct patients after Percutaneous Coronary Intervention. Both of them responded readily to Quinidine. We also discussed the pathophysiology of this arrhythmia and the treatment option of it, namely catheter ablation and antiarrhythmics

Recurrent Cyanotic Spells In An Octogenarian, Chin Tong Kwok, Chun Kit Wong

Journal of the Hong Kong College of Cardiology

We report rare case of an octogenarian who, after years of diagnostic delay, was found to have a patent foramen ovale, and due to an ascending aortic aneurysm that anatomically facilitated right-to-left shunt, presenting with life-threatening cyanotic attacks. The characteristic orthodeoxia-platypnea syndrome and high alveolar arterial gradient hint to the diagnosis. She was eventually treated successfully with urgent percutaneous PFO closure. Routine ordering of a transthoracic echocardiogram, without agitated saline injection under provocation maneuvers, may not be sufficient to rule out shunts.

Roles Of Exercise Treadmill Test In The Diagnosis & Risk Stratification Of Cardiac Channelopathies, Kit Chan

Journal of the Hong Kong College of Cardiology

Channelopathies are the leading causes of SCD in patients without structural heart disease. Missing the diagnosis of high-risk but concealed channelopathies could have lethal clinical consequences. However, the diagnosis of channelopathies is often challenging due to the dynamic clinical presentations and elusive ECG manifestations of these diseases. An integrated approach including clinical assessment, repeated electrocardiography, drug provocation tests, exercise stress test and genetic studies is often required for establishing the diagnosis. Pharmacological provocation tests may have limited sensitivity and may be associated with false positive results. Wide-spread use of genetic studies are limited by low yield, cost-effectiveness and availability issue. …

The Impact Of Renal Insufficiency Upon Admission On The Clinical Outcome Of Patients With Acute St-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention, Wai Lun Kwong, Kwok Ho Yau, Eugene Sin, Kwok Keung Chan

Journal of the Hong Kong College of Cardiology

Background: Coronary artery disease is common in patients with renal insufficiency. In acute coronary syndrome, impaired renal function is present in approximately 30-40% of patients and is associated with worse prognosis. Local data regarding the risks and benefits for those patients suffering from acute ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) is scarce. We evaluated the clinical outcomes of patients suffering from STEMI with and without renal insufficiency upon admission who underwent PPCI.

Methods: From 1^st January 2009 to 30^th September 2017, all patients with STEMI treated with PPCI were identified. The primary …